TY - JOUR
T1 - Bryodulcosigenin a natural cucurbitane-type triterpenoid attenuates dextran sulfate sodium (DSS)-induced colitis in mice
AU - Li, Renshi
AU - Chen, Ce
AU - Liu, Bei
AU - Shi, Wen
AU - Shimizu, Kuniyoshi
AU - Zhang, Chaofeng
N1 - Funding Information:
We would like to thank the National Natural Science Foundation (81773982 for Chaofeng Zhang; 82003937 for Renshi Li), and Youth Academic leaders of the Qinglan Project in Jiangsu province (to Chaofeng Zhang) for financial support. We would like to express our gratitude to EditSprings ( https://www.editsprings.com/ ) for the expert linguistic services provided.
Publisher Copyright:
© 2021
PY - 2022/1
Y1 - 2022/1
N2 - Background: Bryodulcosigenin (BDG) a cucurbitane-type triterpenoid has been isolated from the roots of Bryonia dioca and possesses marked anti-inflammatory effects, although its beneficial effect against intestinal disorders remains unclear. Purpose: To explore the underlying mechanism of BDG on the dysbiosis of chronic ulcerative colitis (UC) and its associated side-effects on lung tissues. Methods: A chronic UC model was established using 2.5% dextran sulfate sodium (DSS) in mice treated for 64 days and diagnostic assessments, western blot analysis and quantitative real time-PCR were employed to determine the protective mechanism of BDG. Results: Oral administration of BDG (10 mg/kg/day) significantly improved colon length, disease activity index, and alleviated colonic histopathological damage in the DSS-induced colitis mice. BDG not only reversed the TNF-α-induced degradation of tight junction proteins (occludin and ZO-1) but also suppressed the elevated apoptosis seen in intestinal epithelial cells (NCM460). In addition, BDG significantly attenuated damage in alveolar epithelial cells (MLE-12) co-cultured with NCM460 cells under inflammatory conditions. Furthermore, BDG in vivo significantly prevented the symptoms of respiratory disorders and repressed alveolar inflammation by regulating DSS-induced chronic colitis in mice. Conclusion: BDG effectively inhibited the apoptosis of intestinal epithelial cells and suppressed the activation of the NLRP3 inflammasome which resulted in the restoration of the intestinal barrier. Therefore, the enhanced integrity of intestinal epithelial cells produced by BDG intervention contributed to its anti-colitis effects, indicating its great potential as an inhibitor of UC and lung injury. Therefore, restoring intestinal integrity may represent a promising strategy in the prevention of pulmonary disease.
AB - Background: Bryodulcosigenin (BDG) a cucurbitane-type triterpenoid has been isolated from the roots of Bryonia dioca and possesses marked anti-inflammatory effects, although its beneficial effect against intestinal disorders remains unclear. Purpose: To explore the underlying mechanism of BDG on the dysbiosis of chronic ulcerative colitis (UC) and its associated side-effects on lung tissues. Methods: A chronic UC model was established using 2.5% dextran sulfate sodium (DSS) in mice treated for 64 days and diagnostic assessments, western blot analysis and quantitative real time-PCR were employed to determine the protective mechanism of BDG. Results: Oral administration of BDG (10 mg/kg/day) significantly improved colon length, disease activity index, and alleviated colonic histopathological damage in the DSS-induced colitis mice. BDG not only reversed the TNF-α-induced degradation of tight junction proteins (occludin and ZO-1) but also suppressed the elevated apoptosis seen in intestinal epithelial cells (NCM460). In addition, BDG significantly attenuated damage in alveolar epithelial cells (MLE-12) co-cultured with NCM460 cells under inflammatory conditions. Furthermore, BDG in vivo significantly prevented the symptoms of respiratory disorders and repressed alveolar inflammation by regulating DSS-induced chronic colitis in mice. Conclusion: BDG effectively inhibited the apoptosis of intestinal epithelial cells and suppressed the activation of the NLRP3 inflammasome which resulted in the restoration of the intestinal barrier. Therefore, the enhanced integrity of intestinal epithelial cells produced by BDG intervention contributed to its anti-colitis effects, indicating its great potential as an inhibitor of UC and lung injury. Therefore, restoring intestinal integrity may represent a promising strategy in the prevention of pulmonary disease.
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U2 - 10.1016/j.phymed.2021.153814
DO - 10.1016/j.phymed.2021.153814
M3 - Article
AN - SCOPUS:85119582990
VL - 94
JO - Phytomedicine
JF - Phytomedicine
SN - 0944-7113
M1 - 153814
ER -