School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue, Zhengzhou 450001, Henan Province, PR China; Department of Pathophysiology, College of Basic Medical Sciences, Zhengzhou University, 100 Kexue, Zhengzhou 450001, Henan Province, PR China.
School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue, Zhengzhou 450001, Henan Province, PR China; Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450001, Henan Province, PR China.
Biomed Pharmacother. 2018 Oct;106:637-645. doi: 10.1016/j.biopha.2018.07.001. Epub 2018 Jul 11.
Methotrexate is one of the most widely used disease-modifying anti-rheumatic drugs. The hepatotoxicity of methotrexate resulted in poor compliance with therapy. The current study was designed to analyse the combined therapy of andrographolide (AD) and methotrexate (MTX) for complete Freund's adjuvant (CFA)-induced arthritis, focusing on hepatoprotective effects, oxidative stress and arthritic-related cytokines.
Wistar rats were injected with CFA into the right hind paw. Ten days post-CFA injection, the Wistar rats were administered with 1% CMC-Na solution, methotrexate (2 mg/kg/week), AD (50 mg/kg/d) and combined therapy for 35 days. The anti-arthritic effect was assessed by paw volume, X-ray and serum tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β levels. Serum samples were also analysed for glutamic oxaloacetic transaminases (GOT), serum glutamic pyruvic transaminase (GPT), alkaline phosphatase (AKP) and lactate dehydrogenase (LDH). Liver tissue samples were used to examine the cellular antioxidant defence activities using catalase activity (CAT) and GSH as well as GSH-Px and MDA. Histopathology analysis was conducted to evaluate liver damage.
AD treatment strengthened the anti-arthritic capacity of MTX. AD and MTX-combined therapy additively reduced the inflammatory symptoms in CFA rats. The combined therapy of AD and MTX showed hepatoprotective effect indicated by an improvement in the serum marker, possibly due to antioxidant action and confirmed by liver histopathological changes. Furthermore, the combined therapy significantly reduced serum TNF-α, IL-6 and IL-1β levels.
A combined therapy of AD and methotrexate significantly alleviated MTX-induced hepatocellular injury and strengthened the anti-arthritic effect. Further clinical studies should be done to further verify the possibility of combined its clinical usage.
甲氨蝶呤是最广泛使用的疾病修饰抗风湿药物之一。甲氨蝶呤的肝毒性导致治疗依从性差。本研究旨在分析穿心莲内酯（AD）和甲氨蝶呤（MTX）联合治疗完全弗氏佐剂（CFA）诱导的关节炎，重点关注肝保护作用、氧化应激和关节炎相关细胞因子。
将 CFA 注入 Wistar 大鼠右后爪。CFA 注射后 10 天，Wistar 大鼠给予 1%CMC-Na 溶液、甲氨蝶呤（2mg/kg/周）、AD（50mg/kg/d）和联合治疗 35 天。通过爪体积、X 射线和血清肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6 和 IL-1β水平评估抗关节炎作用。还分析了血清样本中的谷氨酸草酰乙酸转氨酶（GOT）、血清谷氨酸丙酮酸转氨酶（GPT）、碱性磷酸酶（AKP）和乳酸脱氢酶（LDH）。使用过氧化氢酶活性（CAT）和 GSH 以及 GSH-Px 和 MDA 来检查肝组织样本中的细胞抗氧化防御活性。进行组织病理学分析以评估肝损伤。
AD 治疗增强了 MTX 的抗关节炎能力。AD 和 MTX 联合治疗可减轻 CFA 大鼠的炎症症状。AD 和 MTX 联合治疗具有肝保护作用，表现为血清标志物改善，可能是由于抗氧化作用，通过肝组织病理学变化得到证实。此外，联合治疗可显著降低血清 TNF-α、IL-6 和 IL-1β 水平。
AD 和甲氨蝶呤的联合治疗可显著减轻 MTX 诱导的肝细胞损伤，并增强抗关节炎作用。应进行进一步的临床研究，以进一步验证联合使用的可能性。
