Analysis of target and mechanism of rhynchophylline in treatment of inflammatory bowel disease
- 作者:
Yu LIU
1
;
Lu-Feng CHENG
1
;
Yang WU
1
;
Meng-Jia LI
1
;
Amir ZEB
1
;
Guliruoyi PAERHATI
1
;
Jia-Qi CHEN
1
;
Xu-Wen MAO
1
;
Yu LIU
2
;
Lu-Feng CHENG
2
;
Xu-Wen MAO
2
作者信息
- 出版类型:Journal Article
- 关键字: Caco2 cells; inflammatory bowel disease; JAK; molecular docking; network pharmacology; rhynchophylline
- 来源: Chinese Pharmacological Bulletin 2023;39(10):1929-1937
- 国家China
- 语言:Chinese
- 摘要: Aim To investigate the feasibility and mechanism of rhynchophylline in the treatment of in-rhynchophylline flammatory bowel disease (IBD) based on network pharmacology combined with in vivo and in vitro experiments. Methods The target of rhynchophylline-IBD intersection was obtained from the database, and GO and KEGG enrichment analysis were performed. The binding of key target proteins was screened by molecular docking. In vivo the IBD model of mice was induced by sodium dextran sulfate (DSS). After seven days of rhynchophylline intervention, the signs of mice in each group were observed and DAI scores were recorded. The levels of interleukin-1β (3 (IL-1 β), my-eloperoxidase (MPO) and other inflammatory factors in colon tissue of mice were detected by ELISA. The intestinal permeability of each group was detected. In vitro experiments were conducted to establish the inflammatory model of Caco2 cells induced by DSS, and to clarify the regulatory effect of leptosinine on key targets. Results A total of 70 rhynchophylline-IBD intersection targets were screened, and enrichment analysis showed that they were related to the inflammatory prooess, PI3K-Akt and Hippo signaling pathway s. Molecular docking results showed that was most stable in binding with JAK2 and JAK1. In vivo experiment results showed that compared with model group, body weight, colon length and weight of rhynchophylline group significantly increased (P < 0. 05). DAI score, IL-1β, MPO and other inflammatory factors in colon tissue and intestinal permeability significantly decreased (P < 0. 01). In vitro experiment results showed that compared with model group, rhynchophylline group significantly promoted the proliferation of Caco2 cells (P < 0. 05). The levels of IL-6 and NO were significantly reduced (P < 0. 05). Western blot results showed that rhynchophylline could decrease the expressions of JAK2 and JAK1 (P < 0. 05). Conclusion Rhynchophylline may play a role in the treatment of IBD by inhibiting the expression of JAK2 and JAK1 proteins and reducing inflammatory response in body.
