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通过系统评价和荟萃分析对白藜芦醇在类风湿关节炎临床前模型中的药理学评估。

The pharmacological assessment of resveratrol on preclinical models of rheumatoid arthritis through a systematic review and meta-analysis.

作者信息

Mittal Monika, Mehta Poonam, Rajput Swati, Rajender Singh, Chattopadhyay Naibedya

机构信息

Division of Endocrinology and Centre for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI), CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, India.

Division of Endocrinology and Centre for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI), CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, India.

出版信息

Eur J Pharmacol. 2021 Nov 5;910:174504. doi: 10.1016/j.ejphar.2021.174504. Epub 2021 Sep 11.

DOI:10.1016/j.ejphar.2021.174504
PMID:34520733
Abstract

Resveratrol/RES (3,5,4'-trihydroxy-trans-stilbene) is a natural compound found in many food items and red wine, which exhibits pleiotropic biological effects. Several preclinical studies evaluating the efficacy of RES in animal models of rheumatoid arthritis (RA) have been conducted, but the diversity of the experimental conditions and of their outcomes preclude definitive conclusions about RES's efficacy. We, therefore, performed a meta-analysis to assess its efficacy in mitigating experimental RA. We searched three databases until January 2021 and used the random-effects model for drawing inferences. Eighteen studies involving 544 animals were used in this study. Pooled analysis showed that experimental RA causes paw swelling (Hedge's g = 9.823, p = 0.000), increases polyarthritis score and arthritis index, and RES administration reduces paw volume (Hedge's g = -2.550, p = 0.000), polyarthritis score, and arthritis index besides amelioration in the histopathological score and cartilage loss. RA is accompanied by increased oxidative stress due to high malondialdehyde (MDA) level (p < 0.001) and low superoxide dismutase (SOD) activity (p = 0.002), and RES reduced MDA level (p < 0.001) and increased SOD activity (p < 0.001). Experimental RA exhibited an increase in pro-inflammatory cytokines viz. tumor necrosis factor (TNF)-α (p < 0.001), interleukin (IL)-6 (p = 0.002), and IL-1 (p < 0.001); however, insufficient quantitative data precluded us from assessing changes in the anti-inflammatory cytokine, IL-10. In experimental RA, RES decreased TNF-α (p < 0.001), IL-6 (p < 0.001) and IL-1 (p = 0.001) and increased IL-10. This meta-analysis suggests that RES can be a clinically effective therapy for RA, pending clinical trials.

摘要

白藜芦醇/RES(3,5,4'-三羟基反式芪)是一种存在于许多食品和红酒中的天然化合物,具有多种生物学效应。已经进行了几项评估RES在类风湿性关节炎(RA)动物模型中疗效的临床前研究,但实验条件及其结果的多样性使得关于RES疗效的明确结论难以得出。因此,我们进行了一项荟萃分析,以评估其在减轻实验性RA方面的疗效。我们检索了三个数据库直至2021年1月,并使用随机效应模型进行推断。本研究使用了涉及544只动物的18项研究。汇总分析表明,实验性RA会导致爪肿胀(Hedge's g = 9.823,p = 0.000),增加多关节炎评分和关节炎指数,而RES给药除了改善组织病理学评分和软骨损伤外,还可减少爪体积(Hedge's g = -2.550,p = 0.000)、多关节炎评分和关节炎指数。RA伴随着氧化应激增加,这是由于丙二醛(MDA)水平高(p < 0.001)和超氧化物歧化酶(SOD)活性低(p = 0.002)所致,而RES降低了MDA水平(p < 0.001)并增加了SOD活性(p < 0.001)。实验性RA表现出促炎细胞因子增加,即肿瘤坏死因子(TNF)-α(p < 0.001)、白细胞介素(IL)-6(p = 0.002)和IL-1(p < 0.001);然而,定量数据不足使我们无法评估抗炎细胞因子IL-10的变化。在实验性RA中,RES降低了TNF-α(p < 0.001)、IL-6(p < 0.001)和IL-1(p = 0.001)并增加了IL-10。这项荟萃分析表明,在进行临床试验之前,RES可能是一种对RA临床有效的治疗方法。

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