Shweta Shrivastava, Tribhuwan Bahuguna, Sudipto Mondal, Sunil Kumar, Bijo Mathew, Manish Kumar Jeengar, V G M Naidu
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引用次数: 0
Abstract
Objective: Rheumatoid arthritis (RA), a chronic inflammatory disease, is characterized by joint swelling, cartilage erosion, and bone destruction. This study investigated the therapeutic efficacy of Carnosic acid (CA), a natural compound with anti-inflammatory and antioxidant properties, in an adjuvant-induced arthritis model.
Methods: Paw swelling and arthritis index were measured. Oxidative stress markers, including lipid peroxidation and antioxidant enzyme levels, were assessed. Synovial tissue was analyzed for pro-inflammatory markers using real-time Q-PCR and Western blotting. The expression of mPGES-1 was determined by Western blotting. Peripheral neuropathic pain was assessed using cold and mechanical allodynia tests. Bone loss was quantitatively assessed through microcomputed tomography (μCT) scanning of femurs and X-ray radiography. Indomethacin-induced gastric ulcers were evaluated. Molecular docking studies were conducted to analyze the binding affinity of CA to mPGES-1.
Results: The CA treatment not only demonstrated a significant reduction in joint inflammation and paw swelling but also mitigated oxidative stress and improved the antioxidant defence system. CA inhibited microsomal prostaglandin E synthase-1 (mPGES-1) expression and the expression of pro-inflammatory molecules such as inducible nitric oxide synthase (iNOS) and cyclooxygenases-2 (COX-2), thus attenuating the arthritis symptoms without severe gastrointestinal side effects. Additionally, it inhibited the expression of pro-inflammatory molecules such as iNOS and COX-2, contributing to the reduction of arthritis symptoms. Notably, CA treatment prevented the common side effects of traditional RA treatments like corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs), including weight loss, bone degradation, and gastric ulcers.
Conclusions: These findings suggest that CA, through specific enzyme inhibition, offers a compelling alternative therapeutic approach for RA. Further research is warranted to explore the potential of CA in other arthritis models and its suitability for human RA treatment.
目的：类风湿性关节炎（RA）是一种慢性炎症性疾病：类风湿性关节炎（RA）是一种慢性炎症性疾病，以关节肿胀、软骨侵蚀和骨质破坏为特征。本研究调查了具有抗炎和抗氧化特性的天然化合物卡诺酸（Carnosic acid，CA）在佐剂诱导的关节炎模型中的疗效：方法：测量爪肿胀和关节炎指数。方法：测量爪肿胀和关节炎指数，评估氧化应激标记物，包括脂质过氧化和抗氧化酶水平。使用实时 Q-PCR 和 Western 印迹技术分析滑膜组织中的促炎标记物。mPGES-1 的表达是通过 Western 印迹法测定的。外周神经痛通过冷觉和机械异感试验进行评估。骨质流失通过股骨微计算机断层扫描（μCT）和X射线摄影进行定量评估。对吲哚美辛诱发的胃溃疡进行了评估。分子对接研究分析了 CA 与 mPGES-1 的结合亲和力：结果：CA不仅能明显减轻关节炎症和爪肿，还能减轻氧化应激，改善抗氧化防御系统。CA 可抑制微粒体前列腺素 E 合酶-1（mPGES-1）的表达以及诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2）等促炎分子的表达，从而减轻关节炎症状，且无严重的胃肠道副作用。此外，它还抑制了 iNOS 和 COX-2 等促炎分子的表达，有助于减轻关节炎症状。值得注意的是，CA治疗防止了皮质类固醇激素和非甾体抗炎药（NSAIDs）等传统RA治疗方法的常见副作用，包括体重减轻、骨质退化和胃溃疡：这些研究结果表明，CA 通过特异性酶抑制作用为治疗 RA 提供了一种令人信服的替代疗法。我们有必要进一步研究CA在其他关节炎模型中的潜力及其在人类RA治疗中的适用性。
期刊介绍：
The journal Immunopharmacology and Immunotoxicology is devoted to pre-clinical and clinical drug discovery and development targeting the immune system. Research related to the immunoregulatory effects of various compounds, including small-molecule drugs and biologics, on immunocompetent cells and immune responses, as well as the immunotoxicity exerted by xenobiotics and drugs. Only research that describe the mechanisms of specific compounds (not extracts) is of interest to the journal.
The journal will prioritise preclinical and clinical studies on immunotherapy of disorders such as chronic inflammation, allergy, autoimmunity, cancer etc. The effects of small-drugs, vaccines and biologics against central immunological targets as well as cell-based therapy, including dendritic cell therapy, T cell adoptive transfer and stem cell therapy, are topics of particular interest. Publications pointing towards potential new drug targets within the immune system or novel technology for immunopharmacological drug development are also welcome.
With an immunoscience focus on drug development, immunotherapy and toxicology, the journal will cover areas such as infection, allergy, inflammation, tumor immunology, degenerative disorders, immunodeficiencies, neurology, atherosclerosis and more.
Immunopharmacology and Immunotoxicology will accept original manuscripts, brief communications, commentaries, mini-reviews, reviews, clinical trials and clinical cases, on the condition that the results reported are based on original, clinical, or basic research that has not been published elsewhere in any journal in any language (except in abstract form relating to paper communicated to scientific meetings and symposiums).
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