ABSTRACT
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.
Subject(s)
Alzheimer Disease/immunology , Alzheimer Disease/therapy , Brain/immunology , Brain/pathology , Electroacupuncture , Alzheimer Disease/pathology , Animals , Animals, Outbred Strains , Disease Models, Animal , Female , Fibril-Associated Collagens , Freund's Adjuvant , Male , Mice , Microglia/immunology , Microglia/pathology , Nerve Degeneration/immunology , Nerve Degeneration/pathology , Neuroimmunomodulation/physiology , Neurons/immunology , Neurons/pathology , Nitric Oxide Synthase/metabolism , Random Allocation , Synaptic Transmission/physiologyABSTRACT
The chemical characteristics of Salvia miltiorrhiza , also called "danshen" in China, were investigated on the basis of the simultaneous quantitative determination of 13 hydrophilic and lipophilic compounds, namely, protocatechuic acid, protocatechuic aldehyde, caffeic acid, ferulic acid, isoferulic acid, rosmarinic acid, salvianolic acid B, salvianolic acid A, dihydrotanshinone I, przewalskin, cryptotanshinone, tanshinone I, and tanshinone IIA, in 74 samples collected from different locations using ultraperformance liquid chromatography (UPLC). Hierarchical clustering analysis based on 13 investigated compounds and the similarity of the entire chromatographic pattern showed that S. miltiorrhiza was significantly different from Salvia przewalskii , an adulterant of danshen. The chemical characteristics of S. miltiorrhiza collected from different locations in China were revealed, and salvianolic acid B, rosmarinic acid, cryptotanshinone, and tanshinones I and IIA were optimized as markers for the evaluation, which is helpful in the quality control of S. miltiorrhiza.
