Qasim Sumera, Saleem Muhammad, Alotaibi Nasser Hadal, Bukhari Syed Nasir Abbas, Alharbi Khalid Saad, Irfan Hafiz Muhammad, Anwar Rukhsana
College of Pharmacy, Jouf University, Sakaka 2014, Aljouf, Saudi Arabia.
College of Pharmacy University of Sargodha, Sargodha University Road, Sargodha 40100, Punjab, Pakistan.
ACS Omega. 2021 Jan 15;6(3):2379-2388. doi: 10.1021/acsomega.0c05698. eCollection 2021 Jan 26.
Prazosin, a selective α adrenergic receptor antagonist, with documented anti-inflammatory potential, was evaluated for its antiarthritic efficacy by targeting specifically TNF-α. The antiarthritic attribute of prazosin validated through screening comprised thermally provoked denaturation of bovine serum albumin (BSA) and egg albumin along with membrane stabilization evaluation at a concentration of 100-6400 μg/mL, while screening comprised formaldehyde-instigated arthritis at the doses of 5, 10, and 20 mg/kg and complete Freund's adjuvant (CFA)-induced arthritis at 20 mg/kg dose. Paw swelling, body weight, arthritic score, hematological parameters, and histological and radiographic examination of ankle joints were assessed for a period of 28 days after CFA immunization. Moreover, the proinflammatory cytokine TNF-α level was also assessed through quantitative real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Prazosin revealed significant antiarthritic effect evident through protein denaturation inhibition in the egg albumin and the BSA model, stabilization of red blood cell membrane in the membrane stabilizing assay, and reduction in paw volume in formaldehyde-induced arthritis. Likewise, prazosin exhibited propitious antiarthritic effects in the CFA-provoked arthritis model manifested by paw volume and arthritic score alleviation, substantial weight loss prevention, and preservation of the normal hematological and biochemical profile. Histological and X-ray investigation unveiled no substantive structural alterations in treated rat's ankle joints. The TNF-α expression level was also reduced. Thus, the current study is suggestive that prazosin exhibits a strong antiarthritic potential possibly through inhibition of TNF-α.
哌唑嗪是一种选择性α肾上腺素能受体拮抗剂，具有已被证实的抗炎潜力，通过特异性靶向肿瘤坏死因子-α（TNF-α）来评估其抗关节炎疗效。通过筛选验证的哌唑嗪的抗关节炎特性包括在浓度为100 - 6400μg/mL时对牛血清白蛋白（BSA）和卵白蛋白进行热诱导变性以及进行膜稳定性评估，而筛选包括在5、10和20mg/kg剂量下的甲醛诱导性关节炎以及在20mg/kg剂量下的完全弗氏佐剂（CFA）诱导性关节炎。在CFA免疫后28天内评估爪肿胀、体重、关节炎评分、血液学参数以及踝关节的组织学和放射学检查。此外，还通过定量实时聚合酶链反应（RT-PCR）和酶联免疫吸附测定（ELISA）评估促炎细胞因子TNF-α水平。哌唑嗪显示出显著的抗关节炎作用，这在卵白蛋白和BSA模型中通过蛋白质变性抑制、膜稳定性测定中红细胞膜的稳定以及甲醛诱导性关节炎中爪体积的减小得以体现。同样，哌唑嗪在CFA诱导的关节炎模型中表现出有益的抗关节炎作用，表现为爪体积和关节炎评分减轻、显著防止体重减轻以及维持正常的血液学和生化指标。组织学和X射线检查显示治疗大鼠的踝关节无实质性结构改变。TNF-α表达水平也降低。因此，当前研究表明哌唑嗪可能通过抑制TNF-α展现出强大的抗关节炎潜力。
