ANTIDEPRESSANT ACTIVITY OF AQUEOUS EXTRACTS OF FRUITS OF TERMINALIA CHEBULA AND PHYLLANTHUS EMBLICA IN BEHAVIOURAL MODELS OF DEPRESSION: INVOLVEMENT OF MONOAMINERGIC SYSTEM

Objectives: Terminalia chebula (TCh) and Phyllanthus emblica (PE) posses wide range of central nervous system activity. This study was conducted to investigate the antidepressant activity and mechanism action of aqueous extract of TCh & PE using forced swimming test (FST) and tail suspension test (TST). Methods: Aqueous extracts of TCh (390, 780 & 1560mg/kg) and PE (390, 780, 1560 & 3120 mg/kg) were administered for seven days to mice and immobility time was measured in FST & TST. Extracts were administered for 14 days and immobility time was measured in chronic FST. The mechanisms of antidepressant effect of TCh and PE were studied using prazosin (1mg/kg), levosulpiride (20mg/kg) and p-CPA (300mg/kg) in TST. Results: In FST, 780 & 1560 mg/kg of TCh and 1560 & 3120 mg/kg of PE reduced immobility time while in TST, 1560 mg/kg of TCh and 3120 mg/kg of PE decreased immobility significantly compared to control. In chronic FST, only 780 & 1560 mg/kg of TCh showed significant reduction. Antidepressant effect of TCh was reversed by prazosin while antidepressant effect of PE was reversed by prazosin and levosulpiride significantly in TST. Conclusions: The aqueous extracts of TCh and PE possess antidepressant activity at higher doses. This effect was possibly mediated through mono aminergic pathways

Study of resistance pattern of isolated micro-organisms towards commonly used anti-microbial agents in medical intensive care unit of a tertiary care teaching hospital

Background: The objective of the study was to find out different types of biological samples from admitted patients tested for culture and sensitivity (C&S), prevalence of different types of organisms isolated from those samples, and to analyze the resistance pattern of those isolated organisms against commonly used or tested anti-microbial agents (AMAs).Methods: Following institutional ethics committee approval and written informed consent, adult patients of both genders, receiving AMAs were enrolled from June 2014 to July 2015 and followed up daily till they were in medical intensive care unit (MICU). Demographic data, diagnosis, culture-sensitivity (antibiogram) and other investigation reports and treatment details were recorded. Descriptive statistical analysis of collected data was done.Results: Of the 514 samples (from 600 patients enrolled) sent for C&S testing, 143 were reported as sterile while from the rest 371 samples, 504 organisms were isolated; commonly isolated organisms were Pseudomonas aeruginosa (30%), Acinetobacter baumannii (23%), Klebsiella pneumoniae (16%), Providencia sp. (7.1%), Escherichia coli (5.7%), and Enterobacter sp. (4.2%). Samples were sent in 63% of enrolled patients, the commonest being broncho-alveolar lavage (48% of total). Microbial resistance was high for cephalosporins (ceftriaxone, cefepime, ceftazidime), carbapenems (meropenem, imipenem), penicillins (piperacillin), quinolones (ciprofloxacin, levofloxacin), aminoglycosides (gentamicin, netilmicin, amikacin) and cotrimoxazole. Most organisms were sensitive to colistin (100%), polymyxin B (92%) and tigecycline (69%).Conclusions: The information regarding commonly isolated organisms and their resistant pattern would aid in rational selection of AMAs and thus the present study is useful to clinicians managing MICU and the hospital infection committee to plan future policies regarding AMA use in MICU

Evaluation of the effects of Aegle marmelos and Punica granatum in an experimental model of gastrointestinal barrier dysfunction

Background: The study was conducted to evaluate the effects of Aegle marmelos and Punica granatum in an experimental model of gastrointestinal barrier dysfunction induced by common bile duct ligation.Methods: Institutional animal ethics committee approval was obtained. Forty two Wistar rats (either sex, 150-250 gms) divided into seven groups (n=six/group), were subjected to sham operation (group 1) or bile duct ligation (groups 2-7) and treated with distilled water (groups 1 and 2); 0.75mg/kg glutamine (group 3); 0.27 g/kg and 0.54 g/kg of A. marmelos (groups 4 and 5); 3.6 g/kg and 7.2 g/kg P. granatum (groups 6 and 7) orally once daily for 10 days. On Day 11, animals were sacrificed and samples of the jejunum, ileum and mesenteric lymph nodes were obtained to study jejunal and ileal villous morphology, villous heights, jejunal mucosal sucrase enzyme activity and bacterial translocation to mesenteric lymph nodes.Results: Glutamine prevented blunting of the intestinal villi, bacterial translocation and a fall in the sucrase enzyme activity. Both the plant drugs prevented blunting of the villi (except low dose A. marmelos for ileal villi) and a fall in the villous heights (except low dose P. granatum for jejunal villi), decreased the bacterial translocation (except low dose A. marmelos), and prevented a fall in the sucrase enzyme activity when compared to the disease control. The high doses of both A. marmelos and P. granatum were comparable to glutamine for all the variables tested.Conclusions: Both A. marmelos and P. granatum maintained the gastrointestinal barrier function in this model

Celastrus paniculatus and memantine prevent alcohol dependence and improve decision making in alcohol dependent C57BL6 mice

Background: Alcohol use disorder poses a huge burden with only a handful of approved drugs. AUD is associated with impaired decision-making that leads to compulsive drinking despite negative consequences. A drug that decreases alcohol consumption as well as improves decision-making may thus prove more useful. This study was planned to evaluate the effect of two drugs, Celastrus paniculatus and memantine on alcohol preference and decision impairment in alcohol-dependent mice. Methods: In part 1, the effect of both the study drugs on alcohol consumption was studied using intermittent access model in 70 male C57BL6 mice. In part 2, effect of drugs on decision making was studied using the rodent version of Iowa gambling task. Mice were divided in seven study groups: Group 1-3: Celastrus paniculatus (140, 280, and 560 mg/kg), Group 4: memantine (25 mg/kg), Group 5: vehicle control 1 (Milk), Group 6: vehicle control 2 (normal saline) and Group 7: naltrexone(1mg/kg). Results: Percentage alcohol preference was lower in test groups i.e., Celastrus paniculatus at medium (40.90±15.18%) and high doses (31.79±7.46%) vs. milk (82.74±8.53%; p<0.05); and in memantine group (36.28±10.99%) vs. normal saline (83.27±5.51%; p<0.05). The results were not significantly different to Naltrexone (19.70±6.90%). Percentage preference to disadvantageous arms was also lower in Celastrus paniculatus, at medium (50.52±1.92%) and high doses (48.11±2.43%) compared to milk (54.47±2.73%; p<0.05) and memantine (47.45±1.67%) compared to normal saline (54.00±2.73%; p<0.05), indicating better decision-making ability in the test groups. The findings were comparable to Naltrexone group (45.43±2.52%). Conclusions: These results indicate that Celastrus paniculatus and memantine reduce alcohol consumption and improve decision making in alcohol-dependent mice

Evaluation of prakṛti and quality-of-life in patients with irritable bowel syndrome

Objective: To evaluate the prakṛti of irritable bowel syndrome (IBS) patients and its association with IBS subtypes and quality-of-life (QOL). Methodology: IBS patients with the consistent subtype in the last 6 months were recruited. Prakṛti assessment with a 24-item questionnaire was performed and depending on the scores the patients were categorized into vāta predominant, pitta predominant, and kapha predominant prakṛti. QOL was assessed with prevalidated disease-specific 34-item questionnaire scored on a 0-100 scale. Results: Of 50 IBS patients enrolled, with mean age of 43.5 ± 12.8 years, and male: female as 43:7, 22 patients were of vāta and pitta predominant prakṛti each while six patients had kapha predominant prakṛti. IBS-C was diagnosed in 24 patients, IBS-D in 21, and IBS-M in five patients. In vāta predominant group, IBS-C was found in 13 patients, IBS-D in 8, and IBS-M in 1. In pitta predominant group, IBS-D was found in 13, IBS-C in 6, and IBS-M in 3. In kapha predominant group, IBS-C was found in 5 patients and IBS-M in 1. The median QOL in IBS-C group was 48.897, IBS-D was 38.97, and IBS-M was 66.911. The median QOL score 52.205, 42.27, and 55.51 in vāta, pitta, and kapha predominant group, respectively. Conclusion: Majority of the vāta predominant patients had developed IBS-C, pitta predominant patients had developed IBS-D. QOL was better in pitta predominant individuals of all IBS-disease subtypes. With this, we find that prakṛti examination in IBS helps in detecting the proneness of developing an IBS subtype and predicting their QOL accordingly

Effect of Saraswatarishta in animal models of behavior despair

Background: Saraswatarishta (SA) is a herbo-mineral formulation consisting of 18 plants some of which are Medhyarasayanas. It has been claimed to be useful in treating central nervous system disorders. Objective: To evaluate antidepressant effect of ′Saraswatarishta′(SA) alone and in combination with imipramine and fluoxetine in animal models of depression. Materials and Methods: After obtaining IAEC permission, 144 rats (n = 36/part) were randomized into 6 groups- Group 1: Distilled water (1 mL), Group 2: Imipramine (30 mg/kg), Group 3: Fluoxetine (10 mg/kg), Group 4: SA (1.8 mL/kg), Group 5: Imipramine + SA, Group 6: Fluoxetine + SA. Effects of study drugs were evaluated in forced swim test (FST) with single exposure to FST (Part 1) and repeated exposure for 14 days (Part 2). In Part 3, reserpine was used with FST and effects of study drugs were evaluated against single exposure to FST. Same model was used with repeated exposures to FST (Part 4). In each part, rats were subjected to open field test (OFT) for 5 min prior to final FST. The variables measured: Immobility time in FST; line crossing, rearing and defecation in the OFT. Results: In all four parts, individual drugs and combinations thereof produced significant decrease in immobility time as compared to control, and extent of decrease was comparable amongst these groups. However, values for combination of fluoxetine with SA group were found to be lesser than that for individual agents in Parts 2 and 3. Combination of SA with imipramine did not enhance its anti-depressant effect in any of the parts. OFT findings did not vary significantly amongst the study groups. Conclusion: Decreased immobility in FST and absence of generalized stimulation or depression of motor activity in OFT point towards potential antidepressant effect of Saraswatarishta. Its co-administration with fluoxetine showed more promising effects

Effect of combination of Phyllanthus emblica, Tinospora cordifolia, and Ocimum sanctum on spatial learning and memory in rats

Background: There has been a steady rise in number of patients suffering from dementia including dementia associated with Alzheimer′s disease. Effective treatment of Alzheimer′s disease dementia is an unmet medical need. Objective: To evaluate effects of formulation containing combination of Phyllanthus emblica (Pe) and Tinospora cordifolia (Tc) with and without Ocimum sanctum (Os) on learning and memory performance of normal and memory impaired rats in complex maze and compare with effects of Tinospora cordifolia and Phyllanthus emblica alone. Materials and Methods: Wistar rats; either sex (100-150 g) were divided in seven groups Control, Piracetam, Rivastigmine, Tc, Pe, Formulation 1 (Tc + Pe), and Formulation 2 (Tc + Pe + Os).The study was divided in four parts: In part 1 memory enhancement was tested in normal rats. In part 2, 3, and 4 the effects of drugs were tested in Scopolamine-, Diazepam-, and Cyclosporine-induced amnesia. Hebb-Williams maze was used to test for learning and memory. Time required to trace food and number of errors in maze were noted. Results: In normal rats, all test drugs showed significant reduction in time required to trace the food and number of errors after 24 h compared with vehicle control. Formulations 1 and 2 reduced the time required to trace food and number of errors and the results were comparable with positive control groups and comparators Tc and Pe. Formulations 1 and 2 reversed amnesia produced by Scopolamine, Diazepam, and Cyclosporine when compared with vehicle control and showed comparable results with those of positive control groups and comparators Tc and Pe. Conclusion: Formulations 1 and 2 demonstrated nootropic activity and both the formulations showed comparable nootropic activity with that of Tc and Pe alone

Evaluation of effects of Maṇḍurabhasma on structural and functional integrity of small intestine in comparison with ferrous sulfate using an experimental model of iron deficiency anemia

Background: The present study was planned to assess effects of Maṇḍurabhasma (MB) on structural and functional integrity of small intestine using an animal model of iron deficiency anemia (IDA) in rat. Methods: IDA was induced by giving iron deficient diet and retro-orbital bloodletting for 21 days in Wistar female rats. Rats (n = 72) were divided into six groups: (i) Control group, (ii) IDA rats, (iii) IDA rats receiving vehicle, (iv) rats receiving ferrous sulfate (40 mg/kg), (vi) rats receiving a low dose (22.5 mg/kg) of MB, (vi) rats receiving a high dose (45 mg/kg) of MB. Treatment was conducted for a period of 21 days followed by an assessment of change in hemoglobin (Hb) levels, lactase levels, lipid peroxidation activity by measuring malondialdehyde (MDA) levels and jejunal morphometry. Results: In the present study, the lactase activity was markedly reduced in iron-deficient rats. Our study has demonstrated that intestinal morphology and MDA levels were not altered in the animals with IDA as compared to normal animals. In phase II, improvement in Hb response to ferrous sulfate was accompanied by an improvement in lactase activity. However, it significantly increased MDA levels with derangement of the normal villous structure. Rats receiving a low dose of MB did not have increased MDA levels. It did not alter the jejunal villous structure and improved lactase activity, but hematinic activity was found to be less than that of ferrous sulfate. Rats receiving a high dose of MB showed significantly improved Hb as well as lactase levels. They exhibited damage to the villous structure and increased MDA levels, but the effects were significantly less as compared to ferrous sulfate group. Conclusion: Rats receiving a high dose of MB have shown improvement in hematinic and lactase levels comparable to those receiving ferrous sulfate. However, it causes lesser oxidative damage as compared to ferrous sulfate. This is an encouraging finding because it indicates the potential of MB to cause lesser gastrointestinal side effects compared to ferrous sulfate