Mechanism and Progress of Natural Products in the Treatment of NAFLD-Related Fibrosis

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2023 Dec 9

PMID 38067665

Authors

Jin-Zhong Li

Ning Chen

Nan Ma

Min-Ran Li

Affiliations

Soon will be listed here.

Abstract

Nonalcoholic fatty liver disease (NAFLD) has emerged as the most prevalent chronic liver disorder worldwide, with liver fibrosis (LF) serving as a pivotal juncture in NAFLD progression. Natural products have demonstrated substantial antifibrotic properties, ushering in novel avenues for NAFLD treatment. This study provides a comprehensive review of the potential of natural products as antifibrotic agents, including flavonoids, polyphenol compounds, and terpenoids, with specific emphasis on the role of Baicalin in NAFLD-associated fibrosis. Mechanistically, these natural products have exhibited the capacity to target a multitude of signaling pathways, including Hedgehog, Wnt/β-catenin, TGF-β1, and NF-κB. Moreover, they can augment the activities of antioxidant enzymes, inhibit pro-fibrotic factors, and diminish fibrosis markers. In conclusion, this review underscores the considerable potential of natural products in addressing NAFLD-related liver fibrosis through multifaceted mechanisms. Nonetheless, it underscores the imperative need for further clinical investigation to authenticate their effectiveness, offering invaluable insights for future therapeutic advancements in this domain.

Citing Articles

The Novel Effect and Potential Mechanism of Lactoferrin on Organ Fibrosis Prevention.

Yu Y, Fang J, Li Y, Wang X, Zhang J, Wang J Nutrients. 2025; 17(1.

PMID: 39796631 PMC: 11723014. DOI: 10.3390/nu17010197.

A New Frontier in Phytotherapy: Harnessing the Therapeutic Power of Medicinal Herb-derived miRNAs.

Feng Y Curr Pharm Des. 2024; 30(38):3009-3017.

PMID: 39162273 DOI: 10.2174/0113816128310724240730072626.

References

Hou M, Wang R, Zhao S, Wang Z . Ginsenosides in genus and their biosynthesis. Acta Pharm Sin B. 2021; 11(7):1813-1834. PMC: 8343117. DOI: 10.1016/j.apsb.2020.12.017. View

Dewidar B, Meyer C, Dooley S, Meindl-Beinker A . TGF-β in Hepatic Stellate Cell Activation and Liver Fibrogenesis-Updated 2019. Cells. 2019; 8(11). PMC: 6912224. DOI: 10.3390/cells8111419. View

Lo Y, Tsai Y, Wu S, Chen J, Chao J . Ginsenoside Rb1 inhibits cell activation and liver fibrosis in rat hepatic stellate cells. J Med Food. 2011; 14(10):1135-43. DOI: 10.1089/jmf.2010.1485. View

Carter J, Friedman S . Hepatic Stellate Cell-Immune Interactions in NASH. Front Endocrinol (Lausanne). 2022; 13:867940. PMC: 9218059. DOI: 10.3389/fendo.2022.867940. View

Kitade Y, Watanabe S, Masaki T, Nishioka M, Nishino H . Inhibition of liver fibrosis in LEC rats by a carotenoid, lycopene, or a herbal medicine, Sho-saiko-to. Hepatol Res. 2002; 22(3):196-205. DOI: 10.1016/s1386-6346(01)00132-2. View

Barrott J, Cash G, Smith A, Barrow J, Murtaugh L . Deletion of mouse Porcn blocks Wnt ligand secretion and reveals an ectodermal etiology of human focal dermal hypoplasia/Goltz syndrome. Proc Natl Acad Sci U S A. 2011; 108(31):12752-7. PMC: 3150921. DOI: 10.1073/pnas.1006437108. View

Wong V, Chitturi S, Wong G, Yu J, Chan H, Farrell G . Pathogenesis and novel treatment options for non-alcoholic steatohepatitis. Lancet Gastroenterol Hepatol. 2017; 1(1):56-67. DOI: 10.1016/S2468-1253(16)30011-5. View

Wang C, Duan X, Sun X, Liu Z, Sun P, Yang X . Protective effects of glycyrrhizic acid from edible botanical glycyrrhiza glabra against non-alcoholic steatohepatitis in mice. Food Funct. 2016; 7(9):3716-23. DOI: 10.1039/c6fo00773b. View

Yang Y, Kim B, Park Y, Koo S, Lee J . Astaxanthin prevents TGFβ1-induced pro-fibrogenic gene expression by inhibiting Smad3 activation in hepatic stellate cells. Biochim Biophys Acta. 2014; 1850(1):178-85. DOI: 10.1016/j.bbagen.2014.10.014. View

10.

Gillessen A, Schmidt H . Silymarin as Supportive Treatment in Liver Diseases: A Narrative Review. Adv Ther. 2020; 37(4):1279-1301. PMC: 7140758. DOI: 10.1007/s12325-020-01251-y. View

11.

Wan X, Huang H, Wang X, Hu Z, Liu K, Huang D . and its monomers alleviate liver fibrosis both in mice and LX2 cells by blocking TβR1-Smad2/3 and TNF-α-NF-κB pathways. Am J Transl Res. 2019; 11(1):106-119. PMC: 6357326. View

12.

Xu T, Huang S, Huang Q, Ming Z, Wang M, Li R . Kaempferol attenuates liver fibrosis by inhibiting activin receptor-like kinase 5. J Cell Mol Med. 2019; 23(9):6403-6410. PMC: 6714241. DOI: 10.1111/jcmm.14528. View

13.

Hessin A, Hegazy R, Hassan A, Yassin N, Kenawy S . Resveratrol prevents liver fibrosis via two possible pathways: Modulation of alpha fetoprotein transcriptional levels and normalization of protein kinase C responses. Indian J Pharmacol. 2018; 49(4):282-289. PMC: 5754935. DOI: 10.4103/ijp.IJP_299_16. View

14.

Crocenzi F, Roma M . Silymarin as a new hepatoprotective agent in experimental cholestasis: new possibilities for an ancient medication. Curr Med Chem. 2006; 13(9):1055-74. DOI: 10.2174/092986706776360950. View

15.

Briscoe J, Therond P . The mechanisms of Hedgehog signalling and its roles in development and disease. Nat Rev Mol Cell Biol. 2013; 14(7):416-29. DOI: 10.1038/nrm3598. View

16.

Hagstrom H, Nasr P, Ekstedt M, Hammar U, Stal P, Hultcrantz R . Fibrosis stage but not NASH predicts mortality and time to development of severe liver disease in biopsy-proven NAFLD. J Hepatol. 2017; 67(6):1265-1273. DOI: 10.1016/j.jhep.2017.07.027. View

17.

Swiderska-Syn M, Syn W, Xie G, Kruger L, Machado M, Karaca G . Myofibroblastic cells function as progenitors to regenerate murine livers after partial hepatectomy. Gut. 2013; 63(8):1333-44. PMC: 4006344. DOI: 10.1136/gutjnl-2013-305962. View

18.

Vizzutti F, Provenzano A, Galastri S, Milani S, Delogu W, Novo E . Curcumin limits the fibrogenic evolution of experimental steatohepatitis. Lab Invest. 2009; 90(1):104-15. DOI: 10.1038/labinvest.2009.112. View

19.

Zhao Y, Ma X, Wang J, He X, Hu Y, Zhang P . Curcumin protects against CCl4-induced liver fibrosis in rats by inhibiting HIF-1α through an ERK-dependent pathway. Molecules. 2014; 19(11):18767-80. PMC: 6270950. DOI: 10.3390/molecules191118767. View

20.

Majeed R, Reddy M, Chinthakindi P, Sangwan P, Hamid A, Chashoo G . Bakuchiol derivatives as novel and potent cytotoxic agents: a report. Eur J Med Chem. 2012; 49:55-67. DOI: 10.1016/j.ejmech.2011.12.018. View