Nazir Muhammad Muzammil, Ashraf Asma, Nazir Muhammad Mubashir, Hashmi Mohammad Rameez
Department of Zoology, Government College University, Faisalabad, 38000, Pakistan.
Department of Zoology, Wildlife and Fisheries, Muhammad Nawaz Shareef, University of Agriculture Multan, Multan, Pakistan.
Inflammopharmacology. 2025 Aug 4. doi: 10.1007/s10787-025-01874-z.
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation, joint destruction, and systemic immune dysregulation. Geniposide, an iridoid glycoside derived from Gardenia jasminoides, has shown promising anti-inflammatory and immunomodulatory properties in preclinical studies. This meta-analysis aims to systematically evaluate the therapeutic efficacy and mechanistic pathways of Geniposide in experimental animal models of RA. A comprehensive literature search was conducted using Google Scholar, Science Direct, and PubChem up to June 2025. In vivo studies assessing the effects of Geniposide on arthritis-related outcomes in RA-induced rodent models were included. Data were extracted and analyzed using RevMan 5.4. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. The SYRCLE Risk of Bias tool was used for quality assessment to assess publication bias. Fourteen eligible studies were involved in quantitative synthesis. Geniposide significantly reduced arthritis score, paw swelling, and histopathological joint damage. Pro-inflammatory cytokines IL-6, IL-17, TNF-α, and IL-1β were markedly suppressed, while anti-inflammatory cytokines IL-10 and IL-4 were up-regulated. Mechanistically, Geniposide acted through modulation of NF-κB, MAPK, PTEN/PI3K, and Wnt/β-catenin pathways in reported studies. Geniposide exhibits potent anti-arthritic effects in RA animal models by modulating inflammatory cytokines. These findings highlight its therapeutic potential as a candidate for RA treatment; however, further clinical studies are needed to validate its safety and efficacy in humans.
类风湿性关节炎（RA）是一种慢性自身免疫性疾病，其特征为持续性滑膜炎症、关节破坏和全身免疫失调。栀子苷是一种从栀子中提取的环烯醚萜苷，在临床前研究中已显示出有前景的抗炎和免疫调节特性。本荟萃分析旨在系统评价栀子苷在RA实验动物模型中的治疗效果和作用机制途径。截至2025年6月，使用谷歌学术、科学Direct和PubChem进行了全面的文献检索。纳入了评估栀子苷对RA诱导的啮齿动物模型中关节炎相关结局影响的体内研究。使用RevMan 5.4提取和分析数据。计算了具有95%置信区间（CIs）的标准化平均差（SMDs）。使用SYRCLE偏倚风险工具进行质量评估以评估发表偏倚。14项符合条件的研究参与了定量合成。栀子苷显著降低了关节炎评分、爪肿胀和组织病理学关节损伤。促炎细胞因子IL-6、IL-17、TNF-α和IL-1β受到明显抑制，而抗炎细胞因子IL-10和IL-4上调。从机制上讲，在已报道的研究中，栀子苷通过调节NF-κB、MAPK、PTEN/PI3K和Wnt/β-连环蛋白途径发挥作用。栀子苷通过调节炎性细胞因子在RA动物模型中表现出强大的抗关节炎作用。这些发现突出了其作为RA治疗候选药物的治疗潜力；然而，需要进一步的临床研究来验证其在人类中的安全性和有效性。
