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.
Highlights
Liver fibrosis is a complex pathological process and an intermediate link between various liver diseases including cirrhosis and liver cancer [1, 2]
No.: 201809) detection kits were provided by Nanjing Jiancheng Bioengineering Institute (Nanjing, China). e antibodies of phospho-c-Jun, phospho-MEK1/2, highmobility group box 1 (HMGB1), α-smooth muscle actin (α-SMA), phospho-ERK1/2, and ERK1/2 were bought from Cell Signaling Technology (United States). e antibodies of MEK1/2 and COL-I were purchased from Abcam (United States) and the antibodies of receptor of advanced glycation end products (RAGE) and GAPDH were bought from ABclonal (China)
The serum levels of collagen IV (COL-IV), hyaluronic acid (HA), LN, and PC III which could reflect the degree of hepatic fibrosis were examined [22]
Summary
Liver fibrosis is a complex pathological process and an intermediate link between various liver diseases including cirrhosis and liver cancer [1, 2]. Numerous studies have revealed the pathogenesis of liver fibrosis, such as inflammatory response, activation of hepatic stellate cells, and excessive deposition of extracellular matrix, but it has not yet been transformed into an effective and powerful treatment [4, 5]. Ere is still a lack of safe and effective means of treating liver fibrosis [6, 7]. It is necessary to develop new drugs for treating liver fibrosis [7]. Traditional Chinese medicine has potential advantages in the treatment of chronic diseases, so we tried to find effective drugs for the treatment of liver fibrosis. In traditional Chinese formula, AR is often used for the treatment of liver fibrosis [10]. No significant toxicity or side effects were observed when the dose administered to rats was set to 39.9 g/kg [12]
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