A REVIEW ON HEPATO-PROTECTIVE HERBS USED IN AYURVEDA

Abstract

Liver is considered to be one of the vital organs which helps in maintaining the health of body. Yakrit (liver) is being described right from the vedic period. Modern lifestyles can overstress the liver and make it malfunctioning. No significant and safe hepato-protective drugs are available in modern therapeutics. The nature has bestowed some plants with the property to prevent, treat and cure hepatic disturbances with interception of fewer side effects. The focus of this review is to elucidate the importance of liver and aimed at compiling data based on reported works on medicinal plants that have been tested in hepato-toxicity models and proved as hepato-protective. Also the probable mode of action of a few herbs has been discussed in Ayurvedic and modern aspect.

Headnote

ABSTRACT

Liver is considered to be one of the vital organs which helps in maintaining the health of body. Yakrit (liver) is being described right from the vedic period. Modern lifestyles can overstress the liver and make it malfunctioning. No significant and safe hepato-protective drugs are available in modern therapeutics. The nature has bestowed some plants with the property to prevent, treat and cure hepatic disturbances with interception of fewer side effects. The focus of this review is to elucidate the importance of liver and aimed at compiling data based on reported works on medicinal plants that have been tested in hepato-toxicity models and proved as hepato-protective. Also the probable mode of action of a few herbs has been discussed in Ayurvedic and modern aspect.

KEY WORDS: Liver, Yakrit, Hepato-protective, Medicinal plants.

INTRODUCTION

"Is your life worth living"? It depends on the liver as it is the largest glandular organ in the body which works all the time to keep the body healthy. The liver is important because a person's nutritional level is not only determined by what he or she eats, but by what the liver processes. The incredible complexity of liver chemistry and its fundamental role in human physiology is so daunting to researchers that the thought that simple plant remedies might have something to offer is astonishing and incredible!

Liver is considered to be one of the most vital organs that functions as a centre of metabolism of nutrients such as carbohydrates, proteins and lipids and excretion of waste metabolites. Additionally, it is also handling the metabolism and excretion of drugs and other xenobiotics from the body thereby providing protection against foreign substances by detoxifying and eliminating them.

In Ayurvedic literature, yakrit (liver) is considered as an important anga (organ) of the human body right from the vedic period. Bhavamisra (16th Century) has described that it is situated right and below to the hridaya (heart) and is the sthana (seat) of pitta and sonitha (blood) (Srikantha Murthy, 2002). Susrutha (500 BC) mentioned yakrit (liver) as the abode of ranjaka pitta (Srikantha Murthy, 2004).

Susrutha (500 BC) describes yakrit (liver) as the sthana (seat) of rakta (blood) (Srikantha Murthy, 2005). Charaka (1000 BC) while describing the srotas (body channels), mentioned yakrit (liver) and pleeha (spleen) as the moola (root) of raktavaha Srotas (blood carrying channels) (Sharma and Dash, 2007). But it is Bhavamisra who for the first time introduced the term 'yakrit vikara' (liver disorders). Madhavanidana, in parishista prakarana, explains yakrit roga (liver disease) as a separate entity (Yadunandan Upadhyaya, 2000). The etio-pathogenesis of Yakrit roga has been described in Figure 1.

In dealing with problems of the liver, the primary goal is to enhance liver detoxification processes and to help protect against further liver damage. Significant and safe hepato- protective agents are unavailable in modern therapeutics. Therefore, due importance has been given globally to develop plant-based hepato-protective drugs effective against a variety of liver disorders.

The present review is aimed at compiling data based on reported works on promising phytochemicals from medicinal plants that have been tested on hepato-toxicity models.

Hepatoprotective Drugs

The important herbs used in Ayurveda to treat Liver diseases have been described in Table 1.

Tinospora cordifolia (Willd.) Miers. (Guduchi)

Tinospora cordifolia (Willd.) Miers., known as Guduchi, Amrita is one of the most valuable medicinal herbs of Ayurveda. The term 'Amrita' is attributed to this herb in recognition of its ability to impart youthfulness, vitality and longevity to its patron. In modern medicine, it is well known for its hepatoprotective, adaptogenic, immuno- modulatory activities and anti-fibrolytic activity. The active principle Tinosporin corrects immunosuppression associated with deranged hepatic function (Varsha et al., 2011).

Kupffer cells are major determinants of outcome of liver injury. The effect of Tinospora cordifolia (Willd.) Miers. was evaluated on Kupffer cell function, using carbon clearance test as a parameter. Antihepatotoxic activity of Tinospora cordifolia (Willd.) Miers. was studied in albino rats intoxicated with Carbon tetrachloride (CCl4). Liver function was assessed based on morphological, biochemical (SGPT, SGOT, Serum alkaline phosphatase, Serum bilirubin) and functional (Pentobarbitone sleep time) tests. A study conducted by Nagarkatti et al., (1994) on Tinospora cordifolia (Willd.) Miers. indicates that it had decreased fibrosis in rats, induced by CCl4 and significantly improved the suppressed Kupffer cell function in another rat model of chronic liver damage induced by heterologous serum. This raises the possibility that anti-fibrotic effect of Tinospora cordifolia is mediated through activation of kupffer cells.

Piper longum Linn. (Pippali)

Piper longum Linn. belongs to the family Piperaceae, is a common Indian dietary spice which has been shown to possess a wide range of therapeutic utilities. It has been reported to possess antiasthmatic, antiinflammatory, hepatoprotective, hypocholestremic and immunomodulatory activities. It contains various alkaloids like piperine, piperlongumine, piperlonguminine, etc. which helps in the regeneration of hepatocytes (Gupta AK, 2003).

A study conducted by Jagruti and Urvi (2009) showed a significant hepatoprotective effect on Piper longum Linn. milk extract treatment in CCl4 induced hepatic damage. An evident decrease in level of serum enzymes, total bilirubin and direct bilirubin was observed. Histo-pathological findings indicated that administration of Piper longum Linn. milk extract offered protection to the hepatocytes from damage induced by CCl4, with mild fatty changes in the hepatic parenchymal cells, which corroborated the changes observed in the hepatic enzymes. It also showed regenerating liver cells around the necrotic area.

Boerhavia diffusa Linn. (Punarnava)

The roots of Boerhavia diffusa Linn., commonly known as 'Punarnava', are used by a large number of tribes in India for the treatment of various hepatic disorders and for internal inflammation. Clinical data has also reported effectiveness of Boerhavia diffusa Linn. in cases of oedema and ascites resulting from early cirrhosis of the liver and chronic peritonitis (Varsha et al., 2011). The effect of ethanolic extract of roots of Boerhavia diffusa Linn. on country made liquor induced hepatotoxicity was studied in albino rats by Agarwal et al.(1991). Histo-pathological studies showed marked reduction in fat deposits in animals receiving Boehavia diffusa Linn. along with country made liquor. The plant protected the rats from hepatotoxic action by decreasing the serum alanine amino transferase (ALT), triglycerides, cholesterol and total lipid levels in both serum and tissues.

Punarnava contains alkaloids named as punarnavine and punarnavoside which shows anti-fibrinolytic activity but the hepatoprotective activity has been attributed to ursolic acid. Keppler and co-workers demonstrated that ursolic acid isolated from the leaves showed a dose dependent (5-20 mg/kg) hepatoprotective activity (21-l00%) in rats against thioacetamide, galactosamine and carbon tetrachloride induced hepatotoxicity in rats. These hepatotoxins decreased the viability of hepatocytes as assessed by trypan blue exclusion and rate of oxygen uptake tests and decreased the volume of bile as well as the level of its contents. Pretreatment with ursolic acid increased the viability of rat hepatocytes significantly (Keppler et al., 1968).

Andrographis paniculata Nees. (Kalamegha)

Andrographis paniculata Nees. is an ancient Indian medicinal herb, which has been used for centuries in Asia for its effects on various bodily functions and ailments, ranging from degenerative diseases to the common cold. The plant is known as King of Bitters. Andrographolide is an active constituent extracted and isolated from Andrographis paniculata Nees which is very bitter in taste (Anil Kumar et al., 2012).

A study conducted by Visen et al. (1993) on andrographolide showed a significant dose dependent protective activity against paracetamol-induced toxicity on ex vivo preparation of isolated rat hepatocytes. It significantly increased the percent viability of the hepatocytes as tested by trypan blue exclusion and oxygen uptake tests. It blocked the toxic effects of paracetamol on certain enzymes (GOT, GPT and alkaline phosphatase) in serum as well as in isolated hepatic cells. The bioactive constituent also antagonizes toxic effects of CCl4 and acetaminophen on certain enzymes (GOT, GPT and alkaline phosphates) in serum as well as in isolated hepatic cells. The results clearly depicted the plant extract to exert a choleretic effect that reduces the cholestasis and diminishes retention as well as increase the excretion of toxic xenobiotics from liver. Further, it also stimulated immune system to fight against inflammation, is mediated from the release of cytokinin from immunomodulators (Varsha et al., 2011).

Phyllanthus niruri Linn. (Bhumyamalaki)

Phyllanthus niruri Linn. is a medicinal herb used in connection with secondary hepatitis and other ailments, in ayurvedic medicine for over 2000 years.

It is a proved antiviral drug in Hepatitis-B in human subjects. In the preliminary study, carriers of Hepatitis-B virus were treated with a preparation of the plant 200 mg for 30 days. 22 of the 37(59%) treated patients had lost Hepatitis-B surface antigen, when tested 15- 20days after the end of the treatment, compared with only 1 out of 23 (4%) placebo treated controls. It has exhibited an inhibition of DNA polymerase on Hepatitis-B virus which is responsible for the replication of virus (Mehrotra et al., 1991).

In a study, phyllanthin, hypophyllanthin and tricotanol were isolated from petroleum ether extract of Phyllanthus niruri Linn. shows significant results on rat hepatocytes. Preclinical studies demonstrate that an extract of the Phyllanthus niruri Linn. plant inhibits endogenous DNA polymerase of hepatitis B virus and binds to the surface antigen of Hepatitis B virus. Extracts of Phyllanthus niruri Linn. have been shown to exert hepatoprotective effect against CCl4 induced HepG2 cell damage in rabbits. Pre-treatment with extract of Phyllanthus niruri Linn., reduced paracetamol-induced acute liver damage in rats as monitored by estimating the SGOT. In the in vitro-study, it decreased the release of AST and ALT in rat primary cultured hepatocytes being treated with ethanol (Tabassum et al., 2005).

Berberis aristata DC. (Daruharidra)

Berberis asiatica DC. being an important medicinal plant is used extensively for treating variety of ailments like infection of eyes, skin diseases, jaundice and rheumatism (Kirtikar and Basu, 1933). The major alkaloid of this plant is reported to be berberin which possess anti-oxidant property (Brijesh and Khosa, 2010).

The roots of Berberis aristata DC. possess more effective hepatoprotective activity against CCl4 intoxication in rats because of its antioxidant bearing capacity. Acute CCl4 administration increased serum and liver lipid peroxides significantly. Berberine treatment could reduce these elevated levels. Pathological analysis showed degeneration and necrosis after CCl4 administration. Berberine treatment could minimize these effects to a certain extent. (Brijesh and Khosa, 2010)

Picrorhiza kurroa Royle ex. Benth (Katuki)

Picrorhiza kurroa Royle ex Benth. is a renowned herb in the Ayurvedic system of medicine and has traditionally been used to treat disorders of the liver, upper respiratory tract, reduce fevers, treat dyspepsia, chronic diarrhoea, and scorpion sting. Kutkin, the active principal of Picrorhiza kurroa Royle ex. Benth is comprised of kutkoside and iridoid glycosides like picrosides I, II, and III (Chaturvedi and Singh, 1996).

The hepato-protective action of Picrorhiza kurroa Royle ex Benth. may be attributed to its ability to inhibit the generation of oxygen anions and to scavenge free radicals. Picrorhiza's antioxidant effect has been shown to be similar to that of superoxide dismutase, metal-ion chelators and xanthine oxidase inhibitors. Animal studies indicate that Picrorhiza's constituents exhibit a strong anti- cholestatic activity against a variety of liver- toxic substances, appearing to be even more potent than silymarin (Chander et al., 1992).

Picrorhiza also exhibits a dose-dependent choleretic activity, evidenced by an increase in bile salts and acids, and bile flow (Shukla et al., 1991).

Techoma undulata G. Don (Rohitaka)

Techoma undulata G. Don is a tropical coastal shrub that grows up to 1 m in height. It occurs throughout the Indian subcontinent. Techoma undulata G. Don leaves were tested against liver damage of albino rats. Loss of membrane structure and integrity because of lipid peroxidation was accompanied with the elevated levels of marker enzymes like SGOT, SGPT and total bilirubin. This shows that the plant has got membrane stabilizing function. Techoma undulata G. Don was potentially effective in blunting lipid peroxidation, suggesting that the extract possibly has antioxidant property to reduce ethanol-induced membrane lipid peroxidation and thereby to preserve membrane structure and might be due to the presence of glycosides, flavonoids, proteins, amino acids, tannins, saponins and triterpenoids (Singh D. et al., 2011).

Eclipta alba Hassk. (Bhrngaraja)

Eclipta alba Hassk. known as Bhringraja, is a plant belonging to the family Asteraceae. In ayurvedic medicine, the leaf extract is considered a powerful liver tonic. It possesses a wide range of biological activities and is used for the treatment of hepatitis and cirrhosis (Wagner, H. 1986). A study conducted by Murugaian P et al., 2008 on the whole plant extract of Eclipta alba Hassk. exhibited the protective activity against CCl4 induced liver injury. The plant contains an alkaloid Ecliptine which has got choleretic action. The extract augmented the bile flow in rats suggesting a stimulation of liver secretory capacity.

Tephrosia purpurea Pers. (Sharapunkha)

Tephrosia purpurea Pers. known as Sharapunkha, forms one of the most effective ingredients of formulations available in Indian market for liver ailments. In the traditional Indian medicine it is famous for its effectiveness in bilious febrile attacks, obstruction of liver and spleen apart. Especially, it has shown good results in cirrhosis and viral hepatitis in clinical trials (human studies). Dried ethanolic extract of Tephrosia purpurea Pers. was studied for its efficacy using both acute and chronic models CCl4 of experimentally induced hepatotoxicity. In vitro studies exploiting trypan blue exclusion assay revealed that the alcoholic extract exerted a significant hydroxyl radical scavenging activity (Sree Rama Murthy and Srinivasan, 1993).

Hepato-protective effect of aerial parts was evaluated against CCl4 induced hepatotoxicity in rats. An oral dose of powdered aerial parts to rats prevented the elevation of SGOT, SGPT, Bilirubin levels caused by CCl4. The mechanism of hepato-protection by Tephrosia purpurea Pers. mainly involves membrane stabilization of liver cells as indicated by decrease in levels of SGOT, SGPT and bilirubin levels, wherein it prevents cellular leakage and loss of functional integrity of the liver cell membranes caused by various hepatotoxic agents. Tephrosia purpurea Pers. also leads to increase in hepatic regeneration, which again contributes to its hepatoprotective efficacy (Jain, A. et al., 2006).

DISCUSSION

Yakrit (liver) is the sthana (seat) of pitta dosha (functional entity of the body), rakta dhatu (blood tissue) and agni (power of digestion). Treatment of all liver diseases in Ayurveda concentrates mainly on pitta dosha rather than the organ itself. Most of the hepato- protective drugs are kapha pitta samaka (pacifies pitta & kapha entities). The medicines and diets that normalise pitta are commonly used for all types of liver diseases.

Most of the hepato-protective herbs are having predominantly Tikta- Katu rasa (bitter and pungent taste) and deepana- pachana karma (digestive stimulant and carminative). These herbs are mainly agni vardhaka (increases fire entity in the body) and act on jatharagni (digestive fire) as well as dhatwagni (fire residing in tissues). These rasas (taste) have the property of increasing metabolism (mainly enhancing catabolism), thereby these herbs help in digestion of nitrogenous waste products collected in body, due to disturbed metabolism. Most of the hepato-protective herbs possess laghu (easy to digest) and ruksha (dry) gunas (quality). Laghu guna (easy to digest quality) helps in increasing jatharagni (digestive fire) as they are easily digestible and they form less nitrogenous waste products. Ushna virya (hot potency) help in enhancing the Jatharagni (digestive fire) as well dhatwagni because ushna virya (hot potency) increases metabolism (catabolism).

According to modern pharmacology, the main mechanism involved in the protection of liver could be associated with the strong capability of hepato-protective drugs to reduce the intracellular levels of reactive oxygen species by enhancing the level of both enzymatic and non-enzymatic antioxidants. These drugs protect liver tissues against oxidative damage and somehow help in stimulating the repair mechanism of liver.

The mode of action of hepato-protective herbs varies from herb to herb. Hepatocyte membrane stabilizing capacity is shown by Techoma undulata G. Don., thereby preventing toxins from entering the cell through entero- hepatic recirculation. Berberis aristata DC., Tephrosa purpurea Pers. and Piper longum Linn. help in regeneration of liver cells by stimulating nuclear polymerase A and increasing ribosomal protein synthesis. Tinospora cordifolia (Willd.) Miers. enhance the activity of Kuffer cells which is involved in the production of substances like interleukins and tumour necrosis factors which activate the immune system of the body and act as immuno-modulatory. Phyllanthus niruri Linn. possess antiviral property and help in microsomal induction or inhibition. Boerhavia diffusa Linn possess antifibrinolytic activity. Eclipta alba Hassk., Andrographis paniculata Nees. and Picrorhiza kurroa Royle ex Benth. increase the choleretic activity.

Different single herbs are very much useful in liver disorders as shown by research studies. A few Ayurvedic compound formulations such as Phalatrikadi kwatha, Vasa guduchyadi kashaya, Patola katurohinyadi kashaya, Guda pippali, Arogyavardhini vati, Rohitakarista mentioned in Sharangadhara Samhitha (13th Century) are also found to be promising in hepatopathy.

CONCLUSION

The challenge that modern medical system face with liver disorders is that such drugs would have to be metabolized in the liver. Since the liver itself is in disorder, the problem is how to ensure effective metabolism of the drugs that have been prescribed. In this context, Ayurveda sages have used their genius, to formulate such herbal formulations that can be metabolized even by a sluggish liver. The logic on which such formulations work is that they first heal and reinvigorate the liver and thus contribute to the restoration of its normal functions. Preserving health of the liver means adding healthier years to one's life. Be polite to your liver & Keep it Living and Lively!!

ACKNOWLEDGEMENT

Author is thankful to Dr. Rajasekhara N, Head & Professor and Dr. Vijayalakshmi P.B, Lecturer, Dept. of Dravyaguna, KVG Ayurveda College, Sullia for all the help and guidance in writing this article.

Sidebar

Cite this article:

Giby Abraham (2014), A REVIEW ON HEPATO-PROTECTIVE HERBS USED IN AYURVEDA, Global J Res. Med. Plants & Indigen. Med., Volume 3(7): 303-311

References

REFERENCES

Agarwal S, Gulati R Agarwal SS. (1991) 'Hepatoprotective activity of Boerhaavia diffusa Linn. against country made liquor induced hepatotoxicity in albino rats fed on controlled calorie diet'. Ind J Pharma (23), pp.264-267.

Anil Kumar, Jyotsna Dora, Anup Singh and Rishikant Tripathi (2012) 'A Review On King Of Bitter (Kalmegh)', International Journal Of Research In Pharmacy And Chemistry, (2), pp.116- 124

Brijesh Tiwari K, Khosa R.L. (2010) 'Evaluation of the hepatoprotective and antioxidant effect of Berberis aristata against experimentally induced liver injury in rats' Int J of Pharmacy and Pharmaceutical Sci , 2(1), pp.92-99

Chaturvedi, G.N., Singh, R.H. (1996) 'Jaundice of infectious hepatitis and its treatment with an indigenous drug, Picrorhiza kurrooa. Journal of Research in Indian Medicine (1), pp.1-13.

Chander R, Kapoor NK, Dhawan BN. (1992) 'Picroliv, picroside-I and kutkoside from Picrorhiza kurroa are scavengers of superoxide anion', Biochem Pharmacol, (44), pp.180-183.

Gupta AK (2003) Quantitative analysis of medicinal aromatic plants,( III) pp.125- 129.

Jagruti Patel A & Urvi Shah S. (2009) 'Hepatoprotective activity of Piper longum traditional milk extract on carbon tetrachloride induced liver toxicity in Wistar rats', Bol Latinoam Caribe Plant Med Aromat, 8(2), pp.121-128.

Jain A, Singhai AK, Dixit VK (2006), 'A comparative study of ethanol extract of Leaves of Tephrosia purpurea Pers and the flavonoid isolated for Hepatoprotective activity', Ind J Pharm sci, 68(6), pp.740-743

Jariyawat S, Suksen K, Chuncharunee A, Sophasan S, Piyachaturawat P.(2005), 'Evaluation on the hepatoprotective effects of the standard extracts from Curcuma longa and Andrographis paniculata', 31st Congress on Sci Technol Thailand Suranaree University of Technol, pp.1-3.

Keppler D, Lesch NR, Reutter W, Decker K(1968), 'Experimental hepatitis induced by D galactosamine', Exp Mol Path, (9), pp.279-290.

Kirtikar K R, Basu B D (1993), Indian Medicinal Plants, I. Allahabad, Latit Mohan Basu and Co.

Mehrotra R, Rawat S, Kulshreshtha DK, Goyal P, Patnaik GK, Dhawan BN (1991), In vitro effect of Phyllanthus amarus on Hepatitis-B virus, P.G dept of Pathology, King George's Medical College, Lucknow; Indian J Med Res, pp.71-73

Murugaian P, Ramamurthy V, Karmegam N. (2008), 'Hepatoprotective Activity of Eclipta alba L. Against Acute Hepatotoxicity in Rats', Res J Agri Bio Sci, 4(6), pp.685-687

Nagarkatti DS, Rege NN, Desai NK, Dahanukar SA (1994) 'Modulation of Kupffer cell activity by Tinospora cordifolia in liver damage. J Postgrad Med. (40), pp.65-67.

Sembulingam K, Sembulimgam Prema (2000) Essentials of Medical Physiology, 6th ed. New Delhi: Jaypee Brother Medical Publishers, pp.253

Sharma PV (2009) Dravyaguna Vijnana (II) Varanasi: Chaukhamba Bharathy Academy.

Sharma Ram Karan, Dash Bhagwan (Ed.) (2007) Charaka Samhitha, Vol.II. Vimanasthana 5/8, Varanasi: Chaukhamba Sanskrit Series Office, pp.117

Shukla B, Visen PK, Patnaik GK (1991), 'Choleretic effect of picroliv, the hepatoprotective principle of Picrorhiza kurroa', Planta Med (57), pp.29-33.

Singh D, Gupta RS (2001), 'Hepatoprotective Activity of Methanol Extract of Tecomella undulata against Alcohol and Paracetamol Induced Hepatotoxicity in Rats'; Life Sciences and Medicine Research, pp.261.

Sree Rama Murthy M, Srinivasn M. (1993), 'Hepatoprotective effects of Tephrosia purpurea experimental animals', Ind J Pharmacol, (25), pp.34-36.

Srikantha Murthy KR (2002), Bhavaprakasha Samhitha, Vol II, Madhyama Khanda, 33/9, Varanasi: Chowkamba Krishna Das Academy, pp.446

Srikanta Murthy KR (2004) Susrutha Samhitha, 2nd ed., Sutrasthana 21/10, Varanasi: Chaukhamba Orientalia, pp.155

Srikanta Murthy KR (2005) Susrutha Samhitha, 2nd ed., Sutrasthana 21/16, Varanasi: Chaukhamba Orientalia, pp.157

Tabassum N, Chatturvedi S, Aggrawal SS, Ahmed N. (2005), 'Hepatoprotective studies on Phyllanthus niruri on Paracetamol Induced Liver cell Damage in Albino Mice', Exper Med,12(4), pp. 211-212.

Varsha Kashaw, Amit kumar Nema, Abhinav Agarwal (2011) 'Hepatoprotective Prospective Of Herbal Drugs and Their Vesicular Carriers- A Review', International Journal of Research in Pharmaceutical and Biomedical Science, (2), pp.360-374

Visen PK, Shukla B, Patnaik GK, Dhawan BN (1993), 'Andrographolide protects rat hepatocytes against paracetamol- induced damage', J Ethnopharmacol., 40(2), pp.131-136.

Yadunandan Upadhyaya (2000) Madhava Nidana, 29th ed., Part 2, Parishistam, Yakrit roganidanam, Varanasi: Chaukhamba Sanskrit Sansthan, pp.467.

Wagner H. (1986) 'Coumestans as the main active principles of the liver drugs Eclipta alba and Wedelia calendulacea', Planta Med.,(5), pp.370-374.