Pharmacodynamics of Polysaccharides from Abelmoschus Manihot Radix in Treating Slow Transit Constipation and Mechanistic Study of Network Pharmacology
- VernacularTitle:黄蜀葵根多糖治疗慢传输型便秘作用与网络药理学机制研究
- Author:
Wenli XU
1
;
Zhouyuan LI
;
Ziling WANG
;
Le CHEN
;
Keli CHEN
;
Xiaoying HOU
;
Dahui LIU
;
Hongzhi DU
Author Information
- Publication Type:Journal Article
- Keywords: Abelmoschus Manihot; Non-medicated parts; Polysaccharide; Slow transit constipation; Network pharmacology
- From: World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(12):3071-3085
- CountryChina
- Language:Chinese
- Abstract: Objective The monosaccharide composition of Abelmoschus Manihot Radix polysaccharide was identified and then we evaluated the therapeutic effect on slow transit constipation.Finally,the pharmacodynamic substances and molecular mechanisms in the polysaccharide from Abelmoschus Manihot Radix to improve slow transit constipation were explored by network pharmacology and molecular docking techniques.Methods The polysaccharide from Abelmoschus Manihot Radix has been prepared by aqueous-alcoholic precipitation and has been determined by HPAEC method;The mice model of slow transit constipation was made by sc loperamide(10 mg?kg-1)and the therapeutic effect for the treatment of constipation was evaluated by two indicators:fecal water content and small intestinal propulsion rate;Pathological changes in the colon tissue of STC mice were observed by HE.Immunohistochemical method was used to detect zonula occludens-1(ZO-1)and claudin-1 expression in colon tissue of STC mice;qRT-PCR method was used to detect mRNA expressions of AQP3,AQP4,TNF-α,IL-1β and IL-6 in each group;Network pharmacology and molecular docking technology were used to explore the potential targets and pathways of the polysaccharide from Abelmoschus Manihot Radix in treating slow transit constipation.Results The Polysaccharide from Abelmoschus Manihot Radix significantly increased fecal water content and intestinal propulsion rate in mice caused by slow transit constipation,decreased the expressions of AQP3,AQP4,TNF-α,IL-1β and IL-6 mRNA(P<0.01,P<0.001),protected the integrity of the colonic barrier in STC mice,and increased the protein expressions of ZO-1 and claudin-1 in colon tissues of STC mice.By network pharmacology,it was found that monosaccharides such as rhamnose,fucose and glucuronic acid could mainly act on key targets such as STAT3,JUN,CASP3,HSP90AA1,VEGFA and IL-1β and regulate the Inflammatory mediator regulation of TRP channels,EGFR tyrosine kinase inhibitor resistance and AGE-RAGE signaling pathway in diabetic complications to improve the symptoms of constipation in mice.Western blot results showed that intervention with polysaccharides from the roots of Solanum palmatum significantly reduced the expression of CASP3,VEGFA and IL-1β protein in the colon tissue of constipated mice.Conclusion The polysaccharide from Abelmoschus Manihot Radix can treat slow transit constipation through multi-component,multi-target and multi-pathway therapy.It provides a scientific basis for the further clinical application of Abelmoschus Manihot and drug development(National patent ZL202310894613.3.has been authorized)and it is expected to promote the efficient utilisation of resources from the non-medicinal parts of Abelmoschus Manihot.
