Exploring the efficacy and mechanism of Bailing capsule to improve polycystic ovary syndrome in mice based on intestinal-derived LPS-TLR4 pathway.
Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with reproductive dysfunction and metabolic abnormalities, particularly characterized by insulin resistance and chronic low-grade inflammation. Multiple clinical studies have clearly demonstrated the significant efficacy and safety of the combination of Bailing capsules (BL) in the treatment of PCOS, but its pharmacological effects and mechanisms still require further study.
To evaluate the effect of BL on improving PCOS in mice and explore the mechanism.
In this study, Dehydroepiandrosterone (DHEA) injection was administered alone and in combination with a high-fat and high-sugar diet to induce PCOS-like mouse. They were randomly divided into five groups: normal group (N), PCOS group (P), Bailing capsule low-dose group (BL-L), Bailing capsule high-dose group (BL-H) and Metformin + Daine-35 group (M + D). Firstly, the effects of BL on ovarian lesions, serum hormone levels, HOMA-IR, intestinal barrier function, inflammation levels, along with the expression of IRS1, PI3K, AKT, TLR4, Myd88, NF-κB p65, TNF-α, IL-6, and Occludin of the ovary, liver and colon were investigated. Finally, the composition of the gut microbiome of fecal was tested.
The administration of BL significantly reduced body weight, improved hormone levels, improved IR, and attenuated pathological damage to ovarian tissues, up-regulated the expression of IRS1, PI3K, and AKT in liver. It also decreased serum LPS, TNF-α, and IL-6 levels, while downregulating the expression of Myd88, TLR4, and NF-κB p65. Additionally, BL improved intestinal barrier damage and upregulated the expression of Occludin. Interestingly, the abundance of norank_f__Muribaculacea and Lactobacillus was down-regulated, while the abundance of Akkermansia was significantly up-regulated.
The results of the study showed that BL exerts a treatment PCOS effect, which may be related to the modulation of the gut microbiota, the improvement of insulin resistance and the intestinal-derived LPS-TLR4 inflammatory pathway. Our research will provide a theoretical basis for the clinical treatment of PCOS.
Guan HR
，Li B
，Zhang ZH
，Wu HS
，Wang N
，Chen XF
，Zhou CL
，Bian XR
，Li L
，Xu WF
，He XL
，Dong YJ
，Jiang NH
，Su J
，Lv GY
，Chen SH
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Liuwei Dihuang Pills alleviate the polycystic ovary syndrome with improved insulin sensitivity through PI3K/Akt signaling pathway.
Polycystic ovary syndrome (PCOS) is a complex gynecological endocrine disease commonly occurred in women of childbearing age. The main hallmark of PCOS includes elevated androgen production and insulin resistance (IR). Liuwei Dihuang Pills (LWDH Pills), a commonly prescribed traditional Chinese medicine (TCM) is widely used as a tonic prescription to treat diabetes, female menopause syndrome and other symptoms with'Kidney-Yin' deficiency. It has been reported the effects LWDH pills on PI3K/Akt signaling pathway in T2DM treatment. Recent studies have also indicated that the treatment of menopausal syndrome may be associated with the ovarian sexual hormone levels regulated by LWDH pills to alleviate female infertility. However, its potential benefits on PCOS have not been fully elucidated.
The primary aim of this study was to investigate the alterations of PI3K/Akt pathway in polycystic ovary syndrome-insulin resistance (PCOS-IR) progression induced by letrozole combined with high fat diet (HFD) and then to explore the detailed mechanism of LWDH Pills to alleviate PCOS.
The female Sprague-Dawley rats were continuously treated with letrozole (p.o administration at 1 mg kg-1·day-1) and HFD for 21 days to establish the PCOS-IR model. Concurrently, metformin (200 mg kg-1·day-1) or LWDH Pills was orally administrated (1.2 or 3.6 g kg-1·day-1) to intervene disease progression. The ovarian pathology was evaluated by HE (hematoxylin-eosin) staining. The serum sexual hormones, follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, testosterone, progesterone and fasting insulin (FINS) were determined by radioimmunoassay. The protein expressions of IRS-1, PI3Kp85α, Akt and FoxO1a were analyzed by western blotting, while the mRNA levels of follicle-stimulating hormone receptor (FSHR) and Cyp19a1 in ovarian tissue were measured by qPCR.
The upregulated phosphorylation of IRS-1 (S307), down-regulated phosphorylation of PI3Kp85α, Akt, and FoxO1a were significantly reversed by LWDH Pills (3.6 g kg-1·day-1) in PCOS-IR rats with up-regulated mRNA levels of FSHR and Cyp19a1 in ovary. Also, the index of insulin resistance was gradually adjusted to normal by LWDH Pills. The serum levels of FSH, estradiol, progesterone levels were significantly raised while LH, testosterone were reduced. The ovarian polycystic changes were alleviated while the atresia follicles were reduced.
LWDH Pills therapy obviously improved the ovarian polycystic pathogenesis and regained the development of follicles via upregulating Cyp19a1, alleviated insulin resistance through acting on PI3K/Akt signaling pathway. These findings have provided scientific evidence for LWDH Pills to treat PCOS.
Qiu Z
，Dong J
，Xue C
，Li X
，Liu K
，Liu B
，Cheng J
，Huang F
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Investigating the active components of Huatan Tongjing decoction for the treatment of polycystic ovary syndrome via network pharmacology.
Polycystic ovary syndrome (PCOS) is a common endocrine disease in women, potentially causing ovarian infertility for women at gestational age. Huatan Tongjing Decoction is commonly used to treat PCOS; however, the involved molecular mechanism has not been fully understood. In this study, the active components of Huatan Tongjing Decoction and potentially targeted proteins were downloaded from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. PCOS-related genes were accessed from Malacards database. STRING database was utilized to construct a protein-protein interaction (PPI) network based on the PCOS-related genes and the predicted targets. Subsequently, the PPI network was subjected to Random walk with restart (RWR). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on top 50 genes with the high affinity scores to the drug targets. Subsequently, based on the predicted drug components and targets, a component-gene interaction network was constructed. Finally, the most central drug targets were selected, and the corresponding compounds were subjected to molecular docking and dynamic simulations to examine their bindings. The 122 main active components and 246 potential targets of Huatan Tongjing Decoction were obtained from TCMSP, and a total of 259 nodes and 1919 interactions were acquired from the PPI network. The top 50 genes were mainly enriched in response to peptide hormone function and PI3K-Akt signaling pathway. Molecular docking and dynamic simulations predicted that MMP-quercetin interaction played an important role in the treatment of PCOS using Huatan Tongjing Decoction. Luteolin and quercetin in Huatan Tongjing Decoction potentially bound MMP9 and served as active components. This study preliminarily suggested the efficacy of Huatan Tongjing Decoction against PCOS in molecular degree.
Yu J
，Fu Y
，Zeng L
，Zheng Y
... -
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ResearchGate
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钛学术
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