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alpha-Cyperone inhibitory effects on tumor-derived DNA trigger microglia by STING pathway

Authors Gao, Peng; Ding, Ning; Lv, Jiaxin; Ramzan, Muhammad Noman; Wen, Qingping

Journal JOURNAL OF ETHNOPHARMACOLOGY , JAN 10 2021,:264

DOI 10.1016/j.jep.2020.113246 PubMed 32781257

Abstract Ethnopharmacological relevance: Cyperus rotundus L. (Cyperaceae) is a widespread herbal in China and widely used in Traditional Chinese Medicine for multiple effects such as anti-arthritic, anti-genotoxic, anti-mutagenic, anti-bacterial effects, and analgesic. alpha-Cyperone is an active compound in Cyperus rotundus and has analgesic effects, but the exact molecular mechanisms require further investigations.Materials and methods: Tumor-derived DNA isolated from Lewis cell lines was transfected into microglia, and analyzed for stimulator of interferon genes (STING) effects. The downstream protein, such as interferon regulatory factor 3 (IRF3) and p65 nuclear factor-kappa B (NF-kappa B) were treated with STING siRNA and 5,6-dimethyllxanthenone-4-acetic acid (DMXAA) in micmglia. The alpha-Cyperone effect on microglia was also investigated.Results: Tumor-derived DNA activate micmglia by upregulation of STING and downstream proteins. STING siRNA was reduced to its downstream expression and neuminflammation inhibition was caused by tumorderived DNA. However, DMXAA reversed the STING siRNA effect and increased neuroinflammation. alpha-Cyperone takes inhibitory effects on tumor-derived DNA that trigger microglia by STING pathway.Conclusions: alpha-Cyperone inhibition by tumor-derived DNA activated microglial to neuroinflammation in STING signaling pathway.

Species covered 香附子 Cyperus rotundus