Oral glutamate intake reduces acute and chronic effects of ethanol in rodents

Purpose: To assess the effects of oral glutamate intake on acute motor effects and chronic intake of ethanol in rodents.Methods: The acute effects of ethanol on motor function were studied in ICR mice by giving 2 or 6 g/kg of ethanol 2 h after distilled water or 2.5 g/kg glutamate per os. Thirty minutes after ethanol treatment, behavioral assays, including rotarod tests and foot print analysis were monitored. In chronic ethanol treatment, male Wistar rats were trained to consume ethanol-sucrose solution during a 2-h period daily, starting with 2 % ethanol/10 % sucrose and gradually increasing to 10 % ethanol/5 % sucrose solution over 56 days. After training session, the drug treatment phase was done for 10 days. The animals were force-fed 50 mg/kg/day topiramate or 2.5 g/kg/day glutamate 2 h before ethanol treatment sessions. Each day, ethanol intake, water intake, food intake and body weight were recorded.Results: Mice that received 2 or 6 g/kg of ethanol orally, showed a significant  reduction in time on the rod in the rotarod test and a significant increase in both forelimb and hindlimb stride lengths when compared to control. Oral treatment with 2.5 g/kg of glutamate reversed the acute motor effects of ethanol. In chronic ethanol treatment, the intake of 10 % ethanol/5 % sucrose, accessible for 2 h, was significantly decreased in rats treated with either topiramate or glutamate.Conclusion: These results provide evidence that oral glutamate administration help to reduce the acute motor effects of ethanol in mice and ethanol intake in the chronic ethanol drinking rats.Keywords: Ethanol, Glutamate, Motor functions, Ethanol intake, Rodent

Identification and evaluation of agents isolated from traditionally used herbs against Ophiophagus hannah venom

The aim of this study was firstly to identify active molecules in herbs, that are traditionally used for the treatment of snake bite, such as Curcuma antinaia, Curcuma contravenenum, Andrographis paniculata, and Tanacetum parthenium; secondly to test similar structurally related molecules and finally to prepare and evaluate an efficient formulation against Ophiophagus hannah venom intoxification. Three labdane based compounds, including labdane dialdehyde, labdane lactone, and labdane trialdehyde and two lactones including 14-deoxy-11,12-didehydroandrographolide and parthenolide were isolated by column chromatography and characterised. Using the isolated rat phrenic nerve-hemidiaphragm preparation, the antagonistic effect of crude extracts, isolated compounds and prepared formulations were measured in vitro on the inhibition of the neuromuscular transmission. Inhibition on muscle contraction, produced by the 5 μg/mL venom, was reversed by test agents in organ bath preparations. A labdane trialdehyde, isolated from C. contravenenum, was identified as the best antagonising agent in the low micromolar range. Tests on formulations of the most potent C. contravenenum extract showed, that the suppository with witepsol H15 was an effective medicine against O. hannah venom. This study elucidated the active compounds, accounting for the antivenin activity of traditionally used herbs and suggested the most suitable formulation, which may help to develop potent medicines for the treatment of snake bite in the future

Protective Effects of Streblus asper

This study investigated the effects of Streblus asper leaf extract (SA) on reactive oxygen species (ROS) in SK-N-SH cell culture and on motor functions and behaviors in MPTP-treated C57BL/6 mice. SK-N-SH cell viability after incubation with SA for 24 h was measured by MTT assay. Intracellular ROS levels of SK-N-SH cells were quantified after pretreatment with SA (0, 200, 600, and 1000 µg/mL) in the presence of H2O2 (300 µM). Male C57BL/6 mice were force-fed with water or 200 mg/kg/day SA for 32 days. Intraperitoneal injection of MPTP was used to induce Parkinson’s disease-like symptoms. Catalepsy, beam balance ability, olfactory discrimination, social recognition, and spontaneous locomotor activity were assessed on days 19, 21, 23, 26, and 32, respectively. In cell culture, SA at 200, 600, and 1000 µg/mL significantly decreased ROS levels in H2O2-treated SK-N-SH cells. MPTP-treated C57BL/6 mice showed a significant change in all parameters tested when compared to the control group. Pretreatment and concurrent treatment with 200 mg/kg/day SA could antagonize the motor and cognitive function deficits induced by MPTP. The results show that SA possesses anti-Parkinson effects in MPTP-treated C57BL/6 mice and that reduction in ROS levels might be one of the mechanisms

LUEM PUA RICE EXTRACT ATTENUATES THE SEVERITY OF DEXTRAN SULFATE SODIUMINDUCED ULCERATIVE COLITIS IN RATS THROUGH CHOLINOMIMETIC EFFECTS

Objective: The objective of the study was to investigate the effect of aqueous extract of unpolished dark purple glutinous Thai rice variety Luem Pua(LP) in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in rat and the possible cholinomimetic effects of the extract.Methods: The effect of LP extract (0.5, 1, or 1.5 mg/ml final concentration) on ileum contraction was tested using isolated guinea pig ileum. Certainagonists (acetylcholine, tetramethylammonium, and clonidine) and antagonists (hexamethonium chloride and atropine) were studied to determinethe cholinomimetic effect of the extract. The effects of LP extract (5 g/kg/day) in DSS-induced UC model (drinking water was replaced with 3%DSS in water for 7 days) in rat were evaluated. On each day of treatment, the change of disease activity index (DAI) was recorded. At the end of theexperiments, rats were terminated and disease severity expressed as DAI, colon length, and spleen weight were determined.Results: LP extract at the concentration of 0.5, 1, and 1.5 mg/ml (final concentration) could contract the ileum in a dose-dependent manner and beblocked completely by atropine. Oral administration of LP extract could significantly attenuate the severity of DSS-induced UC as seen by the reductionof DAI, colon length, and spleen weight.Conclusion: Results in isolated guinea pig ileum suggest that LP might contain active substance that could activate muscarinic receptors. In additionto antioxidant activity, through activation of muscarinic receptor, might explain the protective effects of LP extract against DSS-induced UC in rats

Dark Purple Luem Pua rice extract reduces disease severity in rat models of inflammatory bowel disease

Purpose: To investigate the effects of an aqueous extract of unpolished dark purple glutinous Thai rice, variety Luem pua (LP), in two rat models of inflammatory bowel disease (IBD). Methods: Polyphenolic compounds content were determined by HPLC methods and antioxidant activities by DPPH and FRAP assays of the LP extract. The effect of the LP extract at 5 g/kg/day were evaluated in two rat models of IBD that included acetic acid and indomethacin induced IBD. On each day of treatment, changes of body weight, stool consistency and stool blood were scored and expressed as disease activity index (DAI). At the end of the experiments, the animals were euthanized. Colon length and spleen weight were determined, and the degree of inflammation of the colon was scored. Results: Rats in both models of IBD (acetic acid- and indomethacin-induced IBD), exhibited significant increases in DAI, macroscopic inflammation scores and spleen weights, while the lengths of colon were decreased. Pretreatment with LP extract attenuated the disease severity in both models as seen by the reverse of all observed altered parameters. Conclusion: These data suggest that LP extract might be beneficial in preventing and/or treating IBD. Keywords: Inflammatory bowel disease (IBD), Dark purple glutinous rice Var. Luem Pua, Acetic acid, Indomethaci

Antidepressant/Anxiolytic and Anti-Nociceptive Effects of Novel 2-Substituted 1,4-Benzodiazepine-2-ones

Oxazepam (4a) has been used as overall starting material in the synthesis of novel 2-substituted 1,4-benzodiazepines

CCK2–Gastrin Antagonist: Development of PNB-001 (4-Chloro- 5-Hydroxy-1-Phenylethyl-5-Phenyl-1, 5-Dihydro-Pyrrol-2-one) as Anti-Inflammatory Analgesic

Study aim: To prepare and evaluate CCK gastrin antagonists from readily available materials such as furfural and to focus on inflammatory pain management. Methods: Receptor binding assays, isolated tissue preparations and selected animal models were applied to evaluate the lead molecule PNB-001. Results: Arylated 5-hydroxy–pyrrol-2-ones were prepared in 3 synthetic steps from furfural and subsequently optimised as CCK2 selective ligands using radiolabelled binding assays. Originally a CCK1 selective lead structure was identified and from that lead, a potent and selective CCK2 ligand (PNB-001, IC50= 22 nM) was fully SAR optimised. The antagonism was confirmed for PNB-001 by using isolated tissue preparations with CCK5. Subsequent in vivo evaluation revealed analgesic activity for the gastrin CCK2 antagonist PNB-001, in the hotplate and tail immersion test at 0.5mg /kg by IP administration in mice. PNB-001 was superior in the formalin test to the morphine standard by oral administration and in the x-maze test the anxiolytic activity was greater in magnitude than diazepam. Conclusion: The front runner PNB-001 completed preclinical development and will enter clinical phase 1

Anti-inflammatory activity of the dietary supplement Houttuynia cordata fermentation product in RAW264.7 cells and Wistar rats.

Houttuynia cordata Thunb. has been used as a traditional medicine to treat a variety of ailments in Asian countries such as China, Japan, South Korea, and Thailand. In Thailand, H. cordata fermentation products (HCFPs) are commercially produced and popularly consumed throughout the country without experimental validation. Anti-inflammatory activity of H. cordata fresh leaves or aerial parts has previously been reported, however, the anti-inflammatory activity of the commercially available HCFPs produced by the industrialized process has not yet been investigated. The aim of this study was to evaluate in vitro and in vivo anti-inflammatory potential of the selected industrialized HCFP. LPS-induced RAW264.7 and carrageenan-induced paw edema models were used to evaluate the anti-inflammatory activity of HCFP. The phenolic acid components of HCFP aqueous and methanolic extracts were investigated using HPLC analysis. In RAW264.7 cells, the HCFP aqueous and methanolic extracts reduced NO production and suppressed LPS-stimulated expression of PGE2, iNOS, IL-1β, TNF-α and IL-6 levels in a concentration-dependent manner, however, less effect on COX-2 level was observed. In Wistar rats, 3.08 and 6.16 mL/kg HCFP reduced paw edema after 2 h carrageenan stimulation, suggesting the second phase anti-edematous effect similar to diclofenac (150 mg/kg). Whereas, 6.16 mL/kg HCFP also reduced paw edema after 1 h carrageenan stimulation, suggesting the first phase anti-edematous effect. Quantitative HPLC revealed the active phenolic compounds including syringic, vanillic, p-hydroxybenzoic and ferulic acids, which possess anti-inflammatory activity. Our results demonstrated for the first time the anti-inflammatory activity of the industrialized HCFP both in vitro and in vivo, thus validating its promising anti-inflammation potential