Bayesian sample size determination for coefficient of variation of normal distribution.

Sample size determination is an active area of research in statistics. Generally, Bayesian methods provide relatively smaller sample sizes than the classical techniques, particularly average length criterion is more conventional and gives relatively small sample sizes under the given constraints. The objective of this study is to utilize major Bayesian sample size determination techniques for the coefficient of variation of normal distribution and assess their performance by comparing the results with the freqentist approach. To this end, we noticed that the average coverage criterion is the one that provides relatively smaller sample sizes than the worst outcome criterion. By comparing with the existing frequentist studies, we show that a smaller sample size is required in Bayesian methods to achieve the same efficiency.

Synthesis, molecular docking evaluation for LOX and COX-2 inhibition and determination of in-vivo analgesic potentials of aurone derivatives.

In the current study, seven (7) aurone derivatives (ADs) were synthesized and employed to in-vitro LOX and COX-2 assays, in-vivo models of acetic acid-induced mice writhing, formalin-induced mice paw licking and tail immersion test to evaluate their analgesic potential at the doses of 10 mg and 20 mg/kg body weight. Molecular docking was performed to know the active binding site at both LOX and COX-2 as compared to standard drugs. Among the ADs, 2-(3,4-dimethoxybenzylidene)benzofuran-3(2H)-one (WE-4)possessed optimal LOX and COX-2 inhibitory strength (IC50=0.30 µM and 0.22 µM) as compared to standard (ZileutonIC50 = 0.08 µM, CelecoxibIC50 = 0.05 µM). Similarly in various pain models compound WE-4 showed significantly (p < 0.05) highest percent analgesic potency as compared to control at a dose of 20 mg/kg i.e. 77.60 % analgesic effect in acetic acid model, 49.97 % (in Phase-1) and 70.93 % (inPhase-2) analgesic effect in formalin pain model and 74.71 % analgesic response in tail immersion model. By the administration of Naloxone, the tail flicking latencies were reversed (antagonized) in all treatments. The WE-4 (at 10 mg/kg and 20 mg/kg) was antagonized after 90 min from 11.23 ± 0.93 and 13.41 ± 1.21 to 5.30 ± 0.48 and 4.80 ± 0.61 respectively as compared to standard Tramadol (from 17.74 ± 1.33 to 3.70 ± 0.48), showing the opiodergic receptor involvement. The molecular docking study of ADs revealed that WE-4 had a higher affinity for LOX and COX-2 with docking scores of -4.324 and -5.843 respectively. As a whole, among the tested ADs, compound WE-4 demonstrated excellent analgesic effects that may have been caused by inhibiting the LOX and COX-2 pathways.

Sample size determination for time-to-event endpoints in randomized selection trials with generalized exponential distribution.

Randomized selection trials are frequently used to compare experimental treatments that have the potential to be beneficial, but they often do not include a control group. While time-to-event endpoints are commonly applied in clinical investigations, methodologies for determining the required sample size for such endpoints, except exponential distribution, are lacking. In recent times, there has been a shift in clinical trials, with a growing emphasis on progression-free survival as a primary endpoint. However, the utilization of this measure has typically been restricted to specific time points for both sample size determination and analysis. This alteration in approach could wield a substantial influence on the clinical trial process, potentially diminishing the capacity to discern variances between treatment groups. In the calculation of sample sizes for randomized trials, this investigation operates under the assumption that the time-to-event endpoint conforms to either an exponential, Weibull, or generalized exponential distribution.

A comparison of single- and double-threshold ROC plots for mixture distributions.

The receiver operating characteristics (ROC) analysis is commonly used in clinical settings to check the performance of a single threshold for distinguishing population-wise bimodal-distributed test results. However, for population-wise three-modal distributed test results, a single threshold ROC (stROC) analysis showed poor discriminative performance. The purpose of this study is to use a double-threshold ROC analysis for the three-modal distributed test results to provide better discriminative performance than the stROC analysis. A double-threshold receiver operating characteristic plot (dtROC) is constructed by replacing the single threshold with a double threshold. The sensitivity and specificity coordinates are chosen to maximize sensitivity for a given specificity value. Besides a simulation study assuming a mixture of lognormal, Poisson, and Weibull distributions, a clinical application is examined by a secondary data analysis of palpation test results of the C7 spinous process using the modified thorax-rib static technique. For the assumed mixture models, the discrimination performance of dtROC analysis outperforms the stROC analysis (area under ROC (AUROC) increased from 0.436 to 0.983 for lognormal distributed test results, 0.676 to 0.752 for the Poisson distribution, and 0.674 to 0.804 for Weibull distribution).

Can Pharmacists' Counseling Improve the Use of Inhalers and Quality of Life? A Prospective "Pre" and "Post" Education Analysis in Mardan, Pakistan.

Introduction: Asthma is one of the common major non-communicable respiratory diseases, and is associated with a lower health-related quality of life (QOL). Poor inhalation is a significant contributing factor to poor control of asthma. Community pharmacist has a vital role to play in assisting patients and ultimately improving their asthma conditions through the use of inhalers. Aim: This study aimed to assess the effectiveness of "pre" and "post" educational intervention by a community pharmacist within a community pharmacy on asthma patients' QOL, inhaler technique, and adherence to therapy during the endemic phase of COVID-19. Methods: A "pre" and "post" interventional study was performed at a community pharmacy in the city of Mardan, Pakistan, in 2022 during the COVID-19 pandemic. Patients were divided into two groups, ie control and pharmacist-led education groups. After assigning patients to both groups, the baseline data were collected and followed for one month to compare the reduction in errors in the use of inhalers, QOL, and adherence to therapy. A paired sample t-test was performed, keeping a p-value <0.05 as statistical significance. Results: A total of 60 patients were recruited, majority (58.3%) were females, and 28.3% were from the age group of 46-55 years old. A statistically significant difference was observed in the pre- and post-education QOL score among patients in the pharmacist-led education group, from a mean ± SD at pre-education of 40.23±10.03 to a mean±SD at post-education of 48.10±5.68. Similarly, a statistically significant difference was observed for the correct use of inhalers, ie MDIs and DPIs. Similarly, a statistically significant difference was observed in the adherence status between pre-education and post-education by pharmacists. Conclusion: The findings of the study revealed a positive impact of community pharmacist-led education on QOL, inhaler technique, and adherence to therapy among patients with asthma.

The amygdala connectivity with depression and suicide ideation with suicide behavior: A meta-analysis of structural MRI, resting-state fMRI and task fMRI.

In recent decades, the primary intention of neuroscientists and psychiatrics is to evaluate the connectivity between brain regions and psychiatric disorders. The amygdala has central immersion in memory alliance, stress response, emotional perception, and automatic responses to emotional stimuli. This paper uses a meta-analysis approach to establish the relationship between structural resting state and functional amygdala connectivity with depression and suicide ideation with suicide behavior. In addition, this study explores the moderating effect of patients' demographic characteristics (gender and age) based on 30 studies. The results show that structural amygdala connectivity is positively related to the instability of depression, while for resting and task functional connectivity amygdala shows a significant negative connection with depression. Furthermore, the amygdala showed a partial activation for non-suicide self-injuries and suicide ideation. From structural and functional magnetic imaging, the current findings also support the moderating effect of the age of the participants on the amygdala connectivity with psychiatric conditions. Generally, amygdala connectivity with psychiatric disorders was not significantly moderate with the role of gender, however, this study enhances the existing hypothetical review articles and confirms the connectivity of the psychological condition with the amygdala region. It concludes that the amygdala plays a vital role in regulating and responding to emotions.

COVID-19 Pandemic Data Modeling in Pakistan Using Time-Series SIR.

Pakistan is currently facing the fourth wave of the deadly coronavirus, which was first reported in Wuhan, China, in December 2019. This work utilizes the epidemiological models to analyze Pakistan's COVID-19 data. The basic susceptible, infected, and recovered (SIR) model is studied assuming Bayesian and time-series SIR (tSIR) approaches. Many studies have been conducted from different perspectives, but to the best of our knowledge, no study is available using the SIR models for Pakistan. The coronavirus incubation period has been set to 14 days across the globe; however, this study noticed that the assumption of 14 days is not suitable for Pakistan's data. Furthermore, on the basis of R 0, we infer that COVID-19 is not a pandemic in Pakistan, as it was in other nations, such as the United States, India, Brazil, and Italy, among others. We attribute this to the best strategy adopted by the Government of Pakistan to minimize the burden of COVID-19 cases in Pakistani hospitals. It is also noticed that the posterior-based SIR (pSIR) model with uniform prior toR 0 and Poisson distribution (of log-likelihood) provides better results as compared to other distributions. From time-series SIR (tSIR), we observed that the value of the reporting rate (ρ) is less than 1 which means that cases are underreported.

Effects of Artemisia macrocephala Jacquem on Memory Deficits and Brain Oxidative Stress in Streptozotocin-Induced Diabetic Mice.

Different species of Artemisia have been reported to have therapeutic potential in treating various health disorders, including diabetes and memory dysfunction. The present study was planned to evaluate the effects of Artemisia macrocephala Jacquem crude extract and its subfractions as antiamnesic agents in streptozotocin-induced (STZ) diabetic mice. The in vivo behavioral studies were performed using the Y Maze test and novel object recognition test (NORT) test at doses of 100 and 200 mg/kg of crude extract and 75 and 150 mg/kg of fractions. The in vitro and ex vivo anticholinesterase activities, along with biochemical parameters (superoxide dismutase, catalase, glutathione and lipid peroxidation) in the brain, were evaluated. Blood glucose levels were monitored with a glucometer; crude extract and fractions reduced the glucose level considerably, with some differences in the extent of their efficacies. The crude extract and fractions demonstrated significant inhibitory activity against cholinesterases (AChE and BuChE) in vitro. Crude, chloroform and ethyl acetate extract were found to be more potent than the other fractions, with IC50 of Crd-Am = 116.36 ± 1.48 and 240.52 ± 1.35 µg/mL, Chl-Am = 52.68 ± 1.09 and 57.45 ± 1.39 µg/mL and Et-Am = 75.19 ± 1.02 and 116.58 ± 1.09 µg/mL, respectively. Oxidative stress biomarkers like superoxide dismutase, catalase and glutathione levels were elevated, whereas MDA levels were reduced by crude extract and all fractions with little difference in their respective values. The Y-maze test and novel object recognition test demonstrated declines in memory impairment in groups (n = 6) treated with crude extract and fractions as compared to STZ diabetic (amnesic) group. The most active fraction, Chl-Am, was also subjected to isolation of bioactive compounds; three compounds were obtained in pure state and designated as AB-I, AB-II and AB-III. Overall, the results of the study showed that Artemisia macrocephala Jacquem enhanced the memory impairment associated with diabetes, elevated acetylcholine levels and ameliorated oxidative stress. Further studies are needed to explore the beneficial role of the secondary metabolites isolated in the present study as memory enhancers. Toxicological aspects of the extracts are also important and need to be evaluated in other animal models.

Evaluation and identification of essential therapeutic proteins and vaccinomics approach towards multi-epitopes vaccine designing against Legionella pneumophila for immune response instigation.

The Legionellaceae group comprises the Legionella, containing 58 species with 70 serotypes. For instance, Legionella pneumophila is the deadliest serotype to cause Legionnaires infectious and is responsible for 90% of the infections in humans. The bacterial pathogen is associated with a severe lung infection, known as legionaries' disease. It is resistant to multiple drugs, thus warranting novel vaccine candidates identification to immune the host against infections caused by the said pathogen. For this, we applied the subtractive proteomics and reverse vaccinology approaches to annotate the most essential genes suitable for vaccine designing. From the whole proteome, only five proteins (Q5ZVG4, Q5ZRZ1, Q5ZWE6, Q5ZT09, and Q5ZUZ8) as the best targets for further processing as they fulfill all the standard parameters set for in silico vaccine design. Immuno-informatics approaches were further applied to the selected protein sequences to prioritized antigenic epitopes for design a multi-epitope subunit vaccine. A multi-epitopes vaccine was designed by using suitable linkers to link the CTL (cytotoxic T lymphocytes), HTL (Helper T lymphocytes), B cell epitopes, and adjuvant to strengthen the vaccine's immunogenicity. The MEVC(multi-epitopes vaccine construct) was reported to interact with human immune receptor TLR-2 (toll-like receptor) robustly (docking score = -357.18 kcal/mol), and a higher expression was achieved in the Escherichia coli system (CAI = 0.88, and GC contents = 54.34%). Moreover, immune simulation revealed that on the 3rd day, the neutralization of the antigen started, while on the 5th day, the antigen was completely neutralized by the secreted immune factors. In conclusion, the designed vaccine candidate effectively triggered the immune response against eh pathogen; however, wet lab-based experimentations are highly recommended to prove the protective immunological proficiency of the vaccine against L. pneumophila.

Development of multi-epitope subunit vaccine for protection against the norovirus' infections based on computational vaccinology.

Human Norovirus belongs to a family Calciviridae, and was identified in the outbreak of gastroenteritis in Norwalk, due to its seasonal prevalence known as "winter vomiting disease." Treatment of Norovirus infection is still mysterious because there is no effective antiviral drugs or vaccine developed to protect against the infection, to eradicate the infection an effective vaccine should be developed. In this study, capsid protein (A7YK10), small protein (A7YK11), and polyprotein (A7YK09) were utilized. These proteins were subjected to B and T cell epitopes prediction by using reliable immunoinformatics tools. The antigenic and non-allergenic epitopes were selected for the subunit vaccine, which can activate cellular and humoral immune responses. Linkers joined these epitopes together. The vaccine structure was modelled and validated by using Errat, ProSA, and rampage servers. The modelled vaccine was docked with TLR-7. The stability of the docked complex was evaluated by MD simulation. To apply the concept in a wet lab, the reverse translated vaccine sequence was cloned in pET28a (+). The vaccine developed in this study requires experimental validation to ensure its effectiveness against the disease.Communicated by Ramaswamy H. Sarma.

GC/MS analysis, anti-leishmanial and relaxant activity of essential oil of Chenopodium ambrosioides (L.) from Malakand region.

Chenopodium ambrosioides is abundantly available in Malakand region. As constituents and concentrations of essential oils vary based on its geographical location, we carried our current study to extract and evaluate its possible relaxant activity in rabbits' jejunum and anti-leishmanial activity against promastigotes of Leishmania tropica. The essential oil was obtained from aerial fresh parts through steam distillation followed by GC/MS analysis. Antispasmodic activity was performed on spontaneous and KCl induced contractions. Curves for calcium concentration response (CCRCs) were prepared with and without different concentrations of essential oils and verapamil - a standard calcium channel blocker as per our reported procedures. GC/MS analysis indicated that the essential oil contains 4-carene (56.59%) and o-cymene (41.46%), the two most abundant compounds previously reported from this species. The LD50 value for acute toxicity is 279.66±2.2mg/kg. The essential oil have significant antileishmanial activity with LC50 of Log10 (1.83±0.0026) ×10-6mg/ml, potent relaxant activity on rabbits' jejunal preparations with respective EC50 = 1.46±0.15mg/ml for spontaneous activity. For KCl (80mM) induced contractions, EC50=0.26±0.02mg/ml. In CCRCs, the oil produced a right shift as exhibited by verapamil. More, its relaxant activity, which is mediated through calcium channel blocking mechanism, proves a rationale for its traditional use in gut spasm.

Synthesis, crystal studies and biological evaluation of flavone derivatives.

Three substituted flavone derivatives have been synthesized from substituted O-hydroxy acetophenones and 4-trifluoromethyl benzaldehyde in good yield. These compounds were characterized by NMR spectroscopy and single crystal X-ray Diffraction. Compound F1 and F3 were re-crystallized from their concentrated solutions in chloroform ethyl acetate mixture while F2 was re-crystallized in ethyl acetate n-hexane mixture. Compound F1 and F3 are monoclinic (space group P21/c) with lattice parameters: [a, b, c (A) / ß (°)] = 13.332 (2), 15.616 (2) / 6.2898 (8) and 13.9716 (15), 7.1868 (7), 13.6912 (14) / 91.113(6) respectively. Compound F2 is Triclinic (space group P-1) and has lattice parameters: [a, b, c (Å) / α, ß, γ (°)] = 6.5002 (6), 8.3801 (9), 13.5989 (14) / 89.348(5), 85.141(4), 84.521(5). Antioxidant, antibacterial and cytotoxic profile was investigated. The compounds showed moderate to less activity on 1,1-diphenyl-2-picryl-hydrazyl (DPPH), Hydrogen peroxide (H/2/O/2) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) models of radical scavenging activity while promising antibacterial potentials were recorded. Furthermore, these molecules can also be used as potential candidates for new antitumor agents.

Isolation and characterization of bacteriophage to control multidrug-resistant Pseudomonas aeruginosa planktonic cells and biofilm.

Pseudomonas aeruginosa is Gram-negative bacterium, one of the leading cause of drug-resistant nosocomial infections in developing countries. This bacterium possesses chromosomally encoded efflux pumps, poor permeability of outer-membrane and high tendency for biofilm formation which are tools to confer resistance. Bacteriophages are regarded as feasible treatment option for control of resistant P. aeruginosa. The aim of the current study was isolate and characterized a bacteriophage against P. aeruginosa with MDR and biofilm ability. A bacteriophage MA-1 with moderate host range was isolated from waste water. The phage was considerable heat and pH stable. Electron microscopy revealed that phage MA-1 belongs to Myoviridae family. Its genome was dsDNA (≈50 kb), coding for eighteen different proteins (ranging from 12 to 250 KDa). P. aeruginosa-2949 log growth phase was significantly reduced by phage MA-1 (2.5 × 103 CFU/ml) as compared to control (without phage). Phage MA-1 also showed significant reductions of 2.0, 2.5 and 3.2 folds in 24, 48, and 74 h old biofilms after 6 h treatment with phage respectively as compared to control. It was concluded from this study that phage MA-1 has capability of killing P. aeruginosa planktonic cells and biofilm, but for complete eradication cocktail will more effective to avoid resistance.

In vitro and in vivo Antidiabetic Properties of Phenolic Antioxidants From Sedum adenotrichum.

Natural products serve as the mainstay of human life, and today, almost half of the drugs in clinical practice are the natural origin. Keeping in view the importance of medicinal plants and natural products, Sedum adenotrichum also known as Rosularia adenotrichum was selected for the present study. The crude extract of S. adenotrichum whole plant was obtained through a rotary evaporator. The extract was analyzed for a polyphenolic profile using high-performance liquid chromatography with a diode-array detector. The extract was subjected to detail in vivo antidiabetic study. In this study, body weight, blood glucose level, glycated hemoglobin, lipid profile, liver function tests, and renal function tests were performed in animal models. The extract was tested for in vitro α-glucosidase inhibition activity. Results of high-performance liquid chromatography with a diode-array detector chromatogram revealed a total of 22 polyphenolic compounds. No major change in body weight was noted in experimental animals. Alloxan induction led to a significant elevation in plasma glucose level. A significant decline was noted in blood glucose and glycated hemoglobin concentration in rats treated with the extract as well as with glibenclamide. Renal/liver function tests, lipid profile, alkaline phosphatase, and serum cholesterol were normalized by the extract-treated rats. The α-glucosidase inhibitory activity at 62.5 and 1,000 µg/ml was noted to be 63.97 and 80.80, respectively, both approaching to standard. The results reveal that the extract was rich in important phenolic compounds. In the antidiabetic potentials of the crude extract, there might be involved several pancreatic and extra-pancreatic mechanisms acting synergistically to induce the potent antidiabetic effect.

Improvement of catalytic properties of starch hydrolyzing fungal amyloglucosidase: Utilization of agar-agar as an organic matrix for immobilization.

In this study, amyloglucosidase was immobilized within agar-agar through entrapment technique for the hydrolysis of soluble starch. Enzymatic activities of soluble and entrapped amyloglucosidase were compared using soluble starch as a substrate. Partially purified enzyme was immobilized and maximum immobilization yield (80%) was attained at 40 gL-1 of agar-agar. Enzyme catalysis reaction time shifted from 5.0 min to 10 min after immobilization. Similarly, a five-degree shift in temperature (60 °C-65 °C) and a 0.5 unit increase in pH (pH-5.0 to pH-5.5) were also observed. Substrate saturation kinetics revealed that Km of entrapped amyloglucosidase increased from 1.41 mg ml-1 (soluble enzyme) to 3.39 mg ml-1 (immobilized enzyme) whereas, Vmax decreased from 947 kU mg-1 (soluble enzyme) to 698 kU mg-1 (immobilized enzyme). Entrapped amyloglucosidase also exhibited significant catalytic performance during thermal and storage stability when compared with soluble enzyme. Reusability of entrapped amyloglucosidase for hydrolysis of soluble starch demonstrated its recycling efficiency up to six cycles which is an exceptional characteristic for continuous bioprocessing of soluble starch into glucose.

A possible mechanistic approach of synthetic flavonoids in the management of pain.

Flavonoids are phenolic compounds that have always attracted pharmaceutical researchers and food manufacturers. Nature has indirectly provided us flavones in our daily diet i.e. tea, fruits, juices and vegetables. Flavones have got special position in research field of natural and synthetic organic chemistry due to their biological capabilities. Three substituted flavone derivatives have been synthesized from substituted O-hydroxy acetophenones and 4-trifluoromethyl benzaldehyde in good yield. The structures have been established by different spectroscopic techniques like 1HNMR 13CNMR, IR spectroscopy. The compounds were then screened for their enzyme inhibition potential and antinociceptive response in mice models with writhings induced by acetic acid, tail immersion and formalin-induced nociception assay procedures and structure activity relationship was established. The effects following pretreatment with naloxone were also studied to reveal the involvement of opioid receptors in the antinociceptive action. The flavone derivatives showed moderate to weak inhibition against LOX. Moreover, significant to moderate decrease in the number of abdominal constrictions, increase in paw-licking response time in both phases and a significant raise in latency time in nociception models. Moreover, the antinociceptive response was significantly attenuated by pretreatment with opioid receptor antagonist suggesting the involvement of opioidergic system in the analgesic action. The flavone derivatives showed analgesic response in all models of nociception suggesting the possible involvement of opioidergic system in the antinociceptive action.

Antidiabetic potential of flavonoids from Artemisia macrocephalla Jaquem in streptozotocin-induced diabetic rats: Pharmacological and biochemical approach.

Plants belongs to Asteraceae family are reported to be rich in major phytochemical including flavonoids and are documented to acquire antidiabetic response. Antidiabetic effects of salvigenin, eupatilin and cirsilineol were screened on in-vitro enzyme inhibition and in-vivo streptozotocin animal models. Administration of salvigenin, eupatilin and cirsilineol (7.5 and 15mg/kg) produced antidiabteic responses in streptozotocin model for diabetes. All natural flavonoids reduces the blood glucose level to a significant level (*P<0.05, **P<0.01, ***P<0.001, n=8) but promising results were observed in eupatilin at dose of 7.5mk/kg (364.12±4.3 to 128.41±4.2mg/dL, n=8) and at dose of 7.5mk/kg 363.65±4.8 to 126.14±5.1mg/dL, n=8). Administration of salvigenin, eupatilin and cirsilineol (7.5 and 15mg/kg) for 28 days showed a substantial fall (*P<0.05, **P<0.01, ***P<0.001, n=8) in total cholesterol, LDL and triglcerides (TGs) in comparison to diabetic model. The isolated flavonoids reduced considerably the serum ALP, SGPT and SGOT in rats intoxicated with streptozotocin. The results indicate that the flavonoids may be useful in the development of new antidiabetic drugs.

Nootropic effects of synthetic flavonoid derivatives on scopolamine induced memory impairment in mice via cholinesterase inhibition and antioxidant system.

The synthesized flavonoid derivatives (flavonols and flavones) were subjected for in-vitro anticholinesterase evaluation followed by assessment of in-vivo memory enhancing effects using animal models. The ex-vivo analysis of brain was carried out and portions were subjected foe estimation of biochemical parameters that includes AChE, ACh, SOD and CAT level. Among tested flavonoids, the para substituted chloro containing flavonol (OF2) and flavone (F2) revealed a considerable in-vitro AChE and BuChE % inhibition with an IC50 values. It was observed from the in-vivo results that OF1-OF3 at 12.5 mg/kg b.w has significance over F1-F3 in ameliorating the memory in scopolamine induced amnesic mice in passive avoidance step through and novel object recognitions test. Scopolamine elevated significantly the AChE level, decreased the contents of ACh, SOD and CAT in the brain in amnesic model. The flavonoid derivatives showed significant effects on these changes by decreasing the ex-vivo AChE contents, enhancing the level of ACh, SOD and CAT suggesting their possible role as cholinesterase and antioxidant. These findings suggest that synthetic flavonols and flavones may serve as potential candidates for developing safer and effective nootropic agents.

Isolation of flavonoides from Artemisia macrocephala anticholinesterase activity: Isolation, characterization and its in vitro anticholinesterse activity supported by molecular docking.

In this study the flavonoids isolated from Artemisia macrocephala were screened out for anticholinesterase activity. The isolated flvanoids were characterized by HNMR, NOESY, COSY, HMBC, HSQC and mass spectroscopy. The compounds (1-4) in appropriate quantities were isolated from chloroform fraction using gravity column chromatography by eluting ethyl acetate/n-hexane solvent system. The flavonoids were characterized and resulted in the form of mono substituted methoxy flavones to tri substituted flavones. Ellman's assay techniques were used to find out enzyme inhibition. Operating environment (MOE) software was used for molecular docking studies. Compounds (1), (2) and (3) showed 88.42±2.76, 84.50±1.60 and 90.16±2.98 percent inhibition of the acetyl cholinesterase (AChE) respectively at 1000µg/mL concentrations with IC50 value 165, 60, 65µg/mL respectively which were comparable to that of standard galanthamine. While for butyryl cholinesterase (BChE), (1), (2) and (3) showed 91.63±4.32, 81.03±3.53 and 87.69±2.84 percent inhibitions respectively at 1mg/mL as compared to the standard galanthamine which caused 96.50±2.41 percent inhibition at the same concentration. Whereas, compound (4) exhibited moderate activity for both the enzymes. Molecular docking studies confirmed the experimental AChE and BChE inhibitory activities of the test samples by their virtue of multiple teractions with target enzymes. The results confirm that the specie has biologically active constituents that are more useful for the management of several neurodegenerative ailments like ataxia, Parkinson's disease, Alzeimer's disease and some other types of dementia.

Nephrotoxic effects of Valeriana wallichii.

Aminoglycosides are the commonly used antibiotics against Gram negative bacteria. Their clinical applications are limited due to nephrotoxic side effects. Therefore, the current study was undertaken in an attempt to increase the use of these drugs without causing nephrotoxicity by exploring the nephroprotective effects of a medicinal plant with high flavonoid contents and strong antioxidant properties, namely Valeriana wallichii. A daily dose of 200mg/kg of the extract derived from V. wallichii was employed for a period of three weeks. The results obtained revealed that co-therapy of extract with gentamicin protected some changes in renal functions; however, failed to provide a complete protection as assessed by biochemical, physiological and histological parameters. It can be concluded from the current findings that V. wallichii failed to deliver protective effects against gentamicin induced renal damage in spite of strong flavonoid contents and antioxidant properties.