Wenjun Guo1, Yang Wang2, Meiling Fan3, Shengxu Xie3, Hongyu Zhao3, Jifeng Wang4, Yue Liu3, Dongming Xu3, Yajuan Xu5. 1. School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun, Jilin, 130117, China; Key Laboratory of Medicinal Materials, Jilin Academy of Chinese Medicine Sciences, Changchun, Jilin, 130021, China. 2. Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, Jilin, 130117, China; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, 999078, China. Electronic address: white-wing@163.com. 3. Key Laboratory of Medicinal Materials, Jilin Academy of Chinese Medicine Sciences, Changchun, Jilin, 130021, China. 4. Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, Jilin, 130117, China. 5. Key Laboratory of Medicinal Materials, Jilin Academy of Chinese Medicine Sciences, Changchun, Jilin, 130021, China. Electronic address: xyj6492@126.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Tribulus terrestris L. belongs to the family Zygophyllaceae and has been widely used as a folk medicine for a long history in Asian countries. Gross saponins of Tribulus terrestris L. fruit (GSTTF) has an obvious neuroprotective effect on the treatment of ischemic stroke, but its potential therapeutic mechanisms have not been thoroughly studied. AIM OF THE STUDY: To investigate the protective effect of GSTTF against ischemic stroke in rat. MATERIALS AND METHODS: The combination of metabolomics and network pharmacology analysis was applied to investigate the protective effects of GSTTF on ischemic stroke and its putative mechanism. The related pathway of the biomarkers highlighted from metabolomics analysis was explored, then the possible targets of GSTTF were further revealed by network pharmacology analysis. Molecular docking was conducted to investigate the interaction between the active compound and target protein. RESULTS: Metabolomics analysis showed that metabolic disturbances were observed in serum for the rats in middle cerebral artery occlusion (MCAO). These MCAO-induced deviations in serum metabolism can be reversely changed by GSTTF via metabolic pathways regulation. Twenty-four proteins with the connectivity degree larger than 15 were selected by the network pharmacology analysis, which are considered as the possible therapeutic targets of the GSTTF against ischemic stroke. The results of molecular docking showed that the active compounds were capable of binding to the representative potential targets HSD11B1 and AR, respectively. And the docking mode of two compounds with the lowest binding energy to their target protein was illustrated by the ribbon binding map. CONCLUSION: The present study combines metabolomics and network pharmacology analysis to investigate the mechanism of MCAO-induced ischemic stroke and reveal the efficiency and possible mechanisms of GSTTF for ischemic stroke. Further studies on the bioactive saponin as well as their synergistic action on ischemic stroke will be conducted to better reveal the underlying mechanisms.
ETHNOPHARMACOLOGICAL RELEVANCE: Tribulus terrestris L. belongs to the family Zygophyllaceae and has been widely used as a folk medicine for a long history in Asian countries. Gross saponins of Tribulus terrestris L. fruit (GSTTF) has an obvious neuroprotective effect on the treatment of ischemic stroke, but its potential therapeutic mechanisms have not been thoroughly studied. AIM OF THE STUDY: To investigate the protective effect of GSTTF against ischemic stroke in rat. MATERIALS AND METHODS: The combination of metabolomics and network pharmacology analysis was applied to investigate the protective effects of GSTTF on ischemic stroke and its putative mechanism. The related pathway of the biomarkers highlighted from metabolomics analysis was explored, then the possible targets of GSTTF were further revealed by network pharmacology analysis. Molecular docking was conducted to investigate the interaction between the active compound and target protein. RESULTS: Metabolomics analysis showed that metabolic disturbances were observed in serum for the rats in middle cerebral artery occlusion (MCAO). These MCAO-induced deviations in serum metabolism can be reversely changed by GSTTF via metabolic pathways regulation. Twenty-four proteins with the connectivity degree larger than 15 were selected by the network pharmacology analysis, which are considered as the possible therapeutic targets of the GSTTF against ischemic stroke. The results of molecular docking showed that the active compounds were capable of binding to the representative potential targets HSD11B1 and AR, respectively. And the docking mode of two compounds with the lowest binding energy to their target protein was illustrated by the ribbon binding map. CONCLUSION: The present study combines metabolomics and network pharmacology analysis to investigate the mechanism of MCAO-induced ischemic stroke and reveal the efficiency and possible mechanisms of GSTTF for ischemic stroke. Further studies on the bioactive saponin as well as their synergistic action on ischemic stroke will be conducted to better reveal the underlying mechanisms.