A novel colchicine-myricetin heterozygous molecule: design, synthesis, and effective evaluations on the pathological models of acute lung injury in vitro and in vivo

Acute lung injury (ALI) is an inflammatory condition and there are no effective treatments. A novel new compound---colchicine-myricetin hybrid (CMyrH) was herein designed and synthesized. To evaluate the activity of CMyrH in ALI, we used a bleomycin (BLM) induced BEAS-2B injury model and established...

Full description

Saved in:
Bibliographic Details
Published inFrontiers in pharmacology Vol. 14; p. 1224906
Main Authors Li, Zhiyue, Yan, Xueqin, Wei, Jiangchun, Pu, Liuyang, Zhu, Guanbao, Cao, Yongkai, Liu, Zhanyan, Liu, Yaqian, Li, Yan, Li, Limin, Li, Xinping, Wu, Zhengzhi
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 29.06.2023
Subjects
acute lung injury
bleomycin
colchicine
colchicine-myricetin hybrid
inflammation
neutrophil elastase
Pharmacology
bleomycin
colchicine
colchicine-myricetin hybrid
inflammation
acute lung injury
neutrophil elastase
Online AccessGet full text

Cover

More Information
Summary:Acute lung injury (ALI) is an inflammatory condition and there are no effective treatments. A novel new compound---colchicine-myricetin hybrid (CMyrH) was herein designed and synthesized. To evaluate the activity of CMyrH in ALI, we used a bleomycin (BLM) induced BEAS-2B injury model and established a well-recognized rat model of BLM-induced lung injury . The results demonstrated that colchicine-myricetin hybrid protected BEAS-2B cells against BLM-induced cell injury in an increased dose manner, and reduced wet/dry weight ratio, histological scoring, and inflammation cytokines IL-1β, IL-6, IL-18, and TNF-α levels of lung tissue of the rats. Furthermore, we found colchicine-myricetin hybrid inhibited caspase-1, ASC, GSDMD, and NLRP-3 expression . Meanwhile, we used molecular docking to analyze the binding mode of colchicine-myricetin hybrid and human neutrophil elastase (HNE), it revealed that colchicine-myricetin hybrid showed strong binding affinity toward human neutrophil elastase when compared to its parent molecules. In conclusion, It is suggested that colchicine-myricetin hybrid antagonized acute lung injury by focusing on multi-targets via multi-mechanisms, and might be served as a potential therapeutic agent for acute lung injury.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Weiguang Sun, Huazhong University of Science and Technology, China
Vikram Kumar, Amity University Jaipur, India
These authors have contributed equally to this work and share first authorship
Edited by: Zhou Yuan, Huazhong University of Science and Technology, China
Reviewed by: Jun Lu, Chengdu University of Traditional Chinese Medicine, China
ISSN:1663-9812
1663-9812
DOI:10.3389/fphar.2023.1224906