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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS · 2022 · IF 3.571

Simultaneous determination of sex hormones and bile acids in rat plasma using a liquid chromatography-tandem mass spectrometry method

Yun Li,Dan Zhang,Yan Mo,Teng Zeng,Tongzhi Wu,Lingqiao Liu,Hua Zhang,Chang Chen

Endogenous steroids, including sex hormones and bile acids , are a group of essential compounds with various biological functions. In this study, we developed an LC-MS method that simultaneously measures 14 sex hormones and metabolites (SH) and 32 bile acids (BA) in rat plasma. Multiple innovative approaches were applied to increase the sensitivity and specificity, including optimization of the mobile phases , gradients, and dynamic multiple reaction monitoring (DMRM) transitions. The method was validated and applied on plasma samples from pregnant rats before and 0.5 h after oral glucose tolerance test (OGTT) at gestational days 0.5 and 18.5. Results showed that the method was applicable, and 9 SH and 30 BA were measurable in the samples. In summary, this method is applicable in studies on SH and BA in rat plasma, and may also be used on other matrix and species.

研究领域: 分析化学 · 药理学 · 内分泌学
✓ 已验证 DOI PubMed 高影响因子
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Frontiers in Endocrinology · 2022 · IF 6.055

Modified Cangfu Daotan decoction ameliorates polycystic ovary syndrome with insulin resistance via NF-κB/LCN-2 signaling pathway in inflammatory microenvironment

Liu Shuowen,Zhang Yao,Yang Fang,Gu Jingna,Zhang Ruyue,Kuang Yingying,Mai Wantong,Zheng Chengbo,Yu Yang,Lu Ruling,Zeng Lei,Cao Hongying,Long Yongling

This study explored the possible connection between the insulin resistance-targeting protein adipokine lipocalin-2 (LCN-2) and NF-κB signaling pathway in the inflammatory microenvironment in PCOS-IR model rats to determine the pharmacological mechanism of modified Cangfu Daotan decoction (MCDD) intervention for PCOS-IR. We used a high-fat diet (42 days) combined with letrozole (1 mg/kg/day, 42 days) to establish a PCOS-IR rat model. From the third week after modeling, the rats were given continuous administration of MCDD (high dose with 31.68 g/kg, medium dose with 15.84 g/kg, and low dose with 7.92 g/kg) for 28 days. Serum, ovarian tissue, liver, and adipose tissue were collected after the last gavage. Enzyme-linked immunosorbent assay, hematoxylin-eosin (HE) staining, Masson staining, qRT-PCR, and Western blot experiments were performed to detect various indicators. Our results showed that MCDD could reduce body weight and abdominal fat weight; restore normal estrous cycle and ovarian function; alleviate fatty liver; regulate HOMA-IR and OGTT index; reduce serum inflammatory factor levels, LCN-2 level, and gene expression; and regulate the insulin signal transduction and NF-κB pathways in PCOS-IR rats. Thus, MCDD may play a role in improving ovarian function in PCOS-IR rats by downregulating NF-κB/LCN-2 proteins and upregulating the gene expression of Insr/Irs-1/Glut4 in the insulin signaling pathway in the inflammatory environment.

CAS / MDL: 9004-32-4
研究领域: 药理学 · 内分泌学 · 妇科学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BRITISH JOURNAL OF PHARMACOLOGY · 2024 · IF 6.8

Combination therapy enhances efficacy and overcomes toxicity of metal-based anti-diabetic agent

Bing Shang,Yaqiong Dong,Bo Feng,Jingyan Zhao,Zhi Wang,Debbie C. Crans,Xiaoda Yang

Background and Purpose Metal-based therapeutic agents are limited by the required concentration of metal-based agents. Hereby, we determined if combination with 17β-oestradiol (E2) could reduce such levels and the therapy still be effective in type 2 diabetes mellitus (T2DM). Experimental Approach The metal-based agent (vanadyl acetylacetonate [VAC])– 17β-oestradiol (E2) combination is administered using the membrane-permeable graphene quantum dots (GQD), the vehicle, to form the active GQD–E2–VAC complexes, which was characterized by fluorescence spectra, infrared spectra and X-ray photoelectron spectroscopy. In db / db type 2 diabetic mice, the anti-diabetic effects of GQD–E2–VAC complexes were evaluated using blood glucose levels, oral glucose tolerance test (OGTT), serum insulin levels, homeostasis model assessment (homeostasis model assessment of insulin resistance [HOMA-IR] and homeostasis model assessment of β-cell function [HOMA-β]), histochemical assays and western blot. Key Results In diabetic mice, GQD–E2–VAC complex had comprehensive anti-diabetic effects, including control of hyperglycaemia, improved insulin sensitivity, correction of hyperinsulinaemia and prevention of β-cell loss. Co-regulation of thioredoxin interacting protein (TXNIP) activation by the combination of metal complex and 17β-oestradiol contributed to the enhanced anti-diabetic effects. Furthermore, a potent mitochondrial protective antioxidant, coniferaldehyde, significantly potentiates the protective effects of GQD–E2–VAC complexes. Conclusion and Implications A metal complex–E2 combinatorial approach achieved simultaneously the protection of β cells and insulin enhancement at an unprecedented low dose, similar to the daily intake of dietary metals in vitamin supplements. This study demonstrates the positive effects of combination and multi-modal therapies towards type 2 diabetes treatment. Graphical

研究领域: 药理学 · 糖尿病 · 治疗学 · 纳米技术 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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