Acupuncture stimulation attenuates TNF-α production via vagal modulation in the concanavalin A model of hepatitis

Abstract

Background: A growing body of evidence shows that neuronal activity is involved in modulating the efficacy of acupuncture therapy. However, it has been seldom investigated whether neuronal activity following acupuncture stimulation is effective at regulating hepatic inflammation. Objective: Using the concanavalin A (ConA) model of hepatitis, we investigated the regulation of inflammatory cytokine tumor necrosis factor (TNF)-α in the liver tissue and the blood after acupuncture stimulation at ST36. Methods: Mice were subjected to ConA injection, acupuncture stimulation at ST36 by manual acupuncture (MA) or electroacupuncture (EA) procedures, and vagotomy (VNX). Liver tissue and blood were collected for TNF-α analysis. TNF-α mRNA was analyzed by real-time polymerase chain reaction (PCR), and TNF-α, CD11b, CD68, and Erk1/2 proteins were analyzed by Western blotting, immunofluorescence staining, and enzyme-linked immunosorbent assay. Results: TNF-α mRNA and protein were induced in CD11b-positive hepatic cells and the plasma at 6–24 h after ConA injection. The application of MA or EA was very effective at attenuating the production of TNF-α. Anti-inflammatory effects of acupuncture were greatly suppressed by VNX in ConA-injected animals, suggesting the requirement of vagus nerve activity in acupuncture-mediated anti-inflammatory responses. Electrical stimulation of the sciatic nerve (SNS) resulted in an anti-inflammatory effect similar to acupuncture stimulation. In parallel with TNF-α, production of phospho-Erk1/2, which was induced in the liver tissue, was downregulated by MA and EA in liver cells. Conclusion: The regulatory effects of acupuncture stimulation on inflammatory responses in the liver may be modulated through the activation of the vagus nerve pathway.

The Anti-Inflammatory Actions and Mechanisms of Acupuncture from Acupoint to Target Organs via Neuro-Immune Regulation

“…On the other hand, vagotomy strongly suppresses acupuncture effects. 130 Sepsis, often leading to myocardial injury, is effectively abolished by EA at ST36, which reduces TNF-α and NO levels, thereby strongly inhibiting neutrophil accumulation, and lowering the plasma activity of CK-MB. Upon vagotomy, EA stimulation shows considerably fewer anti-inflammatory and protective effects.…”

Changes in Mitochondria-Related Gene Expression upon Acupuncture at LR3 in the D-Galactosamine-Induced Liver Damage Rat Model

“…Acupuncture at ST36, CV4, and KI1 was reported to reduce inflammatory factors, such as TNF- α , and inflammatory cell infiltration in a nonalcoholic fatty liver disease model [ 35 ]. Moreover, MA at ST36 regulated inflammatory factors in hepatitis models [ 36 ].…”

Anti-Inflammatory Effects of Acupuncture at ST36 Point: A Literature Review in Animal Studies

“…Since activated p-ERK1/2 is known to induce TNF-α production in hepatic Kupffer cells, this study investigated CD68 and CD11b proteins as marker proteins of activated Kupffer cells. These results showed that the anti-inflammatory effect of acupuncture is mediated by vagus nerve activity modulating ERK1/2-STAT3 signaling cascade linked to the cholinergic anti-inflammatory mechanism ( 31 ).…”