Flavonoid Compounds of Buah Merah (Pandanus conoideus Lamk) as a Potent Oxidative Stress Modulator in ROS-induced Cancer: In Silico Approach

Buah Merah, a typical fruit from Papua, Indonesia which is used empirically in cancer therapy is rich in carotenoids and flavonoids. However, the mechanisms by which Buah Merah ameliorates cancer remained unknown. Natural antioxidant enzymes and pro-oxidant enzymes modulation significantly suppressed ROS production and cancer growth. Therefore, the determination of target enzymes of Buah Merah contents was studied through an in silico approach. Carotenoid and flavonoid compounds from Buah Merah were docked to 7 ROS modulating enzymes using Autodock Vina and the interaction stability was studied using the CABS Flex 2.0 server. The crucial amino acids of each enzyme were determined using DockFlin and prediction of acute oral toxicity of each test ligand was studied using ProTox-II. Based on the molecular docking results, quercetin 3'-glucoside is the most potent compound in binding to CAT, GR, GPx, SOD, LOX, and NOX with binding energy values of -11.2, -9.7, -8.6, -10.2, -10.7, and -12.8 kcal/mol, respectively. Meanwhile, taxifolin 3-O-α-arabinopyranose produced the highest binding affinity of -10.0 kcal/mol at the XO. Each test ligand formed stable interactions with ROS modulating enzymes and formed bonds with crucial amino acids resulting in strong adhesion compared to native and reference ligands. The glucoside group of quercetin 3'-glucoside plays an essential role in determining the proper position in the attachment and supports the formation of hydrogen bonds with receptors. With low acute oral toxicity, it can be concluded that quercetin 3'-glucoside from Buah Merah is a potent oxidative stress modulator in cancer prevention and therapy

Complexed Polymer Film-Forming Spray: An Optimal Delivery System for Secretome of Mesenchymal Stem Cell as Diabetic Wound Dressing?

Diabetes-related wounds have physiological factors that make healing more complicated. High sugar levels can increase microbial infection risk while limiting nutrition and oxygen transfer to the wound area. The secretome of mesenchymal stem cells has been widely known for its efficacy in regenerative therapy. However, applying the secretome directly to the wound can reduce its effectiveness. In this review, we examined the literature on synthesizing the combinations of carboxymethyl chitosan, hyaluronic acid, and collagen tripeptides, as well as the possibility of physicochemical properties enhancement of the hydrogel matrix, which could potentially be used as an optimal delivery system of stem cell’s secretome for diabetic wound healing

Computational Simulations Reveal the Synergistic Action of Phytochemicals of Morus alba to Exert Anti-Alzheimer Activity via Inhibition of Acetylcholinesterase and Glycogen Synthase Kinase-3β

Morus alba Linn. is a popular medium-sized tree with a potent neuroprotective activity such as anti-Alzheimer. To date, it is not known which phytocompound of M. alba exerts anti-Alzheimer activity. Therefore, the present study was aimed to identify the phytochemicals of M. alba responsible for the anti-Alzheimer activity by targeting proteins such as acetylcholinesterase (AChE) and glycogen synthase kinase-3 beta (GSK-3β) that are associated in the pathogenesis of Alzheimer disease (AD). Molecular docking, molecular dynamics (MD) simulations and MM-GBSA calculations were performed for the study. Phytocompounds with code 32, 41, 67, and 70 showed the best glide gscore against AchE and GSK-3β. All these phytocompounds interacted with multiple crucial amino acids present at the active binding site of the proteins through conventional hydrogen bonds and hydrophobic interactions. MD simulations of 100 ns revealed stable conformation for all protein-ligand complexes. Based on the computational findings, we conclude that M. alba’s phytoconstituents (32, 41 67, and 70) exerts anti-Alzheimer potential by inhibiting AChE and GSK-3β

Phytocompounds as potential inhibitors of SARS-CoV-2 Mpro and PLpro through computational studies.

The inhibition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) and papain-like protease (PLpro) prevents viral multiplications; these viral enzymes have been recognized as one of the most favorable targets for drug discovery against SARS-CoV-2. In the present study, we screened 225 phytocompounds present in 28 different Indian spices to identify compounds as potential inhibitors of SARS-CoV-2 Mpro and PLpro. Molecular docking, molecular dynamics simulation, molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) binding free energy calculations, and absorption, distribution, metabolism, excretion and toxicity (ADMET) studies were done. Based on binding affinity, dynamics behavior, and binding free energies, the present study identifies pentaoxahexacyclo-dotriacontanonaen-trihydroxybenzoate derivative (PDT), rutin, and dihyroxy-oxan-phenyl-chromen-4-one derivative (DOC), luteolin-7-glucoside-4'-neohesperidoside as promising inhibitors of SARS-CoV-2 Mpro and PLpro, respectively.</p

Nanodelivery of Dietary Polyphenols for Therapeutic Applications

Advancement in nanotechnology has unleashed the therapeutic potentials of dietary polyphenols by enhancing bioavailability, improving biological half-life, and allowing site-specific drug delivery. In this review, through citation of relevant literature reports, we discuss the application of nano-pharmaceutical formulations, such as solid lipid nanoparticles, nano-emulsions, nano-crystals, nano-polymersomes, liposomes, ethosomes, phytosomes, and invasomes for dietary polyphenols. Following this, we highlight important studies concerning different combinations of nano formulations with dietary polyphenols (also known as nanophytopolyphenols). We also provide nano-formulation paradigms for enhancing the physicochemical properties of dietary polyphenols. Finally, we highlight the latest patents that were granted on nano-formulations of dietary polyphenols. Based on our review, we observe that nanosized delivery of herbal constituents, spices, and dietary supplements have the ability to improve biological processes and address issues connected with herbal treatments

Identification of bioactive molecules from Triphala (Ayurvedic herbal formulation) as potential inhibitors of SARS-CoV-2 main protease (Mpro) through computational investigations

© 2022 The Author(s)Severe acute respiratory syndrome coronavirus disease (SARS-CoV-2) induced coronavirus disease 2019 (COVID-19) pandemic is the present worldwide health emergency. The global scientific community faces a significant challenge in developing targeted therapies to combat the SARS-CoV-2 infection. Computational approaches have been critical for identifying potential SARS-CoV-2 inhibitors in the face of limited resources and in this time of crisis. Main protease (Mpro) is an intriguing drug target because it processes the polyproteins required for SARS-CoV-2 replication. The application of Ayurvedic knowledge from traditional Indian systems of medicine may be a promising strategy to develop potential inhibitor for different target proteins of SARS-CoV-2. With this endeavor, we docked bioactive molecules from Triphala, an Ayurvedic formulation, against Mpro followed by molecular dynamics (MD) simulation (100 ns) to investigate their inhibitory potential against SARS-CoV-2. The top four best docked molecules (terflavin A, chebulagic acid, chebulinic acid, and corilagin) were selected for MD simulation study and the results obtained were compared to native ligand X77. From docking and MD simulation studies, the selected molecules showed promising binding affinity with the formation of stable complexes at the active binding pocket of Mpro and exhibited negative binding energy during MM-PBSA calculations, indication their strong binding affinity with the target protein. The identified bioactive molecules were further analyzed for drug-likeness by Lipinski's filter, ADMET and toxicity studies. Computational (in silico) investigations identified terflavin A, chebulagic acid, chebulinic acid, and corilagin from Triphala formulation as promising inhibitors of SARS-CoV-2 Mpro, suggesting experimental (in vitro/in vivo) studies to further explore their inhibitory mechanisms