Anti-Inflammatory Effects of Curcumin on Insulin Resistance Index, Levels of Interleukin-6, C-Reactive Protein, and Liver Histology in Polycystic Ovary Syndrome-Induced Rats
Mohammadi S,Karimzadeh Bardei L,Hojati V,Ghorbani AG,Nabiuni M
Published August 25, 2017Cell Journal, 19(3), 425-433
Mohammadi, S., Karimzadeh Bardei, L., Hojati, V., Ghorbani, A. G., & Nabiuni, M. (2017). Anti-Inflammatory Effects of Curcumin on Insulin Resistance Index, Levels of Interleukin-6, C-Reactive Protein, and Liver Histology in Polycystic Ovary Syndrome-Induced Rats. Cell journal, 19(3), 425-433. https://doi.org/10.22074/cellj.2017.4415
Mohammadi S, Karimzadeh Bardei L, Hojati V, Ghorbani AG, Nabiuni M. Anti-Inflammatory Effects of Curcumin on Insulin Resistance Index, Levels of Interleukin-6, C-Reactive Protein, and Liver Histology in Polycystic Ovary Syndrome-Induced Rats. Cell J. 2017;19(3):425-433. doi:10.22074/cellj.2017.4415
Mohammadi, Shima, et al. "Anti-Inflammatory Effects of Curcumin on Insulin Resistance Index, Levels of Interleukin-6, C-Reactive Protein, and Liver Histology in Polycystic Ovary Syndrome-Induced Rats." Cell journal, vol. 19, no. 3, 2017, pp. 425-433.
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Free full text on PubMed Central (PMC5570407)
Author affiliations
4 institutions
Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran.
Laboratorys Animal Center and Cellular and Molecular Research Laboratory, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.
Department of Animal Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.
Department of Cell and Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.Electronic address: devbiokharazmi@gmail.com.
Abstract
Objectives
Curcumin protects the liver against injury and fibrosis through suppressing hepatic inflammation, attenuating hepatic oxidative stress (OS), and inhibiting hepatic stellate cells (HSCs) activation. Non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) are considered as common metabolic disorders. Low-grade chronic inflammation with different markers, such as elevated C-reactive protein (CRP) and interleukin-6 (IL-6) levels, play a crucial role in PCOS. This study aimed to evaluate the therapeutic effects of curcumin on IL-6 and CRP levels as well as insulin resistance (IR) index on liver function in PCOS rats.
Materials and Methods
In this experimental study, 90 adult Wistar rats were divided into control (n=18), sham (n=18), PCOS (n=18) and curcumin-treated PCOS groups (n=36). PCOS group was injected subcutaneously with 2 mg estradio-valerate (E2V). After 60 days, PCOS group was treated with curcumin [100 and 300 mg/kg body weight (BW)] for 14 days and anesthetized by chloroform. Blood and liver samples were collected for histological and serological analyses. Data were analyzed using In-Stat 3 via one-way analysis of variance (ANOVA).
Results
Histological and serological analyses showed a reduction in number of necrotic cells, IR index, as well as IL-6 and CRP levels in PCOS rats that were treated with various concentrations of curcumin.
Conclusions
In this study, curcumin decreased liver inflammation by induction of insulin sensitivity and reduction of hepatic necrosis. Therefore, curcumin may be considered as protective factor against inflammatory state of PCOS.
Duleba AJ, 2012·Steroids·Free full text on PubMed Central
Polycystic ovary syndrome (PCOS) is associated with metabolic derangements including insulin resistance, dyslipidemia, systemic inflammation and endothelial dysfunction. There is a growing need to develop pharmacologic interventions to improve metabolic function in women with PCOS. Medications that have been tested in patients with PCOS include metformin, thiazolidinediones, acarbose, naltrexone, orlistat, vitamin D and statins. Metformin decreases hepatic gluconeogenesis and free fatty acid oxidation while increasing peripheral glucose uptake. Early studies in PCOS suggested that metformin indirectly reduces insulin level, dyslipidemia and systemic inflammation; however, recent placebo-controlled trials failed to demonstrate significant metabolic benefit. Thiazolidinediones act primarily by increasing peripheral glucose uptake. Most studies in PCOS have demonstrated that thiazolidinediones reduce insulin resistance; however, effects on dyslipidemia were disappointing. Use of thiazolidinediones is associated with weight gain and major complications. Acarbose reduces digestion of polysaccharides. Studies in PCOS yielded inconsistent effects of acarbose on insulin sensitivity and no significant improvement of dyslipidemia. Naltrexone reduces appetite and modulates insulin release; its use in PCOS may reduce hyperinsulinemia. Orlistat decreases absorption of dietary fats; studies in PCOS suggest beneficial effects on insulin sensitivity. Vitamin D may improve insulin sensitivity but mixed results on lipid profile in PCOS have been reported. Statins are competitive inhibitors of the key enzyme regulating the mevalonate pathway; their effects are related to reduced cholesterol production as well as anti-inflammatory and anti-oxidant properties. In women with PCOS, statins reduce hyperandrogenism, improve lipid profile and reduce systemic inflammation while the effects on insulin sensitivity are variable. Use of statins is contraindicated in pregnancy.
Supplements and Botanicals · Vitamins and Minerals
Foroozanfard F et al., 2015·Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association
This study was conducted to evaluate the effects of zinc supplementation on glucose homeostasis parameters and lipid concentrations in PCOS women. We are aware of no study evaluating the effects of zinc supplementation on metabolic profiles of patients with polycystic ovary syndrome (PCOS). This randomized, double-blind, placebo-controlled trial was conducted among 52 women diagnosed with PCOS and aged 18-40 years old. Participants were randomly divided into 2 groups to receive 220 mg zinc sulfate (containing 50 mg zinc) supplements (n=26) or placebo (n=26) per day for 8 weeks. Fasting blood samples were taken at baseline and after 8 weeks' intervention to quantify glucose, insulin and lipid concentrations. After 8 weeks of intervention, subjects who received zinc supplements had significantly increased serum zinc levels (+15.6±21.8 vs. -4.1±16.7 mg/dL, P=0.001) compared with placebo. In addition, zinc-supplemented patients had reduced fasting plasma glucose (FPG) (-4.3±9.6 vs. +0.5±6.0 mg/dL, P=0.03), serum insulin levels (-3.0±2.9 vs. +1.5±8.4 µIU/mL, P=0.01), homeostasis model of assessment-insulin resistance (HOMA-IR) (-0.8±0.8 vs. +0.3±1.9, P=0.006), homeostatic model assessment-Beta cell function (HOMA-B) (-10.6±9.5 vs. +4.9±32.1, P=0.02) and increased quantitative insulin sensitivity check index (QUICKI) (+0.02±0.02 vs. -0.004±0.05, P=0.03) compared with placebo. Additionally, a significant reduction in serum triglycerides (-15.6±40.3 vs. +14.5±25.3 mg/dL, P=0.002) and VLDL-cholesterol concentrations (-3.2±8.1 vs. +2.9±5.1 mg/dL, P=0.002) was observed following the administration of zinc supplements compared with placebo. Taken together, 220 mg zinc sulfate supplementation per day for 8 weeks among PCOS women had beneficial effects on metabolic profiles.
Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder characterized by ovulatory dysfunction, hyperandrogenism, and insulin resistance. It results from complex genetic and environmental factors and progressively impairs reproductive and metabolic health. Natural phytotherapy provides holistic regulation through multiple components and targets and is recognized for its favorable safety profile, including low organ toxicity. Consequently, it represents a promising avenue for comprehensive PCOS management. This review aims to comprehensively analyze the ethnopharmacological applications of natural herbs in modulating ferroptosis within the context of PCOS. This study systematically reviewed natural herbal interventions for PCOS, with a focus on their mechanisms in regulating ferroptosis. It consulted traditional medical classics, ethnomedicinal records, and clinical literature, and searched databases including PubMed and the China National Knowledge Infrastructure (CNKI). Keywords such as "PCOS," "ferroptosis," "natural herbal medicines," "traditional Chinese medicine (TCM) compound preparations," "single-herb extracts," and "plant active ingredients" were used to retrieve research from ethnobotany, phytochemistry, and pharmacology. Recent relevant publications were comprehensively collected and analyzed. Integrating natural herbal medicines into the comprehensive management of PCOS offers several advantages, which can be primarily explained from two perspectives. First, the pathological mechanisms of PCOS involve multiple interconnected biological processes, including hormonal imbalance, insulin resistance, oxidative stress, and chronic inflammation. The onset and progression of PCOS are closely linked to cell death pathways such as ferroptosis and are regulated by various molecular pathways, including GPX4/COX2, SLC7A11/GPX4, circ_0097636/miR-186-5p/SIRT3, and AMPK/Nrf2 signaling. Drugs targeting a single molecule often struggle to effectively regulate such a complex network. In contrast, various herbal medicines and their active components-such as platycodin D, nuciferine (NF), baicalein, and berberine (BBR)-exhibit multi-target properties, enabling them to simultaneously modulate key molecules involved in ferroptosis in PCOS, including GPX4, SLC7A11, COX2, FTH1, ACSL4, and ferritin. This allows for synergistic intervention in multiple pathological processes of the disease. Additionally, natural herbal medicines and their active components have demonstrated a high level of safety with long-term use, particularly exhibiting relatively lower risks of liver and kidney toxicity. They offer certain advantages compared to traditional hormones or insulin sensitizers. For example, classic compound prescriptions such as Wenshen Tiaojing decoction (WSTJD), Shoutai pill, and Erchen decoction are commonly used in TCM clinical practice to regulate menstruation, improve insulin resistance, and promote ovulation, supported by extensive practical evidence. In recent years, to clarify their scientific basis, an increasing number of studies have extracted key active components from these effective compound formulations using modern separation techniques. With the aid of cell and animal experiments, researchers have thoroughly elucidated the mechanisms by which these components improve PCOS through pathways such as the regulation of ferroptosis, thereby bridging traditional knowledge and modern pharmacology Traditional Chinese compound formulations hold significant promise for developing drugs targeting PCOS. Notably, certain prescriptions and herbal extracts that focus on regulating ferroptosis as a key mechanism are attracting increasing attention and research within the academic community.
Jamilian M et al., 2016·Biological trace element research
The current study was conducted to evaluate the effects of zinc supplementation on endocrine outcomes, biomarkers of inflammation, and oxidative stress in patients with polycystic ovary syndrome (PCOS). This study was a randomized double-blind, placebo-controlled trial. Forty-eight women (18-40 years) with PCOS diagnosed according to Rotterdam criteria were randomly assigned to receive either 220 mg zinc sulfate (containing 50 mg zinc) (group 1; n = 24) and/or placebo (group 2; n = 24) for 8 weeks. Hormonal profiles, biomarkers of inflammation, and oxidative stress were measured at study baseline and after 8-week intervention. After 8 weeks of intervention, alopecia (41.7 vs. 12.5%, P = 0.02) decreased compared with the placebo. Additionally, patients who received zinc supplements had significantly decreased hirsutism (modified Ferriman-Gallwey scores) (-1.71 ± 0.99 vs. -0.29 ± 0.95, P < 0.001) and plasma malondialdehyde (MDA) levels (-0.09 ± 1.31 vs. +2.34 ± 5.53 μmol/L, P = 0.04) compared with the placebo. A trend toward a significant effect of zinc intake on reducing high-sensitivity C-reactive protein (hs-CRP) levels (P = 0.06) was also observed. We did observe no significant changes of zinc supplementation on hormonal profiles, inflammatory cytokines, and other biomarkers of oxidative stress. In conclusion, using 50 mg/day elemental zinc for 8 weeks among PCOS women had beneficial effects on alopecia, hirsutism, and plasma MDA levels; however, it did not affect hormonal profiles, inflammatory cytokines, and other biomarkers of oxidative stress.
Therapeutics › Supplements and Botanicals › Herbal and Botanical Products
Azita Ghorbani Ghorbani, Vida Hojati, Latifeh Karimzadeh Bardei, Shima Mohammadi, Mohammad Nabiuni
A Ghorbani, V Hojati, L Bardei, S Mohammadi, M Nabiuni
PMID 28836404 28836404 DOI 10.22074/cellj.2017.4415 10.22074/cellj.2017.4415 Mohammadi et al. 2017, Mohammadi 2017
Cite this article
Mohammadi, S., Karimzadeh Bardei, L., Hojati, V., Ghorbani, A. G., & Nabiuni, M. (2017). Anti-Inflammatory Effects of Curcumin on Insulin Resistance Index, Levels of Interleukin-6, C-Reactive Protein, and Liver Histology in Polycystic Ovary Syndrome-Induced Rats. Cell journal, 19(3), 425-433. https://doi.org/10.22074/cellj.2017.4415
Mohammadi S, Karimzadeh Bardei L, Hojati V, Ghorbani AG, Nabiuni M. Anti-Inflammatory Effects of Curcumin on Insulin Resistance Index, Levels of Interleukin-6, C-Reactive Protein, and Liver Histology in Polycystic Ovary Syndrome-Induced Rats. Cell J. 2017;19(3):425-433. doi:10.22074/cellj.2017.4415
Mohammadi, Shima, et al. "Anti-Inflammatory Effects of Curcumin on Insulin Resistance Index, Levels of Interleukin-6, C-Reactive Protein, and Liver Histology in Polycystic Ovary Syndrome-Induced Rats." Cell journal, vol. 19, no. 3, 2017, pp. 425-433.