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.

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.

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.

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.

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.

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.

The Potential of Stilbene Compounds to Inhibit Mpro Protease as a Natural Treatment Strategy for Coronavirus Disease-2019.

COVID-19 disease has had a global impact on human health with increased levels of morbidity and mortality. There is an unmet need to design and produce effective antivirals to treat COVID-19. This study aimed to explore the potential ability of natural stilbenes to inhibit the Mpro protease, an acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enzyme involved in viral replication. The binding affinities of stilbene compounds against Mpro were scrutinized using molecular docking, prime molecular mechanics-generalized Born surface area (MM-GBSA) energy calculations, and molecular dynamic simulations. Seven stilbene molecules were docked with Mpro and compared with GC376 and N3, antivirals with demonstrated efficacy against Mpro. Ligand binding efficiencies and polar and non-polar interactions between stilbene compounds and Mpro were analyzed. The binding affinities of astringin, isorhapontin, and piceatannol were -9.319, -8.166, and -6.291 kcal/mol, respectively, and higher than either GC376 or N3 at -6.976 and -6.345 kcal/mol, respectively. Prime MM-GBSA revealed that these stilbene compounds exhibited useful ligand efficacy and binding affinity to Mpro. Molecular dynamic simulation studies of astringin, isorhapontin, and piceatannol showed their stability at 300 K throughout the simulation time. Collectively, these results suggest that stilbenes such as astringin, isorhapontin, and piceatannol could provide useful natural inhibitors of Mpro and thereby act as novel treatments to limit SARS-CoV-2 replication.

Negative Elongation Factor (NELF) Inhibits Premature Granulocytic Development in Zebrafish.

Gene expression is tightly regulated during hematopoiesis. Recent studies have suggested that RNA polymerase II (Pol II) promoter proximal pausing, a temporary stalling downstream of the promoter region after initiation, plays a critical role in regulating the expression of various genes in metazoans. However, the function of proximal pausing in hematopoietic gene regulation remains largely unknown. The negative elongation factor (NELF) complex is a key factor important for this proximal pausing. Previous studies have suggested that NELF regulates granulocytic differentiation in vitro, but its in vivo function during hematopoiesis remains uncharacterized. Here, we generated the zebrafish mutant for one NELF complex subunit Nelfb using the CRISPR-Cas9 technology. We found that the loss of nelfb selectively induced excessive granulocytic development during primitive and definitive hematopoiesis. The loss of nelfb reduced hematopoietic progenitor cell formation and did not affect erythroid development. Moreover, the accelerated granulocytic differentiation and reduced progenitor cell development could be reversed by inhibiting Pol II elongation. Further experiments demonstrated that the other NELF complex subunits (Nelfa and Nelfe) played similar roles in controlling granulocytic development. Together, our studies suggested that NELF is critical in controlling the proper granulocytic development in vivo, and that promoter proximal pausing might help maintain the undifferentiated state of hematopoietic progenitor cells.

In Silico Design of Dual-Binding Site Anti-Cholinesterase Phytochemical Heterodimers as Treatment Options for Alzheimer's Disease.

The number of patients with neurodegenerative diseases, particularly Alzheimer's disease (AD), continues to grow yearly. Cholinesterase inhibitors (ChEIs) represent the first-line symptomatic drug treatment for mild-to-moderate AD; however, there is an unmet need to produce ChEIs with improved efficacy and reduced side effects. Herein, phytochemicals with reported anti-acetylcholinesterase (AChE) activity were ranked in silico for their anti-AChE potential. Ligands with a similar or higher binding affinity to AChE than galantamine were then selected for the design of novel dual-binding site heterodimeric drugs. In silico molecular docking of heterodimers with the target enzymes, AChE and butyrylcholinesterase (BuChE), were performed, and anti-cholinesterase binding affinities were compared with donepezil. Drug-likeliness properties and toxicity of the heterodimers were assessed using the SwissADME and ProTox-II webservers. Nine phytochemicals displayed similar or higher binding affinities to AChE than galantamine: sanguinarine > huperzine A > chelerythrine > yohimbine > berberine > berberastine > naringenin > akuammicine > carvone. Eleven heterodimeric ligands were designed with phytochemicals separated by four- or five-carbon alkyl-linkers. All heterodimers were theoretically potent AChE and BuChE dual-binding site inhibitors, with the highest affinity achieved with huperzine-4C-naringenin, which displayed 34% and 26% improved affinity to AChE and BuChE, respectively, then the potent ChEI drug, donepezil. Computational pharmacokinetic and pharmacodynamic screening suggested that phytochemical heterodimers would display useful gastrointestinal absorption and with relatively low predicted toxicity. Collectively, the present study suggests that phytochemicals could be garnered for the provision of novel ChEIs with enhanced drug efficacy and low toxicity.

SARS-CoV-2 nucleocapsid and Nsp3 binding: an in silico study.

Severe acute respiratory syndrome virus 2 (SARS-CoV-2) belongs to the single-stranded positive-sense RNA family. The virus contains a large genome that encodes four structural proteins, small envelope (E), matrix (M), nucleocapsid phosphoprotein (N), spike (S), and 16 nonstructural proteins (nsp1-16) that together, ensure replication of the virus in the host cell. Among these proteins, the interactions of N and Nsp3 are essential that links the viral genome for processing. The N proteins reside at CoV RNA synthesis sites known as the replication-transcription complexes (RTCs). The N-terminal of N has RNA-binding domain (N-NTD), capturing the RNA genome while the C-terminal domain (N-CTD) anchors the viral Nsp3, a component of RTCs. Although the structural information has been recently released, the residues involved in contacts between N-CTD with Nsp3 are still unknown. To find the residues involved in interactions between two proteins, three-dimensional structures of both proteins were retrieved and docked using HADDOCK. Residues at N-CTD were detected in interaction with L499, R500, K501, V502, P503, T504, D505, N506, Y507, I508, T509, K529, K530K532, S533 of Nsp3 and N-NTD to synthesize SARS-CoV-2 RNA. The interaction between Nsp3 and CTD of N protein may be a potential drug target. The current study provides information for better understanding the interaction between N protein and Nsp3 that could be a possible target for future inhibitors.

Structures of SARS-CoV-2 RNA-Binding Proteins and Therapeutic Targets.

BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) epidemic has resulted in thousands of infections and deaths worldwide. Several therapies are currently undergoing clinical trials for the treatment of SARS-CoV-2 infection. However, the development of new drugs and the repositioning of existing drugs can only be achieved after the identification of potential therapeutic targets within structures, as this strategy provides the most precise solution for developing treatments for sudden epidemic infectious diseases. SUMMARY: In the current investigation, crystal and cryo-electron microscopy structures encoded by the SARS-CoV-2 genome were systematically examined for the identification of potential drug targets. These structures include nonstructural proteins (Nsp-9; Nsp-12; and Nsp-15), nucleocapsid (N) proteins, and the main protease (Mpro). Key Message: The structural information reveals the presence of many potential alternative therapeutic targets, primarily involved in interaction between N protein and Nsp3, forming replication-transcription complexes (RTCs) which might be a potential drug target for effective control of current SARS-CoV-2 pandemic. RTCs consist of 16 nonstructural proteins (Nsp1-16) that play the most essential role in the synthesis of viral RNA. Targeting the physical linkage between the envelope and single-stranded positive RNA, a process facilitated by matrix proteins may provide a good alternative strategy. Our current study provides useful information for the development of new lead compounds against SARS-CoV-2 infections.

A Novel Statistical Method for Scene Classification Based on Multi-Object Categorization and Logistic Regression.

In recent years, interest in scene classification of different indoor-outdoor scene images has increased due to major developments in visual sensor techniques. Scene classification has been demonstrated to be an efficient method for environmental observations but it is a challenging task considering the complexity of multiple objects in scenery images. These images include a combination of different properties and objects i.e., (color, text, and regions) and they are classified on the basis of optimal features. In this paper, an efficient multiclass objects categorization method is proposed for the indoor-outdoor scene classification of scenery images using benchmark datasets. We illustrate two improved methods, fuzzy c-mean and mean shift algorithms, which infer multiple object segmentation in complex images. Multiple object categorization is achieved through multiple kernel learning (MKL), which considers local descriptors and signatures of regions. The relations between multiple objects are then examined by intersection over union algorithm. Finally, scene classification is achieved by using Multi-class Logistic Regression (McLR). Experimental evaluation demonstrated that our scene classification method is superior compared to other conventional methods, especially when dealing with complex images. Our system should be applicable in various domains such as drone targeting, autonomous driving, Global positioning systems, robotics and tourist guide applications.

Cytotoxic macrocyclic diterpenoids from Jatropha multifida.

Nine new macrocyclic diterpenoids (1-9), jatromultones A-I, along with eight known analogues (10-17) were isolated from the trunks of Jatropha multifida. The structures of the new compounds, including their absolute configurations, were elucidated by combination of spectroscopic analysis, single crystal X-ray diffraction, Rh2(OCOCF3)4-induced CD method, and chemical correlations. All compounds were screened for the cytotoxicity against five cancer cell lines, including one drug-resistant cell line, and seven compounds exhibited significant activity with IC50 values less than 10 µM. Compound 4 with IC50 values ranging from 2.69 to 6.44 µM toward all cell lines was selected for further mechanistic study, which showed that 4 could arrest cell cycle at G2/M phase and induce apoptosis. The brief structure-activity relationships (SARs) of these macrocyclic diterpenoids were also discussed.

Biscembranoids and Cembranoids from the Soft Coral Sarcophyton elegans.

Two novel biscembranoids, sarelengans A and B (1 and 2), five new cembranoids, sarelengans C-G (3-7), along with two known cembranoids (8 and 9) were isolated from the South China Sea soft coral Sarcophyton elegans. Their structures were determined by spectroscopic and chemical methods, and those of 1, 4, 5, and 6 were confirmed by single crystal X-ray diffraction. Compounds 1 and 2 represent the first example of biscembranoids featuring a trans-fused A/B-ring conjunction between the two cembranoid units. Their unique structures may shed light on an unusual biosynthetic pathway involving a cembranoid-∆8 rather than the normal cembranoid-∆¹ unit in the endo-Diels-Alder cycloaddition. Compounds 2 and 3 exhibited potential inhibitory effects on nitric oxide production in RAW 264.7 macrophages, with IC50 values being at 18.2 and 32.5 µM, respectively.

Deubiquitination of NF-κB by Ubiquitin-Specific Protease-7 promotes transcription.

NF-κB is the master regulator of the immune response and is responsible for the transcription of hundreds of genes controlling inflammation and immunity. Activation of NF-κB occurs in the cytoplasm through the kinase activity of the IκB kinase complex, which leads to translocation of NF-κB to the nucleus. Once in the nucleus, NF-κB transcriptional activity is regulated by DNA binding-dependent ubiquitin-mediated proteasomal degradation. We have identified the deubiquitinase Ubiquitin Specific Protease-7 (USP7) as a regulator of NF-κB transcriptional activity. USP7 deubiquitination of NF-κB leads to increased transcription. Loss of USP7 activity results in increased ubiquitination of NF-κB, leading to reduced promoter occupancy and reduced expression of target genes in response to Toll-like- and TNF-receptor activation. These findings reveal a unique mechanism controlling NF-κB activity and demonstrate that the deubiquitination of NF-κB by USP7 is critical for target gene transcription.

Mature cystic teratoma of the pancreas: Role of endoscopic ultrasound.

Cystic teratomas are a rare type of germ cell neoplasms derived from one or more germ layers. They can be classified as mature and immature teratomas based on the maturity of neuroectodermal elements within the tumor. Mature teratomas are benign, well-differentiated lesions, which may be solid or cystic. Mature cystic teratomas (MCTs) are also called dermoid cysts - a term likely coming from early surgical literature when the resected cysts resembled skin. Immature teratomas are malignant, undifferentiated tumors and generally solid. The most common location for MCTs is sacrococcygeus followed by ovaries and testes. MCTs in the pancreas are extremely rare with only few published case reports. Diagnosis of teratomas is challenging since there are no definitive preoperative diagnostic tests or pathognomonic findings. Even though EUS is commonly used for diagnosis of pancreatic cysts, the imaging features and cyst fluid characteristics of MCTs on EUS FNA have not been described. We describe a challenging case of a 65-year-old patient who had a 9 cm × 7 cm MCT in the body of the pancreas and discuss the role of EUS in diagnosis and management of these rare lesions. Complete surgical removal seems to be the current standard of care.

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.

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.