Search

Kiran Shahbaz,1 Alamgeer,1 Vibhu Paudyal,2 Maryam Zubair,3 Maryam Zahra Safdar,4 Momina Tahir,4 Laraib Akram,4 Salamat Ali4 1Department of Pharmacology, University College of Pharmacy, University of the Punjab Lahore, Pakistan; 2Institute of Clinical Sciences, University of Birmingham, Edgbaston Birmingham, UK; 3Faculty of Experimental Medicine Orebro University, Sweden; 4Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, GC University Faisalabad, Faisalabad, PakistanCorrespondence: Salamat Ali, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, GC University Faisalabad, Faisalabad, Pakistan, Tel +00-92-3004189052; +00-92-041-9201036, Email drsalamatali@gcuf.edu.pkBackground: Prevalence of psychological disorders among individuals with diabetes is significantly higher as compared to the general population.Aim: This study aimed to assess the prevalence and impact of psychological disorders on pharmacotherapy of diabetes patients.Methodology: This cross-sectional study was conducted at two primary care hospitals in Pakistan from April to June 2023. The nine-item Patient Health Care Questionnaire (PHQ-9) scale was used to assess depression in the study’s population, and its effects on pharmacotherapy of diabetes. Chi-square test was used to evaluate relationship between ordinal variables/categorical variables and depression whereas; Student’s t-test was used to assess the relationship between numerical variables with depression.Results: A total of 320 patients were assessed, comprising 120 (37.5%) males and 200 (62.5%) females, with a mean age of 52.5 (SD± 11.8) years. The average duration of diabetes is 7.0 (SD± 5.4). The average PHQ-9 score was 8.3 (SD± 5.5). Depression was found to be prevalent in 43.7% of the study population. Gender (female) (p-value 0.002), advanced age (p-value 0.002), lower income (p-value 0.001), education levels (p-value 0.001), longer duration of diabetes (p-value 0.001), poor diabetes control according to BSR value (p-value 0.001), usage of injectable insulin (p-value 0.005), and concomitant diseases (p-value 0.001) were found to be independently linked with depression. Significant association was observed between depression and treatment adherence (p-value 0.0025), number of missed doses (p-value 0.045), and difficulty in diabetes management (p-value 0.0015).Conclusion: Our study highlights significant prevalence of depression in study population and the prevalent depression negatively impacts on treatment adherence. It also revealed that depression complicates diabetes management resulting in poor medication adherence, poor diabetes control and diabetes related complications, making diabetes control more challenging and difficult.Keywords: psychological disorders, diabetes, pharmacotherapy, PHQ-9

Millions of people worldwide suffer from diabetes, a medical condition that is spreading at an accelerating pace. Numerous studies show that risk factors that may arise from diabetes can be avoided if the disease is detected early. The health-care monitoring system has benefited greatly from early diabetes prediction made possible by the integration of Deep Learning (DL) and Machine Learning (ML) algorithms. The objective of many early studies was to increase the prediction model accuracy. However, DL algorithms often cannot fully exploit the potential of the available datasets because they are too small. This study includes a very accurate DL model as well as a novel system that integrates cloud services and allows users to directly enhance an existing data set, which can increase the accuracy of DL techniques. Therefore, the Long Short-Term Memory (LSTM) model with controller is chosen for efficient type-1 diabetes prediction. Experimental validation of the proposed Nonlinear Model Predictive Control (NMPC)_LSTM algorithm method is compared with other conventional DL algorithms. The proposed controller method achieves excellent blood glucose set point tracking and the proposed algorithms achieves 98.95% accuracy for the obtained data. It outperforms other existing methods with an increase in percentage accuracy compared to the Benchmark Pima Indian Diabetes Datasets (PIDD).

Noscapine hydrochloride (benzyl-isoquinoline antitussive alkaloid) is an opium derivative and generally used as a cough suppressant. Numerous studies on noscapine hydrochloride have reported that it has potent anti-inflammatory activity. However, the mechanisms by which it exerts an anti-inflammatory function is not well understood. Protein denaturation is the primary step that leads to the organ destruction and permanent arthritic disability. The above-mentioned facts provided the ground to plan this study using different in-vitro and in-vivo approaches. RT-qPCR and ELISA assays were used to assess the inflammatory markers related to protein denaturation in complete adjuvant persuaded rheumatism in Sprague - Dawley rats. The results were collected as paw volume and body weight changes, arthritic scoring and serum antioxidant enzymes assays. These findings demonstrated that all doses of noscapine hydrochloride (10, 20 and 40 mg/kg) studied in this study, significantly (p

Abstract Hedera nepalensis (H. nepalensis) , belonging to the family Araliaceae, is a medicinal plant traditionally used to treat stomach problems. The current study investigated the gastroprotective potential and the mechanism of action of H. nepalensis in diclofenac-and ethanol-induced ulcer models. Anti-oxidant and lipid peroxidation inhibitory prospects of H. nepalensis were checked out by free radical scavenging assay and UV spectrophotometer respectively. Effect of H. nepalensis on the pH, gastric total acidity of gastric juice and protective effects of H. nepalensis against ulcer models have been examined. Histopathological studies have been carried out. The aqueous methanol extract of H. nepalensis (100 µg/mL) showed anti-oxidant (83.55%) and lipid peroxidation inhibitory (70.88%) potential at 1000 µg/mL; the extract had no buffer potential. The extract (400 mg/kg) significantly (81.12% and 63.46%) showed gastroprotective effect in diclofenac and ethanol-induced rat ulcer models respectively. Histopathological studies confirmed the biochemical findings. FTIR analysis showed the presence of carboxylic acid, alkanes, conjugated alkanes, aldehydes and alkyl-aryl ethers. Gallic acid, M-coumaric acid and quercetin were found by HPLC analysis. H. nepalensis exhibited significant protection against diclofenac and ethanol induced gastric damage by anti-oxidant and lipid peroxidation suppression effects suggesting potential broad utility in treatment of diseases characterized with gastric damage.

Usman Sabir,1 Hafiz Muhammad Irfan,1 Alamgeer,2 Aman Ullah,3 Yusuf S Althobaiti,4,5 Mulazim Hussain Asim1 1Department of Pharmacology, College of Pharmacy, University of Sargodha, Sargodha, Punjab, Pakistan; 2Punjab University College of Pharmacy, University of the Punjab, Lahore, Punjab, Pakistan; 3College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University, Islamabad, Pakistan; 4Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, Taif, Saudi Arabia; 5Addiction and Neuroscience Research Unit, Taif University, Taif, Saudi ArabiaCorrespondence: Hafiz Muhammad Irfan, Department of Pharmacology, College of Pharmacy, University of Sargodha, Sargodha, 40100, Punjab, Pakistan, Tel +92 3334673193, Email muhammad.irfan@uos.edu.pk Yusuf S Althobaiti, Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, P.O. Box 11099, Taif, 21944, Saudi Arabia, Email ys.althobaiti@tu.edu.saIntroduction: Non-alcoholic fatty liver disease (NAFLD) is intimately linked to hepatic steatosis, inflammation, insulin resistance (IR), oxidative stress (OS), and ballooning. A high fat diet (HFD) is considered a major etiological factor that primarily covers the numerous features of NAFLD.Methods: The present study aimed to evaluate the protective effect of safranal on hepatic steatosis, OS, liver index, IR index, liver function enzymes, plasma lipids, TNF-α, malondialdehyde (MDA), advanced oxidation protein products (AOPPs) and nitrite (NO2–) levels in a NAFLD rat model fed with a HFD for 12 weeks. The ELISA kits were used to measure TNF-α and insulin in serum and plasma, respectively.Results: HFD significantly induced hepatic steatosis, OS, IR, liver, and oxidative enzyme elevation and inflammation in experimental animals. Rats treated with safranal in ascending order of doses 250 and 500 mg/kg orally for 4-weeks showed a reduction in hepatic lipid’s accumulation, liver index, hepatic enzymes, collagen, hepatic oxidonitrative stress markers (like AOPP, MDA and NO2–), and raised the levels of catalase (CAT) and superoxide dismutase (SOD) enzymes. Glutathione system components, namely glutathione (GSH), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) levels were also restored in the safranal-treated groups. The reduction in serum TNF-α and IR provided further support to the anti-NAFLD effect of safranal. Moreover, the histopathological images indicated reverse of NAFLD activity score (NAS) through mild fatty degeneration, ballooning and inflammation in hepatocytes of treated groups.Conclusion: Findings of blood and tissue analysis concluded that safranal can be a good choice in the management and cure of NAFLD.Graphical Abstract: Keywords: non-alcoholic fatty liver disease, inflammation, insulin resistance, glutathione, safranal

Objective: Mentha (M.) longifolia (L.) is traditionally used for various ailments. The current study was intended to explore the underlying vasorelaxation mechanisms of M. longifolia. Material and methods: Aqueous-methanol extract from the aerial parts of M. longifolia was prepared and subjected to activity-guided fractionation. The vasorelaxant activity was performed using porcine coronary arteries with intact and denuded endothelium. In-vitro PDE inhibitory activity of the active fraction was carried out using the radio-enzymatic assay. The active fraction was also subjected to GCMS. Docking and molecular dynamic simulation studies were also performed Result: We had observed that aqueous-methanolic extract induced relaxation in the coronary artery in a dose-dependent manner when the endothelium was intact and denuded. n-butanol fraction (MLB) has produced a maximum effect, and it was selected for mechanistic studies. MLB has significantly enhanced the relaxation produced by cAMP and cGMP, elevating atrial natriuretic peptide, sodium nitroprusside, isoproterenol, and forskolin. The pre-treatment with MLB inhibited the contractile response produced by KCl, U46619, and CaCl2 in without endothelium rings. MLB has non-selectively inhibited the PDE isoforms. GCMS analysis of MLB has revealed the presence of menthol, thymol, and carvacrol in the active fraction. Docking and molecular dynamic simulation studies have indicated that thymol can be a competitive inhibitor for PDE1. Conclusion: It is postulated that an n-butanol fraction of Mentha longifolia produced endothelium-independent relaxation due to increased levels of cAMP and cGMP caused by the inhibition of various PDEs.

Western diet style (fast food), which includes fatty frozen junk food, lard, processed meats, whole-fat dairy foods, cream, mayonnaise, butter, snacks, and fructose, is a primary etiological determinant for developing nonalcoholic steatohepatitis (NASH) worldwide. Here the primary focus is to see the impact of naturally identified essential oil on disease mechanisms developed in an animal model using the same ingredients. Currently, symptomatic therapies are recommended for the management of NASH due to non-availability of specific treatments. Therefore, the present study was designed to evaluate the potential anti-NASH effect of nerolidol in a rat model fed with a purpose-built diet. The diet substantially induced insulin resistance, hepatic steatosis, dyslipidemia, and elevation of liver enzymes in the experimental animals. The levels of liver oxidative stress markers, nitrites (NO2–), serum pro-inflammatory cytokine (TNF-α) and hepatic collagen were increased in disease control rats. Nerolidol oral treatment in ascending dose order of 250 and 500 mg/kg substantially reduced the steatosis (macrovesicular and microvesicular), degeneration of hepatocytes, and inflammatory cells infiltration. The amounts of circulatory TNF-α and tissue collagen were also reduced at 500 mg/kg dose of nerolidol, expressing its anti-fibrotic effect. The current study described the multiple-hit pathophysiology of NASH as enhanced steatosis, pro-inflammatory markers, and oxidative stress in rats, which resulted in the development of vicious insulin resistance. Nerolidol treatment significantly reduced hepatic lipid accumulation and halted disease progression induced by a hypercaloric diet.

In this paper, we have explored the steady Poiseuille flow of couple stress fluid between two parallel plates under ‎the influence of non-isothermal effects of Reynold viscosity model, using Optimal Homotopy Asymptotic Method ‎‎(OHAM) and New Iterative Method (NIM). We obtained expressions for velocity profile, temperature distribution, ‎average velocity, volume flux and shear stress. The solutions obtained using these methods are in the form of ‎infinite series; therefore, they can be easily computed. Comparative results of solutions obtained by both methods ‎are given using different tables and graphs.

Abstract In this research work, we have studied the steady generalized Couette flow of couple stress fluid between two parallel plates considering the non-isothermal effects. The governing equations that are, continuity, momentum and energy equations are reduced to ordinary differential equations. The Optimal Homotopy Asymptotic Method (OHAM) and New Iterative Method (NIM) are used to solve this coupled system of differential equations. Using the said methods, we have obtained expressions for velocity profile, temperature distribution, volume flux, average velocity and shear stress. The results of OHAM and NIM are compared numerically as well as graphically and a tremendous agreement is attained.

Background: Juglone, a natural phenolic compound obtained from the walnut tree, is known for its wide range of biological activities. However, it has yet to be tested for its effects on hypertension and vascular tone. This investigation was aimed to explore the antihypertensive effect and the nature of vascular reactivity of juglone in rat models. Methods: Juglone was tested in in vivo and in vitro experiments in rats. The responses were analyzed and recorded through a PowerLab data acquisition system. Results: Intravenous injection of juglone significantly decreased the mean arterial blood pressure (MAP) in normotensive and hypertensive rats (Max. fall, 43.50 ± 2.96 vs 49.66 ± 3.28 mmHg). In rats pretreated with Nω-Nitro l-arginine methyl ester (L-NAME), the effect of juglone on MAP was reduced as compared to the control. However, in rats pretreated with atropine the fall in MAP by juglone was not altered. Juglone induced relaxation in the phenylephrine, K+ (80 mM), and angiotensin II pretreated isolated rat aortic rings. This vasorelaxant effect was reduced with L-NAME pretreatment. Atropine pretreatment did not modify the vasorelaxant effect of juglone. Pre-incubation with juglone attenuated the intracellular Ca2+ release by suppressing phenylephrine peak formation and also shifted CaCl2 concentration–response curves (CRCs) to the right. Of note, combined treatment with 4-aminopyridine and barium chloride also reduced juglone-mediated vasorelaxation suggesting a role of K+-channels as well. Conclusion: In conclusion, juglone exerts its antihypertensive effect through vasorelaxation, which is mediated by nitric oxide, inhibition of intracellular calcium release and opening of K+-channels.

The appropriate combination of semiconducting polymer–inorganic nanocomposites can enhance the existing performance of polymers-only-based photovoltaic devices. Hence, polyaniline (PANI)/zinc oxide (ZnO) nanocomposites were prepared by combining ZnO nanoparticles with PANI in four distinct ratios to optimize their photovoltaic performance. Using a simple coating method, PANI, ZnO, and its nanocomposite, with varying weight percent (wt%) concentrations of ZnO nanoparticles, i.e., (1 wt%, 2 wt%, 3 wt%, and 4 wt%), were fabricated and utilized as an active layer to evaluate the potential for the high-power conversion efficiency of various concentrations, respectively. PANI/ZnO nanocomposites are characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), atomic force microscopy (AFM), Fourier transform infrared (FTIR) spectroscopy, ultraviolet-visible (UV-vis) absorption, energy dispersive X-ray (EDX), and I-V measurement techniques. The XRD analysis showed a distinct, narrow peak, which corresponds to the wurtzite ZnO (101) plane. The SEM analysis verified the production of the PANI/ZnO composite by demonstrating that the crystalline ZnO was integrated into the PANI matrix. The elemental composition was determined by energy dispersive X-ray analysis (EDX), which confirmed the existence of PANI and ZnO without any impurities, respectively. Using Fourier transform infrared (FTIR) spectroscopy, various chemical bonds and stretching vibrations were analyzed and assigned to different peaks. The bandgap narrowing with an increasing PANI/ZnO composition led to exceptional optical improvement. The I-V characterization was utilized to investigate the impact of the nanocomposite on the electrical properties of the PANI/ZnO, and various concentrations of ZnO (1 wt%, 2 wt%, 3 wt%, and 4 wt%) in the PANI matrix were analyzed under both light and dark conditions at an STC of 1.5 AM globally. A high PCE of 4.48% was achieved for the PANI/ZnO (3 wt%), which revealed that the conductivity of the PANI/ZnO nanocomposite thin films improved with the increasing nanocomposite concentration.

This study was designed to determine the effectiveness of 5-(3-Hydroxybenzylidene)-2, 4, 6(1H, 3H, 5H)-pyrimidinetrione (SR-5), 5-(4-Hydroxybenzylidene)-2, 4, 6(1H, 3H, 5H)-pyrimidinetrione (SR-8), 5-(3-Chlorobenzylidene)-2, 4, 6(1H, 3H, 5H)-pyrimidinetrione (SR-9) and 5-(4-Chlorobenzylidene)-2, 4, 6(1H, 3H, 5H)-pyrimidinetrione (SR-10) against hypertension. In deoxycorticosterone acetate-salt rats, SR-5, SR-8, SR-9, and SR-10 reduced blood pressure and normalized renal functions. In isolated rat aortic rings, SR-5, SR-8, SR-9, and SR-10 relaxed phenylephrine (PE) and K+-induced contractions. The vasodilator effect was endothelium-independent. Test compounds caused a rightward shift of Ca++ and PE concentration-response curves with a reduction of maximum response. SR-5, SR-8, SR-9, and SR-10 inhibited PE peak contractions in a Ca++ free medium. In guinea-pig atria, SR5, SR-8, SR-9, and SR-10 caused a mild-to-moderate inhibition of force and rate of contractions. In the aorta and heart tissues, the test compounds enhanced glutathione-s-transferase, reduced glutathione and catalase levels, improved cellular architecture, and decreased lipid peroxidation and expression of inflammatory markers: cyclooxygenase 2, tumor necrosis factor alpha, phosphorylated c-Jun N-terminal kinase, and phosphorylated-nuclear factor kappa B, evidenced in the immunohistochemistry, enzyme-linked immunosorbent assay, western blot molecular investigations and a decreased mRNA expression of calcium channel in RT-PCR analysis. SR-5, SR-8, SR-9, and SR-10 increased the urinary output in rats and inhibited the human platelet aggregation. This study revealed that SR-5, SR-8, SR-9, and SR-10 possess BP lowering, reno-protective, vasodilatory (mediated via Ca++ antagonist, antioxidant and anti-inflammatory pathways), partial cardio-suppressant, diuretic, and antiplatelet effects, demonstrating their therapeutic potential in hypertension management.

The present study was conducted with an intent to evaluate the protective effect of butanolic fraction of Delphinium brunonianum on fructose mediated metabolic abnormalities in rats. Rats in all groups except control group were fed on 10% fructose for 6 weeks; however, rats in the treated group also received butanolic fraction for the last 3 weeks, along with the fructose. Moreover, phytoconstituents present in butanolic fraction were analyzed using LC-MS. All doses of butanolic fraction profoundly reduce the fructose-induced blood pressure, sympathetic over-activity, and weight gain. Furthermore, butanolic fraction prominently reduces the glucose intolerance and hyperinsulinemia in fructose-fed rats. On treatment with butanolic fraction, oxidative enzymes and the functionality of the aorta was also restored. Phytochemical analysis revealed the presence of several active constituents including bergenin, scopolin, rutinoside, kaempferol, coumaric acid, apigenin, and gingerol. In conclusion, butanolic fraction of Delphinium brunonianum has the potential to prevent and recover the fructose-induced metabolic perturbations.

In this paper, we report on the synthesis—via the wet chemical precipitation route method—and thin film characteristics of inorganic semiconductor, cuprous oxide (Cu2O) nanoparticles, for their potential application in enhancing the humidity-sensing properties of semiconducting polymer poly(9,9-dioctylfluorene) (F8). For morphological analysis of the synthesized Cu2O nanoparticles, transmission electron microscope (TEM) and scanning electron microscope (SEM) micrographs are studied to investigate the texture, distribution, shape, and sizes of Cu2O crystallites. The TEM image of the Cu2O nanoparticles exhibits somewhat non-uniform distribution with almost uniform shape and size having an average particle size of ≈24 ± 2 nm. Fourier transformed infrared (FTIR) and X-ray diffraction (XRD) spectra are studied to validate the formation of Cu2O nanoparticles. Additionally, atomic force microscopy (AFM) is performed to analyze the surface morphology of polymer-inorganic (F8-Cu2O) nanocomposites thin film to see the grain sizes, mosaics, and average surface roughness. In order to study the enhancement in sensing properties of F8, a hybrid organic–inorganic (F8-Cu2O) surface-type humidity sensor Ag/F8-Cu2O/Ag is fabricated by employing F8 polymer as an active matrix layer and Cu2O nanoparticles as a dopant. The Ag/F8-Cu2O/Ag device is prepared by spin coating a 10:1 wt% solution of F8-Cu2O nanocomposite on pre-patterned silver (Ag) electrodes on glass. The inter-electrode gap (≈5 μm) between Ag is developed by photolithography. To study humidity sensing, the Ag/F8-Cu2O/Ag device is characterized by measuring its capacitance (C) as a function of relative humidity (%RH) at two different frequencies (120 Hz and 1 kHz). The device exhibits a broad humidity sensing range (27–86%RH) with shorter response time and recovery time, i.e., 9 s and 8 s, respectively. The present results show significant enhancement in the humidity-sensing properties as compared to our previously reported results of Ag/F8/Ag sensor wherein the humidity sensing range was 45–78%RH with 15 s and 7 s response and recovery times, respectively. The improvement in the humidity-sensing properties is attributed to the potential use of Cu2O nanoparticles, which change the hydrophobicity, surface to volume ratio of Cu2O nanoparticles, as well as modification in electron polarizability and polarity of the F8 matrix layer.

Abstract Ethno-pharmacological relevance Plants are providing reliable therapy since time immemorial. Pakistan has a great diversity in medicinal flora and people use these ethno-medicines to deal with many skin problems. This review explores the fundamental knowledge on various dermatological properties of medicinal plants of Pakistan and is aimed to provide a baseline for the discovery of new plants having activities against skin issues. Material and method A total of 244 published articles were studied using different research engines like PubMed, Google, Google-scholar and science direct. Results Review of literature revealed ethno-pharmacological use of 545 plant species, belonging to 118 families and 355 genera, to combat various skin ailments. Out of these, ten most commonly used plant species belonging to ten different families are documented in this review. It was also found out that ehno-medicines are prepared using various parts of the plants including leaves (28.32%), whole plant and roots 13.17% and 10.97% respectively, in the form of powder (23.5%) and paste (22.75%). A total of 13 endangered plant species and ten commercially important plants were recorded. Conclusion Medicinal plants of Pakistan have therapeutic effects against several skin problems; however most of medicinal plants are still not evaluated scientifically to support their ethno-pharmacological claim on skin. Dermatological pathogens are recommended to study. Further, the conservational programs should be established for endangered species.

Abstract Respiratory disorders are a common cause of malady and demise in Pakistan due to its remoteness, cold and harsh climatic conditions as well as scarce health care facilities. The people rely upon the indigenous plant resources to cure various respiratory disorders. The primary objective of this review was to assemble all available ethno-medicinal data of plants used for respiratory disorders in Pakistan. Pharmacological activity of these plants (based upon published scientific research), distribution, diversity, use, preparation methods, economical value, conservation status and various available herbal products of some plants have also been explored. This study scrutinized various electronic databases for the literature on medicinal plants used in Pakistan to treat respiratory disorders. A total of 384 species belonging to 85 families used to treat respiratory disorders in Pakistan has been documented. Cough was the disorder treated by the highest number of species (214) followed by asthma (150), cold (57) and bronchitis (56). Most of the plants belongs to Asteraceae (32) and Solanaceae family (32) followed by moraceae (17), Poaceae (13), and Amaranthaceae (13) with their habit mostly of herb (219) followed by Shrub (112) and tree (69). Traditional healers in the region mostly prepare ethno medicinal recipes from leaves (24%) and roots (11%) in the form of decoction. Among the reported conservation status of 51 plant species, 5 were endangered, 1 critically endangered, 11 vulnerable, 14 rare, 16 least concern, 3 infrequent and 1 near threatened. We found only 53 plants on which pharmacological studies were conducted and 17 plants being used in herbal products available commercially for respiratory disorders. We showed the diversity and importance of medicinal plants used to treat respiratory disorders in the traditional health care system of Pakistan. As such disorders are still causing several deaths each year, it is of the utmost importance to conduct phytochemical and pharmacological studies on the most promising species. It is also crucial to increase access to traditional medicine, especially in rural areas. Threatened species need special attention for traditional herbal medicine to be exploited sustainably.

The current study evaluated antidiabetic and antihyperlipidemic activities of aqueous extract of Sigesbeckia orientalis L. (St. Paul’s Wort) (AESO) in an alloxan-induced diabetic rat model. Following OECD guidelines safe doses of AESO were assessed in rats for the main study. Serum/bood glucose, α-amylase, and lipids levels and histopathological evaluations were conducted to assess antidiabetic and associated antihyperlipidemic efficacies of AESO. AESO was found to be safe up to the dose of 2000 mg/kg. Significant (p < 0.05) reduction in glucose and lipids (total cholesterol, triglycerides, low-density lipoproteins) levels was observed in AESO treatment groups. Serum α-amylase, high-density lipoproteins, and total body weight was increased significantly (p < 0.05) in diabetic rats treated with AESO. Histopathological data showed improvement in hepatocyte and pancreatic β-cells islets architecture. HPLC analysis identified quercetin, gallic acid, vanillic acid, p-coumaric acid, m-coumaric acid and cinnamic acid in AESO which are suggested to be responsible for observed antihyperglycemic and antihyperlipidemic attributes. Further studies to standardise the extract and evaluation of safety profile in long-term toxicity studies are recommended for safe and effective antidiabetic nutraceuticals development.

Rheumatoid arthritis is an autoimmune inflammatory disorder, despite the discovery of numerous drugs there is still need to introduce newer, safer and more effective sources of drugs such as medicinal herbs. Present research work was an attempt to appraise the antiarthritic potential of Ribes alpestre Decne in rheumatoid arthritis. In vitro inhibition of protein (bovine serum albumin and egg albumin) denaturation, Human red blood cell membrane stabilization assays along with formaldehyde induced arthritis in rats were commenced in this study. Findings of present investigation demonstrated significant and dose dependent antiarthritic effect of Ribes alpestre. Aqueous ethanolic extract, butanol and aqueous fraction illustrated 95%, 69.233% and 92.840% protection at 6400 ug/mL against bovine serum albumin denaturation respectively. Similarly, plant extract together with butanol and aqueous fractions showed 3653.47%, 1484.03% and 3563.19% inhibition of pathological alteration of egg albumin in that order. Moreover, hydroethanolic extract with butanol and aqueous fraction exhibited 91.29%, 65.73% and 89.62% stabilization against erythrocyte hemolysis at 6400 ug/mL correspondingly. Furthermore, hydroethanolic extract, butanol and aqueous fraction notably 73.49%, 66.42% and 68.87% decreased paw edema at highest dose (200 mg/kg). Similarly aqueous ethanolic extract, butanol and aqueous fraction illustrated 72.38%, 54.90% and 66.33% decrease in paw thickness at 200 mg/kg. Hence results suggested that Ribes alpestre possess antiarthritic potential thus supporting its use as natural remedy in rheumatic conditions.

The present study was conducted in District Central Jail, Peshawar, Khyber Pakhtunkhwa, Pakistan to assess the factors shaping the criminal attitude of adults. The study proceeded with the objectives to assess the relationship between psychological factors with criminal attitude among criminals. A sample size of N=196 was randomly drawn from the universe. Sampling covered all the adult criminal of the age group of 18-64 years from the total population of N=360 convicted criminals. Frequency distribution and bi-vitiate analysis between dependent variable i.e. criminal attitude and independent variables namely psychological aspects were ascertain through cross tabulation while indexing the dependent variable. At bi-variate level, parents sentence several time was found significant, relatives’ involvement in criminal activities, large family was responsible for crimes, parents using intoxicants, joint family generating criminal attitude. Moreover, feeling of low social status, unhappy family life, commitment to family cause, broken family, low moral values, internalization of criminal values and vicious tendencies of crimes were found significant with criminal attitude.. The study concluded that poor family with large size had high interaction with criminals were some of the attributing factors for committing crimes.

Abstract Background The roots and stem bark of Berberis orthobotrys (Berberidaceae) have long been used traditionally to treat joint pain. Though, it has not been pharmacologically assessed for rheumatoid arthritis. The current study explores anti-arthritic activity and phytochemical analysis of aqueous-methanolic extract (30:70) and fractions (ethyl acetate, n-butanol, and aqueous) of Berberis orthobotrys roots. Methods Anti-arthritic potential was evaluated in vitro using protein denaturation (bovine serum albumin and egg albumin) and membrane stabilization methods at 12.5–800 μg/ml concentration and in vivo via turpentine oil, formaldehyde and Complete Freund Adjuvant (CFA) models at 50, 100 and 150 mg/kg doses. Also, in vitro antioxidant ability was appraised by reducing power assay. Moreover, total flavonoid content, Fourier transform infrared spectroscopy and High performance liquid chromatography of n-butanol fraction were performed. Results The results revealed concentration dependent inhibition of albumin denaturation and notable RBC membrane stabilization, with maximum results obtained at 800 μg/ml. Similarly, plant exhibited dose dependent anti-arthritic effect in turpentine oil and formaldehyde models, with maximum activity observed at 150 mg/kg. The results of CFA model depicted better protection against arthritic lesions and body weight alterations. Also, B.orthobotrys remarkably ameliorated altered hematological parameters, rheumatoid factor and positively modified radiographic and histopathological changes. Additionally, plant exhibited remarkable anti-oxidant activity. Moreover, phytochemical analysis revealed polyphenols and flavonoids. Conclusion Taken together, these results support traditional use of B.orthobotrys as potent anti-arthritic agent that may be proposed for rheumatoid arthritis treatment.

The aim of this study was to validate the traditional uses of ulcerene, a poly-herbal formulation in ethanol, aspirin and stress-induced gastric ulcer model of rat. The extent of gastric ulcer formation was studied, using ulcer score, ulcer index, percentage cure through gross examination and histopathological evaluation. A significant (p

Context: Ficus carica L. (Moraceae) fruit is said to possess cardiovascular activity and has been used empirically in traditional phytotherapies for the treatment of hypertension and various other cardiovascular diseases. Objective: This study investigated the antihypertensive and cardioinhibitory activity of the aqueous-methanol extract of F. carica fruit in rats. Materials and methods: Extract in 250, 500 and 1000 mg/kg doses (p.o.) were administered to normotensive Sprague Dawley rats and blood pressure was measured using non-invasive technique. Hypertension was induced in rats by oral administration of 10% glucose for 3 weeks. Hypotensive effect of extract (1000 mg/kg p.o) was studied in normotensive and glucose-treated hypertensive rats. Langendorff’s isolated heart technique was used to assess the effect of crude extract on force of contraction and heart rate. In addition, antioxidant potential, TPC, TFC were also assessed by DPPH free radical scavenging activity, Folin–Ciocalteu reagent and AlCl3 assay, respectively. Furthermore, phenolic compounds were analyzed using HPLC-DAD technique. Results and discussion: The 1000 mg/kg dose decreased blood pressure significantly in normotensive and glucose-treated hypertensive rats. The isolated heart study showed that the extract produced negative inotropic and chronotropic effects but it failed to block the stimulatory effect of both adrenaline and CaCl2. HPLC studies on the F. carica extract indicated the presence of quercetin, gallic acid, caffeic acid, vanillic acid, syringic acid, coumaric acid and chromotropic acid. Conclusions: This study demonstrated that aqueous methanol extract of F. carica fruit exerted hypotensive and antihypertensive effects in glucose-induced hypertensive rats.

Context: Cuscuta reflexa Roxb. (Cuscutaceae) has been used traditionally for treating sore knees and kidney problems, but its efficacy has not been scientifically examined in treating arthritis and nephrotoxicity. Objective: Present study determines antiarthritic and nephroprotective potential of the aqueous methanolic extract of Cuscuta reflexa (AMECR). Materials and methods: Antiarthritic activity of Cuscuta reflexa in formaldehyde and turpentine oil-induced rat arthritis models was appraised at 200, 400 and 600 mg/kg doses for 10 days and 6 h period, respectively, and in vitro protein denaturation (bovine serum albumin, egg albumin) inhibition was studied at 25–800 μg/mL concentration. The nephroprotective effect involved gentamicin-induced nephrotoxicity in rats at 200, 400 and 600 mg/kg doses. Results: Plant extract at 600 mg/kg significantly reduced paw oedema and joint swelling with maximal inhibition of 71.22% at the 6th hour for turpentine oil and 76.74% on 10th day for formaldehyde. Likewise, in vitro results corroborated significant concentration-dependent increase in percentage protection at 800 μg/mL against both bovine serum albumin (89.30%) and egg albumin (93.51%) denaturation. Similarly, 600 mg/kg dose showed maximum nephroprotection by reducing serum urea (41.400 ± 0.510 mg/dL), uric acid (0.740 ± 0.032 mg/dL), blood urea nitrogen (18.370 ± 0.328), creatinine (3.267 ± 0.076) and minimizing kidney weight gain (0.586 ± 0.005) and histopathological alterations on 8th day. Furthermore, phytochemical and HPLC analysis revealed the presence of important phytoconstituents. Discussion and conclusions: These results suggest that AMECR provides protection against arthritis and nephrotoxicity that might be due to the existence of phytoconstituents, thus supporting folkloric claim.

Zaman Ashraf,1,2 Alamgeer,3 Munazza Kanwal,1 Mubashir Hassan,2 Sahar Abdullah,3 Mamuna Waheed,3 Haseeb Ahsan,3 Song Ja Kim2 1Department of Chemistry, Allama Iqbal Open University, Islamabad, Pakistan; 2Department of Biological Sciences, College of Natural Sciences, Kongju National University, Gongju, Republic of Korea; 3Department of Pharmacology, Faculty of Pharmacy, University of Sargodha, Sargodha, Pakistan Abstract: Flurbiprofen–antioxidant mutual prodrugs were synthesized to reduce the gastrointestinal (GI) effects associated with flurbiprofen. For reducing the GI toxicity, the free carboxylic group (–COOH) was temporarily masked by esterification with phenolic –OH of natural antioxidants vanillin, thymol, umbelliferone, and sesamol. The in vitro hydrolysis of synthesized prodrugs showed that they were stable in buffer solution at pH 1.2, indicating their stability in the stomach. The synthesized prodrugs undergo significant hydrolysis in 80% human plasma and thus release free flurbiprofen. The minimum reversion was observed at pH 1.2, ­suggesting that prodrugs are less irritating to the stomach than flurbiprofen. The anti-inflammatory, analgesic, antipyretic, and ulcerogenic activities of prodrugs were evaluated. All the synthesized prodrugs significantly (P

Female constitute half of country population but still facing problem in almost all sectors of life in the male dominating Pakistani society. The major aim of the present study was to find out the benefits of female education as factor affecting their parent’s attitude towards education. Data for the study were collected from two hundred and fourteen (N=214) respondents belonging to two selected villages of district Bannu. A significant association was found among attitude about female education and by getting education females would become good housewives, good mothers, would be able to get better life partners, would bring up their children in a better way and could help their children in educational and social problems. Furthermore they would have job opportunities, would be socio- economically empowered, would make sensible decisions in important matters and they would be less likely to marry early. On the basis of encouraging findings of the study about expected benefits of female educations it is recommended that government and non-government organizations should keep people aware by highlighting these benefits which will ultimately motivate parents to provide education to their female children.

Education not only enables us to become acceptable members of social sphere but also enable us to take right decision at right time. Parents’ decision play important role in the lives of their children. The major aim of the present study was to find out the major causes of enrolling students in public schools by parents. Data for the study were collected from 280 respondents belonging to three selected villages in Tehsil Oghi, District Mansehra. The study found significant association between perception about enrollment in public schools and children’s education was major priority of the educated parents, they understand their educational problems, teach them at home, give importance to sports, provides them latest technologies and facilities, provide tuition to children if needed, believed in hard work of parents and good grades of children in exams and ultimately educated parents’ children obtain good grades. The study recommends that government should initiate mobilization campaign for illiterate parents, which will enhance the enrollment of children in public school.

Fundamental to this research was the evaluation of anticoagulant and thrombolytic potential of Berberis orthobotrys using clotting time, prothrombin time and activated partial thromboplastin time performed at 2.5, 5, 10% concentration. Aqueous-methanol extract significantly (p

Clematis orientalis has been used traditionally to cure rheumatism, but its efficacy has not been scientifically explored in treating rheumatoid arthritis. The present study was designed to investigate the antiarthritic efficacy of C. orientalis using blockade of heat-induced protein alterations and HRBC membrane stabilization methods along with formaldehyde induced arthritis in rats. Aqueous ethanol (30:70) extract and various fractions (hexane, n-butanol and aqueous) produced concentration-dependent and significant (p

The present research work was conducted to appraise the antithrombotic activity of Mentha longifolia using in vitro and in vivo experiments. Aqueous methanolic (70:30) extract produced significant (p

The present study was carried out to evaluate the seeds of Pennisetum glaucum for its blood pressure lowering effect in rats. Aqueous-methanolic extract of P. glaucum seeds in 250, 500 and 1000 mg/kg doses was studied in normotensive, egg-feed diet and glucose-induced hypertensive rats using non-invasive technique. The extract significantly (p˂0.5 - p˂0.001) decreased blood pressure and heart rate with maximum effect at 1,000 mg/kg dose. The extract was found to prevent rise in blood pressure of egg and glucose fed rats as compared to control group in 21 days study. The extract was safe in mice up to dose of 4 g/kg and sub-chronic toxicity study showed that there was no significant alterations in blood chemistry of extract treated rats. It is conceivable, therefore, that aqueous-methanolic extract of P. glaucum seeds has exerted considerable antihypertensive activity which may be due to the presence of phytochemical constituents.

Pakistan’s decision of participating in the war on terror has put the entire country especially FATA on the mercy of extremist and terrorists. The current layer of terrorism and extremism has destroyed the peaceful traditional tribal society. The present study was conducted during 2013 to probe the effect of illiteracy on peace in the war-affected zone FATA. The major findings of the study reveal that illiteracy ratio was high at FATA, making FATA safe haven for militants and it was one of the main cases of terrorism, leading to violence, making the illiterate youth and madrasa students more vulnerable to militancy. Furthermore lacks of interest in education, dysfunctional education institution, and preference to madrasa education were also the variables, which were affecting peace in FATA. The study also reveals that in the presence of illiteracy sustainable peace is not possible in FATA.

The present study determines the anti-arthritic potential of Ephedra gerardiana ethanolic extract and its ethyl acetate, n-butanol and aqueous fractions adopting in vitro and in vivo tests. In vitro tests included thermally induced bovine serum albumin denaturation and egg albumin denaturation, also membrane stabilizing assay at concentration of 50-6400 µg/mL, whereas in vivo study comprised formaldehyde-induced arthritis at 50, 100 and 200 mg/kg doses. The crude extract and fractions inhibited protein denaturation and stabilized red blood cells membrane in concentration-dependent fashion, with maximal effect achieved at 6,400 µg/mL (p

This study was focused with the aim to investigate the antithrombotic potential of Berberis calliobotrys. Aqueous-methanolic extract and various fractions showed significant (p

The present study was commenced to evaluate the anti-arthritic effect of 70% methanol extract and n-butanol and aqueous fractions of Berberis calliobotrys using both in vitro and in vivo arthritis models. Extract and fractions were investigated in vitro for inhibition of protein (bovine serum and egg albumin) denaturation and human red blood cell membrane stabilization. In vivo anti-arthritic activity of extract and fractions at 50, 100 and 200 mg/kg was assessed using turpentine oil and formaldehyde-induced arthritis, while, 200 mg/kg dose was evaluated against complete Freunds adjuvant-induced arthritis. B. calliobotrys produced significant (p

The present study was undertaken to evaluate antihyperlipidemic effect of aqueous methanolic extract of Berberis orthobotrys in experimentally induced hyperlipidemic animal models. Atorvastatin was used as standard drug. The crude extract (50 and 100 mg/kg) significantly prevented the increase in low density lipoprotein (LDL), very low density lipoprotein (VLDL), total cholesterol (TC), triglyceride (TG), atherogenic index and coronary risk index in high fat diet, cholesterol, fructose and olive oil-induced hyperlipidemic rat models whereas in ethanol treated mice, the extract reduced VLDL, TG and TC levels. The high density lipoprotein (HDL) level was significantly increased in high fat diet, olive oil and cholesterol induced hyperlipidemic rats. The reduction in serum level of above parameters with 100 mg/kg dose of extract was comparable with atorvastatin. It is concluded that B. orthobotrys has atheroprotective and lipid lowering potential.

In the present study, the hepatoprotective activity of aqueous and ether extracts of Thymus linearis (250 and 500 mg/kg orally) was evaluated against carbon tetrachloride- and paracetamol-induced hepatic damage in mice. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) were assessed. Antioxidant activity of both the extracts was also determined using 1-1-diphenyl-2-picryl hydrazine (DPPH) scavenging method. The results indicated that both the extracts significantly produce a dose dependent reduction in serum levels of ALT, AST, ALP when compared to carbon tetrachloride-and paracetamol-treated groups. The maximum effect in all the parameters was observed at a dose of 500 mg/kg. The extracts also demonstrated a significant antioxidant activity. LD50 of both extracts was found to be a 1050 and 900 mg/kg respectively. It is conceivable that the hepatoprotective activity of T. linearis might be due to the presence of certain pharmacologically active compounds.

Dexibuprofen–antioxidant conjugates were synthesized with the aim to reduce its gastrointestinal effects. The esters analogs of dexibuprofen 5a–c were obtained by reacting its –COOH group with chloroacetyl derivatives 3a–c. The in vitro hydrolysis data confirmed that synthesized prodrugs 5a–c were stable in stomach while undergo significant hydrolysis in 80% human plasma and thus release free dexibuprofen. The minimum reversion was observed at pH 1.2 suggesting that prodrugs are less irritating to stomach than dexibuprofen. The anti-inflammatory activity of 5c (p < 0.001) is more significant than the parent dexibuprofen. The prodrug 5c produced maximum inhibition (42.06%) of paw-edema against egg-albumin induced inflammation in mice. Anti-pyretic effects in mice indicated that prodrugs 5a and 5b showed significant inhibition of pyrexia (p < 0.001). The analgesic activity of 5a is more pronounced compared to other synthesized prodrugs. The mean percent inhibition indicated that the prodrug 5a was more active in decreasing the number of writhes induced by acetic acid than standard dexibuprofen. The ulcerogenic activity results assured that synthesized prodrugs produce less gastrointestinal adverse effects than dexibuprofen. The ex vivo antiplatelet aggregation activity results also confirmed that synthesized prodrugs are less irritant to gastrointestinal mucosa than the parent dexibuprofen. Molecular docking analysis showed that the prodrugs 5a–c interacts with the residues present in active binding sites of target protein. The stability of drug–target complexes is verified by molecular dynamic simulation study. It exhibited that synthesized prodrugs formed stable complexes with the COX-2 protein thus support our wet lab results. It is therefore concluded that the synthesized prodrugs have promising pharmacological activities with reduced gastrointestinal adverse effects than the parent drug.