Abstract
The extraction and solvent partition of roots of Incarvillea compacta, a traditional Tibetan folk medicine, and repeated column chromatography and preparative high-performance liquid chromatography for n-butanol fraction yielded four phenylethanoid glycosides, crenatoside (1), 3′′′-O-methylcrenatoside (2), leucoseceptoside A (3), and martynoside (4). The chemical structures were identified on the basis of spectroscopic data analyses including NMR and MS. All compounds were isolated for the first time from the plant. Compound 1 exerted better 1,1-diphenyl-2-picrylhydrazyl free radical scavenging activity. In addition, compounds 1–4 were evaluated for their hepatoprotective activity on carbon tetrachloride (CCl4)-induced liver injury in HepG2 cells. Pretreatment of HepG2 cells with compound 1–4 significantly increased the viability on CCl4-induced cell death. Furthermore, compounds 1–4 also alleviated CCl4-induced hepatotoxicity by enhancement of the antioxidant enzyme activities of superoxide dismutase and reduction of the malondialdehyde content, intracellular ROS as well as NF-κB transactivation. Our results suggest that phenylethanoid glycosides ameliorate CCl4-induced cell injury, and this protection was likely due to antioxidative activity and down-regulation of NF-κB.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Adewusi EA, Afolayan AJ (2010) A review of natural products with hepatoprotective activity. J Med Plants Res 4:1318–1334
Afifi MS, Lahloub MF, El-Khayaat SA, Anklin CG, Rüegger H, Sticher O (1993) Crenatoside: a novel phenylpropanoid glycoside from Orobanche crenata. Planta Med 59:359–362
Akanitapichat P, Phraibung K, Nuchklang K, Prompitakkul S (2010) Antioxidant andhepatoprotective activities of five eggplant varieties. Food Chem Toxicol 48:3017–3021
Balasubramaniyan V, Shukla R, Murugaiyan G, Bhonde RR, Nalini N (2007) Mouse recombinant leptin protects human hepatoma HepG2 against apoptosis, TNF-α response and oxidative stress induced by the hepatotoxin-ethanol. Biochim Biophys Acta 1770:1136–1144
Barrera G (2012) Oxidative stress and lipid peroxidation products in cancer progression and therapy. ISRN Oncol 2012:137289
Bhardwaj A, Khatri P, Soni ML, Ali DJ (2011) Potent herbal hepatoprotective drugs-A review. J Adv Sci Res 2:15–20
Chattopadhyay RR (2003) Possible mechanism of hepatoprotective activity of Azadirachta indica leaf extract: part II. J Ethnopharmacol 89:217–219
Chi YM, Nakamura M, Zhao XY, Yoshizawa T, Yan WM, Hashimoto F, Kinjo J, Nohara T (2005) A monoterpene alkaloid from Incarvillea sinensis. Chem Pharm Bull 53:1178–1179
Dai N, Zou Y, Zhu L, Wang HF, Dai MG (2014) Antioxidant properties of proanthocyanidins attenuate carbon tetrachloride (CCl4)-induced steatosis and liver injury in rats via CYP2E1 regulation. J Med Food 17:663–669
Delectis Florae Reipublicae Popularis Sinicae Agendae Academiae Sinicae Edita (1990) Flora Reipublicae Popularis Sinicae: Tomus 69. Science Press, Beijing, p 46
Flora SJ (2009) Structural, chemical and biological aspects of antioxidants for strategies against metal and metalloid exposure. Oxid Med Cell Longev 2:191–206
Fu JJ, Jin HZ, Shen YH, Zhang WD, Xu WZ, Zeng Q, Yan SK (2007) Two novel monoterpene alkaloid dimers from Incarvillea arguta. Helv Chim Acta 90:2151–2155
Fu GM, Pang HH, Wong YH (2008) Naturally occurring phenylethanoid glycosides: potential leads for new therapeutics. Curr Med Chem 15:2592–2613
Fu JJ, Qin JJ, Zeng Q, Huang Y, Jin HZ, Zhang WD (2010) Four new sesquiterpenoids from the roots of Incarvillea arguta against lipopolysaccharide-induced nitric oxide production. Chem Pharm Bull (Tokyo) 58:1263–1266
Gulçin I, Elmastas M, Aboul-Enein HYA (2012) Antioxidant activity of clove oil—a powerful antioxidant source. Arab J Chem 5:489–499
Hu WC, Wang G, Li P, Wang Y, Si CL, He J, Long W, Bai Y, Feng Z, Wang X (2014) Neuroprotective effects of macranthoin G from Eucommia ulmoides against hydrogen peroxide-induced apoptosis in PC12 cells via inhibiting NF-κB activation. Chem Biol Interact 224:108–116
Huxford T, Ghosh G (2009) A structural guide to proteins of the NF-κB signaling module. Cold Spring Harb Perspect Biol 1:a000075
Kashaw V, Nema AK, Agarwal A (2011) Hepatoprotective prospective of herbal drugs and their vesicular carriers–a review. Inter J Res Pharm Biomed Sci 2:361–374
Li CQ, Li BG, Qi HY, Li QL, Wang FP, Zhang GL (2004) Three cyclooctapeptides and one glycoside from Microtoena prainiana. J Nat Prod 67:978–982
Lobo V, Patil A, Phatak A, Chandra N (2010) Free radicals, antioxidants and functional foods: impact on human health. Pharmacogn Rev 4:118–126
Lu T, Zhang WD, Pei YH, Zhang C, Li JC, Shen YH (2007) A new iridoid from Incarvillea delavayi. Chin Chem Lett 18:1512–1514
Lu LH, Yang M, Lin S, Zheng Q, Zhang WD (2009) Chemical constituents from acetyl acetate extract fraction of Incarvillea delavayi. China J Chin Mater Med 34:1799–1801
Nakamura M, Chi YM, Yan WM, Nakasugi Y, Yoshizawa T, Irino N, Hashimoto F, Kinjo J, Nohara T, Sakurada S (1999) Strong antinociceptive effect of incarvillateine, a novel monoterpene alkaloid from Incarvillea sinensis. J Nat Prod 62:1293–1294
Nakamura M, Chi YM, Yan WM, Yonezawa A, Nakasugi Y, Yoshizawa T, Hashimoto F, Kinjo J, Nohara T, Sakurada S (2001) Structure-antinociceptive activity studies of incarvillateine, a monoterpene alkaloid from Incarvillea sinensis. Planta Med 67:114–117
Si CL, Shen T, Jiang YY, Wu L, Yu GJ, Ren XD, Xu GH, Hu WC (2013) Antioxidant properties and neuroprotective effects of isocampneoside II on hydrogen peroxide-induced oxidative injury in PC12 cells. Food Chem Toxicol 59:145–152
Yan YM, Wu GS, Dong XP, Shen L, Li Y, Su J, Luo HR, Zhu HJ, Cheng YX (2012) Sesquiterpenoids from Incarvillea arguta: absolute configuration and biological evaluation. J Nat Prod 75:1025–1029
Yang YC (1991) Handbook of tibetan medicine. Qinghai People’s Press, Xining, p 465
Yang JY, Lee HS (2012) Evaluation of antioxidant and antibacterial activities of morin isolated from mulberry fruits (Morus alba L.). J Korean Soc Appl Biol Chem 55:485–489
Yang JH, Hu JP, Rena K, Du NS (2009) Structure-activity relationships of phenylethanoid glycosides in plants of Cistanche salsa on antioxidative activity. Zhong Yao Cai 32:1067–1069
Yu WG, Qian J, Lu YH (2011) Hepatoprotective effects of 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone on CCl4-induced acute liver injury in mice. J Agric Food Chem 59:12821–12829
Acknowledgments
This work was financially supported from “Program for Innovative Research Team in IMPLAD”, the technological large platform for comprehensive research and development of new drugs in the Twelfth Five-Year “Significant New Drugs Created” Science and Technology Major Projects (No. 2012ZX09301-002-001-026), Open Science Foundation of Jiangsu Key Laboratory for Biomass-based Energy and Enzyme Technology (No. JSBEET1313), Natural Science Foundation of Jiangsu Province (No. BK20140455), and Natural Science Foundation of the Higher Education Institutions of Jiangsu Province (No. 14KJB550002 and 13KJB210001).
Author information
Authors and Affiliations
Corresponding authors
Additional information
Ting Shen and Xueqin Li contributed equally to this work.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Shen, T., Li, X., Hu, W. et al. Hepatoprotective effect of phenylethanoid glycosides from Incarvillea compacta against CCl4-induced cytotoxicity in HepG2 cells. J Korean Soc Appl Biol Chem 58, 617–625 (2015). https://doi.org/10.1007/s13765-015-0076-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13765-015-0076-0