Abbasi Huda, Sharif Maria, John Peter, Bhatti Attya, Hayat Muhammad Qasim, Mansoor Qaisar
Atta ur Rahman School of Applied Biosciences, National University of Sciences and Technology, Sector H-12, Islamabad 44000, Pakistan.
Institute of Biomedical and Genetic Engineering (IBGE), Sector G-9/4, Islamabad 44000, Pakistan.
Nutrients. 2024 Nov 24;16(23):4020. doi: 10.3390/nu16234020.
Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by severe pain, inflammation, and joint deformity. Currently, it affects 1% of the population, with a projection to exceed 23 million cases by 2030. Despite significant advancements, non-steroidal anti-inflammatory drugs (NSAIDs), the first line of treatment, are associated with a range of adverse effects. Consequently, plant-based derivatives are being utilized as an effective alternative. This study evaluates the anti-inflammatory and safety profile of hydroethanolic extract (CLHE) in comparison to NSAIDs, with a focus on COX-2 and TNFα inhibition.
CLHE potential was evaluated by phytochemical screening and in vitro bioactivity assays. Toxicity profile was conducted in Human Colon Epithelial Cells (HCEC) and Balb/c mice. Anti-inflammatory potential was explored in a collagen-induced arthritic (CIA) mice model. Bioactive compounds were identified computationally from GCMS data and subjected to docking and simulation studies against COX2 and TNFα.
CLHE demonstrated significant antioxidant (IC-50 = 6.78 µg/mL) and anti-inflammatory (IC-50 = 97.39 µg/mL) activity. It maintained 50% cell viability at 78.5 μg/µL in HCEC cells and exhibited no toxicity at a dose of 5000 mg/kg in mice. In the CIA model, CLHE significantly reduced paw swelling, arthritic scoring, C-reactive protein levels, and spleen indices, outperforming ibuprofen. Expression analysis confirmed the downregulation of COX-2, TNFα, and MMP-9. Histopathological analysis indicated the superior efficacy of CLHE compared to ibuprofen in reducing inflammation, synovial hyperplasia, and bone erosion. Computational studies identified compound-15 (CL15), (4-(4,7-dimethoxy-1,3-benzodioxol-5-yl)-2-oxo pyrrolidine-3-carboxylic acid), a non-toxic compound with strong binding affinities to COX-2 (-12.9 KJ/mol), and TNF-α (-5.8 KJ/mol).
The findings suggest the potential of as a safer, anti-inflammatory, and multi-targeted alternative to NSAIDs for RA treatment.
类风湿性关节炎（RA）是一种慢性自身免疫性疾病，其特征为严重疼痛、炎症和关节畸形。目前，它影响着1%的人口，预计到2030年病例数将超过2300万。尽管取得了重大进展，但作为一线治疗药物的非甾体抗炎药（NSAIDs）存在一系列不良反应。因此，植物源性衍生物正被用作一种有效的替代药物。本研究评估了水乙醇提取物（CLHE）与NSAIDs相比的抗炎作用和安全性，重点关注COX-2和TNFα的抑制作用。
通过植物化学筛选和体外生物活性测定评估CLHE的潜力。在人结肠上皮细胞（HCEC）和Balb/c小鼠中进行毒性分析。在胶原诱导的关节炎（CIA）小鼠模型中探究抗炎潜力。从GCMS数据中通过计算鉴定生物活性化合物，并对其进行针对COX2和TNFα的对接和模拟研究。
CLHE表现出显著的抗氧化活性（IC-50 = 6.78 µg/mL）和抗炎活性（IC-50 = 97.39 µg/mL）。在HCEC细胞中，它在78.5 μg/µL时维持50%的细胞活力，在小鼠中5000 mg/kg剂量下未表现出毒性。在CIA模型中，CLHE显著减轻爪肿胀、关节炎评分、C反应蛋白水平和脾脏指数，优于布洛芬。表达分析证实COX-2、TNFα和MMP-9的下调。组织病理学分析表明，与布洛芬相比，CLHE在减轻炎症、滑膜增生和骨侵蚀方面具有更好的疗效。计算研究鉴定出化合物15（CL15），即（4-(4,7-二甲氧基-1,3-苯并二恶唑-5-基)-2-氧代吡咯烷-3-羧酸），一种对COX-2（-12.9 KJ/mol）和TNF-α（-5.8 KJ/mol）具有强结合亲和力的无毒化合物。
研究结果表明，CLHE有潜力作为一种更安全、抗炎且多靶点的药物，替代NSAIDs用于RA治疗。
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