Efficacy and potential mechanisms of the main active ingredients of astragalus mongholicus in animal models of liver fibrosis: A systematic review and meta-analysis

Astragalus mongholicus (AM) is a Qi-tonifying and immune-regulating herb widely used in traditional Chinese medicine (TCM), which is increasingly regarded as a profound complementary medication in the treatment of fibrosis disease. Astragaloside (AS), astragaloside flavonoids (AF) and astragaloside polysaccharides (APS) are the main active ingredients of Astragalus Mongholicus (AM) that have a significant therapeutic effect on liver fibrosis. This systematic review and meta-analysis aims to evaluate the effects and possible mechanisms of the main active ingredients of AM including astragaloside (AS), astragalus flavone (AF) and astragalus polysaccharide (APS) in animal models of liver fibrosis. We systematically searched ten databases PubMed, Web of Science, Embase, Scopus, CINAHL, ProQuest database, China National Knowledge Internet (CNKI), VIP Information Chinese Periodical Service Platform (VIP), WangFang database and China Biology Medicine Disc (CBM) to identify relevant animal studies from inception to November 2022. The SYRCLE's risk of bias tool was used to assess the methodological quality. The statistical analysis was performed using RevMan 5.4 software. Twenty-three studies involving 482 animals were included. Studies quality scores ranged from 4 to 5. Alanine aminotransferase (ALT) (SMD, −3.87; 95% CI, −5.09 to −2.65; P < 0.00001) aminotransferase (AST) (SMD, −4.43; 95% CI, −5.77 to −3.08; P < 0.00001), hydroxyproline (HYP) (SMD, −2.94; 95% CI, −3.83 to −2.05; P < 0.00001) and transforming growth factor-β1 (TGF-β1) (SMD, −2.82; 95% CI, −3.57 to −2.06; P < 0.00001) were the main outcome measures to be analyzed. The meta-analysis revealed that the main active ingredients of AM lowered the levels of known risk factors including liver index (SMD, −1.25; 95% CI, −1.63 to −0.87; P < 0.00001), degree of liver fibrosis (SMD, −1.93; 95% CI, −2.57 to −1.28; P < 0.00001), collagen α type I (Col)-1 (SMD, −3.71; 95% CI, −5.63 to −1.79; P = 0.0001), hyaluronic acid (HA) (SMD, −2.65; 95% CI, −3.69 to −1.61; P < 0.00001), laminin (LN) (SMD, −2.06; 95% CI, −2.51 to −1.61; P < 0.00001), type IV collagen (CIV) (SMD, −3.04; 95% CI, −4.34 to −1.74; P < 0.00001), procollagen typeIII (PCIII) (SMD, −2.60; 95% CI, −3.15 to −2.05; P < 0.00001), albumin (ALB) (SMD, −1.19; 95% CI, −1.63 to −0.75; P < 0.00001), total bilirubin (TBiL) (SMD, −3.63; 95% CI, −5.39 to −1.88; P < 0.0001), α-smooth muscle actin (α-SMA) (SMD, −5.27; 95% CI, −6.94 to −3.61; P < 0.00001) and Smad3 (SMD, −4.11; 95% CI, −7.17 to −1.05; P = 0.009) level. Our meta-analysis demonstrates the effective role of the main active ingredients of AM in preclinical studies of liver fibrosis. The underlying mechanisms may be related to attenuation of oxidative stress, modulation of inflammatory response and inhibition of collagen production. However, due to the significant heterogeneity and poor quality of included studies, positive findings should be treated cautiously. PROSPERO ID CRD42023382282