Network Pharmacology Analysis and Experimental Validation to Explore the Anti-inflammatory Mechanism of Asiatic Acid on Alcoholic Steatohepatitis

Abstract

Objective. The mechanism of action of asiatic acid (AA) on alcoholic steatohepatitis (ASH) was investigated using network pharmacology and experiments. Methods. Through data retrieval, network construction, and enrichment analysis, the potential mechanism of AA in the treatment of alcoholic steatohepatitis was explored. Animal and cell models were established in this study. Animal Model. The mouse model was divided into six groups: normal group; model group; low, medium, and high AA group; and silibinin-positive group. Cell Model. An in vitro inflammatory model of RAW264.7 cells was established by alcohol stimulation. Results. Compared with the model group, the low, medium, and high AA group showed decreased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), and total cholesterol (T-CHO). The inflammatory factor tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) in a dose-dependent manner were decreased. In addition, hematoxylin-eosin staining showed that liver tissue damage and inflammatory cell infiltration in mice were significantly reduced with increasing doses. Further, oil red staining showed that lipid accumulation in hepatocytes in the low, medium, and high AA group was significantly reduced, with increasing dose. In addition, in the cellular model, real-time reverse transcriptase-polymerase chain reaction (Real-Time RT-PCR) and enzyme-linked immunosorbent assay (ELISA) results showed that AA could alleviate alcohol-induced cellular inflammation, while western blot and immunofluorescence results showed that AA might alleviate alcohol-induced cellular inflammation by inhibiting the nuclear factor-κB (NF-κB) pathway. Conclusion. This study provides multiple lines of evidence that asiatic acid may alleviate alcoholic hepatitis in mice by modulating the NF-κB pathway.

Exploring the Potential of Extracts from Sloanea medusula and S. calva: Formulating Two Skincare Gels with Antioxidant, Sun Protective Factor, and Anti-Candida albicans Activities

“…The peak at T R 5.953 and m / z 489.357451 corresponds to ions [M+H] of asiatic acid (C 30 H 48 O 5 ). Asiatic acid is a pentacyclic triterpenoid of ursane-type with anti-inflammatory, antitumor, and antidiabetic properties [ 45 ]. Analysis of the mass spectrum of asiatic acid led to the identification of fragment ions at m / z 187 (C 10 H 35 O 2 ), m / z 205 (molecular ion, C 15 H 25 ), and m / z 223 (C 14 H 23 O 2 ) generated by ring breakage.…”

Asiatic acid inhibits rheumatoid arthritis fibroblast‐like synoviocyte growth through the Nrf2/HO‐1/NF‐κB signaling pathway

“…AA has been found to possess a variety of beneficial biological activities including anti‐inflammatory (Dong et al., 2022), antibacterial, antioxidant, antidepressant, skin care, hypoglycemic, and neuroprotective effects (Nagoor Meeran et al., 2018; Yi et al., 2022). It has the ability to modulate pro‐inflammatory cytokines and slow down the progression of immuno‐inflammatory diseases, and in vitro experiments have further demonstrated that AA can exert a protective effect through the inhibition of NF‐κB activity (Jiang, Xu, Lu, Chen, & Li, 2022; Mioc et al., 2022). Recently, it has also been reported that AA can not only promote apoptosis of tumor cells with little toxicity and side effects, but also confirmed in lung and breast cancer cell models that AA can inhibit tumor growth and has no significant effect on normal cells (Cheng, Zhang, Zhong, Chen, & Peng, 2022; Gou et al., 2020).…”