Inhibition of Angiogenesis by Sanguisorbae Radix and Sophorae Flos in Ulcerative Colitis Mice by Regulating PI3K/Akt Signaling Pathway
10.13422/j.cnki.syfjx.20250522
- VernacularTitle:地榆-槐花通过调节PI3K/Akt信号通路抑制溃疡性结肠炎小鼠血管生成
- Author:
Yuzhuo WEI
1
;
Li LIU
1
;
Shu BU
1
;
Yongqi WANG
1
;
Zhiwei MIAO
2
;
Yi XU
1
Author Information
1. Affiliated Hospital of Nanjing University of Chinese Medicine， Nanjing 210029， China
2. Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine， Suzhou 215628， China
- Publication Type:Journal Article
- Keywords:
Sanguisorbae Radix;
Sophorae Flos;
network pharmacology;
ulcerative colitis;
angiogenesis
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(11):40-50
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the potential mechanism of action of the combination of Sanguisorbae Radix-Sophorae Flos （DH） in the treatment of ulcerative colitis （UC） using network pharmacology methods and molecular docking technology. MethodsNetwork pharmacology analysis was utilized to predict the potential targets of DH for the treatment of UC. The therapeutic effects were experimentally validated by inducing a UC model in mice with 3% dextran sulfate sodium （DSS）. The experimental groups were the normal group， the model group， the salazosulfapyridine group （100 mg·kg-1）， and the low， medium， and high dose groups of DH （1.2， 2.4， and 4.8 g·kg-1）. The efficacy of the treatment was assessed through the general condition of the mice， histopathological examination， and the expression levels of inflammatory markers in the colon. The effect of DH on angiogenesis was explored by messenger RNA （mRNA） detection of colonic angiogenesis-related mediators， vascular endothelial growth factor （VEGF） immunohistochemistry， microvessel density （MVD） detection， and transmission electron microscopy. The phosphatidylinositol-3-kinase （PI3K）-protein kinase B （Akt） signaling pathway proteins were quantitatively analyzed through Western blot to assess whether the suppression of pathological angiogenesis by DH is associated with this pathway. ResultsNetwork pharmacological analysis yielded 112 potential core therapeutic targets for the treatment of UC with DH， of which the core targets were tumor protein 53 （TP53）， JUN， interleukin （IL）-6， Akt1， and tumor necrosis factor （TNF）. Compared with the normal group， mice in the model group showed significant weight loss， colon shortening， and high DAI score， increased expression of inflammatory factors IL-6， IL-1β， and TNF-α， as well as increased mRNA expression levels of angiogenesis-related mediators VEGF， vascular cell adhesion molecule 1 （VCAM1）， angiotensin 1 （Ang1）， matrix metalloproteinase （MMP）-1， MMP-2， and MMP-9. The positive expression of CD31 and VEGF in colonic tissue increased， and the protein expression of the PI3K/Akt pathway was increased （P<0.05）. The endothelial cells of the colonic mucosa and the colonic vasculature were severely damaged. Compared with the model group， mice in the DH groups had significantly reduced weight loss and colon shortening， lower DAI scores， and a significant decrease in mRNA expression of inflammatory factors and angiogenesis-related mediators. In addition， there was decreased positive expression of CD31 and VEGF in colonic tissue and decreased protein expression of the PI3K/Akt pathway （P<0.05）. ConclusionNetwork pharmacology， molecular docking， and experimental validation are applied to explore the mechanism of action of DH in the treatment of UC， and it is found that DH is able to improve the symptoms of colitis and inhibit the pathological angiogenesis in UC mice. Its action might be related to affecting the PI3K/Akt pathway.
