Identification of the multiple bioactive derivatives and their endogenous molecular targets that may mediate the laxative effect of rhubarb in rats

Author: Xie, Ying, Ganqa Luo, Zhou, Jiayan Miao, Tang, Qin, Guan, Xiaoyan

Doi: 10.63059/ctmj.2024.v7.i01.pp1-13

Abstract:

The goal of this study is to use a bioinformatics and in vivo method to figure out how rhubarb (Rheum tanguticum Maxim. ex Balf.) causes rats to go to the toilet more often. Methods: Using high-performance liquid chromatography in conjunction with linear ion-trap quadrupole Orbitrap high-resolution mass spectrometry, substances originating from rhubarb that were found in the colorectum were identified. Using databases and the literature, we identified targets with the potential to have laxative effects. Then, we employed compounds derived from rhubarb in molecular docking modelling. Then, using western blotting, we assessed the expression of potential endogenous target molecules that bind specific rhubarb components in rats that were either given or not given rhubarb for constipation. In the end, the components of compounds that showed promise as bioactive were identified We found 17 anthraquinones and 21 anthrones in the rat colorectum, which is a good indicator of the plant's medicinal value. Based on G-scoring, three proteins—c-kit, 5-hydroxytryptamine receptor 4 (5- HT4), and aquaporin-3 (AQP3)—may mediate the laxative action. Furthermore, ten components derived from rhubarb—aloe-emodin, emodin, rhein, chrysophanol, physcion, sennoside A, sennoside C, physcionanthrone, aloe-emodinanthrone, and rheinanthrone—were chosen as compounds with high probability of activity due to their strong binding affinity for multiple potential targets. It is possible that the laxative action of rhubarb extract is mediated by the fact that it enhanced the expression of c-kit and 5-HT4 while decreasing the expression of AQP3 in the colon of rats that were constipated. Additionally, we discovered that a single prototype component may undergo metabolism into many active metabolites, and that different molecules from the prototype can be combined to form a single active ingredient.The current research concludes that rhubarb's anthraquinones and anthrones may be metabolised into bioactive chemicals that enhance defecation via c-kit, 5-HT4, and/or AQP3.

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