Protecting effect of emodin in experimental autoimmune encephalomyelitis mice by inhibiting microglia activation and inflammation via Myd88/PI3K/Akt/NF-κB signalling pathway

Bioengineered

Zhibing Wu¹  Haoyou Xu²  Zequan Zheng²  Yuanqi Zhao²  Chen Wang³  Kenan Zheng⁴  Lulu Wu⁴  Baojiang Lv⁴  Xiaojun Li⁵ 

[1] Department of Neurology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China;Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China;Department of Traditional Chinese Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China;The First Clinical School, Guangzhou University of Chinese Medicine, Guangzhou, China;The Second Clinical School, Guangzhou University of Chinese Medicine, Guangzhou, China;

关键词: emodin;    MS/EAE;    PI3K/AKT/NF- κB signalling pathway;    TLRs/MyD88 signal;    microglia activation;    myelin protective;   

DOI  :  10.1080/21655979.2022.2052671

来源: DOAJ

【 摘 要 】

Experimental autoimmune encephalomyelitis (EAE) is characterized by demyelination of the central nervous system. Emodin is an anthraquinone derivative with comprehensive anti-inflammatory, anti-cancer, and immunomodulatory effects and is widely used in the treatment of inflammatory, tumor, and immune system diseases. However, none of the clinical or experimental studies have explored the therapeutic efficacy of emodin in EAE/multiple sclerosis (MS). Thus, we evaluated the protective effect of emodin on EAE mediated via inhibition of microglia activation and inflammation. Wild-type mice were randomly divided into the normal control, EAE, low-dose emodin, and high-dose emodin groups. Clinical scores and pathological changes were assessed 21 days after immunization. The network pharmacology approach was used to elucidate the underlying mechanisms by using an online database. Molecular docking, polymerase-chain reaction tests, western blotting, and immunofluorescence were performed to verify the network pharmacology results. An in vivo experiment showed that high-dose emodin ameliorated clinical symptoms, inflammatory cell infiltration, and myelination. Pharmacological network analysis showed AKT1 was the main target and that emodin played a key role in MS treatment mainly via the PI3K–Akt pathway. Molecular docking showed that emodin bound well with PI3K, AKT1, and NFKB1. Emodin decreased the expression of phosphorylated(p)-PI3K, p-Akt, NF-κB, and myeloid differentiation factor 88 and the levels of markers (CD86 and CD206) in M1- and M2-phenotype microglia in EAE. Thus, the emodin inhibited microglial activation and exhibited anti-inflammatory and neuroprotective effects against EAE via the Myd88/PI3K/Akt/NF-κB signalling pathway. In conclusion, emodin has a promising role in EAE/MS treatment, warranting further detailed studies.

【 授权许可】

Unknown