Department of Pharmacology, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Vile Parle (W), Mumbai, India.
Department of Pharmacology, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Vile Parle (W), Mumbai, India.
Chem Biol Interact. 2020 Jun 1;324:109095. doi: 10.1016/j.cbi.2020.109095. Epub 2020 Apr 11.
Rheumatoid Arthritis (RA) affects approximately 1% of the total world population. Despite incessant research and development of new therapeutic agents, management of RA is still a troublesome affair. Histone Deacetylase 1 (HDAC1) is an epigenetic regulator which play important role in pathogenesis of RA. In present study, we hypothesized that Phenethyl isothiocyanate (PEITC), a potent inhibitor of HDAC1, may ameliorate RA. Efficacy of PEITC was evaluated in Complete Freund's Adjuvant (CFA) induced arthritis model in rats. CFA (0.1 ml) was injected subplantarly in the left hind paw on day 0 to all the groups except normal control. The administration of test drug PEITC (10, 24 & 50 mg/kg) and standard drug Ibuprofen started simultaneously and was continued for 21 days. Paw edema, total arthritic index, mobility score, stair climbing ability, behavioral parameters, and bone erosion were evaluated. Further, radiographic studies, TNF-alpha as well as HDAC1 levels in synovial tissue homogenate and histological analysis were performed. Prophylactic treatment of PEITC attenuated paw edema, total arthritic index, mobility score, stair climbing ability, behavioral parameters, and bone erosion in dose dependent manner. Furthermore, there was significant decrease in TNF-alpha as well as HDAC1 levels in synovial tissue homogenate. Histological analysis revealed no cartilage damage, bone erosion, hyperplasia at synovial lining as well as infiltration of inflammatory cells in treatment group. Results of this study suggest potent anti-rheumatoid arthritis activity of Phenethyl isothiocyanate in CFA induced RA model in rats.
类风湿关节炎（RA）影响全球总人口的 1%左右。尽管不断进行新的治疗药物研究和开发，但 RA 的治疗仍然是一个棘手的问题。组蛋白去乙酰化酶 1（HDAC1）是一种表观遗传调节剂，在 RA 的发病机制中发挥重要作用。在本研究中，我们假设苯乙基异硫氰酸酯（PEITC），一种有效的 HDAC1 抑制剂，可能改善 RA。在 CFA 诱导的关节炎大鼠模型中评估了 PEITC 的疗效。除正常对照组外，所有组均于第 0 天在左后足底皮下注射 CFA（0.1 ml）。测试药物 PEITC（10、24 和 50mg/kg）和标准药物布洛芬同时开始给药，并持续 21 天。评估爪肿胀、总关节炎指数、运动评分、爬梯能力、行为参数和骨侵蚀。此外，还进行了放射学研究、滑膜组织匀浆中的 TNF-α以及 HDAC1 水平以及组织学分析。预防性治疗 PEITC 以剂量依赖的方式减轻爪肿胀、总关节炎指数、运动评分、爬梯能力、行为参数和骨侵蚀。此外，滑膜组织匀浆中的 TNF-α和 HDAC1 水平显著降低。组织学分析显示，治疗组的软骨损伤、骨侵蚀、滑膜衬里增生以及炎症细胞浸润均无明显变化。这项研究的结果表明，苯乙基异硫氰酸酯在 CFA 诱导的 RA 大鼠模型中具有强大的抗类风湿关节炎活性。
