TMEA, a Polyphenol in Sanguisorba officinalis, Promotes Thrombocytopoiesis by Upregulating PI3K/Akt Signaling
Thrombocytopenia is closely linked with hemorrhagic diseases, for which induction of thrombopoiesis shows promise as an effective treatment. Polyphenols widely exist in plants and manifest antioxidation and antitumour activities. In this study, we investigated the thrombopoietic effect and mechanism...
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Format: | Article |
Language: | English |
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Frontiers Media S.A.
2021-08-01
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Series: | Frontiers in Cell and Developmental Biology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.708331/full |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hong Li Xueqin Jiang Xueqin Jiang Xin Shen Yueshan Sun Yueshan Sun Nan Jiang Jing Zeng Jing Lin Liang Yue Jia Lai Yan Li Anguo Wu Anguo Wu Long Wang Long Wang Dalian Qin Dalian Qin Feihong Huang Qibing Mei Jing Yang Jianming Wu Jianming Wu |
spellingShingle |
Hong Li Xueqin Jiang Xueqin Jiang Xin Shen Yueshan Sun Yueshan Sun Nan Jiang Jing Zeng Jing Lin Liang Yue Jia Lai Yan Li Anguo Wu Anguo Wu Long Wang Long Wang Dalian Qin Dalian Qin Feihong Huang Qibing Mei Jing Yang Jianming Wu Jianming Wu TMEA, a Polyphenol in Sanguisorba officinalis, Promotes Thrombocytopoiesis by Upregulating PI3K/Akt Signaling Frontiers in Cell and Developmental Biology thrombocytopenia Sanguisorba officinalis L. PI3K megakaryocyte differentiation 3 3′ |
author_facet |
Hong Li Xueqin Jiang Xueqin Jiang Xin Shen Yueshan Sun Yueshan Sun Nan Jiang Jing Zeng Jing Lin Liang Yue Jia Lai Yan Li Anguo Wu Anguo Wu Long Wang Long Wang Dalian Qin Dalian Qin Feihong Huang Qibing Mei Jing Yang Jianming Wu Jianming Wu |
author_sort |
Hong Li |
title |
TMEA, a Polyphenol in Sanguisorba officinalis, Promotes Thrombocytopoiesis by Upregulating PI3K/Akt Signaling |
title_short |
TMEA, a Polyphenol in Sanguisorba officinalis, Promotes Thrombocytopoiesis by Upregulating PI3K/Akt Signaling |
title_full |
TMEA, a Polyphenol in Sanguisorba officinalis, Promotes Thrombocytopoiesis by Upregulating PI3K/Akt Signaling |
title_fullStr |
TMEA, a Polyphenol in Sanguisorba officinalis, Promotes Thrombocytopoiesis by Upregulating PI3K/Akt Signaling |
title_full_unstemmed |
TMEA, a Polyphenol in Sanguisorba officinalis, Promotes Thrombocytopoiesis by Upregulating PI3K/Akt Signaling |
title_sort |
tmea, a polyphenol in sanguisorba officinalis, promotes thrombocytopoiesis by upregulating pi3k/akt signaling |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cell and Developmental Biology |
issn |
2296-634X |
publishDate |
2021-08-01 |
description |
Thrombocytopenia is closely linked with hemorrhagic diseases, for which induction of thrombopoiesis shows promise as an effective treatment. Polyphenols widely exist in plants and manifest antioxidation and antitumour activities. In this study, we investigated the thrombopoietic effect and mechanism of 3,3′,4′-trimethylellagic acid (TMEA, a polyphenol in Sanguisorba officinalis L.) using in silico prediction and experimental validation. A KEGG analysis indicated that PI3K/Akt signalling functioned as a crucial pathway. Furthermore, the virtual molecular docking results showed high-affinity binding (a docking score of 6.65) between TMEA and mTOR, suggesting that TMEA might target the mTOR protein to modulate signalling activity. After isolation of TMEA, in vitro and in vivo validation revealed that this compound could promote megakaryocyte differentiation/maturation and platelet formation. In addition, it enhanced the phosphorylation of PI3K, Akt, mTOR, and P70S6K and increased the expression of GATA-1 and NF-E2, which confirmed the mechanism prediction. In conclusion, our findings are the first to demonstrate that TMEA may provide a novel therapeutic strategy that relies on the PI3K/Akt/mTOR pathway to facilitate megakaryocyte differentiation and platelet production. |
topic |
thrombocytopenia Sanguisorba officinalis L. PI3K megakaryocyte differentiation 3 3′ |
url |
https://www.frontiersin.org/articles/10.3389/fcell.2021.708331/full |
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doaj-b75434d4bbc541e99419c528c589526e2021-08-17T12:14:26ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-08-01910.3389/fcell.2021.708331708331TMEA, a Polyphenol in Sanguisorba officinalis, Promotes Thrombocytopoiesis by Upregulating PI3K/Akt SignalingHong Li0Xueqin Jiang1Xueqin Jiang2Xin Shen3Yueshan Sun4Yueshan Sun5Nan Jiang6Jing Zeng7Jing Lin8Liang Yue9Jia Lai10Yan Li11Anguo Wu12Anguo Wu13Long Wang14Long Wang15Dalian Qin16Dalian Qin17Feihong Huang18Qibing Mei19Jing Yang20Jianming Wu21Jianming Wu22School of Pharmacy, Southwest Medical University, Luzhou, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaState Key Laboratory of Biotherapy and Cancer Center, West China Medical School, Sichuan University, Chengdu, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaMedical Research Center, The Third People’s Hospital of Chengdu, Chengdu, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaThe Key Laboratory of Medical Electrophysiology, Medical Key Laboratory for Drug Discovery and Druggability Evaluation of Sichuan Province, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, Ministry of Education of China, Institute of Cardiovascular Research, Luzhou, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaThe Key Laboratory of Medical Electrophysiology, Medical Key Laboratory for Drug Discovery and Druggability Evaluation of Sichuan Province, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, Ministry of Education of China, Institute of Cardiovascular Research, Luzhou, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaThe Key Laboratory of Medical Electrophysiology, Medical Key Laboratory for Drug Discovery and Druggability Evaluation of Sichuan Province, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, Ministry of Education of China, Institute of Cardiovascular Research, Luzhou, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaThe Key Laboratory of Medical Electrophysiology, Medical Key Laboratory for Drug Discovery and Druggability Evaluation of Sichuan Province, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, Ministry of Education of China, Institute of Cardiovascular Research, Luzhou, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaThe Key Laboratory of Medical Electrophysiology, Medical Key Laboratory for Drug Discovery and Druggability Evaluation of Sichuan Province, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, Ministry of Education of China, Institute of Cardiovascular Research, Luzhou, ChinaThrombocytopenia is closely linked with hemorrhagic diseases, for which induction of thrombopoiesis shows promise as an effective treatment. Polyphenols widely exist in plants and manifest antioxidation and antitumour activities. In this study, we investigated the thrombopoietic effect and mechanism of 3,3′,4′-trimethylellagic acid (TMEA, a polyphenol in Sanguisorba officinalis L.) using in silico prediction and experimental validation. A KEGG analysis indicated that PI3K/Akt signalling functioned as a crucial pathway. Furthermore, the virtual molecular docking results showed high-affinity binding (a docking score of 6.65) between TMEA and mTOR, suggesting that TMEA might target the mTOR protein to modulate signalling activity. After isolation of TMEA, in vitro and in vivo validation revealed that this compound could promote megakaryocyte differentiation/maturation and platelet formation. In addition, it enhanced the phosphorylation of PI3K, Akt, mTOR, and P70S6K and increased the expression of GATA-1 and NF-E2, which confirmed the mechanism prediction. In conclusion, our findings are the first to demonstrate that TMEA may provide a novel therapeutic strategy that relies on the PI3K/Akt/mTOR pathway to facilitate megakaryocyte differentiation and platelet production.https://www.frontiersin.org/articles/10.3389/fcell.2021.708331/fullthrombocytopeniaSanguisorba officinalis L.PI3Kmegakaryocyte differentiation33′ |