Ferulic acid ameliorates TNBS-induced ulcerative colitis through modulation of cytokines, oxidative stress, iNOs, COX-2, and apoptosis in laboratory rats

Ulcerative colitis (UC) is a chronic immune-inflammatory disorder characterized by oxido-nitrosative stress, the release of pro-inflammatory cytokines and apoptosis. Ferulic acid (FA), a phenolic compound is considered to possess potent antioxidant, anti-apoptotic and anti-inflammatory activities. The aim is to evaluate possible mechanism of action of FA against trinitrobenzensulfonic acid (TNBS) induced ulcerative colitis (UC) in rats. UC was induced in Sprague-Dawley rats (150-200 g) by intrarectal administration of TNBS (100 mg/kg). FA was administered (10, 20 and 40 mg/kg, p.o.) for 14 days after colitis was induced. Various biochemical, molecular and histological changes were assessed in the colon. Intrarectal administration of TNBS caused significant induction of ulcer in the colon with an elevation of oxido-nitrosative stress, myeloperoxidase and hydroxyproline activity in the colon. Administration of FA (20 and 40 mg/kg) significantly decrease oxido-nitrosative stress, myelope¬roxidase, and hydroxyproline activities. Up-regulated mRNA expression of TNF-α, IL-1β, IL-6, COX-2, and iNOs, as well as down-regulated IL-10 mRNA expressions after TNBS administration, were significantly inhibited by FA (20 and 40 mg/kg) treatment. Flow cytometric analysis revealed that intrarectal administration of TNBS-induced significantly enhanced the colonic apoptosis whereas administration of FA (20 and 40 mg/kg) significantly restored the elevated apoptosis. FA administration also significantly restored the histopathological aberration induced by TNBS. The findings of the present study demonstrated that FA ameliorates TNBS-induced colitis via inhibition of oxido-nitrosative stress, apoptosis, proinflammatory cytokines production, and down- regulation of COX-2 synthesis

Anticonvulsant Activity of Argyreia speciosa in Mice

Argyreia speciosa commonly known as Vridha daraka in Sanskrit is one of the important plants used in indigenous system of medicine. The root is regarded as an alternative tonic and useful in the diseases of nervous system. To confirm the veracity of aforementioned claim, we have evaluated the anticonvulsant effect of the extract. In this investigation, the mice were pretreated with different doses of Argyreia speciosa extract (100, 200, 400 mg/kg) for 10 days and then, they were subjected to either pentylenetetrazole (80 mg/kg) or maximal electroshock seizures (50 mA, 0.2 s) treatment. The hydroalcoholic extract of Argyreia speciosa at the dose of 200 and 400 mg/kg significantly delayed the latency to the onset of first clonus as well as onset of death in unprotected mice and exhibited protection in 16.66% and 33.33% of pentylenetetrazole treated mice respectively. Whereas in case of maximal electroshock-seizures, the dose of 200 and 400 mg/kg significantly reduced the duration of hind limb extension and both the doses were statistically found to be equipotent. The reference standards, clonazepam (0.1 mg/kg) and phenytoin (20 mg/kg) provided complete protection. Thus, present study revealed anticonvulsant effect of Argyreia speciosa against pentylenetetrazole- and maximal electroshock-induced convulsions in mice

Evaluation of aqueous leaves extract of <i style="">Moringa oleifera</i> Linn for wound healing in albino rats

898-901Aqueous extract of leaves of M. oleifera was investigated and rationalised for its wound healing activity. The aqueous extract was studied at dose level of 300 mg/kg body weight using resutured incision; excision and dead space wound models in rats. Significant increase in wound closure rate, skin-breaking strength, granuloma breaking strength, hydroxyproline content, granuloma dry weight and decrease in scar area was observed. The prohealing actions seem to be due to increased collagen deposition as well as better alignment and maturation. From the results obtained, it may be concluded that the aqueous extract of M. oleifera has significant wound healing property

7-[(4-Substituted phenyl-piperazin-1-yl)-alkoxyl]-4-methylchromene-2-ones as potential atypical antipsychotics: Synthesis and pharmacological evaluation

2295-23007-Hydroxy-4-methylchromene-2-one 1 when reacted respectively with 2-bromo-1-chloroethane and 3-bromo-1-chloropropane in acetonitrile and in the presence of anhydrous K2CO3 yields 7-alkoxy-4-methylchromene-2-ones 2a,b. Compounds 2a,b when refluxed with various arylpiperazines in toluene and in the presence of triethylamine yield the title compounds, 7-[(4-substituted phenyl-piperazin-1-yl)-alkoxyl]-4-methylchromen-2-ones 3a-j.Their atypical antipsychotic activity have been evaluated by their ability to inhibit apomorphine induced climbing behavior (D2 antagonism) and to inhibit the 5–HTP induced head twitches in albino mice (5-HT2A antagonism) alongwith catalepsy studies. All the compounds inhibit apomorphine induced climbing behavior and 5-HTP induced head twitches. The SAR studies reveal that methyl group in the phenyl ring of piperazine and the chain length (n=3) gives more dopaminergic and serotonergic antagonistic activity, while dichlorophenyl piperazines have less dopaminergic and serotonergic antagonistic activity. 3f and 3g have been found to have significant atypical behaviour

Research Letter - Antihypertensive effect of newly synthesized acyl amino substituted propanolamine derivatives, DPJ 890 and DPJ 955 in rats

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Synthesis, -adrenergic receptor binding and antihypertensive potential of vanillin-derived phenoxypropanolamines

903-909Synthesis of vanillin-derived phenoxypropanolamines is carried out by condensing 4-hydroxy-3-methoxybenzaldehyde (vanillin) 1 with epichlorohydrin, followed by treatment with iso-propylamine or tert-butylamine to open the epoxy ring. Percentage inhibition of [³H]dihydroalprenolol binding to both β₁⁻ and β₂⁻adrenergic receptors by the newly synthesized compounds is assessed in vitro using turkey erythrocyte membrane (β₁) and lung homogenate of rats (β₂). Formyl derivatives 8 and 9 showed maximum inhibitory effect in binding assay and are non-selective similar to propranolol. On the other-hand, aldoxime compounds 10 and 11 have preference for 1-adrenergic receptors similar to atenolol. Also four of the compounds 8-11 are evaluated for their anti-hypertensive potential, in left renal artery ligation and fructose induced hypertension models. 4-(3-tert-Butylamino-2-hydroxy-propoxy)-3-methoxy-benzaldehyde oxime 11 shows antihypertensive effect better than propranolol

Evaluation of the bioavailability of major withanolides of Withania somnifera using an in vitro absorption model system

Withania somnifera (L.) Dunal, shows several pharmacological properties which are attributed mainly to the withanolides present in the root. The efficacy of medicinally active withanolides constituents depends on the absorption and transportation through the intestinal epithelium. We examined these characteristics by employing the Sino-Veda Madin-Darby canine kidney cells culture system, which under in vitro condition shows the absorption characteristics similar to the human intestinal epithelium. Thus, the aim of the present investigation was to assess the bioavailability of individual withanolides. Withanolides were diluted in Hank′s buffered saline at a concentration of 2 μg/ml were tested for permeability studies carried out for 1 h duration. Permeability was measured in terms of efflux pump (Peff ) in cm/s. Peff values of withanolide A (WN A), withanone (WNN), 1,2-deoxywithastramonolide (1,2 DWM), withanolide B (WN B), withanoside IV-V (WS IV-V), and withaferin A were 4.05 × 10−5 , 2.06 × 10−5 , 1.97 × 10−5 , 1.80 × 10−5 , 3.19 × 10−6 , 3.03 × 10−6 and 3.30 × 10−7 respectively. In conclusion, the nonpolar and low molecular weight compounds (WN A, WNN, 1,2 DWM, and WN B) were highly permeable. As against this, the glycosylated and polar WS IV and WS V showed low permeability. Surprisingly and paradoxically, the highly biologically active withaferin A was completely impermeable, suggesting that further studies possibly using human epithelial colorectal adenocarcinoma (Caco-2) cells may be needed to delineate the absorption characteristics of withanolides, especially withaferin A