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乙醇提取物对实验性链脲佐菌素诱导的糖尿病大鼠及来曲唑诱导的多囊卵巢综合征的多靶点作用

Multitargeted Effects of Ethanol Extract in Experimental Rat Streptozotocin-Induced Diabetes Mellitus and Letrozole-Induced Polycystic Ovary Syndrome.

作者信息

Usatiuc Lia-Oxana, Pop Raluca Maria, Adrian Surd, Pârvu Marcel, Țicolea Mădălina, Uifălean Ana, Vălean Dan, Gavrilaș Laura-Ioana, Csilla-Enikő Szabo, Leopold Loredana Florina, Ranga Floricuța, Cătoi Florinela Adriana, Pârvu Alina Elena

机构信息

Pathophysiology, Department 2-Functional Sciences, Faculty of Medicine,"Iuliu Hațieganu" University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania.

Pharmacology, Toxicology and Clinical Pharmacology, Department 2-Functional Sciences, Faculty of Medicine, "Iuliu Hațieganu" University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania.

出版信息

Int J Mol Sci. 2025 May 14;26(10):4712. doi: 10.3390/ijms26104712.

Abstract

Polycystic ovary syndrome (PCOS), a common and multifactorial endocrine disorder in reproductive-aged women, is strongly associated with insulin resistance (IR) and type 2 diabetes mellitus (T2DM), and also affects up to one in four women with type 1 diabetes mellitus (T1DM). The current study explored the potential of () seed ethanol extract (POEE) to modulate oxidative stress (OS), inflammatory responses, metabolic profiles, and hormonal levels in rat Streptozotocin (STZ)-induced DM and Letrozole (LET)-induced PCOS. Phytochemical analysis measured total phenolic content (TPC) and total flavonoid content (TFC) using HPLC-DAD-ESI MS for compound identification. POEE's antioxidant activity was evaluated in vitro through DPPH, HO, FRAP, and NO scavenging assays. Rats received POEE, metformin, or Trolox (TX) for 10 days. PCOS confirmation was achieved via ultrasound and histopathology. Serum levels of OS markers (TOS, TAC, OSI, MDA, AOPP, 8-OHdG, NO, 3-NT, AGEs, and SH), inflammatory markers (NF-κB, IL-1β, IL-18, Gasdermin D, and IL-10), metabolic parameters (fasting blood glucose, lipid profile, and liver enzymes), and hormone levels (LH, FSH, estrogen, testosterone, and insulin) were assessed. Additionally, the Triglyceride-Glucose index (TyG) and HOMA-IR were calculated. POEE had a medium content of polyphenols and a good in vitro antioxidant effect. In vivo, POEE administration in diabetic rats led to a reduction in OS markers and an increase in antioxidant levels, alongside decreases in inflammatory cytokines, blood glucose levels, and transaminase activity and improvements in lipid profile. In the PCOS model, POEE treatment effectively reduced total OS and lowered levels of LH, FSH, and testosterone, while elevating estrogen concentrations and reducing insulin resistance. These therapeutic effects were dose-dependent, with higher doses producing more pronounced outcomes, comparable to those observed with metformin and TX treatment.

摘要

多囊卵巢综合征(PCOS)是育龄女性常见的多因素内分泌疾病,与胰岛素抵抗(IR)和2型糖尿病(T2DM)密切相关,并且在1型糖尿病(T1DM)女性中,每四人中就有一人受其影响。本研究探讨了()种子乙醇提取物(POEE)对链脲佐菌素(STZ)诱导的糖尿病大鼠和来曲唑(LET)诱导的PCOS大鼠氧化应激(OS)、炎症反应、代谢谱和激素水平的调节作用。采用HPLC-DAD-ESI MS进行化合物鉴定的植物化学分析测定了总酚含量(TPC)和总黄酮含量(TFC)。通过DPPH、HO、FRAP和NO清除试验在体外评估了POEE的抗氧化活性。大鼠接受POEE、二甲双胍或生育三烯酚(TX)治疗10天。通过超声和组织病理学确诊PCOS。评估了血清中OS标志物(TOS、TAC、OSI、MDA、AOPP、8-OHdG、NO、3-NT、AGEs和SH)、炎症标志物(NF-κB、IL-1β、IL-18、Gasdermin D和IL-10)、代谢参数(空腹血糖、血脂谱和肝酶)和激素水平(LH、FSH、雌激素、睾酮和胰岛素)。此外,还计算了甘油三酯-葡萄糖指数(TyG)和稳态模型评估的胰岛素抵抗(HOMA-IR)。POEE含有中等含量的多酚,体外抗氧化效果良好。在体内,给糖尿病大鼠施用POEE可导致OS标志物减少、抗氧化水平增加,同时炎症细胞因子、血糖水平和转氨酶活性降低,血脂谱得到改善。在PCOS模型中,POEE治疗有效降低了总OS水平,并降低了LH、FSH和睾酮水平,同时提高了雌激素浓度并降低了胰岛素抵抗。这些治疗效果呈剂量依赖性,较高剂量产生更明显的结果,与二甲双胍和TX治疗观察到的结果相当。

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