Jiawei Buzhong Yiqi decoction ameliorates polycystic ovary syndrome via oocyte-granulosa cell communication.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiawei Buzhong Yiqi Decoction (JWBZYQ), from records of FuqingzhuNvke, is a classical formula for treating obese women related infertility. JWBZYQ has been shown to be effective in treating polycystic ovary syndrome (PCOS) in both clinical studies and practical practice, with the pharmacological mechanism remaining unknown. AIM OF THE STUDY: To explore the potential therapeutic effects and mechanistic insights of JWBZYQ in PCOS. MATERIALS AND METHODS: An overweight PCOS rat model was established via testosterone propionate (TP) injection and 45% high-fat diet (HFD). Then they were categorized into five distinct groups: Control group, Model group, low-dose of JWBZYQ (JWBZYQ1) group, high-dose of JWBZYQ (JWBZYQ2) group, and metformin (Met) group. Body weight, estrous cycle, and sex hormone levels were observed. Hematoxylin-Eosin staining was employed to investigate the histological characteristics of the ovaries. To identify the pathways that changed significantly, transcriptome analysis was performed. The protein and mRNA levels of key molecules in ovarian zona pellucida (ZP) organization, transzonal projections (TZPs) assembly, steroid hormone receptors, and steroidogenesis were assessed using phalloidin staining, immunohistochemistry, Western blot, and polymerase chain reaction. RESULTS: RNA-seq analysis demonstrated that regulation of hormone secretion, cilium assembly, cell projection assembly, and ZP production may all have crucial impact on the etiology of PCOS and therapeutic effect of JWBZYQ. In particular, PCOS rats exhibited elevated expressions of ZP1-3, which can be reversed by JWBZYQ2 particularly. Simultaneously, TZPs assembly was totally disrupted in PCOS rats, evidenced by the phalloidin staining, upregulated calcium-/calmodulin-dependent protein kinase II beta (CaMKIIß), and deficient p-CaMKIIß, myosin X (MYO10), proline-rich tyrosine kinase 2 (PTK2), and Fascin. Nonetheless, JWBZYQ or metformin treatment revived the disturbance, repairing the oocyte-granulosa cell communication, regulating steroidogenesis in PCOS rats. In this way, JWBZYQ and metformin exerted remarkable effects in alleviating altered ovarian morphology and function in PCOS rats, with JWBZYQ2 revealing the best effect. CONCLUSIONS: JWBZYQ restored the altered ovarian morphology and function by regulating the oocyte-granulosa cell communication, which was related with ZP organization and TZPs assembly in the ovary.

Permixon®, hexane-extracted Serenoa repens, inhibits human prostate and bladder smooth muscle contraction and exerts growth-related functions in human prostate stromal cells.

AIMS: Recently, the European Association of Urology recommended hexane-extracted fruit of Serenoa repens (HESr) in their guidelines on management of non-neurogenic male lower urinary tracts symptoms (LUTS). Despite previously lacking recommendations, Permixon® is the most investigated HESr in clinical trials, where it proved effective for male LUTS. In contrast, underlying mechanisms were rarely addressed and are only marginally understood. We therefore investigated effects of Permixon® on human prostate and detrusor smooth muscle contraction and on growth-related functions in prostate stromal cells. MAIN METHODS: Permixon® capsules were dissolved using n-hexane. Contractions of human prostate and detrusor tissues were induced in organ bath. Proliferation (EdU assay), growth (colony formation), apoptosis and cell death (flow cytometry), viability (CCK-8) and actin organization (phalloidin staining) were studied in cultured human prostate stromal cells (WPMY-1). KEY FINDINGS: Permixon® inhibited α1-adrenergic and thromboxane-induced contractions in prostate tissues, and methacholine-and thromboxane-induced contractions in detrusor tissues. Endothelin-1-induced contractions were not inhibited. Neurogenic contractions were inhibited in both tissues in a concentration-dependent manner. In WPMY-1 cells, Permixon® caused concentration-dependent breakdown of actin polymerization, inhibited colony formation, reduced cell viability, and proliferation, without showing cytotoxic or pro-apoptotic effects. SIGNIFICANCE: Our results provide a novel basis that allows, for the first time, to fully explain the ubiquitous beneficial effects of HESr in clinical trials. HESr may inhibit at least neurogenic, α1-adrenergic and thromboxane-induced smooth muscle contraction in the prostate and detrusor, and in parallel, prostate stromal cell growth. Together, this may explain symptom improvements by Permixon® in previous clinical trials.

[Antimitotic compounds as modifiers of the radiation lesion of cultured cells]. / Antimitoticheskie soedineniia kak modifikatory luchevogo porazheniia kul'tiviruemykh kletok.

The features of antimitotic substances as radioprotectors were studied. In vitro experiments have demonstrated that taxol revealed radioprotective features concerning the process of polymerization of irradiated microtubules. These results were the basis for the use of taxol and some other substances with high affinity for cytoskeleton proteins as potential radiomodificators in vivo. Experiments with cultivated fibroblasts revealed that colchicine significantly enhances radioactive injuries of cells while taxol and phalloidin manifest their radioprotective features.