Ginsenoside Rg3 promotes regression from hepatic fibrosis through reducing inflammation-mediated autophagy signaling pathway

Abstract

Inflammation and autophagy occur during hepatic fibrosis development caused by various pathogens, and effectively curbing of autophage may delay the occurrence of hepatic fibrosis. The current study aimed to unravel the inhibitory effects of Ginsenoside Rg3 (G-Rg3) on inflammation-mediated hepatic autophagy to curb hepatic fibrosis caused by thioacetamide (TAA)-induced subacute and chronic hepatic injury. TAA is mainly metabolized in the liver to cause liver dysfunction. After intraperitoneal injection of TAA for 4 or 10 weeks (TAA-chronic mouse models), severe inflammatory infiltration and fibrosis occurred in the liver. Treatment with G-Rg3 alleviated hepatic pathological changes and reversed hepatic fibrosis in the TAA-chronic models with decreased deposition of collagen fibers, reduced expression of HSCs activation marker (α-SMA), and reduced secretion of profibrogenic factors (TGF-β1). G-Rg3 decreased expressions of autophagy-related proteins in mice of TAA-chronic models. Notably, G-Rg3 inhibited the survival of activated rat hepatic stellate cells (HSC-T6), but had no cytotoxicity on human hepatocytes (L02 cell lines). G-Rg3 dosedependently inhibited autophagy in vitro with less expression of p62 and fewer LC3a transformation into LC3b in inflammatory inducer lipopolysaccharide (LPS)-induced rat HSC-T6 cells. Furthermore, G-Rg3 enhanced the phosphorylation of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) in vivo and in vitro. Besides, mTOR inhibitor Rapamycin and PI3K inhibitors LY294002 were employed in LPS-treated HSC-T6 cell cultures to verify that Rg3 partially reversed the increase in autophagy in hepatic fibrosis in vitro. Taken together, G-Rg3 exerted anti-fibrosis effect through the inhibition of autophagy in TAA-treated mice and LPS-stimulated HSC-T6 cells. These data collectively unravel that G-Rg3 may serve a promising anti-hepatic fibrosis drug.

Berberine Attenuates Chronic Atrophic Gastritis Induced by MNNG and Its Potential Mechanism

“…HY-10431, MedChem Express, Shanghai, China, 10 μΜ) ( Liu X. S. et al, 2019 ), a small molecular inhibitor, was used to inhibit the expression of TGF-β1, and Rapamycin (Cat No. HY-10219,MedChem Express, Shanghai, China, 100 nΜ) ( Liu X. et al, 2020 ) was used to inhibit the expression of mTOR. As shown in Figure 6A , the level of TGF-β1 in MNNG group increased significantly than control group.…”

“…Berberine shows a good therapeutic effect on ulcerative colitis (Jing et al, 2020) and can improve glucose metabolism and insulin resistance by suppressing the inflammatory response (Shan et al, 2020). Recent studies have shown that BBR also has anti-tumor effects, such as promoting autophagy, anti-proliferation, apoptosis and so on (Liu J. et al, 2020;Samadi et al, 2020). However, the therapeutic effect of BBR on MNNG-induced CAG and its potential mechanism is still unclear.…”

Panax ginseng C. A. Meyer as a potential therapeutic agent for organ fibrosis disease

“…Total ginsenoside, an extensively studied ingredient that isolated from ginseng extract with 60% ethanol following Chinese Pharmacopoeia, is deemed to be one of the popular candidates for fibrosis-associated diseases. Moreover, individual ginsenosides isolated from total ginsenoside such as Rg 1 [ 62 – 65 ], Rb 1 [ 66 – 68 ], Re [ 69 ], Rg 3 [ 70 ], Mc 1 [ 71 ] also exert their anti-fibrosis potential (Fig. 2 ).…”

Panax Ginseng C.A.Mey. as Medicine: The Potential Use of Panax Ginseng C.A.Mey. as a Remedy for Kidney Protection from a Pharmacological Perspective

“…Therapeutic properties of Panax ginseng C.A.Mey. such as anti-inflammatory, altering the composition and metabolism of the microbiota, ameliorating chronic inflammation, enhancing the immunity, resisting the oxidation again, and regulating the glucose and lipid metabolism have been widely reported ( Cao et al, 2019 ; Jang et al, 2019 ; Liu et al, 2019 , 2020 ; Xue et al, 2019 ; Huang et al, 2020 ; Quan et al, 2020 ; Xu et al, 2020 ). Intriguing new data suggest that Panax ginseng C.A.Mey.…”