Veeresh P. Veerapur

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.

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.

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.

Antidiabetic activity of Embelia ribes, embelin and its derivatives: A systematic review and meta-analysis.

Embelia ribes (ER) has been documented in Ayurveda for treating various diseases, including diabetes mellitus (DM). The present systematic review and meta-analysis evaluated the efficacy and safety of ER and its active bio-marker, embelin and its derivatives in the treatment of DM. Literature search was performed in PubMed/MEDLINE, EMBASE, Scopus, ScienceDirect, Scifinder, and Google Scholar. Using Review Manager, meta-analysis of ER/embelin/derivatives of embelin versus diabetic control was performed with inverse-variance model, providing mean differences (MDs) and 95% confidence intervals (CIs). Heterogeneity was determined by I2 statistic. A total of 13 studies were included in the systematic review and meta-analysis, and were conducted in experimental rats. ER and embelin significantly (P≤0.01) resorted blood glucose (MD, -231.30; CI, -256.79, -205.82; and MD, -154.70; CI, -168.65, -140.74) and glycosylated haemoglobin (MD, -6.36; CI, -8.33, -4.39; and MD,-4.68; CI, -7.76, -1.60), respectively. Meta-analysis findings also reported considerable restoration of insulin, lipid profile, haemodynamic parameters, serum and oxidative stress markers. The derivatives of embelin, 6-bromoembelin and vilangin, also improved diabetic condition. In addition, treatments also ameliorated body weight changes due to diabetes. The present systematic review and meta-analysis supports scientific evidence for the antidiabetic activity of ER/embelin/derivatives of embelin. However, further research is warranted in clinical trials to validate the present findings.

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

Antipsychotic activity of embelin isolated from Embelia ribes : A preliminary study

BACKGROUND Embelia ribes is claimed in Indian traditional medical practice to be useful in the treatment of nervous diseases. Embelin, an alkyl substituted hydroxy benzoquinone, is a major active constituent of E. ribes. The present preliminary study was intended to evaluate antipsychotic activity of embelin against apomorphine-induced climbing behaviour in mice and stereotyped behaviour in rats. METHODS Two doses of embelin (5 and 10mg/kg) were administered once daily for 15days before exposure to apomorphine. On the concluding day of pre-treatment, after apomorphine-injection, the rodents were assessed for climbing and stereotyped behaviours according to the published scoring system. Thereafter, neurotransmitters (dopamine, noradrenaline and serotonin) levels were estimated in rodent brains. RESULTS Embelin pre-treatment significantly inhibited apomorphine-induced climbing and stereotyped behaviours in mice and rats, respectively. Further, embelin also statistically reversed elevated levels of dopamine, noradrenaline and serotonin neurotransmitters in the brain of mice and rats. Embelin showed more significant results at high dose (10mg/kg) than low dose (5mg/kg) in both the tested models. CONCLUSION Considering the present pharmacological profile of embelin, it is suggested that embelin possesses antipsychotic activity in the treatment of psychotic disorders. However, further research is warranted for evaluating its exact mechanism of action.

Bioactive phenolic fraction of Citrus maxima abate lipopolysaccharide-induced sickness behaviour and anorexia in mice: In-silico molecular docking and dynamic studies of biomarkers against NF-κB

Sickness behaviour, fever, anxiety, anorexia and depression are interrelated phenomena. The citrus fruit peels offering significant low-cost nutritional dietary supplements due to its rejuvenating biological activities. The present study was undertaken to explore the beneficial effect of enriched phenolic fraction of peel (PFMC) in lipopolysaccharide (LPS)-induced sickness behaviour and anorexia in mice. Further, the HPTLC estimation of hesperidin, total phenolic and flavonoid content in PFMC were carried out. In silico molecular docking and dynamic studies of bioactive compounds against NF-κB (1NFK) were also performed. The amount of hesperidin was found to be 55.33 mg/g of PFCM as per the proposed HPTLC method. Total phenolic and flavonoid content was found to be 71 mg of gallic acid/g and 58.1 mg of quercetin/g of PFCM. The single dose of LPS (400 μg/kg, i.p) treatment exhibited significant reduction in food, water intake and behavioural tests and tissue GSH, whereas significantly higher levels of tissue LPO and plasma IL-6 levels compared to normal control. Pre-treatment of PFCM (100 and 200 mg/kg, i.p) and dexamethasone (1 mg/kg, i.p) showed significantly altered the LPS-induced behavioural, anorexia and biochemical parameters. The bioactive compounds such as hesperidin, naringenine, naringin and dexamethasone showed docking score of -22.49, -21.99, -16.43 and -11.12 respectively against NF-κB (1NFK). Among tested bioactive compounds, naringin clearly exhibited higher inhibiting property on target protein structure. The protective effect of PFCM in LPS-induced anorexia and sickness behaviour is due to its antioxidant, anti-inflammatory and appetizing activities, inhibiting IL-6 and NF-κB.