Dengyinnaotong attenuates atherosclerotic lesions, gut dysbiosis and intestinal epithelial barrier impairment in the high fat diet-fed ApoE−/− mice

Dengyinnaotong (DYNT) is a traditional Chinese medicine-based patent drug officially approved for the treatment of ischemic stroke primarily based on its indigenous application for the treatment of cardiovascular and cerebrovascular diseases in Southwest China. Atherosclerosis is the principal pathology underlying the pathogenesis of ischemic stroke and coronary artery disease. However, whether DYNT is effective at mitigating atherosclerosis remains unknown.The purpose of the current study is to evaluate the potential impact of DYNT treatment on the atherosclerotic lesions and associated pathological mechanisms.Histological, immunohistochemical, molecular biological approaches were adopted to investigate the pharmacological impact of DYNT treatment on atherosclerosis and associated pathophysiological alterations in the high fat diet (HFD)-fed ApoE gene deficient (ApoE-/-) mice.DYNT treatment reduced the size of the atherosclerotic plaques, alleviated the necrotic core, lowered the lipid retention, mitigated the macrophagic burden and decreased the expression of proatherogenic chemokine Ccl2 in the atherosclerotic lesions. DYNT treatment also offered partial protection against atherogenic dyslipidemia and mitigated hepatic lipid content as well as fatty liver pathologies in the HFD-fed ApoE-/- mice. Furthermore, DYNT treatment protected against atherosclerosis-associated gut dysbiosis and impairment in the intestinal epithelial barrier.Our work provides novel preclinical evidence that underpins the multifaceted effects of DYNT in the control of atherosclerosis.