Neuroprotective effect of herbal extracts inhibiting soluble epoxide hydrolase (sEH) and cyclooxygenase (COX) against chemotherapy-induced cognitive impairment in mice.

Chemotherapy-induced cognitive impairment (CICI) is a novel clinical condition characterized by memory, learning, and motor function deficits. Oxidative stress and inflammation are potential factors contributing to chemotherapy's adverse effects on the brain. Inhibition of soluble epoxide hydrolase (sEH) has been proven effective in neuroinflammation and reversal of memory impairment. The research aims to evaluate the memory protective effect of sEH inhibitor and dual inhibitor of sEH and COX and compare its impact with herbal extracts with known nootropic activity in an animal model of CICI. In vitro sEH, the inhibitory activity of hydroalcoholic extracts of Sizygium aromaticum, Nigella sativa, and Mesua ferrea was tested on murine and human sEH enzyme as per the protocol, and IC50 was determined. Cyclophosphamide (50 mg/kg), methotrexate (5 mg/kg), and fluorouracil (5 mg/kg) combination (CMF) were administered intraperitoneally to induce CICI. The known herbal sEH inhibitor, Lepidium meyenii and the dual inhibitor of COX and sEH (PTUPB) were tested for their protective effect in the CICI model. The herbal formulation with known nootropic activity viz Bacopa monnieri and commercial formulation (Mentat) were also used to compare the efficacy in the CICI model. Behavioral parameter such as cognitive function was assessed by Morris Water Maze besides investigating oxidative stress (GSH and LPO) and inflammatory (TNFα, IL-6, BDNF and COX-2) markers in the brain. CMF-induced CICI, which was associated with increased oxidative stress and inflammation in the brain. However, treatment with PTUPB or herbal extracts inhibiting sEH preserved spatial memory via ameliorating oxidative stress and inflammation. S. aromaticum and N. sativa inhibited COX2, but M. Ferrea did not affect COX2 activity. Lepidium meyenii was the least effective, and mentat showed superior activity over Bacopa monnieri in preserving memory. Compared to untreated animals, the mice treated with PTUPB or hydroalcoholic extracts showed a discernible improvement in cognitive function in CICI.

Herbal Combination 'HAGE-101912' Ameliorates Gastroesophageal Reflux Disease in Rats.

Background: Gastroesophageal reflux disease (GERD) is a chronic, relapsing disorder. In this era of modern and fast-track lifestyle and food habits, the incidence of GERD is rapidly increasing. Currently, proton pump inhibitors (PPIs) are the primary choice of treatment. However, the associated side effects and a high relapse rate give rise to the need to explore alternative therapies. Objective: The study aimed to evaluate HAGE-101912, an herbal combination, in different experimental models of GERD. Methods: Antacid activity was assessed based on H+/K+ATPase inhibitory activity of parietal cells using artificial gastric juice. Tonic contraction of the lower esophageal sphincter (LES) was evaluated using an AD Instrument. A GERD model of the pylorus and fundus ligation (preventive and curative models) in rats was selected to assess the efficacy of HAGE-101912 at a dose of 250 mg/kg body weight, and various parameters such as the gastric pH, gastric volume, total acidity, gross esophageal ulcer index, and histopathological changes were evaluated. The prokinetic activity was assessed using the phenol red method. Results: HAGE-101912 increased the acid-neutralizing capacity (P < 0.001), decreased H+/K+ATPase activity (P < 0.01), and increased the contraction of the LES. In the preventive model, HAGE-101912 significantly reduced the gastric acid volume (P < 0.01), total acidity (P < 0.001), and gross esophageal ulcer index (P < 0.01); increased the gastric acid pH (P < 0.01); and protected the esophageal epithelium. In addition, HAGE-101912 increased gastric emptying and gastrointestinal transit through its prokinetic activity (P < 0.05). Conclusion: HAGE-101912 has a beneficial effect in GERD as it effectively inhibits the H+/K+ATPase, increases the gastric pH, restores the LES function, protects the esophageal epithelium, and increases gastric emptying and transit.

Turmeric based oral rinse "HTOR-091516" ameliorates experimental oral mucositis.

BACKGROUND: Prevalence and incidence of oral mucositis (OM) are rigorously increasing and there is no effective treatment. The herbal formulation "HTOR-091516" containing Curcuma longa, Triphala and honey were evaluated for the treatment of OM. AIM: The aim of this study was to evaluate the safety and efficacy of HTOR-091516, employing cellular model, human gingival fibroblasts-1 (HGF-1), and 5-fluorouracil (5-FU)-induced mucositis model in rats. MATERIALS AND METHODS: The cell viability was assessed using 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay and the inhibitory effect of HTOR-091516 on tumor necrosis factor-alpha (TNF-α) was evaluated using TNF-α bioassay in lipopolysaccharides-induced HGF-1. 5-FU and glacial acetic acid were used to induce OM in rats. Animals were divided into two groups, group 1 served as mucositis control and group 2 was treated with HTOR-091516 at the dose of 200 µl and TNF-α was estimated in plasma samples. RESULTS: The in vitro safety of HTOR-091516 was evaluated in reconstructed human oral epidermis and was found to be nontoxic and exhibited concentration-dependent TNF-α inhibition in HGF-1. The treatment with HTOR-091516 reduced mucositis scores and mortality rate and also decreased the plasma TNF-α level. CONCLUSION: The present data indicate that HTOR-091516 is effective in the treatment of OM.