Changhyun Lee1, Jung Won Lee2, Ji Yeon Seo1, Sung Wook Hwang2, Jong Pil Im2, Joo Sung Kim3. 1. Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Internal Medicine and Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Republic of Korea. 2. Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. 3. Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Internal Medicine and Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Republic of Korea. Electronic address: jooskim@snu.ac.kr.
Abstract
AIMS: Lupeol, a natural pentacyclic triterpene, exhibits anti-inflammatory effects. However, its role in colitis has not been investigated. In the present study, we evaluated the effect of lupeol on the NF-κB signaling pathway and experimental colitis in mice. MAIN METHODS: The human intestinal epithelial cells (IECs) COLO 205 and the murine macrophages RAW 264.7 were pretreated with lupeol and then stimulated with lipopolysaccharide (LPS). The production of inflammatory cytokines (IL-8 from COLO 205; IL-6, IL-12 and TNF-α from RAW 264.7) was determined by ELISA. The effect of lupeol on NF-κB pathway was examined by Western blot analysis of IκBα phosphorylation/degradation and an electrophoretic mobility shift assay (EMSA). For in vivo studies, dextran sulfate sodium (DSS)-induced acute colitis model and chronic colitis model in IL-10(-/-) mice were used. Colitis was quantified by disease activity index, colon length and histologic evaluation. KEY FINDINGS: Lupeol strongly suppressed pro-inflammatory cytokine production in IECs and murine macrophages. It also inhibited LPS-induced IκBα phosphorylation/degradation and the DNA binding activity of NF-κB. The oral administration of lupeol significantly reduced the colitis activity and histologic scores in both acute and chronic murine colitis models. Furthermore, the up-regulation of IκBα phosphorylation in the colonic mucosa was attenuated in lupeol-treated mice. SIGNIFICANCE: Lupeol blocks the NF-κB signaling in IECs and murine macrophages, and attenuate experimental murine colitis. These findings suggest that lupeol is a potential therapeutic agent for inflammatory bowel disease.
AIMS: Lupeol, a natural pentacyclic triterpene, exhibits anti-inflammatory effects. However, its role in colitis has not been investigated. In the present study, we evaluated the effect of lupeol on the NF-κB signaling pathway and experimental colitis in mice. MAIN METHODS: The human intestinal epithelial cells (IECs) COLO 205 and the murine macrophages RAW 264.7 were pretreated with lupeol and then stimulated with lipopolysaccharide (LPS). The production of inflammatory cytokines (IL-8 from COLO 205; IL-6, IL-12 and TNF-α from RAW 264.7) was determined by ELISA. The effect of lupeol on NF-κB pathway was examined by Western blot analysis of IκBα phosphorylation/degradation and an electrophoretic mobility shift assay (EMSA). For in vivo studies, dextran sulfate sodium (DSS)-induced acute colitis model and chronic colitis model in IL-10(-/-) mice were used. Colitis was quantified by disease activity index, colon length and histologic evaluation. KEY FINDINGS: Lupeol strongly suppressed pro-inflammatory cytokine production in IECs and murine macrophages. It also inhibited LPS-induced IκBα phosphorylation/degradation and the DNA binding activity of NF-κB. The oral administration of lupeol significantly reduced the colitis activity and histologic scores in both acute and chronic murinecolitis models. Furthermore, the up-regulation of IκBα phosphorylation in the colonic mucosa was attenuated in lupeol-treated mice. SIGNIFICANCE: Lupeol blocks the NF-κB signaling in IECs and murine macrophages, and attenuate experimental murinecolitis. These findings suggest that lupeol is a potential therapeutic agent for inflammatory bowel disease.
Authors: Riaz Ahmad; Amjad Khan; Inayat Ur Rehman; Hyeon Jin Lee; Ibrahim Khan; Myeong Ok Kim Journal: Int J Mol Sci Date: 2022-05-29 Impact factor: 6.208