Anti-arthritis effect of berberine associated with regulating energy metabolism of macrophages through AMPK/ HIF-1α pathway
Authors: Yining Song
Fang Wei
Yun Yu
Feilong Pei
Rui He
Jing Zhou
Huaqiu Lu
Hao Liu
Xiaodie Wang
Renhao Zhang
Weiwei Cai
Ying Wang
Journal: International Immunopharmacology (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: AMP-activated protein kinase; Adjuvant arthritis; Berberine; Energy metabolism; Hypoxia inducible factor 1α
Affiliations: School of Pharmacy, Bengbu Medical College, No.2600, Donghai Avenue, Bengbu 233000, Anhui, China., School of Pharmacy, Bengbu Medical College, No.2600, Donghai Avenue, Bengbu 233000, Anhui, China; Anhui BBCA Pharmaceuticals Co., Ltd, No.6288, Donghai Avenue, Bengbu 233000, Anhui, China., School of Pharmacy, Bengbu Medical College, No.2600, Donghai Avenue, Bengbu 233000, Anhui, China; Anhui BBCA Pharmaceuticals Co., Ltd, No.6288, Donghai Avenue, Bengbu 233000, Anhui, China; School of Chemistry and Chemical Engineering, Anhui University, No.3, Feixi Rode, Hefei 230039, Anhui, China. Electronic address: .

Abstract:  Berberine (BBR) is the effective constituent of Cortex phellodendri and was characterized as an excellent anti-microbial agent with significant anti-inflammatory effects. Previously, we had demonstrated that BBR alleviated the inflammatory response in adjuvant-induced arthritis (AA) rats by regulating polarization of macrophages. However, the exact mechanics by which BBR regulates macrophage polarization remained unclear. Here, we showed that BBR treatment had little influence on total number of macrophages in joints of AA rats, but increased the proportion of M2 macrophages and decreased the proportion of M1 macrophages. Meanwhile, we found BBR up-regulated the expression of AMP-activated protein kinase phosphorylation (p-AMPK) and down-regulated the expression of Hypoxia inducible factor 1α (HIF-1α) in synovial macrophages of AA rats. In vitro, using LPS-stimulated peritoneal macrophages from normal rats, we also verified that pretreatment with BBR promoted transition from M1 to M2 by up-regulating the expression of p-AMPK and suppressing the expression of HIF-1α. Compound C (an AMPK inhibitor) could abrogate the inhibition of BBR on migration of macrophages. Glycolysis of M1 suppressed by BBR through decreasing lactate export, glucose consumption, and increasing intracellular ATP content, which was remarkably reversed by Compound C. These findings indicated that anti-arthritis effect of BBR is associated with regulating energy metabolism of macrophages through AMPK/HIF-1α pathway. 

Retracted: No

PubPeer comments:
 Figure 5B contains two WB bands which appear more similar than expected. ![file] , 
 #1 I appreciate your interest in our work and your efforts to ensure the accuracy of the scientific record, which also extremely important to us. Upon receipt of your query, I regarded the solution of the problem as our top priority and took immediate action to carefully re-examining our manuscripts, raw data and experimental records. Based on our analysis and recheck to date, the error is because of that we placed the WB band of u03b2-actin incorrectly on the graph, but which not affect data interpretation and paper results (the Fig.1 shows the results of our three repeated experiment on the protein expression of u03b2-actin and AMPK). And we will immediately work with the editorial departments of the relevant journals to address this. I would like to add that I remain confident in the validity, reliability and reproducibility of the scientific conclusions in these papers. Although it was an unintentional mistake, I am also deeply sorry for any negligence in my work and any inconvenience that may have been caused. In addition, I will regard it as a valuable learning opportunity and make a greater contribution to safeguarding scientific accuracy and integrity in the future. Sincerely Yun Yu ![file] ,