Aesculetin Exhibited Anti-Inflammatory Activities Through Inhibiting Nf-Кb and Mapks Pathway in Vitro and in Vivo

Wang, Shou-Kai; Chen, Ting-Xiao; Wang, Wei; Xu, Ling Ling; Zhang, Yuqing; Jin, Zhen; Liu, You-Bin; Tang, You-Zhi

doi:10.2139/ssrn.4019139

Cited by 1 publication

(1 citation statement)

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“…Besides, this compound also decreased the colonic levels of IL-1β, IL-6, IL-18 and TNF-α, and inhibited CD11b (+) macrophage in ltration [15]. Moreover, aesculin and aesculetin, another two natural compounds of FC, were proved to relieve the symptoms of DSS-induced colitis, restrain the secretion of TNF-α, IL-1β through inhibiting the activation of NF-κB and MAPKs pathway in colonic tissues and macrophages [16,17]. However, the mechanisms of action of FC on UC treatment still remain elusive.…”

Section: Introductionmentioning

confidence: 99%

Deciphering the pharmacological mechanisms of Fraxini Cortex on ulcerative colitis treatment based on Network pharmacology and in vivo studies

Wang

Peng

et al. 2022

Preprint

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Background Ulcerative colitis (UC) is a common type of inflammatory bowel disease. Due to the elusive pathogenesis, safe and effective treatment strategies are still lacking. Fraxini Cortex (FC) has been widely used as a medicinal herb to treat various diseases. However, the pharmacological mechanisms of FC for UC treatment are still unclear. Methods An integrated platform combining network pharmacology and experimental studies was introduced to decipher the mechanism of FC against UC. The active compounds, therapeutic targets, and the molecular mechanism of action were acquired by network pharmacology, and the interaction between the compounds and target proteins were verified by molecular docking. Dextran sulfate sodium (DSS)-induced colitis model was employed to assess the therapeutic effect of FC on UC, and validate the molecuar mechanisms of action predicted by network pharmacology. Results A total of 20 bioactive compounds were retrieved, and 115 targets were predicted by using the online databases. Ursolic acid, fraxetin, beta-sitosterol, and esculetin were identified as the main active compounds of FC against UC. PPI network analysis achieved 28 FC-UC hub genes which were mainly enriched in IL-17 signaling pathway, TNF signaling pathway and Pathways in cancer. Molecular docking confirmed that the active compounds had high binding affinities to the predictive target proteins. GEO dataset analysis showed that these target genes were highly expressed in the UC clinical samples compared with that in the healthy controls. Experimental studies shown that FC alleviated DSS-induced colitis symptoms, reduced inflammatory cytokines release, and suppressed the expression levels of IL1β, COX2, MMP3, IL-17 and RORγt in colon tissues. Conclusion FC exhibits anti-UC properties through regulating multi-targets and multi-pathways with multi-components. In vivo results demonstrated that FC alleviated DSS-induced colitis.

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Section: Introductionmentioning

confidence: 99%