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.

Protective Effects of Diets Rich in Polyphenols in Cigarette Smoke (CS)-Induced Oxidative Damages and Associated Health Implications.

Cigarette smoking has been responsible for causing many life-threatening diseases such as pulmonary and cardiovascular diseases as well as lung cancer. One of the prominent health implications of cigarette smoking is the oxidative damage of cellular constituents, including proteins, lipids, and DNA. The oxidative damage is caused by reactive oxygen species (ROS, oxidants) present in the aqueous extract of cigarette smoke (CS). In recent years, there has been considerable interest in the potential health benefits of dietary polyphenols as natural antioxidant molecules. Epidemiological studies strongly suggest that long-term consumption of diets (fruits, vegetables, tea, and coffee) rich in polyphenols offer protective effects against the development of cancer, cardiovascular diseases, diabetes, osteoporosis, and neurodegenerative diseases. For instance, green tea has chemopreventive effects against CI-induced lung cancer. Tea might prevent CS-induced oxidative damages in diseases because tea polyphenols, such as catechin, EGCG, etc., have strong antioxidant properties. Moreover, apple polyphenols, including catechin and quercetin, provide protection against CS-induced acute lung injury such as chronic obstructive pulmonary disease (COPD). In CS-induced health problems, the antioxidant action is often accompanied by the anti-inflammatory effect of polyphenols. In this narrative review, the CS-induced oxidative damages and the associated health implications/pathological conditions (or diseases) and the role of diets rich in polyphenols and/or dietary polyphenolic compounds against various serious/chronic conditions of human health have been delineated.

Cerebroprotective effect of Aloe Emodin: In silico and in vivo studies.

This study involved cerebroprotective potential of aloe emodin (AE) by in silico molecular docking analysis against various cerebrotoxic proteins followed by in vivo activity on multiple occlusions and reperfusion of bilateral carotid arteries (MO/RCA) induced cerebral injury in experimental rats. Molecular docking studies were carried out to evaluate the binding affinity (or binding interaction) between AE and various proteins involved in apoptosis such as caspase-3 (CASP3) and Bcl-2-associated X protein (BAX), and proteins involved in inflammation such as interleukin-6 (IL-6), tumor necrosis factor α (TNF α), nitric oxide synthase (NOS), acid-sensing ion channel (ASIC) and glutamate receptor (GR) involved in cerebral stroke, and results were compared with that of standard drugs, minocycline, quercetin, and memantine. Cerebral ischemic reperfusion induced by MO/RCA was assessed for 10 mins reperfusion period as one cycle, and the experiment was conducted for up to 3 cycles in rats. After completion of 3 cycles, the rats were subjected to ethically acceptable animal euthanasia followed by isolation of the brains which were studied for the size of cerebral infarction, and biochemical parameters such as glutathione (GSH), malondialdehyde (MDA), catalase (CAT) were estimated from the brain homogenate. Further, histological studies were done to study neuronal contact. Results of molecular docking indicated that the AE exhibited interaction with active sites of cerebrotoxic proteins usually involved in protein functions or cerebrotoxicity. Biochemical results showed that in the untreated brain, MDA levels increased significantly, and decreased GSH and CAT levels were observed when compared to MO/RCA group, while treated rats showed a decrease in the levels of MDA and an increase in GSH and CAT levels as compared to MO/RCA rats. In comparison with sham rats and normal rats, histopathological analysis revealed neuronal damage in MO/RCA surgery rats which manifested as decreased intact neurons. However, treatment with AE 50 mg/kg b.wt. restored contact between neuronal cells. It can be concluded that AE showed cerebroprotective effect on RO/RCA with promising inhibition of cerebrotoxic proteins (apoptotic and neuroinflammatory) as evident from molecular docking studies. The cerebroprotective potential of AE could be due to its anti-inflammatory, antioxidant, and antiapoptotic principles.

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

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.

In silico screening of phytopolyphenolics for the identification of bioactive compounds as novel protease inhibitors effective against SARS-CoV-2.

Due to the unavailability specific drugs or vaccines (FDA approved) that can cure COVID-19, the development of potent antiviral drug candidates/therapeutic molecules against COVID-19 is urgently required. This study was aimed at in silico screening and study of polyphenolic phytochemical compounds in a rational way by virtual screening, molecular docking and molecular dynamics studies against SARS-CoV-2 main protease (Mpro) and papain-like protease (PLpro) enzymes. The objective of the study was to identify plant-derived polyphenolic compounds and/or flavonoid molecules as possible antiviral agents with protease inhibitory potential against SARS-CoV-2. In this study, we report plant-derived polyphenolic compounds (including flavonoids) as novel protease inhibitors against SARS-CoV-2. From virtual docking and molecular docking study, 31 polyphenolic compounds were identified as active antiviral molecules possessing well-defined binding affinity with acceptable ADMET, toxicity and lead-like or drug-like properties. Six polyphenolic compounds, namely, enterodiol, taxifolin, eriodictyol, leucopelargonidin, morin and myricetin were found to exhibit remarkable binding affinities against the proteases with taxifolin and morin exhibiting the highest binding affinity toward Mpro and PLpro respectively. Molecular dynamics simulation studies of these compounds in complex with the proteases showed that the binding of the compounds is characterized by structural perturbations of the proteases suggesting their antiviral activities. These compounds can therefore be investigated further by in vivo and in vitro techniques to assess their potential efficacy against SARS-CoV-2 and thus serve as the starting point for the development of potent antiviral agents against the deadly COVID-19.