Compatibility Mechanism of Shangerhuang Wan in Enhancing Intestinal Motility in Rat Model of Functional Constipation by Regulating Bile Acid Metabolism
10.13422/j.cnki.syfjx.20250105
- VernacularTitle:上二黄丸通过调节胆汁酸代谢促进功能性便秘大鼠肠动力的配伍机制
- Author:
Yaoying ZENG
1
;
Guangli DU
1
Author Information
1. School of Traditional Chinese Medicine（TCM），Shanghai University of TCM， Shanghai 201203，China
- Publication Type:Journal Article
- Keywords:
Shangerhuang Wan;
functional constipation;
bile acid metabolism;
intestinal motility;
compatibility
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(6):1-8
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the mechanism of Shangerhuang Wan （SEHW） and its subdivisions in alleviating loperamide-induced functional constipation （FC） in rats by regulating bile acid metabolism. MethodsSixty rats were randomly assigned into six groups （n=10）： normal control， model， positive control （domperidone， 8 mg·kg-1）， Cimicifugae Rhizoma-Bupleuri Radix （SC， 1.33 g·kg-1）， Scutellariae Radix-Coptidis Rhizoma （QL， 1.20 g·kg-1）， and SEHW （3.33 g·kg-1）. The remaining groups except the normal control group were subjected to subcutaneous injection with loperamide at 3 mg·kg-1 twice daily （total dose of 6 mg·kg-1·d-1） for 7 days to induce a model of FC. Drug administration was initiated on day 3 of modeling， which continued throughout the modeling period. The small intestinal propulsion rate of each group was measured via the ink propulsion method. LC-MS/MS was employed to measure the fecal bile acid content in each group， and the serum bile acid level was measured by a microplate. The 5-hydroxytryptamine （5-HT） and cyclic adenosine monophosphate （cAMP） levels in the colon tissue of each group were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to determine the protein levels of apical sodium-dependent bile acid transporter （ASBT） in the ileum terminus and Takeda G protein-coupled receptor 5 （TGR5） in the colon. ResultsCompared with the normal control group， the model group exhibited decreases in the small intestinal propulsion rate and total fecal bile acid content （P<0.01）， an elevation in the serum total bile acid level， lowered 5-HT and cAMP levels （P<0.01）， up-regulation in the protein level of ASBT （P<0.01）， and down-regulation in the protein level of TGR5 （P<0.05）. Compared with the model group， the positive control， SEHW， and QL groups showed increases in the small intestinal propulsion rate （P<0.05， P<0.01） and total fecal bile acid content （P<0.01） and a decline in the serum bile acid level. Compared with the SEHW group， the SC group had decreased total fecal bile acid content （P<0.01） and an elevated serum bile acid level， while the QL group showed increased total fecal bile acid content （P<0.01） and a lowered serum bile acid level. Compared with the model group， the positive control， SEHW， and QL groups demonstrated down-regulation in the protein level of ASBT （P<0.05， P<0.01） and up-regulation in the protein level of TGR5 （P<0.05， P<0.01）. The SC group showed no significant change in the protein level of ASBT and up-regulation in the protein level of TGR5 compared with the model group （P<0.05）. Additionally， compared with the model group， the positive control， SEHW， and QL groups showed elevated 5-HT and cAMP levels （P<0.05， P<0.01）. The SC group showed no significant difference in the 5-HT level but a rise in the cAMP level （P<0.01）. ConclusionSEHW， through the compatibility of QL and SC， demonstrates a dual regulatory effect on bile acid metabolism， embodying the principle of descending turbidity and ascending lucidity， which highlights the compatibility and scientific rationale of this formula. SEHW inhibits ASBT expression in the ileum to reduce ileal bile acid reabsorption， increase colonic bile acid content， and bind to colonic TGR5 to release 5-HT， thereby enhancing intestinal motility and promoting intestinal contraction.
