Sini decoction intervention on atherosclerosis via PPARγ-LXRα-ABCA1 pathway in rabbits

Abstract

AimSini decoction (SND) is a commonly used herbal formula showing lipid-lowering effects and is applied in traditional Chinese medicine (TCM) for the treatment of cardiovascular disease (CVD) and atherosclerosis (AS). However, the mechanisms behind its anti-atherosclerotic effects are still unknown, and will be investigated in this study.MethodsAS was induced in rabbits by high fat diet (HFD) and treated with solvent (HFD group), atorvastatin (Ator group), or SND (SND group) for 12 weeks. Healthy rabbits (Chow group) were used as control. Serum and liver homogenates were collected, and lipid profiles as well as serum ApoA-I and ApoB were examined. Histopathological changes and lipid deposition in the proximal aorta and liver were detected by Oil red O staining. Western blot was used to detect the expression of ABCA1, ApoA-I, ApoB, PPARγ, and LXRα in liver, peritoneal macrophages, peripheral mononuclear cells (PMC), and adipose tissues.ResultsSND significantly attenuated the levels of total cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol(LDL-C) in serum and liver. However, high density lipoprotein cholesterol (HDL-C) dramatically increased. SND treatment also decreased lipid deposition and improved the structure of the liver and aorta. Furthermore, SND enhanced the expression levels of ABCA1, PPARγ, and LXRα in liver, adipose tissues, PMC, and peritoneal macrophages. It also upregulated hepatic and serum ApoA-I expression and serum ApoA-I/ApoB ratio. CONCLUSIONS:SND treatment relieved AS, improved lipid profiles, and increased serum HDL-C level. The potential mechanism behind this might be the improvement of reverse cholesterol transport (RCT) involved with enhanced expression of ABCA1, ApoA-I, PPARγ, and LXRα.

Natural products in atherosclerosis therapy by targeting PPARs: a review focusing on lipid metabolism and inflammation

“…Qi-Huang-Zhu-Yu Formula (QHZY, 岐黄茱萸方) enhances cholesterol efflux by activating PPARγ-LXRα-ABCA1/ABCG1 signaling pathways (37). Notably, Qing-Xue-Xiao-Zhi formula (QXXZ, 清血消脂方), Si-Ni decoction (四逆汤), Qi-Shen-Yi-Qi Pill (芪参益气丸), and Yin-Xing-Tong-Mai decoction (银杏通脉汤) have been demonstrated to attenuate hyperlipidemia and atherosclerosis by facilitating RCT through upregulation of PPARγ-LXRα-ABCA1/ABCG1 signaling pathways (38)(39)(40)(41). Moreover, Dang-Gui-Shao-Yao-San (当归芍药散), a well-known Chinese medicine formula, improves lipid metabolism and inhibits neuroinflammation by activating LXR-PPARγ signaling pathway (42).…”

Role of ABCA1 in Cardiovascular Disease

“…Interestingly, many traditional Chinese medicines are involved in ABCA1 regulation and demonstrate efficacy against atherosclerosis. Yin-xing-tong-mai and Sini decoctions [ 193 ] increase ABCA1 expression in macrophages by activating the PPARγ–LXRα pathway to attenuate atherosclerosis [ 194 ]. The Qing-Xue-Xiao-Zhi formula inhibits the TLR4/MyD88/NF-κB pathway to promote ABCA1 expression [ 195 ].…”