Rheumatoid arthritis (RA) is a multifactorial disease which is complicated by apoptosis resistance. Autophagy is one of the key mechanisms which are involved in the development of resistance to apoptosis as well as to the standard therapies against RA. Aberration in autophagy and apoptosis homeostasis results in the development of oxidative stress thus complicates the pathogenesis of RA. In the given study, tomorou, an indigenous herb of Hunza-Nagar Valley, has been evaluated for its pro-apoptotic, anti-inflammatory, and anti-rheumatic activity. Several major classes of bioactive phytochemicals including steroids, terpenoids, phenols, flavonoids, and essential oils have been detected in the aqueous and ethyl acetate extracts of tomorou through phytochemical analysis. Plant extracts depicted enhanced free radical scavenging activity through di-phenyl-2-picryl hydrazyl hydrate (DPPH) assay and ameliorated the symptoms of arthritis in collagen induced arthritic (CIA) mice model. Moreover, the 6 week extract treatment resulted in the reduction of IL-6 serum levels thus making it an effective anti-inflammatory agent. Upregulation of microtubule-associated proteins light chain 3b (LC3b) and downregulation of UNC51-like kinase 1 (ULK-1) in arthritic mice proposed a ULK-1 independent non-canonical autophagy pathway. Treatment with extracts upregulated the expression of caspase 3 which in turn inhibited the activity of LC3b thus altering the autophagy pathway. However, ULK-1 expression was restored to normal in aqueous extract treated group whereas it was upregulated in ethyl acetate extract treated group. On the other hand, a novel LC3b-independent autophagy pathway was observed in mice treated with ethyl acetate extract due to ULK-1 upregulation. Despite of significantly high IL-6 levels, the arthritic symptoms waned off which suggested the participation of IL-6 in LC3b-independent autophagy pathway in the extract prepared in ethyl acetate. Conclusively, the study established pro-apoptotic, antioxidant, anti-inflammatory and anti-rheumatic activity of tomorou and suggested an intricate autophagy pathway shift.

类风湿关节炎（RA）是一种多因素疾病，并伴有细胞凋亡抗性。自噬是细胞凋亡抗性以及针对RA的标准疗法发展的关键机制之一。自噬畸变和细胞凋亡稳态导致氧化应激的发展，从而使RA的发病机理复杂化。在给定的研究中，已对Tomorou（Hunza-Nagar Valley的一种本土草药）的促凋亡，抗炎和抗风湿活性进行了评估。通过植物化学分析，已经在桃的水和乙酸乙酯提取物中检测到几种主要类别的生物活性植物化学物质，包括类固醇，萜类，酚，类黄酮和精油。植物提取物通过二苯基-2-吡啶基水合肼（DPPH）分析显示出增强的清除自由基活性，并改善了胶原诱导的关节炎（CIA）小鼠模型中的关节炎症状。此外，经过6周的提取物处理导致IL-6血清水平降低，因此使其成为有效的抗炎药。关节炎小鼠中微管相关蛋白轻链3b（LC3b）的上调和UNC51样激酶1（ULK-1）的下调提出了独立于ULK-1的非典型自噬途径。用提取物处理可上调caspase 3的表达，进而抑制LC3b的活性，从而改变自噬途径。然而，在水提取物处理组中ULK-1表达恢复正常，而在乙酸乙酯提取物处理组中其上调。另一方面，由于ULK-1上调，在用乙酸乙酯提取物治疗的小鼠中观察到了一种新的独立于LC3b的自噬途径。尽管IL-6水平明显升高，但关节炎症状逐渐消失，这表明IL-6参与了乙酸乙酯制备的提取物中LC3b非依赖性自噬途径的参与。结论是，该研究建立了促凋亡，抗氧化，抗炎和抗风湿活性的桃金娘，并提出了复杂的自噬途径转移。