Study on the Effect and Mechanism of Weichang'an Pill and Its Extract on Slow Transit Constipation

ABSTRACT Background Weichang'an pill (WCA) possesses potential advantages in promoting gastrointestinal motility and treating constipation. Ethanol extract (EE) and aqueous extract (AE) of WCA were used to investigate its efficacy in treating slow transit constipation (STC) and the material basis for exerting this effect. Methods The STC model was established in vivo by gavage of loperamide (Lop) in Sprague–Dawley rats, followed by gavage of WCA, EE, and AE. In vitro, norepinephrine (NE) was used to stimulate isolated ileal smooth muscle of rats to imitate the state of insufficient gastrointestinal motility during STC, and a model of excessive relaxation of isolated ileal smooth muscle was established. This model was used to observe and record the changes in contraction tension, amplitude, and frequency of ileal smooth muscle after treatment with WCA, EE, AE, and the active ingredients of WCA. Key Results In vivo, WCA, EE, and AE treatment increased fecal parameters, improved gastrointestinal transit time, and alleviated pathological damage to the colon in STC rats. Its mechanism might be closely related to c‐kit/SCF, RhoA/ROCK/MYPT1/MLC signaling pathways. In vitro, WCA, EE, AE, and the active ingredients of WCA, including costunolide (Cos), dehydrocostus lactone (Deh), agarotetrol (Aga), muscone (Mus), gallic acid (GA), oleic acid (Oleic), linoleic acid (Lin), umbelliferone (Umb), synephrine (Syn), ferulic acid (FA), chlorogenic acid (ChA), betaine (Bet), and riboflavin (Rib), significantly inhibited the NE‐induced excessive relaxation of ileal smooth muscles. Conclusions WCA, EE, and AE significantly improved constipation in STC rats. Moreover, the active ingredients in WCA, including Cos, Deh, Aga, Mus, GA, Oleic, Lin, Umb, Syn, FA, ChA, Bet, and Rib, might be the material basis for promoting intestinal motility.