In vitro inhibitory effects of cirsiliol on IL-6-induced STAT3 activation through anti-inflammatory activity. Issue 13 (1st July 2019)

• Record Type: Journal Article
• Authors: Lim, Hyung Jin; Jang, Hyun Jae; Bak, Seon Gyeong; Lee, Soyoung; Lee, Seung Woong; Lee, Kang Min; Lee, Seung-Jae; Rho, Mun-Chual
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 29:Issue 13(2019)
• Page Start: 1586
• Page End: 1592
• Publication Date: 2019-07-01
• Subjects: Cirsiliol -- Inflammation -- IL-6 -- STAT3 -- Jak2; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2019.04.053
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Highlights: We investigated the inhibitory effects of cirsiliol on IL-6/STAT3 activation. Cirsiliol inhibited the expression of p-JAK2 and p-ERK but not the interaction of IL-6 and IL-6R. Cirsiliol could serve as a natural immunoregulatory compound. Abstract: Many studies have identified and described various medicinal effects of cirsiliol. Here, we investigated the signaling pathway involved in the anti-inflammatory effects of cirsiliol on IL-6-induced activity. Cirsiliol showed no cytotoxicity and inhibited pSTAT3-induced luciferase activity. At the molecular level, cirsiliol suppressed the expression of IL-6-induced inflammatory marker genes such as CRP, IL-1β, ICAM-1 and SOCS3, IL-6-induced activation of Jak2, gp130, STAT3 and ERK and nuclear translocation of STAT3, as measured by PCR, immunofluorescence staining and western blot analysis. However, the interaction between IL-6 and its receptor was not affected by cirsiliol treatment. These results indicate that cirsiliol attenuates IL-6-induced cellular signaling by regulating Jak2 phosphorylation. Therefore, cirsiliol could be a therapeutic agent for IL-6-related inflammatory diseases.