Therapeutic Potential of Cornus Genus: Navigating Phytochemistry, Pharmacology, Clinical Studies, and Advanced Delivery Approaches.

The genus Cornus (Cornaceae) plants are widely distributed in Europe, southwest Asia, North America, and the mountains of Central America, South America, and East Africa. Cornus plants exhibit antimicrobial, antioxidative, antiproliferative, cytotoxic, antidiabetic, anti-inflammatory, neuroprotective and immunomodulatory activities. These plants are exploited to possess various phytoconstituents such as triterpenoids, iridoids, anthocyanins, tannins and flavonoids. Pharmacological research and clinical investigations on various Cornus species have advanced significantly in recent years. Over the past few decades, a significant amount of focus has also been made into developing new delivery systems for Cornus mas and Cornus officinalis. This review focuses on the morphological traits, ethnopharmacology, phytochemistry, pharmacological activities and clinical studies on extracts and active constituents from plants of Cornus genus. The review also highlights recent novel delivery systems for Cornus mas and Cornus officinalis extracts to promote sustained and targeted delivery in diverse disorders. The overwhelming body of research supports the idea that plants from the genus Cornus have therapeutic potential and can be investigated in the future for treatingseveral ailments.

Antioxidant, anti-inflammatory and epigenetic potential of curcumin in Alzheimer's disease.

Alzheimer's disease (AD) constitutes a multifactorial neurodegenerative pathology characterized by cognitive deterioration, personality alterations, and behavioral shifts. The ongoing brain impairment process poses significant challenges for therapeutic interventions due to activating multiple neurotoxic pathways. Current pharmacological interventions have shown limited efficacy and are associated with significant side effects. Approaches focusing on the early interference with disease pathways, before activation of broad neurotoxic processes, could be promising to slow down symptomatic progression of the disease. Curcumin-an integral component of traditional medicine in numerous cultures worldwide-has garnered interest as a promising AD treatment. Current research indicates that curcumin may exhibit therapeutic potential in neurodegenerative pathologies, attributed to its potent anti-inflammatory and antioxidant properties. Additionally, curcumin and its derivatives have demonstrated an ability to modulate cellular pathways via epigenetic mechanisms. This article aims to raise awareness of the neuroprotective properties of curcuminoids that could provide therapeutic benefits in AD. The paper provides a comprehensive overview of the neuroprotective efficacy of curcumin against signaling pathways that could be involved in AD and summarizes recent evidence of the biological efficiency of curcumins in vivo.

Effect of Extraction Methods on the Antioxidant Potential and Cytotoxicity of the Combined Ethanolic Extracts of Daucus carota L., Beta vulgaris L., Phyllanthus emblica L. and Lycopersicon esculentum against Gastric Adenocarcinoma Cells.

Frequent consumption of fruits and vegetables in the daily diet may alleviate the risk of developing chronic diseases. Daucus carota L. (carrot), Beta vulgaris L. (beetroot) Phyllanthus emblica L. (amla), and Lycopersicon esculentum M (tomatoes) are traditionally consumed functional foods that contain a high concentration of antioxidants, ascorbic acid, polyphenols, and numerous phytochemicals. This study assessed how three distinct preparation methods affect the phenolic, flavonoid, carotenoid, and ascorbic acid contents, antioxidant level, and cytotoxicity of the combined fruit extract. The fruit samples were taken in the ratio of carrot (6): beetroot (2): tomato (1.5): amla (0.5) and processed into a lyophilized slurry (LS) extract, lyophilized juice (LJ) extract, and hot-air oven-dried (HAO) extract samples. The sample extracts were assessed for their phytoconstituent concentrations and antioxidant and cytotoxic potential. The total phenolic content in LS, LJ, and HAO extracts was 171.20 ± 0.02, 120.73 ± 0.02, and 72.05 ± 0.01 mg gallic acid equivalent/100 g, respectively and the total flavonoid content was 23.635 ± 0.003, 20.754 ± 0.005, and 18.635 ± 0.005 mg quercetin equivalent/100 g, respectively. Similarly, total ascorbic acid content, carotenoids, and antioxidant potential were higher in the LS and LJ extracts than in HAO. Overall, the LS extract had a substantially higher concentration of phytochemicals and antioxidants, as well as higher cytotoxic potential, compared to the LJ and HAO extracts. The LS extract was tested in the MKN-45 human gastric cancer cell line to demonstrate its effective antioxidant potential and cytotoxicity. Hence, lyophilization (freezing) based techniques are more effective than heat-based techniques in preserving the phytoconstituents and their antioxidant and cytotoxic potential.

Cupressus sempervirens L. flavonoids as potent inhibitors to xanthine oxidase: in vitro, molecular docking, ADMET and PASS studies.

Excessive intake of purine-rich foods such as seafood and red meat leads to excess xanthine oxidase activity and provokes gout attacks. The aim of this paper is to evaluate in vitro and in silico, the inhibition effect of Cupressus sempervirens plant extracts (flavonoids (Cae) and alkaloids (CaK)) and its six derivative compounds on bovine xanthine oxidase (BXO). The in silico study consists of molecular docking with GOLD v4.0 based on the best PLPchem score (PLP) and prediction of biological activity with the PASS server tool. The inhibitors used were lignan (cp1), Amentoflavone (cp2), Cupressuflavone (cp3), Isocryptomerin (cp4), Hinokiflavone (cp5), and Neolignan (cp6). The in vitro results showed that CaK gives an IC50 of 3.52 ± 0.04 µg/ml. Similarly, Cae saved an IC50 of 8.46 ± 1.98 µg/ml compared with the control (2.82 ± 0.10 µg/ml). The in silico results show that cp1 was the best inhibitor model (PLP of 88.09) with approved pharmacokinetics. These findings suggest that cp1 and cp2 may offer good alternatives for the treatment of hyperuricemia; cp3 was moderate, while the others (cp4 to cp6) were considered weak inhibitors according to their PLP.Communicated by Ramaswamy H. Sarma.

Desmodin and isopongachromene as potential inhibitors of cyclin-dependent kinase 5: phytoconstituents targeting anticancer and neurological therapy.

Cyclin-dependent kinase 5 (CDK5) is a proline-directed serine-threonine protein kinase vital for neuronal cell cycle arrest and differentiation. It activates by binding with p35 and p39 and is important for the functioning of the nervous system. A growing body of evidence suggests that CDK5 contributes to the onset and progression of neurodegeneration and tumorigenesis and represents itself as a potential therapeutic target. Our research illustrates virtual screening of phytochemicals from the IMPPAT (Indian Medicinal Plants, Phytochemistry and Therapeutics) library to search for potential inhibitors of CDK5. Initially, the compounds from the parent library were filtered out via their physicochemical properties following the Lipinski rule of five. Then sequentially, molecular docking-based virtual screening, PAINS filter, ADMET, PASS analysis, and molecular dynamics (MD) simulation were done using various computational tools to rule out adversities that can cause hindrances in the identification of potential inhibitors of CDK5. Finally, two compounds were selected via the extensive screening showing significant binding with CDK5 ATP-binding pocket and ultimately were selected as potent ATP-competitive inhibitors of CDK5. Finally, we propose that the elucidated compounds Desmodin and Isopongachromene can be used further in the drug discovery process and act as therapeutics in the medical industry to treat certain complex diseases, including cancer and neurodegeneration.Communicated by Ramaswamy H. Sarma.

In Vitro and In Vivo Anti-Arthritic Potential of Caralluma tuberculata N. E. Brown. and Its Chemical Characterization.

Present research was planned to assess the in vitro and in vivo anti-arthritic potential of Caralluma tuberculata N. E. Brown. methanolic (CTME) and aqueous (CTAQ) extracts. Chemical characterization was done by high-performance liquid chromatography and gas chromatography−mass spectrometry analysis. The Complete Freund's Adjuvant (CFA) was injected in left hind paw of rat at day 1 and dosing at 150, 300 and 600 mg/kg was started on the 8th day via oral gavage in all groups except normal and disease control rats (which were given distilled water), whereas methotrexate (intraperitoneal; 1 mg/kg/mL) was administered to standard control. The CTME and CTAQ exerted significant (p < 0.01−0.0001) in vitro anti-arthritic action. Both extracts notably reduced paw edema, and restored weight loss, immune organs weight, arthritic score, RBCs, ESR, platelet count, rheumatoid factor (RF), C-reactive protein, and WBCs in treated rats. The plant extracts showed significant (p < 0.05−0.0001) downregulation of tumor necrosis factor-α, Interleukin-6, -1ß, NF-κB, and cyclooxygenase-2, while notably upregulated IL-4, IL-10, I-κBα in contrast to disease control rats. The plant extracts noticeably (p < 0.001−0.0001) restored the superoxide dismutase and catalase activities and MDA levels in treated rats. Both extracts exhibited significant anti-arthritic potential. The promising potential was exhibited by both extracts probably due to phenolic, and flavonoids compounds.

Ameliorating Effect of Malva neglecta Wallr on Obesity and Diabetes in Wistar Rats: A Mechanistic Study.

A high caloric food causes deposition of fats that may progress to obesity. Obesity is a risk factor for various metabolic and cardiovascular diseases, including but limited to diabetes mellitus. This study is aimed at determining the ameliorating effect of Malva Neglecta wallr aqueous-methanolic extract (MNME) on obesity and diabetes in Wistar rats. The MNME was chemically characterized by high-performance liquid chromatography (HPLC). The plant extract was evaluated by in vitro α-amylase inhibition and DPPH scavenging activities. Obesity was induced by administering high sugar and fat diet (HSFD) to rats for six weeks, followed by intraperitoneal injection of alloxan monohydrate (150 mg/kg) to induce diabetes. Oral treatments with MNME 250, 500, and 750 mg/kg/day were given to diabetic obese rats for 14 days. The HPLC analysis showed the presence of phenolic acids and flavonoids. The plant extract showed significant antioxidant (P < 0.001) and alpha-amylase (P < 0.0001) inhibition activities. The administration of MNME displayed a considerable decrease in fasting blood glucose, body weight, liver function tests, urea, cholesterol, leptin, and insulin levels in diabetic obese rats as compared to the disease control group and maximum effect were observed at 750 mg/kg/day of MNME. The MNME significantly increased (P < 0.05 - 0.001) the levels of GSH, SOD, and CAT in the liver, kidney, and pancreas while notably (P < 0.05 - 0.001) reduced the malondialdehyde level in kidney and pancreas of diabetic obese rats in contrast to disease control rats. This experimental study concludes that the MNME had exhibited antiobesity and antidiabetic activities through reduction of oxidative stress, leptin, α-amylase activity, and insulin resistance due to the presence of phenolic acid and flavonoid compounds.

Ameliorative Effects of Phytomedicines on Alzheimer's Patients.

INTRODUCTION: Alzheimer's disease (AD) is a progressive, neurodegenerative disease that severely affects individuals' cognitive abilities, memory, and quality of life. It affects the elderly population, and there is no permanent prevention or cures available to date, treatments mainly aiming to alleviate the symptoms as and when they appear. Alternate therapeutic approaches are being researched constantly, and there is a growing focus on phytomedicine, herbal medicine, organic compounds, and ayurvedic compounds for the treatment of AD. METHODS: The current study aims to provide an extensive review of these plants against AD from the currently existing literature. Most relevant keywords like Alzheimer's Disease, phytomedicines, ethnic medicines, the role of phytomedicine in neuroprotection, common phytomedicines against AD, etc., were used to select the plants and their metabolites effective in treating AD. The study focuses on six plants: Panax ginseng, Ginkgo biloba, Bacopa monnieri, Withania somnifera, Curcuma longa, and Lavandula angustifolia. Their active components have been studied along with neuroprotective properties, and evidence of in-vitro, pre-clinical, and clinical studies conducted to prove their therapeutic potential against the disease have been presented. RESULTS: All plants envisaged in the study show potential for fighting against AD to varying degrees. Their compounds have shown therapeutic effects by reversing the neurological changes such as clearing Aß plaque and neurofibrillary tangle formation, and ameliorative effects against neurodegeneration through processes including improving concentration, memory, cognition and learning, higher working and cue memory, improved spatial memory, inhibition of NF-κB expression, inhibiting the release of pro-inflammatory cytokines, inhibition of AChE and lipid peroxidase enzymes, and reduction of interleukin levels and tumor necrosis factor-alpha. CONCLUSION: The present review is a comprehensive and up-to-date analysis supported by the evidentiary proofs from pre-clinical studies, meta-analyses, and review papers related to natural phytochemicals' impact on neurodegenerative disorders like AD.

5-fluorouracil and curcumin with pectin coating as a treatment regimen for titanium dioxide with dimethylhydrazine-induced colon cancer model.

Colorectal cancer was inducted in Wister rats using titanium dioxide nanoparticles (TiO2NPs) and dimethylhydrazine (DMH) and treatment using 5-fluorouracil (5-FU) and curcumin (CUR), individually and following a synergistic approach. Compatibility studies are evaluated by using FT-IR spectra analysis, and Vero cell lines as well as HCT-116 cell lines are used for evaluating the synergistic approach. It was then followed by induction of colorectal cancer in rats for 70 days and treatment using 5-FU and CUR with pectin coating (individually and in combination) for 28 days. The reports state that 5-FU and CUR combination was found to be compatible. The synergistic effect was evaluated for1:1, 1:2, 1:4, and 2:1 ratio of 5-FU:CUR, where 1:4 ratio shows a CI50 value of 0.853, selected further for the animal studies. The 1:4 ratio of 5-FU and CUR (50:200) shows to be effective for the treatment of colorectal cancer within 28 days, proven using histopathology report, bodyweight analysis, and hematological reports. 5-FU and CUR (1:4) ratio with pectin coating was proven effective for the treatment of colorectal cancer induced by TiO2NPs with DMH and was found to produce a synergistic effect.

Isolation, characterization and in vitro antioxidant activity screening of pure compound from black pepper (Piper nigrum).

The present study's aims of isolation, characterization and in vitro antioxidant activity screening of pure compound from Black pepper (Piper nigrum) were investigated. Nowadays, scientific exploration of medicinal plants from natural sources has become the prime concern globally. All the crude drugs that have been isolated from natural plant origin (herbs, root, stem, bark, fruit and flower) have great significance in drug discovery as well as a lead compound to demonstrate great synergistic effect on pharmacology. For this research work, methanol was selected as a mother solvent, and the crude methanolic extract of black pepper was partitioned in between the solvent chloroform and di-ethyl-ether. A crystal fraction has been eradicated from the chloroform extract of black pepper (Piper nigrum). The crystal compound (C1) was isolated and purified by using thin layer chromatography (TLC) and recrystallization technique. The purified crystal compound (C1) isolated from black pepper possesses a strong in vitro antioxidant activity. The IC50 value of crystal compound (C1) was 4.1 µg/ml where the standard one had 3.2 µg/ml. Physical, phytochemical and chromatographical characterization of pure crystal compound (C1) has been explored, and from the analysis of all characteristics, it was found that, crystal compound (C1) might have resembling features of the standard Piperine of black pepper. The overall research work was really remarkable and introduced a convenient way of isolating pure compound from the natural source which will be a great referential resource in isolating crude drugs for future analysis.

Citrus limon L. (lemon) seed extract shows neuro-modulatory activity in an in vivo thiopental-sodium sleep model by reducing the sleep onset and enhancing the sleep duration.

Citrus limon L. is an ingenious alternative medication and has a broad scope in managing several health conditions as part of natural remedies. Recently, medicinal plants have witnessed incredible consideration worldwide in the field of neuroscience for remedial intervention. The present work has investigated the phytochemical compounds and neuropharmacological potential of the seed extract of Citrus limon as a step to partially validate its formulations as nutraceuticals using an in vivo model. Diverse phytochemical groups such as alkaloids, glycosides, flavonoids, tannins, gums, saponins, steroids were qualitatively identified through colorimetric methods utilizing standard compounds. The neuropharmacological properties were studied in Swiss albino mice with the sleep time induced by thiopental sodium taken as an end-point, in standard hole cross, hole board, and open-field experiments at varying doses of 50 and 100 mg/kg body weight. Phytochemical screening showed that alkaloids, flavonoids, saponins, tannins, steroids, and glycosides are present in the aqueous extract of the seed. The extracts demonstrated a significant reduction in sleep onset and enhanced the sleep duration in a dose-dependent manner in thiopental sodium-induced sleeping time, along with a marked decrease in unconstrained locomotors and explorative properties in both hole cross and open field tests. Moreover, in the hole board study, the extracts minimized the count of head dips observed in the treated mice. The results shown in this study demonstrate that Citrus limon extracts have neuropharmacological properties that can be further examined for their potential role as an adjuvant with conventional medications or nutraceuticals.

Re-establishing the comprehension of phytomedicine and nanomedicine in inflammation-mediated cancer signaling.

Recent mounting evidence has revealed extensive genetic heterogeneity within tumors that drive phenotypic variation affecting key cancer pathways, making cancer treatment extremely challenging. Diverse cancer types display resistance to treatment and show patterns of relapse following therapy. Therefore, efforts are required to address tumor heterogeneity by developing a broad-spectrum therapeutic approach that combines targeted therapies. Inflammation has been progressively documented as a vital factor in tumor advancement and has consequences in epigenetic variations that support tumor instigation, encouraging all the tumorigenesis phases. Increased DNA damage, disrupted DNA repair mechanisms, cellular proliferation, apoptosis, angiogenesis, and its incursion are a few pro-cancerous outcomes of chronic inflammation. A clear understanding of the cellular and molecular signaling mechanisms of tumor-endorsing inflammation is necessary for further expansion of anti-cancer therapeutics targeting the crosstalk between tumor development and inflammatory processes. Multiple inflammatory signaling pathways, such as the NF-κB signaling pathway, JAK-STAT signaling pathway, MAPK signaling, PI3K/AKT/mTOR signaling, Wnt signaling cascade, and TGF-ß/Smad signaling, have been found to regulate inflammation, which can be modulated using various factors such as small molecule inhibitors, phytochemicals, recombinant cytokines, and nanoparticles (NPs) in conjugation to phytochemicals to treat cancer. Researchers have identified multiple targets to specifically alter inflammation in cancer therapy to restrict malignant progression and improve the efficacy of cancer therapy. siRNA-and shRNA-loaded NPs have been observed to downregulate STAT3 signaling pathways and have been employed in studies to target tumor malignancies. This review highlights the pathways involved in the interaction between tumor advancement and inflammatory progression, along with the novel approaches of nanotechnology-based drug delivery systems currently used to target inflammatory signaling pathways to combat cancer.

Epigallocatechin 3-gallate: From green tea to cancer therapeutics.

Epigallocatechin 3-gallate (EGCG) possesses various biological functions, including anti-cancer and anti-inflammatory properties. EGCG is an abundant polyphenolic component originating from green tea extract that has exhibited versatile bioactivities in combating several cancers. This review highlights the pharmacological features of EGCG and its therapeutic implications in cancer and other metabolic diseases. It modulates numerous signaling pathways, regulating cells' undesired survival and proliferation, thus imparting strong tumor chemopreventive and therapeutic effects. EGCG initiates cell death through the intrinsic pathway and causes inhibition of EGFR, STAT3, and ERK pathways in several cancers. EGCG alters and inhibits ERK1/2, NF-κB, and Akt-mediated signaling, altering the Bcl-2 family proteins ratio and activating caspases in tumor cells. This review focuses on anti-cancer, anti-oxidant, anti-inflammatory, anti-angiogenesis, and apoptotic effects of EGCG. We further highlighted the potential of EGCG in different types of cancer, emphasizing clinical trials formulations that further improve our understanding of the therapeutic management of cancer and inflammatory diseases.

Potential innovation against Alzheimer's disorder: a tricomponent combination of natural antioxidants (vitamin E, quercetin, and basil oil) and the development of its intranasal delivery.

Alzheimer's disorder (AD) is very difficult to manage and treat. The complexity of the brain, the blood-brain barrier influencing a multitude of parameters/biomarkers, as well as numerous other factors involved often contribute to the decline in the chances of treatment success. Development of the new drug moiety also takes time, being necessary to consider both its toxicity and related issues. As a strategic plan, a combined strategy is being developed and considered to address AD pathology using several approaches. A combination of vitamin E, quercetin, and basil oil in a nano-based formulation is designed to be administered nasally. The antioxidant present in these natural-based products helps to treat and alleviate AD if a synergistic approach is considered. The three active substances mentioned above are well known for the treatment of neurodegenerative disorders. The nanoformulation helps the co-delivery of the drug moiety to the brain through the intranasal route. In this review, a correlation and use of vitamin E, quercetin, and basil oil in a nano-based formulation is described as an effective way to treat AD. The intranasal administration of drugs is a promising approach for the treatment of neurodegenerative and mental disorders, as this route is non-invasive, enhances the bioavailability, allows a drug dose reduction, bypasses the blood-brain barrier, and reduces the systemic undesired effect. The use of natural products is generally considered to be just as safe; therefore, by using this combined approach, the level of toxicity can be minimized.

Antioxidant and Signal-Modulating Effects of Brown Seaweed-Derived Compounds against Oxidative Stress-Associated Pathology.

The biological and therapeutic properties of seaweeds have already been well known. Several studies showed that among the various natural marine sources of antioxidants, seaweeds have become a potential source of antioxidants because of their bioactive compounds. Most of the metabolic diseases are caused by oxidative stress. It is very well known that antioxidants have a pivotal role in the treatment of those diseases. Recent researches have revealed the potential activity of seaweeds as complementary medicine, which have therapeutic properties for health and disease management. Among the seaweeds, brown seaweeds (Phaeophyta) and their derived bioactive substances showed excellent antioxidant properties than other seaweeds. This review focuses on brown seaweeds and their derived major bioactive compounds such as sulfated polysaccharide, polyphenol, carotenoid, and sterol antioxidant effects and molecular mechanisms in the case of the oxidative stress-originated disease. Antioxidants have a potential role in the modification of stress-induced signaling pathways along with the activation of the oxidative defensive pathways. This review would help to provide the basis for further studies to researchers on the potential antioxidant role in the field of medical health care and future drug development.

In Silico Identification of Novel Interactions for FABP5 (Fatty Acid-Binding Protein 5) with Nutraceuticals: Possible Repurposing Approach.

Fatty Acid Binding-Protein 5 (FABP5) is a cytoplasmic protein, which binds long-chain fatty acids and other hydrophobic ligands. This protein is implicated in several physiological processes including mitochondrial ß-oxidation and transport of fatty acids, membrane phospholipid synthesis, lipid metabolism, inflammation and pain. In the present study, we used molecular docking tools to determine the possible interaction of FABP5 with six selected compounds retrieved form Drugbank. Our results showed that FABP5 binding pocket included 31 polar and non-polar amino acids, and these residues may be related to phosphorylation, acetylation, ubiquitylation, and mono-methylation. Docking results showed that the most energetically favorable compounds are NADH (-9.12 kcal/mol), 5'-O-({[(Phosphonatooxy)phosphinato]oxy}phosphinato)adenosine (-8.62 kcal/mol), lutein (-8.25 kcal/mol), (2S)-2-[(4-{[(2-Amino-4-oxo-1,4,5,6,7,8-hexahydro-6-pteridinyl)methyl]amino}benzoyl)amino]pentanedioate (-7.17 kcal/mol), Pteroyl-L-glutamate (-6.86 kcal/mol) and (1S,3R,5E,7Z)-9,10-Secocholesta-5,7,10-triene-1,3,25-triol (-6.79 kcal/mol). Common interacting residues of FABP5 with nutraceuticals included SER16, LYS24, LYS34, LYS40 and LYS17. Further, we used the SwissADME server to determine the physicochemical and pharmacokinetic characteristics and to predict the ADME parameters of the selected nutraceuticals after molecular analysis by docking with the FABP5 protein. Amongst all compounds, pteroyl-L-glutamate is the only one meeting the Lipinski's rule of five criteria, demonstrating its potential pharmacological use. Finally, our results also suggest the importance of FABP5 in mediating the anti-inflammatory activity of the nutraceutical compounds.

Identification of new BACE1 inhibitors for treating Alzheimer's disease.

Alzheimer's disease (AD) is a type of brain disorder, wherein a person experiences gradual memory loss, state of confusion, hallucination, agitation, and personality change. AD is marked by the presence of extracellular amyloid plaques and intracellular neurofibrillary tangles (NFTs) and synaptic losses. Increased cases of AD in recent times created a dire need to discover or identify chemical compounds that can cease the development of AD. This study focuses on finding potential drug molecule(s) active against ß-secretase, also known as ß-site amyloid precursor protein cleaving enzyme 1 (BACE1). Clustering analysis followed by phylogenetic studies on microarray datasets retrieved from GEO browser showed that BACE1 gene has genetic relatedness with the RCAN1 gene. A ligand library comprising 60 natural compounds retrieved from literature and 25 synthetic compounds collected from DrugBank were screened. Further, 350 analogues of potential parent compounds were added to the library for the docking purposes. Molecular docking studies identified 11-oxotigogenin as the best ligand molecule. The compound showed the binding affinity of - 11.1 Kcal/mole and forms three hydrogen bonds with Trp124, Ile174, and Arg176. The protein-ligand complex was subjected to 25 ns molecular dynamics simulation and the potential energy of the complex was found to be - 1.24579e+06 Kcal/mole. In this study, 11-oxotigogenin has shown promising results against BACE1, which is a leading cause of AD, hence warrants for in vitro and in vivo validation of the same. In addition, in silico identification of 11-oxotigogenin as a potential anti-AD compound paves the way for designing of chemical scaffolds to discover more potent BACE1 inhibitors.Graphical abstract.

Promising Anti-stroke Signature of Voglibose: Investigation through In- Silico Molecular Docking and Virtual Screening in In-Vivo Animal Studies.

BACKGROUND: Postprandial hyperglycemia considered to be a major risk factor for cerebrovascular complications. OBJECTIVE: The current study was designed to elucidate the beneficial role of voglibose via in-silico in vitro to in-vivo studies in improving the postprandial glycaemic state by protection against strokeprone type 2 diabetes. MATERIALS AND METHODS: In-Silico molecular docking and virtual screening were carried out with the help of iGEMDOCK+ Pymol+docking software and Protein Drug Bank database (PDB). Based on the results of docking studies, in-vivo investigation was carried out for possible neuroprotective action. T2DM was induced by a single injection of streptozotocin (90mg/kg, i.v.) to neonates. Six weeks after induction, voglibose was administered at the dose of 10mg/kg p.o. for two weeks. After eight weeks, diabetic rats were subjected to middle cerebral artery occlusion, and after 72 hours of surgery, neurological deficits were determined. The blood was collected for the determination of serum glucose, CK-MB, LDH and lipid levels. Brains were excised for determination of brain infarct volume, brain hemisphere weight difference, Na+-K+ ATPase activity, ROS parameters, NO levels, and aldose reductase activity. RESULTS: In-silico docking studies showed good docking binding score for stroke associated proteins, which possibly hypotheses neuroprotective action of voglibose in stroke. In the present in-vivo study, pre-treatment with voglibose showed a significant decrease (p<0.05) in serum glucose and lipid levels. Voglibose has shown significant (p<0.05) reduction in neurological score, brain infarct volume, the difference in brain hemisphere weight. On biochemical evaluation, treatment with voglibose produced significant (p<0.05) decrease in CK-MB, LDH, and NO levels in blood and reduction in Na+-K+ ATPase, oxidative stress, and aldose reductase activity in brain homogenate. CONCLUSION: In-silico molecular docking and virtual screening studies and in-vivo studies in MCAo induced stroke, animal model outcomes support the strong anti-stroke signature for possible neuroprotective therapeutics.

Nutraceuticals in Neurological Disorders.

Neurological diseases are one of the major healthcare issues worldwide. Posed lifestyle changes are associated with drastically increased risk of chronic illness and diseases, posing a substantial healthcare and financial burden to society globally. Researchers aim to provide fine treatment for ailing disorders with minimal exposed side effects. In recent decades, several studies on functional foods have been initiated to obtain foods that have fewer side effects and increased therapeutic activity. Hence, an attempt has been made to unravel several extraction techniques to acquire essential bioactive compounds or phytochemicals from therapeutically active food products. This has led to the conception of the term functional foods being meddled with other similar terms like "pharmafoods," "medifoods", "vitafoods", or "medicinal foods". With a dire need to adhere towards healthy options, the demand of nutraceuticals is widely increasing to combat neurological interventions. An association between food habits and the individual lifestyle with neurodegeneration has been manifested, thereby proposing the role of nutraceuticals as prophylactic treatment for neurological interventions. The current review covers some of the major neurological disorders and nutraceutical therapy in the prevention of disease.

TV 3326 for Alzheimer's dementia: a novel multimodal ChE and MAO inhibitors to mitigate Alzheimer's-like neuropathology.

OBJECTIVES: Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders and a well-recognized cause of dementia with ageing. In this review, we have represented the ChE and MAO inhibitory potential of TV 3326 against AD based on current scientific evidence. KEY FINDINGS: The aetiology of AD is quite complex and not completely understood. However, it has been observed that AD involves the deposition of abnormal amyloid beta (Aß), along with hyperphosphorylation of tau, oxidative stress, low acetylcholine (ACh) level and biometal dyshomeostasis. Due to the complex nature of AD aetiology, active research is required in the areas of development of multitarget drugs with 2 or more complementary biological functions, as they might represent significant progress in the AD treatment. Interestingly, it has been found that TV 3326 (i.e. ladostigil) is regarded as a novel therapeutic agent since it has the potential to cause inhibition of monoamine oxidase (MAO) A and B, and acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in the brain. Furthermore, it has the capacity to reverse memory impairments, which further suggests the ability of this drug to elevate cholinergic activity in the brain. SUMMARY: TV 3326 can avert oxidative-nitrative stress and gliosis. It has also been confirmed that TV 3326 contains neuroprotective and anti-apoptotic properties. Therefore, this distinctive combined inhibition of ChE and MAO along with its neuroprotective property makes TV 3326 a useful drug in the treatment of AD.