The aim of this study was to explore the mechanism underlying the antidepression activity of paeoniflorin, the main active ingredient of paeony extract and Shuyu capsules, and determine its effect on the calmodulin/calmodulin-dependent protein kinase II (CaM/CaMKII) signalling pathway and on the possible target, the voltage-gated calcium channel (). Rats at the nonacceptance stage were selected for premenstrual syndrome (PMS) depression modelling. Behavioural assays were used for model testing. Rats were given Shuyu capsules, paeony extract, and bupleurum. Western blot analysis was used to assess the expression levels of calcium voltage-gated channel subunit alpha 1 C (CACNA1C), brain-derived neurotrophic factor, and CaM/CaMKII signalling pathway proteins. Intracellular Ca²⁺ concentration in CHO cell line was measured using Fluo-4-AM and whole-cell patch clamps. The PMS depression model was successfully established and demonstrated that Shuyu can mitigate depressive behaviour in a rat PMS model. Paeony extract did not affect CACNA1C protein expression in rat hippocampi but did affect 1.2-mediated CaM/CaMKII signalling pathways. Paeoniflorin significantly inhibited KCl-induced increases in intracellular Ca²⁺ concentration and 1.2 current density. Further, it may function via the CaM/CaMKII pathway and its downstream signalling molecules by regulating 1.2, thus playing an important role in the treatment and alleviation of affective disorders.

中文翻译：

---

yu药胶囊的主要活性成分药苷抑制Cav1.2并调节钙调蛋白/钙调蛋白依赖性蛋白激酶II信号传导。

这项研究的目的是探讨underlying药提取物和舒愈胶囊的主要活性成分pa药苷的抗抑郁作用的机制，并确定其对钙调蛋白/钙调蛋白依赖性蛋白激酶II（CaM / CaMKII）信号传导途径和在可能的目标上，电压门控钙通道（）。选择处于非接受阶段的大鼠进行经前期综合症（PMS）抑郁建模。行为测定用于模型测试。给予鼠俞胶囊，pa药提取物和柴胡。Western印迹分析用于评估钙电压门控通道亚基α1 C（CACNA1C），脑源性神经营养因子和CaM / CaMKII信号通路蛋白的表达水平。细胞内Ca ²⁺使用Fluo-4-AM和全细胞膜片钳测量CHO细胞系中的浓度。成功建立了PMS抑郁模型，并证明了Shuyu可以减轻大鼠PMS模型的抑郁行为。牡丹提取物不影响大鼠海马中CACNA1C蛋白的表达，但确实影响1.2介导的CaM / CaMKII信号通路。eon药苷显着抑制KCl诱导的细胞内Ca ²⁺浓度和1.2电流密度的增加。此外，它可能通过调节1.2通过CaM / CaMKII途径及其下游信号分子发挥功能，因此在情感障碍的治疗和缓解中起着重要的作用。