In Vivo Chemical Screening in Zebrafish Embryos Identified FDA-Approved Drugs That Induce Differentiation of Acute Myeloid Leukemia Cells.

Acute myeloid leukemia (AML) is characterized by the abnormal proliferation and differentiation arrest of myeloid progenitor cells. The clinical treatment of AML remains challenging. Promoting AML cell differentiation is a valid strategy, but effective differentiation drugs are lacking for most types of AML. In this study, we generated Tg(drl:hoxa9) zebrafish, in which hoxa9 overexpression was driven in hematopoietic cells and myeloid differentiation arrest was exhibited. Using Tg(drl:hoxa9) embryos, we performed chemical screening and identified four FDA-approved drugs, ethacrynic acid, khellin, oxcarbazepine, and alendronate, that efficiently restored myeloid differentiation. The four drugs also induced AML cell differentiation, with ethacrynic acid being the most effective. By an RNA-seq analysis, we found that during differentiation, ethacrynic acid activated the IL-17 and MAPK signaling pathways, which are known to promote granulopoiesis. Furthermore, we found that ethacrynic acid enhanced all-trans retinoic acid (ATRA)-induced differentiation, and both types of signaling converged on the IL-17/MAPK pathways. Inhibiting the IL-17/MAPK pathways impaired ethacrynic acid and ATRA-induced differentiation. In addition, we showed that ethacrynic acid is less toxic to embryogenesis and less disruptive to normal hematopoiesis than ATRA. Thus, the combination of ethacrynic acid and ATRA may have broader clinical applications. In conclusion, through zebrafish-aided screening, our study identified four drugs that can be repurposed to induce AML differentiation, thus providing new agents for AML therapy.

JRK binds satellite III DNA and is necessary for the heat shock response.

JRK is a DNA-binding protein of the pogo superfamily of transposons, which includes the well-known centromere binding protein B (CENP-B). Jrk null mice exhibit epilepsy, and growth and reproductive disorders, consistent with its relatively high expression in the brain and reproductive tissues. Human JRK DNA variants and gene expression levels are implicated in cancers and neuropsychiatric disorders. JRK protein modulates ß-catenin-TCF activity but little is known of its cellular functions. Based on its homology to CENP-B, we determined whether JRK binds centromeric or other satellite DNAs. We show that human JRK binds satellite III DNA, which is abundant at the chromosome 9q12 juxtacentromeric region and on Yq12, both sites of nuclear stress body assembly. Human JRK-GFP overexpressed in HeLa cells strongly localises to 9q12. Using an anti-JRK antiserum we show that endogenous JRK co-localises with a subset of centromeres in non-stressed cells, and with heat shock factor 1 following heat shock. Knockdown of JRK in HeLa cells proportionately reduces heat shock protein gene expression in heat-shocked cells. A role for JRK in regulating the heat shock response is consistent with the mouse Jrk null phenotype and suggests that human JRK may act as a modifier of diseases with a cellular stress component.

Rare simultaneous fetal posterior cerebral artery and conventional posterior cerebral artery duplication in a patient with a ruptured posterior communicating artery aneurysm: illustrative case.

BACKGROUND: The fetal-type posterior cerebral artery (PCA) is defined as a variant anatomy in which the posterior communicating artery (PCOM) is larger than the hypoplastic or aplastic P1 segment of the PCA. The authors present the novel case of a patient with a duplicated right PCA in parallel with fetal-type and conventional PCAs supplying adjacent components of the PCA cerebral territory. OBSERVATIONS: A 59-year-old woman presented with a modified Fisher Scale score 4 subarachnoid hemorrhage. A right irregular PCOM aneurysm that measured 9.5 mm × 4.5 mm × 4.5 mm arose from the base of a variant branch supplying a portion of the PCA, rather than a conventional PCOM, and was found on digital subtraction angiography. Following endovascular coil embolization, the patient was discharged home. LESSONS: The fetal-type variant has implications for thromboembolic events. If an embolism occludes the anterior circulation in a patient with a fetal-type PCA, it may result in an infarct in the PCA territory. Awareness of cerebral arterial anatomy, including an atypical collateral supply, informs a treating team's latitude in tolerance of which sites must be preserved and which can be safely sacrificed. https://thejns.org/doi/10.3171/CASE23735.

An In Vivo and In Silico Approach Reveals Possible Sodium Channel Nav1.2 Inhibitors from Ficus religiosa as a Novel Treatment for Epilepsy.

Epilepsy is a neurological disease that affects approximately 50 million people worldwide. Despite an existing abundance of antiepileptic drugs, lifelong disease treatment is often required but could be improved with alternative drugs that have fewer side effects. Given that epileptic seizures stem from abnormal neuronal discharges predominately modulated by the human sodium channel Nav1.2, the quest for novel and potent Nav1.2 blockers holds promise for epilepsy management. Herein, an in vivo approach was used to detect new antiepileptic compounds using the maximum electroshock test on mice. Pre-treatment of mice with extracts from the Ficus religiosa plant ameliorated the tonic hind limb extensor phase of induced convulsions. Subsequently, an in silico approach identified potential Nav1.2 blocking compounds from F. religiosa using a combination of computational techniques, including molecular docking, prime molecular mechanics/generalized Born surface area (MM/GBSA) analysis, and molecular dynamics (MD) simulation studies. The molecular docking and MM/GBSA analysis indicated that out of 82 compounds known to be present in F. religiosa, seven exhibited relatively strong binding affinities to Nav1.2 that ranged from -6.555 to -13.476 kcal/mol; similar or with higher affinity than phenytoin (-6.660 kcal/mol), a known Na+-channel blocking antiepileptic drug. Furthermore, MD simulations revealed that two compounds: 6-C-glucosyl-8-C-arabinosyl apigenin and pelargonidin-3-rhamnoside could form stable complexes with Nav1.2 at 300 K, indicating their potential as lead antiepileptic agents. In summary, the combination of in vivo and in silico approaches supports the potential of F. religiosa phytochemicals as natural antiepileptic therapeutic agents.

The Need for Health Policy Training for Surgeons.

BACKGROUND: Improvements in surgery at a systems level can be mediated by effective health policy. METHODS: We reviewed three contemporary challenges in surgical care to understand the potential role of health policy. RESULTS: The pandemic-related backlog, and international economic and logistical challenges to surgical care may be improved through policy change and advocacy by surgeons. CONCLUSIONS: A surgeon-policy expert training pathway and professional role will ensure surgeons contribute meaningfully to health policy development.

An In Silico and In Vitro Assessment of the Neurotoxicity of Mefloquine.

Mefloquine (MQ) is a quinoline-based anti-malarial drug used for chemoprophylaxis or as a treatment in combination with artesunate. Although MQ has clear anti-Plasmodium falciparum properties, it can induce neurotoxicity and undesired neuropsychiatric side effects in humans. Hence, this study aimed to characterize the neurotoxicity of MQ using human neuroblastoma SH-SY5Y cells. The effects of MQ on neuronal toxicity and cell viability were investigated over a concentration range of 1-100 µM using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. The influence of MQ on cellular bioenergetics was examined by measuring cellular ATP levels and from the induction of reactive oxygen species (ROS). An in silico approach was used to assess the potential neurotoxicity of MQ mediated via binding to the active sites of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) and then experimentally validated via in vitro enzymatic assays. MQ was cytotoxic to neuronal cells in a concentration and exposure duration dependent manner and induced a significant reduction in viability at concentrations of ≥25 µM after a 24 h exposure. MQ adversely impacted cellular bioenergetics and significantly depleted ATP production at concentrations of ≥1 µM after 24 h. MQ-induced cellular ROS production, which was correlated with the induction of apoptosis, as revealed by flow cytometry. In silico studies suggested that MQ was a dual cholinesterase inhibitor and one with remarkably potent binding to BuChE. Modelling data were supported by in vitro studies which showed that MQ inhibited both human AChE and BuChE enzymes. In summary, MQ is an antimalarial drug that may induce neurotoxicity by impacting cellular bioenergetics and perturbing the activity of cholinesterases at exposure concentrations relevant to human dosage.

The efficacy of Linum usitatissimum seeds to inhibit estrogen receptor as a natural therapy for PCOS: An in silico and in vitro analysis.

Polycystic ovarian syndrome (PCOS) is an endocrinological disorder aroused due to hormonal disturbances. It is characterized by anovulation due to an excess of androgen and estrogen hormones, thus leading to the formation of multiple cysts, imposing life-threatening conditions. This manuscript aimed to introduce a natural estrogen receptor (ESR) inhibitors that can provide protection against PCOS. The computational analysis of Linum usitatissimum seeds  compounds against ESR alpha receptor was performed, and the binding affinities of the ligand compounds and receptor proteins were scrutinized. Nine lignin compounds were docked, and the results were compared with that of reference estrogen receptor inhibitors, clomiphene, and tamoxifen. The binding affinity scores for pinoresinol, lariciresinol, secoisolariciresinol, and matairesinol were -10.67, -10.66, -10.91, and -10.60 kcal mol-1 , respectively. These were comparable to the binding affinity score of reference compounds -11.406 kcal mol-1 for clomiphene and -10.666 kcal mol-1 for tamoxifen. Prime MM-GBSA studies showcased that Linum usitatissimum seeds compounds exhibit significant efficacy and efficiency towards receptor protein. Moreover, MD-simulation studies were performed and the results depict that the lignin compounds form stable complexes at 300 K throughout the simulation time. For further clarity, in-vitro experiments were carried out. The results exhibit the decline in cell proliferation in a concentration-dependent manner by extract 1 (ethyl acetate) EX1 and extract 2 (petroleum ether) EX2. Hence, providing evidence regarding the anti-estrogenic activity of the sample extracts. Collectively, these results showed that flax seed can reduce the levels of estrogen, which can induce ovulation and prevent cyst formation, and ultimately can provide protection against PCOS.

The anticancer potential of chemical constituents of Moringa oleifera targeting CDK-2 inhibition in estrogen receptor positive breast cancer using in-silico and in vitro approches.

Most of the breast cancers are estrogen receptor-positive recurring with a steady rate of up to 20 years dysregulating the normal cell cycle. Dinaciclib is still in clinical trials and considered as a research drug against such cancers targeting CDK2.The major goal of this study was to identify the potential inhibitors of CDK-2 present in Moringa oleifera for treating hormonal receptor positive breast cancers. For this purpose, in silico techniques; molecular docking, MM-GBSA and molecular dynamics simulations were employed to screen Moringa oleifera compounds and their anticancer potential was determined against CDK-2 protein targets. Among 36 compounds of Moringa oleifera reported in literature, chlorogenic acid (1), quercetin (2), ellagic acid (3), niazirin (4), and kaempferol (5) showed good affinity with the target. The interaction of the compounds was visualized using PYMOL software. The profiles of absorption, distribution, metabolism, excretion (ADME) and toxicity were determined using SWISS and ProTox II webservers. The MTT assay was performed in-vitro using MCF-7 cancer cell lines to validate the anticancer potential of Moringa oleifera leaf extract.MTT assay results revealed no significant change in proliferation of Mcf-7 cells following 24 h treatment with fraction A (petroleum ether). However, significant antiproliferative effect was observed at 200 µg/mL dose of fraction B (ethyl acetate) and cell viability was reduced to 40%.In conclusion, the data suggested that all the compounds with highest negative docking score than the reference could be the potential candidates for cyclin dependent kinase-2 (CDK-2) inhibition while ellagic acid, chlorogenic acid and quercetin being the most stable and potent inhibitors to treat estrogen receptor positive breast cancer targeting CDK-2. Moreover, the data suggested that further investigation is required to determine the optimum dose for significant antiproliferative effects using in-vivo models to validate our findings of in-silico analysis.

Incidence of Inborn Errors of Metabolism in Newborn Infants: Five Years' Single-Center Experience, Jeddah, Saudi Arabia.

Inborn errors of metabolism (IEMs) are inherited biochemical/metabolic disorders that are commonly present in the immediate neonatal period. The aim of this retrospective study was to determine the incidence and distribution of IEMs in newborn infants delivered in our hospital and to evaluate its outcome. A total of 16 494 (99.9%) newborn infants were screened for IEMs. We found 29 newborn infants diagnosed with IEMs, representing an incidence of 1 per ~569 live births and a cumulative incidence of 176 per 100 000 live births of the IEM-positive newborn infants. We detected 11 different types of IEMs, and the top 6 categories were endocrinopathies followed by carbohydrates disorders, vitamin-responsive disorders, organic acid defects, and ketogenesis and ketolysis defects. This study does reflect upon the importance of educating the general population about the perils of Consanguineous Marriages (CMs) in order to reduce related disorders significantly, especially in families who have a history of IEMs.

Pulmonary disease detection and classification in patient respiratory audio files using long short-term memory neural networks.

Introduction: In order to improve the diagnostic accuracy of respiratory illnesses, our research introduces a novel methodology to precisely diagnose a subset of lung diseases using patient respiratory audio recordings. These lung diseases include Chronic Obstructive Pulmonary Disease (COPD), Upper Respiratory Tract Infections (URTI), Bronchiectasis, Pneumonia, and Bronchiolitis. Methods: Our proposed methodology trains four deep learning algorithms on an input dataset consisting of 920 patient respiratory audio files. These audio files were recorded using digital stethoscopes and comprise the Respiratory Sound Database. The four deployed models are Convolutional Neural Networks (CNN), Long Short-Term Memory (LSTM), CNN ensembled with unidirectional LSTM (CNN-LSTM), and CNN ensembled with bidirectional LSTM (CNN-BLSTM). Results: The aforementioned models are evaluated using metrics such as accuracy, precision, recall, and F1-score. The best performing algorithm, LSTM, has an overall accuracy of 98.82% and F1-score of 0.97. Discussion: The LSTM algorithm's extremely high predictive accuracy can be attributed to its penchant for capturing sequential patterns in time series based audio data. In summary, this algorithm is able to ingest patient audio recordings and make precise lung disease predictions in real-time.

Building Resilient communities: Techno-economic assessment of standalone off-grid PV powered net zero energy (NZE) villages.

The use of renewable energy resources for off-grid electricity production has gained more importance in recent decades for meeting the energy needs of remote areas, even with limited resources. This research aims to provide an optimized and cost-effective approach for generating electricity in rural areas. By using current methodology, a stand alone energy source of PV is designed for development of NZE village. Solar irradiance of the selected location is 6.16 kWh/m2/day while the estimated electric load data for whole village is 64.259 kWh. Electric load and solar irradiance of the loaction is used in the Hybrid Optimization Model for Electric Renewable (HOMER) to design and analyze the techno-economic feasibility of the stand alone PV system to meet the load requirements. The study obtained the total Net Present Cost (NPC) of $0.511 M and the Cost Of Electricity (COE) is 2.26$/unit through the HOMER analysis, which is further refined by performing sensitivity analysis using parameters such as PV panel price, battery price, solar irradiance, variations in electric load and discount rates. According to the results, system is feasibile by annual electricity production of 30,078 kWh with initial capital investment of $0.434 M. This analysis compared the system performance and showed that it is economically and technically viable to meet the complete electricity needs of the village with a payback period of 7.2 years. Research can be utilized for policy making and implementation of NZE approach in remote areas by the government.

Bioassay-guided isolation and in silico study of antihyperlipidemic compounds from Onosma hispidum Wall.

Isolation of bioactive compounds from plants and their therapeutic evaluation is crucial in the pursuit of novel phytochemicals and contributes an indispensable role in drug discovery and design. The literature has documented the hypolipidemic effect of numerous Onosma species. Taking that into consideration, the current study was designed to isolate, purify and evaluate the antihyperlipidemic potential of leaves of Onosma hispidum Wall. For the first time, the bioassay-guided isolation led to the separation of 3 compounds that were identified by spectroscopic techniques as o-phthalic acid bis-(2-ethyl decyl)-ester (1), bis (2-ethyloctyl) phthalate (2), and 1,2 benzenedicarboxylic acid bis(2-methyl heptyl) ester (3). Lipase inhibition assay was utilized to scrutinize the antihyperlipidemic potential of methanolic extract fractions and subsequently isolated compounds. Further, the isolated compounds were employed for in silico studies via molecular docking, molecular mechanics with generalized born and surface area solvation (MM-GBSA), and MD simulations with Pancreatic Lipase Colipase (PDB ID: 1LPB). Molecular docking and MM-GBSA of isolated compounds were employed to explain the mode of binding between the protein-ligand complex and binding free energy calculation, respectively. Since compound (3) displayed the best docking score of -6.689 kcal/mol as compared to orlistat -5.529 kcal/mol with PDB: 1LPB. So, it was chosen for MD simulations to evaluate ligand stability and flexibility of the complex which was validated by the fluctuation of α-carbon chain, root mean square deviation (RMSD), root mean square fluctuation (RMSF), and type of interactions involved which authenticated the in vitro lipase inhibitory potential. Overall, in silico and in vitro results validated that compound (3) could be exploited as a promising pancreatic lipase inhibitor.Communicated by Ramaswamy H. Sarma.

Phytochemical, anti-hyperlipidemic and in silico studies of extracts of Ficus carica seeds.

Hyperlipidemia has been considered a disease primarily causing death along with other prevailing diseases such as coronary heart diseases, atherosclerosis and stroke. The present study aims to evaluate the anti-hyperlipidemic potential of Ficus carica. Extracts of seeds of Ficus carica were investigated for bioactive compounds and screened using in-vitro and in-vivo anti-hyperlipidemic activities. Fig seeds showed potential in-vitro by inhibition of pancreatic lipase while in-vivo study revealed that methanol extract of fig seeds exhibited the anti-hyperlipidemic property by beneficially modifying lipid profile of albino mice comparable to standard drug. GC-MS analysis of methanol extract of seeds of Ficus carica exhibited a variety of bioactive compounds. After further evaluation of ligands for their activity by using molecular docking and MM-GBSA study, it is concluded that 1,2,3-benzentriol has the highest binding affinity for pancreatic lipase enzyme. Hence, it is concluded that seeds of Ficus carica are medicinally important and have promising anti-hyperlipidemic potential.

Magnetic resonance imaging datasets with anatomical fiducials for quality control and registration.

Tools available for reproducible, quantitative assessment of brain correspondence have been limited. We previously validated the anatomical fiducial (AFID) placement protocol for point-based assessment of image registration with millimetric (mm) accuracy. In this data descriptor, we release curated AFID placements for some of the most commonly used structural magnetic resonance imaging datasets and templates. The release of our accurate placements allows for rapid quality control of image registration, teaching neuroanatomy, and clinical applications such as disease diagnosis and surgical targeting. We release placements on individual subjects from four datasets (N = 132 subjects for a total of 15,232 fiducials) and 14 brain templates (4,288 fiducials), totalling more than 300 human rater hours of annotation. We also validate human rater accuracy of released placements to be within 1 - 2 mm (using more than 45,000 Euclidean distances), consistent with prior studies. Our data is compliant with the Brain Imaging Data Structure allowing for facile incorporation into neuroimaging analysis pipelines.

Effect of gravity on the spreading of a droplet deposited by liquid needle deposition technique.

This study represents an experimental investigation, complemented with a mathematical model, to decipher the effect of gravity on the spreading dynamics of a water droplet. For the theoretical discussion, an overall energy balance approach is adopted to explain the droplet spreading under both microgravity (µg) and terrestrial gravity condition. Besides explaining the mechanism of the droplet spreading under microgravity condition achieved during the parabolic flight, a technique with a detailed experimental set-up has also been developed for the successful deposition of droplet. A rational understanding is formulated through experimental investigation and theoretical analysis, which allows us to distinguish the transient variation of the spreading of a droplet, between microgravity and terrestrial gravity condition. The spreading of the droplet is predicted by the non-linear overall energy balance equation, which accounts for the operating parameters in the form of non-dimensional groups like Reynolds number ([Formula: see text]), Weber number (We) and Bond number (Bo). To distinctly identify the difference in the drop spreading at terrestrial and microgravity conditions, the Bo with transient gravitational field obtained through the on-board accelerometer is considered. The obtained theoretical results are further corroborated by experimental results which are obtained from the parabolic flight.

The inhibitory potential of chemical constituents of Ficus carica targeting interleukin-6 (IL-6) mediated inflammation.

Inflammation is an innate reaction of the body of an individual when subjected to the noxious factors repeatedly. Pharmacological approaches focused at disrupting cytokine signaling networks have become significant therapeutic alternatives for the treatment of inflammatory illnesses, cancer and autoimmune disorders. High levels of inflammatory mediators, particularly interleukin IL-1, IL-6, IL-18, IL-12, and tumor necrosis factor alpha leads to a cytokine storm in the body. Among all the released cytokines in a patient suffering from inflammatory disorder, IL-6 mediator has a pivotal role in this inflammatory cascade which progresses to a cytokine storm. Therefore, the blockage of the IL-6 inflammatory mediator could be a promising treatment option for the patients with hyper inflammatory conditions. The phytochemicals could provide the new lead compounds against the IL-6 mediator. Ficus carica has been the ideal plant of research and investigation due to its commercial, economic and medical importance. The anti-inflammatory properties of F. carica were further investigated by in silico and in vivo approaches. The docking scores of Cyanidin-3,5-diglucoside, Kaempferol-7-O-rutinoside, Cyanidin-3-rhamnoglucoside, and Rutin are -9.231, -8.921, -8.840, and -8.335 Kcal/mole respectively. The free energy of binding and stability of the docked complexes of these top four phytochemicals with the IL-6 were further analyzed by Molecular Mechanics-Generalized Born Surface Area and Molecular Dynamic simulations, respectively. The in vivo anti-inflammatory carrageenan-induced rat paw edema model was used for the validation of in silico results. The maximum percentage paw edema inhibition with petroleum ether and ethyl acetate was 70.32% and 45.05%, respectively. The in vivo anti-inflammatory activity confirms the anti-inflammatory potential of F. carica. Therefore, it is predicted that Cyanidin-3,5-diglucoside, Kaempferol-7-O-rutinoside, Cyanidin-3-rhamnoglucoside, and Rutin have the potential to inhibit the IL-6 mediator which will aid in mitigating the cytokine storm in patients with acute inflammations.

Diagnostic accuracy of transthoracic echocardiography for the identification of proximal aortic dissection: a systematic review and meta-analysis.

This systematic review and meta-analysis evaluated the performance of transthoracic echocardiography (TTE) for diagnosis of proximal aortic dissections based on the identification of specific sonographic features. A systematic literature search of major databases was conducted on human studies investigating the diagnostic accuracy of TTE for proximal aortic dissection. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The quality of studies was evaluated using Quality Assessment of Diagnostic Accuracy Studies 2 tool. Data were gathered for the following sonographic findings: intimal flap, tear, or intramural hematoma; enlargement of aortic root or widening of aortic walls; aortic valve regurgitation; or pericardial effusion. Sensitivity, specificity, diagnostic odds ratio, number needed to diagnose values, and likelihood ratios were determined. Fourteen studies were included in our final analysis. More than half of the included studies demonstrated low risk of bias. The identification of intimal flap, tear, or intramural hematoma was shown to have an exceptional ability as a diagnostic tool to rule in proximal aortic dissections. TTE should be considered during the initial evaluation of patients presenting to the emergency department with suspected proximal aortic dissection. Positive sonographic findings on TTE may aid in rapid assessment, coordination of care, and treatment of individuals awaiting advanced imaging.

Silybum marianum: An Overview of its Phytochemistry and Pharmacological Activities with Emphasis on Potential Anticancer Properties.

Silybum marianum (SM) belongs to the family Asteraceae, which holds therapeutic significance in medicinal chemistry. Phytochemistry analysis revealed an abundance of active constituents, particularly silymarin, composed of polyphenols and flavonolignans. Silymarin is majorly found in leaves, seeds, and fruits and is comprised of seven flavonolignans. Silymarin derivatives, specifically silybin, were reported for their medicinal properties. This review summarizes the studies conducted to evaluate SM's pharmacological properties and proposed mechanisms. SM exhibited anticancer properties due to being capable of modifying the induction of apoptosis, inhibiting the STAT3 pathway, decreasing the transcription of various growth factors, impeding the growth of 4T1 cells and inducing cell cycle arrest in various types of cancers, i.e., skin cancer, liver cancer, breast cancer, ovarian cancer etc. Silymarin and its derivatives protect the liver and ameliorate various immune-mediated and autoimmune hepatic diseases. Moreover, antimicrobial, antidiabetic, cardioprotective, nephroprotective, and neuroprotective activities were also reported. Based on testified in vitro and in vivo studies, SM can serve as an alternative to cure various pathological ailments.

Assessment of the antidiabetic potential of extract and novel phytoniosomes formulation of Tradescantia pallida leaves in the alloxan-induced diabetic mouse model.

Diabetes inflicts health and economic burdens on communities and the present antidiabetic therapies have several drawbacks. Tradescantia pallida leaves have been used as a food colorant and food preservative; however, to our knowledge antidiabetic potential of the leaves of T. pallida has not been explored yet. The current study aimed to investigate the antidiabetic potential of T. pallida leaves extract and its comparison with the novel nisosome formulation of the extract. The leaves extract and phytoniosomes of T. pallida in doses of 15, 25 and 50 mg/kg were used to assess the oral glucose loaded, and alloxan-induced diabetic mice models. The biological parameters evaluated were; change in body weight, blood biochemistry, relative organ to body weight ratio and histopathology of the liver, pancreas and kidney. Results revealed that the extract 50 mg/kg and phytoniosomes 25 and 50 mg/kg remarkably reduced the blood glucose level in all hyperglycemic mice by possibly inhibiting α-amylase and α-glucosidase production. Body weight and blood biochemical parameters were considerably improved in phytoniosomes 50 mg/kg treated group. The relative body weight was similar to those of healthy mice in extract 50 mg/kg, phytoniosomes 25 mg/kg, and phytoniosomes 50 mg/kg treated groups. Histopathology showed the regeneration of cells in the CHN50 treated group. Hyphenated chromatographic analysis revealed potent metabolites, which confirmed the antidiabetic potential of the extract by inhibiting α-amylase and α-glucosidase using in silico analysis. The present data suggested that phytoniosomes have shown better antidiabetic potential than crude extract of these leaves.