Ameliorative effect of chromium-d-phenylalanine complex on indomethacin-induced inflammatory bowel disease in rats.

Present study was designed to evaluate the effect of chromium-d-phenylalanine complex (Cr (d-phe)3) on indomethacin-induced inflammatory bowel disease (IBD) in rats. Adult Wistar rats were pretreated with vehicle/Cr (d-phe)3 (30, 60 and 90µg/kg, p.o.) for 11days. On day 8 and 9, after one h of the above mentioned treatment, indomethacin (7.5mg/kg/day,s.c.) was administered to induce IBD. On day 12, blood samples were collected from animals for lactate dehydrogenase (LDH) estimation and ileum was isolated for macroscopic scoring, biochemical estimation (lipid peroxidation, reduced glutathione and myeloperoxidase activity) and histopathological study. Administration of indomethacin significantly altered the serum LDH, macroscopic and microscopic appearance and biochemical parameters in ileum tissue. Cr (d-phe)3, at all the tested doses, caused a significant reversal of changes induced by indomethacin. Present study demonstrates the protective effect of Cr (d-phe)3 against indomethacin-induced IBD in rats. The observed protective effect might be attributed to the antioxidant and anti-inflammatory properties of Cr (d-phe)3.

Polyphenolic enriched extract of Cassia glauca Lamk, improves streptozotocin-induced type-1 diabetes linked with partial insulin resistance in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditionally Cassia glauca (CG) has been used to treat diabetes. AIM OF THE STUDY: The study was undertaken to evaluate anti-diabetic and antioxidant activity of polyphenolic enriched extract of CG in standardized streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS: The effect of ethanol (CGE) and water (CGW) extracts of CG (200 and 400mg/kg) treatment were evaluated in STZ (50mg/kg, iv) induced diabetic rats. On 10th day, oral glucose tolerance test and degree of insulin resistance was calculated. On 13th day, insulin tolerance test was performed to know the peripheral utilization of glucose. On 15th day, blood glucose, lipid profiles and endogenous antioxidant levels were estimated. In addition, the effects on oral glucose/sucrose tolerance test in normal rats. Further, HPLC fingerprinting profile of CGE and simultaneous quantification of biomarkers were carried out. RESULTS: Supplementation with CGE and CGW significantly reduced STZ-induced deleterious effects and improved glucose tolerance, and insulin tolerance. In addition, supplementation also decreased oxidative stress by improving endogenous antioxidant levels. Furthermore, administration significantly improves sucrose tolerance suggesting that extract possess inhibition of α-glucosidase enzyme. Further, HPLC studies revealed that CGE contains three bioactive polyphenolic compounds viz., rutin (0.10±0.01mg/g), luteolin-7-glucoside (0.06±0.01mg/g) and isorhoifolin (0.7±0.05mg/g). CONCLUSION: Observed beneficial outcome of CG might be attributed to the presence of polyphenolic compounds and mediated by interacting with multiple targets of diabetes and oxidative stress. Taken together, this study provided the scientific evidence for the traditional use of CG.

Effect of Embelin Against Lipopolysaccharide-induced Sickness Behaviour in Mice.

Sickness behaviour is a coordinated set of adaptive behavioural changes that develop in ill individuals during the course of an infection. It is relevant to understanding depression and some aspects of the suffering that in cancer. Embelin has been reported to possess antiinflammatory, neuroprotective and anxiolytic assets and has been shown to inhibit nuclear factor κB pathway and cytokine production. The present study was undertaken to investigate the effect of embelin isolated from Embelia ribes Burm in lipopolysaccharide (LPS)-induced sickness behaviour in mice. Adult male Swiss albino mice were pre-treated with embelin (10 and 20 mg/kg, p.o.) or dexamethasone (1 mg/kg, i.p.) for 3 days and then challenged with LPS (400 µg/kg, i.p.). At different time intervals of post-LPS challenge, sickness behaviour was evaluated in the animals by battery of behavioural tests (plus maze, open field, light-dark box, forced swim, social behaviour assessment, sucrose preference and food and water intake). Levels of oxidative stress makers (reduced glutathione and lipid peroxidation) in mice brain were also analysed. LPS induced behavioural alterations, anhedonia and anorexia, in mice. Pre-treatment with embelin attenuated behavioural changes induced by LPS. In addition, embelin prevented anhedonia, anorexia and ameliorated brain oxidative stress markers. The experimental outcomes of the present study demonstrated protective effect of embelin in LPS-induced sickness behaviour in mice. Copyright © 2016 John Wiley & Sons, Ltd.

Effect of embelin against 3-nitropropionic acid-induced Huntington's disease in rats.

3-Nitropropionic acid (3-NP) causes severe neurotoxicity in animals, which depicts Huntington's disease (HD) in humans. Embelin, the main active constituent of Embelia ribes, has been reported to possess various pharmacological actions, mainly anti-inflammatory, antioxidant, anticonvulsant and neuroprotective. The aim of the present study was to evaluate the neuroprotective effect of embelin against 3-NP induced experimental HD in rats. Adult Wistar rats were pretreated with vehicle/embelin (10 and 20mg/kg p.o.) for 7 days. From 8th day onwards, embelin was co-treated with 3-NP (15mg/kg, i.p.) for 7 days. At the end of the treatment schedule, animals were evaluated for behavioral alterations and brain homogenates were used for estimation of oxidative stress parameters (lipid peroxidation, reduced glutathione, catalase and glutathione-S-transferase). 2,3,5-Triphenyl tetrazolium chloride (TTC) stained brain slices were used for lesion size measurement. Administration of 3-NP significantly altered the behavioral and neuronal antioxidant status and caused significant neuronal damage in striatal region. Embelin, at both the tested doses, caused a significant reversal of behavioral and antioxidant status alterations and reversed the striatal neuronal damage induced by 3-NP. These findings suggest the neuroprotective effect of embelin against HD. The observed protective effect might be attributed to the antioxidant properties of embelin.

Immunomodulatory and antioxidant effect of Leptadenia reticulata leaf extract in rodents: possible modulation of cell and humoral immune response.

CONTEXT: Leptadenia reticulata Linn. (Asclpiadaceae) commonly known as "dodi," is an Indian medicinal plant which is known to have ethno-medical uses such as stimulant, tonic, immunostimulant and is one of the ingredient in ayurvedic formulation called as "Chawanprash," which is widely used in India to increase the strength of immune system. OBJECTIVE: The aim of present study is to evaluate immunomodulatory and antioxidant activity of ethanolic extract of L. reticulata L. leaves in rodents. METHODS: Haemagglutinating antibody (HA) titre, haematological profile (Hb, WBC, RBC), lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), delayed type of hypersensitivity (DTH) response, neutrophil adhesion test and carbon clearance assay were determined by in vivo experiments. RESULTS: The evaluation of immunomodulatory potential of L. reticulata (100, 200 mg/kg, p.o.) evoked a significant dose-dependent increase in antibody titre values; DTH reaction induced by SRBC and potentiated percentage neutrophil adhesion to nylon fibers as well as phagocytosis in carbon clearance assay. Also it caused significant increase in haematological profile, GSH, SOD, CAT activity and significantly decreased LPO levels in cyclophosphamide-induced immunosuppressed rats. CONCLUSION: The results obtained in this study indicate that L. reticulata possesses potential immunomodulatory and antioxidant activity and can play a major role in reducing the risk to develop immunodeficiency disorders.

Protective effect of hydroalcoholic extract of Mimusops elengi Linn. flowers against middle cerebral artery occlusion induced brain injury in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: In the traditional Indian and Thai system of medicine, Mimusops elengi Linn., flower is used as brain tonic and to calm anxiety and panic attacks. AIM OF THE STUDY: The present study was designed to investigate the neuroprotective effect of hydroalcoholic extract of Mimusops elengi (ME) against cerebral ischemic reperfusion injury in rats. MATERIALS AND METHODS: Male rats were pretreated with ME (100 and 200mg/kg) for seven days and focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) method. After 60min of MCAO and 24h of reperfusion, a battery of behavioral tests assessed the extent of neurological deficits. Infarct volume and brain edema were measured in TTC stained brain sections and the extent of blood brain barrier (BBB) disruption was observed by Evan's blue extravasation. Oxidative and nitrative stress parameters were estimated in the brain homogenates. Further, simultaneous quantification of five polyphenolic biomarkers were done using HPLC. RESULTS: Pretreatment with ME at doses of 100 and 200mg/kg significantly improved the neurobehavioral alterations and reduced the infarct volume, edema and extent of BBB disruption induced by ischemia reperfusion injury. It also prevented the alteration in the antioxidant status and reduced the nitrite levels when compared to ischemic animals. Further, HPLC studies revealed that ME contains five bioactive polyphenolic compounds. CONCLUSIONS: These results clearly indicate the neuroprotective effect of ME against stroke like injury. The observed protective effect might be attributed to the polyphenolic compounds and their antioxidant and anti-inflammatory property.

Restoration of brain antioxidant status by hydroalcoholic extract of Mimusops elengi flowers in rats treated with monosodium glutamate.

Monosodium glutamate (MSG) is commonly used as a flavor enhancer in many countries. However, overconsumption of MSG has been reported to produce detrimental effects on several organs. It mainly affects the normal physiology and function of the brain and causes severe oxidative stress. Mimusops elengi Linn. traditionally is used in many countries as a brain tonic and to calm anxiety and panic attacks. The effect of standardized hydroalcoholic extract of M. elengi flowers (ME) was evaluated against MSG-induced oxidative stress and excitotoxicity in Wistar rats. Excitotoxicity was induced by intraperitoneal administration of MSG (2 g/kg) for 7 days, and ME (100 and 200 mg/kg) was administered for 3 days before and for 7 days with administration of MSG. Animals were evaluated for locomotor activity, and brain homogenates were estimated for the levels of antioxidants and nitrite. In animals treated with MSG, pretreatment with ME improved ambulatory behavior, reduced lipid peroxidation and nitrite levels, and restored the enzymatic and nonenzymatic antioxidant (glutathione, total thiols, glutathione-S-transferase and catalase) status to near-normal levels; these were altered in the MSG control animals. Altogether, this investigation demonstrates the neuroprotective effect of ME against excitotoxicity and oxidative stress induced by MSG, and the observed protective effect might be attributed to the potential antioxidant property of ME.

Antidiabetic, antihyperlipidemic and antioxidant activities of methanolic extract of Amaranthus viridis Linn in alloxan induced diabetic rats.

The aim of this study was to investigate the antidiabetic, antihyperlipidemic and antioxidant activities of methanolic extract of whole plant of Amaranthus viridis (MEAV) in alloxan (ALX) induced diabetic rats. Diabetes was confirmed after 5 days of single intraperitoneal injection of ALX (140 mg/kg) in albino Wister rats. MEAV (200 and 400 mg/kg) and glibenclamide (10 mg/kg, p.o.) orally administered daily for 15 days, blood was withdrawn for glucose determination on 0, 1, 10 and 15 days respectively. On the 15th day, overnight fasted rats were sacrificed and blood was collected for the determination of high density lipoproteins cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), total cholesterol (TC), total glycerides (TG) and total proteins (TP). For in vivo antioxidant activity of MEAV, liver tissues were homogenized and the assay of lipid peroxidation and was measured as Malondialdehyde (MDA), glutathione (GSH), catalase (CAT) and total thiols (TT) were performed in control, ALX and MEAV treated rats. MEAV at doses of 200 and 400 mg/kg showed significant reduction is blood glucose, lipid profiles and significant improvement in MDA, GSH, CAT and TT when compared to diabetic control group. In vitro α-amylase inhibition activity of MEAV was also studied. We concluded that MEAV possess antidiabetic, antihyperlipidemic and antioxidant activities.

Modulation of the cyclooxygenase pathway via inhibition of nitric oxide production contributes to the anti-inflammatory activity of kaempferol.

Kaempferol has been reported to inhibit nitric oxide synthase and cyclooxygenase enzymes in animal models. The present study was designed to investigate whether kaempferol modulates the cyclooxygenase pathway via inhibition of nitric oxide production, which in turn contributes to its anti-inflammatory activity. Investigations were performed using carrageenan induced rat air pouch model. Inflammation was assessed by measurement of nitrites (nitrite, a breakdown product of nitric oxide), prostaglandin-E(2) levels and cellular infiltration in the pouch fluid exudates. To assess the anti-inflammatory effect of the extract, rat air pouch linings were examined histologically. The levels of nitrite and prostaglandin-E(2) in pouch fluid were measured by using Griess assay and ELISA respectively. Cell counts and differential counts were performed using a Coulter counter and Wright-Giemsa stain respectively. Kaempferol when administered orally at 50 and 100mg/kg dose showed significant inhibition of carrageenan induced production of nitrite (40.12 and 59.74%, respectively) and prostaglandin-E(2) generation (64.23 and 78.55%, respectively). Infiltration of the cells into the rat granuloma air pouch was also significantly inhibited by kaempferol. Modulation of cyclooxygenase pathway via inhibition of nitric oxide synthesis significantly contributes to kaempferol's anti-inflammatory activity. The present study characterizes the effects and mechanisms of naturally occurring phenolic flavonoid kaempferol, on inducible nitric oxide synthase expression and nitric oxide production. These results partially explain the pharmacological efficacy of flavonoids in general and kaempferol in particular as anti-inflammatory compounds.

Antidiabetic effect of Dodonaea viscosa (L). Lacq. aerial parts in high fructose-fed insulin resistant rats: a mechanism based study.

To study the effect and mode of action of water extract (DVW) and polar fraction of ethanol extract (DVE-4) of D. viscosa in high-fructose diet induced insulin resistance in male Wistar rats. D. viscosa's effects were evaluated on a battery of targets involved in glucose homeostasis (in vitro studies). Rats were rendered insulin resistant by feeding 66% (w/w) fructose and 1.1% (v/w) coconut oil mixed with normal pellet diet (NPD) for six weeks. DVW and DVE4 at different doses were administered simultaneously. At the end of the study, blood glucose, oral glucose tolerance test, lipid profile and insulin were estimated and homeostatic model assessment (HOMA) levels were calculated. In addition, enzymatic and nonenzymatic liver antioxidant levels were also estimated. Quantification of biomarker quercetin was done using HPLC. Fructose diet with DVW, DVE-4 significantly reduced blood glucose, serum insulin, HOMA, lipid profiles and significantly improved glucose tolerance and HDL-c levels. In addition, these extract and fraction also decreased oxidative stress by improving endogenous antioxidants. In different bioassays, DVW and DVE-4 inhibited protein tyrosine phosphatase-1B with IC50 65.8 and 54.9 microg/ml respectively and showed partial inhibition of dipeptidyl peptidase-IV. Moreover, DVW and DVE-4, at 10 microg/ml showed 60 and 54.2% binding to peroxisome proliferator-activated receptor-gamma. Further, 2.1% (w/w) of quercetin was quantified in bioactive-DVE-4 using HPLC method. The results provide pharmacological evidence of D. viscosa in treatment of prediabetic conditions and these effects may be mediated by interacting with multiple targets operating in diabetes mellitus.