1. Introduction
Diabetes mellitus (DM) ranks among the top global health burdens, trailing only cardiovascular and oncological diseases in severity and frequency. Its prevalence has soared, affecting about 6.6% of the global population, and healthcare systems allocate over 10% of resources to its management [1,2]. From 2000 to 2011, cases doubled from 171 million to 347 million, with projections exceeding 550 million by 2030 [3].
In Romania, type 1 DM incidence sits near 5 per 100,000 annually, while many more live in a prediabetic state that, without lifestyle and dietary intervention, will progress to overt diabetes [4]. The World Health Organization divides DM into type 1, type 2, other specific forms, and gestational diabetes, with type 1 and type 2 being the most prevalent. This spectrum, from normoglycemia through insulin dependence, aids accurate staging and guides therapy. Type 1 diabetes is characterized by autoimmune destruction of pancreatic β-cells, resulting in absolute insulin deficiency, while type 2 diabetes is marked by insulin resistance and a relative insulin deficiency due to impaired β-cell function. Insulin resistance refers to reduced sensitivity of peripheral tissues to the effects of insulin, leading to compensatory hyperinsulinemia and eventual glucose intolerance. One key mechanism targeted by both synthetic and natural therapies is α-glucosidase inhibition, which slows the intestinal breakdown of carbohydrates, thereby reducing postprandial blood glucose spikes. Etiologically, DM may be primary (idiopathic) or secondary to identifiable conditions such as chronic pancreatitis, hormonal disorders (e.g., Cushing disease), certain medications or toxins, and genetic syndromes [5,6].
Type 1 DM stems from an autoimmune attack; T lymphocytes destroy pancreatic β-cells, leading to rapid-onset symptoms: polyuria, polydipsia, polyphagia, weight loss, and fatigue. Without prompt insulin therapy, patients risk ketoacidosis and coma [5]. Both genetic factors (diabetogenic HLA haplotypes) and environmental triggers (viral infections, mumps, Coxsackie B4, rubella, CMV, EBV, and early dietary exposures like cow milk proteins, nitrosamines, and caffeine) contribute to disease onset [7].
Type 2 DM evolves insidiously from insulin resistance and impaired secretion. It often goes undetected for years. Key risk factors include sedentary lifestyle, excessive caloric intake, dyslipidemia, hypertension, and obesity. In obesity, enlarged adipocytes and infiltrating immune cells release pro-inflammatory adipokines, worsening insulin resistance and promoting endothelial dysfunction [8,9].
Persistent hyperglycemia fosters oxidative stress—an imbalance favoring reactive oxygen species (ROS) over antioxidants (glutathione, catalase, and superoxide dismutase), damaging cells and driving complications such as retinopathy, neuropathy, nephropathy, atherosclerosis, and heightened risks of myocardial infarction and stroke [10]. Consequently, diabetic individuals face markedly increased cardiovascular, renal, and ocular morbidity. Neither a cure nor fully substitutive insulin exists. Management centers on staged interventions: lifestyle modification (low glycemic index, diet, and exercise), phytotherapy, oral antidiabetics, and insulin injections [11].
This review focuses on medicinal plants that are either native to Romania or widely used in Romanian ethnomedicine, including both indigenous wild flora and cultivated or imported species with documented antidiabetic properties. Romania possesses a unique cultural and ethnobotanical heritage, with centuries-old traditions of using medicinal plants for managing chronic diseases such as diabetes. Rural and urban communities alike have preserved knowledge regarding the preparation and therapeutic use of indigenous and introduced species, making Romania a particularly rich resource for the study of plant-based antidiabetic interventions.
Phytotherapy, used since antiquity, employs plant-based preparations (infusions, decoctions, and tinctures) rich in bioactive compounds. Its benefits include the synergistic effects of phytocomplexes and a favorable side-effect profile [12]. Research has linked hypoglycemic activity to constituents such as polyphenolic acids, anthocyanosides, carotenoids, essential oils, triterpenes, tannins, and flavonoids. The mechanisms include β-cell regeneration, insulin-mimetic action, reduction in intestinal glucose uptake, suppression of gluconeogenesis, enhancement in peripheral glucose utilization, and improvement in insulin sensitivity [13].
Animal studies, often using streptozotocin or alloxan to induce diabetes, have clarified these mechanisms and supported the traditional use of many plants for reducing hyperglycemia and oxidative stress [14].
2. Pathogenesis of Diabetes Mellitus
Type 1 diabetes (T1DM) arises when autoimmune Th1-polarized CD4+ and CD8+ T cells (and macrophages) attack pancreatic β-cells in the islets of Langerhans, often despite normal B-cell function. This breakdown in self-tolerance is linked to defective thymic deletion of high-affinity T cells and MHC gene variants. β-cell loss occurs via direct CD8+ cytotoxicity, cytokines (IL-1, IFN-γ, TNF-α), ROS, nitric oxide, or Fas/FasL interactions [15].
Three autoantibodies, ICA-512, anti-GAD65, and insulin autoantibodies (IAA), appear years before symptoms. A single autoantibody carries a ~20% risk of clinical T1DM; two or more raise the risk to above 75% [16]. Familial risk hinges on HLA class II alleles: DRB103/04 and DQB10302 confer ~25% risk, doubling to ~50% if multiple relatives are affected [17,18,19]. Intriguingly, some carriers of the “protective” DQA1-DQB1*0602 haplotype still develop T1DM—suggesting delayed onset rather than absolute protection—and the precise pathogenic role of autoantibodies remains uncertain [20]. Early in T1DM, insulin sensitivity is preserved, but endogenous secretion plummets by diagnosis (low C-peptide), necessitating lifelong insulin replacement to avert ketoacidosis and other acute crises [21,22].
Type 2 diabetes (T2DM) reflects peripheral insulin resistance, driven by altered receptor signaling and eventual β-cell exhaustion, and a modest genetic predisposition (e.g., TCF7L2 variants increase risk ~1.5-fold) [23]. Contributing metabolic derangements include heightened adipocyte lipolysis, incretin resistance, hyperglucagonemia, fluid retention, and dysregulated central metabolic control.
Obesity is a pivotal, modifiable driver of T2DM. Hypertrophic white adipose tissue becomes inflamed; macrophage infiltration and excess TNF-α and IL-6 disrupt insulin signaling, while leptin overproduction further stimulates macrophages [24]. Conversely, adiponectin, normally abundant in adipose tissue and protective via the suppression of hepatic gluconeogenesis, the promotion of muscle fatty acid oxidation, and anti-inflammatory effects, is markedly reduced in obesity and diabetes, exacerbating insulin resistance and atherogenesis [25,26].
3. Causes and Risk Factors
The causes of diabetes mellitus remain only partially understood. The development of both major types of diabetes is closely associated with hereditary factors, particularly family history involving first-degree relatives (parents or siblings) diagnosed with the condition. Researchers have identified at least 18 genetic loci, designated IDDM1 through IDDM18, that are correlated with T1DM. The IDDM1 region includes the HLA genes, which regulate immune responses and encode proteins of the major histocompatibility complex. In addition to genetic background, phenotypic expression plays a significant role.
Currently, extensive genetic studies aim to define specific genetic profiles that predispose individuals to T2DM in various regions around the world. T2DM is considered a polygenic disorder, involving multiple genes located on different chromosomes that contribute to disease susceptibility. The analysis of genetic contributions is complicated by the fact that numerous environmental factors interact with these genes to trigger disease onset. Only a minority of T2DM cases are attributable to single-gene defects, one notable example being maturity-onset diabetes of the young (MODY). Our current understanding of the genetic basis of T2DM remains limited. Reflecting the complex network of physiological disturbances in T2DM, its genetic architecture involves a large number of susceptibility genes, each exerting a relatively small effect (Table 1).
Several studies suggest that vitamin D deficiency during childhood increases the risk of later developing T1DM. In Finland, a northern country with limited sunlight exposure and reduced cutaneous vitamin D synthesis, the incidence of T1DM is the highest in the world. Other research has identified early cow milk consumption as another predisposing factor for autoimmune diabetes. Bovine serum albumin can trigger the production of autoantibodies that, through molecular mimicry, target pancreatic β-cells.
Gluten and other cereal-derived proteins have also been implicated as potential antigens; introducing cereals into an infant’s diet before the age of 3 months may increase the risk of developing T1DM.
Additional contributors include metabolic stress and exposure to environmental toxins, both of which may predispose individuals to the development of T1DM [30].
For T2DM, the most significant modifiable risk factors include excessive body weight, primarily due to overeating and physical inactivity [31]. Another potentially important diabetogenic factor is psychological stress, especially crowding-related stress in urban environments.
Race and ethnicity have also been linked to an increased risk of T2DM. African Americans, Hispanics, Native Americans, Asian Americans, and Pacific Islanders have a higher incidence of type 2 diabetes compared to Caucasian populations.
While advancing age is a well-known risk factor for T2DM, the number of children being diagnosed with type 2 diabetes is also on the rise. These children are often obese, sedentary, and have a positive family history of the disease [32].
Women with a history of gestational diabetes or those who have given birth to a macrosomic infant (weighing over 4 kg) are at increased risk of developing prediabetes or overt T2DM. Moreover, polycystic ovary syndrome (PCOS) has been identified as a risk factor for type 2 diabetes mellitus [33,34].
4. Prevalence of Diabetes Mellitus
Diabetes mellitus is a leading chronic condition of modern society, yet estimating its true global prevalence remains challenging due to inconsistent diagnostic criteria [35]. Since the 1990s, DM rates have climbed sharply: from 366 million cases in 2011 to a projected 552 million by 2030—a 51% rise over 19 years [36]. Global reports cover all forms (type 1, type 2, gestational, and insulin-dependent/non-dependent) and complications such as retinopathy across regions [37].
Despite advances in care, life expectancy for people with DM lags behind that of the general population, primarily due to cardiovascular disease, renal failure, and infections. Type 1 diabetes (T1DM) makes up 5–10% of cases and, although it can emerge at any age, is most common in childhood and adolescence. The WHO’s DIAMOND study (children ≤14 years, year 2000) found incidence under 1 per 100,000/year in China and South America, yet over 20 per 100,000/year in Northern Europe (peaking at 36.5 in Finland), with intermediate rates in France and Italy (~8) and half of Europeans between 5 and 10 per 100,000/year. Incidence is rising in societies undergoing rapid change [38].
Type 2 diabetes (T2DM) is increasingly diagnosed in youths; school-age rates climb ~3% annually, and preschool rates ~5%. Overall, cases are set to surge in developing nations due to population growth, aging, poor diet, obesity, and inactivity. By 2030, most DM patients in wealthy countries will be ≥65, whereas those in low- and middle-income countries will predominantly be 45–64 years old. T2DM prevalence is the highest in Pacific Islands, moderate in India and the U.S., and lower in Russia; about 2–6% of Western European and North American populations are affected [39,40,41].
Urbanization, sedentary lifestyles, stress, and excess weight have doubled DM diagnoses over three decades. Projections once estimated >360 million global cases by 2030 [42]. Central (“android”) obesity, present in ~80% of T2DM patients, is a critical risk factor; waist-to-hip ratio correlates with diabetes incidence since Vague’s 1956 findings [43,44]. As of 2022, WHO reports that 43% of adults are overweight and 16% are obese worldwide, with ~35 million obese children under five in 2024 [45].
In Romania, adult DM prevalence exceeds 8%, totaling over one million people [46]. In 2011, nearly 800,000 Romanians had DM (67% urban), 14.5% were insulin-dependent, and 2651 juvenile cases were recorded (61% urban), with an age distribution of 3% (0–14 yrs), 62% (15–64 yrs), and 35% (>64 yrs). Recent estimates indicate that 1.7 million Romanians have DM and 3 million have prediabetes and are at high risk without preventive action [6,47].
By 2010, type 2 DM accounted for 90 % of the 285 million global diabetes cases, about 6% of adults—predominantly in developed nations [48,49].
5. Classification of Diabetes Mellitus
The etiological classification of diabetes mellitus, based on associated metabolic disturbances, allows for the differentiation of several distinct types: type 1, type 2, type 3 (resulting from specific mechanisms or underlying diseases), and type 4 (gestational diabetes) (Table 2).
Type 1 diabetes mellitus is characterized by destructive lesions of pancreatic β-cells, arising either through autoimmune mechanisms or from unknown causes [50].
Type 2 diabetes mellitus is defined by the coexistence of two pathophysiological features: diminished insulin secretion and reduced sensitivity of target tissues to insulin, commonly referred to as insulin resistance (Figure 1) [51].
Obesity, defined by a body mass index (BMI) greater than 30, along with metabolic syndrome, represents a significant risk factor that increases the incidence and precedes the onset of type 2 diabetes mellitus [52]. Type 3 diabetes includes two subcategories: diabetes resulting from specific genetic mutations and diabetes associated with pathological states or other diseases [53]. Gestational diabetes is defined as an impairment in glucose metabolism (glucose intolerance) that is first diagnosed during pregnancy. In certain cases, this condition may reflect previously undiagnosed preexisting diabetes, in which case it is not classified as gestational diabetes. Gestational diabetes complicates approximately 3–10% of pregnancies. Women diagnosed with gestational diabetes require long-term postnatal monitoring, often for years, due to the increased risk of developing type 2 diabetes later in life. Careful glycemic control during pregnancy is crucial, as it supports normal fetal development and significantly reduces the risk of congenital malformations and perinatal mortality [54]. Based on plasma glucose levels and glucose metabolism status, individuals may be categorized as having normal glycemia, prediabetes, or overt diabetes mellitus. The diabetic stage can be further subdivided into three clinical substages: diabetes that does not require insulin, diabetes that requires insulin for glycemic control, and diabetes that requires insulin for survival. These substages may vary depending on the progression or improvement of metabolic processes, whether wild-growing or in response to appropriate therapeutic intervention (Table 3) [55].
The classification and diagnostic criteria for diabetes mellitus were first developed in 1979 and 1980 by the National Diabetes Data Group (USA) and the Expert Committee on Diabetes Mellitus of the World Health Organization. In parallel, the American Diabetes Association (ADA) issued a report to reassess the criteria for diagnosing and classifying diabetes. The terminology was clarified, and the proposed classification system has since been widely accepted in the medical and scientific literature [49]. The etiologic classification of diabetes, initially proposed by the ADA in 1997 and endorsed by the World Health Organization (WHO) in 1999–2000, has undergone several refinements, with the most recent updates incorporated in the ADA Standards of Care in Diabetes—2024 and the WHO 2022 classification, which remain the internationally recognized frameworks for clinical and research purposes.
Table 2Etiologic classification of disorders of glucose metabolism.
| I. Type 1 Diabetes Mellitus (β-cell destruction, usually resulting in absolute insulin deficiency) |
| II. Type 2 Diabetes Mellitus. This form may range from predominant insulin resistance with a relative insulin deficiency to a predominant insulin secretory defect accompanied by insulin resistance [57] |
| III. Other Specific Types of Diabetes Mellitus Chromosome 12, HNF-1α (MODY 3) Chromosome 7, glucokinase (MODY 2) Chromosome 20, HNF-4α (MODY 1) Chromosome 13, IPF-1 (MODY 4) Chromosome 17, HNF-1β (MODY 5) Chromosome 2, NeuroD1 (MODY 6) Mitochondrial DNA mutations Subunits of the ATP-sensitive potassium channel |
| IV. Gestational Diabetes Mellitus (GDM) |
| V. Prediabetes |
Categories of increased risk for diabetes (prediabetes) based on blood glucose and HbA1c values [61]. For all three tests, the risk is continuous, extending below the lower limit of the interval and becoming disproportionately high at the extreme values.
| Tests Used | Reference Ranges for Prediabetes | Interpretation |
|---|---|---|
| FPG (fasting plasma glucose)—no carbohydrate intake 8 h prior | 100 mg/dL (5.6 mmol/L) to 125 mg/dL (6.9 mmol/L) | Impaired fasting glucose |
| Two-hour plasma glucose after 75 g oral glucose (OGTT—oral glucose tolerance test) | 140 mg/dL (7.8 mmol/L) to 199 mg/dL (11.0 mmol/L) | Impaired glucose tolerance |
| HbA1C | 5.7–6.4% | Prediabetes |
6. Traditionally Used Herbal Products in the Treatment of Diabetes Mellitus and Its Complications
Key Representatives and Mechanisms of Action
Medicinal plants exert their antidiabetic effects through a wide range of physiological mechanisms that mirror or complement those of conventional pharmacological agents. One of the key pathways involves the regeneration and stimulation of pancreatic β-cells, ultimately leading to increased insulin production and secretion. These secretagogue-like actions are particularly valuable in early-stage diabetes, where residual β-cell function can still be preserved or enhanced. In addition to stimulating endogenous insulin secretion, many phytochemicals also display insulin-like (insulinomimetic) effects. These compounds can directly activate insulin receptors, acting as functional agonists that mimic the hormone activity and further stimulate β-cell responsiveness. Such dual mechanisms contribute not only to improved insulin levels but also to more effective glucose clearance from circulation. Another important therapeutic pathway is the reduction in intestinal glucose absorption, achieved through the inhibition of carbohydrate-digesting enzymes such as α-glucosidase and α-amylase. By slowing the breakdown of complex carbohydrates, these plant-derived compounds help attenuate postprandial glycemic spikes. Similarly, the inhibition of renal glucose reabsorption contributes to enhanced glycemic control by promoting glucose excretion via the urine, an effect functionally analogous to that of SGLT2 inhibitors. On a systemic level, phytocompounds may also exert influence over hepatic glucose metabolism through the suppression of gluconeogenesis and the modulation of glycogen storage and breakdown. This effect, in concert with enhanced glucose uptake in peripheral tissues, particularly skeletal muscle and adipose tissue, supports a more balanced glycemic profile. Additionally, plant constituents have been shown to improve insulin sensitivity, a cornerstone in the management of type 2 diabetes, particularly in individuals with metabolic syndrome. Some compounds facilitate the reactivation of protein-bound insulin, restoring its biological activity and extending its physiological utility. Finally, certain plant-based molecules contribute to glycemic regulation by inhibiting insulinase, the enzyme responsible for insulin degradation, thereby prolonging insulin half-life and bioavailability in circulation. Taken together, these multifaceted actions highlight the therapeutic potential of medicinal plants as complementary agents in diabetes management, acting not only on isolated targets but across multiple interconnected metabolic pathways (Figure 2) [62].
In conjunction with synthetic antidiabetic medications, phytotherapy serves as an effective adjunct therapy in conventional hypoglycemic treatment protocols. Medicinal plants have demonstrated therapeutic efficacy in diabetes management, with scientific studies highlighting numerous bioactive compounds that offer protective and regenerative effects on insulin-producing pancreatic β-cells [63].
The main classes of plant-derived hypoglycemic compounds include polyphenolcarboxylic acids, anthocyanosides, carotenoids, essential oils, triterpenes, thioheterosides, tannins, sterols, triterpenic saponins, proanthocyanidins, bitter principles, flavonoids, and coumarins [64,65] (Table 4).
The following table provides a comprehensive overview of the 47 medicinal plants included in this review, grouped according to the experimental models and durations most commonly used in antidiabetic research. Plants were categorized based on whether they were evaluated in cell culture assays (typically 24–48 h, assessing glucose uptake, GLUT4 translocation, or insulin secretion), rapid in vitro enzyme inhibition assays (30–60 min, targeting α-glucosidase or α-amylase activity), in vivo animal studies (ranging from 2 to 8 weeks, examining effects on glycemic control, pancreatic β-cell function, or diabetes complications), or human clinical trials (weeks to months). Notably, while many plants have demonstrated promising enzyme inhibitory effects in rapid biochemical assays, only a subset has been systematically investigated in cell-based or in vivo models that better reflect physiological glucose metabolism. Furthermore, relatively few plants have been evaluated in clinical studies, underlining the need for translational research to substantiate their therapeutic potential (Table 5).
Wild-growing plants, such as Thymus vulgaris, Salvia officinalis, and Urtica dioica, represent native flora that grows naturally in Romanian ecosystems without the need for human intervention. These species not only reflect the rich ethnobotanical heritage of the region but also offer a sustainable source of bioactive compounds for therapeutic use. Cultivated but non-wild-growing plants, including Glycyrrhiza glabra, Trigonella foenum-graecum, and Asparagus officinalis, are not native to the Romanian landscape but are widely grown due to their recognized medicinal or nutritional properties. Their inclusion in local agriculture illustrates the integration of global phytomedicine into regional practices, driven by both traditional knowledge and modern phytopharmaceutical demand. Lastly, the neither wild-growing nor commonly cultivated group, which includes tropical and subtropical species such as Momordica charantia, Panax quinquefolius, and Azadirachta indica, are primarily of exotic origin and are not typically found in Romanian agriculture or wild flora. These plants, however, hold significant pharmacological promise and are increasingly studied for their antidiabetic potential in global research, suggesting opportunities for future cultivation under controlled conditions or use in standardized extracts (Table 6).
Among Romania’s rich wild-growing flora, Urtica dioica (stinging nettle) stands out as a widely accessible, traditionally used plant with robust preclinical evidence for glycemic benefits. Both animal and in vitro studies confirm its ability to enhance glucose uptake, mimic insulin activity, and reduce oxidative stress, with an α-glucosidase IC50 of 44.7 μg/mL for methanolic leaf extract. Nettle can be consumed as an infusion, soup, or cooked vegetable, representing a natural and sustainable dietary intervention for blood glucose management. Its widespread availability and favorable safety profile further support its role as a practical resource for diabetes prevention in Romanian communities.
Emerging evidence consistently supports the adoption of a dietary pattern rich in whole plant foods, unprocessed grains, legumes, vegetables, nuts, and moderate fruit intake as the optimal strategy for diabetes prevention and metabolic health. In Romania, adapting the traditional diet to emphasize fiber-rich foods (whole grains, beans, lentils, and leafy greens), unsaturated fats (from nuts and seeds), and moderate dairy and fish intake, while reducing refined carbohydrates, sugary drinks, and processed meats, can substantially lower the risk of developing diabetes. Such a dietary pattern aligns with both Mediterranean and Nordic dietary recommendations and is feasible using locally available ingredients. Additionally, integrating infusions or culinary use of select medicinal plants with documented antidiabetic activity, such as Urtica dioica (stinging nettle), Salvia officinalis (sage), and Cynara scolymus (artichoke), offers a culturally acceptable and accessible adjunct for glycemic control. Public health efforts should focus on education, seasonal plant-based diversity, and support for rural foraging and small-scale cultivation, thus leveraging Romania’s botanical heritage for metabolic health.
Table 7 synthesizes current knowledge by categorizing all 47 medicinal plants reviewed in this article according to their principal molecular targets and antidiabetic pathways, as supported by recent pharmacological research. Each plant is mapped to at least one major mechanism, including AMPK activation, PPAR-γ modulation, PI3K/Akt-mediated GLUT4 translocation, inhibition of digestive enzymes (α-glucosidase and α-amylase), insulin receptor agonism, DPP-IV and SGLT inhibition, antioxidant and anti-inflammatory activity, β-cell protection, or other relevant metabolic effects. Notably, several plants possess multi-target actions, reflecting the polypharmacological potential of botanical therapies for diabetes management [66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138,139,140,141,142,143,144,145,146,147,148,149,150,151,152,153,154,155].
7. Materials and Methods
This review was carried out as a narrative survey with systematic search elements, guided by key PRISMA recommendations. The search was performed on PubMed, Scopus, and Web of Science for publications between January 2000 and June 2025, using broad and specific search strings such as “diabetes”, “hypoglycemic plants”, “Romania”, “phytotherapy”, “antidiabetic activity”, “in vitro”, “in vivo”, and “clinical trial”. We limited inclusion to peer-reviewed, full-text articles in English or Romanian that investigated wild or cultivated medicinal plants traditionally used in Romania for glycemic control and provided phytochemical analyses (e.g., flavonoid, alkaloid, or terpenoid profiling) and/or pharmacological assessments (enzyme assays, cell-based glucose uptake studies, animal models, or human trials). Non-original reports, abstracts, commentaries, and studies lacking clear phytochemical or efficacy data were excluded. Priority was given to controlled in vivo experiments and clinical investigations, though older or foundational phytochemical studies were retained where recent data were sparse. Extracted information encompassed plant identity, part used, extraction techniques, active constituents, experimental models, and observed outcomes. The goal was to present a comprehensive, qualitative overview of the phytochemical constituents and reported antidiabetic effects of Romanian medicinal plants rather than to conduct a formal meta-analysis or bias appraisal.
8. Study Limitations
Most studies rely on in vitro or animal models, and human clinical trials are limited. Additionally, herbal formulations vary in composition, which may affect reproducibility and efficacy across populations
9. Conclusions
Our review demonstrates that many medicinal plants used in Romanian traditional medicine possess significant antidiabetic activity, as shown by numerous in vitro and in vivo studies. Plants such as Urtica dioica, Silybum marianum, and Momordica charantia stand out for their strong preclinical evidence and preliminary clinical results. Their mechanisms of action, including insulin-mimetic effects, stimulation of β-cell regeneration, and reduction in oxidative stress, highlight their clinical relevance and support the idea that these species could be considered as adjuncts in diabetes management.
Despite these encouraging findings, the current body of clinical evidence remains limited. Therefore, future research should prioritize the standardization of plant extracts to ensure consistency and reproducibility across studies. Moreover, there is a clear need for well-designed, randomized controlled clinical trials to validate the efficacy and safety of these promising medicinal plants in human populations. Mechanistic studies that clarify the molecular pathways involved and incorporate biomarkers of glycemic control will also be important for understanding which patient groups are most likely to benefit from phytotherapy.
Bridging the gap between traditional use and clinical application will require collaboration between ethnobotanical research, pharmacology, and clinical sciences. By focusing on these directions, we can move closer to integrating the most effective Romanian medicinal plants into evidence-based strategies for diabetes prevention and treatment.
Conceptualization, R.M.V. and C.E.S.; Methodology, D.D. and N.S.A.; Software, and N.E.C.; Validation, R.M.V. and G.-A.S.; Formal analysis, D.M.T. and D.D.; Investigation, Resources, C.E.S. and N.E.C.; Data curation, D.M.T. and G.-A.S.; Writing—original draft preparation, D.D., and N.E.C.; Writing—review and editing, R.M.V., and C.E.S.; Visualization, G.-A.S. and D.M.T.; Supervision, R.M.V. and N.E.C.; Project administration, D.M.T. and C.E.S.; Funding acquisition, D.D. and G.-A.S. All authors have read and agreed to the published version of the manuscript.
Data are contained within the article.
There was no support received (administrative and technical support, or donations in kind) to realize the study.
The authors declare no conflicts of interest.
Footnotes
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.
Figure 1 Comparative mechanisms in the development of type 1 and type 2 diabetes mellitus: immune-mediated β-cell destruction versus cytokine-induced insulin resistance (
Figure 2 Bioactive compounds from medicinal plants exert antidiabetic effects through multiple pathways, including pancreatic β-cell stimulation and regeneration, inhibition of intestinal carbohydrate-digesting enzymes, modulation of hepatic glucose production, enhancement of peripheral insulin sensitivity, and oxidative stress reduction. Created with Biorender
Genetic and Environmental Factors Influencing Type 2 Diabetes Susceptibility Across Populations.
| Factor/Gene (Variant) | Description | Population (s)/Effect | Reference |
|---|---|---|---|
| South Asian origin populations | Heightened sensitivity to diabetes and increased insulin resistance; protective Pro12Ala PPARγ polymorphism in Caucasians shows no protection in Indians | Indian descent vs. Caucasians | [ |
| Candidate genes (overall) | >50 genes associated with T2DM have been studied; results often inconsistent due to small samples, ethnic differences, environment, gene–environment interplay | Various worldwide populations | – |
| PPARγ Pro allele | Variant reduces insulin sensitivity and markedly increases T2DM risk; carries significant burden of cases | ~98% of Europeans carry ≥1 Pro allele (~25% of Caucasian T2DM cases) | [ |
| KCNJ11 (Lys allele) and ABCC8 (Ala variant) | Both encode subunits of the ATP-sensitive K+ channel (Kir6.2/SUR1) critical for insulin secretion; associated with T2DM | Pancreatic β-cells | [ |
| CAPN10 | Encodes calpain-10, a Ca2+-dependent protease; altered activity impairs insulin secretion; higher genetic risk in Mexican-Americans, lower in Caucasians | Mexican-American (↑ risk); Caucasian (↓ risk) | [ |
| Viral infections (EBV, Coxsackie, mumps, CMV) | Proposed triggers for diabetes via direct β-cell destruction or autoimmune activation | – | – |
Plant-based hypoglycemic products used in Romania for the treatment of diabetes mellitus.
| Plant Species (Family) | Active Compounds | Effective Concentration (In Vitro In Vivo) | IC50/EC50 (Target/Assay) | Mechanism of Action |
|---|---|---|---|---|
| Dillenia indica (Dilleniaceae), elephant apple | Tannins, pentacyclic triterpenic alcohols (betulin, betulinic acid, betulinic aldehyde), sterols (β-sitosterol), flavonosides, phenolic compounds | Betulinic acid (approx. 0.3% DW; tested as part of methanolic fruit extract at 100–400 μg/mL, in vitro) | α-glucosidase IC50: 30.75 μg/mL (methanolic fruit extract) | Similar to glibenclamide; has beneficial effects on the histopathological changes in the pancreas, liver, and kidneys [ |
| Momordica charantia (Cucurbitaceae), bitter melon | Polypeptide-P, gurmarin (“plant insulin”), bitter principles (charantin) | mcIRBP peptide (natural content in fresh fruit: approx. 0.5–1.2 mg/g; tested in vitro/in vivo); cucurbitane triterpenoids (content not specified; tested at 10 μM, in vitro) | Charantin α-glucosidase IC50: 10.8 μg/mL (isolated compound); mcIRBP EC50: 0.96 μg/mL | Action begins 30–60 min after oral administration with peak activity at 4 h; mimics bovine insulin, has antioxidant properties, regenerates β-cells, stimulates insulin secretion (sulfonylurea-like mechanism), increases glycogenogenesis, insulin-like activity [ |
| Glycyrrhiza glabra (Fabaceae), licorice | Sterols, flavones, tannins, enzymes, saponins, volatile oils | Glycyrrhizin (natural content in root: approx. 2–9% DW; tested as part of ethanolic root extract at 10–100 μM, in vitro) | α-glucosidase IC50: 12.8 μg/mL (ethanolic root extract) | Acts as a PPAR agonist, improving hyperinsulinemia [ |
| Trigonella foenum-graecum (Fabaceae), fenugreek | Sterols (lecithin, phytic acid, other phytosterols), bitter substances, volatile oil, tannins, saponins, coumarins | Diosgenin (natural content in seeds: approx. 0.1–0.3%; tested at 8–19 mM, in vitro); ethanolic seed extract (galactomannan: 30–50%; tested at 3–11 μg/mL, in vitro) | Diosgenin EC50 (GLUT4): 8 mM (pure compound); α-glucosidase IC50: 30.15 μg/mL (ethanolic seed extract) | Stimulates glucose transport; regulates glycolysis, gluconeogenesis, and fatty acid synthesis; reduces oxidative stress associated with hyperglycemia; and delays the progression of diabetic retinopathy and neuropathy [ |
| Pueraria lobata (Fabaceae), kudzu | Sterols, coumarins, saponins, isoflavones | Puerarin (natural content in root: approx. 3–9%; tested at 100 μM, in vitro; as part of ethanolic root extract) | α-glucosidase IC50: 45.4 μg/mL (ethanolic root extract) | Restores secretory function of β-cells, enhances insulin secretion, inhibits glucose absorption; isoflavones act as PPAR agonists, block IL-12 synthesis, inhibit TH-1 differentiation; prevent and delay T2DM and cardiovascular complications [ |
| Phaseolus vulgaris (Fabaceae), common bean | Sulfur-containing amino acids, alkaloids, anthocyanins, flavonoids, saponins, tannins, terpenoids | Phaseolamin (natural content in extract: approx. 0.5–2%; tested as part of aqueous seed extract at 100 μg/mL, in vitro | α-amylase IC50: 44.2 μg/mL (aqueous seed extract) | Stimulates insulin secretion, increases glucose tolerance; potency similar to tolbutamide [ |
| Pimpinella anisum (Apiaceae), anise | Volatile oil (80–90% anethole, methyl chavicol or isomethylchavicol, small amounts of anisic ketones and aldehydes) | Anethole (main component, essential oil; tested as methanolic seed extract at 50–200 μg/mL, in vitro) | α-glucosidase IC50: ~67 μg/mL (methanolic seed extract) | Increases glutathione-S-transferase activity, has antioxidant effect, reduces cholesterol and triglyceride levels [ |
| Apium graveolens (Apiaceae), celery | Sedanenolides, neocnidilide, neophytadiene, essential oil (limonene, β-selinene, nerolidol, α-selinene, β-pinene, carvone, β-myrcene) | Phthalides and apigenin (main actives; natural content not specified; tested as ethanolic seed extract at 100–400 μg/mL, in vitro) | Not available (no IC50 for glucose uptake); α-glucosidase IC50: ~80 μg/mL (ethanolic seed extract) | Induces insulin receptor phosphorylation |
| Daucus carota (Apiaceae), carrot | Mineral salts, carotenoids, vitamins (C, B-complex, folic acid), fibers (cellulose and lignin), acids (glutamic, succinic, lactic, glycolic), polyphenolcarboxylic acids (caffeic acid), anthocyanins | Carotenoids, caffeic acid derivatives (natural content: β-carotene ~7–14 mg/100g; extract tested at 100–400 μg/mL, in vitro) | α-glucosidase IC50: 75 μg/mL (aqueous root extract) | Improves glucose tolerance |
| Thymus vulgaris (Lamiaceae), thyme | Volatile oils (thymol, p-cymene, borneol, geraniol, carvacrol, linalool, bornyl acetate, α-pinene), saponins, ursolic acid, oleanolic acid, caffeic acid, flavonoids (luteolin, luteolin-7-glycoside), sterols, waxes, triterpenes, bitter principles | Thymol, carvacrol (essential oil; tested as ethanolic aerial part extract at 50–200 μg/mL, in vitro) | α-glucosidase IC50: 49.8 μg/mL (ethanolic aerial part extract) | Reduces hyperinsulinemia, increases SOD (superoxide dismutase) concentration, counteracts oxidative effects, preventing diabetic complications [ |
| Lavandula angustifolia (Lamiaceae), lavender | Volatile oil (linalyl acetate, linalyl butyrate, geraniol, free linalool, linalyl valerate, borneol, α-pinene), coumarins, caryophyllene, tannins, bitter principles | Linalool (main in oil; natural content not specified; hydroalcoholic flower extract tested at 50–200 μg/mL, in vitro) | α-glucosidase IC50: 72.8 μg/mL (hydroalcoholic flower extract) | Stimulates glucose uptake in muscle cell cultures, increases insulin secretion via a sulfonylurea-like mechanism [ |
| Salvia officinalis (Lamiaceae), sage | Essential oil, thujone, α- and β-pinene, camphor, borneol, cineole, tannins, sitosterols, estrogen-like substances, bitter principles (picrosalvin), nicotinic acid, caffeic acid, fumaric acid, resins, vitamins B1 and C, mineral salts | Thujone, rosmarinic acid (thujone ~30–50% oil; extract tested at 50–200 μg/mL, in vitro) | α-glucosidase IC50: 59.4 μg/mL (ethanolic leaf extract) | Stimulates insulin production and secretion; increases glucose utilization in tissues similarly to metformin; inhibits glucose absorption [ |
| Phyllanthus emblica (Phyllanthaceae), Indian gooseberry | Tannins (gallic acid, ellagic acid), norsesquiterpenoids, flavonosides | Gallic/ellagic acid (main actives; total phenolics ~50–100 mg GAE/g; extract tested at 50–200 μg/mL, in vitro) | α-glucosidase IC50: 46.2 μg/mL (ethanolic fruit extract) | Inhibits neuropathic pain by modulating oxidative stress, nitrite levels, cytokines (IL-1β, TGF-β1); used as a strong antioxidant and immunomodulator; inhibits α-amylase and α-glucosidase; reduces severity of acute pancreatitis and promotes pancreas repair; lowers cholesterol and triglycerides, improves liver function via ALT normalization [ |
| Asparagus racemosus (Asparagaceae), shatavari | Tannins, saponins (shatavarins A and B, filiasparoside C, asparanin A), isoflavones, satavarin (a glycoside of glucose, rhamnose, and sarsapogenin), vanillin, coniferin, sarsaponin | Shatavarin IV (main saponin; content ~0.1–0.2% root; extract tested at 50–200 μg/mL, in vitro) | α-glucosidase IC50: 85 μg/mL (ethanolic root extract) | Tannic acid induces insulin receptor phosphorylation, mediates GLUT-4 translocation; inhibits adipogenesis-related gene expression; prevents diabetic nephropathy; used for polydipsia in diabetes insipidus [ |
| Azadirachta indica (Meliaceae), Neem | Bitter compounds: nimbin, nimbinin, and nimbidin. Leaves contain quercetin, beta-sitosterol, the diterpenoids mahogany and nimbogone, vitamins (A, E, C, riboflavin, and niacin), and minerals (Se, Zn, Cu, Mg, Cr) | Nimbin, nimbidin (main actives; extract tested at 50–200 μg/mL, in vitro) | α-amylase IC50: 52.4 μg/mL (aqueous leaf extract) | Decreases glucose absorption |
| Garcinia cambogia (Clusiaceae), garcinia | Tartaric, citric, and phosphoric acids; two poly-isoprenylated benzophenones; mangostin derivatives of camboginol and cambogin | Hydroxycitric acid (HCA; content in fruit rind ~16–20%; extract tested at 100–500 μg/mL, in vitro) | α-amylase IC50: 60.5 μg/mL (aqueous fruit extract) | The mentioned acids suppress lipogenesis by inhibiting citrate lyase, which assists in converting excess carbohydrates into fat |
| Cinnamomum zeylanicum (Lauraceae), cinnamon tree | Diterpenes, essential oil rich in eugenol, cinnamaldehyde, cinnamyl acetate, cinnamic alcohol, and 2-hydroxycinnamaldehyde, coumarins, terpenes, tannins, proanthocyanidins | Cinnamaldehyde, polyphenols (content in bark oil: cinnamaldehyde 65–80%; extract tested at 10–100 μg/mL, in vitro) | α-glucosidase IC50: 16.3 μg/mL (aqueous bark extract) | Mimics insulin action (via tannic acid) |
| Panax quinquefolius (Araliaceae), American ginseng | Saponozide, saponins, tannins, bitter principles, vitamins A, B1, B2, B5, B6, B12, D3, E, folic acid, nicotinamide, mucilage, waxes, Zn, K, Fe, Si | Ginsenosides (content in root: 3–5%; extract tested at 10–100 μg/mL, in vitro) | α-glucosidase IC50: 38.2 μg/mL (ethanolic root extract) | Stabilizes blood glucose levels by increasing tissue insulin sensitivity |
| Ginkgo biloba (Ginkgoaceae), maidenhair tree | Diterpenes (ginkgolides A, B, C and ginkgolide J), sesquiterpenes (bilobalide); leaves contain flavonols (kaempferol, quercetin, isorhamnetin), biflavones (bilobetin, ginkgetin, isoginkgetin), catechins, proanthocyanidins, sterols, 6-hydroxymurenic acid | Ginkgolide/flavone (leaf extract; content: ginkgolide 0.5–1% DW; tested at 50–200 μg/mL, in vitro) | α-glucosidase IC50: 41.3 μg/mL (ethanolic leaf extract) | Improves blood circulation and prevents complications |
| Silybum marianum (Asteraceae), milk thistle | Saponins, essential oil; fruits contain silymarin (silibinin, silidianin, silicristin), betaine hydrochloride, amino acids (L-cysteine, glycine, glutamic acid, D-2-aminobutyric acid, D-leucine, tyramine), lipids (3–4%), polyhydroxyphenylchromones, fumaric acid | Silymarin (fruit/seed extract; content: silymarin 1.5–3% seeds; tested at 50–200 μg/mL, in vitro) | α-glucosidase IC50: 32.4 μg/mL (methanolic seed extract) | Stimulates glucose transport |
| Acorus calamus (Araceae), sweet flag | Volatile oil (1.5–3.5%) containing asarone, azaril aldehyde, methyl isoeugenol, linalool, sesquiterpenes, α-pinene, camphene, camphor, eugenol, tannins, bitter substances, resins, mineral salts | β-asarone (rhizome oil; content: 1–3% in oil; extract tested at 25–100 μg/mL, in vitro) | α-glucosidase IC50: 28.1 μg/mL (ethanolic rhizome extract) | Increases insulin release and secretion similarly to gliclazide; inhibits α-glucosidase and improves insulin resistance; inhibits preadipocyte differentiation into adipocytes; β-asarone attenuates ERK1/2 phosphorylation involved in early adipogenesis [ |
| Achillea millefolium (Asteraceae), yarrow | Volatile oil, chamazulene, azulenes, asarone, proazulenes, cineole, borneol, pinene, limonene, caryophyllene, achilleine, achilleic acid, organic acids (formic, valeric), tannins | Chamazulene, apigenin (extract tested at 50–200 μg/mL, in vitro) | α-glucosidase IC50: 61.2 μg/mL (methanolic aerial part extract) | Regenerates β-pancreatic cells; hypolipidemic effect [ |
| Arctium lappa (Asteraceae), burdock | Arctiin, essential oil, flavonoids, inulin, palmitic acid, caffeic acid, stigmasterol, sitosterol, bitter substances, carotenoids, mineral salts | Arctiin, inulin (inulin content: 30–50% root DW; extract tested at 100–400 μg/mL, in vitro) | α-glucosidase IC50: 37.4 μg/mL (aqueous root extract) | β-sitosterol-D glucopyranoside inhibits α-glucosidase; inulin improves glucose tolerance [ |
| Artemisia absinthium (Asteraceae), wormwood | Essential oil (0.5%) with myrcene, α-pinene, thujone, nerol, camphor, limonene, phellandrene, β-caryophyllene, sesquiterpene lactones (artabsin, absinthin) | Thujone, absinthin (oil: thujone 30–50%; extract tested at 50–200 μg/mL, in vitro) | α-glucosidase IC50: 43.1 μg/mL (methanolic aerial part extract) | Hypoglycemic effects similar to metformin; stimulates glycogenogenesis [ |
| Cichorium intybus (Asteraceae), chicory | Inulin, cichorin, chicoric acid, volatile oil, flavonoids, anthocyanins, bitter triterpenes (lactucopicrin), tannins, mineral salts | Inulin (root content: 15–20% DW; methanolic root extract tested at 100–400 μg/mL, in vitro) | α-glucosidase IC50: 45.5 μg/mL (methanolic root extract) | Improves glucose tolerance; reduces hepatic glucose-6-phosphatase activity [ |
| Cynara scolymus (Asteraceae), artichoke | Polyphenols (caffeic acid, chlorogenic acid, cynarin), flavones, potassium, and magnesium salts | Cynarin, chlorogenic acid (leaf content: chlorogenic acid 1–2% DW; extract tested at 50–200 μg/mL, in vitro) | α-glucosidase IC50: 36.5 μg/mL (methanolic leaf extract) | Insulin-mimetic, hypolipidemic, antioxidant effects [ |
| Taraxacum officinale (Asteraceae), dandelion | Flavones (rutoside, hyperoside, quercetol), hydroxycinnamic acid derivatives (caffeic and chlorogenic acid), catechin tannins, sterols, triterpenes, carotenoids, coumarins, mucilage | Caffeic acid, inulin (root: inulin 15–25% DW; extract tested at 100–400 μg/mL, in vitro) | α-glucosidase IC50: 42.7 μg/mL (aqueous root extract) | Tannins reduce amylase activity by chelating calcium; hypolipidemic effects [ |
| Sambucus nigra (Caprifoliaceae), elderberry | Anthocyanins, essential oil, quercetin derivatives, cyanogenic glycoside (sambunigrin), mucilage, flavonosides | Anthocyanins, flavonols (flower content: total anthocyanins ~200–400 mg/100g DW; extract tested at 50–200 μg/mL, in vitro) | α-glucosidase IC50: 55.1 μg/mL (aqueous flower extract) | Insulin-like effect; increases insulin secretion and release [ |
| Spinacia oleracea (Chenopodiaceae), spinach | Flavonoids (quercetin, myricetin, kaempferol, apigenin, luteolin, spinacetin), phenolic acids (ferulic, coumaric), carotenoids, vitamins (A, E, C, K, folic acid), minerals | Quercetin, kaempferol (leaf content: quercetin 10–30 mg/100 g FW; extract tested at 50–200 μg/mL, in vitro) | α-glucosidase IC50: 62.3 μg/mL (aqueous leaf extract) | Potentiates insulin and protects β-pancreatic cells from oxidative damage similar to glibenclamide [ |
| Juglans regia (Juglandaceae), walnut | Riboflavin, niacin, vitamin C, ellagic tannins, inositol, juglone, essential oil. The pericarp contains juglone (5-hydroxy-1,4-naphthoquinone), tannins, etheric oil, chlorophylls, starch, pectins, organic acids | Juglone, ellagitannins (leaf content: juglone ~20–50 mg/100 g; extract tested at 50–200 μg/mL, in vitro) | α-glucosidase IC50: 35.2 μg/mL (methanolic leaf extract) | Increases tissue sensitivity to insulin, induces phosphorylation of insulin receptors, involved in GLUT-4 translocation, and inhibits the expression of certain genes [ |
| Aloe vera, (Liliaceae), aloe | Aloe-emodin, aloin A and B, aloe-emodin, chrysophanol (free or glycosidic), resins (10–20%), essential oil in small quantities, mineral salts | Aloin, aloe-emodin (gel content: aloin 0.1–0.4%; extract tested at 50–200 μg/mL, in vitro) | α-glucosidase IC50: 50.9 μg/mL (aqueous gel extract) | Reduces blood glucose in type 2 diabetes with insulin-like activity. Lowers blood lipids and triglycerides |
| Asparagus officinalis (Liliaceae), asparagus | Asparagine, lipids, carbohydrates, phytohormones, enzymes, sterols, cellulose, mineral salts | Asparagine, saponins (root: asparagine ~0.03%; extract at 50–200 μg/mL, in vitro) | α-glucosidase IC50: 69.3 μg/mL (methanolic root extract) | Potentiates insulin and protects β-pancreatic cells from oxidative damage [ |
| Allium cepa (Liliaceae), onion | Cycloalliin, methylalliin, propylalliin, cepaenes, flavonoid derivatives (quercetin and kaempferol glycosides), saponins, amines, enzymes | Quercetin, alliin (bulb: quercetin ~10–30 mg/100 g FW; extract at 50–200 μg/mL, in vitro) | α-glucosidase IC50: 40.1 μg/mL (aqueous bulb extract) | Hypoglycemic effect similar to glibenclamide and insulin [ |
| Allium sativum (Liliaceae), garlic | Sulfur compounds; flavonosides; vitamins (A, B1, B2, C); phytosterol; glycerides of palmitic, stearic, oleic, linoleic, and myristic acids; allicin; steroid derivatives (erubosides) | Allicin, alliin (bulb: allicin ~0.1–0.5%; extract at 50–200 μg/mL, in vitro) | α-glucosidase IC50: 28.9 μg/mL (ethanolic bulb extract) | Hypoglycemic and hypolipidemic effects, similar to glibenclamide and insulin [ |
| Viscum album (Loranthaceae), mistletoe | Triterpenic saponins, oleanolic acid derivatives, viscotoxin, viscol, amines (choline, acetylcholine), β-phenylethylamine, lipids, glycosidic substances | Oleanolic acid glycosides, viscotoxins (leaf: oleanolic acid ~0.2–0.4%; extract at 50–200 μg/mL, in vitro) | α-glucosidase IC50: 58.4 μg/mL (aqueous leaf extract) | Increases insulin secretion and peripheral glucose utilization; hypoglycemic effect comparable to glibenclamide [ |
| Morus alba / nigra (Moraceae), mulberry | Citric, aspartic, folic, and folinic acids, volatile compounds, β-carotene, tannins, phenolic compounds, alkaloids, anthocyanins, minerals, vitamins C, B2, B3 | DNJ (1-deoxynojirimycin, leaf: 0.1–0.2%; extract at 50–200 μg/mL, in vitro) | α-glucosidase IC50: 32.1 μg/mL (methanolic leaf extract) | Stimulates cellular glucose uptake; insulin-mimetic effect [ |
| Alchemilla vulgaris (Rosaceae), lady mantle | Ellagic tannins, polyphenolcarboxylic acids (chlorogenic acid), saponins, flavonoids, ellagic and luteic acid, fatty compounds (stearic and palmitic acids), phytosterols, mineral salts | Ellagitannins, chlorogenic acid (aerial part: ellagitannins ~1%; extract at 50–200 μg/mL, in vitro) | α-glucosidase IC50: 57.6 μg/mL (aqueous aerial part extract) | Improves glucose tolerance; anorexigenic effect [ |
| Fragaria ananassa (Rosaceae), strawberry | Fragarol; oily substances; citric, malic, and ascorbic acids; anthocyanins; citrol; polyphenols; vitamins A, B, C | Anthocyanins, ellagic acid (fruit: anthocyanins 20–50 mg/100 g FW; extract at 50–200 μg/mL, in vitro) | α-glucosidase IC50: 47.9 μg/mL (methanolic fruit extract) | Inhibits α-glucosidase; antioxidant effect [ |
| Rosa canina (Rosaceae), rosehip | Carotenoids, terpenoids, anthocyanins, vitamins C, B1, B2, PP, K | Ascorbic acid, flavonoids (fruit: ascorbic acid 0.3–0.7%; extract at 50–200 μg/mL, in vitro) | α-glucosidase IC50: 53.2 μg/mL (methanolic fruit extract) | Stimulates insulin secretion [ |
| Agrimonia eupatoria (Rosaceae), common agrimony | Catechin-type tannins, gallotannins, ellagitannins, free quercetin, hyperin, rutin, apigenin and luteolin glycosides, bitter substances, traces of essential oil, ursolic acid, organic acids, mucilage, coumarins, vitamins (C, K), triterpenes, fatty acids, flavonoids, saponins | Catechin, ellagitannins (aerial part: ellagitannins ~0.8%; extract at 50–200 μg/mL, in vitro) | α-glucosidase IC50: 50.2 μg/mL (methanolic aerial part extract) | Stimulates glucose uptake in cultured muscle cells |
| Citrus aurantium (Rutaceae), bitter orange | Citric and malic acids, calcium and potassium citrate, vitamins A, B1, B2, B3, D, E, PP, essential oil (limonene, nerolidol, terpineol, farnesol, pinene, phellandrene), flavonoids | Hesperidin, synephrine (peel: hesperidin ~0.2–0.5%; extract at 50–200 μg/mL, in vitro) | α-glucosidase IC50: 54.5 μg/mL (ethanolic fruit peel extract) | Reduces insulin resistance, lowers LDL-cholesterol and triglycerides, antioxidant activity [ |
| Lycopersicon esculentum (Solanaceae), tomato | Flavonoids, lycopene, organic acids (malic, pectic, citric), vitamins A, B1, B2, B6, C, PP, E, K, β-carotene, minerals | Lycopene, β-carotene (fruit: lycopene 2–5 mg/100g FW; extract at 50–200 μg/mL, in vitro) | α-glucosidase IC50: 60.1 μg/mL (methanolic fruit extract) | Stimulates insulin secretion, improves insulin resistance [ |
| Urtica dioica (Urticaceae), stinging nettle | Polyphenols, amino acids, sterols, essential oil, sitosterols, ursolic acid, vitamins C, B2, K, chlorophylls, protoporphyrin, β-carotene, alkaloids | Phenolic compounds, sterols (leaf: total phenolics 20–40 mg/g DW; extract at 50–200 μg/mL, in vitro) | α-glucosidase IC50: 44.7 μg/mL (methanolic leaf extract) | Insulin-mimetic effect, reduces LDL-cholesterol [ |
| Vitis vinifera (Vitaceae), grapevine | Polyphenols, resveratrol, anthocyanins, flavonosides, tartaric and malic acid, tannins, minerals, vitamins A, C, E | Resveratrol, proanthocyanidins (seed: proanthocyanidins 5–10%; extract at 50–200 μg/mL, in vitro) | α-glucosidase IC50: 38.6 μg/mL (methanolic seed extract) | Antioxidant, reduces oxidative stress, insulin-like effect, lowers glucose absorption, regenerates β-pancreatic cells [ |
| Vaccinium arctostaphylos (Ericaceae), bearberry | Flavonoids (quercetin), tannins | Quercetin, arbutin (leaf: arbutin 5–7% DW; extract at 50–200 μg/mL, in vitro) | α-amylase IC50: 42.2 μg/mL (aqueous leaf extract) | Inhibits α-amylase [ |
| Hippophae rhamnoides (Elaeagnaceae), sea buckthorn | Carotenoids, flavonoids, proanthocyanidins, catechin tannins, triterpenic acids, vitamin C | Carotenoids, flavonoids, vitamin C (fruit: carotenoids 3–8 mg/100g FW; extract at 50–200 μg/mL, in vitro) | α-glucosidase IC50: 48.3 μg/mL (ethanolic fruit extract) | Inhibits α-glucosidase [ |
IC50—half maximal inhibitory concentration; FW—fresh weight; DW—dry weight; n.a.—not available.
Distribution of the antidiabetic medicinal plants by experimental model and duration in antidiabetic research.
| Experiment Duration/Model | Plants Tested in This Model |
|---|---|
| Cell culture (glucose uptake/GLUT4, 24–48 h, insulin secretion) | Momordica charantia, Trigonella foenum-graecum, Pueraria lobata, Glycyrrhiza glabra, Phaseolus vulgaris, Agrimonia eupatoria, Spinacia oleracea, Juglans regia, (unele studii pentru Allium cepa, Allium sativum, Morus alba/nigra, Rosa canina, Apium graveolens, Silybum marianum, Cichorium intybus, Asparagus officinalis, Aloe vera, Urtica dioica, Vitis vinifera) |
| Enzyme inhibition (α-glucosidase/α-amylase, 30–60 min, in vitro enzyme assay) | Dillenia indica, Glycyrrhiza glabra, Phaseolus vulgaris, Trigonella foenum-graecum, Pueraria lobata, Apium graveolens, Daucus carota, Thymus vulgaris, Lavandula angustifolia, Salvia officinalis, Pimpinella anisum, Silybum marianum, Acorus calamus, Achillea millefolium, Arctium lappa, Artemisia absinthium, Cichorium intybus, Cynara scolymus, Taraxacum officinale, Sambucus nigra, Spinacia oleracea, Juglans regia, Urtica dioica, Vitis vinifera, Vaccinium arctostaphylos, Hippophae rhamnoides, Alchemilla vulgaris, Fragaria ananassa, Rosa canina, Citrus aurantium, Lycopersicon esculentum, Morus alba/nigra, Allium cepa, Allium sativum, Viscum album, Asparagus racemosus, Azadirachta indica, Garcinia cambogia, Cinnamomum zeylanicum, Panax quinquefolius, Phyllanthus emblica |
| Animal studies (in vivo, 2–8 weeks, effect on glycemia, β-cell, complications, etc.) | Momordica charantia, Trigonella foenum-graecum, Glycyrrhiza glabra, Silybum marianum, Achillea millefolium, Cynara scolymus, Taraxacum officinale, Sambucus nigra, Juglans regia, Urtica dioica, Rosa canina, Citrus aurantium, Hippophae rhamnoides, Allium cepa, Allium sativum, Viscum album, Azadirachta indica, Panax quinquefolius, Phyllanthus emblica, Cichorium intybus, Pueraria lobata, Spinacia oleracea, Alchemilla vulgaris, Fragaria ananassa, Agrimonia eupatoria, Asparagus racemosus, Morus alba/nigra, Acorus calamus, Daucus carota, Apium graveolens, Arctium lappa, Lavandula angustifolia, Salvia officinalis, Thymus vulgaris, Vaccinium arctostaphylos, Aloe vera, Vitis vinifera, Garcinia cambogia, Dillenia indica, Phyllanthus emblica, Pimpinella anisum, Thymus vulgaris |
| Human/clinical studies (weeks–months, when available) | Momordica charantia, Trigonella foenum-graecum, Silybum marianum, Cinnamomum zeylanicum, Allium sativum, Vitis vinifera, Salvia officinalis, Panax quinquefolius, Morus alba/nigra, Aloe vera, Glycyrrhiza glabra |
Ethnobotanical categorization of antidiabetic plants based on their occurrence in Romania.
| Wild-Growing Plants in Romania (Native Wild Flora) | Not Wild-Growing but Cultivated in Romania: | Neither Wild-Growing nor Commonly Cultivated in Romania: |
|---|---|---|
| Apium graveolens Daucus carota Thymus vulgaris Lavandula angustifolia Salvia officinalis Achillea millefolium Arctium lappa Artemisia absinthium Silybum marianum Cichorium intybus Taraxacum officinale Sambucus nigra Juglans regia Acorus calamus Viscum album Morus alba/nigra Alchemilla vulgaris Rosa canina Agrimonia eupatoria Urtica dioica Vaccinium arctostaphylos Hippophae rhamnoides | Glycyrrhiza glabra Trigonella foenum-graecum Phaseolus vulgaris Spinacia oleracea Asparagus officinalis Fragaria ananassa Citrus aurantium Lycopersicon esculentum Pimpinella anisum Apium graveolens Allium cepa Allium sativum Vitis vinifera | Dillenia indica Momordica charantia Pueraria lobata Phyllanthus emblica Asparagus racemosus Azadirachta indica Garcinia cambogia Cinnamomum zeylanicum Panax quinquefolius Ginkgo biloba Aloe vera |
Molecular target and pathway distribution of antidiabetic medicinal plants.
| Molecular Target/Pathway | Medicinal Plants (Main Bioactive Compounds) |
|---|---|
| AMPK activation | Momordica charantia (charantin), Silybum marianum (silymarin), Vitis vinifera (resveratrol), Viscum album, Arctium lappa (oleanolic acid), Spinacia oleracea (quercetin), Pueraria lobata (puerarin), Glycyrrhiza glabra (possibly via anti-inflam.), Lavandula angustifolia (rosmarinic acid) |
| PPAR-γ modulation | Glycyrrhiza glabra (glycyrrhizin), Pueraria lobata (puerarin), Viscum album, Silybum marianum, Vitis vinifera |
| PI3K/Akt → GLUT4 translocation | Trigonella foenum-graecum (diosgenin), Momordica charantia (mcIRBP), Glycyrrhiza glabra, Pueraria lobata, Allium cepa (quercetin), Spinacia oleracea |
| α-glucosidase inhibition | Morus alba/nigra (DNJ), Phaseolus vulgaris (phaseolamin), Cinnamomum zeylanicum (cinnamaldehyde), Dillenia indica, Arctium lappa (arctiin), Vaccinium arctostaphylos, Salvia officinalis, Apium graveolens, Cichorium intybus, Silybum marianum, Acorus calamus, Achillea millefolium, Cynara scolymus, Taraxacum officinale, Sambucus nigra, Allium cepa, Urtica dioica, Fragaria ananassa, Rosa canina, Hippophae rhamnoides, Allium sativum, Azadirachta indica, Asparagus racemosus, Morus alba, Citrus aurantium, Phyllanthus emblica, Vitis vinifera, Garcinia cambogia, Panax quinquefolius, Aloe vera, Vitis vinifera |
| α-amylase inhibition | Dillenia indica, Phaseolus vulgaris, Taraxacum officinale, Garcinia cambogia, Vaccinium arctostaphylos, Azadirachta indica |
| Insulin receptor agonism/similar effect | Momordica charantia (mcIRBP, polypeptide-p), Allium sativum (allicin), Urtica dioica, Salvia officinalis, Citrus aurantium |
| DPP-IV inhibition | Trigonella foenum-graecum (trigonelline), Glycyrrhiza glabra, Salvia officinalis, Citrus aurantium |
| SGLT inhibition | Trigonella foenum-graecum (trigonelline), Morus alba (DNJ), Citrus aurantium |
| Antioxidant/Anti-inflammatory | Vitis vinifera, Sambucus nigra, Rosa canina, Spinacia oleracea, Lavandula angustifolia, Achillea millefolium, Thymus vulgaris, Fragaria ananassa, Phyllanthus emblica, Asparagus officinalis, Artemisia absinthium |
| β-cell regeneration/insulin secretion | Pueraria lobata, Sambucus nigra, Allium sativum, Salvia officinalis, Citrus aurantium, Agrimonia eupatoria, Artemisia absinthium |
| Miscellaneous (hepatic glucose regulation, lipid metabolism) | Cichorium intybus (hepatic effect), Garcinia cambogia (ATP citrate lyase), Cynara scolymus (lipid/glucose), Aloe vera (GLUT4), Hippophae rhamnoides |
1. Sun, H.; Saeedi, P.; Karuranga, S.; Pinkepank, M.; Ogurtsova, K.; Duncan, B.B.; Stein, C.; Basit, A.; Chan, J.C.; Mbanya, J.C.
2. Ahmad, E.; Lim, S.; Lamptey, R.; Webb, D.R.; Davies, M.J. Type 2 Diabetes. Lancet; 2022; 400, pp. 1803-1820. [DOI: https://dx.doi.org/10.1016/S0140-6736(22)01655-5]
3. Matheus, A.S.; Tannus, L.R.; Cobas, R.A.; Palma, C.C.; Negrato, C.A.; Gomes, M.B. Impact of Diabetes on Cardiovascular Disease: An Update. Int. J. Hypertens.; 2013; 2013, 653789. [DOI: https://dx.doi.org/10.1155/2013/653789]
4. Ştefan, A.G.; Clenciu, D.; Mitrea, A.; Vladu, I.M.; Protasiewicz-Timofticiuc, D.C.; Roşu, M.M.; Maria, D.T.; Dinu, I.R.; Gheonea, T.C.; Vladu, B.E.
5. Chiles, N.S.; Phillips, C.L.; Volpato, S.; Bandinelli, S.; Ferrucci, L.; Guralnik, J.M.; Patel, K.V. Diabetes, Peripheral Neuropathy, and Lower-Extremity Function. J. Diabetes Complicat.; 2014; 28, pp. 91-95. [DOI: https://dx.doi.org/10.1016/j.jdiacomp.2013.08.007]
6. Mota, M.; Popa, S.G.; Mota, E.; Mitrea, A.; Catrinoiu, D.; Cheta, D.M.; Guja, C.; Hancu, N.; Ionescu-Tirgoviste, C.; Lichiardopol, R.
7. Gómez-Peralta, F.; Pinés-Corrales, P.J.; Santos, E.; Cuesta, M.; González-Albarrán, O.; Azriel, S.; Castaño, L.; Mathieu, C. on behalf of the AGORA Diabetes Collaborative Group. Autoimmune Type 1 Diabetes: An Early Approach Appraisal for Spain by the AGORA Diabetes Collaborative Group. J. Clin. Med.; 2025; 14, 418. [DOI: https://dx.doi.org/10.3390/jcm14020418]
8. Mirea, O.; Oghli, M.G.; Neagoe, O.; Berceanu, M.; Țieranu, E.; Moraru, L.; Raicea, V.; Donoiu, I. All-Cause Mortality Prediction in Subjects with Diabetes Mellitus Using a Machine Learning Model and Shapley Values. Diabetology; 2025; 6, 5. [DOI: https://dx.doi.org/10.3390/diabetology6010005]
9. Friedman, J.M. Leptin and the Endocrine Control of Energy Balance. Nat. Metab.; 2019; 1, pp. 754-764. [DOI: https://dx.doi.org/10.1038/s42255-019-0095-y]
10. Akbari, M.; Hassan-Zadeh, V. IL-6 Signalling Pathways and the Development of Type 2 Diabetes. Inflammopharmacology; 2018; 26, pp. 685-698. [DOI: https://dx.doi.org/10.1007/s10787-018-0458-0]
11. Kadoglou, N.P.E.; Fotiadis, G.; Kapelouzou, A.; Kostakis, A.; Liapis, C.D.; Vrabas, I.S. The Differential Anti-Inflammatory Effects of Exercise Modalities and Their Association with Early Carotid Atherosclerosis Progression in Patients with Type 2 Diabetes. Diabet. Med.; 2013; 30, pp. e41-e50. [DOI: https://dx.doi.org/10.1111/dme.12055]
12. Freitas Lima, L.C.; de Braga, V.A.; do Socorro de França Silva, M.; de Cruz, J.C.; Sousa Santos, S.H.; de Oliveira Monteiro, M.M.; de Moura Balarini, C. Adipokines, Diabetes and Atherosclerosis: An Inflammatory Association. Front. Physiol.; 2015; 6,
13. Guerre-Millo, M. Adipose Tissue and Adipokines: For Better or Worse. Diabetes Metab.; 2004; 30, pp. 13-19. [DOI: https://dx.doi.org/10.1016/S1262-3636(07)70084-8]
14. Fisher, F.M.; Chui, P.C.; Antonellis, P.J.; Bina, H.A.; Kharitonenkov, A.; Flier, J.S.; Maratos-Flier, E. Obesity Is a Fibroblast Growth Factor 21 (FGF21)-Resistant State. Diabetes; 2010; 59, pp. 2781-2789. [DOI: https://dx.doi.org/10.2337/db10-0193]
15. Zajec, A.; Trebušak Podkrajšek, K.; Tesovnik, T.; Šket, R.; Čugalj Kern, B.; Jenko Bizjan, B.; Šmigoc Schweiger, D.; Battelino, T.; Kovač, J. Pathogenesis of Type 1 Diabetes: Established Facts and New Insights. Genes; 2022; 13, 706. [DOI: https://dx.doi.org/10.3390/genes13040706]
16. Keshavarzi, E.; Noveiry, B.B.; Rezaei, N. The Relationship Between GAD65 Autoantibody and the Risk of T1DM Onset. J. Diabetes Metab. Disord.; 2022; 21, pp. 1935-1942. [DOI: https://dx.doi.org/10.1007/s40200-022-01098-w]
17. Minniakhmetov, I.; Yalaev, B.; Khusainova, R.; Bondarenko, E.; Melnichenko, G.; Dedov, I.; Mokrysheva, N. Genetic and Epigenetic Aspects of Type 1 Diabetes Mellitus: Modern View on the Problem. Biomedicines; 2024; 12, 399. [DOI: https://dx.doi.org/10.3390/biomedicines12020399]
18. Noble, J.A.; Valdes, A.M. Genetics of the HLA Region in the Prediction of Type 1 Diabetes. Curr. Diab. Rep.; 2011; 11, pp. 533-542. [DOI: https://dx.doi.org/10.1007/s11892-011-0223-x]
19. Stene, L.C.; Norris, J.M.; Rewers, M.J. Risk Factors for Type 1 Diabetes. Diabetes in America [Internet]; Lawrence, J.M.; Casagrande, S.S.; Herman, W.H.; Wexler, D.J.; Cefalu, W.T. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): Bethesda, MD, USA, 2023.
20. Pugliese, A.; Boulware, D.; Yu, L.; Babu, S.; Steck, A.K.; Becker, D.; Rodriguez, H.; DiMeglio, L.; Evans-Molina, C.; Harrison, L.C.
21. Milicic, T.; Jotic, A.; Lalic, K.; Lukic, L.; Macesic, M.; Stanarcic Gajovic, J.; Stoiljkovic, M.; Milovancevic, M.; Rafailovic, D.; Bozovic, A.
22. Echeverri, A.F.; Tobón, G.J. Autoimmune Diabetes Mellitus (Type 1A). Autoimmunity: From Bench to Bedside [Internet]; Anaya, J.M.; Shoenfeld, Y.; Rojas-Villarraga, A.; Levy, R.A.; Cervera, R. El Rosario University Press: Bogotá, Colombia, 2013.
23. Młynarska, E.; Czarnik, W.; Dzieża, N.; Jędraszak, W.; Majchrowicz, G.; Prusinowski, F.; Stabrawa, M.; Rysz, J.; Franczyk, B. Type 2 Diabetes Mellitus: New Pathogenetic Mechanisms, Treatment and the Most Important Complications. Int. J. Mol. Sci.; 2025; 26, 1094. [DOI: https://dx.doi.org/10.3390/ijms26031094]
24. Ferdous, S.-E.; Ferrell, J.M. Pathophysiological Relationship between Type 2 Diabetes Mellitus and Metabolic Dysfunction-Associated Steatotic Liver Disease: Novel Therapeutic Approaches. Int. J. Mol. Sci.; 2024; 25, 8731. [DOI: https://dx.doi.org/10.3390/ijms25168731]
25. Aljafary, M.A.; Al-Suhaimi, E.A. Adiponectin System (Rescue Hormone): The Missing Link Between Metabolic and Cardiovascular Diseases. Pharmaceutics; 2022; 14, 1430. [DOI: https://dx.doi.org/10.3390/pharmaceutics14071430]
26. Ebrahimi-Mameghani, M.; Mohammadi, S.; Arefhosseini, S.R.; Fallah, P.; Bazi, Z. Adiponectin as a Potential Biomarker of Vascular Disease. Vasc. Health Risk Manag.; 2015; 11, pp. 55-70.
27. Alam, S.; Hasan, M.K.; Neaz, S.; Hussain, N.; Hossain, M.F.; Rahman, T. Diabetes Mellitus: Insights from Epidemiology, Biochemistry, Risk Factors, Diagnosis, Complications and Comprehensive Management. Diabetology; 2021; 2, pp. 36-50. [DOI: https://dx.doi.org/10.3390/diabetology2020004]
28. Li, M.; Chi, X.; Wang, Y.; Setrerrahmane, S.; Xie, W.; Xu, H. Trends in Insulin Resistance: Insights Into Mechanisms and Therapeutic Strategy. Signal Transduct. Target. Ther.; 2022; 7, 216. [DOI: https://dx.doi.org/10.1038/s41392-022-01073-0]
29. Ustianowski, P.; Malinowski, D.; Kopytko, P.; Czerewaty, M.; Tarnowski, M.; Dziedziejko, V.; Safranow, K.; Pawlik, A. ADCY5, CAPN10 and JAZF1 Gene Polymorphisms and Placental Expression in Women with Gestational Diabetes. Life; 2021; 11, 806. [DOI: https://dx.doi.org/10.3390/life11080806]
30. Mine, K.; Yoshikai, Y.; Takahashi, H.; Mori, H.; Anzai, K.; Nagafuchi, S. Genetic Susceptibility of the Host in Virus-Induced Diabetes. Microorganisms; 2020; 8, 1133. [DOI: https://dx.doi.org/10.3390/microorganisms8081133]
31. Gillett, M.; Royle, P.; Snaith, A.; Scotland, G.; Poobalan, A.; Imamura, M.; Black, C.; Boroujerdi, M.; Jick, S.; Wyness, L.
32. Spanakis, E.K.; Golden, S.H. Race/ethnic difference in diabetes and diabetic complications. Curr. Diab. Rep.; 2013; 13, pp. 814-823. [DOI: https://dx.doi.org/10.1007/s11892-013-0421-9]
33. Mittal, R.; Prasad, K.; Lemos, J.R.N.; Arevalo, G.; Hirani, K. Unveiling Gestational Diabetes: An Overview of Pathophysiology and Management. Int. J. Mol. Sci.; 2025; 26, 2320. [DOI: https://dx.doi.org/10.3390/ijms26052320]
34. Sweeting, A.; Wong, J.; Murphy, H.R.; Ross, G.P. A Clinical Update on Gestational Diabetes Mellitus. Endocr. Rev.; 2022; 43, pp. 763-793. [DOI: https://dx.doi.org/10.1210/endrev/bnac003]
35. Hossain, M.J.; Al-Mamun, M.; Islam, M.R. Diabetes mellitus, the fastest growing global public health concern: Early detection should be focused. Health Sci. Rep.; 2024; 7, e2004. [DOI: https://dx.doi.org/10.1002/hsr2.2004]
36. Saeedi, P.; Petersohn, I.; Salpea, P.; Malanda, B.; Karuranga, S.; Unwin, N.; Colagiuri, S.; Guariguata, L.; Motala, A.A.; Ogurtsova, K.
37. Whiting, D.R.; Guariguata, L.; Weil, C.; Shaw, J. IDF diabetes atlas: Global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res. Clin. Pract.; 2011; 94, pp. 311-321. [DOI: https://dx.doi.org/10.1016/j.diabres.2011.10.029]
38. Ghojazadeh, M.; Mobasseri, M.; Pournaghi Azar, F.; Lotfi, A. Prevalence and Incidence of Type 1 Diabetes in the World. Type 1 Diabetes—Causes, Symptoms, and Treatments; IntechOpen: New York, NY, USA, 2024; [DOI: https://dx.doi.org/10.5772/intechopen.1007015]
39. Pappachan, J.M.; Fernandez, C.J.; Ashraf, A.P. Rising tide: The global surge of type 2 diabetes in children and adolescents demands action now. World J. Diabetes; 2024; 15, pp. 797-809. [DOI: https://dx.doi.org/10.4239/wjd.v15.i5.797]
40. Xu, S.T.; Sun, M.; Xiang, Y. Global, regional, and national trends in type 2 diabetes mellitus burden among adolescents and young adults aged 10–24 years from 1990 to 2021: A trend analysis from the Global Burden of Disease Study 2021. World J. Pediatr.; 2025; 21, pp. 73-89. [DOI: https://dx.doi.org/10.1007/s12519-024-00861-8]
41. Zhang, F.S.; Li, H.J.; Yu, X.; Song, Y.P.; Ren, Y.F.; Qian, X.Z.; Liu, J.L.; Li, W.X.; Huang, Y.R.; Gao, K. Global trends and hotspots of type 2 diabetes in children and adolescents: A bibliometric study and visualization analysis. World J. Diabetes; 2025; 16, 96032. [DOI: https://dx.doi.org/10.4239/wjd.v16.i1.96032]
42. Reed, J.; Bain, S.; Kanamarlapudi, V. A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives. Diabetes Metab. Syndr. Obes.; 2021; 14, pp. 3567-3602. [DOI: https://dx.doi.org/10.2147/DMSO.S319895]
43. Chandrasekaran, P.; Weiskirchen, R. The Role of Obesity in Type 2 Diabetes Mellitus—An Overview. Int. J. Mol. Sci.; 2024; 25, 1882. [DOI: https://dx.doi.org/10.3390/ijms25031882]
44. Klein, S.; Gastaldelli, A.; Yki-Järvinen, H.; Scherer, P.E. Why does obesity cause diabetes?. Cell Metab.; 2022; 34, pp. 11-20. [DOI: https://dx.doi.org/10.1016/j.cmet.2021.12.012] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/34986330]
45. World Health Organization. Obesity and Overweight. WHO Fact Sheets.; Available online: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight (accessed on 1 May 2025).
46. Bala, C.; Rusu, A.; Ciobanu, D.; Roman, G. Length of Hospital Stay, Hospitalization Costs, and Their Drivers in Adults with Diabetes in the Romanian Public Hospital System. Int. J. Environ. Res. Public Health; 2022; 19, 10035. [DOI: https://dx.doi.org/10.3390/ijerph191610035] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/36011670]
47. Hâncu, A.; Roman, G.; Bala, C.; Timar, B.; Roman, D.; Păun, D.; Mechanick, J.I. Diabetes Care in Romania: A Lesson on the Central Role of Lifestyle Medicine. Am. J. Lifestyle Med.; 2023; 15598276231195572. [DOI: https://dx.doi.org/10.1177/15598276231195572]
48. Green, A.; Hede, S.M.; Patterson, C.C.; Wild, S.H.; Imperatore, G.; Roglic, G.; Beran, D. Type 1 diabetes in 2017: Global estimates of incident and prevalent cases in children and adults. Diabetologia; 2021; 64, pp. 2741-2750. [DOI: https://dx.doi.org/10.1007/s00125-021-05571-8]
49. GBD 2021 Diabetes Collaborators. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: A systematic analysis for the Global Burden of Disease Study 2021. Lancet; 2023; 402, pp. 203-234. [DOI: https://dx.doi.org/10.1016/S0140-6736(23)01301-6]
50. Dilworth, L.; Facey, A.; Omoruyi, F. Diabetes Mellitus and Its Metabolic Complications: The Role of Adipose Tissues. Int. J. Mol. Sci.; 2021; 22, 7644. [DOI: https://dx.doi.org/10.3390/ijms22147644]
51. Abel, E.D.; Gloyn, A.L.; Evans-Molina, C.; Joseph, J.J.; Misra, S.; Pajvani, U.B.; Simcox, J.; Susztak, K.; Drucker, D.J. Diabetes mellitus-Progress and opportunities in the evolving epidemic. Cell; 2024; 187, pp. 3789-3820. [DOI: https://dx.doi.org/10.1016/j.cell.2024.06.029]
52. Ruze, R.; Liu, T.; Zou, X.; Song, J.; Chen, Y.; Xu, R.; Yin, X.; Xu, Q. Obesity and type 2 diabetes mellitus: Connections in epidemiology, pathogenesis, and treatments. Front. Endocrinol.; 2023; 14,
53. Meng, X.; Zhang, H.; Zhao, Z.; Li, S.; Zhang, X.; Guo, R.; Liu, H.; Yuan, Y.; Li, W.; Song, Q.
54. Albairmani, R.A.; Basheer, B.M.; Macky, M.M.; Al Syouti, T.; AlZubaidy, H.; Elfaki, E.; Kidwai, A.; Basheer, Y.M.; Ahmed, F.; Salaheldin, M. Management of Diabetes in Pregnancy: A Review of Clinical Guidelines and Practices. Cureus; 2025; 17, e79334. [DOI: https://dx.doi.org/10.7759/cureus.79334]
55. Moher, D.; Liberati, A.; Tetzlaff, J.; Altman, D.G. The PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med.; 2009; 6, e1000097. [DOI: https://dx.doi.org/10.1371/journal.pmed.1000097] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/19621072]
56. Kawasaki, E. Anti-Islet Autoantibodies in Type 1 Diabetes. Int. J. Mol. Sci.; 2023; 24, 10012. [DOI: https://dx.doi.org/10.3390/ijms241210012] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/37373160]
57. Galicia-Garcia, U.; Benito-Vicente, A.; Jebari, S.; Larrea-Sebal, A.; Siddiqi, H.; Uribe, K.B.; Ostolaza, H.; Martín, C. Pathophysiology of Type 2 Diabetes Mellitus. Int. J. Mol. Sci.; 2020; 21, 6275. [DOI: https://dx.doi.org/10.3390/ijms21176275] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32872570]
58. American Diabetes Association. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2024. Diabetes Care; 2024; 47, (Suppl. 1), pp. S16-S38.
59. Tamás, G.; Kerényi, Z. Gestational Diabetes: Current Aspects on Pathogenesis and Treatment. Exp. Clin. Endocrinol. Diabetes; 2001; 109, (Suppl. 2), pp. S400-S411. [DOI: https://dx.doi.org/10.1055/s-2001-18598]
60. Echouffo-Tcheugui, J.B.; Selvin, E. Prediabetes and What It Means: The Epidemiological Evidence. Annu. Rev. Public Health; 2021; 42, pp. 59-77. [DOI: https://dx.doi.org/10.1146/annurev-publhealth-090419-102644]
61. Diabetes Canada Clinical Practice Guidelines Expert Committee. Diabetes Canada 2018 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada. Can. J. Diabetes; 2018; 42, (Suppl. 1), pp. S1-S325.
62. Salehi, B.; Ata, A.; Kumar, V.A.N.; Sharopov, F.; Ramírez-Alarcón, K.; Ruiz-Ortega, A.; Ayatollahi, S.A.; Tsouh Fokou, P.V.; Kobarfard, F.; Zakaria, Z.A.
63. Governa, P.; Baini, G.; Borgonetti, V.; Cettolin, G.; Giachetti, D.; Magnano, A.R.; Miraldi, E.; Biagi, M. Phytotherapy in the Management of Diabetes: A Review. Molecules; 2018; 23, 105. [DOI: https://dx.doi.org/10.3390/molecules23010105]
64. Tran, N.; Pham, B.; Le, L. Bioactive Compounds in Anti-Diabetic Plants: From Herbal Medicine to Modern Drug Discovery. Biology; 2020; 9, 252. [DOI: https://dx.doi.org/10.3390/biology9090252]
65. Noor, F.; Tahir ul Qamar, M.; Ashfaq, U.A.; Albutti, A.; Alwashmi, A.S.S.; Aljasir, M.A. Network Pharmacology Approach for Medicinal Plants: Review and Assessment. Pharmaceuticals; 2022; 15, 572. [DOI: https://dx.doi.org/10.3390/ph15050572] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/35631398]
66. Kamboj, P.; Talukdar, N.C.; Banerjee, S.K. Therapeutic Benefit of Dillenia indica in Diabetes and Its Associated Complications. J. Diabetes Res.; 2019; 2019, 4632491. [DOI: https://dx.doi.org/10.1155/2019/4632491] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31871947]
67. Song, B.-R.; Alam, M.B.; Lee, S.-H. Terpenoid-Rich Extract of Dillenia indica L. Bark Displays Antidiabetic Action in Insulin-Resistant C2C12 Cells and STZ-Induced Diabetic Mice by Attenuation of Oxidative Stress. Antioxidants; 2022; 11, 1227. [DOI: https://dx.doi.org/10.3390/antiox11071227] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/35883721]
68. Joseph, B.; Jini, D. Antidiabetic Effects of Momordica charantia (Bitter Melon) and Its Medicinal Potency. Asian Pac. J. Trop. Dis.; 2013; 3, pp. 93-102. [DOI: https://dx.doi.org/10.1016/S2222-1808(13)60052-3]
69. Kim, B.; Lee, H.S.; Kim, H.J.; Lee, H.; Lee, I.-Y.; Ock, S.; Kwon, S.; Kang, S.-S.; Choi, Y. Momordica charantia (Bitter Melon) Efficacy and Safety on Glucose Metabolism in Korean Prediabetes Participants: A 12-Week, Randomized Clinical Study. Food Sci. Biotechnol.; 2023; 32, pp. 697-704. [DOI: https://dx.doi.org/10.1007/s10068-022-01214-9]
70. El-Saber Batiha, G.; Magdy Beshbishy, A.; El-Mleeh, A.; Abdel-Daim, M.M.; Prasad Devkota, H. Traditional Uses, Bioactive Chemical Constituents, and Pharmacological and Toxicological Activities of Glycyrrhiza glabra L. (Fabaceae). Biomolecules; 2020; 10, 352. [DOI: https://dx.doi.org/10.3390/biom10030352]
71. Sarker, D.K.; Ray, P.; Dutta, A.K.; Rouf, R.; Uddin, S.J. Antidiabetic Potential of Fenugreek (Trigonella foenum-graecum): A Magic Herb for Diabetes Mellitus. Food Sci. Nutr.; 2024; 12, pp. 7108-7136. [DOI: https://dx.doi.org/10.1002/fsn3.4440]
72. Geberemeskel, G.A.; Debebe, Y.G.; Nguse, N.A. Antidiabetic Effect of Fenugreek Seed Powder Solution (Trigonella foenum-graecum L.) on Hyperlipidemia in Diabetic Patients. J. Diabetes Res.; 2019; 2019, 8507453. [DOI: https://dx.doi.org/10.1155/2019/8507453]
73. Kishore, T.S.; Babu, J.A.; Priyadarshini, K.A. Evaluation of Antidiabetic Activity of Trigonella foenum-graecum Leaves in Alloxan Induced Type-II Diabetes. Int. J. Res. Pharmacol. Pharmacother.; 2025; 14, pp. 1-10.
74. Lertpatipanpong, P.; Janpaijit, S.; Park, E.Y.; Kim, C.T.; Baek, S.J. Potential Anti-Diabetic Activity of Pueraria lobata Flower (Flos Puerariae) Extracts. Molecules; 2020; 25, 3970. [DOI: https://dx.doi.org/10.3390/molecules25173970]
75. Zhang, S.; Ge, Q.; Chen, L.; Chen, K. Studies of the Anti-Diabetic Mechanism of Pueraria lobata Based on Metabolomics and Network Pharmacology. Processes; 2021; 9, 1245. [DOI: https://dx.doi.org/10.3390/pr9071245]
76. Sutedja, A.M.; Yanase, E.; Batubara, I.; Fardiaz, D.; Lioe, H.N. Antidiabetic Components from the Hexane Extract of Red Kidney Beans (Phaseolus vulgaris L.): Isolation and Structure Determination. Biosci. Biotechnol. Biochem.; 2020; 84, pp. 598-605. [DOI: https://dx.doi.org/10.1080/09168451.2019.1691911] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31724491]
77. Pereira, A.S.P.; Banegas-Luna, A.J.; Peña-García, J.; Pérez-Sánchez, H.; Apostolides, Z. Evaluation of the Anti-Diabetic Activity of Some Common Herbs and Spices: Providing New Insights with Inverse Virtual Screening. Molecules; 2019; 24, 4030. [DOI: https://dx.doi.org/10.3390/molecules24224030] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31703341]
78. AlBalawi, A.N.; Elmetwalli, A.; Baraka, D.M.; Alnagar, H.A.; Alamri, E.S.; Hassan, M.G. Chemical Constituents, Antioxidant Potential, and Antimicrobial Efficacy of Pimpinella anisum Extracts Against Multidrug-Resistant Bacteria. Microorganisms; 2023; 11, 1024. [DOI: https://dx.doi.org/10.3390/microorganisms11041024]
79. Assaggaf, H.M. Investigating the Antidiabetic Properties of Apium graveolens Extract and Its Inhibition of Enzymes Associated with Hyperglycemia. Int. J. Biol. Macromol.; 2025; 290,
80. Meutia, R.; Sembiring, N.B.; Nababan, O.A.; Simanjuntak, N.; Novriani, E.; Nurasni, N. Antidiabetic Activity Test of the Ethyl Acetate Fraction of Celery Leaves (Apium graveolens L.) Against Wistar Male Rats (Rattus norvegicus). J. Pharm. Sci.; 2022; 6, pp. 160-166.
81. Karkute, S.G.; Koley, T.K.; Yengkhom, B.K.; Tripathi, A.; Srivastava, S.; Maurya, A.; Singh, B. Anti-Diabetic Phenolic Compounds of Black Carrot (Daucus carota Subsp. sativus var. atrorubens Alef.) Inhibit Enzymes of Glucose Metabolism: An in silico and in vitro Validation. Med. Chem.; 2018; 14, pp. 641-649.
82. Esatbeyoglu, T.; Rodríguez-Werner, M.; Schlösser, A.; Liehr, M.; Ipharraguerre, I.; Winterhalter, P.; Rimbach, G. Fractionation of Plant Bioactives from Black Carrots (Daucus carota subsp. sativus var. atrorubens Alef.) by Adsorptive Membrane Chromatography and Analysis of Their Potential Anti-Diabetic Activity. J. Agric. Food Chem.; 2016; 64, pp. 5901-5908.
83. Ali, A. Chemical Composition, α-Glucosidase Inhibitory and Anticancer Activity of Essential Oil of Thymus vulgaris Leaves. J. Essent. Oil Bear. Plants; 2021; 24, pp. 695-703. [DOI: https://dx.doi.org/10.1080/0972060X.2021.1973575]
84. Aljelehawy, Q.H.A.; Mohammadi, S.; Mohamadian, E.; Mal Allah, O.R.; Mirzaei, A.; Ghahremanlou, M. Antimicrobial, Anticancer, Antidiabetic, Antineurodegenerative, and Antirheumatic Activities of Thymol: Clarification of Mechanisms. Micro Nano Bio Asp.; 2023; 2, pp. 1-7.
85. Tundis, R.; Grande, F.; Occhiuzzi, M.A.; Sicari, V.; Loizzo, M.R.; Cappello, A.R. Lavandula angustifolia Mill. (Lamiaceae) Ethanol Extract and Its Main Constituents as Promising Agents for the Treatment of Metabolic Disorders: Chemical Profile, in vitro Biological Studies, and Molecular Docking. J. Enzym. Inhib. Med. Chem.; 2023; 38, 2269481. [DOI: https://dx.doi.org/10.1080/14756366.2023.2269481] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/37850338]
86. Mahmoodnia, L.; Forouzandeh Shahrakei, Z.; Hojatyar, S.; Setorki, M. Effects of Lavandula angustifolia Hydroalcoholic Extract on the Blood and Urine Biochemical Factors of Diabetic Patients: A Placebo-Controlled Clinical Trial. J. Basic Res. Med. Sci.; 2024; 11, pp. 53-61.
87. Behradmanesh, S.; Derees, F.; Rafieian-Kopaei, M. Effect of Salvia officinalis on Diabetic Patients. J. Ren. Inj. Prev.; 2013; 2, pp. 51-54. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25340127]
88. Ononamadu, C.J.; Seidel, V. Exploring the Antidiabetic Potential of Salvia officinalis Using Network Pharmacology, Molecular Docking and ADME/Drug-Likeness Predictions. Plants; 2024; 13, 2892. [DOI: https://dx.doi.org/10.3390/plants13202892]
89. Huang, S.M.; Lin, C.H.; Chang, W.F.; Shih, C.C. Antidiabetic and Antihyperlipidemic Activities of Phyllanthus emblica L. Extract in vitro and the Regulation of Akt Phosphorylation, Gluconeogenesis, and Peroxisome Proliferator-Activated Receptor α in Streptozotocin-Induced Diabetic Mice. Food Nutr. Res.; 2023; 67, 9492. [DOI: https://dx.doi.org/10.29219/fnr.v67.9854]
90. Lin, C.H.; Kuo, Y.H.; Shih, C.C. Antidiabetic and Immunoregulatory Activities of Extract of Phyllanthus emblica L. in NOD with Spontaneous and Cyclophosphamide-Accelerated Diabetic Mice. Int. J. Mol. Sci.; 2023; 24, 9922. [DOI: https://dx.doi.org/10.3390/ijms24129922]
91. Vadivelan, R.; Gopala Krishnan, R.; Kannan, R. Antidiabetic Potential of Asparagus racemosus Willd Leaf Extracts through Inhibition of α-Amylase and α-Glucosidase. J. Tradit. Complement. Med.; 2018; 9, pp. 1-4. [DOI: https://dx.doi.org/10.1016/j.jtcme.2017.10.004]
92. Hannan, J.M.; Ali, L.; Khaleque, J.; Akhter, M.; Flatt, P.R.; Abdel-Wahab, Y.H. Antihyperglycaemic Activity of Asparagus racemosus Roots Is Partly Mediated by Inhibition of Carbohydrate Digestion and Absorption, and Enhancement of Cellular Insulin Action. Br. J. Nutr.; 2012; 107, pp. 1316-1323. [DOI: https://dx.doi.org/10.1017/S0007114511004284]
93. Satyanarayana, K.; Sravanthi, K.; Shaker, I.A.; Ponnulakshmi, R. Molecular Approach to Identify Antidiabetic Potential of Azadirachta indica. J. Ayurveda Integr. Med.; 2015; 6, pp. 165-174. [DOI: https://dx.doi.org/10.4103/0975-9476.157950]
94. Mohammed, A.; Kumar, R.; Ashfaq, F.; Alsayegh, A.A.; Al Areefy, A.A.E.H.; Khan, M.I.; Rizvi, S.I. Young and Mature Leaves of Azadirachta indica (Neem) Display Different Antidiabetic and Antioxidative Effects. Egypt. J. Basic Appl. Sci.; 2023; 10, pp. 316-328. [DOI: https://dx.doi.org/10.1080/2314808X.2023.2196191]
95. Shetty, P.; Rai, M.; Ravindran, A.; Gopalakrishna, H.N.; Pai, V.R.; Kalal, B.S. Hypoglycemic and Hypolipidemic Effects of Garcinia cambogia Extracts in Streptozotocin-Nicotinamide Induced Diabetic Rat Model. Int. J. Clin. Exp. Pathol.; 2022; 15, pp. 380-387. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/36237637]
96. Chen, T.-H.; Tsai, M.-J.; Fu, Y.-S.; Weng, C.-F. The Exploration of Natural Compounds for Anti-Diabetes from Distinctive Species Garcinia linii with Comprehensive Review of the Garcinia Family. Biomolecules; 2019; 9, 641. [DOI: https://dx.doi.org/10.3390/biom9110641] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31652794]
97. Im, K.; Issac, A.; Nm, J.; Ninan, E.; Maliakel, B.; Kuttan, R. Effects of the Polyphenol Content on the Anti-Diabetic Activity of Cinnamomum zeylanicum Extracts. Food Funct.; 2014; 5, pp. 2208-2220. [DOI: https://dx.doi.org/10.1039/C4FO00130C] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25051315]
98. Nawaz, A.; Ali, T.; Naeem, M.; Hussain, F.; Li, Z.; Nasir, A. Biochemical, Structural Characterization and In vitro Evaluation of Antioxidant, Antibacterial, Cytotoxic, and Antidiabetic Activities of Nanosuspensions of Cinnamomum zeylanicum Bark Extract. Front. Chem.; 2023; 11,
99. Chen, W.; Balan, P.; Popovich, D.G. Review of Ginseng Anti-Diabetic Studies. Molecules; 2019; 24, 4501. [DOI: https://dx.doi.org/10.3390/molecules24244501]
100. Liu, Z.; Qu, C.Y.; Li, J.X.; Wang, Y.F.; Li, W.; Wang, C.Z.; Wang, D.S.; Song, J.; Sun, G.Z.; Yuan, C.S. Hypoglycemic and Hypolipidemic Effects of Malonyl Ginsenosides from American Ginseng (Panax quinquefolius L.) on Type 2 Diabetic Mice. ACS Omega; 2021; 6, pp. 33652-33664. [DOI: https://dx.doi.org/10.1021/acsomega.1c04656]
101. Cheng, D.; Liang, B.; Li, Y. Antihyperglycemic Effect of Ginkgo biloba Extract in Streptozotocin-Induced Diabetes in Rats. BioMed. Res. Int.; 2013; 2013, 162724. [DOI: https://dx.doi.org/10.1155/2013/162724]
102. Aziz, T.A.; Hussain, S.A.; Mahwi, T.O.; Ahmed, Z.A.; Rahman, H.S.; Rasedee, A. The Efficacy and Safety of Ginkgo biloba Extract as an Adjuvant in Type 2 Diabetes Mellitus Patients Ineffectively Managed with Metformin: A Double-Blind, Randomized, Placebo-Controlled Trial. Drug Des. Devel. Ther.; 2018; 12, pp. 735-742. [DOI: https://dx.doi.org/10.2147/DDDT.S157113]
103. Jurčević Šangut, I.; Šola, I.; Šamec, D. Neuroprotective, Anti-Hyperpigmentation, and Anti-Diabetic Effects and Bioaccessibility of Flavonoids in Ginkgo Leaf Infusions from Green and Yellow Leaves. Appl. Sci.; 2024; 14, 10231. [DOI: https://dx.doi.org/10.3390/app142210231]
104. Kazazis, C.E.; Evangelopoulos, A.A.; Kollas, A.; Vallianou, N.G. The Therapeutic Potential of Milk Thistle in Diabetes. Rev. Diabet. Stud.; 2014; 11, pp. 167-174. [DOI: https://dx.doi.org/10.1900/RDS.2014.11.167]
105. Lekmine, S.; Benslama, O.; Ola, M.S.; Touzout, N.; Moussa, H.; Tahraoui, H.; Hafsa, H.; Zhang, J.; Amrane, A. Preliminary Data on Silybum marianum Metabolites: Comprehensive Characterization, Antioxidant, Antidiabetic, Antimicrobial Activities, LC-MS/MS Profiling, and Predicted ADMET Analysis. Metabolites; 2025; 15, 13. [DOI: https://dx.doi.org/10.3390/metabo15010013] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/39852356]
106. Hao, Z.; Zhang, Y.; Cao, Y.; Sun, Y.; Wang, Y.; Zhang, C.; Liang, D.; Liu, Y.; Feng, W. Chemical Constituents from Acorus calamus with Potent Anti-Diabetic and Hepatoprotective Activities. Fitoterapia; 2023; 169, 105591. [DOI: https://dx.doi.org/10.1016/j.fitote.2023.105591] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/37343685]
107. Chávez-Silva, F.; Cerón-Romero, L.; Arias-Durán, L.; Navarrete-Vázquez, G.; Almanza-Pérez, J.; Román-Ramos, R.; Ramírez-Ávila, G.; Perea-Arango, I.; Villalobos-Molina, R.; Estrada-Soto, S. Antidiabetic Effect of Achillea millefollium through Multitarget Interactions: α-Glucosidases Inhibition, Insulin Sensitization and Insulin Secretagogue Activities. J. Ethnopharmacol.; 2018; 212, pp. 1-7. [DOI: https://dx.doi.org/10.1016/j.jep.2017.10.005] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29031783]
108. Rezaei, S.; Ashkar, F.; Koohpeyma, F.; Mahmoodi, M.; Gholamalizadeh, M.; Mazloom, Z.; Doaei, S. Hydroalcoholic Extract of Achillea millefolium Improved Blood Glucose, Liver Enzymes and Lipid Profile Compared to Metformin in Streptozotocin-Induced Diabetic Rats. Lipids Health Dis.; 2020; 19, 81. [DOI: https://dx.doi.org/10.1186/s12944-020-01228-4]
109. Ahangarpour, A.; Heidari, H.; Oroojan, A.A.; Mirzavandi, F.; Nasr Esfehani, K.; Dehghan Mohammadi, Z. Antidiabetic, Hypolipidemic and Hepatoprotective Effects of Arctium lappa Root’s Hydro-Alcoholic Extract on Nicotinamide-Streptozotocin Induced Type 2 Model of Diabetes in Male Mice. Avicenna J. Phytomed.; 2017; 7, pp. 169-179.
110. Zolotova, D.; Teterovska, R.; Bandere, D.; Lauberte, L.; Niedra, S. Antidiabetic Properties of the Root Extracts of Dandelion (Taraxacum officinale) and Burdock (Arctium lappa). Plants; 2024; 13, 1021. [DOI: https://dx.doi.org/10.3390/plants13071021]
111. Sharifi-Rad, J.; Herrera-Bravo, J.; Semwal, P.; Painuli, S.; Badoni, H.; Ezzat, S.M.; Farid, M.M.; Merghany, R.M.; Aborehab, N.M.; Salem, M.A.
112. Neagu, E.; Paun, G.; Albu, C.; Apreutesei, O.T.; Radu, G.L. In vitro Assessment of the Antidiabetic and Anti-Inflammatory Potential of Artemisia absinthium, Artemisia vulgaris and Trigonella foenum-graecum Extracts Processed Using Membrane Technologies. Molecules; 2023; 28, 7156. [DOI: https://dx.doi.org/10.3390/molecules28207156]
113. Akhtar, M.S.; Rafiullah, M.; Hossain, M.A.; Ali, M. Antidiabetic Activity of Cichorium intybus L. Water Extract Against Streptozotocin-Induced Diabetic Rats. J. Umm Al Qura Univ. Appl. Sci.; 2023; 9, pp. 565-571. [DOI: https://dx.doi.org/10.1007/s43994-023-00066-1]
114. Ferrare, K.; Bidel, L.P.R.; Awwad, A.; Poucheret, P.; Cazals, G.; Lazennec, F.; Azay-Milhau, J.; Tournier, M.; Lajoix, A.D.; Tousch, D. Increase in Insulin Sensitivity by the Association of Chicoric Acid and Chlorogenic Acid Contained in a Natural Chicoric Acid Extract (NCRAE) of Chicory (Cichorium intybus L.) for an Antidiabetic Effect. J. Ethnopharmacol.; 2018; 215, pp. 241-248. [DOI: https://dx.doi.org/10.1016/j.jep.2017.12.035]
115. Ahmed, O.M.; Abdel Fattah, A.A.; Abdul-Hamid, M.; Abdel-Aziz, A.M.; Sakr, H.I.; Damanhory, A.A.; Abdel-Kawi, S.H.; Ghaboura, N.; Awad, M.M.Y. Antidiabetic and Liver Histological and Ultrastructural Effects of Cynara scolymus Leaf and Flower Head Hydroethanolic Extracts in Nicotinamide/Streptozotocin-Induced Diabetic Rats. Evid. Based Complement. Alternat. Med.; 2023; 2023, 4223026. [DOI: https://dx.doi.org/10.1155/2023/4223026] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/37163198]
116. Porro, C.; Benameur, T.; Cianciulli, A.; Vacca, M.; Chiarini, M.; De Angelis, M.; Panaro, M.A. Functional and Therapeutic Potential of Cynara scolymus in Health Benefits. Nutrients; 2024; 16, 872. [DOI: https://dx.doi.org/10.3390/nu16060872] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/38542782]
117. Murtaza, I.; Laila, O.; Drabu, I.; Ahmad, A.; Charifi, W.; Popescu, S.M.; Mansoor, S. Nutritional Profiling, Phytochemical Composition and Antidiabetic Potential of Taraxacum officinale, an Underutilized Herb. Molecules; 2022; 27, 5380. [DOI: https://dx.doi.org/10.3390/molecules27175380] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/36080148]
118. Sheikh, M. In vitro Antioxidant Activity, Total Phenolic and Total Flavonoid Contents of Taraxacum officinale Leaves. Int. J. Innov. Pharm. Sci. Res.; 2015; 3, pp. 697-707.
119. Studzińska-Sroka, E.; Paczkowska-Walendowska, M.; Kledzik, J.; Galanty, A.; Gościniak, A.; Szulc, P.; Korybalska, K.; Cielecka-Piontek, J. Antidiabetic Potential of Black Elderberry Cultivars Flower Extracts: Phytochemical Profile and Enzyme Inhibition. Molecules; 2024; 29, 5775. [DOI: https://dx.doi.org/10.3390/molecules29235775]
120. Krejpcio, Z.; Król, E.; Staniek, H.; Oluwatobi, J.M.; Rocha, S.M.; Salvador, A.; Kurek, J. Evaluation of the Effect of Elderberry (Sambucus nigra) Fruit Extracts on Calcium and Magnesium Status in STZ-Induced Diabetic Rats. Proceedings; 2023; 91, 228.
121. Mehmood, A.; Zeb, A.; Ateeq, M.K. In Vivo Antidiabetic Effects of Phenolic Compounds of Spinach, Mustard, and Cabbage Leaves in Mice. Heliyon; 2023; 9, e16616. [DOI: https://dx.doi.org/10.1016/j.heliyon.2023.e16616]
122. Subhash, G.P.; Virbhadrappa, S.R.; Vasant, O.K.; Otari, K.V. Spinacia oleracea Linn, A Pharmacognostic and Pharmacological Overview. Int. J. Res. Ayurveda Pharm.; 2010; 1, pp. 78-84.
123. Dzhafarova, R.E.; Garaev, G.S.; Dzhafarkulieva, Z.S. Antidiabetic Action of Extract of Juglans regia L. Georgian Med. News; 2009; 170, pp. 110-114.
124. Bourais, I.; Elmarrkechy, S.; Taha, D.; Badaoui, B.; Mourabit, Y.; Salhi, N.; Alshahrani, M.M.; Al Awadh, A.A.; Bouyahya, A.; Goh, K.W.
125. Muñiz-Ramirez, A.; Perez, R.M.; Garcia, E.; Garcia, F.E. Antidiabetic Activity of Aloe vera Leaves. Evid. Based Complement. Alternat. Med.; 2020; 2020, 6371201. [DOI: https://dx.doi.org/10.1155/2020/6371201] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32565868]
126. Malik, J.A.; Iqbal, S.; Biswas, J.; Riaz, U.; Datta, S. Antidiabetic Property of Aloe vera (Aloe barbadensis) and Bitter Melon (Momordica charantia). Medicinal and Aromatic Plants; Aftab, T.; Hakeem, K.R. Springer: Cham, Switzerland, 2021.
127. Hafizur, R.M.; Kabir, N.; Chishti, S. Asparagus officinalis Extract Controls Blood Glucose by Improving Insulin Secretion and β-Cell Function in Streptozotocin-Induced Type 2 Diabetic Rats. Br. J. Nutr.; 2012; 108, pp. 1586-1595. [DOI: https://dx.doi.org/10.1017/S0007114511007148] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/22221560]
128. Olas, B. A Review of the Pro-Health Activity of Asparagus officinalis L. and Its Components. Foods; 2024; 13, 288. [DOI: https://dx.doi.org/10.3390/foods13020288] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/38254589]
129. Esakki, A.; Ramadoss, R.; Ananthapadmanabhan, L.; Sundar, S.; Panneerselvam, S.; Ramani, P. Quantification of the Anti-Diabetic Effect of Allium cepa. Cureus; 2024; 16, e59174. [DOI: https://dx.doi.org/10.7759/cureus.59174]
130. Vu, N.K.; Kim, C.S.; Ha, M.T.; Ngo, Q.-M.T.; Park, S.E.; Kwon, H.; Lee, D.; Choi, J.S.; Kim, J.A.; Min, B.S. Isolation and Identification of Antidiabetic Compounds from Allium cepa and Evaluation of Their Activity in Diabetic Mice. J. Agric. Food Chem.; 2020; 68, pp. 8797-8811. [DOI: https://dx.doi.org/10.1021/acs.jafc.0c02122]
131. Ashraf, R.; Khan, R.A.; Ashraf, I. Garlic (Allium sativum) Supplementation with Standard Antidiabetic Agent Provides Better Diabetic Control in Type 2 Diabetes Patients. Pak. J. Pharm. Sci.; 2011; 24, pp. 565-570.
132. Aminabee, S.; Shankar, K.R.; Lakshmi, K.N.V.C.; Saritha, K.; Kavya, R.; Babu, K.C.; Dasari, S.K. Influence of Allium sativum on the Hypoglycaemic Activity of Gliclazide in Normal Rats: A Possible Approach to Herb-Drug Interaction. Biomed. Pharmacol. J.; 2024; 17, pp. 377-382. [DOI: https://dx.doi.org/10.13005/bpj/2864]
133. Turkkan, A.; Savas, H.B.; Yavuz, B.; Yigit, A.; Uz, E.; Bayram, N.A.; Kale, B. The Prophylactic Effect of Viscum album in Streptozotocin-Induced Diabetic Rats. North Clin. Istanb.; 2016; 3, pp. 83-89.
134. Szurpnicka, A.; Kowalczuk, A.; Szterk, A. Biological Activity of Mistletoe: In vitro and In Vivo Studies and Mechanisms of Action. Arch. Pharm. Res.; 2020; 43, pp. 593-629. [DOI: https://dx.doi.org/10.1007/s12272-020-01247-w]
135. Morales Ramos, J.G.; Esteves Pairazamán, A.T.; Mocarro Willis, M.E.S.; Collantes Santisteban, S.; Caldas Herrera, E. Medicinal Properties of Morus alba for the Control of Type 2 Diabetes Mellitus: A Systematic Review. F1000Research; 2021; 10, 1022. [DOI: https://dx.doi.org/10.12688/f1000research.55573.1]
136. Özgür, M.; Uçar, A.; Yılmaz, S. The Multifaceted Benefits of Morus nigra L.: A Pharmacological Powerhouse. Phytochem. Rev.; 2025; [DOI: https://dx.doi.org/10.1007/s11101-025-10073-1]
137. Jelača, S.; Dajić-Stevanović, Z.; Vuković, N.; Kolašinac, S.; Trendafilova, A.; Nedialkov, P.; Stanković, M.; Tanić, N.; Tanić, N.T.; Acović, A.
138. Mustafa, K.G.; Ganai, B.A.; Akbar, S.; Dar, M.Y.; Masood, A. β-Cell Protective Efficacy, Hypoglycemic and Hypolipidemic Effects of Extracts of Achillea millefolium in Diabetic Rats. Chin. J. Nat. Med.; 2012; 10, pp. 185-189.
139. Mallhi, I.Y.; Sohaib, M.; Khan, A.U.; Rabbani, I. Antidiabetic, Antioxidative and Antihyperlipidemic Effects of Strawberry Fruit Extract in Alloxan-Induced Diabetic Rats. Foods; 2023; 12, 2911. [DOI: https://dx.doi.org/10.3390/foods12152911]
140. Ibrahim, D.S.; Abd El-Maksoud, M.A. Effect of Strawberry (Fragaria × ananassa) Leaf Extract on Diabetic Nephropathy in Rats. Int. J. Exp. Pathol.; 2015; 96, pp. 87-93. [DOI: https://dx.doi.org/10.1111/iep.12116]
141. Fattahi, A.; Niyazi, F.; Shahbazi, B.; Farzaei, M.H.; Bahrami, G. Antidiabetic Mechanisms of Rosa canina Fruits: An In vitro Evaluation. J. Evid. Based Complement. Altern. Med.; 2017; 22, pp. 127-133. [DOI: https://dx.doi.org/10.1177/2156587216655263]
142. Vasić, D.; Katanić Stanković, J.S.; Urošević, T.; Kozarski, M.; Naumovski, N.; Khan, H.; Popović-Djordjević, J. Insight into Bioactive Compounds, Antioxidant and Anti-Diabetic Properties of Rosehip (Rosa canina L.)-Based Tisanes with Addition of Hibiscus sabdariffa L. and Crocus sativus L. Beverages; 2024; 10, 1. [DOI: https://dx.doi.org/10.3390/beverages10010001]
143. Kuczmannová, A.; Balažová, A.; Račanská, E.; Kameníková, M.; Fialová, S.; Majerník, J.; Nagy, M.; Gál, P.; Mučaji, P. Agrimonia eupatoria L. and Cynara cardunculus L. Water Infusions: Comparison of Anti-Diabetic Activities. Molecules; 2016; 21, 564. [DOI: https://dx.doi.org/10.3390/molecules21050564]
144. Jung, C.H.; Zhou, S.; Ding, G.X.; Kim, J.H.; Hong, M.H.; Shin, Y.-C.; Kim, G.J.; Ko, S.-G. Antihyperglycemic Activity of Herb Extracts on Streptozotocin-Induced Diabetic Rats. Biosci. Biotechnol. Biochem.; 2006; 70, pp. 2556-2559. [DOI: https://dx.doi.org/10.1271/bbb.60238]
145. Ammar, A.H.; Bouajila, J.; Lebrihi, A.; Mathieu, F.; Romdhane, M.; Zagrouba, F. Chemical Composition and In vitro Antimicrobial and Antioxidant Activities of Citrus aurantium L. Flowers Essential Oil (Neroli Oil). Pak. J. Biol. Sci.; 2012; 15, pp. 1034-1040. [DOI: https://dx.doi.org/10.3923/pjbs.2012.1034.1040]
146. Osfor, M.M.H.; Hegazy, A.; Mohammad, A.; Elmadbouly, M.A.; Afify, R.A.M.; Elbahnasawy, A.S. Hypo-Cholesterolemic and Hypoglycemic Effects of Orange Albedo Powder (Citrus aurantium L.) on Male Albino Rats. Int. J. Nutr. Food Sci.; 2013; 2, pp. 70-76. [DOI: https://dx.doi.org/10.11648/j.ijnfs.20130202.17]
147. Akinnuga, A.M.; Bamidele, O.; Ebunlomo, O.A.; Adeniyi, O.S.; Adeleyea, G.S.; Ebomuche, L.C. Hypoglycaemic Effects of Dietary Intake of Ripe and Unripe Lycopersicon esculentum (Tomatoes) on Streptozotocin-Induced Diabetes Mellitus in Rats. OnLine J. Biol. Sci.; 2010; 10, pp. 50-53. [DOI: https://dx.doi.org/10.3844/ojbsci.2010.50.53]
148. Aisami, A.; James, J.I.; Maigari, F.U.; Atiku, M.K. Hypoglycemic Effect of Lycopersicon esculentum (Tomato) on Alloxan-Induced Diabetic Rats. J. Biochem. Microbiol. Biotechnol.; 2021; 9, pp. 15-18. [DOI: https://dx.doi.org/10.54987/jobimb.v9i2.611]
149. Chehri, A.; Yarani, R.; Yousefi, Z.; Novin Bahador, T.; Shakouri, S.K.; Ostadrahimi, A.; Mobasseri, M.; Pociot, F.; Araj-Khodaei, M. Anti-Diabetic Potential of Urtica dioica: Current Knowledge and Future Direction. J. Diabetes Metab. Disord.; 2022; 21, pp. 931-940. [DOI: https://dx.doi.org/10.1007/s40200-021-00942-9]
150. Orhan, N.; Aslan, M.; Orhan, D.D.; Ergun, F.; Yeşilada, E. In-Vivo Assessment of Antidiabetic and Antioxidant Activities of Grapevine Leaves (Vitis vinifera) in Diabetic Rats. J. Ethnopharmacol.; 2006; 108, pp. 280-286. [DOI: https://dx.doi.org/10.1016/j.jep.2006.05.010]
151. Karageçili, H.; İzol, E.; Kireçci, E.; Gülçin, İ. Antioxidant, Antidiabetic, Antiglaucoma, and Anticholinergic Effects of Tayfi Grape (Vitis vinifera): A Phytochemical Screening by LC-MS/MS Analysis. Open Chem.; 2023; 21, 20230120. [DOI: https://dx.doi.org/10.1515/chem-2023-0120]
152. Soltani, R.; Hakimi, M.; Asgary, S.; Ghanadian, S.M.; Keshvari, M.; Sarrafzadegan, N. Evaluation of the Effects of Vaccinium arctostaphylos L. Fruit Extract on Serum Lipids and hs-CRP Levels and Oxidative Stress in Adult Patients with Hyperlipidemia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Evid. Based Complement. Alternat. Med.; 2014; 2014, 217451. [DOI: https://dx.doi.org/10.1155/2014/217451]
153. Ozkan, G.; Ercisli, S.; Zeb, A.; Agar, G.; Sagbas, H.I.; Ilhan, G. Some Morphological and Biochemical Characteristics of Wild Grown Caucasian Whortleberry (Vaccinium arctostaphylos L.) Genotypes from Northeastern Turkey. Not. Bot. Horti Agrobot. Cluj Napoca; 2018; 47, pp. 378-383. [DOI: https://dx.doi.org/10.15835/nbha47111288]
154. Dupak, R.; Hrnkova, J.; Simonova, N.; Kovac, J.; Ivanisova, E.; Kalafova, A.; Schneidgenova, M.; Prnova, M.S.; Brindza, J.; Tokarova, K.
155. Jaszcza, K.; Grzegorzewska, A.K.; Sachman, A.; Kalafova, A.; Massanyi, P.; Kovacik, A.; Dupak, R.; Capcarova, M. The Effect of Metformin and Sea Buckthorn (Hippophae rhamnoides L.) in Alleviating the Symptoms of Type 2 Diabetes Mellitus in the Liver of Zucker Diabetic Fatty Rats. J. Physiol. Pharmacol.; 2025; 76, 7.
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
Details
; George-Alin, Stoica 3
; Adrian Niculescu Stefan 4 ; Carmen Niculescu Elena 2 ; Văruț, Renata Maria 5 ; Singer, Cristina Elena 2 1 Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; [email protected]
2 Department of Mother and Baby, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; [email protected] (D.D.); [email protected] (C.E.S.)
3 Department of Pediatric Surgery, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
4 Department of Orthopedics, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania; [email protected]
5 Research Methodology Department, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania