Mechanism prediction and verification of Cistanche deserticola in the treatment of inflammatory bowel disease
- VernacularTitle:肉苁蓉治疗炎症性肠病的作用机制预测及验证
- Author:
Ming QIAO
1
;
Yi ZHU
1
;
Junping HU
2
;
Jianhua YANG
3
Author Information
1. Dept. of Pharmacy，the First Affiliated Hospital of Xinjiang Medical University，Urumqi 830011，China;Xinjiang Key Laboratory of Clinical Drug Research，Urumqi 830011，China
2. College of Pharmacy，Xinjiang Medical University，Urumqi 830017，China
3. Dept. of Pharmacy，the First Affiliated Hospital of Xinjiang Medical University，Urumqi 830011，China
- Publication Type:Journal Article
- Keywords:
Cistanche deserticola;
inflammatory bowel disease;
network pharmacology;
molecular docking;
experimental
- From:
China Pharmacy
2024;35(21):2582-2589
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the mechanism of Cistanche deserticola in the treatment of inflammatory bowel disease （IBD）. METHODS The active components of C. deserticola were screened based on TCMSP and literature reports. The targets of active ingredients were obtained via Swiss Target Prediction platform. Then the disease targets were obtained by searching GeneCards and OMIM databases. PPI network and “drug-compound-disease-target” network were constructed. The core components and core targets were screened. GO and KEGG enrichment analyses were performed， and molecular docking verification was conducted for core targets and core components. The IBD mice model was established and divided into model group， positive control group （dexamethasone， 0.4 mg/kg） and C. deserticola extract group （100， 200， 400 mg/kg）； blank control group was set， with 8 mice in each group. Each group was given relevant medicine， once a day， for 7 consecutive days. Disease activity index （DAI） score and colon length were calculated， and the pathological morphology of the colon of mice was observed. The levels of inflammatory factors [interleukin-6 （IL-6）， IL-1β， IL-10， myeloperoxidase （MPO），tumor necrosis factor-α （TNF-α）] in colon tissue， and protein expressions of core targets were detected. RESULTS A total of 39 active ingredients and 232 potential targets of C. deserticola in the treatment of IBD were obtained. The treatment of IBD with C. deserticola might be related to core components such as quercetin， suchilactone， β-sitosterol and cistanoside H， and core targets such as TNF， AKT1， STAT3， EGFR and SRC. GO and KEGG pathway analysis predicted that the biological processes of C. deserticola in the treatment of IBD were mainly related to protein phosphorylation， and negative regulation of apoptosis， mainly involving PI3K/AKT and EGFR tyrosine kinase inhibitor resistance signaling pathways. The results of molecular docking showed that the binding energy between the core components and core target of C. deserticola was less than －4.7 kJ/mol. Animal experiment results showed that after intervention with C. deserticola extract， the body weight and colon length of mice significantly increased （P＜0.05 or P＜0.01）， while DAI decreased significantly （P＜0.05 or P＜0.01）. The congestion and edema of colon mucosa were significantly reduced， and the pathological score of colon tissue was significantly decreased （P＜0.05 or P＜0.01）； the levels of IL-6， IL-1β， MPO and TNF-α， as well as the protein expressions of PI3K， phosphorylated PI3K （p-PI3K）， EGFR， TNF- α， STAT3， phosphorylated STAT3 （p-STAT3）， AKT1， phosphorylated AKT1 （p-AKT1） and SRC in colon tissue were reduced significantly （P＜0.05 or P＜0.01）， while the level of IL-10 was significantly increased in model group （P＜0.01）. CONCLUSIONS C. deserticola may alleviate IBD by regulating the SRC/EGFR/PI3K/AKT signaling pathway.
