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.

Background: To confirm the metabolites of the Aconite and Cinnamon herb couple in rat, and characterize its pharmacokinetics.Methods: Microdialysis probes were inserted into the jugular vein and knee joint of Sprague Dawley rat, and dialysates of different administration groups were collected. Target analytes were separated on a hydrophilic interaction liquid chromatography column (ACQUITY UPLC BEH C8 2.1×100 mm, 1.7 μm) and analyzed with an ultra-performance liquid chromatography (UPLC) under multiple reaction monitoring modes.Results: The experiment shows that the concentrations of quality of the three metabolites in mixing extraction of the herb couple were 0.3701% for trans-cinnamic acid, 0.1249 % for mesaconitine, and 0.0469 % for hypoaconitine, and Cinnamon group was 0.1731 % for trans-cinnamic acid, Aconite group were 0.0017 % for mesaconitine, and 0.0300 % for hypoaconitine. The concentrations of quality of the metabolites in rat plasma of the herb couple group were 0.0028% for trans-cinnamic acid, 0.0947% for mesaconitine, and 0.1124% for hypoaconitine. And the concentrations of quality of Aconite group and Cinnamon group were 0.0019% for trans-cinnamic acid, 0.0307% for mesaconitine, and 0.0220% for hypoaconitine. Pharmacokinetic results showed that the mean half-lives of the microdialysis samples of blood of Cinnamon group was 492.18 min for trans-cinnamic acid, and Aconite group were 102.48 min for mesaconitine and 93.27 min for hypoaconitine, and the herb couple ware 181.36 min for trans-cinnamic acid, 103.9 min for mesaconitine and 116.01 min for hypoaconitine, and the microdialysis samples of joint of Cinnamon group was 190.85 min for trans-cinnamic acid, and Aconite group were 48.51 min for mesaconitine and 46.01 min for hypoaconitine, and the herb couple was 131.19 min for trans-cinnamic acid, 49.36 min for mesaconitine and 146.68 min for hypoaconitine.Conclusions: The mixed extraction of aconite and cinnamon can promote the dissolution of the active ingredients. The herb couple can promote the absorption of the active ingredients, improve the distribution of the active ingredients in the joint and blood, prolong the half-lives of the active ingredients. It shows that the compatibility of aconite and cinnamon can increase the bioavailability of the drug and improve the clinical efficacy.