Astragaloside IV Relieves Atherosclerosis and Hepatic Steatosis via MAPK/NF-κB Signaling Pathway in LDLR−/− Mice

Abstract

Astragaloside IV (AS-IV) is the main active compound of Astragalus membranaceus. In this study, we investigated whether AS-IV could attenuate atherosclerosis and hepatic steatosis in LDLR−/−mice and its potential mechanisms. After 12 weeks of high fat diet, the LDLR−/−mice were randomly divided into four groups. Then, the mice were administrated with 0.9% saline or AS-IV (10 mg/kg) or atorvastatin (1.3 mg/kg) for 12 weeks. Serum lipid profiles and inflammatory cytokines were detected by ELISA, hepatic TC and TG by colorimetric enzymatic kits, gene expression by RT-qPCR, plaque sizes by H&E staining, Oil Red O, liver pathology by H&E staining, collagen content by Masson, α-SMA, caspase-3 and NF-κB p65 production by immunofluorescence staining. MAPK/NF-κB pathway and inflammation related proteins were detected by Western Blot. The results showed that AS-IV decreased the levels of serum lipids, reduced plaque area and increased plaque stability in HFD-induced LDLR−/− mice. AS-IV also decreased the levels of inflammatory cytokines in the serum, aortas and liver tissue, and NF-κB p65 in aortic roots. The phosphorylation of JNK, ERK1/2, p38 and NF-κB, and inflammatory proteins (iNOS, VCAM-1and IL-6) was inhibited in AS-IV-treated group. In summary, AS-IV inhibited inflammation to attenuate atherosclerosis and hepatic steatosis via MAPK/NF-κB signaling pathway in LDLR−/− mice.

Natural products of traditional Chinese medicine treat atherosclerosis by regulating inflammatory and oxidative stress pathways

“…Geniposide combined with Panax notoginsenoside R1 inhibits the secretion of serum inflammatory and oxidative stress factors by inducing activation of the Nrf2 signaling pathway and synergistically reduces blood lipid levels and inhibits plaque formation (Liu et al, 2021). Other natural saponins, such as amygdalin (Wang et al, 2020), astragaloside IV (Zhang et al, 2022a), and saikosaponin (Yang et al, 2017) can also protect against AS plaques by modulating the MAPK/NF-κB signaling pathway and reducing inflammatory factors and oxidative stress responses.…”

Mechanism of Tao Hong Decoction in the treatment of atherosclerosis based on network pharmacology and experimental validation

“…The characteristics of a vulnerable plaque include a low fibrous cap area ( 28 , 29 ). Then the collagen content was detected by Masson staining to explore the effect of THD on the stability of atherosclerotic plaques.…”

Astragalus saponins and its main constituents ameliorate ductular reaction and liver fibrosis in a mouse model of DDC-induced cholestatic liver disease

“…It is found that astragaloside IV is able to inhibit liver inflammation via mitogen-activated protein kinase (MAPK)/nuclear factor kappa-B (NF-κB) signaling pathway, which in turn reduce lipid levels, hepatic steatosis in hyperlipidemic mice ( Zhang Y. et al, 2022 ). Astragaloside IV significantly reduces body weight, white fat and liver/body weight ratio in senescent mice by targeting mitochondrial activity, and promotes fatty acid in white adipose tissue mobilization in aging mice ( Luo et al, 2021 ).…”