A comprehensive review on rhubarb astringent/ laxative actions and the role of aquaporins as hub genes

Rhubarb, the rhizome and root of Rheum palmatum L. from the Polygonaceae family, is a globally important medicinal plant, especially in eastern Asia. It has been indicated for enteritis, gastritis, constipation, and diarrhea in Persian medicine. Several pharmacological investigations in previous decades have been conducted on anthraquinones of rhubarb responsible for diarrheagenic activities and rhubarb tannins initiating anti-diarrheagenic effects. Aloe-emodin, chrysophanol, emodin, physcion, rhein, and their glycosides are major rhubarb anthraquinones. Moreover, catechin, catechin gallate, catechin-glucopyranoside, gallic acid, galloyl glucose, carboxyl-chrysophanol-O- glucose, coumaroyl-O-galloyl-glucose, di-O-galloyl-glucose, glucopyranosyl-galloyl-glucose, and di-, tri-, tetra-, and pentamer of catechin units are major rhubarb tannins. In this paper, a review of relevant pharmacological studies on rhubarb tannins and anthraquinones published in PubMed and Scopus databases is performed. In addition, the hub genes and common targets of rhubarb anthraquinones and tannins were investigated using gene expression databases. Thirty common differentially expressed target genes were identified. According to the survey, the pharmacology of rhubarb is linked to aquaporin expression and maintained inflammatory responses in the intestinal environment, where anthraquinones and tannins play as positive and negative regulators. Furthermore, their opposing effects on intestinal motility, fluid absorption, and water/electrolyte secretion are explained. Anthraquinones inhibit the Na⁺/K⁺ATPase pump while stimulating cystic fibrosis transmembrane conductance regulator (CFTR) and Ca²⁺-activated Cl⁻ channels (CACC). Tannins reduce fluid secretion and smooth muscle contraction by inhibiting CACC and CFTR. This linkage opens new aspects for rhubarb pharmacology, its diarrheagenic/anti-diarrheagenic effects, and philosophical concepts of Hot and Cold temperaments in traditional medicine.