Nao-Xin-Qing tablet inhibits macrophage inflammatory response in atherosclerosis via AMPK-α/SIRT1/PPAR-γ pathway

Nao-Xin-Qing (NXQ) tablets are standardized proprietary herbal products containing an extract of Chinese persimmon leaves (Diospyros kaki L.f., World Checklist) and other natural ingredients. NXQ has also been indicated for atherosclerosis (AS), but the mechanisms of its antiatherosclerotic activity are unclear. In this study, its mechanisms were investigated by using preclinical models, and provide evidence for its potential application against cardiovascular disorders. In vivo, the apolipoprotein E-deficient (ApoE−/−) mice were fed with a high-fat diet to induce AS. And the mice were treated with different concentrations of NXQ and Lipitor for 12 weeks. After the intervention, serum lipid levels and serum inflammatory factor levels were measured. The pathological changes in the aorta were observed by Oil-red-O staining and Hematoxylin and Eosin (HE) staining. Additionally, we investigated macrophage polarization both in vivo and in vitro. Using the NXQ fingerprint, we conducted network pharmacological analysis to predict and explore its antiatherosclerotic mechanism, which was validated in AS mice and LPS-induced macrophages. In our study, we found that NXQ significantly reduced atherosclerotic plaques in the aortic root and aorta and decreased serum lipid levels in HFD-fed ApoE−/− mice. Meanwhile, NXQ promoted M2 macrophage polarization, which is regulated by the AMPK-α/SIRT1/PPAR-γ axis. Importantly, suppressing AMPK-α eliminated the effect of NXQ on macrophages. NXQ exerted a preventive effect on the development and progression of AS by promoting M2 macrophage polarization through modulation of the AMPK-α/SIRT1/PPAR-γ axis.