B.S. Thippeswamy

Protective effect of embelin against acetic acid induced ulcerative colitis in rats

The aim of the present study is to evaluate the effect of embelin isolated from Embelia ribes on acetic acid induced colitis in rats. Experimental animals received embelin (25 and 50 mg/kg, p.o.) and sulfasalazine (100mg/kg, p.o.) for five consecutive days before induction of colitis by intra-rectal acetic acid (3% v/v) administration and the treatment continued up to 7 days. The colonic mucosal injury was assessed by clinical, macroscopic, biochemical and histopathological examinations. Embelin treatment significantly decreased clinical activity score, gross lesion score, percent affected area and wet colon weight when compared to acetic acid induced controls. The treatment also reduced significantly the colonic myeloperoxidase activity, lipid peroxides and serum lactate dehydrogenase and significantly increased the reduced glutathione. The histopathological studies also confirmed the foregoing findings. The protective effect may be due to its antioxidant and anti-inflammatory activities.

Antidiabetic effect of Ficus racemosa Linn. stem bark in high-fat diet and low-dose streptozotocin-induced type 2 diabetic rats: a mechanistic study.

The present study was designed to investigate the effects of the ethanol extract of Ficus racemosa (FRE) on biochemical parameters in type 2-like diabetes, induced by a combination of standardised high-fat diet and low-dose streptozotocin (25mgkg(-1), i.p.) in rats. To elucidate the mode of action of FRE, its effects on a battery of targets involved in glucose homeostasis was evaluated. FRE (200 and 400mgkg(-1), p.o.), in a dose-dependent manner, altered the biochemical parameters and significantly improved glucose tolerance and HDL-c levels. In different bioassays, FRE showed inhibition of PTP-1B (IC50 12.1μg/mL) and DPP-IV (42.5%). FRE exhibited 82.6% binding to PPAR-γ. Furthermore FRE exhibited stimulation of glucose uptake by skeletal muscles (hemi-diaphragm). Bergenin was quantified in bioactive-FRE by high-performance liquid chromatography (0.15%w/w). This is the first report demonstrating the effectiveness of F. racemosa stem bark in type 2 diabetes and targets involved in it.

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.

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 Evans 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.

Effect of tramadol on behavioral alterations and lipid peroxidation after transient forebrain ischemia in rats

N-methyl-D-aspartate (NMDA) antagonists and γ-aminobutyric acid (GABA) agonists are proven protective in various animal models of ischemic brain damage. Tramadol, a centrally acting opioid analgesic reportedly possesses NMDA antagonistic and GABA agonistic properties, with additional ion channel blocking activity. The aim of the present study was to evaluate the possible neuroprotective effect of tramadol hydrochloride in a rat model of transient forebrain ischemia. Male Wistar rats were pretreated with tramadol hydrochloride at doses of 10 and 20 mg/kg b.w. intraperitoneally for 4 days and were subjected to 30 min occlusion of bilateral common carotid arteries followed by reperfusion for 24 h. Impairment in sensorimotor functions was evaluated by beam walking task, spontaneous locomotor activity and hanging wire test. Animals were sacrificed and the brain homogenates were used for estimating the levels of lipid peroxidation, a marker for extent of oxidative stress. Ischemic rats exhibited a significant decrease in locomotion, grip strength and increase in beam walking latency. Tramadol attenuated the post ischemic motor impairment evidenced by improvement in the performance in sensorimotor tests. The extent of lipid peroxidation was significantly (p < 0.001) reduced by tramadol pretreatment which was higher in ischemic control. This study demonstrates the neuroprotective effect of tramadol against transient forebrain ischemia in rats.

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 Huntingtons 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.

Protective effect of Calendula officinalis Linn. flowers against 3-nitropropionic acid induced experimental Huntington’s disease in rats

Abstract Oxidative stress (OS) and nitric oxide mechanisms have been recently proposed in 3-nitropropionic acid (3-NP)-induced neurotoxicity. The compounds, having antioxidant, anti-inflammatory and estrogenic effects, have been suggested for neuroprotection in different experimental models. Calendula officinalis Linn. flower extract (COE) is known for its potent antioxidant, anti-inflammatory, estrogenic and neuroprotective activities. Hence, the present study was designed to evaluate the neuroprotective effect of COE on 3-NP-induced neurotoxicity in rats by observing behavioral changes, OS and striatal damage in rat brain. Adult female Wistar rats were pretreated with vehicle or COE (100 and 200 mg/kg) for 7 days, followed by cotreatment with 3-NP (15 mg/kg, intraperitoneally) for the next 7 days. At the end of the treatment schedule, rats were evaluated for alterations in sensory motor functions and short-term memory. Animals were sacrificed and brain homogenates were used for the estimation of lipid peroxidation (LPO), glutathione, total thiols, glutathione S-transferase, catalase and nitrite. A set of brain slices was used for the evaluation of neuronal damage in the striatal region of the brain. 3-NP caused significant alterations in animal behavior, oxidative defense system evidenced by raised levels of LPO and nitrite concentration, and depletion of antioxidant levels. It also produced a loss of neuronal cells in the striatal region. Treatment with COE significantly attenuated behavioral alterations, oxidative damage and striatal neuronal loss in 3-NP-treated animals. The present study shows that COE is protective against 3-NP-induced neurotoxicity in rats. The antioxidant, anti-inflammatory and estrogenic properties of COE may be responsible for its neuroprotective action.

Sedative and antiepileptic effects of Anthocephalus cadamba Roxb. in mice and rats.

Objective: The aim of the present study was to evaluate the sedative and antiepileptic activities of ethanolic extract of Anthocephalus cadamba (ACE) bark in various experimental animal models. Materials and Methods: ACE was tested at three doses viz. 100, 200 and 400 mg/kg p.o. We used ketamine-induced sleeping time model to test the sedative property of the extract where, onset and duration of sleep were observed. A paradigm of anticonvulsant models (pentylenetetrazole, isoniazid and maximal electroshock-induced seizures) were used to evaluate its protective effect against absence and generalized types of seizures. Onset of clonic convulsions, tonic extension and time of death were observed in PTZ and INH-induced seizure models. In MES model, duration of tonic hind leg extension and onset of stupor were observed. Results: ACE showed significant increase in ketamine induced sleeping time. It also exhibited significant increase (P<0.05, 0.01 and 0.001) in latency to clonic convulsion, tonic extension and time of death in PTZ and INH models at all tested doses, whereas in the MES model, the lower dose was found to be effective when compared with the higher doses (200 and 400 mg/kg, p.o.). Conclusion: The results of the present investigation demonstrated that ACE possesses sedative and antiepileptic activities.

Piroxicam attenuates 3-nitropropionic acid-induced brain oxidative stress and behavioral alteration in mice.

Abstract 3-Nitropropionic acid (3-NP) is a fungal toxin that produces Huntington’s disease like symptoms in both animals and humans. Piroxicam, a non-selective cyclooxygenase (COX) inhibitor, used as anti-inflammatory agent and also known to decrease free oxygen radical production. In this study, the effect of piroxicam was evaluated against 3-NP-induced brain oxidative stress and behavioral alteration in mice. Adult male Swiss albino mice were injected with vehicle/piroxicam (10 and 20 mg/kg, i.p.) 30 min before 3-NP challenge (15 mg/kg, i.p.) regularly for 14 days. Body weights of the mice were measured on alternative days of the experiment. At the end of the treatment schedule, mice were evaluated for behavioral alterations (movement analysis, locomotor test, beam walking test and hanging wire test) and brain homogenates were used for the estimation of oxidative stress markers (lipid peroxidation, reduced glutathione and catalase). Administration of 3-NP significantly altered the behavioral activities and brain antioxidant status in mice. Piroxicam, at both the tested doses, caused a significant reversal of 3-NP-induced behavioral alterations and oxidative stress in mice. These findings suggest piroxicam protects the mice against 3-NP-induced brain oxidative stress and behavioral alteration. The antioxidant properties of piroxicam may be responsible for the observed beneficial actions.

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.