Paeoniflorin, the Main Active Ingredient of Shuyu Capsule, Inhibits Ca_v1.2 and Regulates Calmodulin/Calmodulin-Dependent Protein Kinase II Signalling

Abstract

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 (Cav). 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 Cav1.2-mediated CaM/CaMKII signalling pathways. Paeoniflorin significantly inhibited KCl-induced increases in intracellular Ca2+ concentration and Cav1.2 current density. Further, it may function via the CaM/CaMKII pathway and its downstream signalling molecules by regulating Cav1.2, thus playing an important role in the treatment and alleviation of affective disorders.

Gene Expression in the Hippocampus in a Rat Model of Premenstrual Dysphoric Disorder After Treatment With Baixiangdan Capsules

“…Cacna1a also serves as a key gene in the GABA synapse pathway and dopamine synapse pathway, so it can be deduced that BXD can influence various signal pathways in the central nervous system by acting on genes for calcium ion pathway protein, thus realizing the treatment of PMDD irritability. The signaling pathways through Ca 2+ channels was described in our previous report, in which we found that paeoniflorin, one of the active compounds of BXD, could inhibit one of the subtypes of the Ca 2+ channels ( Song et al, 2017 ).…”

To Explore the Network Pharmacology and Molecular Docking Mechanism of Chaihu Shugan Powder with the “Same Treatment for Different Diseases” for Insomnia and Depression Based on the COVID-19 Pandemic

“…Paeoni orin has neuroprotective and antidepressant biological activities, and it can treat related insomnia diseases through adenosine A1R to play a hypnotic effect [36]. Regulating the calmodulin/calmodulin-dependent protein kinase II (CaM/CaMKII) pathway and its downstream signaling molecules play an important role in the treatment and alleviation of affective disorders [37]. Glycyrrhizin can reduce IL-6 cytokines in brain tissue, and it is also a cytokine closely related to sleep/deprivation.…”

Allopregnanolone-mediated GABAA-Rα4 function in amygdala and hippocampus of PMDD liver qi-invasion syndrome model rats

“…The voltage stimulation scheme of the whole cell patch clamp recording GABA current was as follows [40]: after formation of the whole cell seal, the cell membrane voltage was clamped at −70 mV and the cell surface injected with 30 µM GABA, 10 µM Str, and 300 nm TTX. The peak value of the current was recorded in the gap-free mode.…”