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 ACh-induced 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) of AniHBr was 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.
Wan et al. (Wed,) studied this question.