Isochlorogenic Acid A Attenuates the Progression of Liver Fibrosis Through Regulating HMGB1/TLR4/NF-κB Signaling Pathway

Xin Liu; Kai Huang; Ru Jiao Zhang; Dan Mei; Bo Zhang

doi:10.3389/fphar.2020.00582

Isochlorogenic Acid A Attenuates the Progression of Liver Fibrosis Through Regulating HMGB1/TLR4/NF-κB Signaling Pathway

Front Pharmacol. 2020 May 1:11:582. doi: 10.3389/fphar.2020.00582. eCollection 2020.

Authors

Xin Liu^{1

2}, Kai Huang³, Ru Jiao Zhang⁴, Dan Mei¹, Bo Zhang¹

Affiliations

¹ Department of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
² Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, China.
³ Drug Clinical Trial Institution, Wuxi People's Hospital, Nanjing Medical University, Wuxi, China.
⁴ Health Science Center, Hebei University, Baoding, China.

Abstract

Liver fibrosis, a chronic damage process related to further progression of hepatic cirrhosis, has yet no truly effective treatment. Isochlorogenic acid A (ICQA), isolated from a traditional Chinese herbal medicine named Laggera alata (DC.) Sch.Bip. ex Oliv. (Asteraceae), is proved to exhibit anti-inflammatory, hepatoprotective and antiviral properties. However, the actions of ICQA on liver fibrosis are poorly understood. The purpose of this study was to evaluate the actions of ICQA on liver fibrosis and clarify the underlying mechanism. It was found that ICQA had significant protective actions on liver injury, inflammation as we as fibrosis in rats. Meanwhile, ICQA prevented hepatic stellate cells (HSC) activation, indicated by its inhibitory effect on the overexpression of α-smooth muscle actin (α-SMA). In addition, the reduced fibrosis was found to be associated with the decreased protein expression of high-mobility group box 1 (HMGB1) as well as toll like receptor (TLR) 4. Simultaneously, ICQA can suppress the cytoplasmic translocation of HMGB1 in rat liver. Further investigations indicated that ICQA treatment dramatically attenuated the nuclear translocation of the nuclear factor-kB (NF-κB) p65 and suppressed the hepatic expression of p-IκBα in rats with liver fibrosis. Taken together, our study indicated that ICQA could protect against CCl₄-induced liver fibrosis probably through suppressing the HMGB1/TLR4/NF-κB signaling pathways.

Keywords: high-mobility group box 1; isochlorogenic acid A; liver fibrosis; nuclear factor-κB; toll like receptor 4.