TMEA, a Polyphenol in Sanguisorba officinalis, Promotes Thrombocytopoiesis by Upregulating PI3K/Akt Signaling.
TMEA, a Polyphenol in Sanguisorba officinalis, Promotes Thrombocytopoiesis by Upregulating PI3K/Akt Signaling.
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TMEA 是地榆中的一种多酚，通过上调 PI3K/Akt 信号传导促进血小板生成
DOI：
10.3389/fcell.2021.708331
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发表时间：
2021
影响因子：
5.5
通讯作者：
Wu J
中科院分区：
文献类型：
--
作者：
Li H;Jiang X;Shen X;Sun Y;Jiang N;Zeng J;Lin J;Yue L;Lai J;Li Y;Wu A;Wang L;Qin D;Huang F;Mei Q;Yang J;Wu J
血小板减少症与出血性疾病密切相关，诱导血小板生成是一种有效的治疗方法。多酚广泛存在于植物中，具有抗氧化和抗肿瘤活性。本研究探讨了地榆多酚3，3 ′，4 ′-三甲基鞣花酸（TMEA）的促血小板生成作用及其机制。使用计算机预测和实验验证。KEGG分析表明，PI 3 K/Akt信号通路起着关键作用。此外，虚拟分子对接结果显示TMEA和mTOR之间的高亲和力结合（对接得分为6.65），表明TMEA可能靶向mTOR蛋白以调节信号传导活性。TMEA分离后，体外和体内验证显示该化合物可促进巨核细胞分化/成熟和血小板形成。此外，它还能增强PI 3 K、Akt、mTOR和P70 S6 K的磷酸化，增加加塔-1和NF-E2的表达，证实了其作用机制的预测。总之，我们的研究结果是第一个证明TMEA可能提供一种新的治疗策略，依赖于PI 3 K/Akt/mTOR通路，以促进巨核细胞分化和血小板生成。
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.
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影响因子：
--
作者：
Castro V
通讯作者：
Castro V
影响因子：
20.3
作者：
Geue，Sascha;Aurbach，Katja;Borst，Oliver
通讯作者：
Borst，Oliver
影响因子：
4.6
作者：
Daina A;Michielin O;Zoete V
通讯作者：
Zoete V
影响因子：
4.6
作者：
Cullmann K;Jahn M;Spindler M;Schenk F;Manukjan G;Mucci A;Steinemann D;Boller K;Schulze H;Bender M;Moritz T;Modlich U
通讯作者：
Modlich U
影响因子：
14.9
作者：
Gfeller D;Grosdidier A;Wirth M;Daina A;Michielin O;Zoete V
通讯作者：
Zoete V