[Mechanism of Kuntai Capsules in treatment of polycystic ovary syndrome rat models based on AGE-RAGE signal pathway].

This study aims to investigate the impact of Kuntai Capsules(KTC) on polycystic ovarian syndrome(PCOS) rat models and explore the underlying mechanism. Fifty female SD rats were randomly divided into five groups(10 rats in each group), including control group, model group, low-, medium-, and high-dose KTC group. Except for the control group, the other groups were injected with dehydroepiandrosterone(DHEA) combined with a high-fat diet(HFD) to induce the PCOS rat model for 28 days. 0.315, 0.63, and 1.26 g·kg~(-1)·d~(-1) KTC was dissolved in the same amount of normal saline and given to low-, medium-, and high-dose KTC groups by gavage. Both control group and model group were given the same amount of normal saline for 15 days. After administration, fasting blood glucose(FBG) was measured by a glucose meter. Fasting insulin(FINS), luteinizing hormone(LH), testosterone(T), and follicle-stimulating hormone(FSH) were detected by enzyme-linked immunosorbent assay(ELISA), and LH/FSH ratio and insulin resistance index(HOMA-IR) were calculated. The pathological morphology of ovarian tissue was observed by hematoxylin-eosin(HE) staining. The expression levels of collagen α type Ⅲ 1 chain(COL3A1), apoptotic factors Bax, and Bcl-2 were detected using Western blot and immunofluorescence. The mRNA expressions of COL3A1, Bax, and Bcl-2 in ovarian tissue were performed by real-time PCR(RT-PCR). The results show that compared with the control group, the body weight, serum levels of FBG, FINS, LH, T, LH/FSH, and HOMA-IR are higher in model group(P<0.05 or P<0.01), and the level of FSH is lower(P<0.05). In model group, a large number of white blood cells are found in the vaginal exfoliated cells, mainly in the interictal phase. There are more cystic prominences on the surface of the ovary. The thickness of the granular cell layer is reduced, and oocytes are absent. COL3A1 and Bax protein expression levels are increased(P<0.01), while Bcl-2 protein expression levels are decreased(P<0.05) in the ovarian tissue COL3A1 and Bax mRNA expression levels are increased in ovarian tissue(P<0.05). Compared with the model group, the body weight, FBG, FINS, LH, T, LH/FSH, and HOMA-IR in low-, medium-, and high-dose KTC groups are decreased(P<0.05 or P<0.01), while the levels of FSH in medium-, and high-dose KTC groups are increased(P<0.05 or P<0.01). Low-, medium-, and high-dose KTC groups gradually show a stable interictal phase. The surface of the ovary is smooth. Oocytes and mature follicles can be seen in ovarian tissue, and the thickness of the granular cell layer is increased. The expression level of COL3A1 protein decreases in low-and medium-dose KTC groups(P<0.05 or P<0.01), and that of Bax protein decreases in low-dose KTC group(P<0.05 or P<0.01), and the expression level of Bcl-2 protein increases in low-dose KTC group(P<0.01). The expression levels of COL3A1 and Bax mRNA decreased in the low-dose KTC group(P<0.05), while the expression levels of Bcl-2 mRNA increased(P<0.05). In summary, KTC can inhibit ovarian granulosa cell apoptosis and reduce follicular atresia by regulating the AGE-RAGE signaling pathway. It can promote insulin secretion, reduce blood sugar and body weight, restore serum hormone levels, improve symptoms of PCOS, alleviate morphological damage of the ovary, and restore ovarian function, which is of great value in the treatment of PCOS.

The mechanism of Bai He Gu Jin Tang against non-small cell lung cancer revealed by network pharmacology and molecular docking.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related burden and deaths, thus effective treatment strategies with lower side effects for NSCLC are urgently needed. To systematically analyze the mechanism of Bai He Gu Jin Tang (BHGJT) against NSCLC by network pharmacology and molecular docking. METHODS: The active compounds of BHGJT were obtained by searching the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine and Encyclopaedia of Traditional Chinese Medicine. Search tool for interactions of chemicals was used for acquiring the targets of BHGJT. The component-target network was mapped by Cytoscape. NSCLC-related genes were obtained by searching Genecards, DrugBank and Therapeutic Target Database. The protein-protein interaction network of intersection targets was established based on Search Tool for Recurring Instances of Neighboring Genes (STRING), and further, the therapeutic core targets were selected by topological parameters. The hub targets were transmitted to Database for Annotation, Visualization and Integrated Discovery for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Finally, AutoDock Vina and MglTools were employed for molecular docking validation. RESULTS: Two hundred fifty-six compounds and 237 putative targets of BHGJT-related active compounds as well as 1721potential targets of NSCLC were retrieved. Network analysis showed that 8 active compounds of BHGJT including kaempferol, quercetin, luteolin, isorhamnetin, beta-sitosterol, stigmasterol, mairin and liquiritigenin as well as 15 hub targets such as AKR1B10 and AKR1C2 contribute to the treatment of BHGJT against NSCLC. GO functional enrichment analysis shows that BHGJT could regulate many biological processes, such as apoptotic process. Three modules of the endocrine related pathways including the inflammation, hypoxia related pathways as well as the other cancer related pathways based on Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis might explain the biological mechanisms of BHGJT in treating BHGJT. The results of molecular docking verified that AKR1B10 and AKR1C2 had the strongest binding activity with the 8 key compounds of NSCLC. CONCLUSION: Our study reveals the mechanism of BHGJT in treating NSCLC involving multiple components, multiple targets and multiple pathways. The present study laid an initial foundation for the subsequent research and clinical application of BHGJT and its active compounds against NSCLC.