Hunan University of Chinese Medicine, Changsha, Hunan Province, China.
Hunan University of Science and Technology, Xiangtan, China.
J Ethnopharmacol. 2024 Apr 6;323:117589. doi: 10.1016/j.jep.2023.117589. Epub 2023 Dec 15.
Shou Tai Wan (STW), a traditional Chinese medicine formula, has been historically used for the treatment of recurrent spontaneous abortion (RSA). Despite its long-standing usage, the exact mechanism underlying the therapeutic effects of STW remains unclear in the existing literature.
To explore the Pharmacological Mechanism of STW on RSA.
A network pharmacological methodology was utilized to predict the active compounds and potential targets of STW, collect the RSA targets and other human proteins of STW, and analyze the STW related networks. The animal experiments were also performed to validate the effect of STW on RSA.
The results of network analysis showed that STW may regulate PI3K/AKT, MAPK, FoxO signaling pathways and so on. Animal experiment established the RSA model with CBA/J × DBA/2 mice. It was found that STW can reduce the embryo absorption rate of RSA group (p < 0.05) and balance the expression of Th 1/Th2 type cytokines compared with the model group. After 14 days of administration, the decidual and placental tissues were taken and the CD4 T cells were isolated, and the phosphorylation level of signaling pathway was detected by Springbio720 antibody microarray. This experiment found that STW can significantly up-regulate the phosphorylation levels of STAT3 and STAT6 proteins in the STAT signaling pathway, and down-regulating the phosphorylation level of STAT1 protein. STW also significantly up-regulated the phosphorylation levels of Raf1, A-Raf, Ask1, Mek1, Mek2, JKK1, ERK1, ERK2, c-fos, c-Jun and CREB proteins in the MAPK signaling pathway, and down-regulate the phosphorylation levels of MEK6 and IKKb proteins. Compared with the RSA group, the STW group increased the expression levels of ERK1/2 mRNA and proteins and p-ERK1/2 proteins, and there was a statistical difference (p < 0.05). This is consistent with the chip results.
STW may achieve therapeutic effects by interfering with the signaling pathways, biological processes and targets discovered in this study. It provides a new perspective for revealing the immunological mechanism of STW in the treatment of RSA, and also provides a theoretical basis for the clinical use of STW in the treatment of RSA.
寿胎丸(STW)是一种传统的中药方剂,历史上一直用于治疗复发性自然流产(RSA)。尽管它的使用历史悠久,但 STW 治疗效果的确切机制在现有文献中仍不清楚。
探索 STW 治疗 RSA 的药理学机制。
采用网络药理学方法预测 STW 的活性成分和潜在靶点,收集 RSA 靶点和 STW 的其他人类蛋白,并分析 STW 相关网络。还进行了动物实验以验证 STW 对 RSA 的作用。
网络分析结果表明,STW 可能调节 PI3K/AKT、MAPK、FoxO 信号通路等。采用 CBA/J×DBA/2 小鼠建立 RSA 模型的动物实验发现,STW 可降低 RSA 组胚胎吸收率(p<0.05),并平衡 Th1/Th2 型细胞因子的表达与模型组相比。给药 14 天后,取蜕膜和胎盘组织,分离 CD4 T 细胞,用 Springbio720 抗体微阵列检测信号通路的磷酸化水平。该实验发现,STW 可显著上调 STAT 信号通路中 STAT3 和 STAT6 蛋白的磷酸化水平,并下调 STAT1 蛋白的磷酸化水平。STW 还显著上调 MAPK 信号通路中 Raf1、A-Raf、Ask1、Mek1、Mek2、JKK1、ERK1、ERK2、c-fos、c-Jun 和 CREB 蛋白的磷酸化水平,并下调 MEK6 和 IKKb 蛋白的磷酸化水平。与 RSA 组相比,STW 组 ERK1/2mRNA 和蛋白及 p-ERK1/2 蛋白表达增加,差异有统计学意义(p<0.05)。这与芯片结果一致。
STW 可能通过干扰本研究发现的信号通路、生物过程和靶点来发挥治疗作用。它为揭示 STW 治疗 RSA 的免疫学机制提供了新的视角,也为 STW 治疗 RSA 的临床应用提供了理论依据。