Astragali Radix Contributes to the Inhibition of Liver Fibrosis via High-Mobility Group Box 1-Mediated Inflammatory Signaling Pathway

Abstract

Astragali Radix (AR), the dried root of Astragali Radix membranaceus (Fisch.) Bge. or Astragali Radix membranaceus (Fisch.) Bge. var. mongholicus (Bge) Hsiao, is a commonly used traditional Chinese medicine for the treatment of liver diseases. This study aimed to comprehensively evaluate the pharmacological action and explore the potential mechanism of AR on liver fibrosis. Rats were administered with carbon tetrachloride for eight weeks, followed by oral treatment with AR for six weeks. The efficacy was confirmed by measuring liver function and liver fibrosis levels. The underlying mechanisms were explored by detecting the expression of related proteins. AR significantly decreased the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), collagen IV (COL-IV), hyaluronic acid (HA), laminin (LN), and precollagen type III (PCIII). In addition, AR inhibited the deposition of collagen and the activation of hepatic stellate cells. Those data strongly demonstrated that AR alleviated liver fibrosis by CCl4. In order to illustrate the potential inflammatory, the mRNA levels of IL-6, TNF-α, and IL-1β were detected. Subsequently, immunohistochemistry analysis was performed to further verify the expression of type I collagen. Finally, the expression of key proteins in the inflammatory signaling pathway was detected. AR significantly reduced the expression of high-mobility group box 1 (HMGB1), TLR4, Myd88, RAGE, and NF-κ B p65 genes and proteins. In addition, western blotting showed AR decreased the protein expression of RAGE, p-MEK1/2, p-ERK1/2, and p-c-Jun. Taken together, our data reveal that AR significantly inhibits liver fibrosis by intervening in the HMGB1-mediated inflammatory signaling pathway and secretion signaling pathway. This study will provide valuable references for the in-depth research and development of Astragali Radix against liver fibrosis.

Diacerein ameliorates cholestasis-induced liver fibrosis in rat via modulating HMGB1/RAGE/NF-κB/JNK pathway and endoplasmic reticulum stress

“…In this experiment, BDL rats showed up-regulation of hepatic protein and gene expression of HMGB1 and gene expression of RAGE, which is in harmony with the study by Wen et al 42 . These findings suggest that the HMGB1/RAGE pathway may contribute to the molecular mechanisms of cholestasis-induced liver fibrosis.…”

“…Wu et al 65 reported that TGF-β1 expression in HSCs could be promoted via activated JNK. Furthermore, Wen et al 42 demonstrated that activated MAPKs, including JNK, triggered collagen expression in HSCs in fibrotic rat livers induced by CCL 4 . More importantly, the same study found that MAPKs' fibrotic effects were mediated through the HMGB/RAGE pathway.…”

HMGB1 as an extracellular pro-inflammatory cytokine: Implications for drug-induced organic damage

“…Astragali Radix (AR), curcumin, oxymatrine (OMT), ethyl pyruvate (EP), insulin-like growth factor 1 (IGF-1), chloroquine (CQ), as well as quercetin have may decrease CCl4-induced liver inflammation via suppressing HMGB1/TLR4/NF-κB axis(Dai et al 2018 ; Li et al 2016 ; Tu et al 2012 ; Wen et al 2021 ; Zhang et al 2018b ; Zhao et al 2016 ; Zhao et al 2021 ). The use of AR can greatly decrease the generation of type 1 collagen in mice via inhibiting HSCs activation and collagen secreted via HMGB1-RAGE-c-Jun pathway(Wen et al 2021 ). γ-mangostin (γ-man) induces the activation of Sirtuin 3 (Sirt3), leading to an anti-fibrotic action.…”

Study on the Anti-Inflammatory Effect and Mechanism of Yuxuebi Tablet Based on Network Pharmacology

“…DS could downregulate TNF-α, COX-2, inducible nitric oxide synthase (iNOS), and ILs by activating Nrf2, thus inhibiting the inflammatory response . Other TCMs included in YXB also have good anti-inflammatory effects. − However, as a complex Chinese traditional patent medicine, the anti-inflammatory mechanisms of YXB are still poorly understood.…”