Gaosong Wu1, Linlin Chen1, Yu Gu1, Ying Hong1, Junli Ma1, Ningning Zheng1, Jing Zhong2, Ai-Jun Liu3, Lili Sheng1, Weidong Zhang4, Houkai Li5. 1. Interdisciplinary Science Research Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. 2. Interdisciplinary Science Research Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Huzhou Key Laboratory of Molecular Medicine, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, 313000, China. 3. Department of Phytochemistry, School of Pharmacy, Second Military Medical University, Shanghai, 200433, China. 4. Interdisciplinary Science Research Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Department of Phytochemistry, School of Pharmacy, Second Military Medical University, Shanghai, 200433, China. Electronic address: wdzhangy@hotmail.com. 5. Interdisciplinary Science Research Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: houkai1976@126.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Shexiang Baoxin Pill (SBP) is a commercial Chinese medicine included in the Chinese Pharmacopoeia with well-established cardiovascular protect effect in clinic. However, the mechanism of SBP underlying protective effect on cardiovascular disease has not been clearly elucidated yet. AIM OF THE STUDY: We aimed to investigate the underlying protective mechanisms of SBP on an acute myocardial infarction (AMI) rat model by using comprehensive metabolomics. MATERIALS AND METHODS: The rat model of AMI was generated by ligating the left anterior descending coronary artery. After two weeks of treatment with SBP, comprehensive metabolomics and echocardiography index was performed for a therapeutic evaluation. The wiff data were processed using Progenesis QI and metabolites were identified based on the database of HMDB and LIPIDMAPS. Meanwhile, the untargeted metabolomics data from LC-MS combined with correlation analysis to characterize the metabolic alterations. RESULTS: The metabolomics profiles of different groups in different biological samples (heart, serum, urine and feces) were significantly different, in which a total of 217 metabolites were identified. AMI caused comprehensive metabolic changes in amino acid metabolism, glycerophospholipid metabolism and pyrimidine metabolism, while SBP reversed more than half of the differential metabolic changes, mainly affecting amino acid metabolism, butanoate metabolism and glycerophospholipid metabolism. Correlation analysis found that SBP could significantly alter the metabolic activity of six key metabolites (5-hydroxyindoleacetic acid, glycerophosphocholine, PS (20:4/0:0), xanthosine, adenosine and L-phenylalanine) related to AMI. The key role of these metabolites was further validated with correlation analysis with echocardiography indexes. CONCLUSION: This study demonstrated that SBP was effective for protecting cardiac dysfunction by regulating amino acid, lipid and energy metabolisms. The results also suggested that the modulation on gut microbiota might be involved the cardioprotective effect of SBP.
ETHNOPHARMACOLOGICAL RELEVANCE: Shexiang Baoxin Pill (SBP) is a commercial Chinese medicine included in the Chinese Pharmacopoeia with well-established cardiovascular protect effect in clinic. However, the mechanism of SBP underlying protective effect on cardiovascular disease has not been clearly elucidated yet. AIM OF THE STUDY: We aimed to investigate the underlying protective mechanisms of SBP on an acute myocardial infarction (AMI) rat model by using comprehensive metabolomics. MATERIALS AND METHODS: The rat model of AMI was generated by ligating the left anterior descending coronary artery. After two weeks of treatment with SBP, comprehensive metabolomics and echocardiography index was performed for a therapeutic evaluation. The wiff data were processed using Progenesis QI and metabolites were identified based on the database of HMDB and LIPIDMAPS. Meanwhile, the untargeted metabolomics data from LC-MS combined with correlation analysis to characterize the metabolic alterations. RESULTS: The metabolomics profiles of different groups in different biological samples (heart, serum, urine and feces) were significantly different, in which a total of 217 metabolites were identified. AMI caused comprehensive metabolic changes in amino acid metabolism, glycerophospholipid metabolism and pyrimidine metabolism, while SBP reversed more than half of the differential metabolic changes, mainly affecting amino acid metabolism, butanoate metabolism and glycerophospholipid metabolism. Correlation analysis found that SBP could significantly alter the metabolic activity of six key metabolites (5-hydroxyindoleacetic acid, glycerophosphocholine, PS (20:4/0:0), xanthosine, adenosine and L-phenylalanine) related to AMI. The key role of these metabolites was further validated with correlation analysis with echocardiography indexes. CONCLUSION: This study demonstrated that SBP was effective for protecting cardiac dysfunction by regulating amino acid, lipid and energy metabolisms. The results also suggested that the modulation on gut microbiota might be involved the cardioprotective effect of SBP.
Authors: Ran Joo Choi; Siti Zuraidah Mohamad Zobir; Ben Alexander-Dann; Nitin Sharma; Marcella K L Ma; Brian Y H Lam; Giles S H Yeo; Weidong Zhang; Tai-Ping Fan; Andreas Bender Journal: Front Pharmacol Date: 2021-02-10 Impact factor: 5.810