Search

Ethnopharmacological Relevance: Colebrookea oppositifolia Smith is one of the extensively used plants to treat neurological conditions such as epilepsy by the various ethnic communities in sub-Himalayan regions of India such as Bhoxa, Tharu and nomadic Gujjars., Aim of the Study: This study was conducted to evaluate the cerebroprotective effect of C. oppositifolia methanolic root (MeCO) extract in Wistar rats., Materials and Methods: The MeCO was characterized for total phenolic content and later subjected for detailed liquid chromatography-mass spectrometry analysis. Further, it was evaluated for in vitro antioxidant activity using 2, 2-diphenyl-1-picrylhydrazyl, ferric reducing antioxidant power and oxygen radical absorbance capacity assays. In addition, the MeCO was investigated on generation of ROS, nitrite, and TNF-α in LPS-stimulated RAW 264.7 cell lines. Finally, the cerebroprotective effect of MeCO was examined against global ischemia and reperfusion (I/R)-induced brain injury in Wistar rats. Male Wistar rats were allocated in to five groups (G-I to G-V, n = 10). G-I and G-II served as sham control and I/R control, respectively, and received only vehicle (0.5% w/v carboxy methyl cellulose, 10 ml/kg, p.o.). G-III served as reference standard and received quercetin (20 mg/kg, p.o.). G-IV and G-V animals received 200 and 400 mg/kg oral doses of MeCO, respectively. All the treatments were given for a period of seven days and the parameters such as neurobehavioral (neurological, and cognitive), and motor functions, biochemical (enzymatic and non-enzymatic antioxidants, TNF-α, IL-6, IL-10, ICAM-I), morphological (cerebral edema and infarct area) and histopathological evaluations were performed., Results: The MeCO showed a total phenolic content of 137.28 mg gallic acid equivalents/g, and LC-MS/MS analysis of MeCO showed presence of acteoside, gossypin, quercetin and ferulic acid as major ingredients (6680.3, 1.55, 3.52 and 431.1 ng/mg). In in vitro antioxidant assays, the MeCO exhibited potent activity with IC 50 of 49.10 µg/ml in DPPH assay; FRAP and ORAC values of 1180.5 and 2983.5 respectively. Furthermore, the MeCO significantly inhibited generation of ROS, nitrite and TNF-α in LPS-stimulated RAW 264.7 cell lines. Sixty min of global ischemia with 24 h reperfusion produced substantial alterations in neurobehavioral functions in the I/R control group compared to sham control. In addition, a significant reduction in catalase and superoxide dismutase activities was observed. Moreover, lipid peroxidation increased and reduced glutathione levels decreased significantly. Furthermore, the levels of pro-inflammatory cytokines (TNF-α, IL-6, and ICAM-I) increased significantly and those of anti-inflammatory (IL-10) decreased. I/R insult increased the brain volume and aggravated cerebral infarct formation. Histopathological examination of the rat brain revealed vascular congestion, cerebral edema, leukocyte infiltration, and brain tissue necrosis. Interestingly, seven days pretreatment with MeCO (200 and 400 mg/kg) alleviated all the I/R-induced perturbances (neurobehavioral, and motor functions, biochemical, morphological and histopathological) compared with the I/R control., Conclusions: The MeCO exhibit potent cerebroprotective activity through its potent antioxidant and anti-inflammatory mechanisms, and hence may be useful in the management of ischemic stroke and associated complications., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: The present study was aimed to evaluate the anti-hyperlipidemic activity of newly synthesized tricyclic benzothieno 1, 2, 3-triazine derivatives namely CP-1 (3-(methyl)- 5,6,7,8-tetrahydro,3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4-one), CP-2 (3-(ethyl)- 5,6,7,8-tetrahydro,3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4-one) and CP-6 (3-(2-chloro phenyl)-5,6,7,8-tetrahydro,3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4-one) against dexamethasone and Triton WR-1339-induced hyper-lipidemia in rats., Methods: Anti-hyperlipidemic activity of the test compounds were evaluated against dexamethasone (10 mg/kg, subcutaneous [s.c.]) and Triton WR-1339 (200 mg/kg, intraperitoneal [i.p]) induced hyperlipidemia in rats., Results: Administration of single dose of Triton WR-1339 (200 mg/kg i.p) and dexamethasone (10 mg/kg s.c.) for 8 consecutive days to adult wistar rats caused severe hyperlipidemia characterized by marked increase in serum cholesterol, LDL-C, VLDL-C and triglyceride levels along with an increase in atherogenic index. Serum HDL-C levels were decreased significantly compared to normal control. Pretreatment with Atorvastatin (10 mg/kg, p.o.), CP-1 (25 and 50 mg/kg), CP-2 (25 and 50 mg/kg) and CP-6 (25 and 50 mg/kg) showed significant and dose-dependent protection against dexamethasone and Triton WR-1339-induced hyperlipidemia in rats by maintaining serum total cholesterol, LDL-C, VLDL-C and HDL-C levels within the normal range. Also, a significant decrease in atherogenic index was observed. The anti-hyperlipidemic effect of CP-6 was comparable with reference standard Atorvastatin. Furthermore, CP-6 was found to be more potent than CP-1 and CP-2., Conclusion: These findings suggest that CP-1, CP-2 and CP-6 possess significant anti-hyperlipidemic activity against experimental animal models of hyperlipidemia.

In the present study the antihistaminic activity of tricyclic benzothieno 1,2,3-triazine derivatives namely CP-3 (3-(phenyl)-5,6,7,8-tetrahydro,3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4-one), CP-5 (3-(3-methyl phenyl)-5,6,7,8-tetrahydro,3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4-one) and CP-8 (3-(4-chloro phenyl)-5,6,7,8-tetrahydro,3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4-one) were evaluated using in vitro (isolated guinea pig ileum) and in vivo (bronchodilator activity in guinea pigs) models and the sedative potential of the test compounds were evaluated using actophotometer in mice. In in vitro antihistaminic study, the CP-3, CP-5, CP-8 and chlorpheniramine maleate (CPM) have shown a rightward shift in concentration response curve (CRC) of histamine with a change in EC50 values of histamine in all the four tissue preparations. The slope obtained in the schild plot indicated that CP-5, CP-8 and CPM were competitive in nature for H1-receptors. However, CP-3 has shown non-competitive antagonism. In in vivo antihistaminic study, the CP-3, CP-5, CP-8 and CPM have shown mean increase in exposition time against histamine challenge compared to control group (p < 0.001). All the test drugs (10 mg/kg) and CPM (2 mg/kg) have offered a significant (p < 0.001) protection against preconvulsive dyspnoea (PCD) compared to control. In conclusion, all the test drugs have shown very good antihistaminic activity and the test drugs have very little sedative action compared to CPM.

Objective: To evaluate antidiarrheal activity of the fractions of aqueous extract from stem barks of Thespesia populnea (Malvaceae)., Methods: From the aqueous extract three fractions namely ethyl acetate fraction (EAF), methanolic fraction (MF) and residue fraction (RF) were made and studied for antidiarrheal activity. Antidiarrheal activity of the fractions were evaluated in castor oil induced diarrhea, prostaglandin E(2) (PG-E(2)) induced diarrhea and charcoal meal test as in vivo models and the most potent fraction was further evaluated with in vitro models to determine the possible antimotility effect., Results: In castor oil induced diarrhea model, the RF (10, 25, 50 and 100 mg/kg, po.) and MF (100 mg/kg, po.) has significantly reduced the cumulative wet faecal mass, where as the EAF have not shown any significant antidiarrheal activity, RF was found to be more potent than MF. Based on these results and percentage yield, only RF was evaluated in PG-E(2) induced enteropooling and charcoal meal test. RF (10, 25 and 50 mg/kg) had shown significant inhibition of PG-E(2) induced secretions (antisecretory) and decreased the movement of charcoal in charcoal meal test indicating its antimotility activity. Furthermore, RF has showed significant inhibition of acetylcholine, histamine and BaCl(2) induced contractions on rat colon, guinea pig ileum and rabbit jejunum with EC(50) values of 241.7, 303.1 and 286.1 μg/mL, respectively indicating the antimotility effect of RF. The phytochemical analysis of RF showed presence of gums and mucilages and the possible mechanism may be the combination inhibition of elevated prostaglandin biosynthesis and reduced propulsive movement of the intestine., Conclusions: RF possesses good antidiarrheal activity comparing with other two fractions and the possible mechanism thought to be associated with combination of antisecretory and antimolity., (Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.)