姜黄素和没食子酸联合给药可抑制没食子酸诱导的类固醇生成、精子产量、抗氧化防御和炎症反应基因的抑制作用。

Combined administration of curcumin and gallic acid inhibits gallic acid-induced suppression of steroidogenesis, sperm output, antioxidant defenses and inflammatory responsive genes.

作者信息

Abarikwu Sunny O, Akiri Oghenetega F, Durojaiye Mojisola A, Alabi Adenike F

机构信息

Department of Chemical Sciences, Redeemer's University, Redemption Camp, Ogun State, Nigeria.

Department of Chemical Sciences, Redeemer's University, Redemption Camp, Ogun State, Nigeria.

出版信息

J Steroid Biochem Mol Biol. 2014 Sep;143:49-60. doi: 10.1016/j.jsbmb.2014.02.008. Epub 2014 Feb 22.

Abstract

In this study, we investigated the effects of administration of gallic acid (Gal) with or without curcumin (Cur) on the sperm output, steroid level and antioxidant defenses in rat testis in vivo and the expression of inflammatory responsive genes in vitro. Male Wistar rats were divided randomly into four groups and given oral Gal (100mg/kg/day) and Cur (100mg/kg/day) alone or in combination for four weeks. The sperm quality was impaired following Gal treatment, while Cur prevented this and also improved the sperm count as well as the efficiency of sperm production (DSP/gm testis). The inhibitory effects of Gal on plasma testosterone level, glutathione levels, activities of glutathione peroxidase, catalase, superoxide dismutase and steroidogenic enzymes, 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-HSD in the rat testis was blocked by Cur. Interestingly, the level of testosterone and the activities of the steroidogenic enzymes were significantly increased after treatment with Cur alone. Malondialdehyde concentration was unchanged following Gal treatment, while a significant decrease in malondialdehyde level was observed following treatment with Cur alone or in combination with Gal. We further analyzed the effects of Cur and Gal (25-100 μM) on the 93RS2 Sertoli cell-lines and observed that Cur blocked the Gal-induced suppression of inflammatory mediators such as TNF-α and IL-6, while Gal blocked the suppressive effect of Cur on IL-1α expression. Furthermore, the stimulatory or inhibitory effects of Gal on the expressions Tgf-β1 and CD-14 was concentration-dependent and could be blocked by Cur. When cultures of primary Sertoli cells were exposed to both Cur and Gal for 24h, p-JNK/SAPK expression remain stable, whereas Gal-induced p-p65 (NF-κB) expression and IκBα degradation was seen to be blocked by Cur but not Gal-induced expression of pERK1/2. Overall, Cur has stimulatory reproductive effects and could protect the testis from the toxic effects of Gal by mechanisms that could not be explained by its effects on the expressions of inflammatory cytokines but by its anti-oxidant properties.

摘要

在本研究中,我们调查了单独或联合给予没食子酸(Gal)和姜黄素(Cur)对大鼠睾丸精子产量、类固醇水平和抗氧化防御的体内影响以及对体外炎症反应基因表达的影响。雄性Wistar大鼠被随机分为四组,单独或联合口服Gal(100mg/kg/天)和Cur(100mg/kg/天),持续四周。Gal处理后精子质量受损,而Cur可防止这种情况并提高精子数量以及精子产生效率(DSP/g睾丸)。Cur可阻断Gal对大鼠睾丸血浆睾酮水平、谷胱甘肽水平、谷胱甘肽过氧化物酶、过氧化氢酶、超氧化物歧化酶和类固醇生成酶3β-羟基类固醇脱氢酶(3β-HSD)和17β-羟基类固醇脱氢酶(17β-HSD)活性的抑制作用。有趣的是,单独用Cur处理后,睾酮水平和类固醇生成酶的活性显著增加。Gal处理后丙二醛浓度未改变,而单独用Cur或与Gal联合处理后丙二醛水平显著降低。我们进一步分析了Cur和Gal(25 - 100μM)对93RS2支持细胞系的影响,观察到Cur可阻断Gal诱导的炎症介质如TNF-α和IL-6的抑制作用,而Gal可阻断Cur对IL-1α表达的抑制作用。此外,Gal对Tgf-β1和CD-14表达的刺激或抑制作用呈浓度依赖性,且可被Cur阻断。当原代支持细胞培养物同时暴露于Cur和Gal 24小时时,p-JNK/SAPK表达保持稳定,而Gal诱导的p-p65(NF-κB)表达和IκBα降解可被Cur阻断,但Gal诱导的pERK1/2表达不受影响。总体而言,Cur具有刺激性生殖作用,可通过其抗氧化特性而非对炎症细胞因子表达的影响来保护睾丸免受Gal的毒性作用。

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