Protective effect of isochlorogenic acid B on liver fibrosis in non‐alcoholic steatohepatitis of mice

Abstract

Liver fibrosis is a common symptom of non-alcoholic steatohepatitis (NASH) and a worldwide clinical issue. The miR-122/HIF-1α signalling pathway is believed to play an important role in the genesis of progressive fibrosis. Isochlorogenic acid B (ICAB), naturally isolated from Laggera alata, is verified to have antioxidative and hepatoprotective properties. The aim of this study was to investigate the effect of ICAB on liver fibrosis in NASH and its potential protective mechanisms. NASH was induced in a mouse model with a methionine- and choline-deficient (MCD) diet for 4 weeks, and ICAB was orally administered every day at three doses (5, 10 and 20 mg/kg). Pathological results indicated that ICAB significantly improved the pathological lesions of liver fibrosis. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatic hydroxyproline (Hyp), cholesterol (CHO) and triglyceride (TG) were also significantly decreased by ICAB. In addition, ICAB inhibited hepatic stellate cells (HSCs) activation and the expressions of hepatic genes involved in liver fibrosis including LOX, TGF-β1, MCP-1, COL1α1 and TIMP-1. ICAB also attenuated liver oxidative stress through Nrf2 signalling pathway. What is more, the decreased levels of miR-122 and over-expression of hepatic HIF-1α could be reversed by ICAB treatment. These results simultaneously confirmed that ICAB had a significant protective effect on fibrosis in NASH by inhibiting oxidative stress via Nrf2 and suppressing multiple profibrogenic factors through miR-122/HIF-1α signalling pathway.

Herbal Medicine in the Treatment of Non-Alcoholic Fatty Liver Diseases-Efficacy, Action Mechanism, and Clinical Application

“…It has been reported that scutellarin (a flavonoid glycoside), swertiamarin (a secoiridoid glycoside) (Yang Y. et al, 2019) and gastrodin (isolated from Gastrodia elata Bl) enhance Nrf2-mediated antioxidant system via activating the mRNA and protein levels of PPARg and its coactivator-1a, HO-1, GST, and NQO1 expressions (Ahmad et al, 2019), thus ameliorate NAFLD. Isochlorogenic acid B [extracted from Laggera alata (Asteraceae)] shows its protective effects on fibrosis in NASH by Nrf2 signaling pathway, and reverse the downregulation of miR-122 level and upregulation of hepatic HIF-1a expression to inhibit multiple profibrogenic factors (COL1a1, MCP-1, LOX, TGF-b1, and TIMP-1) (Liu et al, 2019c).…”

The Crosstalk of miRNA and Oxidative Stress in the Liver: From Physiology to Pathology and Clinical Implications

“…With these properties miR-122 is suitable to act as a biomarker. Liu et al was able to show that isochlorogenic acid B (ICAB) has a protective effect and is possibly associated with the ability to attenuate OS by up-regulating Nrf2 and suppressing fibrogenic factors through miR-122/HIF1α pathway [172]. Carnosic acid, an antioxidant, provides protection against NAFLD by decreasing miR-34a expression and stimulating the SIRT1/p66shc pathway [88].…”

Preventive effect of insect tea primary leaf (Malus sieboldii (Regal) Rehd.) extract on D‐galactose‐induced oxidative damage in mice

“…Neochlorogenic acid, cryptochlorogenic acid, isochlorogenic acid A, and isochlorogenic acid B are chlorogenic acid compounds, which have antioxidant effects when present alone, (Xu, Chen, Liao, Zhang, & Wang, 2015), as they prevent abnormal blood pressure, dyslipidemia, oxidative damage, and nerve injury (Lan, Liu, Chen, & Wang, 2014; Liu, Huang, Niu, Mei, & Zhang, 2019; Sasikala, Rooban, Sahasranamam, & Abraham, 2013; Wang, Wang, Peng, Wang, & Hao, 2016; Wang, Xi, Fan, Cao, & Jiang, 2019; Zhang & Wang, 2007). Rutin is a commonly used antioxidant that scavenges free radicals (Vázquez‐Medina et al., 2011).…”