Search

AbstractPolice were utilised in British India to put down resistance to colonial rule. The role of the police varied from region to region. This article discusses the style of policing and police administration designed by the British administrators in the province of erstwhile Northwest Frontier Province (Presently Khyber Pakhtunkhwa Province of Pakistan) and tribal areas adjacent to the province. Internal security was enforced by the police within the provinces, supplementing military efforts. Instead of using direct coercion, colonial authorities in the northwest frontier and border regions focused on integrating local populations into the system of regional security and coordinating their interests with those of the ruling class. The analysis in this article is based on the Indian archival records in the British Library London and other primary sources available in archives. This analysis demonstrates the importance of understanding colonial policing and police administration in the erstwhile Northwest Frontier province and tribal region near the border between British India and Afghanistan in particular leading to the postcolonial police administration in the northwestern frontier province of present-day Pakistan.

Background/Objectives: Inflammation and analgesia are two prominent symptoms and often lead to chronic medical conditions. To control inflammation and analgesia, many marketed drugs are in practice but the majority of them have severe side effects. Methods: This study involved the synthesis of a pivalate-based Michael product and evaluated it for in vitro COX-1, COX-2, and 5-LOX inhibitory potentials using specific assays. Molecular docking studies were also assessed. Based on the in vitro results, the compound was also subjected to in vivo anti-inflammatory and antinociceptive studies. Results: The pivalate-based Michael product (MAK01) was synthesized by an organocatalytic asymmetric Michael addition of ethyl isobutyrate to N-phenylmaleimide with an isolated yield of 96%. The structure of the compound was confirmed through 1H and 13C NMR analyses. The observed IC50 values for COX-1, COX-2, and 5-LOX were 314, 130, and 105 μg/mL, respectively. The molecular docking studies on the synthesized compound showed binding interactions with the minimized pockets of the respective enzymes. In a carrageenan model, a percent reduction in edema when administered at 10 mg/kg (a reduction of 33.3 ± 0.77% at the second hour), 20 mg/kg (a reduction of 34.7 ± 0.74% at the second hour), and 30 mg/kg (a reduction of 40.58% ± 0.84% after the fifth hour) was observed. The compound showed a significant response at concentrations of 50, 100, and 150 mg/kg with latency times of 10.32 ± 0.82, 12.16 ± 0.51, and 12.93 ± 0.45 s, respectively. Conclusion: In this study, we synthesized a pivalate-based Michael product for the first time. Moreover, based on its rationality and potency, it was found to be an effective future medicine for the management of analgesia and inflammation.

Cultivation of high-yield varieties and unbalanced fertilization have induced micronutrient deficiency in soils worldwide. Zinc (Zn) is an essential nutrient for plant growth and its deficiency is most common in alkaline and calcareous soils. Therefore, this study aimed to evaluate the effect of Zn applied either alone or in combination with foliar application on the quality and production of wheat grown in alkaline soils. Zn was applied in the form of zinc sulfate (ZnSo4) to the soil and as a foliar spray during the sowing and tillering stages, respectively. Results showed that Zn fertilization of wheat, irrespective of modes of application, significantly increased grain and biological yield, grain per spike, and 1,000 grains weight over control; however, its effect was more noticeable when applied as 7.5 kg ha−1 of soil Zn combined with foliar Zn at 2.5 kg ha−1. Zn application significantly increased the grain protein content from 9.40% in the control to a maximum of 11.83% at soil Zn of 10 kg ha−1. Similarly, Zn application improved Zn, phosphorus (P), and potassium (K) concentrations in wheat grains. Moreover, correlation analysis showed that the grain Zn concentration was positively correlated with the grain P concentration. The correlation between P concentration in wheat grains and 1,000 grain weight was not significant. A total of 1,000 grains weight was positively correlated with tillers per plant, grain yield, and biological yield. There were positive correlations between protein content, biological yield, grain yield, and tillers per plant. Therefore, soil-applied Zn + foliar application in alkaline soils with limited Zn availability is crucial for improving wheat yield and grain quality.

[Objective] The differences in aggregate stability and infiltration characteristics of loess under different forest and grass vegetation restoration types were compared in order to provide a theoretical basis for the optimization of ecological restoration patterns in the Loess Plateau. [Methods] Abandoned land (C1, control), alfalfa land (C2), natural grassland (C3), mixed forest land of Pinus tabuliformis and Platycladus orientalis (L1), and mixed forest land of Robinia pseudoacacia and P. orientalis (L2) were used to investigate differences in aggregate stability and infiltration characteristics and their exogenous factors. Water-stable aggregate composition and saturated hydraulic conductivity were determined by the Savinov method and a single-ring two-ponding depth infiltrometer, respectively. Mean weight diameter (MWD), geometric mean diameter (GMD), fractal dimension (D), percentage of aggregate destruction (PAD), water-stable macroaggregate content (>0.25 mm, Mw), and saturated hydraulic conductivity sample (Ks) were used as evaluation indicators. [Results] ① In the 0—30 cm soil layer, C1 had the lowest GMD and MWD, and GMD and MWD in forest and grass vegetation restoration types followed the order of 〔L1 and C3〕>〔L2 and C2〕, respectively, whereas PAD and D showed the opposite order. ② In the 0—10 cm soil layer, L1 dominated the highest macroaggregate (>0.25 mm) content (47.24%), followed by C3 and L2, while C1 had the lowest content (24.00%). In the 10—30 cm soil layer, C3 dominated the highest macroaggregate (>0.25 mm) content (35.41% at 10—20 cm ; 27.96% at 20—30 cm), while L2 had the lowest content (11.46% at 10—20 cm; 8.00% at 20—30 cm). ③ The variation coefficients of topsoil infiltration characteristics for different restoration types ranged from 0.001 to 0.360. The Ks (0.307 cm/min) of L1 was the highest, while the Ks (0.044 cm/min) of C1 was the lowest. ④ Aggregate stability indicators (except PAD) and Ks were significantly correlated with soil organic carbon, porosity, and bulk density. [Conclusion] The restoration of forest and grass vegetation was beneficial for improving aggregate stability and infiltration performance. Compared with natural grassland, long-term forest restoration exhibited better aggregate stability and infiltration characteristics, but those characteristics were worse for short-term forest restoration than for natural grassland. Time accumulation should be emphasized when evaluating the effects of vegetation restoration.

Abstract Hyphaene thebaica fruits were used for the fabrication of spherical erbium oxide nanoparticles (HT-Er2O3 NPS) using a one-step simple bioreduction process. XRD pattern revealed a highly crystalline and pure phase with crystallite size of ~ 7.5 nm, whereas, the W–H plot revealed crystallite size of 11 nm. FTIR spectra revealed characteristic Er-O atomic vibrations in the fingerprint region. Bandgap was obtained as 5.25 eV using K-M function. The physicochemical and morphological nature was established using Raman spectroscopy, reflectance spectroscopy, SAED and HR-TEM. HT-Er2O3 NPS were further evaluated for antidiabetic potential in mice using in-vivo and in-vitro bioassays. The synthesized HT-Er2O3 NPS were screened for in vitro anti-diabetic potentials against α-glucosidase enzyme and α-amylase enzyme and their antioxidant potential was evaluated using DPPH free radical assay. A dose dependent inhibition was obtained against α-glucosidase (IC50 12 μg/mL) and α-amylase (IC50 78 μg/mL) while good DPPH free radical scavenging potential (IC50 78 μg mL−1) is reported. At 1000 μg/mL, the HT-Er2O3 NPS revealed 90.30% and 92.30% inhibition of α-amylase and α-glucosidase enzymes. HT-Er2O3 NPs treated groups were observed to have better glycemic control in diabetic animals (503.66 ± 5.92*** on day 0 and 185.66 ± 2.60*** on day 21) when compared with positive control glibenclamide treated group. Further, HT-Er2O3 NPS therapy for 21 days caused a considerable effect on serum total lipids, cholesterol, triglycerides, HDL and LDL as compared to untreated diabetic group. In conclusion, our preliminary findings on HT-Er2O3 NPS revealed considerable antidiabetic potential and thus can be an effective candidate for controlling the post-prandial hyperglycemia. However, further studies are encouraged especially taking into consideration the toxicity aspects of the nanomaterial.

Dengue is an endemic viral fever transmitted by mosquitoes that may be asymptomatic or cause a nonspecific flu-like illness. The disease’s most severe manifestations are dengue hemorrhagic fever and dengue shock syndrome. Various atypical manifestations have been observed that constitute the expanded dengue syndrome. Although uncommon, it is now known to cause cardiac complications that can be life-threatening and difficult to diagnose. We illustrate a case of a 16-year-old boy infected with dengue who experienced syncope, dizziness, and lethargy. His electrocardiogram showed third degree atrioventricular block which did not resolve with atropine and fluid resuscitation. After excluding all possible causes of complete heart block, transvenous pacing was done. A detailed workup was carried out that favored a diagnosis of subclinical myocarditis leading to complete heart block. The patient did not regain a normal rhythm and was considered for permanent pacemaker implantation. Myocarditis, pericarditis, rhythm disturbances, first- and second-degree atrioventricular blocks, and rarely third-degree heart blocks have been seen in dengue patients. However, a case of dengue illness associated complete heart blocks that is irreversible and necessitates a permanent pacemaker has never been described in the literature, and this is the first such case being reported. This article intends to increase clinicians’ awareness, particularly those in dengue-endemic regions, about better recognition and comprehension of cardiac problems associated with dengue fever.

Purpose – The study aims to analyze the influence of hedonic, utilitarian, and self-esteem motivations on online shopping behavior. Likewise, the mediating role of impulsive shopping and shopping intentions is also analyzed. Design/methodology/approach – The study was carried out with the results of a survey in which 450 respondents participated, and the data was analyzed by using structural equation modeling (SmartPLS 3.0 software). Findings – All the hypothesized links were significant and positive except for the relationship of self-esteem motive with impulsive shopping tendency, which was negative as hypothesized. Moreover, hedonic motive had a strong positive impact on impulsive shopping tendency, whereas, in contrast, utilitarian motive had a strong positive impact on shopping intentions. Practical implications – Managers should focus on functional value rather than emotional value to attract customers who tend to be utilitarian. In contrast, for customers who tend to be hedonic, the product offerings should be visually appealing, stimulating and inspiring, as well as have emotional value. Originality/value – This study investigates the roles of self-esteem and hedonic motives in impulsive shopping behavior. Moreover, by using the theory of planned behavior, this study highlights the roles of hedonic and utilitarian motives in attitude toward engaging in online shopping. Motivos utilitarios, hedónicos y de austoestima en las compras en línea Propósito – El estudio pretende analizar la influencia de las motivaciones hedónicas y utilitarias y la autoestima en el comportamiento de compra online. Asimismo, se analiza el papel mediador de la compra impulsiva y la intención de compra. Metodología – El estudio se realizó con los resultados de una encuesta en la que participaron 450 encuestados y los datos se analizaron mediante el modelo de ecuaciones estructurales (software Smart PLS 3.0). Resultados – Todos los vínculos planteados como hipótesis fueron significativos y positivos, excepto la relación del motivo autoestima con la tendencia a la compra impulsiva, que fue negativa según la hipótesis. Además, el motivo hedónico tuvo un fuerte impacto positivo en la tendencia de compra impulsiva, mientras que, por el contrario, el motivo utilitario tuvo un fuerte impacto positivo en las intenciones de compra. Originalidad – Este estudio investiga el papel de la autoestima y los motivos hedónicos en la conducta de compra impulsiva. Además, al emplear la teoría del comportamiento planificado, este estudio pone de relieve el papel de los motivos hedónicos y utilitarios en la actitud hacia la realización de compras en línea. Implicaciones – Los directivos deberían centrarse en el valor funcional más que en el valor emocional para atraer a los clientes que tienden a ser utilitarios. En cambio, para los clientes que tienden a ser hedónicos, las ofertas de productos deben ser visualmente atractivas, estimulantes e inspiradoras, además de tener valor emocional. 功利动机、享乐动机、和自尊动机在网上购物中的作用 目的 – 本研究旨在分析享乐动机和功利动机以及自尊心对网上购物行为的影响。 而且, 本文也分析了冲动性购物和购物意向在其中的中介作用。 方法 – 本研究采用了由450名受访者参与的调查结果, 并使用结构方程模型（Smart PLS 3.0软件）对数据进行了分析。 研究结果 – 除自尊动机与冲动性购物符合假设所提议的负相关倾向外, 其他所有关系均为显著正相关。此外, 享乐动机对冲动性购物倾向有较强的正向影响, 而功利动机则对购物意向有较强的正向影响。 原创性 – 本研究调查了自尊和享乐动机在冲动性购物行为中的作用。此外, 通过采用计划行为理论, 本研究强调了享乐和功利动机在对参与网上购物态度中的作用。 意义 – 管理者应该关注功能价值而不是情感价值, 以吸引那些倾向于功利主义的顾客。相反, 对于倾向于享乐主义的顾客, 产品应该具有视觉吸引力、刺激性和启发性, 并具有情感价值。

Abstract Aim The study was planned to investigate the phytochemicals, antidiabetic and antioxidant studies of A. consanguineum. Methods The preliminary studies were performed on crude extract and different solvent fractions. Based on the potency, the chloroform fraction was semi-purified to phyto-fractions CHF-1 – 5. Furthermore, CHF-3 was subjected to isolation of pure compounds using column chromatography. The α-glucosidase, α-amylase and antioxidant assays (DPPH, ABTS, H2O2) were performed on all samples. The in-vivo experiments on compounds 1 and 2 were also performed using oral glucose tolerance test. Docking studies were performed on α-glucosidase and α-amylase targets. Results Among all fractions, the chloroform fraction exhibited excellent activities profile giving IC50 values of 824, 55, 117, 58 and 85 μg/ml against α-glucosidase, α-amylase, DPPH, ABTS and H2O2 targets respectively. Among the five semi-purified chloroform phyto-fractions (CHF-1-5), CHF-3 was the leading fraction in activities giving IC50 values of 85.54, 61.19 and 26.58 μg/ml against α-glucosidase, α-amylase and DPPH respectively. Based on the overall potency and physical amount of CHF-3, it was subjected to purification to get compounds 1 and 2. The two compounds were also found potent in in-vitro activities. The observed IC50 values for compound 1 were 7.93, 28.01 and 6.19 μg/ml against α-glucosidase, α-amylase and DPPH respectively. Similarly, the compound 2 exhibited IC50 of 14.63, 24.82 and 7.654 μg/ml against α-glucosidase, α-amylase and DPPH respectively. Compounds 1 and 2 were potent in decreasing the blood glucose levels in experimental animals. Compounds 1 and 2 also showed interactions with the respective enzymes with molecular docking. Conclusions We can conclude that A. Consanguineum is a rich source of natural antidiabetic agents. Bioguided isolation of compound 1 and 2 showed potential inhibitions in all tested in-vitro antidiabetic targets. Further, both the compounds were also able to decrease the blood glucose levels in experimental animals.

Abstract Background Natural phenolic compounds and Phenolics-rich medicinal plants are also of great interest in the management of diabetes. The current study was aimed to analyze phenolics in P. hydropiepr L extracts via HPLC-DAD analysis and assess their anti-diabetic potentials using in-vitro and in-silico approaches. Methods Plant crude methanolic extract (Ph.Cme) was evaluated for the presence of phenolic compounds using HPLC-DAD analysis. Subsequently, samples including crude (Ph.Cr), hexane (Ph.Hex), chloroform (Ph.Chf), ethyl acetate (Ph.EtAc), butanol (Ph.Bt), aqueous (Ph.Aq) and saponins (Ph.Sp) were tested for α-glucsidase and α-amylase inhibitory potentials and identified compounds were docked against these target enzymes using Molecular Operating Environment (MOE) software. Fractions were also analyzed for the nutritional contents and acute toxicity was performed in animals. Results In HPLC-DAD analysis of Ph.Cme, 24 compounds were indentfied and quantified. Among these, Kaemferol-3-(p-coumaroyl-diglucoside)-7-glucoside (275.4 mg g− 1), p-Coumaroylhexose-4-hexoside (96.5 mg g− 1), Quercetin-3-glucoronide (76.0 mg g− 1), 4-Caffeoylquinic acid (58.1 mg g− 1), Quercetin (57.9 mg g− 1), 5,7,3′-Trihydroxy-3,6,4′,5′-tetramethoxyflavone (55.5 mg g− 1), 5-Feruloylquinic acid (45.8 mg g− 1), Cyanidin-3-glucoside (26.8 mg g− 1), Delphinidin-3-glucoside (24 mg g− 1), Quercetin-3-hexoside (20.7 mg g− 1) were highly abundant compounds. In α-glucosidase inhibition assay, Ph.Sp were most effective with IC50 value of 100 μg mL-1. Likewise in α-amylase inhibition assay, Ph.Chf, Ph.Sp and Ph.Cme were most potent fractions displayed IC50 values of 90, 100 and 200 μg mL-1 respectively. Docking with the α-glucosidase enzyme revealed top ranked conformations for majority of the compounds with Kaemferol-3-(p-coumaroyl-diglucoside)-7-glucoside as the most active compound with docking score of − 19.80899, forming 14 hydrogen bonds, two pi-H and two pi-pi linkages with the Tyr 71, Phe 158, Phe 177, Gln 181, Arg 212, Asp 214, Glu 276, Phe 300, Val 303, Tyr 344, Asp 349, Gln 350, Arg 439, and Asp 408 residues of the enzyme. Likewise, docking with α-amylase revealed that most of the compounds are well accommodated in the active site residues (Trp 59, Tyr 62, Thr 163, Leu 165, Arg 195, Asp 197, Glu 240, Asp 300, His 305, Asp 356) of the enzyme and Cyanidin-3-rutinoside displayed most active compound with docking score of − 15.03757. Conclusions Phytochemical studies revealed the presence of highly valuable phenolic compounds, which might be responsible for the anti-diabetic potentials of the plant samples.

Abstract Background Edible oils have proven health benefits in the prevention and treatment of various disorders since the establishment of human era. This study was aimed to appraise neuropharmacological studies on the commonly used edible oils including Cinnamomum verum (CV), Zingiber officinale (ZO) and Cuminum cyminum (CC). Methods The oils were analyzed via GC-MS for identifications of bioactive compounds. Anti-radicals capacity of the oils were evaluated via 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radicals scavenging assays. The samples were also tested against two important acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) which are among the important drug targets in Alzheimer’s disease. Lineweaver-Burk plots were constructed for enzyme inhibition studies which correspond to velocity of enzymes (Vmax) against the reciprocal of substrate concentration (K m ) in the presence of test samples and control drugs following Michaelis-Menten kinetics. Docking studies on AChE target were also carried out using Molecular Operating Environment (MOE 2016.0802) software. Results (Gas chromatography-mass spectrometry GC-MS) analysis revealed the presence of thirty-four compounds in Cinnamon oil (Cv.Eo), fourteen in ginger oil (Zo.Eo) and fifty-six in cumin oil (Cc.Eo). In the antioxidant assays, Cv.Eo, Zo.Eo and Cc.Eo exhibited IC50 values of 85, 121, 280 μg/ml sequentially against DPPH radicals. Whereas, in ABTS assay, Cv.Eo, Zo.Eo and Cc.Eo showed considerable anti-radicals potentials with IC50 values of 93, 77 and 271 μg/ml respectively. Furthermore, Cv.Eo was highly active against AChE enzyme with IC50 of 21 μg/ml. Zo.Eo and Cc.Eo exhibited considerable inhibitory activities against AChE with IC50 values of 88 and 198 μg/ml respectively. In BChE assay, Cv.Eo, Zo.Eo and Cc.Eo exhibited IC50 values of 106, 101 and 37 μg/ml respectively. Our results revealed that these oils possess considerable antioxidant and cholinesterase inhibitory potentials. As functional foods these oils can be effective remedy for the prevention and management of neurological disorders including AD. Synergistic effect of all the identified compounds was determined via binding energy values computed through docking simulations. Binding orientations showed that all the compounds interact with amino acid residues present in the peripheral anionic site (PAS) and catalytic anionic site (CAS) amino acid residues, oxyanion hole and acyl pocket via π-π stacking interactions and hydrogen bond interactions.

Abstract Background Diabetes mellitus is a common disease effecting the lifestyles of majority world population. In this research work, we have embarked the potential role of crude extracts and isolated compounds of Notholirion thomsonianum for the management diabetes mellitus. Methods The crude extracts of N. thomsonianum were initially evaluated for α-glucosidase, α-amylase and antioxidant activities. The compounds were isolated from the activity based potent solvent fraction. The structures of isolated compounds were confirmed with NMR and MS analyses. The isolated compounds were tested for α-glucosidase, α-amylase, protein tyrosine phosphatase 1B (PTP1B) and DPPH activities. The molecular docking studies were carried out to find the binding interactions of isolated compounds for α-glucosidase, α-amylase and PTP1B. Results Initially, we screened out crude extracts and subfractions of N. thomsonianum against different in-vitro targets. Among all, Nt.EtAc was observed a potent fraction among all giving IC50 values of 67, 70,

Soil water infiltration is a key mechanism for meeting plant water demand and groundwater recharge cycles; however, unreasonable land use practices cause reduced infiltration capacity and greater soil erosion. To date, differences in the properties of aeolian sandy soil and Pisha sandstone soil under different utilization methods as well as in soil properties, aggregates, and infiltration among kind of soil types, remain poorly understood. In this work, 54 soil samples of cropland and grassland were selected to identify the unique characteristics of soil infiltration processes under transition from cropland to grassland and contributions of soil properties to soil infiltrability in the Loess Plateau of China. The results showed that converting cropland to grassland could enhance the stable infiltration capacity of shallow soils of aeolian sandy soil and loess soil by 43.6% and 35.7%, respectively. Compared with cropland, the root properties and soil aggregate formation of the three soil types increased during grassland use, with the largest increase in soil organic matter content (32.14%) and total porosities (6.4%). As determined by the ring knife method, the saturated infiltration capacity of Pisha sandstone soil was significantly lower than in aeolian sandy soil and loess soil (p < 0.5). Moreover, its saturated infiltration capacity of cropland was better than grassland. Spearman’s correlation analysis and structural equation modeling (SEM) revealed that soil infiltration capacity appeared to be the most influenced by soil organic matter, and aggregate structure. These results highlight that fifteen years of returning cropland to grassland is not enough to affect the infiltration ability of deep soil (≥20 cm), and this improvement requires longer term maintenance.

Abstract Background According to the recent global cancer statistics, breast cancer is the leading cause of deaths among women with 2.3 million new cases globally. Likewise, cervical cancer is also among the leading causes of mortality among women. Polygonum hydropiper is traditionally known for its cytotoxic effects and several bioactive cytotoxic compounds were isolated from it. This study was aimed to isolate potential anticancer compounds from its most potent fractions and evaluate their anticancer potentials. Methods Based on our earlier studies, active fractions including chloroform and ethyl acetate were subjected to column chromatography for isolation of compounds. Chemical structures of isolated compounds were confirmed via 1H NMR, 13C NMR, mass spectrometry. Purified compounds were tested for cytotoxicity against breast cancer cells (MCF-7), cervical cancer cells (HeLA) and NIH/3T3 fibroblasts cells cultures using MTT assy. Anti-angiogenic potentials of isolated compounds were evaluated via chorioallantoic membrane assay. Anti-tumor studies were done using Agrobacterium tumefaciens induced potato tumor assay. Furthermore, to understand the binding modes of Isolated compounds, molecular docking was performed against EGFR, HER2 and VEGFR using MOE as docking software. Results Two bioactive compounds PH-1 (4-methyl-5-oxo-tetrahydrofuran-3-yl acetate) and PH-2 (methyl 4-hydroxy-3-methoxybenzoate) were purified from the active fractions. In cytotoxicity studies, PH-1 exhibited highest cytotoxicity against HeLA cells with 87.50% lethality at 1 mgmL−1 concentration and LD50 of 60 µgmL−1. Likewise, PH-2 showed 82.33% cytotoxicity against HeLA cells with LD50 of 160 µgmL−1. Similarly, PH-1 and PH-2 exhibited LD50 of 170 and 380 µgmL−1 respectively. Moreover, PH-1 and PH-2 were also very potent cytotoxic compounds against NIH/3T3 cells with 81.45 and 85.55% cytotoxicity at 1 mgL−1 concentration and LD50 of 140 and 58 µgL−1 respectively. Isolated compounds exhibited considerable anti-angiogenic potentials with IC50 of 340 and 500 µgL−1 respectively for PH-1 and PH-2. In anti-tumor assay, PH-1 and PH-2 exhibited 81.15 and 76.09% inhibitions with LD50 of 340 and 550 µgL−1 respectively. Both compounds selectively binds with EGFR and HER2 receptors with low binding energies. Both compounds exhibited stronger interactions with VEGFR through binding pocket residues Lys868, Val916 and Asp1046. Conclusions Both compounds cause considerable cytotoxicity against cancer cells. The anti-angiogenic and anti-tumor results suggests additional tumor suppressive properties. Docking analysis suggests that these compound not only has the ability to bind to EGFR and HER2 but also equally binds to VEGFR and may act as potential anti-angiogenic agents.

Abstract Our case highlights the occurrence of severe cutaneous adverse reactions with flurbiprofen use and alerts physicians to its odds with safer drugs.

Coordination complexes (1–4) of 2-amino-4-methylbenzothiazole and 2-amino-3-methylpyridine with Cu(CH3COO)2 and AgNO3 were prepared and characterized by UV/Vis and FT-IR spectroscopy. The molecular structure for single crystals of silver complexes (2 and 4) were determined by X-ray diffraction. The coordination complex (2) is monoclinic with space group P21/c, wherein two ligands are coordinated to a metal ion, affording distorted trigonal geometry around the central Ag metal ion. The efficient nucleophilic center, i.e., the endocyclic nitrogen of the organic ligand, binds to the silver metal. Ligands are coordinated to adopt cis arrangement, predominantly due to steric reasons. The O(2) and O(3) atoms of the NO3− group further play an important role in such type of ligand arrangement by hydrogen bonding with the NH2 group of ligands. Complex (4) is orthorhombic, P212121, comprising two molecules of 2-amino-3-methylpyridine as ligand coordinated with the metal ion, affording a polymeric structure. The coordination behavior of the ligand is identical to that in complex 2, wherein ring nitrogen is coordinated to the metal center and bridged to another metal ion through an NH2 group. The resulting product is polymeric in nature with the Ag metal in the backbone and ligand as the bridge. Compounds (2–4) were found to be luminescent, while 1 did not show such activity. All compounds were screened for their preliminary biological activities such as antibacterial, antioxidant and enzyme inhibition. Compounds exhibited moderate activity in these tests.

The classical convolution neural network architecture adheres to static declaration procedures, which means that the shape of computation is usually predefined and the computation graph is fixed. In this research, the concept of a pluggable micronetwork, which relaxes the static declaration constraint by dynamic layer configuration relay, is proposed. The micronetwork consists of several parallel convolutional layer configurations and relays only the layer settings, incurring a minimum loss. The configuration selection logic is based on the conditional computation method, which is implemented as an output layer of the proposed micronetwork. The proposed micronetwork is implemented as an independent pluggable unit and can be used anywhere on the deep learning decision surface with no or minimal configuration changes. The MNIST, FMNIST, CIFAR-10 and STL-10 datasets have been used to validate the proposed research. The proposed technique is proven to be efficient and achieves appropriate validity of the research by obtaining state-of-the-art performance in fewer iterations with wider and compact convolution models. We also naively attempt to discuss the involved computational complexities in these advanced deep neural structures.

The goal of the current work was to create structural analogues of a beta lactam antibiotic that might be possibly effective against bacterial resistant strains. FTIR, 1H NMR, 13C NMR, and CHNS analyses were used to perform the spectroscopic study on the compounds M1-8. The effects of the aforementioned substances on gram-positive and gram-negative bacterial strains were investigated. Most of the eight compounds had antibacterial activity that was lower than or equivalent to that of the original medication, but two molecules, M2 and M3, surprisingly, had stronger antibacterial activity. The findings of synthesized analogues against alpha-glucosidase and DPPH inhibition were found to be modest, whereas M2, M3, and M7 strongly inhibited the urease. To comprehend the potential mode of action, a molecular docking research was conducted against urease and -amylase. The research may help in the quest for novel chemical compounds that would be effective against bacteria that are resistant to antibiotics.

Cancer therapies are associated with various challenges including the emergence of multidrug resistant tumors, toxicological issues, severe side effects, and economic burden. To counteract these effects, natural products as substitutes and adjuvant therapies have received considerable attention owing to their safety, efficacy, and economic aspects. Various preclinical and clinical studies revealed that natural products and their combinations with chemotherapeutics mediate their anticancer effects via modulation of various signaling pathways implicated in promoting apoptosis, inhibiting excessive cellular proliferation, and mobilizing the immune system. Several lead phytochemicals including curcumin, resveratrol, quercetin, and cannabinoids synergistically act with cancer chemotherapeutics reducing cell proliferation and inducing apoptosis and cell cycle arrest. However, clinical studies on the subject matter are limited and need further extensive studies. It has been observed that patients undergoing chemotherapy use alternative therapies to ameliorate the symptoms associated with the use of chemotherapeutic agents. Nevertheless, some of the patients inform their physicians regarding herbal medicine during chemotherapy while others do not, and even most of the patients do not know the composition of herbal medicine they consume during chemotherapy. Herbal interactions with chemotherapeutics are associated with both beneficial and harmful aspects, but the beneficial aspect overweighs the harmful ones in terms of controlling the symptoms associated with the chemotherapy. Nonetheless, a large number of herbal medicines have been demonstrated to have synergistic effect with chemotherapy and alleviate the side effects of chemotherapeutic agents. The concomitant use of the majority of herbal medicines with chemotherapy has been demonstrated to be beneficial in multiple malignant tumors like cancer of blood, lungs, kidneys, liver, skin, and gastrointestinal tract. However, herbal medicines which possess positive interaction and improve the quality of life of patients should be sorted out and integrated with the chemotherapy. There should be a quality control system for the appraisal of herbal medicine, and there should also be an appropriate system of patient-doctor communication to counsel the patients regarding the beneficial and deleterious effects of the herbal medicine in combination with chemotherapy.

This study aimed to evaluate 2-(N-((2′-(2H-tetrazole-5-yl)-[1,1′-biphenyl]-4yl)-methyl)-pentanamido)-3-methyl butanoic acid-based ester derivatives as a new class of angiotensin-II receptor antagonists. For this purpose, a series of compounds were synthesized using a variety of phenols. Their chemical characterization was established by FTIR, 1HNMR, and 13CNMR techniques. The biological activities including antioxidant potentials using the DPPH assay, the antihypertensive assay, the urease enzyme inhibition assay, and the antibacterial assay using agar well diffusion methods were performed. All the new compounds showed significant free radical scavenging potentials more than the parent drug while retaining antihypertensive potentials along with urease inhibition properties. However, the AV2 test compound was found to be the most potent against hypertension. Most of the synthesized analogs showed urease inhibitory actions. Molecular docking studies were performed for all the active analogs to decode the binding detail of the ligands with receptors of the enzyme’s active site.

Diabetes mellitus (DM) is a metabolic disorder majorly arising from the pathophysiology of the pancreas manifested as a decline in the insulin production or the tissue’s resistance to the insulin. In this research, we have rationally designed and synthesized new succinimide–thiazolidinedione hybrids for the management of DM. In a multistep reaction, we were able to synthesize five new derivatives (10a–e). All the compounds were new containing a different substitution pattern on the N-atom of the succinimide ring. Initially, all the compounds were tested against the in vitro α-glucosidase, α-amylase, PTP1B, and DPP4 targets. In all of these targets, the compound 10d was observed to be the most potential antidiabetic agent. Based on this, the antidiabetic activity of the compound 10d was further investigated in experimental animals, which overall gave us encouraging results. The molecular docking studies of the compound 10d was also performed against the target enzymes α-glucosidase, α-amylase, PTP1B, and DPP4 using MOE. Overall, we observed that we have explored a new class of compounds as potential antidiabetic agents.

Modern technologies such as the Internet of Things (IoT) and physical systems used as navigation systems play an important role in locating a specific location in an unfamiliar environment. Due to recent technological developments, users can now incorporate these systems into mobile devices, which has a positive impact on the acceptance of navigational systems and the number of users who use them. The system that is used to find a specific location within a building is known as an indoor navigation system. In this study, we present a novel approach to adaptable and changeable multistory navigation systems that can be implemented in different environments such as libraries, grocery stores, shopping malls, and official buildings using facial and speech recognition with the help of voice broadcasting. We chose a library building for the experiment to help registered users find a specific book on different building floors. In the proposed system, to help the users, robots are placed on each floor of the building, communicating with each other, and with the person who needs navigational help. The proposed system uses an Android platform that consists of two separate applications: one for administration to add or remove settings and data, which in turn builds an environment map, while the second application is deployed on robots that interact with the users. The developed system was tested using two methods, namely system evaluation, and user evaluation. The evaluation of the system is based on the results of voice and face recognition by the user, and the model’s performance relies on accuracy values obtained by testing out various values for the neural network parameters. The evaluation method adopted by the proposed system achieved an accuracy of 97.92% and 97.88% for both of the tasks. The user evaluation method using the developed Android applications was tested on multi-story libraries, and the results were obtained by gathering responses from users who interacted with the applications for navigation, such as to find a specific book. Almost all the users find it useful to have robots placed on each floor of the building for giving specific directions with automatic recognition and recall of what a person is searching for. The evaluation results show that the proposed system can be implemented in different environments, which shows its effectiveness.

Plants’ bioactives are well-known safe drugs for vital diseases. Flavones and Flavonoid-rich dietary supplements are known to exhibit neuroprotective potential. In this study, we isolated a flavone 2-(3,4-dimethoxyphenyl)-3,7-dihydroxy-4H-chromen-4-one from Notholirion thomsonianum and it was evaluated against various targets of the oxidative stress-related neurological disorders. The compound showed excellent acetyl and butyrylcholinesterase inhibitions in its profile, giving IC50 values of 1.37 and 0.95 μM, respectively. Similarly, in in-vitro MAO-B assay, our flavone exhibited an IC50 value of 0.14 μM in comparison to the standard safinamide (IC50 0.025 μM). In in-vitro anti-inflammatory assay, our isolated compound exhibited IC50 values of 7.09, 0.38 and 0.84 μM against COX-1, COX-2 and 5-LOX, respectively. The COX-2 selectivity (SI) of the compound was 18.70. The compound was found safe in animals and was very effective in carrageenan-induced inflammation. Due to the polar groups in the structure, a very excellent antioxidant profile was observed in both in-vitro and in-vivo models. The compound was docked into the target proteins of the respective activities and the binding energies confirmed the potency of our compound. Furthermore, absorption, distribution, metabolism, excretion, and toxicity (ADMET) results showed that the isolated flavone has a good GIT absorption ability and comes with no hepatic and cardiotoxicity. In addition, the skin sensitization test, in-vitro human cell line activation test (h-CLAT) and KeratinoSens have revealed that isolated flavone is not skin sensitive with a confidence score of 59.6% and 91.6%. Herein, we have isolated a natural flavone with an effective profile against Alzheimer’s, inflammation and oxidative stress. The exploration of this natural flavone will provide a baseline for future research in the field of drug development.

Rumex hastatus being used for medicinal and nutritional purposes as a functional food in various countries is hereby evaluated by the gas chromatography-mass spectroscopy, proximate analysis, physicochemical (fluorescence) analysis, quantitative analysis of secondary metabolites and sensory evaluations studies. Various samples of R. hastatus were also evaluated for in vitro anti-diabetic potential. The investigational study demonstrated that R. hastatus is a rich source of carbohydrate, i.e., 432.4 mg/g. Moisture content, protein, fiber, ash content and fats were recorded as 22.8%, 133.9 mg/g, 124.4 mg/g, 54.5 mg/g and 25.6 mg/g, respectively. In the same way, the secondary metabolite displayed a relatively greater amount of flavonoids (84.5 mg/g) followed by saponins (65.5 mg/g) and alkaloids (49.5 mg/g). Similarly, the GC (FID-MS) analysis of R. hastatus revealed the detection of 120 compounds. Out of those identified compounds, selected anti-diabetic compounds were sorted out, viz butyl phthalate, phytol, ethylthreonine, dihydrobenzofuran, indoline, guanidine, nerolidol, myristic acid, palmitic acid, caryophyllene, anozol. In physicochemical fluorescence analysis and the sensory evaluation, data were also recorded along with the anti-diabetic with IC50 value of 42.09 µg/ml. The overall investigational analysis of R. hastatus obviously demonstrated that this plant was a rich source of primary and secondary metabolites. It may be concluded from the GC (FID-MS) analysis that R. hastatus is a potential source of anti-diabetic constituents, which may confer hypoglycemic potential. Based on the recorded data it may also be inferred that R. hastatus is among safe and nutritious herbs, which can be used in lieu of green vegetables and functional food with anti-diabetic potential.

Polygonum hydropiper L. and related species are reported to possess neuroprotective potentials. In an attempt to validate its anti-Alzheimer’s potentials, leaf oils (Ph. Lo) were extensively evaluated in this study against several in vitro and in vivo models of Alzheimer’s disease. The Ph. Lo were tested against pathological targets of Alzheimer’s diseases (ADs). The in vitro and in vivo assays were done for cholinesterase inhibition, anti-radical properties and cognitive assessments using transgenic animal models. In preliminary cholinesterase inhibition assays, Ph. Lo were more active against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2-azinobis (3-ethylbenzthiazoline)-6-sulfonic acid (ABTS), and hydrogen peroxide (H2O2) radicals. Subsequently, Ph. Lo was evaluated for its effects on special memory, exploratory behavior, and coordination using shallow water maze (SWM), Y-maze, open filed, and balance beam tests. Animal pre-genotyping was done via polymerase chain reaction (PCR) to confirm amyloid precursor protein (APP) transgene, and after completion of drug therapy, brain homogenates from the cortex and hippocampus were evaluated for cholinesterase and free radical studies. In SWM task, disease control animals treated with 10 mg/kg of Ph. Lo for 5 days exhibited significant improvement in cognitive performance indicated by low escape times on 5th day compared with normal animals. In the Y-maze test, transgenic animals showed higher spontaneous alternation behavior than disease control animals and standard control group animals. Ph. Lo therapy has improved the exploratory behavior and declined anxiety behavior in diseased animals as accessed via open field test. Ph. Lo administration significantly augmented the motor and coordination abilities of transgenic animals when compared to other groups of animals and declined AChE, BChE activities as well as free radicals load in the cortex and hippocampus tissues. Based on our finding, it is concluded that Ph. Lo exhibit significant neuroprotective potentials preliminary due to their anti-radicals and cholinesterase inhibitory activities. Ph. Lo need further detailed studies as potential aromatherapy against neurodegenerative disorders.

Diabetes mellitus is a metabolic disorder and is a global challenge to the current medicinal chemists and pharmacologists. This research has been designed to isolate and evaluate antidiabetic bioactives from Fragaria indica. The crude extracts, semi-purified and pure bioactives have been used in all in vitro assays. The in vitro α-glucosidase, α-amylase and DPPH free radical activities have been performed on all plant samples. The initial activities showed that ethyl acetate (Fi.EtAc) was the potent fraction in all the assays. This fraction was initially semi-purified to obtain Fi.EtAc 1–3. Among the semi-purified fractions, Fi.EtAc 2 was dominant, exhibiting potent IC50 values in all the in vitro assays. Based on the potency and availability of materials, Fi.EtAc 2 was subjected to further purification to obtain compounds 1 (2,4-dichloro-6-hydroxy-3,5-dimethoxytoluene) and 2 (2-methyl-6-(4-methylphenyl)-2-hepten-4-one). The two isolated compounds were characterized by mass and NMR analyses. The compounds 1 and 2 showed excellent inhibitions against α-glucosidase (21.45 for 1 and 15.03 for 2 μg/mL), α-amylase (17.65 and 16.56 μg/mL) and DPPH free radicals (7.62 and 14.30 μg/mL). Our study provides baseline research for the antidiabetic bioactives exploration from Fragaria indica. The bioactive compounds can be evaluated in animals-based antidiabetic activity in future.

Natural-based drugs are believed to be safe, effective and economical. Based on the medicinal importance of the genus Eryngium and unexplored nature of Eryngium caeruleum, we have evaluated its antidiabetic and antioxidant potentials. Both in-vitro and in-vivo assays have been carried out for antidiabetic assays. The antioxidant activity was determined by using different free radicals [i.e., 1,1-diphenyl,2-picrylhydrazyl (DPPH), 2,2-azinobis[3-ethylbenzthiazoline]-6-sulfonic acid (ABTS), and hydrogen peroxide (H2O2)]. Moreover, different phytoconstituents were identified in the most active solvent fraction by GC-MS analysis. Furthermore, comparative fingerprints of methanolic extract and chloroform fraction were also analyzed via High Performance Liquid Chromatography coupled with Diode Array Detector (HPLC-DAD). The crude methanolic extract of E. caeruleum (Ec.Cr) and its sub-fractions [i.e., n-hexane (Ec.Hex), chloroform (Ec.Chf), ethyl acetate (Ec.EtAc), and aqueous (Ec.Aq) were employed in this study]. In the α-glucosidase inhibition assay, a concentration-dependent inhibitory response was observed against the enzyme. The most active sample was Ec.Chf which revealed an IC50 of 437 μg/ml in comparison to the standard acarbose (IC50 25 μg/ml). The rest of the samples showed moderate inhibition of α-glucosidase. In antioxidant assays, Ec.Chf and Ec.Cr exhibited a considerable scavenging effect against all the free radicals. The IC50 values recorded for Ec.Chf were 112, 109, and 150 μg/ml against DPPH, ABTS, and H2O2 respectively. Based on the in-vitro potential of Ec.Chf, this was subjected to the in-vivo model experiment. The Ec.Chf lowered the blood glucose level up to 10.3 mmol/L at 500 μg/Kg. The Ec.Chf was also subjected to GC-MS analysis. The GC-MS analysis confirmed the presence of 60 compounds. The identified phytoconstituents consist of some essential compounds previously reported with antidiabetic and antioxidant studies, which include thymol, tocopherol, phytol, nerolidol, (I)-neophytadiene, linolenic acid, and falcarinol. Similarly, the HPLC-DAD chromatograms of Ec.Cr and Ec.Chf exhibited a variety of peaks, which further demonstrates the possibility of important phytochemicals. In a nutshell, we can conclude that Eryngium caeruleum is a potential source of bioactive compounds which may be beneficial for the management of ailments like diabetes and free radicals mediated disorders. Molecular docking was performed to explore the possible role of all the identified bioactive compounds in the chloroform fraction of Eryngium caeruleum into active sites of the homology model of α-glucosidase.

The colossal depths of the deep neural network sometimes suffer from ineffective backpropagation of the gradients through all its depths, whereas the strong performance of shallower multilayer neural structures proves their ability to increase the gradient signals in the early stages of training, which easily gets backpropagated for global loss corrections. Shallow neural structures are always a good starting point for encouraging the sturdy feature characteristics of the input. In this research, a shallow, deep neural structure called PrimeNet is proposed. PrimeNet is aimed to dynamically identify and encourage the quality visual indicators from the input to be used by the subsequent deep network layers and increase the gradient signals in the lower stages of the training pipeline. In addition to this, the layer-wise training is performed with the help of locally generated errors, which means the gradient is not backpropagated to previous layers, and the hidden layer weights are updated during the forward pass, making this structure a backpropagation free variant. PrimeNet has obtained state-of-the-art results on various image datasets, attaining the dual objective of: (1) a compact dynamic deep neural structure, which (2) eliminates the problem of backward-locking. The PrimeNet unit is proposed as an alternative to traditional convolution and dense blocks for faster and memory-efficient training, outperforming previously reported results aimed at adaptive methods for parallel and multilayer deep neural systems.

The present report is concerned with the synthesis and coordination compounds of 2-amino-(N-aminobezoyl) benzohydrazide[ABH]. The ligand was charcterized by proton NMR, mass spectrometry, elemental and infrared studies. The ligand has got –NH2 moeity which is capable of chelation. Therefore complexes of Ni, Cu, and Zn were prepared. These complexes were characterized by elemental, infrared, thermal, conductance, and magnetic susceptibility studies. Infrared spectra shows that the ligand form complexes through –NH2 moeity, while the elemental studies suggest M(ABH)X2 composition of the coordination compounds. Knowing about the importance of -N-N- linkage in the biologically active compounds, the synthesized complexes were studied for their biological activities against Gram Negative bacteria which include E. coli, Salmonella typhi, Enterobacter aerogenes, Proteus vulgaris and Pseudomonas aeruginosa, selected Gram Positive bacterial strain is Staph aureus and Fungus like Candida albican. These activities show that the hydrazide containing metal complexes become more potentially resistive to the microbial activities as compared to the sole ligand.

The Pirkoh and Drazinda formations in the Sulaiman Range, central Pakistan, yielded assemblages of (early) Bartonian orthophragminids, characterized predominantly by discocyclinids with a significant number of species probably endemic to Indian Subcontinent. The rarity of Asterocyclina and the absence of Orbitoclypeus and Nemkovella are noteworthy. Ten species of Discocyclina Gümbel and two species of Asterocyclina Gümbel, referable to the Shallow Benthics Zone (SBZ) 17 are described for the first time from Pakistan. The discocyclinids, i.e. Discocyclina praeomphalus, D. sulaimanensis, D. kutchensis, along with the new taxa established here, D. zindapirensis sp. nov., D. rakhinalaensis sp. nov., and D. pseudodispansa sp. nov., seem to be confined to the Indo-Pakistani region (Eastern Tethys). The Discocyclina dispansa, D. discus, D. nandori, and D. augustae lineages known from Western Tethys are also common in the Indian Subcontinent, as are asterocyclinids, such as Asterocyclina sireli and A. stellata. The upper part of the Drazinda Formation (‘Pellatispira beds’), referable to latest Bartonian and/or the early Priabonian, is poor in orthophragminids and is characterized by the occurrence of reticulate Nummulites, Heterostegina, Pellatispira and Silvestriella. The records of ‘Lepidocyclina of Caribbean affinity’ with large embryons from the Eocene of the Indian Subcontinent correspond to misidentified Discocyclina discus.

In this study six unsymmetrical thiourea derivatives, 1-isobutyl-3-cyclohexylthiourea (1), 1-tert-butyl-3-cyclohexylthiourea (2), 1-(3-chlorophenyl)-3-cyclohexylthiourea (3), 1-(1,1-dibutyl)-3-phenylthiourea (4), 1-(2-chlorophenyl)-3-phenylthiourea (5) and 1-(4-chlorophenyl)-3-phenylthiourea (6) were obtained in the laboratory under aerobic conditions. Compounds 3 and 4 are crystalline and their structure was determined for their single crystal. Compounds 3 is monoclinic system with space group P21/n while compound 4 is trigonal, space group R3:H. Compounds (1–6) were tested for their anti-cholinesterase activity against acetylcholinesterase and butyrylcholinesterase (hereafter abbreviated as, AChE and BChE, respectively). Potentials (all compounds) as sensing probes for determination of deadly toxic metal (mercury) using spectrofluorimetric technique were also investigated. Compound 3 exhibited better enzyme inhibition IC50 values of 50, and 60 µg/mL against AChE and BChE with docking score of −10.01, and −8.04 kJ/mol, respectively. The compound also showed moderate sensitivity during fluorescence studies.

Abstract Background Nonea micrantha Boiss. & Reut . being an unexplored member of Boraginaceae was investigated for GC/MS analysis, acetylcholinesterase (AChE), butyrylcholinesterase (BChE) inhibitory and antioxidant activities in an attempt to find its effectiveness in neurological disorders. Methods The AChE and BChE inhibitory activities of crude methanolic extract (Nm.Cr), subsequent fractions; n-hexane (Nm.Hex), chloroform (Nm.Cf), ethyl acetate (Nm.EtAc), aqueous (Nm.Aq) and crude saponins (Nm.Sp) from N. micrantha were conducted using Ellman’s assay. The antioxidant activity of the plant samples using DPPH and ABTS free radical scavenging potential following quantitative spectrophotometric and qualitative TLC method were also studied. Moreover the total reducing power (TRP) of all the samples was also figured out. Results The GC/Ms analysis confirmed that the plant is rich in bioactive molecules. Among different fractions, Nm.Hex, Nm.EtAc and Nm.Cf exhibited highest AChE inhibitory activities causing 75.51 ± 0.73, 68.54 ± 0.59 and 63.48 ± 0.59% enzyme inhibition respectively and IC50 of 44, 100 and 144 μg/mL respectively. In BChE inhibiton assay, Nm.Aq, Nm.Sp and Nm.Cr showed highest activity causing 83.49 ± 0.27, 81.49 ± 0.89 and 75.31 ± 0.56% enzyme inhibition with IC50 of 90, 110 and 44 μg/mL respectively. In DPPH assay, Nm.Aq, Nm.Cf, Nm.Hex and Nm.Cr were most potent exhibiting IC50 values of 3, 5, 93 and 120 μg/ml respectively. In ABTS assay Nm.EtAc, Nm.Aq, Nm.Sp and Nm.Cr showed IC50 values of 60, 95, 100 and 150 μg/mL respectively. Likewise ABTS inhibition was most prominent for Nm.Sp, Nm.EtAc and Nm.Aq causing 78.26 ± 0.49, 67.67 ± 0.73 and 63.58 ± 0.45% inhibition respectively at 1 mg/mL. These results were further confirmed by qualitative screening using DPPH and ABTS staining. Conclusions Our anticholinesterase and antioxidant results signify the N. micrantha as a potential source of natural bioactive compounds. Moreover isolation of natural bioactive compounds from this plant may lead to novel drug candidates against neurodegenerative disorders.

Abstract Background Since long, natural sources have been explored for possible managements of various diseases. In this context, the study is designed to evaluate Isodon rugosus Wall. ex Benth for biological potentials including antibacterial, anthelmintic, insecticidal, anti-termites and anti-Pharaoh activities followed by GC-MS analysis of active fraction to identify various bioactive compounds. Methods I. rugosus was investigated against eight bacterial strains using well diffusion method and microdilution method with ceftriaxone as positive control. Similarly, the insecticidal activity was carried out against Tribolium castaneum, Rhyzopertha dominica, Monomorium pharaonis and Heterotermis indicola following contact toxicity method. Likewise, anthelmintic activity was performed against Ascaridia galli and Pherethima posthuma using albendazole as positive control, in which the paralysis and death times of the worms were observed. The GC-MS analysis of the most active solvent fraction was performed for identifications of various bioactive compounds. Results Among the tested samples of I. rugosus, flavonoids and ethyl acetate fraction exhibited high antibacterial activities. The crude saponins showed highest anthelmintic activity against Pherethima posthuma and Ascaridia galli with death times of 27.67 and 29.22 min respectively at concentrations of 40 mg/ml. In insecticidal activity, chloroform fraction and saponins exhibited notable results against R. dominica (60 and 70%) and T. castaneum (70 and 76%) at concentration of 200 mg/ml. In anti-termite assay, all the plant samples showed overwhelming results, i.e. all the 25 termites were killed on the 3rd day. Similarly, in anti-Pharaoh activity, the chloroform, ethyl acetate and saponins fractions were most potent, each exhibiting LD50 of

Modern research has revealed that dietary consumption of flavonoids and flavonoids-rich foods significantly improve cognitive capabilities, inhibit or delay the senescence process and related neurodegenerative disorders including Alzheimer’s disease (AD). The flavonoids rich foods such as green tea, cocoa, blue berry and other foods improve the various states of cognitive dysfunction, AD and dementia-like pathological alterations in different animal models. The mechanisms of flavonoids have been shown to be mediated through the inhibition of cholinesterases including acetylcholinesterase (AChE), and butyrylcholinesterase (BChE), β-secretase (BACE1), free radicals and modulation of signaling pathways, that are implicated in cognitive and neuroprotective functions. Flavonoids interact with various signaling protein pathways like ERK and PI3-kinase/Akt and modulate their actions, thereby leading to beneficial neuroprotective effects. Moreover, they enhance vascular blood flow and instigate neurogenesis particularly in the hippocampus. Flavonoids also hamper the progression of pathological symptoms of neurodegenerative diseases by inhibiting neuronal apoptosis induced by neurotoxic substances including free radicals and β-amyloid proteins (Aβ). All these protective mechanisms contribute to the maintenance of number, quality of neurons and their synaptic connectivity in the brain. Thus flavonoids can thwart the progression of age-related disorders and can be a potential source for the design and development of new drugs effective in cognitive disorders.

Foodborne diseases are one of the major causes of morbidity and mortality, especially in low-income countries with poor sanitation and inadequate healthcare facilities. The foremost bacterial pathogens responsible for global outbreaks include Salmonella species, Campylobacter jejuni, Escherichia coli, Shigella sp., Vibrio, Listeria monocytogenes and Clostridium botulinum. Among the viral and parasitic pathogens, norovirus, hepatitis A virus, Giardia lamblia, Trichinella spiralis, Toxoplasma and Entamoeba histolytica are commonly associated with foodborne diseases. The toxins produced by Staphylococcus aureus, Bacillus cereus and Clostridium perfringens also cause these infections. The currently available therapies for these infections are associated with various limited efficacy, high cost and side-effects. There is an urgent need for effective alternative therapies for the prevention and treatment of foodborne diseases. Several plant extracts and phytochemicals were found to be highly effective to control the growth of these pathogens causing foodborne infections in in vitro systems. The present review attempts to provide comprehensive scientific information on major foodborne pathogens and the potential role of phytochemicals in the prevention and treatment of these infections. Further detailed studies are necessary to evaluate the activities of these extracts and phytochemicals along with their mechanism of action using in vivo models.

Alzheimer’s disease (AD) is characterized by cognitive inability manifested due to the accumulation of β-amyloid, formation of hyper phosphorylated neurofibrillary tangles, and a malfunctioned cholinergic system. The degeneration integrity of the neuronal network can appear long after the onset of the disease. Nanotechnology-based interventions have opened an exciting area via theranostics of AD in terms of tailored nanomedicine, which are able to target and deliver drugs across the blood–brain barrier (BBB). The exciting interface existing between medicinal plants and nanotechnology is an emerging marvel in medicine, which has delivered promising results in the treatment of AD. In order to assess the potential applications of the medicinal plants, their derived components, and various nanomedicinal approaches, a review of literature was deemed as necessary. In the present review, numerous phytochemicals and various feats in nanomedicine for the treatment of AD have been discussed mechanistically for the first time. Furthermore, recent trends in nanotechnology such as green synthesis of metal nanoparticles with reference to the treatment of AD have been elaborated. Foreseeing the recent progress, we hope that the interface of medicinal plants and nanotechnology will lead to highly effective theranostic strategies for the treatment of AD in the near future.

Isodon rugosus Wall. ex. Benth is an important species and is used in folk medicine for different types of pains such as abdominal pain, earache, toothache, gastric, and generalized body pain. Recently, we also have reported the antinociceptive potential of chloroform fraction of I. rugosus. In this research, we have investigated the antinociceptive, antioxidant and anti-cholinesterase potentials of essential oils from I. rugosus (Ir.EO), and have determined a possible mechanism of anti-nociception. The Ir.EO was subjected to gas chromatography-mass spectroscopy analysis to find out its chemical constituents. The Ir.EO was assayed for analgesic potential following acetic acid induced writhing, formalin test and hot plate method in animal models. The antioxidant activity was conducted against DPPH and ABTS free radicals following spectroscopic analysis. The cholinesterase inhibitory assays were performed using Ellman's assay. The GC-MS analysis of Ir.EO revealed the identification of 141 compounds. Ir.EO demonstrated strong antinociceptive potential in all three in-vivo models. With the use of nalaxone, it was confirmed that the essential oil was acting on the central pathway of nociception. The Ir.EO also exhibited strong free radicals scavenging potential, exhibiting IC50 values of 338 and 118 μg/ml for DPPH and ABTS free radicals respectively. In AChE and BChE inhibitory assays, the observed IC50 values were 93.56 and 284.19 μg/ml respectively. The encouraging antinociceptive, antioxidant and anticholinesterase results revealed that Ir.EO is a rich source of bioactive compounds as obvious from the GC-MS results.

BACKGROUND: Rumex species are traditionally used for the treatment of neurological disorders including headache, migraine, depression, paralysis etc. Several species have been scientifically validated for antioxidant and anticholinestrase potentials. This study aims to investigate Rumex hastatus D. Don crude methanolic extract, subsequent fractions, saponins and flavonoids for acetylcholinestrase, butyrylcholinestrase inhibition and diverse antioxidant activities to validate its folkloric uses in neurological disorders. Rumexhastatus crude methanolic extract (Rh. Cr), subsequent fractions; n-hexane (Rh. Hex), chloroform (Rh. Chf), ethyl acetate (Rh. EtAc), aqueous fraction (Rh. Aq), crude saponins (Rh. Sp) and flavonoids (Rh. Fl) were investigated against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) at various concentrations (125, 250, 500,1000 μg/mL) using Ellman's spectrophotometric analysis. Antioxidant potentials of Rh. Sp and Rh. Fl were evaluated using DPPH, H2O2 and ABTS free radical scavenging assays at 62.5, 125, 250, 500, 1000 μg/mL. RESULTS: All the test samples showed concentration dependent cholinesterase inhibition and radicals scavenging activity. The AChE inhibition potential of Rh. Sp and Rh. Fl were most prominent i.e., 81.67 ± 0.88 and 91.62 ± 1.67 at highest concentration with IC50 135 and 20 μg/mL respectively. All the subsequent fractions exhibited moderate to high AChE inhibition i.e., Rh. Cr, Rh. Hex, Rh. Chf, Rh. EtAc and Rh. Aq showed IC50 218, 1420, 75, 115 and 1210 μg/mL respectively. Similarly, against BChE various plant extracts i.e., Rh. Sp, Rh. Fl, Rh. Cr, Rh. Hex, Rh. Chf, Rh. EtAc and Rh. Aq resulted IC50 165,175, 265, 890, 92, 115 and 220 μg/mL respectively. In DPPH free radical scavenging assay, Rh. Sp and Rh. Fl showed comparable results with the positive control i.e., 63.34 ± 0.98 and 76.93 ± 1.13% scavenging at 1 mg/mL concentration (IC50 312 and 104 μg/mL) respectively. The percent ABTS radical scavenging potential exhibited by Rh. Sp and Rh. Fl (1000 μg/mL) were 82.58 ± 0.52 and 88.25 ± 0.67 with IC50 18 and 9 μg/mL respectively. Similarly in H2O2 scavenging assay, the Rh. Sp and Rh. Fl exhibited IC50 175 and 275 μg/mL respectively. CONCLUSION: The strong anticholinesterase and antioxidant activities of Rh. Sp, Rh. Fl and various fractions of R. hastatus support the purported ethnomedicinal uses and recommend R. hastatus as a possible remedy for the treatment of AD and neurodegenerative disorders.

BACKGROUND: Atriplex laciniata L. was investigated for phenolic, flavonoid contents, antioxidant, anticholinesterase activities, in an attempt to explore its effectiveness in Alzheimer's and other neurological disorders. Plant crude methanolic extract (Al.MeF), subsequent fractions; n-hexane (Al.HxF), chloroform (Al.CfF), ethyl acetate (Al.EaF), aqueous (Al.WtF), Saponins (Al.SPF) and Flavonoids (Al.FLVF) were investigated for DPPH, ABTS and H2O2 free radical scavenging activities. Further these extracts were subjected to acetylcholinesterase (AChE) & butyrylcholinesterase (BChE) inhibitory activities using Ellman's assay. Phenolic and Flavonoid contents were determined and expressed in mg Gallic acid GAE/g and Rutin RTE/g of samples respectively. RESULTS: In DPPH free radicals scavenging assay, Al.FLVF, Al.SPF and Al.MeF showed highest activity causing 89.41 ± 0.55, 83.37 ± 0.34 and 83.37 ± 0.34% inhibition of free radicals respectively at 1 mg/mL concentration. IC50 for these fractions were 33, 83 and 82 μg/mL respectively. Similarly, plant extracts showed high ABTS scavenging potential, i.e. Al.FLVF (90.34 ± 0.55), Al.CfF (83.42 ± 0.57), Al.MeF (81.49 ± 0.60) with IC50 of 30, 190 and 70 μg/ml respectively. further, H2O2 percent scavenging was highly appraised in Al.FLVF (91.29 ±0.53, IC50 75), Al.SPF (85.35 ±0.61, IC50 70) and Al.EaF (83.48 ± 0.67, IC50 2 70 μg/mL). All fractions exhibited concentration dependent AChE inhibitory activity as; Al.FLVF, 88.31 ± 0.57 (IC50 70 μg/mL), Al.SPF, 84.36 ± 0.64 (IC50 90 μg/mL), Al.MeF, 78.65 ± 0.70 (IC50 2 80 μg/mL), Al.EaF, 77.45 ± 0.46 (IC50 2 70 μg/mL) and Al.WtF 72.44 ± 0.58 (IC50 2 63 μg/mL) at 1 mg/mL. Likewise the percent BChE inhibitory activity was most obvious in Al.FLVF 85.46 ± 0.62 (IC50 1 00 μg/mL), Al.CfF 83.49 ± 0.46 (IC50 160 μg/mL), Al.MeF 82.68 ± 0.60 (IC50 2 20 μg/mL) and Al.SPF 80.37 ± 0.54 (IC50 1 20 μg/mL. CONCLUSIONS: These results stipulate that A. laciniata is enriched with phenolic and flavonoid contents that possess significant antioxidant and anticholinestrase effects. This provide pharmacological basis for the presence of compounds that may be effective in Alzheimer's and other neurological disorders.

Development of multidrug resistance (MDR) to antimicrobial, antiparasitic and chemotherapeutic agents is a global challenge for the scientific community. Despite of the emergence of MDR pathogens, the development of novel and more effective drugs is slow and scientist even speculate that we are going back the pre-antibiotic era. This work aims to study and evaluate the preliminary antibacterial, anthelmintic and cytotoxic potentials of ethyl 3-oxo-2-(2,5-dioxopyrrolidin-3-yl)butanoates. Among all of the four compounds, compound 2 has displayed remarkable potency with MIC values of 0.125, 0.083, 0.073, and 0.109 mg/ml against E. sakazakii, E. coli. S. aureus, and K. pneumonia, respectively. Compared to etoposide (LC50 9.8 μg/ml), the compounds demonstrated LC50 values from 280 to 765 μg/ml. For anthelmintic assay, three concentrations of each compound and standard drug were studied in determination of time of death of the two species. Excellent anthelmintic activity was observed by all four compounds against P. posthuma and A. galli better than standard albendazole. High GOLD fitness score data from docking analysis toward the targets represent better protein–ligand binding affinity and thus indicate a high propensity for all the active compounds to bind to the active site. The promising in-vitro antimicrobial, anthelmintic activity, and cytotoxicity data conclusively revealed that these compounds may serve as viable lead compounds for the treatment of bacterial and parasitic infections, and therefore, could help the medicinal chemists to design future chemotherapeutic agents to avoid rapid drug resistance.

The family Polygonaceae is known for its traditional use in the management of various neurological disorders including Alzheimer’s disease (AD). In search of new anti-AD drugs, β-sitosterol isolated from Polygonum hydropiper was subjected to in vitro, in vivo, behavioral and molecular docking studies to confirm its possibility as a potential anti-Alzheimer’s agent. The in vitro AChE, BChE inhibitory potentials of β-sitosterol were investigated following Ellman’s assay. The antioxidant activity was tested using DPPH, ABTS and H2O2 assays. Behavioral studies were performed on a sub-strain of transgenic mice using shallow water maze (SWM), Y-maze and balance beam tests. β-sitosterol was tested for in vivo inhibitory potentials against cholinesterase’s and free radicals in the frontal cortex (FC) and hippocampus (HC). The molecular docking study was performed to predict the binding mode of β-sitosterol in the active sites of AChE and BChE as inhibitor. Considerable in vitro and in vivo cholinesterase inhibitory effects were observed in the β-sitosterol treated groups. β-sitosterol exhibited an IC50 value of 55 and 50 μg/ml against AChE and BChE respectively. Whereas, the activity of these enzymes were significantly low in FC and HC homogenates of transgenic animals. Molecular docking studies also support the binding of β-sitosterol with the target enzyme and further support the in vitro and in vivo results. In the antioxidant assays, the IC50 values were observed as 140, 120, and 280 μg/ml in the DPPH, ABTS and H2O2 assays respectively. The free radicals load in the brain tissues was significantly declined in the β-sitosterol treated animals as compared to the transgenic-saline treated groups. In the memory assessment and coordination tasks including SWM, Y-maze and balance beam tests, β-sitosterol treated transgenic animals showed gradual improvement in working memory, spontaneous alternation behavior and motor coordination. These results conclude that β-sitosterol is a potential compound for the management of memory deficit disorders like AD.

Peptic ulceration is among the most prevalent gastrointestinal disorders characterized by pepsin and gastric acid mediated mucosal damage, as result of imbalance between defensive and offensive processes. The main objective of the current study was to investigate the antiulcer potentials of Polygonum hydropiper crude methanolic ectract (Ph.Cr) in aspirin induced ulcerogenesis using pylorus ligated rat model. In-vitro urease and Proteus mirabilis inhibitory potentials were evaluated using standard protocols. All fractions were analyzed using GC-MS to identify major components. The aspirin induced ulcerogenesis in pylorus ligated rat model was associated with significant changes in the mean ulcer score [F(5, 30) = 7.141, P = 0.0002], gastric juice volume [F(5, 30) = 8.245, P < 0.0001], gastric juice pH [F(5, 30) = 5.715, P = 0.0008], free acidity [F(5, 30) = 4.544, P = 0.0033], total acidity [F(5, 30) = 2.740, P = 0.0373], and pepsin concentration [F(5, 30) = 2.335, P = 0.0664]. Pre-treatment with Ph.Cr at 100, 200, and 400 mg/kg dose exhibited marked gastroprotective and anti-ulcerogenic effect in the aspirin induced pyloric ligation ulcerogenesis model at 100, 200, and 400 mg/kg as indicated by ulcerative biochemical parameters. In urease inhibition assay, leaves essential oil (Ph.Lo), saponins (Ph.Sp), and chloroform extract (Ph.Chf) exhibited highest activities with IC50 of 90, 98, and 520 μg/ml, respectively. Ph.Sp, Ph.Chf, ethyl acetate (Ph.EtAc), and Ph.Cr showed MICs of 25, 30, 32.25, and 40.50 μg/ml, respectively against P. mirabilis. Several compounds were identified in GC-MS analysis of samples. Significant in-vivo antiulcer, urease inhibitory as well as anti-proteus potentials of P. hydropiper solvent extracts, signify its potential use for the management of peptic ulcers and may provide scientific bases for the traditional uses of the plant.

Crataegus oxyacantha is an important herbal supplement and famous for its antioxidant potential. The antioxidant in combination with anticholinesterase activity can be considered as an important target in the management of Alzheimer’s disease. The compounds isolated from C. oxyacantha were evaluated for cholinesterases inhibitory activity using Ellman’s assay with Galantamine as standard drug. Total of nine (1–9) compounds were isolated. Compounds 1 and 2 were isolated for the first time from natural source. Important natural products like β-Sitosterol-3-O-β-D-Glucopyranoside (3), lupeol (4), β-sitosterol (5), betulin (6), betulinic acid (7), oleanolic acid (8), and chrysin (9) have also been isolated from C. oxyacantha. Overall, all the compounds exhibited an overwhelming acetylcholinesterase (AChE) inhibition potential in the range 5.22–44.47 μM. The compound 3 was prominent AChE inhibitor with IC50 value of 5.22 μM. Likewise, all the compounds were also potent in butyrylcholinesterase (BChE) inhibitions with IC50s of up to 0.55–15.36 μM. All the compounds, except 3, were selective toward BChE. Mechanism of the inhibition of both the enzymes were further studied by docking procedures using Genetic Optimization for Ligand Docking suit v5.4.1. Furthermore, computational blood brain barrier prediction of the isolated compounds suggest that these are BBB+.

The use of essential oils (EOs) and their components is known since long in traditional medicine and aromatherapy for the management of various diseases, and is further increased in the recent times. The neuroprotective and anti-aging potentials of EOs and their possible mechanism of actions were evaluated by numerous researchers around the globe. Several clinically important EOs and their components from Nigella sativa, Acorus gramineus, Lavandula angustifolia, Eucalyptus globulus, Mentha piperita, Rosmarinus officinalis, Jasminum sambac, Piper nigrum and so many other plants are reported for neuroprotective effects. This review article was aimed to summarize the current finding on EOs tested against neurodegenerative disorders like Alzheimer disease (AD) and dementia. The effects of EOs on pathological targets of AD and dementia including amyloid deposition (Aβ), neurofibrillary tangles (NFTs), cholinergic hypofunction, oxidative stress and glutamatergic abnormalities were focused. Furthermore, effects of EOs on other neurological disorders including anxiety, depression, cognitive hypofunction epilepsy and convulsions were also evaluated in detail. In conclusion, EOs were effective on several pathological targets and have improved cognitive performance in animal models and human subjects. Thus, EOs can be developed as multi-potent agents against neurological disorders with better efficacy, safety and cost effectiveness.

BACKGROUND: Isodon rugosus is used traditionally in the management of hypertension, rheumatism, tooth-ache and pyrexia. Present study was arranged to investigate I. rugosus for phytoconstituents, phytotoxic and cytotoxic activities to explore its toxicological, pharmacological potentials and to rationalize its ethnomedicinal uses. Briefly, qualitative phytochemical analysis of the plant extracts were carried out for the existence of alkaloids, flavonoids, saponins, oils, glycosides, anthraquinones, terpenoids, sterols and tannins. Plant crude methanolic extract (Ir.Cr), its subsequent fractions; n-hexane (Ir.Hex), chloroform (Ir.Chf), ethyl acetate (Ir.EtAc), aqueous (Ir.Aq) and saponins (Ir.Sp) in different concentrations were tested for phytotoxic and cytotoxic activities using radish seeds and brine shrimps (Artemia salina) respectively. The phytotoxic activity was determined by percent root length inhibition (RLI) and percent seeds germination inhibition (SGI) while the cytotoxicity was obtained with percent lethality of the brine shrimps. RESULTS: Ir.Cr was tested positive for the presence of alkaloids, glycosides, flavonoids, oils, terpenoids, saponins, tannins and anthraquinones. Among different fractions Ir.Sp, Ir.Chf, Ir.EtAc, and Ir.Cr were most effective causing 93.55, 89.32, 81.32 and 58.68% inhibition of seeds in phytotoxicity assay, with IC50 values of 0.1, 0.1, 0.1 and 52 μg/ml respectively. Similarly, among all the tested samples, Ir.Sp exhibited the highest phytotoxic effect causing 91.33% root length inhibition with IC50 of 0.1 μg/ml. Ir.Sp and Ir.Chf were most effective against brine shrimps showing 92.23 and 76.67% lethality with LC50 values of 10 and 12 μg/ml respectively. CONCLUSIONS: It may be inferred from the current investigations that I. rugosus contains different secondary metabolites and is a potential source for the isolation of natural anticancer and herbicidal drug molecules. Different fractions exhibited phytotoxic and cytotoxic activities, thus providing pharmacological basis for ethnomedicinal uses of this plant.

BACKGROUND: Based on the ethnomedicinal uses and the effective outcomes of natural products in various diseases, this study was designed to evaluate Isodon rugosus as possible remedy in oxidative stress, alzheimer's and other neurodegenerative diseases. Acetylecholinestrase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of crude methanolic extract (Ir.Cr), resultant fractions (n-hexane (Ir.Hex), chloroform (Ir.Cf), ethyl acetate (Ir.EtAc), aqueous (Ir.Aq)), flavonoids (Ir.Flv) and crude saponins (Ir.Sp) of I. rugosus were investigated using Ellman's spectrophotometric method. Antioxidant potential of I. rugosus was determined using DPPH, H2O2 and ABTS free radicals scavenging assays. Total phenolic and flavonoids contents of plant extracts were determined and expressed in mg GAE/g dry weight and mg RTE/g of dry sample respectively. RESULTS: Among different fractions Ir.Flv and Ir.Cf exhibited highest inhibitory activity against AChE (87.44 ± 0.51, 83.73 ± 0.64%) and BChE (82.53 ± 0.71, 88.55 ± 0.77%) enzymes at 1 mg/ml with IC50 values of 45, 50 for AChE and 40, 70 μg/ml for BChE respectively. Activity of these fractions were comparable to galanthamine causing 96.00 ± 0.30 and 88.61 ± 0.43% inhibition of AChE and BChE at 1 mg/ml concentration with IC50 values of 20 and 47 μg/ml respectively. In antioxidant assays, Ir.Flv, Ir.Cf, and Ir.EtAc demonstrated highest radicals scavenging activities in DPPH and H2O2 assays which were comparable to ascorbic acid. Ir.Flv was found most potent with IC50 of 19 and 24 μg/ml against DPPH and H2O2 radicals respectively. Whereas antioxidant activates of plant samples against ABTS free radicals was moderate. Ir.Cf, Ir.EtAc and Ir.Cr showed high phenolic and flavonoid contents and concentrations of these compounds in different fractions correlated well to their antioxidant and anticholinestrase activities. CONCLUSION: It may be inferred from the current investigations that the Ir.Sp, Ir.Flv and various fractions of I. rugosus are good sources of anticholinesterase and antioxidant compounds. Different fractions can be subjected to activity guided isolation of bioactive compounds effective in neurological disorders.

Malaria is one of the serious diseases threatening human health in Pakistan and contributes to a large proportion of the total malaria deaths in South Asia. However, little is known about the nature and extent of genetic diversity of the malarial parasites circulating in Pakistan. This study was designed to assess the infection status of Plasmodium and the genetic diversity of Plasmodium vivax and Plasmodium falciparum by analyzing msp-3α, msp-3β and msp-1, msp-2 genes respectively using allele specific nested PCR and RFLP assays. For this purpose, 130 field isolates were collected from the individuals who exhibited clinical symptoms associated with malaria in the Kohat region of Khyber Pakhtoonkhwa (KPK), Pakistan. Among 130 blood samples collected, P. vivax was detected in 105/130 (80.8%) and P. falciparum in 21/130 (16.2%). Mixed infections with both parasites were detected in 4/130 (3%) of the isolates. A large number of distinguishable alleles were found for msp genetic markers: 10 alleles for msp-3α and seven for msp-3β with one mixed infection in case of msp-3β. The genotyping of P. falciparum showed that K1+MAD20 mixed genotype was dominant in msp-1 and FC27 in msp-2. The results collectively suggest that P. vivax and P. falciparum populations in this region are highly polymorphic and mixed infections are prevalent. Keywords: Plasmodium vivax, Plasmodium falciparum, Genetic variation, Pakistan