Network pharmacological prediction and molecular docking analysis of the combination of Atractylodes macrocephala Koidz. and Paeonia lactiflora Pall. in the treatment of functional constipation and its verification

Abstract

Background We aimed to reveal the mechanism of functional constipation in the treatment of Atractylodes macrocephala Koidz. (AMK) and Paeonia lactiflora Pall. (PLP). Methods The main active ingredients of AMK and PLP were screened by the Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform. A database of functional constipation targets was established by GeneCard and OMIM. An “ingredient‐target” network map was constructed with Cytoscape software (version 3.7.1), and molecular docking analysis was performed on the components and genes with the highest scores. The rats in the normal group were given saline, and those in the other groups were given 10 mg/kg diphenoxylate once a day for 14 days. The serum and intestinal tissue levels of adenosine monophosphate (cAMP), protein kinase A (PKA), and adenylyl cyclase (AC) of the rats and aquaporin (AQP)1, AQP3, and AQP8 were measured. Results AMK and PLP had a significant role in the regulation of targets in the treatment of functional constipation. After treatment with AMK, PLP, or mosapride, the serum and intestinal tissue levels of AC, cAMP, and PKA were significantly downregulated. Groups receiving AMK and PLP or mosapride exhibited a reduction in the level of AQP1, AQP3, and AQP8 to varying degrees. Conclusion Molecular docking analysis revealed that AMK and PLP had a significant role in the regulation of targets in the treatment of functional constipation. Studies have confirmed that AMK and PLP can also affect AC, cAMP, and PKA. AC, cAMP, and PKA in model rats were significantly downregulated. AQP expression is closely related to AC, cAMP, and PKA. AMK and PLP can reduce the expression of AQP1, AQP3, and AQP9 in the colon of constipated rats.

Arctiin alleviates functional constipation by enhancing intestinal motility in mice

“…Of note, suppression of AQP3 function in the colon results in diarrhoea (52). FC mice show increased levels of AQP3 and AQP9 compared with those in controls, which is consistent with the present results (56). Here, loperamide-induced elevation in AQP3 and AQP9 were decreased by Arc treatment.…”

Activation of ASIC3/ERK pathway by paeoniflorin improves intestinal fluid metabolism and visceral sensitivity in slow transit constipated rats

“…For example, Painong San, a Chinese herbal compound for the treatment of colitis, increased the expression of MUC2 protein in the colon, 27 and P. lactiflora downregulated the expression level of AQP3 in the colon of constipated rats. 28 Our study also showed that PF significantly increased MUC2 protein expression and the number of colonic goblet cells and decreased AQP3 protein expression in CDiph-induced STC rats, thereby improving intestinal fluid metabolism disorders.…”

Baizhu‐Baishao herb pair ameliorates functional constipation and intestinal microflora disorder in rats

“…Previous studies have shown that BZBS can treat FC by regulating aquaporins. 18 In this study, we explored another underlying mechanism of BZBS on FC rats induced by diphenoxylate, and provide a more theoretical basis for the clinical treatment of FC by BZBS. University, Hangzhou, China).…”

“…At present, studies of the BZBS herb pair have focused on intestinal stress syndrome and less attention has been paid to FC. Previous studies have shown that BZBS can treat FC by regulating aquaporins 18 . In this study, we explored another underlying mechanism of BZBS on FC rats induced by diphenoxylate, and provide a more theoretical basis for the clinical treatment of FC by BZBS.…”