Effect and Mechanism of Zuojinwan on DSS-induced Ulcerative Colitis
10.13422/j.cnki.syfjx.20231105
- VernacularTitle:左金丸对DSS诱导的溃疡性结肠炎的作用及其机制
- Author:
Zhao ZHANG
1
;
Ju YANG
1
;
Jiawei WANG
1
;
Shuying XIE
2
;
Wenbin WU
3
;
Manyi JING
2
;
Liwei LANG
2
;
Haotian LI
2
;
Shizhang WEI
2
;
Jian WANG
1
;
Yanling ZHAO
1
Author Information
1. Chengdu University of Traditional Chinese Medicine，Chengdu 611137，China
2. The Fifth Medical Center of Chinese PLA General Hospital，Beijing 100039，China
3. Central Military Commission General Administration Bureau of Military Affairs，Beijing 100034，China
- Publication Type:Journal Article
- Keywords:
Zuojinwan;
ulcerative colitis;
network pharmacology;
molecular docking;
phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway;
apoptosis
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2023;29(16):1-11
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the effect and mechanism of Zuojinwan （ZJW） in the treatment of ulcerative colitis （UC） through network pharmacology and experimental validation. MethodUsing network pharmacology and molecular docking， the active components and potential mechanism of ZJW in treating UC were preliminarily identified. Forty-eight male C57BL/6J mice were randomly divided into a normal group， a model group， a sulfasalazine group （300 mg·kg-1）， and low-， medium-， and high-dose ZJW groups （1.82， 3.64， 7.28 g·kg-1）. The UC model was induced by dextran sulfate sodium （DSS）， and oral administration of drugs began on the third day of modeling， lasting for 7 days. The general condition of mice was observed daily， and the disease activity index （DAI） was evaluated. Hematoxylin-eosin （HE） staining was performed to observe histopathological changes in colon tissue. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of tumor necrosis factor （TNF）-α， interleukin （IL）-6， and IL-10 in mouse serum. The molecular mechanism was validated using Western blot. ResultNetwork pharmacology predicted that the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway might be a key pathway in the regulation of UC by ZJW. Molecular docking results showed good binding ability between the key components of ZJW and core targets. Animal experiment results showed that compared with the normal group， the model group had shortened colon length （P<0.01）， increased DAI scores， spleen index， colon tissue pathology scores， and levels of TNF-α and IL-6 in serum （P<0.05， P<0.01）， increased PI3K， phosphorylated Akt （p-Akt）， and B-cell lymphoma-2 （Bcl-2）-associated X protein （Bax） expression in colon tissue （P<0.05， P<0.01）， and decreased serum IL-10 levels and colon tissue Bcl-2 protein expression （P<0.01）. Compared with the model group， the ZJW groups showed significant improvement in UC symptoms， relieved colon tissue pathological damage， downregulated levels of inflammatory cytokines TNF-α and IL-6 in serum （P<0.01）， inhibited expression of PI3K， p-Akt， and Bax proteins in colon tissue （P<0.05， P<0.01）， and increased serum IL-10 levels and colon tissue Bcl-2 protein expression （P<0.01）， with the high-dose group showing the best effect. ConclusionZJW effectively alleviates DSS-induced UC， and its mechanism may be related to the inhibition of the PI3K/Akt signaling pathway and regulation of apoptosis-related protein expression.
