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ORIGINAL RESEARCH article
Front. Mol. Biosci.
Sec. Molecular Diagnostics and Therapeutics
Volume 12 - 2025 | doi: 10.3389/fmolb.2025.1573294
This article is part of the Research Topic The Role of Calcium Channels in Human Health and Disease Volume III View all 8 articles
Role of Ca 2+ /calmodulin and PI3K/AKT signaling pathways and active ingredients of BaoTaiYin in treatment of recurrent miscarriage
Provisionally accepted
Ji Li 1 Anqi Deng 2 Huiying Chen 2 Shuangyan Guo 2 Pingyu Wang 2 Ruiyi Zhang 2 Wenyang Chen 3 Taotao Fan 2 Lijuan Jiang 1*
Bing Shen 4*- 1 Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
- 2 Anhui Medical University, Hefei, Anhui Province, China
- 3 Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- 4 Macau University of Science and Technology, Taipa, Macao, SAR China
Introduction: BaoTaiyin (BTY) is a traditional Chinese medicine decoction. It has been used to treat recurrent miscarriage (RM). However, there are no comprehensive systematic studies to identify the chemical compositions of BTY and molecular mechanisms on RM. Finding the chemical components of BTY and clarifying the underlying processes in the treatment of RM were the goals of the study. Methods: We used ultra-high-performance liquid chromatography coupled with triple quadruple timeof-flight tandem mass spectrometry to analyze the chemical components of BTY, network analysis to predict the pharmacological effects of the identified active ingredients, and cell experiments to identify potential molecular mechanisms. Results: We found 12 active ingredients among 61 components identified in BTY. These identified activities were linked to regulatory effects on 127 key signaling pathways, targeting 107 proteins. Through network analysis, we determined that insulin-like growth factor 1 receptor, matrix metalloproteinases, PI3K, and STAT3 may be the core targets of BTY's therapeutic effects on RM. We further explored this mechanism to find that aqueous extracts of BTY significantly enhanced IGFBP2 and CaMKK2 expression and trophoblast proliferation, whereas inhibitors of IGF1R/PI3K/AKT pathway or CaMKK2 blocked the effect of BTY on trophoblast proliferation. In addition, IGFBP2 siRNA suppressed BTY-induced CaMKK2 expression. Caffeic acid, as one of components of BTY, increased intracellular Ca 2+ concentration and proliferation in trophoblast. Conclusions: Our research showed that BTY may have therapeutic benefits on RM through multiple targets and pathways, such as the IGF1R/PI3K/AKT and Ca 2+ /calmodulin signaling pathways.
Keywords: recurrent miscarriage, BaoTaiYin, Trophoblast proliferation, Ca 2+ signal, Mass Spectrometry, proliferation
Received: 08 Feb 2025; Accepted: 10 Mar 2025.
Copyright: © 2025 Li, Deng, Chen, Guo, Wang, Zhang, Chen, Fan, Jiang and Shen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Lijuan Jiang, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
Bing Shen, Macau University of Science and Technology, Taipa, Macao, SAR China
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