Phospholipase Cγ2 Signaling Cascade Contribute to the Antiplatelet Effect of Notoginsenoside Fc
Scope: Bleeding, the main drawback of clinically used chemical anti-thrombotic drug is resulted from the unidirectional suppression of platelet activity. Therefore, dual-directional regulatory effect on platelet is the main preponderance of Panax notoginseng over these drugs. The dual-directional re...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-11-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2018.01293/full |
| _version_ | 1819054184491646976 |
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| author | Yingqiu Liu Tianyi Liu Kevin Ding Zengyuan Liu Yuanyuan Li Taotao He Weimin Zhang Yunpeng Fan Wuren Ma Li Cui Xiaoping Song |
| author_facet | Yingqiu Liu Tianyi Liu Kevin Ding Zengyuan Liu Yuanyuan Li Taotao He Weimin Zhang Yunpeng Fan Wuren Ma Li Cui Xiaoping Song |
| author_sort | Yingqiu Liu |
| collection | DOAJ |
| description | Scope: Bleeding, the main drawback of clinically used chemical anti-thrombotic drug is resulted from the unidirectional suppression of platelet activity. Therefore, dual-directional regulatory effect on platelet is the main preponderance of Panax notoginseng over these drugs. The dual-directional regulatory effect should be ascribed to the resourceful Panax notoginseng saponins (PNS). Clarifying the mechanism of main PNS in both inhibiting and promoting platelet aggregation will give a full outlook for the dual-directional regulatory effect. The present study is aimed at explaining the mechanism of Notoginsenoside Fc (Fc), a main PNS, in inhibiting platelet aggregation.Methods: In the in vitro study, after incubating platelets with Fc and m-3M3FBS, platelet aggregation was triggered by thrombin, collagen or ADP. Platelet aggregation was measured by aggregometer. Phospholipase Cγ2 (PLCγ2) and protein kinase C (PKC) activities were studied by western blotting. Diacylglycerol (DAG), thromboxane B2 (TXB2) and 1,4,5-inositol trisphosphate (IP3) concentrations were measured by corresponding ELISA kits. Calcium concentrations ([Ca2+]) were estimated through the fluorescence intensity emitted from Fluo-4. In the in vivo study, thrombus model was induced by FeCl3. The effect of Fc on thrombosis was evaluated by measurement of protein content and observation of injured blood vessel.Results: thrombin, collagen and ADP induced platelet aggregation were all suppressed by incubating platelets with Fc. Platelet PLCγ2 and subsequent DAG-PKC-TXA2 and IP3 were down-regulated by Fc as well. However, the basal [Ca2+] in platelet was not altered by Fc. Nevertheless, thrombin triggered activation of PLCγ2 and subsequent DAG-PKC-TXA2 and IP3-[Ca2+] were all abolished by Fc. Fc also attenuated platelet aggregation and PLCγ2 signaling activation induced by PLC activator, m-3M3FBS. In the in vivo study, FeCl3 induced thrombosis in rat femoral artery was significantly alleviated by administration of Fc.Conclusion: The results above suggested the antiplatelet and antithrombotic effects of Fc are carried out through oppression of PLCγ2 and subsequent DAG-PKC-TXA2 and IP3-[Ca2+]. The present study provided theoretical support for new anti-thrombotic drug exploitation by Panax notoginseng. |
| first_indexed | 2024-12-21T12:47:35Z |
| format | Article |
| id | doaj.art-327cb21770ce4254a2f913334afb3c2c |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-21T12:47:35Z |
| publishDate | 2018-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-327cb21770ce4254a2f913334afb3c2c2022-12-21T19:03:35ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-11-01910.3389/fphar.2018.01293353119Phospholipase Cγ2 Signaling Cascade Contribute to the Antiplatelet Effect of Notoginsenoside FcYingqiu Liu0Tianyi Liu1Kevin Ding2Zengyuan Liu3Yuanyuan Li4Taotao He5Weimin Zhang6Yunpeng Fan7Wuren Ma8Li Cui9Xiaoping Song10Laboratory of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, ChinaDepartment of Neurosurgery, The First Hospital of Jilin University, Changchun, ChinaUniversity of Illinois at Urbana–Champaign, Urbana, IL, United StatesLaboratory of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, ChinaLaboratory of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, ChinaLaboratory of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, ChinaLaboratory of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, ChinaLaboratory of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, ChinaLaboratory of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, ChinaDepartment of Neurosciences, University of California, San Diego School of Medicine, La Jolla, CA, United StatesLaboratory of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, ChinaScope: Bleeding, the main drawback of clinically used chemical anti-thrombotic drug is resulted from the unidirectional suppression of platelet activity. Therefore, dual-directional regulatory effect on platelet is the main preponderance of Panax notoginseng over these drugs. The dual-directional regulatory effect should be ascribed to the resourceful Panax notoginseng saponins (PNS). Clarifying the mechanism of main PNS in both inhibiting and promoting platelet aggregation will give a full outlook for the dual-directional regulatory effect. The present study is aimed at explaining the mechanism of Notoginsenoside Fc (Fc), a main PNS, in inhibiting platelet aggregation.Methods: In the in vitro study, after incubating platelets with Fc and m-3M3FBS, platelet aggregation was triggered by thrombin, collagen or ADP. Platelet aggregation was measured by aggregometer. Phospholipase Cγ2 (PLCγ2) and protein kinase C (PKC) activities were studied by western blotting. Diacylglycerol (DAG), thromboxane B2 (TXB2) and 1,4,5-inositol trisphosphate (IP3) concentrations were measured by corresponding ELISA kits. Calcium concentrations ([Ca2+]) were estimated through the fluorescence intensity emitted from Fluo-4. In the in vivo study, thrombus model was induced by FeCl3. The effect of Fc on thrombosis was evaluated by measurement of protein content and observation of injured blood vessel.Results: thrombin, collagen and ADP induced platelet aggregation were all suppressed by incubating platelets with Fc. Platelet PLCγ2 and subsequent DAG-PKC-TXA2 and IP3 were down-regulated by Fc as well. However, the basal [Ca2+] in platelet was not altered by Fc. Nevertheless, thrombin triggered activation of PLCγ2 and subsequent DAG-PKC-TXA2 and IP3-[Ca2+] were all abolished by Fc. Fc also attenuated platelet aggregation and PLCγ2 signaling activation induced by PLC activator, m-3M3FBS. In the in vivo study, FeCl3 induced thrombosis in rat femoral artery was significantly alleviated by administration of Fc.Conclusion: The results above suggested the antiplatelet and antithrombotic effects of Fc are carried out through oppression of PLCγ2 and subsequent DAG-PKC-TXA2 and IP3-[Ca2+]. The present study provided theoretical support for new anti-thrombotic drug exploitation by Panax notoginseng.https://www.frontiersin.org/article/10.3389/fphar.2018.01293/fullPanax notoginsengNotoginsenoside Fcplatelet aggregationantiplatelet effectthrombosisphospholipase Cγ2 |
| spellingShingle | Yingqiu Liu Tianyi Liu Kevin Ding Zengyuan Liu Yuanyuan Li Taotao He Weimin Zhang Yunpeng Fan Wuren Ma Li Cui Xiaoping Song Phospholipase Cγ2 Signaling Cascade Contribute to the Antiplatelet Effect of Notoginsenoside Fc Frontiers in Pharmacology Panax notoginseng Notoginsenoside Fc platelet aggregation antiplatelet effect thrombosis phospholipase Cγ2 |
| title | Phospholipase Cγ2 Signaling Cascade Contribute to the Antiplatelet Effect of Notoginsenoside Fc |
| title_full | Phospholipase Cγ2 Signaling Cascade Contribute to the Antiplatelet Effect of Notoginsenoside Fc |
| title_fullStr | Phospholipase Cγ2 Signaling Cascade Contribute to the Antiplatelet Effect of Notoginsenoside Fc |
| title_full_unstemmed | Phospholipase Cγ2 Signaling Cascade Contribute to the Antiplatelet Effect of Notoginsenoside Fc |
| title_short | Phospholipase Cγ2 Signaling Cascade Contribute to the Antiplatelet Effect of Notoginsenoside Fc |
| title_sort | phospholipase cγ2 signaling cascade contribute to the antiplatelet effect of notoginsenoside fc |
| topic | Panax notoginseng Notoginsenoside Fc platelet aggregation antiplatelet effect thrombosis phospholipase Cγ2 |
| url | https://www.frontiersin.org/article/10.3389/fphar.2018.01293/full |
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