Comparison of enteroprotective efficacy of triphala formulations (Indian Herbal Drug) on methotrexate‐induced small intestinal damage in rats

Abstract

Triphala is categorized as a rejuvenator and antioxidant-rich Ayurvedic herbal formulation and has traditionally been used in various gastric problems including intestinal inflammation. The aim of the present study was to examine the comparative enteroprotective effect of Triphala formulations against methotrexate-induced intestinal damage in rats. Triphala formulations were prepared by mixing equal (1:1:1) and unequal (1:2:4) proportions of Terminalia chebula Retz., Terminalia belerica (Gaertn.) Roxb. and Emblica officinalis Gaertn. Intestinal damage was induced by administering methotrexate (MTX) in a dose of 12 mg/kg, orally for 4 days to albino rats. The intestinal damage response was assessed by gross and microscopical injury, measuring the intestinal permeability to phenol red and tissue biochemical parameters. Triphala equal and unequal formulations at the dose of 540 mg/kg significantly restored the depleted protein level in brush border membrane of intestine, phospholipid and glutathione content and decreased the myeloperoxidase and xanthine oxidase level in intestinal mucosa of methotrexate-treated rats. In addition, Triphala unequal formulation showed significant decrease in permeation clearance of phenol red with significant attenuation in the histopathological changes, level of disaccharidase in brush border membrane vesicles and lipid peroxidation content of intestinal mucosa. Based on the data generated, it is suggested that Triphala unequal formulation provides significantly more protection than Triphala equal formulation against methotrexate-induced damage in rat intestine.

Effects of Polyphenols from Seed Shells of Japanese Horse Chestnut (Aesculus turbinata BLUME) on Methotrexate-Induced Intestinal Injury in Rats

“…Our results revealed that MTX induced severe morphological intestinal injury and increase in the level of lipid oxidation marker, MDA, and decrease in the levels of the antioxidant markers, GSH and GSH-Px, similarly to previous studies [12,16,25,29]. JHP supplementation ameliorated the MTX-induced morphological intestinal injury and preserved intestinal MDA, GSH and GSH-Px levels.…”

“…Previous studies suggested that lipid peroxidation was a contributing factor to the development of MTX-induced intestinal damage [12,16,25,29]. It has been reported that polyphenol extracted from apple [8,24], green tea [14,22] and rhizome of Curcuma longa [30] could diminish lipid peroxidation.…”

“…It was also demonstrated that MTX caused a significant reduction in antioxidant protein and enzyme levels and an increase in levels of oxidant markers such as malondialdehyde (MDA) [12,16,25,29]. Therefore, In order to minimize side-effects of MTX in patients, the studies focused on antioxidants [12,16,25,29,32].Many polyphenols are known to be antioxidants, and the possibility exists that they protect against oxidative damage by directly neutralizing reactive oxidants [8,14,21,22,24,30]. However, to our knowledge, there are no reports showing the protective effects of polyphenols from seed shells of Japanese horse chestnut (JHP) against oxidative stressrelated pathologic conditions in vivo.…”

“…It was also demonstrated that MTX caused a significant reduction in antioxidant protein and enzyme levels and an increase in levels of oxidant markers such as malondialdehyde (MDA) [12,16,25,29]. Therefore, In order to minimize side-effects of MTX in patients, the studies focused on antioxidants [12,16,25,29,32].…”

“…Glutathione S-transferase (GST) and GSH-Px are GSH-dependent antioxidant enzymes [23]. MTX treatment depletes intestinal GSH levels significantly [25,29,32]. The significant reduction in GSH levels promoted by MTX, represents an alteration in the cellular redox state, suggesting that cells could be more sensitive to ROS and thus lead to a reduction in the effectiveness of the antioxidant enzyme defense system [2].…”