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DOI: 10.1055/a-1828-2671
Euryachincoside, a Novel Phenolic Glycoside with Anti-Hepatic Fibrosis Activity from Eurya chinensis
Supported by: National Natural Science Foundation of China 81903509
Abstract
Eurya chinensis has been recorded as a folk medicine traditionally used for treatment of a variety of symptoms. However, the phytochemical and pharmacological investigations of this plant are still scarce. A novel phenolic glycoside named Euryachincoside (ECS) was isolated by chromatographic separation from E. chinensis, and its chemical structure was identified by analysis of HRMS and NMR data. Its anti-hepatic fibrosis effects were evaluated in both HSC-T6 (rat hepatic stellate cells) and carbon tetrachloride (CCl4)-induced mice with Silybin (SLB) as the positive control. In an in vitro study, ECS showed little cytotoxicity and inhibited transforming growth factor-beta (TGF-β)-induced Collagen I (Col1) along with alpha-smooth muscle actin (α-SMA) expressions in HSC-T6. An in vivo study suggested ECS significantly ameliorated hepatic injury, secretions of inflammatory cytokines, and collagen depositions. Moreover, ECS markedly mediated Smad2/3, nuclear factor kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways both in vitro and vivo. These present findings confirmed that ECS is a novel phenolic glycoside from E. chinensis with promising curative effects on hepatic fibrosis, and its mechanisms may include decreasing extracellular matrix accumulation, reducing inflammation and attenuating free radicals via Smad2/3, NF-κB and Nrf2 signaling pathways, which may shed light on the exploration of more effective phenolic glycoside-based anti-fibrotic agents.
Supporting Information
- Supporting Information
HR-ESI-MS (Fig. 1S), 1H and 13C NMR (Fig. 2S and 3S), 1H-1H COSY (Fig. 4S), HSQC (Fig. 5S), HMBC (Fig. 6S), IR (Fig. 7S), UV (Fig. 8S) and Chromatogram of L-glucose, D-glucose and hydrolyzed ECS derivatized by L-cysteine methyl ester hydrochloride and aryl isothiocyanate (Fig. 9S) spectra of ECS and PCR primers sequences of Col1, α-SMA and GAPDH (Table 1S) are available in the Supporting Information. Also the instruments and materials for the purification of the compound from the title plant and for the spectroscopic measurements of the purified compound are detailed in the Supporting Information.
Publication History
Received: 04 January 2022
Accepted after revision: 14 April 2022
Accepted Manuscript online:
19 April 2022
Article published online:
23 January 2023
© 2022. Thieme. All rights reserved.
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References
- 1 Younossi ZM, Stepanova M, Younossi Y, Golabi P, Mishra A, Rafiq N, Henry L. Epidemiology of chronic liver diseases in the USA in the past three decades. Gut 2020; 69: 564-568
- 2 Pimpin L, Cortez-Pinto H, Negro F, Corbould E, Lazarus JV, Webber L, Sheron N, Comm EHS. Burden of liver disease in Europe: Epidemiology and analysis of risk factors to identify prevention policies. J Hepatol 2018; 69: 718-735
- 3 Balsano C, Alisi A, Nobili V. Liver fibrosis and therapeutic strategies: The goal for improving metabolism. Curr Drug Targets 2009; 10: 505-512
- 4 Lee UE, Friedman SL. Mechanisms of hepatic fibrogenesis. Best Pract Res Clin Gastroenterol 2011; 25: 195-206
- 5 Arteel GE, Naba A. The liver matrisome – looking beyond collagens. JHEP Rep 2020; 2: 100115
- 6 Tan Z, Sun HB, Xue TX, Gan CL, Liu HY, Xie YT, Yao YQ, Ye TH. Liver fibrosis: Therapeutic targets and advances in drug therapy. Front Cell Dev Biol 2021; 9: 730176-730193
- 7 Fang YY, Hegazy L, Finck BN, Elgendy B. Recent advances in the medicinal chemistry of farnesoid x receptor. J Med Chem 2021; 64: 17545-17571
- 8 Gadaleta RM, Moschetta A. Dark and bright side of targeting fibroblast growth factor receptor 4 in the liver. J Hepatol 2021; 75: 1440-1451
- 9 Chang ZF, Chen JL, Fan DM. Study on the effect of medical plants of Theaceae. J Beijing Univ TCM 1996; 19: 28-30
- 10 Yu B, Zeng GF. Flora reipublicae popularis sinicae. Beijing: Science Press; 1998
- 11 Committee HR. Chinese Herbal Medicine in Huiyang Area of Guangdong Province. Huiyang City: Guangdong Huiyang area garrison, Guangdong Huiyang District Revolutionary Committee; 1969
- 12 Editorial Board of Chinese Materia Medica of State Administration of Traditional Chinese Medicine. Chinese Materia Medica. Shanghai: Shanghai Science and Techology Press; 1999
- 13 Fang J, Hu YX, Ying HZ, Yu WY, Jin XY, Yu CH. Identification of MicroRNAs from Eurya chinensis and function analysis on their target genes. Chin Tradi and Herb Drugs 2015; 46: 80-85
- 14 Song JL, Yuan Y, Nie LH, Li BL, Qin XB, Li Y, Wu JW, Qiu SX. A new ent-kaurane diterpene derivative from the stems of Eurya chinensis R.Br. Nat Prod Res 2018; 32: 182-188
- 15 Song JL, Yuan Y, Nie LH, Li BL, Qin XB, Li Y, Wu JW, Qiu SX. Two new ent-kaurane diterpenes from the stems of Eurya chinensis . J Asian Nat Prod Res 2018; 20: 962-968
- 16 Song JL, Yuan Y, Tan HB, Wu JW, Huang RM, Li H, Xu ZF, Na N, Qiu SX. Euryachins A and B, a new type of diterpenoids from Eurya chinensis with potent NO production inhibitory activity. RSC Adv 2016; 6: 85958-85961
- 17 Pan XQ, Ma X, Jiang YX, Wen JX, Yang L, Chen DY, Cao XY, Peng C. A comprehensive review of natural products against liver fibrosis: flavonoids, quinones, lignans, phenols, and acids. Evid Based Complement Alternat Med 2020; 2020: 7171498-7171516
- 18 Saijo R, Nonaka G, Nishioka I. Tannins and related compounds. LXXXIV. Isolation and characterization of five new hydrolyzable tannins from the bark of Mallotus japonicus . Chem Pharm Bull (Tokyo) 1989; 37: 2063-2070
- 19 Zhang YJ, Abe T, Tanaka T, Yang CR, Kouno I. Phyllanemblinins A–F, new ellagitannins from Phyllanthus emblica . J Nat Prod 2001; 64: 1527-1532
- 20 Jiang ZH, Tanaka T, Iwata H, Sakamoto S, Hirose Y, Kouna I. Ellagitannins and lignan glycosides from Balanophora japonica (Balanophoraceae). Chem Pharm Bull 2005; 53: 339-341
- 21 Friedman SL. Mechanisms of hepatic fibrogenesis. Gastroenterology 2008; 134: 1655-1669
- 22 Mederacke I, Hsu CC, Troeger JS, Huebener P, Mu XR, Dapito DH, Pradere JP, Schwabe RF. Fate tracing reveals hepatic stellate cells as dominant contributors to liver fibrosis independent of its aetiology. Nat Commun 2013; 4: 2823-2833
- 23 Puche JE, Saiman Y, Friedman SL. Hepatic stellate cells and liver fibrosis. Compr Physiol 2013; 3: 1473-1492
- 24 Loguercio C, Festi D. Silybin and the liver: From basic research to clinical practice. World J Gastroenterol 2011; 17: 2288-2301
- 25 Abdelmegeed MA, Banerjee A, Yoo SH, Jang S, Gonzalez FJ, Song BJ. Critical role of cytochrome P450 2E1 (CYP2E1) in the development of high fat-induced non-alcoholic steatohepatitis. J Hepatol 2012; 57: 860-866
- 26 Sid B, Glorieux C, Valenzuela M, Rommelaere G, Najimi M, Dejeans N, Renard P, Verrax J, Calderon PB. AICAR induces Nrf2 activation by an AMPK-independent mechanism in hepatocarcinoma cells. Biochem Pharmacol 2014; 91: 168-180
- 27 Xu L, Zheng N, He Q, Li R, Zhang K, Liang T. Puerarin, isolated from Pueraria lobata (Willd.), protects against hepatotoxicity via specific inhibition of the TGF-beta1/Smad signaling pathway, thereby leading to anti-fibrotic effect. Phytomedicine 2013; 20: 1172-1179
- 28 Giannini EG, Testa R, Savarino V. Liver enzyme alteration: a guide for clinicians. CMAJ 2005; 172: 367-379
- 29 Tanaka T, Nakashima T, Ueda T, Tomii K, Kouno I. Facile discrimination of aldose enantiomers by reversed-phase HPLC. Chem Pharm Bull 2007; 55: 899-901
- 30 Li BL, Hu JJ, Xie JD, Ni C, Liang HJ, Li QR, Yuan J, Wu JW. Rosanortriterpenes A–B, two promising agents from Rosa laevigata var. leiocapus, alleviate inflammatory responses and liver fibrosis in in vitro cell models. Evid Based Complement Alternat Med 2020; 2020: 8872945-8872953
- 31 Yuan Y, Wu JW, Li BL, Niu J, Tan HB, Qiu SX. Regulation of signaling pathways involved in the anti-proliferative and apoptosis-inducing effects of M22 against non-small cell lung adenocarcinoma A549 cells. Sci Rep 2018; 8: 992-1000