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探索姜黄素基水凝胶珠对弗氏完全佐剂诱导的类风湿性关节炎大鼠的有益作用。

Exploring the beneficial effects of curcumin-based hydrogel beads in rats with rheumatoid arthritis induced by Freund's complete adjuvant.

作者信息

Djordjevic Katarina, Pindovic Bozidar, Mihajlovic Katarina, Ilic Igor, Terzic Jelena, Milojevic-Samanovic Andjela, Stanic Zorka, Postolovic Katarina, Ekkert Natalia, Reshetnikov Vladimir, Zivkovic Vladimir, Jakovljevic Vladimir, Turnic Tamara Nikolic

机构信息

Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, 34000, Kragujevac, Serbia.

Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, 34000, Kragujevac, Serbia.

出版信息

Mol Cell Biochem. 2025 Sep 5. doi: 10.1007/s11010-025-05380-2.

Abstract

The aim of this study was to examine the potential antioxidant activity of curcumin in therapeutic and preventive condition and its potential role as adjuvant to conventional drug methotrexate in treatment of rheumatoid arthritis (RA). The study included 104 female Wistar albino rats, 6 weeks old, body weight of 200-250 g, which were divided into 8 groups (n=13 in each group): 1. CTRL: negative control, 2. CUR: positive control 1 (curcumin 200 mg/kg three times a week for 4 weeks per os), 3. MTX: positive control 2 (methotrexate 0,75 mg/kg i.p. two times a week for 4 weeks), 4. RA: positive control 3 (induced RA), 5. RA+pCUR: rats with induced RA + preventive administration of curcumin (curcumin 200 mg/kg three times a week for 4 weeks per os before the induction of RA), 6. RA+tCUR: rats with induced RA + curcumin therapy, 7. RA+MTX+pCUR; rats with induced RA + preventive administration of curcumin + methotrexate 0.75 mg/kg i.p. twice weekly for 4 weeks, 8. RA+MTX+tCUR: rats with induced RA + therapeutic administration of curcumin + methotrexate 0.75 mg/kg i.p. twice weekly for 4 weeks. Potential therapeutic effect of curcumin (200 mg/kg three times a week for 4 weeks orally) and RA induction were initiated on the same day; for preventive protocol, curcumin was administered 4 weeks before the start of RA induction at a dose of 200 mg/kg orally three times a week. Rheumatoid arthritis was triggered by administering 0.1 ml of Complete Freund's Adjuvant (CFA) subcutaneously at the base of the rat tail. Rats were sacrificed 28 days after immunization. During the experimental period, we collected data for arthritis score, radiography testing, and blood sample collecting for specific biochemical analysis for prooxidative and antioxidative parameters (superoxide anion radical, hydrogen peroxide, nitric oxide, index of lipid peroxidation, superoxide dismutase, catalase, and reduced glutathione). Our experimental study confirmed that the therapeutic administration of curcumin reduced disease activity and significantly increased the activities of antioxidative enzymes and reduced prooxidants. Also, preventive administration, especially in combination with methotrexate, offers superior protection by limiting the onset and development of oxidative stress. These findings support the claim that curcumin as turmeric can effectively inhibit inflammatory reactions and reduces symptoms through changing the redox status. Future large randomized controlled trials on the effects of turmeric substance are needed.

摘要

本研究的目的是检测姜黄素在治疗和预防条件下的潜在抗氧化活性,以及其作为传统药物甲氨蝶呤辅助药物治疗类风湿关节炎(RA)的潜在作用。该研究纳入了104只6周龄、体重200 - 250克的雌性Wistar白化大鼠,将其分为8组(每组n = 13):1. CTRL:阴性对照组;2. CUR:阳性对照组1(姜黄素200毫克/千克,每周口服3次,共4周);3. MTX:阳性对照组2(甲氨蝶呤0.75毫克/千克,腹腔注射,每周2次,共4周);4. RA:阳性对照组3(诱导性RA);5. RA + pCUR:诱导性RA大鼠 + 预防性给予姜黄素(在诱导RA前,姜黄素200毫克/千克,每周口服3次,共4周);6. RA + tCUR:诱导性RA大鼠 + 姜黄素治疗组;7. RA + MTX + pCUR:诱导性RA大鼠 + 预防性给予姜黄素 + 甲氨蝶呤0.75毫克/千克,腹腔注射,每周2次,共4周;8. RA + MTX + tCUR:诱导性RA大鼠 + 治疗性给予姜黄素 + 甲氨蝶呤0.75毫克/千克,腹腔注射,每周2次,共4周。姜黄素(200毫克/千克,每周口服3次,共4周)的潜在治疗效果和RA诱导在同一天开始;对于预防性方案,在RA诱导开始前4周给予姜黄素,剂量为200毫克/千克,每周口服3次。通过在大鼠尾部基部皮下注射0.1毫升完全弗氏佐剂(CFA)诱发类风湿关节炎。免疫后28天处死大鼠。在实验期间,我们收集了关节炎评分、放射学检测数据以及血液样本,用于进行促氧化和抗氧化参数(超氧阴离子自由基、过氧化氢、一氧化氮、脂质过氧化指数、超氧化物歧化酶、过氧化氢酶和还原型谷胱甘肽)的特定生化分析。我们的实验研究证实,姜黄素的治疗性给药降低了疾病活动度,并显著提高了抗氧化酶的活性,降低了促氧化剂水平。此外,预防性给药,尤其是与甲氨蝶呤联合使用时,通过限制氧化应激的发生和发展提供了更好的保护。这些发现支持了姜黄素作为姜黄可以通过改变氧化还原状态有效抑制炎症反应并减轻症状的说法。未来需要进行关于姜黄物质作用的大型随机对照试验。

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