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.

Modern pharmacological studies have shown that emodin, the main effective component of rhubarb, has good anti-inflammatory and antioxidant effects, but its pharmacodynamic mechanism remains unclear yet. This study aims to elucidate the multitarget action mechanism of emodin in ischemic stroke through network pharmacology and in vivo experiments. Sprague–Dawley rats were randomly divided into control (normal saline), sham (normal saline), model (normal saline), and emodin groups ( n = 9 per group). Emodin was administered at 40 mg/kg/d for 3 consecutive days. The rats were subjected to middle cerebral artery occlusion for 2 h, followed by reperfusion for 24 h to establish the cerebral ischemia–reperfusion injury. To search for relevant studies in databases, emodin, ischemic stroke, and stroke were used as keywords. Subsequently, protein–protein interaction networks and complex disease target networks were established, and an enrichment analysis and molecular docking of core targets were performed. Gene expression was detected through western blotting and reverse-transcription polymerase chain reaction. Localization and expression of proteins were detected through immunohistochemistry. Furthermore, the neurological function, 2,3,5-triphenyltetrazolium chloride staining, levels of brain tissue inflammatory factors, the role of the blood–brain barrier (BBB), and relevant signaling pathways were assessed in vivo . The molecular docking of core targets revealed that the docking between vascular endothelial growth factor A (VEGF-A) and emodin was the most efficient. Emodin pretreatment decreased the neurological score from 2.875 to 1.125. Moreover, emodin inhibited the degradation of occludin and claudin-5 caused by matrix metalloprotein kinase (MMP)-2/MMP-9, thereby protecting the BBB. Additionally, related proteins such as hypoxia-inducible factor-1α/VEGF-A and nuclear factor kappa B were down-regulated. Thus, emodin may play a protective role during cerebral ischemia reperfusion through mediation of the Hif-1α/VEGF-A signaling pathway to inhibit the expression of inflammatory factors.

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