Sengupta Siddhartha, Tripathi Anusri
Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical, Medicine, Kolkata, West Bengal, India.
J Med Virol. 2023 Mar;95(3):e28661. doi: 10.1002/jmv.28661.
Chikungunya virus (CHIKV) infection, a global public health problem, might lead to acute/chronic polyarthritis causing long-term morbidity among infected patients. But, except nonsteroidal anti-inflammatory drugs (NSAIDs) with gastrointestinal, cardiovascular, and immune-related side-effects, no Food and Drug Administration (FDA)-approved analgesic drug is available till date for the treatment of CHIKV-induced arthritis. Curcumin, a plant product with minimal toxicity has been FDA-approved as a Generally Recognized As Safe drug. This study aimed to determine the analgesic and prophylactic effect of curcumin, if any, among CHIKV-induced arthralgic mice. Arthritic pain was evaluated by von Frey assay, locomotory behavior by open-field test, and feet swelling by calipers. Cartilage integrity and proteoglycan loss were evaluated by Safranin O staining followed by Osteoarthritis Research Society International (OARSI), Standardized Microscopic Arthritis Scoring of Histological sections (SMASH) score, and type II collagen loss by immunohistochemistry. Mice were administered high (HD), mid (MD), and low (LD) curcumin doses, before (PT: pretreatment), during (CT: cotreatment) and after (Post-T: posttreatment) CHIKV-infection. Curcumin treatment using PT (2000 mg/kg), CT , and Post-T (1000 mg/kg) significantly alleviated CHIKV-induced arthritic pain by improving pain-threshold, locomotory behavior and reducing feet swelling of infected mice. Also, decreased proteoglycan loss and cartilage erosion with lower OARSI, SMASH scores were observed among these three subgroups compared to infected ones. Compared to infected ones, one- to twofold increased intensity of type II collagen in knee medial femoral condyle and medial tibial plateau regions of these subgroups was observed by immunohistochemical staining. Thus, this study highlighted both the analgesic (CT, Post-T), and prophylactic (PT) activity of curcumin in alleviating CHIKV-induced acute/chronic arthritis within mouse model.
基孔肯雅病毒（CHIKV）感染是一个全球性的公共卫生问题，可能导致急性/慢性多关节炎，使受感染患者长期患病。但是，除了具有胃肠道、心血管和免疫相关副作用的非甾体抗炎药（NSAIDs）外，迄今为止尚无美国食品药品监督管理局（FDA）批准的用于治疗CHIKV诱导性关节炎的镇痛药。姜黄素是一种毒性极小的植物产品，已被FDA批准为一般认为安全的药物。本研究旨在确定姜黄素在CHIKV诱导的关节疼痛小鼠中是否具有镇痛和预防作用。通过von Frey试验评估关节炎疼痛，通过旷场试验评估运动行为，通过卡尺评估足部肿胀。通过番红O染色，然后根据国际骨关节炎研究学会（OARSI）的标准组织学切片显微镜关节炎评分（SMASH）对软骨完整性和蛋白聚糖损失进行评估，并通过免疫组织化学评估II型胶原蛋白损失。在CHIKV感染之前（PT：预处理）、期间（CT：联合治疗）和之后（Post-T：治疗后），给小鼠施用高（HD）、中（MD）和低（LD）剂量的姜黄素。使用PT（2000mg/kg）、CT和Post-T（1000mg/kg）进行姜黄素治疗，通过提高疼痛阈值、运动行为和减少受感染小鼠的足部肿胀，显著减轻了CHIKV诱导的关节炎疼痛。此外，与受感染小鼠相比，在这三个亚组中观察到蛋白聚糖损失减少和软骨侵蚀减少，OARSI、SMASH评分较低。通过免疫组织化学染色观察到，与受感染小鼠相比，这些亚组的膝关节内侧股骨髁和内侧胫骨平台区域的II型胶原蛋白强度增加了一到两倍。因此，本研究强调了姜黄素在小鼠模型中减轻CHIKV诱导的急性/慢性关节炎方面的镇痛（CT，Post-T）和预防（PT）活性。
