Citric Acid-Enriched Extract of RipePrunus mume(Siebold) Siebold & Zucc. Induces Laxative Effects by Regulating the Expression of Aquaporin 3 and Prostaglandin E₂in Rats with Loperamide-Induced Constipation

Abstract

Previously, we demonstrated that extracts of the ripe fruit (rPM) and unripe fruit (uPM) of Prunus mume (Siebold) Siebold & Zucc. and citric acid have a laxative effect, which is at least partially mediated by the increase in fecal parameters as seen in the low-fiber diet-induced constipation model rats. This study aims at investigating the laxative effects of citric acid-enriched aqueous extracts of rPM, uPM, and its active compounds, such as citric acid and malic acid, on loperamide-induced constipation rat models. Animal studies were conducted with loperamide-induced constipation animal models. The results showed that rPM and citric acid, the major organic acid compounds, significantly improved stool parameters (number, weight, and water content of the stools) generated in loperamide-induced constipation rats, without adverse effects of diarrhea. The gastrointestinal (GI) motility was activated fully in the rPM- and citric acid-treated rats than in rats treaded with loperamide alone. In addition, when rPM and citric acid were added to RAW264.7 cells and used to treat loperamide-induced constipation model rats, the secretion of prostaglandin E 2 (PGE 2 ) increased significantly in cells and tissue. Furthermore, rPM and citric acid decreased the expression of the aquaporin 3 (AQP3) in the rat colons. Our results demonstrated that rPM and citric acid, the major organic acid compound in rPM, can effectively promote defecation frequency and regulate PGE 2 secretion and AQP3 expression in the colon, providing scientific evidence to support the use of rPM as a therapeutic application.

Ligilactobacillus acidipiscis YJ5 modulates the gut microbiota and produces beneficial metabolites to relieve constipation by enhancing the mucosal barrier

“…Choi et al reported that vanillic acid could significantly enhance the amplitude and frequency of contractile responses of the isolated rat colon in vitro . 45 In Na et al 's study, 46 malic acid significantly increased the relief of Lop-induced constipation in rats and the secretion of mucin in the colon. Therefore, the effect of increasing goblet cells to secrete mucin of L. acidipiscis YJ5 in our study may be mainly related to its organic acid metabolites.…”

Evaluation of the Efficacy of Kombucha-Based Drink Enriched with Inulin and Vitamins for the Management of Constipation-Predominant Irritable Bowel Syndrome in Females: A Randomized Pilot Study

“…Although the kombucha drink used in our study underwent pasteurization during the production process [ 19 ], rendering it unable to function as a probiotic, we cannot rule out the potential additive positive effects of organic acids and other bioactive components present in the kombucha drink itself. Several experimental studies have demonstrated that acetic, lactic, malic or citric acids can regulate bowel movements through different mechanisms, including the increase of prostaglandin E 2 secretion and decreased expression of aquaporin 3 [ 31 , 32 ]. The kombucha drink we utilized in our study contains several organic acids (for example, acetic, malic, citric, lactic, and tartaric) in substantial amounts, which explains the relatively low pH value (3.57) of the drink [ 19 ].…”

Roles and regulation of Aquaporin-3 in maintaining the gut health: an updated review

“…It should be noted that the laxative effects of Maren pills ( Zhan et al, 2020 ) or Pekinenin C ( Yu et al, 2018 ) in alleviating constipation may be associated with the increased expression of AQP3 via nuclear factor κB (NF-κB) signal pathway. Moreover, a recent study reported that the citric acid-enriched extract of ripe Prunus mume (Siebold) effectively improved the symptoms of constipation without causing diarrhea and tolerance by regulating the expression of AQP3 and prostaglandin E2 in the rat colons ( Na et al, 2022 ).…”