Neuroprotective Effects of Longxuetongluo Capsule on Ischemic Stroke Rats Revealed by LC-MS/MS-Based Metabolomics Approach

Longxuetongluo Capsule (LTC) that was prepared from the phenolic compound cluster of Chinese dragon’s blood, has been clinically utilized for years towards ischemic stroke. However, LTC therapeutic mechanisms remain unclear, which restricts its further application and promotion. The present study aimed to evaluate the therapeutic effect and to explore the underlying mechanisms of LTC on ischemic stroke rats characterized by cerebral ischemia reperfusion injury. Ischemic stroke rats were simulated by middle cerebral artery occlusion (MCAO), and LTC therapy was validated by the assays in terms of histological assessments. The plasma metabolite profiling was used to clarify the molecules in respond to the LTC treatment. A total of 13 potential biomarkers contributing to ischemic stroke were observed, and Youden index of 11 biomarkers such as LysoPC, SM, and PE (24:1/18:3) were more than 0.7, which are involved in neuroprotective process. The correlation and pathway analysis showed that LTC was beneficial to ischemic stroke rats via regulating glycerophospholipid and sphingolipid metabolism, together with bicotinate and nicotinamide metabolism. Heatmap and ternary analysis indicated the synergistic effect of carbohydrates and lipids may be induced by flavonoid intake from LTC. Funding Information: This work was financially supported by the National Natural Science Foundation of China (81573572, 81530097), China Agriculture Research System of MOF and MARA, and Central Public-interest Scientific Institution Basal Research Fund (Y2020XK24) Declaration of Interests: Authors declare no conflict of interest. Ethics Approval Statement: All animal experiment protocols were approved by the Medical Ethics Committee of Beijing University of Chinese Medicine