RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Dyslipidemia is the leading risk factor of atherosclerosis (AS). Adipose tissue macrophages (ATMs) can regulate postprandial cholesterol levels via uptake and hydrolyzation of lipids and regulation of macrophage cholesterol efflux (MCE). San-wei-tan-xiang (SWTX) capsule, a Traditional Chinese medicine, exerts clinical benefits in patients with atherosclerotic cardiovascular diseases. AIM OF THE STUDY: This work is aimed to evaluate the chemical ingredients and mechanisms of SWTX in anti-AS. MATERIALS AND METHODS: The chemical ingredients of SWTX identified by liquid chromatography coupled with tandem mass spectrometry were used for network pharmacological analysis. The atheroprotective function of SWTX was evaluated in ApoE-/- mice fed a cholesterol-enriched diet. RESULTS: The chemical ingredients identified in SWTX were predicated to be important for lipid metabolism and AS. Animals studies suggested that SWTX effectively attenuated the atherosclerotic plaque growth, elevated postprandial HDL cholesterol levels, elevated the proportion of Tim4 and CD36-expressed ATMs, and upregulated the uptake of lipid and lysosomal activity in ATMs. SWTX-induced elevation of postprandial HDL cholesterol levels was dependent on increased lysosomal activity, since chloroquine, an inhibitor of lysosomal function, blocked the effect of SWTX. Lastly, some predicated bioactive compounds in SWTX can elevate lysosomal activity in vitro. CONCLUSION: SWTX could attenuate atherosclerotic plaque formation by elevating lysosomal activity and enhancing MCE in ATMs.
Asunto(s)
Aterosclerosis , Placa Aterosclerótica , Ratones , Animales , Placa Aterosclerótica/metabolismo , HDL-Colesterol , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/prevención & control , Aterosclerosis/etiología , Macrófagos , Colesterol/metabolismo , Lisosomas/metabolismo , Apolipoproteínas ERESUMEN
Phytomedicine has shown a promising potential for the prevention of cardiovascular system diseases and disorders. This study aimed to evaluate protective effect of ergosterol (ER) on isoproterenol (ISO)-induced myocardial cardiotoxicity. We found that pretreatment with ER significantly decreased levels of myocardial CK-MB and LDH, and alleviated myocardial damage induced by ISO in rat model. In addition, ER restored Nrf2 and HO-1 expression and inhibited apoptosis through upregulating Bcl-2 and downregulating Bax, cytochrome c, cleaved caspase-3, caspase-9, and PARP in rat hearts. Hypoxia-reoxygenation model in H9C2 cells confirmed the cardioprotective effects of ER. In conclusion, we provide both in vitro and in vivo evidence that ER significantly enhances Nrf2-mediated anti-oxidative activities, and exerts a protective effect on cardiomyocyte apoptosis. ER could be considered as a potential therapeutic agent to prevent myocardial injury.