Broad-spectrum and eicosanoid-targeted serum lipidomics reveal the therapeutic mechanism of moxibustion in a rat model of collagen-induced arthritis☆

Abstract

Objective

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by progressive joint destruction and high disability rates. Moxibustion, a traditional Chinese medicine therapy with a long history of use in RA management, has attracted increasing clinical attention. Although previous studies have explored the mechanisms underlying the efficacy of moxibustion in RA, its lipidomic mechanisms remain unclear. Therefore, this study aimed to elucidate the lipidomic mechanisms of moxibustion by integrating broad-spectrum targeted lipidomics and eicosanoid-targeted lipidomics to identify key lipid metabolites associated with its therapeutic effects.

Methods

Thirty-two male Sprague–Dawley rats were randomly assigned to four groups (n = 8 per group): control, model, moxibustion control, and moxibustion model groups. The collagen-induced arthritis (CIA) model was established by two rounds of immunization. Moxibustion was applied bilaterally at “Zusanli (ST 36)” and “Shenshu (BL23)” for 10 min per acupoint (40 min per session). Treatment was administered once daily for 6 consecutive days per cycle, for three cycles, with a 1-day interval between cycles. After 3 weeks of treatment, therapeutic effects were evaluated based on body weight, paw volume, arthritis index (AI) score, visceral indices, and histopathological examination. Serum lipid profiles were analyzed to identify differential metabolites and metabolic pathways associated with moxibustion.

Results

Compared with the control group, rats in the model group exhibited poor general condition, significant body weight loss, and marked increases in paw volume and AI score (P < 0.05), as well as significantly elevated visceral indices (P < 0.05). In contrast, moxibustion treatment significantly improved general condition, restored body weight, and reduced paw volume, AI score, and visceral indices compared with the model group (P < 0.05). Histopathological examination revealed marked synovial hyperplasia, inflammatory cell infiltration, and cartilage destruction in the ankle joints of the model group, whereas these pathological changes were significantly alleviated by moxibustion. Lipidomic analysis identified 81 differential metabolites between the model and control groups, and moxibustion ameliorated disruptions in the arachidonic acid (ARA) and linoleic acid (LA) pathways. Broad-spectrum targeted lipidomics showed that moxibustion regulated 19 lipid species. Eicosanoid-targeted profiling further demonstrated that, under pathological conditions, moxibustion modulated eight of these lipids to attenuate proinflammatory mediators, whereas under physiological conditions, it adjusted six lipids to maintain lipid homeostasis.

Conclusion

CIA rats exhibited significant disturbances in lipid metabolism, mainly involving the ARA and LA pathways. Moxibustion effectively regulated broad-spectrum lipid classes and specific eicosanoid mediators, thereby alleviating inflammation under pathological conditions and contributing to physiological homeostasis.