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Abnormal production of pro-inflammatory mediators and generation of reactive oxygen species (ROS) play a key role in the development and progression of various human disorders. The study aims to investigate the in vitro anti-inflammatory and antioxidant activity of 4-allyl pyrocatechol (4-APC) and its derivatives (APC-1 and APC-2) by albumin denaturation and 1,1-Diphenyl-2-picrylhydrazyl (DPPH) methods, respectively. Also, the test compounds are studied in silico for their inhibitory potential against the pro-inflammatory and oxidative markers (calpain, FAAH, and TNF-α) via molecular docking. The compounds have exhibited appreciable in vitro anti-inflammatory and antioxidant activities. The APC-2 compound has demonstrated significant anti-inflammatory and antioxidant activity (percentage inhibition = 69±0.76 and 77.05±0.92, respectively, at 100 μg/ml) compared to the standard drugs, aspirin and ascorbic acid (percentage inhibition = 82±0.83 and 92.35±0.75, respectively, at 100 μg/ml). The docking study has showed that APC-2 significantly inhibited calpain (PDB ID: 2R9C), FAAH (2WJ1) and TNF-α (2AZ5) inflammatory markers. The drug-likeness, bioactivities, ADME profile (pharmacokinetic) and toxicity properties have also been determined using online tools (Molinspiration, pkCSM, SwissADME, PreADMET). The test compounds have showed acceptable drug-likeness, bioactivity score, ADME and toxicity properties. Finally, we conclude that the 4-allylpyrocatechol and its derivatives can be used as lead molecules for their further development as therapeutically useful anti-inflammatory agents.

Coronaviruses are a type of virus that can infect both animals and humans. Coronaviruses are divided into thirty-nine species and twenty-seven subgenus in the family Coronaviridae, according to the current classification. Seven of these are known to induce respiratory infections, while four others can cause cold-like symptoms on a regular basis. SARS CoV, MERS-CoV, and SARS CoV-2 infection are three examples of viral rebound. They are to blame for SARS, MERS, and the most recent Coronavirus epidemic discovered in 2019. (COVID-19). The World Health Organization declared the respiratory sickness caused by the SARS-CoV-2 infection to be a pandemic (WHO). For this COVID-19, there are currently no properly shown managements. The virology of SARS-CoV-2 has yielded a large number of therapeutic targets. Remdesivir appears to be the most promising treatment. Currently, COVID-19 is treated with Dexamethasone, Tocilizumab, Remdesivir, Chloroquine and Hydroxychloroquine, Lopinavir, Favipiravir, Niclosamide, Azithromycin, Sarilumab, Baricitinib, Ruxolitinib, Ribavarin, Nitazoxanide, Umifenovir, Camostat, Ciclesonide, Darun They exert their effects through blocking receptors such as IL 6, TMPRSS2, CD147, and AAKI, as well as RNA dependent RNA polymerase, membrane fusion, endocytosis, and proteolysis. The authors of this study looked at the available literature on the SARS-CoV-2 virus and the COVID-19 virus in terms of therapeutic evidence. This in-depth and thorough examination provides an excellent overview of the most up-to-date information on the medications used to treat COVID-19.

Tissue-type plasminogen activator (t-PA) expression is known to increase following transient focal cerebral ischemia and reperfusion. Previously, we reported downregulation of t-PA upon suppression of matrix metalloproteinase-12 (MMP-12), following transient focal cerebral ischemia and reperfusion. We now present data on the temporal expression of t-PA in the brain after transient ischemia, as well as the interaction between MMP-12 and t-PA, two proteases associated with the breakdown of the blood-brain barrier (BBB) and ischemic brain damage. We hypothesized that there might be reciprocal interactions between MMP-12 and t-PA in the brain after ischemic stroke. This hypothesis was tested using shRNA-mediated gene silencing and computational modeling. Suppression of t-PA following transient ischemia and reperfusion in rats attenuated MMP-12 expression in the brain. The overall effect of t-PA shRNA administration was to attenuate the degradation of BBB tight junction protein claudin-5, diminish BBB disruption, and reduce neuroinflammation by decreasing the expression of the microglia/macrophage pro-inflammatory M1 phenotype (CD68, iNOS, IL-1β, and TNFα). Reduced BBB disruption and subsequent lack of infiltration of macrophages (the main source of MMP-12 in the ischemic brain) could account for the decrease in MMP-12 expression after t-PA suppression. Computational modeling of in silico protein-protein interactions indicated that MMP-12 and t-PA may interact physically. Overall, our findings demonstrate that MMP-12 and t-PA interact directly or indirectly at multiple levels in the brain following an ischemic stroke. The present findings could be useful in the development of new pharmacotherapies for the treatment of stroke.

Mechanistic/mammalian target of rapamycin (mTOR) belongs to the phosphatidylinositol kinase-related kinase (PIKK) family. mTOR signaling is required for the commencement of essential cell functions including autophagy. mTOR primarily governs cell growth in response to favourable nutrients and other growth stimuli. However, it also influences aging and other aspects of nutrient-related physiology such as protein synthesis, ribosome biogenesis, and cell proliferation in adults with very limited growth. The major processes for survival such as synaptic plasticity, memory storage and neuronal recovery involve a significant mTOR activity. mTOR dysregulation is becoming a prevalent motif in a variety of human diseases, including cancer, neurological disorders, and other metabolic syndromes. The use of rapamycin to prolong life in different animal models may be attributable to the multiple roles played by mTOR signaling in various processes involved in ageing, protein translation, autophagy, stem cell pool turnover, inflammation, and cellular senescence. mTOR activity was found to be altered in AD brains and rodent models, supporting the notion that aberrant mTOR activity is one of the key events contributing to the onset and progression of AD hallmarks This review assesses the molecular association between the mTOR signaling pathway and pathogenesis of Alzheimer's disease. The research data supporting this theme are also reviewed.

The recent emergence of COVID-19 influenced the layman’s knowledge of drugs. Although several drugs have been discovered serendipitously, research has moved to the next-generation era of drug discovery. The use of drugs is inevitable and they have become lifesavers in the present era. Although research from different scientific backgrounds has supported the translational research of drug discovery, the prime role of pharmacy has to be remembered. Here we have summarized the role of some important subjects in pharmacy education, which have paved different ways in drug discovery and development.

Chrysin belongs to the flavonoids and has been used as traditional medicine from ancient and has been reported to exhibit a wide range of pharmacological properties. The biochemical and molecular mechanisms involved in the hepato- and nephroprotective activities of chrysin were discussed in this review. Chrysin exhibited hepatoprotective activity against 2,3,7,8-tetrachlorodibenzo-p-dioxin, carbon tetrachloride, cisplatin, d-galactosamine, doxorubicin, ethanol, lipopolysaccharide/d-galactosamine, methotrexate, ammonium chloride, paracetamol, diethylnitrosamine, streptozotocin, tert-butyl hydroperoxide, thioacetamide, 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP), ischemia/reperfusion-induced hepatotoxicity and nephroprotective activity against cisplatin, doxorubicin, paracetamol, gentamicin, streptazotocin, N-nitrosodiethyl amine, 5-fluorouracil, adenine, carbon tetrachloride, copper, 2,3,7,8-tetrachlorodibenzo- p-dioxin, colistin, Nω-nitro-l-arginine-methylester and ethanol in various animal models due to its antioxidant, anti-apoptotic activities. In this review, we provide an overview of the possible mechanisms by which chrysin reduced the hepatotoxicity and nephrotoxicity of different toxicants. This will help the toxicologists, pharmacologists and chemists to develop new safer pharmaceutical products with chrysin and other toxicants.

N-acetyl-p-benzoquinoneimine (NAPQI) is toxic metabolite of paracetamol formed primarily by cytochrome P4502E1 (CYP2E1) metabolic pathway when administered at therapeutic doses or overdose. The influence of quercetin (flavonoid) on the bioactivation of paracetamol to NAPQI was investigated using rat liver microsomes and rats in vivo. Paracetamol (80 mg/kg) was administered orally without or with silymarin (100 mg/kg), a known inhibitor of CYP2E1, CYP3A4 and quercetin (10 and 20 mg/kg) to rats for 15 consecutive days. Area under the plasma concentration-time curve (AUC0-∞ ) and the peakplasma concentration (Cmax ) of paracetamol were dose-dependently increased with quercetin (10 and 20 mg/kg) compared to paracetamol control group (p < 0.001). On the other hand, the AUC0-∞ and Cmax of NAPQI were decreased significantly with quercetin. The same results were observed with silymarin also. The elevated liver and kidney functional enzymes/compounds were significantly reduced by quercetin and silymarin compared to paracetamol control group. The formation of NAPQI was reduced in the incubation samples in presence of quercetin in experiment using isolated rat hepatocytes. The presentstudy results revealed that quercetin might be inhibited the CYP2E1-mediated metabolism of paracetamol; thereby decreased the formation of NAPQI and protected the liver and kidney.

OBJECTIVES: Granny Smith is a cultivated hybrid variety of apple with a high antioxidant content relative to all other species of apple. Acute pancreatitis (AP) is an instantly emerging inflammatory condition with a high mortality rate. The preferred treatment is restricted to symptomatic relief and supportive care. The present study was undertaken to evaluate the favorable effects of Granny Smith apple extract (GSAE) as a prophylactic treatment for L-arginine-induced AP in rats. MATERIALS AND METHODS: Male Sprague Dawley rats were divided in to five groups (n=6): Normal control (saline), disease control (a single dose of L-arginine 2.5 g/kg I.P.), positive control (pelatonin 10 mg/kg I.P.), and GSAE I and II (200 mg/kg and 400 mg/kg, orally, respectively). All groups were treated for 7 days. At the end of the study, blood samples were collected from the retro-orbital plexus, serum separated, and subjected to estimation of biomarker enzymes such as amylase, lipase, antioxidant enzymes, etc. The animals were then sacrificed, and the pancreas was isolated and subjected to estimation of tissue biomarkers, DNA fragmentation assay, and histopathological studies. RESULTS: Serum levels of amylase and lipase were significantly (p

The intense inflammatory response triggered in the brain after focal cerebral ischemia is detrimental. Recently we showed that the suppression of toll-like receptors (TLRs) 2 and 4 attenuates infarct size and reduces the expression of pro-inflammatory cytokines in the ischemic brain. In this study, we tested the effect of unrestricted induction of TLRs 2 and 4 on the expression of its downstream signaling molecules and pro-inflammatory cytokines one week after reperfusion. The primary purpose of this study was to investigate the effect of simultaneous knockdown of TLRs 2 and 4 on M1/M2 microglial polarization dynamics and post-stroke neurological deficits and the recovery. Transient focal cerebral ischemia was induced in young adult male Sprague-Dawley rats by the middle cerebral artery occlusion (MCAO) procedure using a monofilament suture. Appropriate cohorts of rats were treated with a nanoparticle formulation of TLR2shRNA and TLR4shRNA (T2sh+T4sh) expressing plasmids (1 mg/kg each of T2sh and T4sh) or scrambled sequence inserted vector (vehicle control) expressing plasmids (2 mg/kg) intravenously via tail vein immediately after reperfusion. Animals from various cohorts were euthanized during reperfusion, and the ischemic brain tissue was isolated and utilized for PCR followed by agarose gel electrophoresis, real time PCR, immunoblot, and immunofluorescence analysis. Appropriate groups were subjected to a battery of standard neurological tests at regular intervals until fourteen days after reperfusion. The increased expression of both TLRs 2 and 4 and their downstream signaling molecules including the pro-inflammatory cytokines was observed even at one-week after reperfusion. T2sh+T4sh treatment immediately after reperfusion attenuated the post-ischemic inflammation, preserved the motor function, and promoted recovery of the sensory and motor functions. We conclude that the post-ischemic induction of TLRs 2 and 4 persists for at least seven days after reperfusion, contributes to the severity of acute inflammation, and impedes neurological recovery. Unlike previous studies in TLRs 2 or 4 knockout models, results of this study in a pharmacologically relevant preclinical rodent stroke model have translational significance.

Alzheimer's disease (AD) isaprogressive neurodegenerative disorder characterized by chronic inflammation due to the presence of neurotoxic Aβ and tau proteins. Increased microglial activation and inflated immune response are the other factors to be considered in AD pathology. Microglial cells own biochemical machinery that synthesizes and release endocannabinoids. The exploitation of therapeutic actions of endocannabinoid system has newly emerged in the field of Alzheimer's disease. The activation of cannabinoid receptors/ cannabinoid system modulates inflammatory responses. This review assesses the association between the microglial endocannabinoid system and neuroinflammation in AD. The data supporting the anti-inflammatory role of pharmacological agents modulating cannabinoid system are also reviewed.

Objective: To assess the success rate of DOTS for tuberculosis patients and the secondary objective was to identify the factors associated with unsuccessful treatment outcome. Methods: A retrospective study was conducted to review the medical records of patients (n = 1113) registered at the Directly Observed Treatment Short-Course (DOTS) clinic of Government Infectious Disease (Govt. ID) Hospital, Guntur, India. Multivariate logistic regression model was used to determine the factors associated with the treatment success rate. Results: The overall mean success rate of TB patients was found to be 82.8%. Treatment success rate (TSR) was steadily increased across the years from 73.9% in 2015 to 84.3% in 2016 and 88.9% in 2017 while the death rate was steadily decreased from 11.2% in 2015 to 6.25% in 2016 and 4.33% in 2017. Risk factors significantly associated with unsuccessful treatment outcome were found to be HIV positive (P Key words: Directly observed treatment short-course, Retrospective study, Risk factors, Treatment success rate, Tuberculosis.

Introduction: We recently showed in a rodent model of transient focal cerebral ischemia that matrix metalloproteinase-12 (MMP-12) induction in the ischemic brain promotes post-stroke blood-brain barrier disruption, apoptosis, demyelination, and infarction. The purpose of the present study is to investigate the role of elevated MMP-12 on post-stroke neurological function and to identify the time window of therapeutic opportunity for MMP-12 suppression. Methods: Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion and reperfusion. Cohorts of rats (n =8-15/group) were administered with either MMP-12 shRNA or scrambled shRNA sequence (vehicle control) expressing plasmids (1 mg/Kg; intravenous) formulated as nanoparticles. The differences in sample size of various cohorts were attributed to the exclusion criteria followed, high mortality rate in vehicle control-treated group, and sample size required for statistical analysis. To assess the reflex, balance, sensory, and motor functions, rats from various cohorts were subjected to modified neurological severity scoring (mNSS), adhesive removal test, beam walk test and rotarod test at day 1, 3 and 5 of reperfusion. To assess the time window of therapeutic opportunity, various cohorts of rats were treated at 5 min, 3h, and 6h of reperfusion. Investigators blinded to study groups analyzed all outcome parameters. Results: The post-stroke percent survival rate in cohorts treated with MMP12shRNA expressing plasmids range from 82 to 89 as compared to 67 in vehicle control-treated group. The cohort of rats treated at 5 min of reperfusion with MMP-12snRNA expressing plasmids showed significantly better functional recovery as assessed by various neurological tests. However, delayed administration of MMP-12snRNA expressing plasmid (either at 3h or 6h of reperfusion) failed to promote any significant improvement in post-stroke neurological recovery. Conclusions: Post-stroke induction of MMP-12 in the ischemic brain contributes to neurological deficits and impedes recovery. MMP-12 targeting treatments immediately after reperfusion could offer substantial therapeutic benefits.

Quercetin is one of the most abundant flavonoids in human diet that has been reported to exhibit a wide range of pharmacological properties. The biochemical and molecular mechanisms involved in the hepatoprotective activity of quercetin were discussed in this review. Quercetin exhibited hepatoprotective activity against 2-butoxyethanol, acrylamide, acrylonitrile, aflatoxin B1, aroclor-1254, arsenic, sodium arsenite, azathioprine, cadmium chloride, carbon tetrachloride, chlorpyrifos, cyclosporine A, diazinon, dimethylnitrosamine, doxorubicin, epirubicin, ethanol, fenvalerate, isoniazide, rifampicin, lead acetate, lindane, D-galactosamine, methotrexate, methylmercury, nickel sulfate, paracetamol, perfluorooctanoic acid, polychlorinated biphenyls, pyrrolizidine alkaloid clivorine, rotenone, sodium fluoride, streptazotocin, tert-butyl hydroperoxide, thioacetamide, titanium dioxide, tumor necrosis factor-α, tripterygium glycoside, triptolide, ultraviolet A light, concavalin A, bisphenol, and ischemia-induced hepatotoxicity in various animal models due to its antioxidant, free radical-scavenging,anti-inflammatory, antiapoptotic, and cytochrome P450 2E1 (CYP2E1) inhibitory activities. In this review, we provide an overview of the possible mechanisms by which quercetin reduced the hepatotoxicity of different hepatotoxicants. This will help the toxicologists, pharmacologists, and chemists to develop new safer pharmaceutical products with quercetin and other hepatotoxicants.

Genetic, environmental, and metabolic risk factors are interrelated and contributed to the development of type 2 diabetes mellitus (T2DM). The American Association of Clinical Endocrinologists (AACE) guidelines are gold standard for the management of T2DM. The objective of the study was to assess the prescription adherence to AACE treatment guidelines and risk factors for T2DM in a South Indian tertiary care hospital. A cross-sectional study was carried out in 950 subjects (with or without T2DM), and prescription adherence was assessed by comparing with the AACE guidelines. Odds ratios were calculated in univariate logistic regression analysis for risk factors. T2DM was significantly higher in the subjects of age above 40 years, females, married, BMI, urban residence, higher socioeconomic class, hypertension as comorbidity, physical inactivity, smokers, alcoholics, and stress. Metformin was the most widely prescribed drug followed by α-glucosidase inhibitors in monotherapy. The overall rate of prescription adherence was 88.0 % (when HbA1c 9 %, P 25 kg/m2), urban residence, body weight (above 50 kg), high economic class, hypertension, past alcoholic, physical inactivity, and stress are the significantly risk factors for T2DM. The present study results suggested that prescription adherence to AACE guidelines was optimal. Female gender, age (above 50 years), hypertension, stress, physical inactivity, urban residence, body weight, BMI, and high socioeconomic status are the major risk factors for T2DM.

Objective: The present study aimed to assess the effect of Chrysin on mechanical hyperalgesia in chronic constriction injury (CCI)-induced neuropathic pain in Wistar rats. Materials and Methods: Neuropathic pain was induced by CCI to the sciatic nerve in rats. Oral treatment of chrysin was given at doses of 50 mg/kg, 100 mg/kg, and 200 mg/kg in neuropathic rats. Mechanical hyperalgesia (in terms of paw withdrawal threshold [PWT]) was measured using Randall–Selitto analgesy-meter, and percent PWT was determined. Statistical analysis was carried out using GraphPad Prism 5 tool. Results: In mechanical hyperalgesia test, treatment with chrysin 200 mg/kg, naive PWT, predose PWT, 0.5 h, 1 h, 2 h, and 4 h postdose PWT were found to be 141 ± 8.94 g, 60 ± 7.91 g, 107 ± 9.08 g, 113 ± 5.70 g, 106.0 ± 7.42 g, and 97 ± 9.08 g, respectively. The peak effect was observed at 2 h posttreatment for 50 mg and 100 mg while the peak effect for 200 mg was reached at 1 h, and the same was maintained till 2 h posttreatment. Chrysin 200 mg dose has shown maximal percent reversal (74%) at 2 h posttreatment. The percent reversal PWT of 50 mg/kg, 100 mg/kg, and 200 mg/kg at 2 h were 68%, 67%, and 74%, respectively. Chrysin has exhibited dose-dependent efficacy in CCI-induced neuropathic pain. In mechanical allodynia test, In chrysin (200 mg/kg) treatment group, naive PWT, predose PWT, 0.5 h, 1 h, 2 h, and 4 h postdose PWT were found to be 60.0 ± 0.0 g, 5.0 ± 1.10 g, 22.45 ± 6.62 g, 52.64 ± 18.29 g, 37.33 ± 17.56 g, and 29.83 ± 9.22 g, respectively. The percent reversal PWT of 50 mg/kg, 100 mg/kg, and 200 mg/kg at 2 h were 43%, 68%, and 87%, respectively. Conclusion: Chrysin attenuates neuropathic pain by ameliorating mechanical hyperalgesia and allodynia. Further studies are warranted to establish the mechanism.

The study was aimed to evaluate the protective effects of alcoholic extracts of Strawberry and Blueberry fruits [AESF and AEBF] in acute pancreatitis in rats. Treatment groups received AESF and AEBF at doses of 200 and 400 mg/kg for 7 days with prior injections of L-arginine on 5th day. Biochemical parameters were estimated in serum and pancreatic tissue samples. Histopathological studies and DNA fragmentation assay were carried out in isolated pancreatic tissue. The results of the study indicated that treatment of AESF and AEBF exhibited a significant dose dependent protective effect. Upon the treatment, anti-oxidant enzymes were significantly (*pless than 0.05) increased. Biochemical results were correlated with the histopathological findings. In addition, the DNA fragmentation assay showed an intact DNA in pancreatic cells of treated groups. In conclusion, berry fruit extracts exerted a potential protective effect against L-arginine induced damage in rat pancreas, at least in part, due to its antioxidant properties.

Paracetamol (N-acetyl-para amino phenol) is the most commonly used analgesic and antipyretic around the world. Its causes hepatotoxicity and nephrotoxicity at overdose or even at therapeutic doses. It is primarily metabolized by glucuronidation and sulfate conjugation. It is also metabolized by cytochrome-P450 system (CYP2E1, CYP1A2 and CYP 3A4), leading to the formation of N-acetyl-p-benzoquinoneimine (NAPQI). The present study was planned to investigate the influence of chrysin (known CYP2E1 and CYP3A4 inhibitor) on the bioactivation of paracetamol to NAPQI using rat liver microsomes in vitro and rats in vivo. Paracetamol (80 mg/kg) was administered orally without or with silymarin (100 mg/kg), a known CYP2E1 inhibitor and chrysin (100 and 200 mg/kg) to rats for 15 consecutive days. The area under the plasma concentration–time curve (AUC0-∞) and the peak plasma concentration (Cmax) of paracetamol were dose-dependently increased with chrysin (100 and 200 mg/kg) compared to paracetamol control group. On the other hand, the AUC0-∞ and Cmax of NAPQI were decreased significantly with chrysin (100 and 200 mg/kg). The elevated liver and kidney function markers were significantly reduced by chrysin and silymarin compared to paracetamol control group (P

Introduction: Education of the patients regarding KAP management has shown to improve patient outcomes in various health care settings across the world. Aim: To assess the impact of patient counselling by the pharmacist on KAP, Health related Quality of life and glycaemic control. Materials and Methods: A prospective observational study was conducted in hospitalised patients of various departments of the tertiary care hospital during the period of November 2016 to April 2017. Patient counselling was given by pharmacist at baseline visit and first follow-up (after three months). Patients were followed for six months with first follow-up at third month and with second follow-up at sixth month and KAP and HR-QoL were assessed using WHO-BREF QoL and KAP questionnaire respectively in all visits. Similarly, glycaemic control (HbA1C) values were noted at each visit. Results: A total of 50 patients were recruited in the study. KAP score at baseline visit, follow up-1 and follow up-2 were found to be 87.92±7.82, 117.47±6.98 and 119.9±5.30 respectively. Data analysis indicated that KAP score was improved at follow up-1 (p

Aim: This study was aimed to investigate the immunomodulatory activity of water soluble polysaccharides isolated from Metroxylon sagu (PSMS) by dilute acid extraction, ethanol precipitation in rats by using three different in-vivo experimental models of immunosuppression. Methodology: Three models of immunosuppression include metronidazole (MTZ) induced immunosuppression, pyrogallol induced immunosuppression and Ethanol-induced immunosuppression. Immunological indices like humoral antibody titer values, cellular immune response, percent change in phagocytosis, serum immunoglobulins were estimated. Histopathology of spleen was done in all control and treated groups. The doses of 500 and 250 mg/kg of PSMS were administered orally to evaluate the immunomodulatory activity. Results: Though PSMS was demonstrated to have immunostimulatory activity in almost all three models of immunosuppression, PSMS was found to be more effi cacious against ethanol-induced immunosuppression when compared with pyrogallol induced immunosuppression and MTZ induced immunosuppression. However, dose-dependent improvement in immunological indices was evident in all three models. Conclusion: In summary, water soluble polysaccharides isolated from M. sagu stimulate the immunity in the animal models of immunosuppression.

The study was undertaken to evaluate the effect of quercetin on the pharmacokinetics of Metoprolol tartrate. A single dose in vivo pharmacokinetic study was carried out in rat models. In this study, rats were treated with quercetin (10 mg/kg) and metoprolol tartrate (20 mg/kg) orally and blood samples were collected 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, 12 h post treatment. Plasma concentration of metoprolol tartrate was estimated using reverse phase-high-performance liquid chromatography method. Area under the plasma concentration-time curve (AUC 0-12 ) of metoprolol has significantly (P < 0.001) decreased by 9.8 times in the metoprolol and quercetin combination group (9434.65 ± 3525.02) when compared with AUC 0-12 metoprolol of metoprolol-alone treated group (962.17 ± 242.81). AUC 0-∞ of metoprolol has significantly (P < 0.001) decreased by 14.9 times in the combination group (16670.79 ± 12129.06) in comparison to AUC 0-∞ of metoprolol of metoprolol-alone treated group (1113.68 ± 441.83). the results obtained herein indicate that quercetin remarkably declines the plasma exposure of metoprolol when concomitantly administered by oral route.

Background The study was undertaken to assess the pharmacokinetic and pharmacodynamic correlation of Lamotrigine (LMT) was determined following oral administration to prove that there was a direct relationship between daily dose, plasma level of LMT and analgesic effects. Methods Neuropathic pain was induced by chronic constriction injury of the sciatic nerve. This technique allows consecutive measurements of the paw withdrawal thresholds and paw withdrawal duration on hyperalgesia and allodynia respectively. Increase in threshold and decrease in the duration of paw withdrawals was used as an analgesic effect against neuropathy. Results and discussion The results demonstrate that there was a positive correlation between plasma correlation and pharmacodynamic effects in neuropathic pain. Conclusion Since there was a positive correlation between plasma correlation and pharmacodynamic effects in neuropathic pain, the plasma levels of Lamotrigine are good indicators of efficacy of the same in animal models of neuropathic pain.

Background It is widely accepted that Duloxetine and Metoprolol are concomitantly administered for clinical conditions like diabetic neuropathic pain and diabetic cardiovascular disorders respectively. Since these two drugs interfere with Cytochrome P2D6 (CYP2D6), there is likelihood of possible potential drug–drug interactions between these two drugs. Hence, this study was undertaken to investigate the effect of Duloxetine on the in-vivo pharmacokinetics of Metoprolol in rat models. Methods In-vivo pharmacokinetic studies were performed on rats. Rats were treated with Duloxetine (20 mg/kg) and Metoprolol (25 mg/kg) orally and blood samples were collected (0), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12 and 24 h post treatment. Plasma concentration of Metoprolol was estimated by Reverse Phase High Performance Liquid Chromatography (RP-HPLC) method. Results Duloxetine treatment along with Metoprolol results in 3.38 fold significant (p

Objective To evaluate the effects of Montelukast and Curcumin against indomethacin induced gastric damage in rats in order to assess the role of leukotriene (LTs) if any, in non steroidal anti-inflammatory drug (NSAID) induced gastroinflammation. Methods The effects of Montelukast (10 mg/kg) and Curcumin (100 mg/kg) were observed on gastric lesion induced by Indomethacin. The blood samples were analyzed for neutrophil adhesion and lipid peroxide levels in gastric tissue measured spectrophotometrically. The skin vascular permeability study was performed by using compound 48/80 induced vascular permeability model. Results Montelukast and Curcumin significantly reduced Indomethacin induced gastric lesion score. Pretreatment with Montelukast and Curcumin significantly counteracted Indomethacin induced gastropathy by a combination of its effect on inhibition of neutrophil adherence, through decrease in related production of free radicals that disrupts integrity of stomach mucosa and decrease in vascular permeability as compared to Indomethacin group. The results of the present study further indicates the role of 5-LOX metabolites in NSAIDs induced gastro inflammation and suggests that Montelukast and Curcumin counteracted the Indomethacin induced gastropathy by a combination of its effect on inhibition of neutrophil adherence and through decrease in related production of free radicals that disrupts integrity of stomach mucosa. Conclusions Experimental data clearly demonstrated the role of LTs was indomethacin induced gastric ulcers. However, inhibition of ulcerogenic events by Montelukast and Curcumin is suggestive of an important balance between COX and 5-LOX products.

Aim: The aim of the study is to evaluate the oxidant and antioxidant balance in experimentally induced testicular injury by ischemia reperfusion in rats with different time intervals of torsion/detorsion of the spermatic cord. Method: Male rats were divided into thirteen groups and each group containing six rats. All rats were subjected to right spermatic cord torsion followed by detorsion for different time intervals except the sham control group. Result: Malondialdehyde, super oxide dismutase, catalase levels were estimated in testicular tissue of each rat. Spermatic cord torsion/ detorsion induced a significant increase in testicular malondialdehyde contents and significant decrease in SOD, catalase levels when compared to sham control group in a time dependent manner. Conclusion: Our findings clearly represents that torsion for 4 hours followed by detorsion for 4 hours induces the highest oxidative stress with a great extent of lipid peroxidation and drastic reduction of SOD and catalase levels of the testis and is, therefore, a valid model for studying the oxidative antioxidant effects of the ischemia/ reperfusion injury in rat testis.

Background and Objective: Morinda citrifolia (MC) commonly known as Noni is being used for many ailments and is considered as wellness drink. It is traditionally used for anti-inflammatory, anti-aging, and immunostimulant properties. The present study has been initiated to investigate the protective effects of MC fruit extract (MCFE) on L-arginine-induced acute pancreatitis (AP) in rats. Materials and Methods: Male Sprague-Dawley rats were randomly divided into groups of control, disease control, positive control, and treatment groups. AP is induced by the administration of a single dose of L-arginine (2 × 2.5 g/kg, intraperitoneally, 1 h apart). Positive control received melatonin (10 mg/kg); treatment groups received 200 mg/kg and 400 mg/kg MCFE 6 days before administration of L-arginine. After 12 h of induction, the serum samples were analyzed for biomarker enzymes such as amylase, lipase, C-reactive protein, superoxide dismutase, glutathione, catalase, tissue nitrate, lactate dehydrogenase, and myeloperoxidase. Histopathological studies and deoxyribonucleic acid (DNA) fragmentation assay were performed from the isolated pancreatic tissue. Results: MCFE administration showed a dose-dependent significant (P

Aim: The aim of this study was to investigate the protective effects of bioflavonoid compounds i.e. rutin and naringin on gentamycin induced testicular oxidative stress in rats. Method: A total of 42 male wistar albino rats were divided in to 7 groups, each contains 6 rats. Gentamycin, 5 mg/kg, I.P was administered to the rats from day 1 to day 10. Rutin and naringin were given in different doses (5mg/kg, 10/kg) for a period of 35 days from day 1 to day 35 to the gentamycin treated animals. A sham control group animals with water, control group animals with gentamycin and vehicle control group animals with 0.1% sod CMC were also maintained until completion of 35 days. On 36th day bilateral orchiectomies were performed for all the animals. The testicular tissue was evaluated for various sperm parameters, biochemical estimations and histological changes. Result: Animals treated with 5mg/kg and 10mg/kg of rutin and naringin (Groups 4, 5, 6, 7) have shown significant and dose dependent reduction in MDA levels and increase in levels of antioxidant enzymes, SOD and Catalase when compared to control group animals (Group 2). Sperm count, motility, viability were also protected and normalized with rutin and naringin. Specimens from group 2 had a histological injury with disordered germinal cells. Drug treated groups shown improved testicular architecture. Rutin was more effective in all the parameters when compared to Naringin. Both the bioflavonoids were effective in reducing the gentamycin induced testicular oxidative stress. Conclusion: Rutin and Naringin pretreatment have shown protective and beneficial effect on gentamycin induced oxidative stress in rats.

Tremendous progress in pathogenic role of cyclooxygenase-2 (COX-2) in diverse cancers triggering the cancer research in the direction of COX-2 inhibitors. Several experimental studies reported overexpression of COX-2 in cancer cells. Mechanisms mediating the pathobiology of COX-2 in cancer are still unclear and needs to be clarified. However, recent studies have shown that the levels of COX-2 isoenzymes are elevated in certain cancers like colo-rectal carcinoma, squamous cell carcinoma of head and neck and certain cancers of lung and breast. Our review article aims to summarize the role of COX-2 in various types of cancer and mechanisms emerged from recent research and their interaction with other cytokines. It seems mechanisms mediating COX-2 and its role in each cancer may be different. In general, possible signaling from the lipids (prostaglandins) can inhibit apoptosis and increase proliferation, motility, and metastatic potential. Furthermore, under certain conditions COX-2 can contribute to angiogenesis. Even, COX-2 is found in lung cancer cells that are responsible for suppressing patients’ immune systems and therefore contributing to the growth of lung cancer. COX-2 inhibitors are already in clinical trials for the prevention of colorectal, oral, skin, esophageal and non-small-cell lung cancers and for the treatment of cervical, prostate, and metastatic breast cancers. Heightened role of COX-2 in cancer prompts the pharmaceutical research to design new and safer COX-2 inhibitors to minimize the cardiovascular side effects and improves the treatment of cancer.

Diabetic cardiomyopathy is a distinct clinical entity that produces asymptomatic heart failure in diabetic patients without evidence of coronary artery disease and hypertension. Abnormalities in diabetic cardiomyopathy include: myocardial hypertrophy, impairment of contractile proteins, accumulation of extracellular matrix proteins, formation of advanced glycation end products, and decreased left ventricular compliance. These abnormalities lead to the most common clinical presentation of diabetic cardiomyopathy in the form of diastolic dysfunction. We evaluated the role of various proteins that are likely to be involved in diabetic cardiomyopathy by employing multiple sequence alignment using ClustalW tool and constructed a Phylogenetic tree using functional protein sequences extracted from NCBI. Phylogenetic tree was constructed using Neighbour—Joining Algorithm in bioinformatics approach. These results suggest a causal relationship between altered calcium homeostasis and diabetic cardiomyopathy that implies that efforts directed to normalize calcium homeostasis could form a novel therapeutic approach.