Ge-gen decoction alleviates primary dysmenorrhoea symptoms in a rat model.

BACKGROUND: Existing treatments for primary dysmenorrhoea (PD), such as NSAIDs, impart side effects. Ge-Gen decoction (GGD), a traditional Chinese medicine, has shown promise in treating PD, but its exact mechanisms remain unclear. Here, we aimed to investigate the efficiency of GGD in alleviating PD using a rat model to understand its precise mechanism of action. METHODS: We established a rat model of dysmenorrhoea induced by oestradiol and oxytocin. The PD rats were administered GGD or Ibuprofen (positive control) intragastrically once daily for seven consecutive days. Serum levels of prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2α), ß-endorphin (ß-EP), thromboxane B2 (TXB2), 6-keto-prostaglandin F1α (6-keto-PGF1α) were determined using an enzyme-linked immunosorbent assay (ELISA). The expression levels of oestrogen receptor alpha (ERα) and cyclooxygenase-2 (COX-2) in uterine tissue were measured using immunohistochemical assays, and those of phosphorylated and total extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) were assessed using western blot analysis. RESULTS: Treatment with GGD significantly reduced writhing behaviour, histopathological scores, and levels of COX-2, PGE2, and PGF2α in the serum of PD rats. Additionally, GGD increased ß-EP content and inhibited ERK1/2 activation and ERα expression in uterine tissues. CONCLUSIONS: The results of this study suggest that GGD alleviates PD in rats by suppressing the COX-2-mediated release of PGE2 and PGF2α, modulating the ERα/ERK1/2/COX-2 pathway, and increasing ß-EP content. These results provide insights into the potential mechanisms of GGD in treating PD and support its further investigation as an alternative therapy for this condition.

Ge-Gen decoction is commonly used to alleviate primary dysmenorrhoea. However, its anti-dysmenorrhoea mechanism remains elusive. In this study, using a rat model of primary dysmenorrhoea, we demonstrate that Ge-Gen decoction reduced the levels of cyclooxygenase-2, prostaglandin E2, and prostaglandin F2 alpha in serum and phosphorylated extracellular signal-regulated protein kinases 1 and 2 in the uterus. These results suggest that Ge-Gen decoction alleviates primary dysmenorrhoea via inactivation of the oestrogen receptor alpha/extracellular signal-regulated protein kinases 1 and 2/cyclooxygenase-2 pathway. This study enhances our understanding of the pathogenesis of primary dysmenorrhoea and may potentially inform the development of novel treatment approaches.

The Therapeutic Effect of Ge-Gen Decoction on a Rat Model of Primary Dysmenorrhea: Label-Free Quantitative Proteomics and Bioinformatic Analyses.

Ge-Gen decoction (GGD) is widely used for the treatment of primary dysmenorrhea (PD) in China. However, the mechanisms that underlie this effect are unclear. We investigated the protective mechanism of GGD in a rat model of PD using label-free quantitative proteomics. The model was established by the administration of estradiol benzoate and oxytocin. Thirty rats were divided into three groups (ten rats/group): a control group (normal rats), a model group (PD rats), and a treatment group (PD rats treated with GGD). The serum levels of prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) were measured by ELISA. Nanohigh-performance liquid chromatography-tandem mass spectrometry (nano-HPLC-MS/MS) was used to identify differentially expressed proteins (DEPs), and bioinformatics was used to investigate the protein function. Proteomic data were validated by western blot analysis. Oxytocin-induced writhing responses and abnormal serum levels of PGE2 and PGF2α were reversed following the administration of GGD. A total of 379 DEPs were identified; 276 were identified between the control group and the model group, 144 were identified between the model group and the treatment group, and 41 were identified as DEPs that were common to all groups. Bioinformatics revealed that the DEPs between the control group and the model group were mainly associated with cellular component biogenesis and binding processes. The DEPs between the model group and the treatment group were mainly involved in the protein binding and metabolic process. The expression levels of HSP90AB1 and the phosphorylation levels of ERK, JNK, and P-p38 in the uteri of rats in the three groups were consistent with the proteomic findings; MAP kinases (ERK, JNK, and p38) are known to be involved in the production of inflammatory cytokines and oxytocin signaling while HSP90AB1 is known to be associated with estrogen signaling. Collectively, these data indicate that GGD may exert its protective function on PD by regulating the inflammatory response and signaling pathways associated with oxytocin and estrogen.

Proteomic Analysis of Differentially Expressed Proteins in the Placenta of Anticardiolipin Antibody- (ACA-) Positive Pregnant Mice after Anzi Heji Treatment.

Anzi Heji (AZHJ) has been used to treat anticardiolipin antibody- (ACA-) positive pregnant women at risk of spontaneous abortion for many years. The aim of this study was to investigate the protective mechanism of AZHJ in a mouse model of ACA-positive pregnancy at risk of spontaneous abortion using label-free quantitative proteomics. Mice were divided into three groups: normal pregnant mice (control group), ACA-positive pregnant mice administered normal saline (model group), and ACA-positive pregnant mice administered AZHJ (AZHJ group). The model was established by injecting ß2-glycoprotein I (GPI) into mice for 18 days. The DEPs and their functions were analyzed by label-free quantitative proteomic and bioinformatic analyses. The levels of IL-6, IL-10, ACA, and TNF-α in the serum and placentas of the mice were measured by enzyme-linked immunosorbent assays (ELISAs). Proteomic data were validated by western blot analysis. The abnormal serum and placental levels of IL-6, ACA, and TNF-α in the model group were reversed by AZHJ. There were 39 upregulated and 10 downregulated DEPs in the AZHJ group relative to the model group. Bioinformatic analysis revealed that the DEPs were mainly involved in nucleic acid binding, signal conduction, and posttranslational modification. The placental levels of T-cell immunoglobulin mucin 3 (Tim-3) and Toll-like receptor 4 (TLR4) expression and AKT phosphorylation in the three groups were consistent with the proteomic findings. Tim-3/AKT signaling is involved in maternal-fetal immune tolerance, while TLR4 is associated with inflammatory responses. Collectively, these results indicate that AZHJ may exert its protective effect in ACA-positive pregnant mice by regulating the maternal-fetal immune tolerance and inflammatory response.