Shabeer Amina, Manzoor Wajiha, Younis Waqas, Uttra Ambreen Malik, Mushtaq Naveed, Lateef Mehreen, Hasan Umme Habiba, Nasim Maaz Bin, Hassan Mohd Zaheen, Uddin Jalal, Aslam Sania, Higashijima Arisa Namie, Dos Lívero Francislaine Aparecida Reis, Gasparotto Junior Arquimedes
Department of Pharmacology, Faculty of Pharmacy, The University of Lahore, Lahore, Pakistan.
Division of Endocrinology Diabetes and Metabolism, New York University Medical Center, Science Building, 623-D, New York, 10016, USA.
Inflammopharmacology. 2025 Jul;33(7):3983-3999. doi: 10.1007/s10787-025-01847-2. Epub 2025 Jul 17.
Pulegone, a monoterpene phytochemical, was evaluated for its anti-inflammatory and anti-arthritic properties. This study investigated its preventive efficacy against rheumatoid arthritis using in vivo animal models and in vitro assays. The in vitro analysis included the inhibition of egg albumin and bovine serum albumin (BSA) denaturation, as well as the stabilization of red blood cell membranes against hemolysis, across concentrations of 50-6400 μg/mL. For in vivo evaluation, arthritis was induced using formaldehyde and Complete Freund's Adjuvant (CFA) models, with pulegone administered at doses of 20, 40, and 80 mg/kg. The mRNA expression levels of key inflammatory mediators, including interleukin-1 beta (IL-1β), interleukin-17 (IL-17), nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin receptor-associated kinase (IRAK), and interleukin (IL)-10 and IL-17, were also analyzed. Results showed concentration-dependent inhibition of egg albumin and BSA denaturation, with maximum erythrocyte membrane-stabilizing effects observed at 6400 μg/mL. Pulegone exhibited dose-dependent anti-arthritic activity in the formaldehyde model, with the highest efficacy at 80 mg/kg. In the CFA model, pulegone significantly reduced arthritic lesions, mitigated weight loss, reversed hematological and biochemical abnormalities, and improved radiographic and histopathological outcomes. Additionally, pulegone demonstrated potent antioxidant effects in superoxide dismutase and reducing power assays. Treatment with pulegone significantly reduced pro-inflammatory cytokines (IL-1β, TNF-α, IRAK, and NF-κB) while increasing anti-inflammatory cytokines (IL-10 and IL-17) compared to the control group. In conclusion, pulegone effectively suppressed inflammatory responses in rheumatoid arthritis by modulating cytokine levels and enhancing antioxidant activity, making it a promising candidate for therapeutic development.
长叶薄荷酮是一种单萜类植物化学物质，已对其抗炎和抗关节炎特性进行了评估。本研究使用体内动物模型和体外试验研究了其对类风湿性关节炎的预防效果。体外分析包括在50 - 6400μg/mL浓度范围内抑制蛋清蛋白和牛血清白蛋白（BSA）变性，以及稳定红细胞膜防止溶血。对于体内评估，使用甲醛和完全弗氏佐剂（CFA）模型诱导关节炎，长叶薄荷酮以20、40和80mg/kg的剂量给药。还分析了关键炎症介质的mRNA表达水平，包括白细胞介素-1β（IL-1β）、白细胞介素-17（IL-17）、核因子-κB（NF-κB）、肿瘤坏死因子-α（TNF-α）、白细胞介素受体相关激酶（IRAK）以及白细胞介素（IL）-10和IL-17。结果显示蛋清蛋白和BSA变性受到浓度依赖性抑制，在6400μg/mL时观察到最大的红细胞膜稳定作用。长叶薄荷酮在甲醛模型中表现出剂量依赖性抗关节炎活性，在80mg/kg时效果最佳。在CFA模型中，长叶薄荷酮显著减少关节炎病变，减轻体重减轻，逆转血液学和生化异常，并改善影像学和组织病理学结果。此外，长叶薄荷酮在超氧化物歧化酶和还原能力试验中表现出强大的抗氧化作用。与对照组相比，长叶薄荷酮治疗显著降低促炎细胞因子（IL-1β、TNF-α、IRAK和NF-κB），同时增加抗炎细胞因子（IL-10和IL-17）。总之，长叶薄荷酮通过调节细胞因子水平和增强抗氧化活性有效抑制类风湿性关节炎中的炎症反应，使其成为治疗开发的有希望的候选药物。
