Affiliation:
1. Chengdu University of Traditional Chinese Medicine
2. Université Paris-Saclay: Universite Paris-Saclay
3. chongqing traditional chinese medicine hospital
4. Sichuan Academy of Medical Sciences and Sichuan People's Hospital
5. The Affiliated Hospital of Traditional Chinese Medicine of Southwest Medical University
Abstract
Abstract
Background
Macrophage polarization plays an essential role in the anti-inflammation process. Moxibustion, a traditional Chinese medicine therapy, has been reported to have an anti-inflammatory effect via enhancing α-ketoglutarate (α-KG) and succinate levels. Succinate/α-KG ratio is a hallmark of M1 and M2 macrophage shift. Glutamate dehydrogenase 1 (GLUD1) is a vital enzyme for α-KG production and can be deacetylated by Sirtuin5 (SIRT5). Currently, the role of moxibustion in SIRT5-GLUD1-α-KG-related macrophage alteration in inflammatory diseases has not been discussed yet.
Methods
In this study, complete Freund's adjuvant (CFA)-induced adjuvant arthritis models were established. On day 4 post-CFA, moxibustion and acupoint MC3482 injection were administered. Foot volume was measured before and after the model was established, and after the moxibustion and acupoint injection interventions. ELISA assays were then performed to quantify inflammatory factors, including IL-1β, TNF-α, IL-4, TGF-β, succinate, and α-ketoglutarate (α-KG). Flow cytometry (FCM) and immunofluorescence were used to test M1- and M2-like macrophage expressions in the right arthrodial cartilages of mice. Furthermore, western blotting and immunoprecipitation (IP) were used to detect SIRT5, GLUD1, and GLUD1 succinylation expressions.
Results
Moxibustion and SIRT5 desuccinylation inhibitor MC3482 decreased inflammation by increasing M2 macrophage and reducing M1 macrophage levels in CFA model. The potential mechanism may relate to the effects of moxibustion and SIRT5 inhibition, which could invert succinate and α-KG levels in the CFA group, which displayed low succinate, high α-KG and increased GLUD1 succinylation modification after treatment.
Conclusion
This study supports that moxibustion's anti-inflammation effects are related to the consequences of macrophage conversion after SIRT5 post-translational modification.
Publisher
Research Square Platform LLC
Reference72 articles.
1. Chronic inflammation in the etiology of disease across the life span;Furman D;Nat Med,2019
2. The role of HIF in immunity and inflammation;McGettrick A;Cell Metabol,2020
3. Analgesic and Anti-Inflammatory Effects of Moxibustion on Immune-ï¼²elated Disease;Huangan W;World Chin Med,2016
4. Therapeutic effects of moxibustion simultaneously targeting Nrf2 and NF-κB in diabetic peripheral neuropathy;Li J;Appl Biochem Biotechnol,2019
5. Moxibustion promoted transformation of inflammatory phase to facilitate wound healing in rats with full-thickness cutaneous wounds;Yu K;Acupunct Res,2019