Chronic cerebral ischemia (CCI) is a serious human health condition with lacking therapeutic agents. Moreover, its mechanism of action remains elusive, and thus novel treatment options are required. Lipid metabolism disorder are closely related to CCI. In this study, a CCI-rats model was established by the permanent occlusion of rat bilateral common carotid arteries, and then the rats were treated with a Xiao-Xu-Ming decoction (XXMD). Lipidomic profiling was conducted in both plasma and brain o determine the effects of the injury and therapy on lipid metabolism. Sphingolipid (particularly long acyl chain and total ceramides), glyceryl phosphatide, and glyceride profiles significantly changed in the brain after model induction and again after dosing. A total of 35 potential biomarkers were found in the brain and four were found in the plasma, representing both CCI injury and XXMD action. Correlations between endogenous lipids and exogenous XXMD compounds were analyzed using linear regression. Two exogenous compounds (cimifugin and 5-O-methylvisamminol) in the brain and 17 exogenous compounds in the plasma, which may represent the active constituents in XXMD, were significantly associated with lipid metabolism. This study provides a new perspective on the potential mechanism of CCI and its treatment with XXMD, as well as on discovering effective components in traditional Chinese medicines.
Keywords: Xiao-Xu-Ming decoction; chronic cerebral ischemia; lipid metabolic network; lipidomics; potential biomarkers.