Structurally diverse steroids from an endophyte of Aspergillus tennesseensis 1022LEF attenuates LPS-induced inflammatory response through the cholinergic anti-inflammatory pathway. (1st August 2022)

• Record Type: Journal Article
• Authors: Su, Jun-Cheng; Pan, Qianrong; Xu, Xingyuan; Wei, Xia; Lei, Xueping; Zhang, Peng
• Is Part Of: Chemico-biological interactions. Volume 362(2022)
• Publication Date: 2022-08-01
• Subjects: Steroids -- Acetylcholinesterase -- Inflammation -- The cholinergic anti-inflammatory pathway; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2022.109998
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: The emerging cholinergic anti-inflammatory pathway plays a key role in regulating inflammation. Steroids are known to possess remarkable anti-inflammatory activity. However, the links between steroids and the cholinergic anti-inflammatory pathway remain unidentified. In this study, eight steroids (1 –8 ) featuring five different structural types were characterized from an endophytic fungus Aspergillus tennesseensis 1022LEF, and were subsequently evaluated for their potential role in regulating the cholinergic anti-inflammatory pathway. As a result, compound 8, with the best potency, showed remarkable anti-inflammatory activity at the nanomolar to low micromolar level. Further pharmacological study indicated that 8 notably increased α7nAchR expression and inhibited the activation of its down-stream signaling pathways. Collectively, the present study not only highlighted the potential correlation between steroids and the cholinergic anti-inflammatory pathway, but also identified 8 as a dual-functional modulator via directly inhibition to acetylcholinesterase as well as up-regulation of α7nAchR expression. Highlights: Eight steroids featuring five distinct skeletons were discovered from Aspergillus tennesseensis 1022LEF concurrently. The correlation between steroids and the cholinergic anti-inflammatory pathway was revealed for the first time. A steroid dual-functional cholinergic anti-inflammatory pathway regulator was identified.