Effects of Diacerein on Indomethacin-Induced Gastric Ulceration

Abstract

We investigated the effect of diacerein, an antiosteoarthritic agent, and its metabolite, rhein, on the production of reactive oxygen species (ROS) from neutrophils as well as the protective effect of diacerein on indomethacin-induced gastric ulceration and its protection mechanism. Rhein inhibited the ROS production from N-formyl-methionyl-leucyl-phenylalanine or phorbol-12-myristate-13-acetate-activated human peripheral neutrophils. Indomethacin-induced gastric ulceration was significantly inhibited by oxygen radical scavengers and 16,16-dimethyl-prostaglandin E₂ (dmPGE₂) but not by allopurinol. Diacerein inhibited indomethacin-induced gastric ulceration in a dose-dependent manner. Diacerein did not affect the gastric mucosal PGE₂ content. In addition, diacerein inhibited HCl + ethanol-induced gastric ulceration. These data indicate that the inhibitory effect of diacerein on indomethacin-induced gastric ulceration could be mediated not by the augmentation of gastric mucosal PGE₂ production but by the suppression of ROS production based on its inhibition of neutrophil activation.

Protective Effect of Ascorbic Acid and Ranitidine on the Indomethacin Induced Gastric Injury in Adult Albino Rats; Light and Electron Microscopy

“…These finding were in agreement with [18] who postulated that, indomethacin's ability to cause cell damage may be related in part to its accumulation in these cells because of the phenomenon of ion trapping. Moreover, [19] suggested that, NSAIDs-induced impairment of the tight junction complex morphology and permeability between viable gastric mucosal epithelial cells may be a major contributing factor in the etiology of stomach disorder.…”

A comparative pharmacokinetic study of three flavonoids and three anthraquinones in normal and gastrointestinal motility disorders rat plasma after the oral administration of Wei‐Chang‐Shu tablet using high‐performance liquid chromatography–tandem mass spectrometry

“…and Citrus aurantium L. Modern pharmacological research has demonstrated that WCST exerts a therapeutic effect by up‐regulating nitric oxide and acetylcholine (Li, Liu, & Liu, ), increasing the Ca 2+ level in gastrointestinal smooth muscle cells (Song et al, ) and increasing motilin, substance P and somatostatin in plasma (Guo, Liu, Wang, & Sun, ). In the early literature, related studies found that flavonoids (liquiritigenin, isoliquiritigenin and formononetin) and anthraquinones (emodin, rhein and aloe‐emodin) are the major effective constituents of corresponding individual herbs, and all of them have significant pharmacological activity, especially against Helicobacter pylori , gastric and duodenal ulcers, and spasmolysis (Goel, Das Gupta, Ram, & Pandey, ; Choi, Kim, Chae, & Chin, ; Chen et al, ; Wang & Chung, , Wang, Chung, Ho, Wu, & Chang, ; Chung et al, ; Tamura, Yokoyama, & Ohmori, ; Kakegawa, Matsumoto, & Satoh, ). Therefore, these six compounds are considered to be the main bioactive components of WCST based on their pharmacological activities.…”

Antitumor activity of rhein lysinate against human glioma U87 cells in vitro and in vivo

“…Rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid) is a natural product derived from the rhizome of rhubarb which has been used medicinally in China for more than 1,000 years (7). Rhein possesses diverse biological properties such as antioxidant (8)(9)(10), anti-inflammatory (11,12), antiviral (13), antibacterial (14), antifungal (15), antiallergic (16) and anticancer (17)(18)(19)(20)(21)(22)(23)(24). The reported mechanism of the antitumor activity of rhein in cancer cells is due to its ability to induce apoptosis and/or cell cycle arrest in corresponding cancer cells (20,21).…”