Preventive effects of astragaloside IV and its active sapogenin cycloastragenol on cardiac fibrosis of mice by inhibiting the NLRP3 inflammasome.
Cardiac fibrosis is a common feature of many cardiac pathophysiologic conditions. Recently, it has been shown that the activation of NLRP3 inflammasome plays an important role in the pathophysiology of cardiac fibrosis. Here, the inhibitory effects and possible mechanism of astragaloside IV (AST) and its active sapogenin cycloastragenol (CAG) on isoproterenol (ISO)-induced cardiac fibrosis were investigated. In our study, BALB/c mice were subcutaneously injected with 5 mg/kg ISO for 7 consecutive days to induce cardiac fibrosis. AST or CAG was administrated to the mice intragastrically at different doses beginning on the same day of ISO injection. Primary cardiac fibroblasts were isolated from the hearts of neonatal rats, and treated with 10 μmol/L ISO for 24 h with or without incubation of CAG simultaneously. The results indicated that 62.5 mg/kg CAG could significantly inhibit ISO-induced cardiac fibrosis, which was evidenced by sirius red staining, collagen volume fraction and mRNA expressions of collagen-1, collagen-3 and TGF-β1. Hematoxylin-eosin staining showed that 62.5 mg/kg CAG markedly reduced the inflammatory cell infiltration in heart tissues. To elucidate the related mechanism, NLRP3/caspase-1/IL-18 pathway was studied. The mRNA expressions of NLRP3, caspase-1, IL-18 and IL-6 in mice heart tissues were significantly down-regulated by 62.5 mg/kg CAG and 200 mg/kg AST. And incubation with 31.25 μg/ml CAG markedly attenuated ISO-induced mRNA over-expressions of NLRP3, caspase-1, IL-18 and IL-6 in primary cardiac fibroblasts. These findings showed that CAG effectively inhibited ISO-induced cardiac fibrosis, and both CAG and AST exhibited anti-fibrosis effects through inhibition of the NLRP3 inflammasome pathway.
['Wan|Yu|Y|', 'Xu|Lu|L|', 'Wang|Yunxia|Y|', 'Tuerdi|Nuerbiya|N|', 'Ye|Min|M|', 'Qi|Rong|R|']
D000818:Animals D002318:Cardiovascular Diseases D002478:Cells, Cultured D004195:Disease Models, Animal D004365:Drugs, Chinese Herbal D005347:Fibroblasts D005355:Fibrosis D006321:Heart D006801:Humans D058847:Inflammasomes D007545:Isoproterenol D008297:Male D051379:Mice D008807:Mice, Inbred BALB C D009206:Myocardium D000071199:NLR Family, Pyrin Domain-Containing 3 Protein D061251:Primary Cell Culture D051381:Rats D017207:Rats, Sprague-Dawley D012502:Sapogenins D012503:Saponins D014315:Triterpenes
Astragaloside IV Cycloastragenol Cardiac fibrosis NLRP3 inflammasome