RESUMEN
Wenjinghuoluo (WJHL) prescription, the typical rheumatoid arthritis (RA) treatment compound in traditional Chinese medicine, shows favorable efficacy. The precise mechanism of WJHL on RA therapy is yet to be elucidated. This study aimed to determine the metabolic biomarkers in the early onset of RA and evaluate the regulation effect of WJHL on metabolite levels. Multivariate statistical analysis identified 93 biomarkers by precise MS/MS. These biomarkers played an important role in the regulation of key metabolic pathways associated with collagen-induced arthritis (CIA). A total of 68 biomarkers were related to the treatment of CIA by WJHL therapy. In addition, pathway analysis results showed six and three significant related pathways according to corresponding differential metabolites before and after WJHL therapy. Finally, disease and function prediction of ingenuity pathway analysis indicated that lipid metabolism, small molecule biochemistry, and carbohydrate metabolism were associated functions of WJHL therapy on CIA. Furthermore, top analysis-ready molecules of up-regulated thiamine and down-regulated arachidonic acid maybe the most related metabolites of WJHL therapy on CIA. The present work indicates that a metabolomics platform provides a new insight into understanding the mechanisms of action of natural medicines, such as WJHL.
RESUMEN
OBJECTIVE: The etiological initiators of neuroinflammation remain inconclusive, and effective interventions to block neurodegeneration are unavailable. Surprisingly, we found collagen II-combined complete Freund's adjuvant (CC) that usually induces rheumatoid arthritis (RA) also drives Alzheimer's disease (AD)-like neurodegeneration in mice. CC not only upregulates the cerebral pro-inflammatory cytokines including tumor necrosis factor α (TNF-α) and interleukin 8 (IL-8), but also downregulates the cerebral interleukin 10 (IL-10), an anti-inflammatory cytokine, and tyrosine hydroxylase (TH), a ratelimiting enzyme for biosynthesis of the anti-inflammatory neurotransmitter dopamine. In contrast, electroacupuncture (EA) elevates TNF-α/IL-8 and declines IL-10/TH at first, but declines TNF-α/IL-8 and elevates IL-10/TH later. Upon impact on mitochondrial biogenesis, ubiquitination, and autophagy, EA firstly potentates but secondly attenuates CC-triggered signaling cascades leading to oxidation, nitrosylation, hypoxia, and angiogenesis. Eventually, EA compromises neurodegeneration by decreasing amyloid- ß peptide (Aß) and phosphorylated tau protein (p-tau), and also rectifies neuronal dysfunctions by increasing the cholinergic neurotransmitter acetylcholine (Ach) and its rate-limiting biosynthetic enzyme choline acetyltransferase (ChAT). RESULTS: Conclusively, EA initially aggravates and subsequently ameliorates CC-evoked AD-like earlyphase brain pathogenesis via conversion from pro-inflammatory microglia to anti-inflammatory microglia.