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The Inhibitory Effect of Anisodamine Hydrobromide Against Contraction of Intestinal Smooth Muscles Induced by Acetylcholine, With Its Pharmacokinetics and Mechanism Investigation
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DOI：10.1177/1934578X261449324.png)
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Abstract
En 中文
Objective: To investigate the inhibitory effects of Anisodamine hydrobromide (AniHBr) on acetylcholine (ACh)-induced contractions and pharmacodynamics, and the potential mechanism. Methods: The inhibitory effect of AniHBr on AChinduced contraction of isolated rat and rabbit intestinal smooth muscles (n=10) was studied. The average strain was measured by a multiple physiological signal acquisition and processing system equipped with a muscle tension sensor. The plasma drug concentrations in Beagle dogs were detected using liquid chromatography-tandem mass spectrometry (LC-MS/ MS) to investigate the AniHbr pharmacokinetic profile. Based on network pharmacology, qRT-PCR and Western blot experiment used to detect the expression changes of key factors in IM-R069 cells. Results: Results showed that AniHBr significantly inhibited the Ach-induced contraction of rat and rabbit intestinal smooth muscles, reduced the average strain. A peak plasma concentration (C-max, 51.01 +/- 37.99 ng/mL) ofAniHBrwas observed within 0.72h post-dose. Moreover, the mean elimination half-life of AniHBr was 1.02 +/- 0.19 h. Network pharmacology analysis identified 148 key targets of AniHBr associated with gastrointestinal diseases. qRT-PCR and Western blot experiment showed 20 ug/mL AniHBr significantly increased the mRNA expression of EFGR and STAT3, and suppressed PI3K-AKT signaling pathway. Conclusions: AniHBr effectively inhibits Ach-induced contraction of isolated rat and rabbit intestinal smooth muscles, might be through regulating EFGR, STAT3 and PI3K-AKT signaling pathway.
Keywords:
anisodamine hydrobromide
bioavailability
pharmacodynamics
smooth muscle
PI3K-AKT signaling pathway
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