Saleem Noviara, Raza Syed Atif, Khalil-Ur-Rehman Muhammad, Anwar Rukhsana, Ahmed Abrar, Irfan Hafiz Muhammad
Punjab University College of Pharmacy University of the Punjab Lahore, Lahore, Pakistan.
Faculty of Pharmacy, University of Sargodha, Sargodha, Pakistan.
Inflammopharmacology. 2025 May 7. doi: 10.1007/s10787-025-01736-8.
Syringic acid with reported anti-inflammatory attribute was investigated in the present study to assess its anti-arthritic potential at doses of 25 mg/kg, 50 mg/kg and 100 mg/kg using adjuvant-induced arthritic rats. The rat's paw size (mm), arthritic index and behavioral parameters were observed at baseline and subsequently at seven days' interval until the completion of the study, following complete Freund's adjuvant (CFA) induction. The animals were anesthetized on 28th day and blood samples were obtained for the determination of numerous biochemical, hematological, pro-inflammatory, anti-inflammatory and oxidative biomarkers. Afterwards, the weight of lymphoid organs and radiographic, as well as histopathological examinations of the inflamed paw, were conducted. Furthermore, molecular docking was done to find out the interaction between syringic acid and Interleukins-1β, tumor necrosis factor-α, Interleukins-6 (IL-6), Interleukins-4 (IL-4) and Cyclooxygenase-2 (Cox-2). Results revealed that chronic syringic acid administration significantly reduced the paw size, arthritic index, and showed improvement in behavioral parameters with retrieval of altered hematological and biochemical parameters. Treatment with syringic acid also exhibited substantial recovery from oxidative stress markers and lymphoid organ weight was retrieved. Upon quantitative real-time polymerase chain reaction (qRT-PCR) examination, syringic acid significantly reduced the mRNA expression of tumor necrosis factor-α and all the other inflammatory cytokines while enhancing the mRNA expression of anti-inflammatory cytokines. Decreased serum concentration of PGE2 was noted with syringic acid as determined by enzyme-linked immunosorbent assay (ELISA). Histopathological analysis and radiographs further confirmed the findings. Molecular docking studies showed good interaction between syringic acid and IL-1β, tumor necrosis factor-α, IL-6, IL-4 and COX-2 when compared against standard.
本研究对具有抗炎特性的丁香酸进行了研究，以评估其在25毫克/千克、50毫克/千克和100毫克/千克剂量下对佐剂诱导性关节炎大鼠的抗关节炎潜力。在完全弗氏佐剂（CFA）诱导后，于基线期观察大鼠爪大小（毫米）、关节炎指数和行为参数，随后每隔七天观察一次，直至研究结束。在第28天对动物进行麻醉，并采集血样以测定多种生化、血液学、促炎、抗炎和氧化生物标志物。之后，对淋巴器官重量进行测定，并对发炎爪子进行影像学和组织病理学检查。此外，进行分子对接以研究丁香酸与白细胞介素-1β、肿瘤坏死因子-α、白细胞介素-6（IL-6）、白细胞介素-4（IL-4）和环氧化酶-2（Cox-2）之间的相互作用。结果显示，长期给予丁香酸可显著减小爪大小、降低关节炎指数，并改善行为参数，同时恢复改变的血液学和生化参数。丁香酸治疗还使氧化应激标志物显著恢复，淋巴器官重量也得以恢复。通过定量实时聚合酶链反应（qRT-PCR）检测发现，丁香酸可显著降低肿瘤坏死因子-α及所有其他炎性细胞因子的mRNA表达，同时增强抗炎细胞因子的mRNA表达。酶联免疫吸附测定（ELISA）结果表明，丁香酸可降低血清中PGE2的浓度。组织病理学分析和X光片进一步证实了这些发现。分子对接研究表明，与标准物相比，丁香酸与IL-1β、肿瘤坏死因子-α、IL-6、IL-4和COX-2之间具有良好的相互作用。
