Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 40
Filter
Add more filters

Country/Region as subject
Publication year range
1.
Toxicol Appl Pharmacol ; 486: 116945, 2024 May.
Article in English | MEDLINE | ID: mdl-38688424

ABSTRACT

Cytochrome P450 enzymes (CYPs) play a crucial role in the metabolism and synthesis of various compound classes. While drug-metabolizing CYP enzymes are frequently investigated as anti-targets, the inhibition of CYP enzymes involved in adrenal steroidogenesis is not well studied. The steroidogenic enzyme CYP17A1 is a dual-function enzyme catalyzing hydroxylase and lyase reactions relevant for the biosynthesis of adrenal glucocorticoids and androgens. Inhibition of CYP17A1-hydroxylase leads to pseudohyperaldosteronism with subsequent excessive mineralocorticoid receptor activation, hypertension and hypokalemia. In contrast, specific inhibition of the lyase function might be beneficial for the treatment of prostate cancer by decreasing adrenal androgen levels. This study combined in silico and in vitro methods to identify drugs inhibiting CYP17A1. The most potent CYP17A1 inhibitors identified are serdemetan, mocetinostat, nolatrexed, liarozole, and talarozole. While some of these drugs are currently under investigation for the treatment of various cancers, their potential for the treatment of prostate cancer is yet to be explored. The DrugBank database was screened for CYP17A1 inhibitors, to increase the awareness for the risk of drug-induced pseudohyperaldosteronism and to highlight drugs so far unknown for their potential to cause side effects resulting from CYP17A1 inhibition.


Subject(s)
Computer Simulation , Steroid 17-alpha-Hydroxylase , Steroid 17-alpha-Hydroxylase/antagonists & inhibitors , Steroid 17-alpha-Hydroxylase/metabolism , Humans , Male , Molecular Docking Simulation
2.
Metab Brain Dis ; 39(1): 15-27, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38008885

ABSTRACT

Fish oil has been known for its antioxidant, cardioprotective, anti-inflammatory, and neuroprotective characteristics due to the presence of polyunsaturated fatty acids (PUFAs) that are essential for optimal brain function and mental health. The present study investigated the effect of Carcharhinus Bleekeri (Shark Fish) oil on learning and memory functions in scopolamine-induced amnesia in rats. Locomotor and memory-enhancing activity in scopolamine-induced amnesic rats was investigated by assessing the open field and passive avoidance paradigm. Forty male Albino mice were divided into 4 equal groups (n = 10) as bellow: 1 - control (received 0.9% saline), 2 - SCOP (received scopolamine 2 mg/kg for 21 days), 3 - SCOP + SFO (received scopolamine and fish oil 5 mg/kg/ day for 21 days), 4 - SCOP + Donepezil groups (received 3 mg/kg/day for 21 days). SFO produced significant (P < 0.01) locomotor and memory-enhancing activities in open-field and passive avoidance paradigm models. Additionally, SFO restored the Acetylcholine (ACh) concentration in the hippocampus (p < 0.05) and remarkably prevented the degradation of monoamines. Histology of brain tissue showed marked cellular distortion in the scopolamine-treated group, while the SFO treatment restored distortion in the brain's hippocampus region. These results suggest that the SFO significantly ameliorates scopolamine-induced spatial memory impairment by attenuating the ACh and monoamine concentrations in the rat's hippocampus.


Subject(s)
Fish Oils , Scopolamine , Animals , Male , Mice , Rats , Acetylcholine/pharmacology , Fish Oils/pharmacology , Hippocampus/metabolism , Maze Learning , Memory Disorders/chemically induced , Memory Disorders/drug therapy , Memory Disorders/prevention & control , Models, Theoretical
3.
Pak J Pharm Sci ; 37(2): 275-289, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38767094

ABSTRACT

The capsule is a major virulence factor for Streptococcus pneumoniae which causes global morbidity and mortality. It is already known that there are few conserved genes in the capsular biosynthesis pathway, which are common among all known serotypes, called CpsA, CpsB, CpsC and CpsD. Inhibiting capsular synthesis can render S. pneumoniae defenseless and vulnerable to phagocytosis. The Inhibitory potential of active Zingiber officinale compounds was investigated against the 3D (3-dimensional) structural products of Cps genes using in silico techniques. A 3D compound repository was created and screened for drug-likeness and the qualified compounds were used for molecular docking and dynamic simulation-based experiments using gallic acid for outcome comparison. Cavity-based docking revealed five different cavities in the CpsA, CpsB and CpsD proteins, with gallic acid and selected compounds of Zingiber in a binding affinity range of -6.8 to -8.8 kcal/mol. Gingerenone A, gingerenone B, isogingerenone B and gingerenone C showed the highest binding affinities for CpsA, CpsB and CpsD, respectively. Through the Molegro Virtual Docker re-docking strategy, the highest binding energies (-126.5 kcal/mol) were computed for CpsB with gingerenone A and CpsD with gingerenone B. These findings suggest that gingerenone A, B and C are potential inhibitors of S. pneumoniae-conserved capsule-synthesizing proteins.


Subject(s)
Bacterial Proteins , Molecular Docking Simulation , Streptococcus pneumoniae , Zingiber officinale , Zingiber officinale/chemistry , Streptococcus pneumoniae/drug effects , Streptococcus pneumoniae/metabolism , Bacterial Proteins/metabolism , Bacterial Proteins/antagonists & inhibitors , Computer Simulation , Bacterial Capsules/metabolism , Bacterial Capsules/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Molecular Dynamics Simulation , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/biosynthesis , Gallic Acid/pharmacology , Gallic Acid/chemistry
4.
Pak J Pharm Sci ; 36(2): 467-476, 2023 Mar.
Article in English | MEDLINE | ID: mdl-37530154

ABSTRACT

High levels of reactive oxygen species (ROS) in the body and diabetes are key factors for the development of hypercholesteremia and related neuropathic pains. Current study aimed to compare the antioxidant, antidiabetic and analgesic activities of aqueous methanolic extracts of C. viminalis L. and A. rosea L. leaves. HPLC method was used for phenolic content evaluation. Antioxidant capacity was determined by DPPH and analgesic activity was performed via acetic acid induced writhing reflex test. Whereas the antidiabetic activity was performed on Alloxan induced diabetes model. HPLC analysis indicated the presence of phenols in both extracts. Based on DPPH radical scavenging activity, C. viminalis and A.rosea L. both leaves extracts showed strong scavenging activity (IC50, 11.96±0.64lg/mL) and (IC50, 10.11±0.74lg/mL) respectively. Antidiabetic effect of C. viminalis L and A. rosea L. were also significant (p<0.05). Further biochemical analysis showed both leaves extracts significantly (P<0.05) reduces glucose, Low density lipid (LDL), triglycerides (TG), total cholesterol (TC) and urea while high density lipid (HDL) were improved. In writhing reflex test both extracts exhibited significant (P<0.01) analgesic activity which was comparable to Aspirin. In conclusion both C. viminalis L. and A. rosea L. leaves extracts displayed significant antioxidant, analgesic and antidiabetic activity.


Subject(s)
Antioxidants , Malvaceae , Antioxidants/chemistry , Hypoglycemic Agents/chemistry , Plant Extracts/chemistry , Analgesics/pharmacology , Lipids/analysis , Plant Leaves/chemistry
5.
Pak J Pharm Sci ; 34(6): 2131-2139, 2021 Nov.
Article in English | MEDLINE | ID: mdl-35034873

ABSTRACT

Methylphenidate (MPH) is a psychostimulant, beneficial in attention deficit hyperactivity disorder (ADHD). Previously it has been shown that MPH-induced locomotor sensitization could be attenuate by buspirone co administration however the effect of chronic MPH and co-administration of MPH-buspirone on biochemical and hematological parameters are unknown. This study is designed to investigate these parameters after long term administration of MPH, Buspirone and their combination in rats. 40 male Wister rats were divided in to 4 groups, and treated with saline, MPH (2mg/kg/day), Buspirone (10mg/kg/day) and MPH-Buspirone co-administration (2mg/kg/day ±10mg/kg/day; respectively) up to six weeks. Administration of MPH significantly increase blood glucose level in saline treated control rats, however co-administration of MPH-buspirone exhibited less effect on blood glucose levels. Serum creatinine levels significantly decreased in all treated groups as compared to control but highly significant results were seen with combination treatment. Co-administration of MPH-buspirone and buspirone treated rats exhibited increased cholesterol and hemoglobin values. All treated groups showed increased values of hematocrit, MCV, MCH and MCHC compared to control group. RBCs and WBC's count were decreased in all treated groups. The platelet count rose significantly by Buspirone and MPH-buspirone administration, while MPH showed decreased platelet count. Thus, results suggested that prolong co-administration of MPH-buspirone is safe and effective for ADHD patients by preventing adverse effects not only on behavioral but also on biochemical and hematological parameter.


Subject(s)
Buspirone/toxicity , Methylphenidate/toxicity , Animals , Biomarkers/blood , Blood Glucose/drug effects , Blood Glucose/metabolism , Blood Platelets/drug effects , Blood Platelets/metabolism , Buspirone/administration & dosage , Cholesterol/blood , Creatinine/blood , Drug Administration Schedule , Erythrocytes/drug effects , Erythrocytes/metabolism , Hemoglobins/metabolism , Leukocytes/drug effects , Leukocytes/metabolism , Male , Methylphenidate/administration & dosage , Rats, Wistar , Time Factors
6.
Pak J Pharm Sci ; 34(6): 2247-2252, 2021 Nov.
Article in English | MEDLINE | ID: mdl-35034887

ABSTRACT

COVID-19 has taken over the world as the largest viral outbreak in the past 100 years. With over 13 million confirmed cases and 0.5 million-plus people dead, it has affected the life around us. With Pakistan being amongst the top 15 countries affected by it, the government of Pakistan has started vaccination, issued SOPs on daily life and smart lockdown continues in the country, but a part of this activity developing countries are still facing even greater difficulties in handling this crisis. This paper was designed to evaluate the status of scientific literature available on Covid-19 pandemic and to relate this situation from Pakistan perspective. A detailed review of published literature was conducted from March 2020 to August 2020. Covid-19, pandemic, Pakistan, healthcare setup, psychological impact, educational activities and challenges SOPs were utilized as key vocabulary. Miscellaneous searching tools including, Science Direct, Embase, PubMed, Google Scholar and Covid-19 portal from Government of Pakistan were visited for relevant information. A total of 30 research commentaries, articles, opinions and editorial letters were selected based on the required information. This article discusses the effects of COVID-19 on society and focus on SOPs introduced and their effects on the physical and mental health of the general public.


Subject(s)
COVID-19 , Pandemics , COVID-19 Vaccines , Communicable Disease Control , Cost of Illness , Developing Countries , Humans , Mass Vaccination , Pakistan
7.
Pak J Pharm Sci ; 34(2): 499-506, 2021 Mar.
Article in English | MEDLINE | ID: mdl-34275822

ABSTRACT

Natural oils are rich in polyunsaturated fatty acids (PUFs) like omega 3, omega 6 and other nutrients that boost physical and mental health. Traditionally these oils have been used to treat joint pain associated with several inflammatory conditions. In this study, we investigated the antioxidant and analgesic properties of the sesame oil (SO), fish oil (FO) and combination of these two oils (SO+FO). Different concentrations of the SO, FO and SO+FO combination 0.02-4mg/ml were used for assessing the free radical scavenging activity by DPPH method and the IC50 value was calculated. Acetic acid-induced abdominal writhing test, tail immersion and hot plate models were used to determined analgesic effect. Results showed that both oils were well tolerated as no signs of toxicity or death were noticed during the observational study period. SO+FO combination showed the best antioxidant properties as shown by DPPH assay. Similarly in analgesic models, SO and FO significantly reduced the number of abdominal contractions (p<0.05) however, SO+FO (1:1) exhibited highly significant results (p<0.001) in writhing reflex test. Furthermore, SO and FO both increased the reaction time on a hot plate as well as in tail flick test (p<0.05) whereas, SO+FO significantly increased reaction time (p<0.001) in hot plate and in tail flick test as compared to SO and FO single treatments. Conclusively, our results suggest that the combination of both oils (SO+FO) exhibited significant antioxidant and analgesic potential that it could be considered as one of the active combinations for relieving pain in adjunctive treatment for joint pain associated with rheumatoid arthritis.


Subject(s)
Analgesics/pharmacology , Antioxidants/pharmacology , Behavior, Animal/drug effects , Fish Oils/pharmacology , Nociception/drug effects , Sesame Oil/pharmacology , Acetic Acid , Animals , Biphenyl Compounds , Hot Temperature , Indicators and Reagents , Injections, Intraperitoneal , Mice , Oxidative Stress/drug effects , Picrates , Reaction Time/drug effects , Reflex/drug effects , Sharks
8.
Arch Virol ; 165(4): 967-972, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32060792

ABSTRACT

In Pakistan, the HIV situation has gone from an outbreak to a concentrated epidemic, and the virus has now crossed into the low-risk population. In addition, several new HIV outbreaks have occurred in different parts of the country. HIV-1 subtype A has been the major epidemic subtype in Pakistan; however, as the epidemic has grown, the emergence of several new subtypes and recombinant forms has been observed. Here, we present the first case and genetic analysis of an unassigned, complex recombinant form in a Pakistani HIV-infected individual with virological failure. Genetic analysis of the sequence indicated that this recombinant form is multi-drug resistant, harboring drug resistance mutations against more than one class of antiretroviral drugs.


Subject(s)
HIV Infections/virology , HIV-1/genetics , Recombination, Genetic , Adult , Anti-HIV Agents/therapeutic use , Drug Resistance, Viral , Genotype , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV-1/classification , HIV-1/drug effects , HIV-1/isolation & purification , Humans , Male , Pakistan/epidemiology , Phylogeny
9.
Pak J Pharm Sci ; 33(4): 1747-1753, 2020 Jul.
Article in English | MEDLINE | ID: mdl-33583812

ABSTRACT

The novel coronavirus (nCOVID-19) has spread to endless nations and turn out to be a pandemic around the globe. Because of the developing number of affirmed cases and open public hazard owing to its high risk of infection rate, it has expected a lot of consideration from world health organizations and national health regulatory and monitoring agencies. The world is in surge to explore or discover novel treatment options and vaccine that can lead to cure. There is no proven effective treatment for nCOVID-19 however along with available antiviral therapy Chinese researchers recommended herbal treatments as effective and alternative treatments options to treat this pandemic. Herbal products are wealthy in dynamic phytochemicals, such as the terpenoids, various collection of flavonoids, sulfides, lignans constiuents, coumarins concentrates, saponins moities, polyphenolics composite, numerous alkaloids, polyines, furyl mixtures, proteins and related compounds, thiophenes and peptides groups. In this review we discussed pathogeneis, immunity and current herbal treatment strategies of nCOVID-19 to cure this world wide pandemic.


Subject(s)
COVID-19 Drug Treatment , Phytotherapy , Plant Preparations/therapeutic use , COVID-19/immunology , COVID-19/prevention & control , Citrus , Curcuma , Drugs, Chinese Herbal/therapeutic use , Zingiber officinale , Glycyrrhiza , Humans , Immunity, Cellular/immunology , Immunity, Humoral/immunology , Immunity, Innate/immunology , Nigella sativa , SARS-CoV-2
10.
Pak J Pharm Sci ; 33(5): 1945-1953, 2020 Sep.
Article in English | MEDLINE | ID: mdl-33824100

ABSTRACT

We determined anti-Parkinson's activity of M. chamomilla L. tea in chlorpromazine (CPZ) developed investigational animal model. In this research, effects of M. chamomilla L. tea 2.14ml/ kg P.O were studied on cataleptic behavior and its effect on brain histopathological changes and immunohistochemistry (IHC) in rats. The experimental design was developed by administering CPZ (3mg/kg, I/P) for twenty-one days to produce Parkinson's disease-like symptoms to 4 animal groups. We observed that chlorpromazine significantly produced motor dysfunctions (catalepsy) in a time period of twenty-one days. The M. chamomilla L. significantly (P<0.005) minimized/shorten/taper down catalepsy in rats just like standard group (Levodopa/carbidopa treated group). The maximum reduction was observed from both treated and standard groups on the 21st day. M. chamomilla L. treated rats mid brain sections showed presence of proliferative blood vessels, increase cellularity with reactive glial cells as compared to CPZ group. Furthermore, immunostaining CD68 & CD21 of M. chamomilla L. treated rats mid brain region showed few CD68 cells & no polymorphs neutrophils after CD21 staining. Thus, this research work disclosed the neuroprotective effect of M. chamomilla L. tea against Parkinson's disease-like symptoms or anti-Parkinson's activity induced by CPZ.


Subject(s)
Antiparkinson Agents/pharmacology , Behavior, Animal/drug effects , Brain/drug effects , Catalepsy/prevention & control , Matricaria , Motor Activity/drug effects , Neuroprotective Agents/pharmacology , Parkinsonian Disorders/prevention & control , Plant Extracts/pharmacology , Animals , Antiparkinson Agents/isolation & purification , Brain/metabolism , Brain/pathology , Brain/physiopathology , Catalepsy/chemically induced , Catalepsy/pathology , Catalepsy/physiopathology , Chlorpromazine , Disease Models, Animal , Male , Matricaria/chemistry , Neuroprotective Agents/isolation & purification , Parkinsonian Disorders/chemically induced , Parkinsonian Disorders/pathology , Parkinsonian Disorders/physiopathology , Plant Extracts/isolation & purification , Rats, Wistar
11.
Pak J Pharm Sci ; 33(2(Supplementary)): 821-826, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32863257

ABSTRACT

Clinical and hospital pharmacy services are not just medical and pharmaceutical sciences but also occupy significant placement in healthcare system. Pakistan is a developing state with a huge prerequisite for changes in the general wellbeing framework, specially hospital and clinical aspect of pharmaceutical services. The principal intention of this study is to analyze the services offered by different pharmacies in hospitals of Karachi in terms of infrastructure and personnel service qualities. The study was conducted in a cross sectional way that included stratified sampling technique. Reactions were broken down utilizing descriptive and inferential insights of measurements. The fundamental result procedures incorporated the scope of hospital pharmacy services, the general recruitment of clinical drug specialists (pharmacist), the product and equipment used in hospital pharmacy services, the background of staff (educational), acquisition of proficient training mode, practical involvement and experience. The clinical pharmacy facilities coverage mutually on the departmental scale (median =22.43%) and patient scale (median =17.25%) do not comply the 100% coverage that is obligatory for standard practices. In addition, 48.65% of the pooled hospitals data has shown absence of distinct administration rules for hospital and clinical pharmacists, and 45.33% lacks the use of rational drug software. It is concluded that important parameters like drug monitoring, medication records keeping; appropriate drug information software's and quality assurance in hospitals still need attention for better patient outcomes.


Subject(s)
Pharmacy Service, Hospital/statistics & numerical data , Career Mobility , Cross-Sectional Studies , Humans , Pakistan , Pharmacists/statistics & numerical data , Workforce/statistics & numerical data
12.
Pak J Pharm Sci ; 33(3): 937-945, 2020 May.
Article in English | MEDLINE | ID: mdl-33191216

ABSTRACT

The majority of the world population suffers from mental and behavioral disorder. It is the need of the time to find an alternate of presently available medicines in order to decrease the medical expense. Homeopathic remedies are available and prescribed by homeopaths for treatment of anxiety and depression. Unfortunately, no data are available that proves its potential to relieve mental illness. The current study is designed to assess neuro behavioral and antidepressant like effects of homeopathic remedies Staphysagria, Argentum nitricum and Ignatia amara in comparison with standard drug (escitalopram). Different neuro behavioral activities were analyzed. The animals were administered the doses of all homeopathic remedied (60 µl to the rats) and escitalopram (0.042 mg to rats) through the oral route. The activities were observed on day 30th and day 60th. Our result suggests that the swimming time in Staphysagria treated group were significantly improved (p<0.001) after day 60th and significance rise was observed (p<0.01) in Ignatia amara treated animals, whereas significant decline (p<0.05) in struggling time was observed in Argentum nitricum administered animals after the 60th day as compared to 30th day. The central square crossings were improved highly significantly (p<0.001) after the 30th day dosing, by all three remedies and peripheral squares crossing were found highly significantly increased (p<0.001) after chronic dosing in Staphysagria and Ignatia amara treated groups. It is concluded from the results that all three homeopathic remedies produce comparable effects like standard drug while among all three remedies Staphysagria possess a potent antidepressant activity. To the best of our knowledge the current study reports first time the anti-depressant potential of homeopathic remedies in rodents.


Subject(s)
Antidepressive Agents/pharmacology , Behavior, Animal/drug effects , Depression/drug therapy , Homeopathy , Locomotion/drug effects , Plant Extracts/pharmacology , Silver Nitrate/pharmacology , Animals , Delphinium , Depression/physiopathology , Disease Models, Animal , Female , Male , Open Field Test , Rats , Strychnos , Swimming , Time Factors
13.
Pak J Pharm Sci ; 33(2): 511-521, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32276892

ABSTRACT

Natural oils are enriched with polyunsaturated fatty acids (PUFAs) which are important for our health. Recent experimental data explained that PUFAs might have a beneficial effect on various brain functions such as anxiety, dementia, epileptic seizures, depression or bipolar and other neurobehavioral diseases. The objective of the current research work was to evaluate the effect of sesame oil, fish oil and mixture of both oils (1:1) on neurobehavioral changes and cognition. For this purpose shark fish oil and sesame oil were extracted out and there poly unsaturated and saturated fatty acids were analyzed by using GCFID that exposed the presence of different PUFs in shark fish oil, sesame oil and mixture of both oils. Neurobehavioral changes were seen after 5ml/kg/day sesame oil, 5ml/kg/day shark fish oil and 1:1 combination of both oil 5ml/kg/day administration on open field, cage crossing, light and dark, stationary rod, forced swimming induced depression test and water maze test. Our GCFID results showed sesame and fish oil enriched with higher amount of PUFs and showed significant anxiolytic and antidepressant like effect after 30 days of treatment (P<0.05) however combination of these both oils exhibited greater efficacy (P<0.01) in reducing anxiety and depression as imipramine standard drug. Results showed that combination of both oils (sesame oil and fish oil) could be a better option to treat neurobehavioral problems as compared to alone.


Subject(s)
Dietary Supplements , Fish Oils/pharmacology , Locomotion/drug effects , Maze Learning/drug effects , Sesame Oil/pharmacology , Swimming/psychology , Animals , Fish Oils/isolation & purification , Locomotion/physiology , Male , Maze Learning/physiology , Mice , Sesame Oil/isolation & purification , Sharks
14.
Pak J Pharm Sci ; 33(1(Supplementary)): 355-360, 2020 Jan.
Article in English | MEDLINE | ID: mdl-32122868

ABSTRACT

Current outbreak of dengue has shown serious health concerns in Pakistan. The present study reports the anti-dengue potential of Carica papaya natural compounds. The leaves of C. papaya have previously shown promising results in cure of Dengue fever. The aim of this project is to find specific bioactive compounds by computational screening and biological activities of C. papaya against serine NS2B, NS3 and NS5 proteases of dengue virus. Docking study resulted in the screening of nine bioactive compounds having highest docking scores. However, three compounds namely epigallocatchin, catechin and protocatechuric acid had the strongest binding affinity with the active residues i.e., Ser135, His51 and Asp75 of dengue virus serine proteases. Results also indicated that the extract of C. papaya was a strong antimicrobial and antioxidant agent. It is concluded that the C. papaya compounds can be commercially applied for medical formulations against dengue virus.


Subject(s)
Carica , Dengue Virus/drug effects , Phytochemicals/pharmacology , Protease Inhibitors/pharmacology , Serine Endopeptidases , Viral Nonstructural Proteins/antagonists & inhibitors , Dengue/drug therapy , Dengue Virus/enzymology , Humans , Molecular Docking Simulation/methods , Phytochemicals/therapeutic use , Protease Inhibitors/isolation & purification , Protease Inhibitors/therapeutic use , Serine Endopeptidases/metabolism , Viral Nonstructural Proteins/metabolism
15.
Metab Brain Dis ; 34(4): 1191-1199, 2019 08.
Article in English | MEDLINE | ID: mdl-31055785

ABSTRACT

Neuroinflammation plays a key role in progressive degeneration of dopaminergic cells. Upregulation of prostaglandins and free radicals formation are involved in the mechanisms of cell death in Parkinson's disease (PD). The present study aimed to investigate the neuroprotective effect of diclofenac against chlorpromazine (CPZ) induced catalepsy and motor impairment in mice. Adult Wistar rats treated with CPZ (3 mg/kg/day, IP) were orally dosed with diclofenac and L-dopa/carbidopa for 21 days. Catalepsy was measured after 21 days of dosing by using standard bar test at 30, 60, 90, 120 and 180 min then motor performances were assessed via open field test and wire hanging test. Histopathological investigation and determination of dopamine (DA) and 3,4-Dihydroxyphenylacetic acid (DOPAC) levels of rat's brain was also carried out. We found that CPZ treated group exhibited reduced motor impairment after 21 days of treatment in open field and wire hanging test (P < 0.01) as compared to control group. The cataleptic scores of CPZ treated rats were also significantly increased (P < 0.01) after 21 days of chronic dosing, however diclofenac treated groups showed significant reduction in cataleptic scores with improved motor performances. Histopathology of CPZ treated rats showed marked degeneration with architecture distortion in the mid brain region. Dopaminergic degeneration is confirmed by neurochemical results that showed reduced amount of dopamine and DOPAC levels in mid brain. Moreover, histopathological slides of diclofenac treated rats showed improved architecture with reduced gliosis of mid brain region as well as improved dopamine and DOPAC levels were achieved after 21 days dosing of diclofenac. Taken together, the present work provide an evidence that diclofenac ameliorated behavioral performances by mediating neuroprotection against CPZ induced PD via preventing dopaminergic neuronal cell death.


Subject(s)
Catalepsy/drug therapy , Chlorpromazine , Diclofenac/therapeutic use , Neuroprotective Agents/therapeutic use , 3,4-Dihydroxyphenylacetic Acid/metabolism , Animals , Carbidopa/pharmacology , Carbidopa/therapeutic use , Catalepsy/chemically induced , Corpus Striatum/drug effects , Corpus Striatum/metabolism , Diclofenac/pharmacology , Dopamine/metabolism , Female , Levodopa/pharmacology , Levodopa/therapeutic use , Male , Motor Activity/drug effects , Rats , Rats, Wistar
16.
Pak J Pharm Sci ; 32(3 (Supplementary)): 1207-1213, 2019 May.
Article in English | MEDLINE | ID: mdl-31303592

ABSTRACT

Ligand based virtual screening (LBVS) is based on the hypothesis that similar structures have similar biological functions. In this research paper, ligand based virtual screening has been performed in order to predict the inhibitors for monoamine oxidase (MAO-B), an enzyme specifically involved in the metabolism of non-hydroxylated amines such as benzylamine and beta-phenylethylamine (PEA), thus, could be the target to treat various neurodegenerative disorders like Parkinson's disease. For this purpose, Afro Database, a subset of ZINC natural compound database has been screened using Random Forest Modeling (RF). For the training of RF model, 36 reference molecules, the known inhibitors of MAO have been collected from Duke's phyto-chemical and ethno-botanical database. As an outcome of this screening, 31 compounds out of 968 compounds from Afro Database (compounds from African medicinal plants) are predicted to be active as MAO-B inhibitor, Out of the 31 predicted active compounds, Norlichexanthone (ZINC05765089) is predicted to be most active against MAO-B with highest RF score 0.795181, along with the other top hits, could be the putative drug candidates for the prevention/ treatment of Parkinson's disease.


Subject(s)
Monoamine Oxidase Inhibitors/pharmacology , Phytochemicals/pharmacology , Plants, Medicinal/chemistry , Africa , Drug Evaluation, Preclinical/methods , Ligands , Models, Theoretical , Monoamine Oxidase Inhibitors/chemistry , Phytochemicals/chemistry , Xanthones/chemistry , Xanthones/pharmacology
17.
Pak J Pharm Sci ; 32(4(Supplementary)): 1829-1834, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31680079

ABSTRACT

Monoamine oxidase A (MAO-A), an enzyme found on outer mitochondrial membrane, catalyzes the oxidative deamination of biogenic amines. Recently, it has been studied that MAO-A have a role in the cancer progression by elevating the generation of Reactive oxygen species (ROS) and by promoting epithelial to mesenchymal transition (EMT) through activation of Vascular endothelial growth factor (VEGF) and its co-receptor neuropilin-1. In this study, an attempt has been made to identify new lead candidates for inhibiting the MAO-A induced initiation and progression of cancer by using molecular docking method. For this purpose, 967 phyto-chemicals from African medicinal plants (AfroDb) were docked gainst the MAO-A (PDB ID: 2Z5X) using Molegro Virtual Docker (MVD) software. MVD calculates the binding energies of target enzyme and ligands at lowest energy conformations by using the piecewise linear potential (PLP) scoring functions. Evaluation of docking studies suggests that compounds Quercetin (ZINC03869685), Apigenin (ZINC03871576), Luteolin (ZINC18185774), [(2R,3S,4R,5S) 3,4,5 trihydroxytetrahydropyran-2-yl]methyl (ZINC14422042) and Scutellarein (ZINC05842416) are docked with highest MVD score -104.412 kcal/mol, -100.189 kcal/mol, -98.5797 kcal/mol, -98.1878 kcal/mol, -97.5296 kcal/mol respectively, therefore, can effectively inhibit MAO-A enzyme and can serve a role as potential lead compounds for developing new drugs for the suppression of cancer.


Subject(s)
Monoamine Oxidase Inhibitors/pharmacology , Monoamine Oxidase/metabolism , Neoplasms/drug therapy , Neoplasms/metabolism , Phytochemicals/pharmacology , Epithelial-Mesenchymal Transition/drug effects , Humans , Kinetics , Models, Molecular , Molecular Conformation , Molecular Docking Simulation , Protein Binding , Quercetin/pharmacology , Vascular Endothelial Growth Factor A
18.
Pak J Pharm Sci ; 32(2 (Supplementary)): 895-898, 2019 Mar.
Article in English | MEDLINE | ID: mdl-31103989

ABSTRACT

Methylphenidate is a psychostimulant used for the treatment of (ADHD) attention deficit hyperactivity syndrome in children and adults. After chronic administration it is known to produce behavioral disorders including anxiety. Previous studies demonstrated that co-administration of buspirone can reduce behavioral and cognitive adverse effects produced by methylphenidate. The aim of the present study is to measure the levels vanillylmandelic acid (VMA) excretion in urine following prolong administration of methylphenidate, buspirone and their combination. Samples of urine for the estimation of the urinary VMA excretion were collected from treated and control male Wistar rats. We found significant (P<0.01) raised urinary VMA excretion in methylphenidate group however significant (P<0.01) reduction in VMA levels were seen after buspirone co-administration. Excretion of VMA in urine would allow the monitoring of sympatho-adrenomedullary system activity. This study could be helpful to increase the clinical use of methylphenidate in the treatment of different disoders.


Subject(s)
Buspirone/pharmacokinetics , Methylphenidate/pharmacokinetics , Vanilmandelic Acid/urine , Animals , Buspirone/administration & dosage , Male , Methylphenidate/administration & dosage , Rats, Wistar
19.
Pak J Pharm Sci ; 32(4(Supplementary)): 1861-1867, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31680084

ABSTRACT

Drug utilization evaluation (DUE) is an arrangement of continuous, orderly, criteria-based assessment of medication utilizes to guarantee that medicines are utilized suitably. In the event that treatment is regarded to be improper, provider and patient intervention may be important to optimize therapeutic efficacy. In the present study drug utilization evaluation of Piperacillin/Tazobactam was carried out in prospective manner. A well structured data collection form was constructed to collect the related information regarding demographic, clinical use, indication, culture sensitivity criteria, outcomes of therapy, renal impairment cases of dose adjustments and appropriate use. Results of chi square indicated insignificant relationship between gender and as p value was found to be p=0.446 and 0.111 for use of drug alone and in combination. Similarly insignificant relationship between gender and use of drug in combination with other antibiotics as p value was found to be p=0.111. It was found that from 61-70 years (Therapeutic Effectiveness; n=12, 9.37%), (Therapeutic Failure; n=10, 45.45%) and mortality (n=1, 50%) were quite higher. The prescription pattern was in accordance with standard guidelines. Study indicated need to elevate prescribers to pursue generic prescribing and rationally utilize antibiotics to avert advancement of resistance at the level of hospital and community. These sorts of studies are valuable for acquiring data about medication utilize designs and for recognizing inconceivable expense of medicines.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Piperacillin, Tazobactam Drug Combination/therapeutic use , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Drug Therapy, Combination/methods , Drug Utilization , Drug Utilization Review , Female , Humans , Male , Middle Aged , Prospective Studies , Tertiary Healthcare , Young Adult
20.
Pak J Pharm Sci ; 32(4(Supplementary)): 1879-1883, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31680087

ABSTRACT

Opioids and non-opioids have long been used as analgesic, anti-inflammatory and antipyretic. Long-term use of these drugs may lead to severe toxicities. Therefore natural remedies are now being explored to avoid risk of adverse effects associated with the use of these conventional medicines. Bioactive components from milk of different species have been identified as nutraceuticals, but no experimental or clinical study is conducted so far to explore the analgesic and anti-inflammatory potential of camel milk. In this study we evaluated camel milk for its possible analgesic and antiinflammatory activity. The anti-inflammatory effects of camel milk was studied in rats using paw edema method (induced by acetic acid) while tail-flick method was used to evaluate its analgesic effect in mice. Significantly increased tail-flick latency was shown after camel milk (33ml/kg) treatment when compared with acetylsalicylic acid at all time intervals. Anti-inflammatory activity of camel milk was significant (p<0.001) at 4th hour of treatment as shown by maximum percentage inhibition in edema volume (46.84%) in comparison to control. Results of our present study suggested possible use of camel milk as adjuvant therapy in treating various chronic pain and inflammatory ailments. Camel milk could further be investigated in future for recognition of biochemical constituents responsible for its antiinflammatory and pain relieving activities.


Subject(s)
Analgesics/pharmacology , Anti-Inflammatory Agents/pharmacology , Biological Products/pharmacology , Camelus/metabolism , Milk/metabolism , Animals , Antipyretics/pharmacology , Carrageenan/pharmacology , Edema/chemically induced , Edema/drug therapy , Female , Fever/chemically induced , Fever/drug therapy , Male , Mice , Models, Animal , Pain/chemically induced , Pain/drug therapy , Rats
SELECTION OF CITATIONS
SEARCH DETAIL