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.

Investigation of HPLF-111624 in Modified Experimental Models of Ulcerative Proctitis and Anal Fissure in Rats.

Background: Although ulcerative proctitis (UP) and anal fissure (AF) are common anorectal diseases, there are no appropriate experimental models to screen the drugs intended for these conditions. In this context, existing experimental models mimicking these diseases were modified and the polyherbal formulation, HPLF-111624 was evaluated in these models. Objective: To establish animal model for UP and AF and to evaluate polyherbal formulation, HPLF-111624 in these disease models. Methods: An experimental model of UP was selected based on the modification of the ulcerative colitis model using different concentrations of acetic acid. The concentration used for induction were 2.5%, 5% and 10% v/v and different weights used to induce AF were 25 g, 50 g and 100 g, which were selected based on the severity of inflammation, fecal score, gross pathology, and histopathological evaluation. Furthermore, these animal models were used to evaluate the efficacy of HPLF-111624, a polyherbal formulation known to be beneficial in anal diseases. Results: Acetic acid at 5% produced typical pathological changes that resembled UP, with a significant increase in the fecal score, gross lesion, and histopathological changes. Similarly, among the three weights, physical injury with a 100 g weight produced significant changes in the histopathological score in the model of AF. Intervention with HPLF-111624 at doses of 250 and 500 mg/kg b.wt., showed a reduction in the inflammatory cytokines and a significant improvement in the histopathological findings in both the conditions. Conclusion: The results showed that the modified experimental models for UP and AF resemble the human pathological conditions and are simple, versatile and may be used for screening drugs intended for these conditions. Intervention with HPLF-111624 was found to be effective in improving the pathological state of UP and AF.

Pharmacological investigation of 'HIM-CHX': A herbal combination in the experimental muscle wasting condition.

Muscle wasting diseases are gradually increasing with the increase in global life expectancy. This study was designed to evaluate the efficacy of HIM-CHX, a herbal combination of Boswellia serrata, Cissus quadrangularis, and Withania somnifera, on Sarcopenia. The effects of HIM-CHX on parameters such as muscle mass, grip strength, motor coordination, gait, locomotor activity and endurance were measured in rats. In addition to this, inflammatory cytokines, myokine and growth hormone levels were also evaluated. In the first experiment, HIM-CHX was administered orally to rats at the dose of 125, 250, and 500 mg/kg body weight for 12 weeks. At the end of the treatment period, muscle mass, grip strength, motor coordination and proinflammatory cytokines were evaluated. In the second experiment, HIM-CHX was administered orally at a dose of 500 mg/kg body weight for 4 weeks and gait analysis, locomotor activity, endurance and endogenous antioxidant activity were evaluated. The animals treated with HIM-CHX showed a significant improvement in gastrocnemius muscle weight, carcass weight, gait, locomotor activity and endurance. HIM-CHX exerts its effect by reducing the levels of TNF-α, IL-6, and Myostatin while increasing the IGF-1 levels which are the typical biomarkers of muscle wasting. Furthermore, the study findings indicate that HIM-CHX has the potential to correct the pathophysiological changes associated with sarcopenia.

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.