Phenolic Acid Derivatives, Flavonoids and Other Bioactive Compounds from the Leaves of Cardiocrinum cordatum (Thunb.) Makino (Liliaceae)

Abstract

Cardiocrinum cordatum (Thunb.) Makino (Family: Liliaceae), commonly known as ‘Ubayuri’, is native to Japan and some islands in the Russian Far East. It has high value as food, medicinal, and ornamental species. The aim of this study was to isolate and characterize the main chemical constituents of the leaves of C. cordatum. A total of 19 compounds, namely caffeic acid (1), caffeic acid methyl ester (2), caffeic acid β-glucopyranosyl ester (3), caffeic acid 4-O-β-glucopyranoside (4), ferulic acid (5), isoferulic acid (6), protocatechuic acid (7), syringic acid (8), 2,6-dimethoxy-p-hydroquinone 1-O-β-glucopyranoside (9), esculetin (10), taxifolin (11), quercetin 3-O-(6-O-α-rhamnopyranosyl)β-glucopyranoside-7-O-β-rhamnopyranoside (12), 2,7-dimethyl-2,4-diene-deca-α,ω-diacid β-glucopyranoside (13), 4-[formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoic acid (14), (3Z)-3-hexenyl β-glucopyranoside (15), tryptophan (16), adenine (17), adenosine (18), and 2-deoxyadenosine (19) were isolated using various chromatographic methods. The structures of isolated compounds were elucidated on the basis of their NMR spectroscopic data. All these compounds were isolated for the first time from the genus Cardiocrinum. Phenolic acid derivatives and flavonoids can be considered as chemotaxonomic markers in the leaves of Cardiocrinum species.

1. Introduction

The genus Cardiocrinum (Liliaceae) comprises of three perennial bulbiferous herb species, C. cathayanum (E. H. Wilson) Stearn, C. cordatum (Thunb.) Makino., and C. giganteum (Wall.) Makino [1,2]. Among them, C. cathayanum is endemic to China [1,3] and C. giganteum is distributed in Bhutan, China, India, Myanmar, and Nepal [1,3,4]. Cardiocrinum cordatum (Figure 1), commonly known as ‘Ubayuri’ in Japan, is native to Japan and some islands in the Russian Far East [1,5]. It is a perennial herb with the height of about 60–100 m. In traditional medicines, the bulbs are used for the treatment of fever and stomachache [6]. The starch obtained from the bulbs is used as food [6,7,8]. Although the Cardiocrinum species have high value as food, medicinal, and ornamental plants [4,6], only a few studies have been performed regarding their chemical constituents. Some previous studies reported the flavonoids from the seeds of C. giganteum [9,10,11] and the starch composition of the bulbs of C. cordatum var. glehnii (F.Schmidt) H.Hara [7,8]. However, there is no report on the chemical constituents of the leaves of C. cordatum. Detailed understanding of bioactive chemical composition of plant species is necessary to explore their potential as raw materials for pharmaceutical, cosmetic, and nutraceutical also to understand the role of these compounds in chemotaxonomy. Thus, the main aim of this study was to isolate and identify the major chemical constituents of the leaves of C. cordatum.

2. Results and Discussion

The dried young leaves of C. cordatum were extracted with methanol (MeOH) and the extract was then subjected to repeated column chromatography on MCI gel CHP20P, Sephadex LH-20, ODS and silica gel to isolate 19 pure compounds. The structures of isolated compounds were elucidated on the basis of their ¹H, ¹³C- and 2D-nuclear magnetic resonance (NMR) spectroscopic data, and by comparison with literature values as caffeic acid (1) [12], caffeic acid methyl ester (2) [12], caffeic acid β-glucopyranosyl ester (3) [13], caffeic acid 4-O-β-glucopyranoside (4) [13], ferulic acid (5) [14], isoferulic acid (6) [14], protocatechuic acid (7) [15], syringic acid (8) [15], 2,6-dimethoxy-p-hydroquinone 1-O-β-glucopyranoside (9) [16], esculetin (10) [17], taxifolin (11), quercetin 3-O-(6-O-α-rhamnopyranosyl)β-glucopyranoside-7-O-α-rhamnopyranoside (12) [18], 2,7-dimethyl-2,4-diene-deca-α,ω-diacid β-glucopyranoside (13) [19], 4-[formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoic acid (14) [20], (3Z)-3-hexenyl β-glucopyranoside (15) [21], tryptophan (16), adenine (17), adenosine (18) [22] and 2-deoxyadenosine (19) [22] (Figure 2).

All these compounds belonging to different chemical classes such as phenylpropanoids (1–6), simple phenolic compounds (7–9), coumarin (10) and flavonoids (11, 12), 2,7-dimethyl-2,4-diene-deca-α,ω-diacid glucopyranoside (13), 4-[formyl-5-(methoxymethyl)-1H-pyrrol-1-yl] butanoic acid (14), (3Z)-3-hexenyl β-glucopyranoside (15), amino acid (16), and nucleic acid derivatives (17–19) were isolated and identified for the first time from the genus Cardiocrinum. The genus Cardiocrinum comprises only three species, C. cathayanum, C. cordatum, and C. giganteum [1,2]. Further, two varieties of C. giganteum i.e., C. giganteum var. giganteum and C. giganteum var. yunnanense (Leichtlin ex Elwes) Stearn [3], and one variety of C. cordatum, i.e., C. cordatum var. glehnii (F.Schmidt) H.Hara. are reported [8]. Cardiocrinum species are not well explored regarding their chemical constituents except the isolation and identification of bioflavonoids from the seeds of C. giganteum. Shou et al. [10] reported two new racemic bioflavonoids, CGY-1 ((S)-2R,3″R- and (R)-2″S,3″S-dihydro-3″-hydroxyamentoflavone-7-methyl ether) and CGY-2 ((S)-2″R,3″R- and (R)-2″S,3″S-dihydro-3″-hydroxyamentoflavone) from the 95% ethanol extract of the seeds of C. giganteum var. giganteum having antitussive properties. CGY-1 was further reported as a potent agent to improve memory deficit for the treatment of cognitive dysfunction [9]. Similarly, Xia et al. [11] reported the isolation of a new biflavonoid, 3”-hydroxyrobustaflavone along with 3”-hydroxyamentoflavone, quercetin, apigenin, and kaempferol with antioxidative activities from the 95% ethanol extract of seeds of C. giganteum var. yunnanense.

Phenolic acids belonging to the both groups of hydroxycinnamic acid derivatives (phenylpropanoid derivatives) and hydroxybenzoic derivatives are abundantly present in many plant species and specially in berries, fruits, and vegetables [23,24]. Phenolic acids and flavonoids are reported to play an important role in plants as antioxidants, as defense regulators, during unfavorable conditions such as drought and infections and as signaling molecules in plant-microbe symbiosis [25,26,27,28,29,30,31]. These compounds exert potent pharmacological activities in humans and animals and are of great interest as food, nutrition, and medicine [32,33,34,35,36]. Phenolic acid derivatives and flavonoids are reported as common constituents of plants of various genera of Liliaceae family such as Fritillaria [37], Hosta [38], and Lilium [39]. Another compound, 2,7-dimethyl-2,4-diene-deca-α,ω-diacid β-glucopyranoside (13) was reported previously from Orycatanthus sp. (Loranthaceae) [19] and Cydonia vulgaris Pers. (Rosaceae) [40]. It was reported as a potent antitumor compound as it inhibited the ligand binding to vascular endothelial growth factor (VEGF) receptor [19]. Its aglycone, 2,7-dimethyl-2,4-diene-deca-α,ω -diacid, was reported from Phaseolus multiflorus Lam. (Fabaceae) [41]. Similarly, 4-[formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoic acid (14), a pyrrole alkaloid derivative, was previously reported from Lycium chinense Mill. (Solanaceae) as a hepatoprotective compound [42]. (3Z)-3-Hexenyl β-glucopyranoside (15) has been previously reported from Pertya glabrescens Sch.Bip. (Asteraceaae) [43], Codonopsis Radix [21], Celosia argentea L. (Amaranthaceae) [44], Roscoea purpurea Sm. (Zingiberaceae) [45], among others. An amino acid, tryptophan (16) and three nucleic acid derivatives (17–19), which are common primary metabolites, were also isolated and identified in this study.

As there have been no previous studies on the leaves of other Cardiocrinum species and varieties, a chemotaxonomic comparison at present is difficult and needs further research. These compounds isolated in this study might also be specific to one genotype of the plant species under investigation in this study, thus the comparison of the chemical constituent profile of plants collected in different localities in necessary. As only very few studies have reported the activity of isolated compounds form Cardiocrinum plants, thus detailed bioassay guided isolation of the compound may result in the isolation of other bioactive compounds. Similarly, the quantitative analysis of the compounds may also help to explore these species as potential new sources of bioactive compounds.

3. Materials and Methods

3.1. General Experimental Procedures

¹H-, ¹³C- and 2D-NMR spectra were measured on Bruker AVANCE-I 600 NMR Spectrometer (¹H-NMR: 600 MHz and ¹³C-NMR: 125 MHz). Column chromatography (CC) was carried out with MCI gel CHP20P (75–150 μm, Mitsubishi Chemical Industries Co., Ltd., Tokyo, Japan), Sephadex LH-20 (Amersham Pharmacia Biotech, Tokyo, Japan) and Chromatorex ODS (30–50 μm, Fuji Silysia Chemical Co., Ltd., Aichi, Japan). TLC was performed on a precoated silica gel 60 F254 (0.2 mm, aluminum sheet, Merck KGaA, Darmstadt, Germany).

3.2. Plant Materials

The young leaves of C. cordatum were collected in Kochi Prefecture, Japan in May 2015 and identified by Prof. Takashi Watanabe, Kumamoto University. A voucher specimen (No. KUT [exp]004) has been deposited at the Department of Medicinal Botany, School of Pharmacy, Kumamoto University, Kumamoto, Japan.

3.3. Extraction and Isolation

The shade dried young leaves of C. cordatum (960 g) were extracted twice with MeOH (15 L each time). The extracts were then combined and evaporated under reduced pressure to give 202.0 g extract. The extract was then subjected on MCI gel CHP20P column chromatography (CC) and eluted successively with water, 20%, 40%, 60%, 80%, 100% MeOH and CHCl₃:MeOH (1:1) to give 10 fractions (1–10). Fraction 3 (5.8 g, H₂O eluate) was subjected on Sephadex LH-20 CC (50% MeOH) to give four subfractions (3-1–3-4). Fraction 3-4 was subjected on ODS CC (5–100% MeOH) to afford compound 7 (9.7 mg). Fraction 4 (3.0 g, H₂O eluate) was subjected on Sephadex LH-20 CC (50% MeOH) to give seven subfractions (4-1–4-7). Subfraction 4-3 (311.0 mg) was subjected to repeated column chromatography on silica gel CC (CH₂Cl₂:MeOH:H₂O = 8:2:0.1) to afford compound 9 (6.9 mg). Subfraction 4-4 (589.0 mg) was subjected to silica gel CC (CH₂Cl₂:MeOH:H₂O = 8:2:0.1) followed by ODS CC (10% MeOH) to afford compounds 17 (6.1 mg) and 18 (1.4 mg) and 19 (4.2 mg). Subfraction 4-6 (138.3 mg) was ODS CC (20–40% MeOH) followed by repeated CC using Sephadex LH-20 (50% MeOH) to afford compounds 1 (4.7 mg), 3 (14.2 mg), 4 (11.0 mg), and 16 (23.0 mg). Fraction 5 (711.0 mg, 20% MeOH eluate) was subjected to Sephadex LH-20 CC (50% MeOH) and then to repeated CC on silica gel (CH₂Cl₂:MeOH:H₂O = 8:2:0.1) to afford compound 10 (2.4 mg). Fraction 6 (3.98 g, 40% MeOH eluate) was subjected to Sephadex LH-20 CC (50% MeOH) to obtain 4 subfractions (6-1–6-4). These subfractions were further purified using silica gel, Sephadex LH-20, and ODS CC to afford compounds 12 (15.9 mg), 13 (4.3 mg), 14 (11.0 mg) and 15 (4.6 mg). Fraction 7 (4.8 g, 60% MeOH eluate) was subjected to silica gel CC (CH₂Cl₂:MeOH:H₂O = 8:2:0.1) to obtain 5 subfractions (7-1–6-5). These subfractions were further purified using silica gel, Sephadex LH-20 and ODS CC to afford compounds 2 (1.8 mg), 5 (4.1 mg), 6 (1.1 mg), 8 (5.0 mg), and 11 (11.5 mg).

3.4. Esculetin (10)

¹H-NMR (in CD₃OD) δ_H 7.84 (1H, d, J = 9.4 Hz, H-4), 7.34 (1H, s, H-8), 7.04 (1H, s, H-7), 6.21 (1H, d, J = 9.4 Hz, H-3). ¹³C-NMR (in CD₃OD) δ_C 163.7 (C-2), 153.4 (C-7), 152.7 (C-6), 146.1 (C-4), 144.5 (C-9), 116.8 (C-5), 113.2 (C-3), 112.9 (C-10), 104.4 (C-8).

3.5. 2,7-Dimethyl-2,4-diene-deca-α,ω-diacid β-glucopyranoside (13)

¹H-NMR (in CD₃OD) δ_H 7.17 (1H, d, J = 11.4 Hz, H-3), 6.47 (1H, dd, J = 14.9, 11.4 Hz, H-4), 6.11 (1H, dt, J = 14.9 Hz, H-5), 4.33 (1H, d, J = 7.6 Hz, Glc-1), 4.02 (1H, m, H-8), 3.83–3.65 (2H, m, Glc-6), 3.45–3.15 (4H, m, Glc-2–Glc-5), 2.64–2.54 (2H, m, H-9), 2.47–2.16 (2H, m, H-6), 1.95 (1H, m, H-7), 0.95 (3H, d, J = 6.8 Hz, H-11). ¹³C-NMR (in CD₃OD) δ_C 176.6 (C-10), 172.3 (C-1), 142.6 (C-5), 140.1 (C-3), 129.0 (C-4), 126.5 (C-2), 104.8 (Glc-1), 81.9 (C-8), 78.2 (Glc-3), 77.8 (Glc-5), 75.4 (Glc-2), 71.6 (Glc-4), 62.9 (Glc-6), 39.4 (C-9), 38.7 (C-7), 37.0 (C-6), 15.6 (C-11), 12.7 (C-12).

3.6. 4-[Formyl-5-(methoxymethyl)-1H-pyrrol-1-ly]butanoic acid (14)

¹H-NMR (in CD₃OD) δ_H 9.45 (1H, s, CHO), 6.98 (1H, d, J = 4.0 Hz, H-3), 6.28 (1H, d, J = 4.0 Hz, H-4), 4.49 (2H, s, H-6), 4.37 (2H, t, J = 7.3 Hz, H-1′), 3.35 (3H, s, OCH₃), 2.32 (2H, t, J = 7.3 Hz, H-3′), 2.01 (2H, q, J = 7.3 Hz, H-2′). ¹³C-NMR (in CD₃OD) δ_C 181.1 (CHO), 176.6 (COOH), 141.1 (C-5), 133.9 (C-2), 125.9 (C-3), 112.9 (C-4), 66.4 (C-6), 58.3 (OCH₃), 45.9 (C-1′), 31.8 (C-3′), 27.7 (C-2′).

3.7. (3-Z)-3-Hexenyl β-glucopyranoside (15)

¹H-NMR (in CD₃OD) δ_H 5.47 (1H, dt, J = 10.7 Hz, H-3), 5.37 (1H, dt, J = 10.7, 7.0 Hz, H-4), 4.33 (1H, d, J = 7.5 Hz, Glc-1), 3.86 (2H, m, Glc-6), 3.68–3.18 (4H, m, Glc-2–Glc-5), 2.37 (2H, q, H-2), 2.05 (2H, q, H-5), 0.94 (3H, t, H-6); ¹³C-NMR (in CD₃OD) δ_C 135.3 (C-3), 125.8 (C-4), 104.1 (Glc-1), 77.7 (Glc-3,Glc-5), 74.9 (Glc-2), 71.4 (Glc-4), 71.0 (C-1), 62.5 (Glc-6), 28.7 (C-2), 21.6 (C-5), 14.8 (C-6).

4. Conclusions

A total of 19 compounds belonging to different chemical classes such as phenylpropanoids, benzoic acid derivatives, flavonoids, coumarins, etc., were isolated and identified for the first time from the genus Cardiocrinum. From the results of current study and with the previous reports, it can be assumed that the flavonoids and other phenolic compounds can be considered as main components in the aerial parts including leaves, stems, and seeds, which may serve as the chemotaxonomic markers of these species. Future studies are necessary to isolate and identify chemical constituents from the aerial parts of other two species and comparison of interspecific variation. On the other hand, bioactivity evaluations of the extracts and isolated compounds is necessary to explore the potential of C. cordatum for use in pharmaceutical, cosmetic, and functional food industries.

Author Contributions

Conceptualization, H.P.D.; methodology, K.H. and H.P.D.; formal analysis, K.H. and H.P.D.; investigation, K.H. and H.P.D.; resources, T.W. and H.P.D.; data curation, K.H. and H.P.D.; writing—original draft preparation, K.H. and H.P.D.; writing—review and editing, H.P.D.; supervision, project administration and funding acquisition, H.P.D. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported in part by Program for Leading Graduate Schools, Health life science: Interdisciplinary and Glocal Oriented (HIGO) Program, MEXT, Japan.

Data Availability Statement

Samples of isolated compounds are available from authors upon request.

Acknowledgments

We are grateful to Teruo Tanaka of Institute of Resource Development and Analysis, Kumamoto University for measurement of NMR spectra.

Conflicts of Interest

K.H. is a staff of Astellas Pharma Inc., Japan. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Figure 1. Photographs of Cardiocrinum cordatum (From left: Young leaves, plant at flowering stage and flower).

Figure 2. Structures of compounds isolated from Cardiocrinum cordatum.

References

1. Lu, R.S.; Li, P.; Qiu, Y.X. The complete chloroplast genomes of three Cardiocrinum (Liliaceae) species: Comparative genomic and phylogenetic analyses. Front. Plant Sci.; 2017; 7, 2054. [DOI: https://dx.doi.org/10.3389/fpls.2016.02054]

2. Li, R.; Yang, J.; Yang, J.; Dao, Z. Isolation and characterization of 21 microsatellite loci in Cardiocrinum giganteum var. yunnanense (Liliaceae), an important economic plant in China. Int. J. Mol. Sci.; 2012; 13, pp. 1437-1443.

3. Songyun, L.; Tamura, M.N. 19. Cardiocrinum (Endlicher) Lindley, Veg. Kingd. 205. 1846. Flora of China. (Flagellariaceae through Marantaceae); Wu, Z.Y.; Raven, P.H. Science Press: Beijing, China, Missouri Botanical Garden Press: St. Louis, MI, USA, 2000; Volume 24, pp. 134-135.

4. Watanabe, T.; Rajbhandari, K.R.; Malla, K.J.; Devkota, H.P.; Yahara, S. A Handbook of Medicinal Plants of Nepal Supplement I; Ayurseed L.E.I.: Kanagawa, Japan, 2013.

5. Araki, K.; Shimatani, K.; Nishizawa, M.; Yoshizane, T.; Ohara, M. Growth and survival patterns of Cardiocrinum cordatum var. glehnii (Liliaceae) based on a 13-year monitoring study: Life history characteristics of a monocarpic perennial herb. Botany; 2010; 88, pp. 745-752.

6. Watanabe, M.; Devkota, H.P.; Sugimura, K.; Watanabe, T. A Guidebook of Medicinal Plant Park; School of Pharmacy, Kumamoto University: Kumamoto, Japan, 2018.

7. Iwata, H.; Hashino, A.; Takagi, H. Edible wild plants. XVII. Starches from wild plants. Eiyo Shokuryo Gakkaishi; 1955; 7, pp. 143-145. [DOI: https://dx.doi.org/10.4327/jsnfs1949.7.143]

8. Shiozaki, M.; Ishii, S. Composition of Cardiocrinum cordatum var. glehnii and Traditional Derived Dried Foods of the Ainu. Jpn. J. Nutr. Diet.; 2004; 62, pp. 303-306.

9. Zhang, R.R.; Lin, Z.X.; Lu, X.Y.; Xia, X.; Jiang, R.W.; Chen, Q.B. CGY-1, a biflavonoid isolated from Cardiocrinum giganteum seeds, improves memory deficits by modulating the cholinergic system in scopolamine-treated mice. Biomed. Pharmacother.; 2019; 111, pp. 496-502. [DOI: https://dx.doi.org/10.1016/j.biopha.2018.12.100]

10. Shou, J.W.; Zhang, R.R.; Wu, H.Y.; Xia, X.; Nie, H.; Jiang, R.W.; Shaw, P.C. Isolation of novel biflavonoids from Cardiocrinum giganteum seeds and characterization of their antitussive activities. J. Ethnopharmacol.; 2018; 222, pp. 171-176. [DOI: https://dx.doi.org/10.1016/j.jep.2018.05.003]

11. Xia, X.; Wang, G.N.; Wu, H.Y.; Tian, H.Y.; Shaw, P.C.; Jiang, R. Isolation and identification of antioxidant flavonoids from the seeds Cardicrinum giganteum var. yunnanense. J. Pharm. Biomed. Sci.; 2016; 6, pp. 374-377.

12. Chang, S.W.; Kim, K.H.; Lee, I.K.; Choi, S.U.; Ryu, S.Y.; Lee, K.R. Phytochemical constituents of Bistorta manshuriensis. Nat. Prod. Sci.; 2009; 15, pp. 234-240.

13. Cui, C.-B.; Tezuka, Y.; Kikuchi, T.; Nakano, H.; Tamaoki, T.; Park, J.-H. Constituents of a Fern, Davallia mariesii Moore. I. Isolation and Structures of Davallialactone and a New Flavanone Glucuronide. Chem. Pharm. Bull.; 1990; 38, pp. 3218-3225. [DOI: https://dx.doi.org/10.1248/cpb.38.3218] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/2092929]

14. Song, Y.; Zhou, J.; Wang, X.; Xie, X.; Zhao, Y.; Ni, F.; Huang, W.; Wang, Z.; Xiao, W. A new ferulic acid ester from Rhodiola wallichiana var. cholaensis (Crassulaceae). Nat. Prod. Res.; 2018; 32, pp. 77-84. [DOI: https://dx.doi.org/10.1080/14786419.2017.1335724] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28610437]

15. Liao, C.R.; Kuo, Y.H.; Ho, Y.L.; Wang, C.Y.; Yang, C.S.; Lin, C.W.; Chang, Y.S. Studies on cytotoxic constituents from the leaves of Elaeagnus oldhamii Maxim. In non-small cell lung cancer A549 cells. Molecules; 2014; 19, pp. 9515-9534. [DOI: https://dx.doi.org/10.3390/molecules19079515]

16. Otsuka, H.; Takeuchi, M.; Inoshiri, S.; Sato, T.; Yamasaki, K. Phenolic compounds from Coix lachryma-jobi var. Ma-yuen. Phytochemistry; 1989; 28, pp. 883-886. [DOI: https://dx.doi.org/10.1016/0031-9422(89)80136-0]

17. Joshi, K.R.; Devkota, H.P.; Yahara, S. Chemical analysis of flowers of Bombax ceiba from Nepal. Nat. Prod. Commun.; 2013; 8, pp. 583-584. [DOI: https://dx.doi.org/10.1177/1934578X1300800508]

18. Yoshimitsu, H.; Nishida, M.; Hashimoto, F.; Tanaka, M.; Sakata, Y.; Okawa, M.; Nohara, T. Chromone and flavonol glycosides from Delphinium hybridum cv. “Belladonna Casablanca”. J. Nat. Med.; 2007; 61, pp. 334-338. [DOI: https://dx.doi.org/10.1007/s11418-007-0142-y]

19. Hegde, V.R.; Pu, H.; Patel, M.; Jachens, A.; Gullo, V.P.; Chan, T.M. A new antitumor compound from the plant Oryctanthus sp. as a VEGF receptor binding inhibitor. Bioorganic Med. Chem. Lett.; 2005; 15, pp. 4907-4909. [DOI: https://dx.doi.org/10.1016/j.bmcl.2005.08.022] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16183284]

20. Li, J.; Pan, L.; Naman, C.B.; Deng, Y.; Chai, H.; Keller, W.J.; Kinghorn, A.D. Pyrrole alkaloids with potential cancer chemopreventive activity isolated from a goji berry-contaminated commercial sample of African mango. J. Agric. Food Chem.; 2014; 62, pp. 5054-5060. [DOI: https://dx.doi.org/10.1021/jf500802x] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/24792835]

21. Mizutani, K.; Yuda, M.; Tanaka, O.; Saruwatari, Y.I.; Fuwa, T.; Jia, M.R.; Ling, Y.K.; Pu, X.F. Chemical Studies on Chinese Traditional Medicine, Dangshen. I. Isolation of (Z)-3- and (E)-2-Hexenyl β-D-Glucosides. Chem. Pharm. Bull.; 1988; 36, pp. 2689-2690. [DOI: https://dx.doi.org/10.1248/cpb.36.2689] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/3240491]

22. Ciuffreda, P.; Casati, S.; Manzocohi, A. Spectral assignments and reference data complete ¹H and ¹³C NMR spectral assignment of α- And β-adenosine, 2′-deoxyadenosine and their acetate derivatives. Magn. Reson. Chem.; 2007; 45, pp. 781-784. [DOI: https://dx.doi.org/10.1002/mrc.2036]

23. Zadernowski, R.; Naczk, M.; Nesterowicz, J. Phenolic acid profiles in some small berries. J. Agric. Food Chem.; 2005; 53, pp. 2118-2124. [DOI: https://dx.doi.org/10.1021/jf040411p] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/15769144]

24. Mattila, P.; Hellström, J.; Törrönen, R. Phenolic acids in berries, fruits, and beverages. J. Agric. Food Chem.; 2006; 54, pp. 7193-7199. [DOI: https://dx.doi.org/10.1021/jf0615247]

25. Agati, G.; Azzarello, E.; Pollastri, S.; Tattini, M. Flavonoids as antioxidants in plants: Location and functional significance. Plant Sci.; 2012; 196, pp. 67-76. [DOI: https://dx.doi.org/10.1016/j.plantsci.2012.07.014]

26. Harborne, J.B.; Williams, C.A. Advances in flavonoid research since 1992. Phytochemistry; 2000; 55, pp. 481-504. [DOI: https://dx.doi.org/10.1016/S0031-9422(00)00235-1]

27. Khalid, M.; Bilal, M.; Huang, D.F. Role of flavonoids in plant interactions with the environment and against human pathogens—A review. J. Integr. Agric.; 2019; 18, pp. 211-230. [DOI: https://dx.doi.org/10.1016/S2095-3119(19)62555-4]

28. Nakabayashi, R.; Saito, K. Integrated metabolomics for abiotic stress responses in plants. Curr. Opin. Plant Biol.; 2015; 24, pp. 10-16. [DOI: https://dx.doi.org/10.1016/j.pbi.2015.01.003]

29. Mandal, S.M.; Chakraborty, D.; Dey, S. Phenolic acids act as signaling molecules in plant-microbe symbioses. Plant Signal. Behav.; 2010; 5, pp. 359-368. [DOI: https://dx.doi.org/10.4161/psb.5.4.10871] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/20400851]

30. Carl, H.B. Phenolic-storing cells: Keys to programmed cell death and periderm formation in wilt disease resistance and in general defence responses in plants?. Physiol. Mol. Plant Pathol.; 2000; 57, pp. 101-110.

31. Dietrich, H. Bioactive compounds in fruit and juice. Fruit Process.; 2004; 1, pp. 50-55.

32. Barros, L.; Dueñas, M.; Ferreira, I.C.F.R.; Baptista, P.; Santos-Buelga, C. Phenolic acids determination by HPLC-DAD-ESI/MS in sixteen different Portuguese wild mushrooms species. Food Chem. Toxicol.; 2009; 47, pp. 1076-1079. [DOI: https://dx.doi.org/10.1016/j.fct.2009.01.039]

33. Nile, S.H.; Park, S.W. Edible berries: Bioactive components and their effect on human health. Nutrition; 2014; 30, pp. 134-144. [DOI: https://dx.doi.org/10.1016/j.nut.2013.04.007] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/24012283]

34. Raffa, D.; Maggio, B.; Raimondi, M.V.; Plescia, F.; Daidone, G. Recent discoveries of anticancer flavonoids. Eur. J. Med. Chem.; 2017; 142, pp. 213-228. [DOI: https://dx.doi.org/10.1016/j.ejmech.2017.07.034]

35. Kumar, N.; Goel, N. Phenolic acids: Natural versatile molecules with promising therapeutic applications. Biotechnol. Rep.; 2019; 24, [DOI: https://dx.doi.org/10.1016/j.btre.2019.e00370] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31516850]

36. Romano, B.; Pagano, E.; Montanaro, V.; Fortunato, A.L.; Milic, N.; Borrelli, F. Novel insights into the pharmacology of flavonoids. Phyther. Res.; 2013; 27, pp. 1588-1596. [DOI: https://dx.doi.org/10.1002/ptr.5023]

37. Shen, S.; Li, G.; Huang, J.; Tan, Y.; Chen, C.; Ren, B.; Lu, G.; Zhang, C.; Li, X.; Wang, J. Chemical constituents from Fritillaria pallidiflora Schrenk. Biochem. Syst. Ecol.; 2012; 45, pp. 183-187. [DOI: https://dx.doi.org/10.1016/j.bse.2012.07.034]

38. Yang, L.; He, J. Traditional uses, phytochemistry, pharmacology and toxicological aspects of the genus Hosta (Liliaceae): A comprehensive review. J. Ethnopharmacol.; 2021; 265, 113323. [DOI: https://dx.doi.org/10.1016/j.jep.2020.113323] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32871235]

39. Wang, P.; Li, J.; Attia, F.A.K.; Kang, W.; Wei, J.; Liu, Z.; Li, C. A critical review on chemical constituents and pharmacological effects of Lilium. Food Sci. Hum. Wellness; 2019; 8, pp. 330-336. [DOI: https://dx.doi.org/10.1016/j.fshw.2019.09.001]

40. Fiorentino, A.; D’Abrosca, B.; Pacifico, S.; Mastellone, C.; Piscopo, V.; Monaco, P. Spectroscopic identification and antioxidant activity of glucosylated carotenoid metabolites from Cydonia vulgaris fruits. J. Agric. Food Chem.; 2006; 54, pp. 9592-9597. [DOI: https://dx.doi.org/10.1021/jf062125e]

41. MacMillan, J.; Suter, P.J. The structure of a C12-acid from the seed of Phaseolus multiflorus. Tetrahedron; 1967; 23, pp. 2417-2419. [DOI: https://dx.doi.org/10.1016/0040-4020(67)80076-0]

42. Chin, Y.W.; Lim, S.W.; Kim, S.H.; Shin, D.Y.; Suh, Y.G.; Kim, Y.B.; Kim, Y.C.; Kim, J. Hepatoprotective pyrrole derivatives of Lycium chinense fruits. Bioorganic Med. Chem. Lett.; 2003; 13, pp. 79-81. [DOI: https://dx.doi.org/10.1016/S0960-894X(02)00846-6]

43. Nagumo, S.; Kawai, K.; Nagase, H. Sesquiterpenoids and (Z)-3-hexenyl glucoside from Pertya glabrescens and a glucosidic sesquiterpene from P. scandens. Yakugaku Zasshi; 1984; 104, pp. 1223-1231. [DOI: https://dx.doi.org/10.1248/yakushi1947.104.12_1223]

44. Sawabe, A.; Obata, T.; Nochika, Y.; Morita, M.; Yamashita, N.; Matsubara, Y.; Okamoto, T. Investigation of functional molecules in African Celosia argentea L. Stud. Plant Sci.; 1999; 6, pp. 290-296.

45. Miyazaki, S.; Devkota, H.P.; Joshi, K.R.; Malla, K.J.; Watanabe, T.; Yahara, S. Chemical constituents from the aerial parts and rhizomes of Roscoea purpurea. Jpn. J. Pharmacogn.; 2014; 68, pp. 99-100.