Natural Products and Nutrients against Different Viral Diseases: Prospects in Prevention and Treatment of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a global pandemic and is posing a serious challenge to mankind. As per the current scenario, there is an urgent need for antiviral that could act as a protective and therapeutic against SARS-CoV-2. Previous studies have shown that SARS-CoV-2 is much similar to the SARS-CoV bat that occurred in 2002-03. Since it is a zoonotic virus, the exact source is still unknown, but it is believed bats may be the primary reservoir of SARS-CoV-2 through which it has been transferred to humans. In this review, we have tried to summarize some of the approaches that could be effective against SARS-CoV-2. Firstly, plants or plant-based products have been effective against different viral diseases, and secondly, plants or plant-based natural products have the minimum adverse effect. We have also highlighted a few vitamins and minerals that could be beneficial against SARS-CoV-2.

Genotoxic and Cytotoxic Properties of Zinc Oxide Nanoparticles Phyto-Fabricated from the Obscure Morning Glory Plant Ipomoea obscura (L.) Ker Gawl.

The study was undertaken to investigate the antioxidant, genotoxic, and cytotoxic potentialities of phyto-fabricated zinc oxide nanoparticles (ZnO-NPs) from Ipomoea obscura (L.) Ker Gawl. aqueous leaf extract. The UV-visible spectral analysis of the ZnO-NPs showed an absorption peak at 304 nm with a bandgap energy of 3.54 eV, which are characteristics of zinc nanoparticles. Moreover, the particles were of nano-size (~24.26 nm) with 88.11% purity and were agglomerated as observed through Scanning Electron Microscopy (SEM). The phyto-fabricated ZnO-NPs offered radical scavenging activity (RSA) in a dose-dependent manner with an IC50 of 0.45 mg mL-1. In addition, the genotoxicity studies of ZnO-NPs carried out on onion root tips revealed that the particles were able to significantly inhibit the cell division at the mitotic stage with a mitotic index of 39.49%. Further, the cytotoxic studies on HT-29 cells showed that the phyto-fabricated ZnO-NPs could arrest the cell division as early as in the G0/G1 phase (with 92.14%) with 73.14% cells showing early apoptotic symptoms after 24 h of incubation. The results of the study affirm the ability of phyto-fabricated ZnO-NPs from aqueous leaf extract of I. obscura is beneficial in the cytotoxic application.

Prospective therapeutic potential of Tanshinone IIA: An updated overview.

In the past decades, the branch of complementary and alternative medicine based therapeutics has gained considerable attention worldwide. Pharmacological efficacy of various traditional medicinal plants, their products and/or product derivatives have been explored on an increasing scale. Tanshinone IIA (Tan IIA) is a pharmacologically active lipophilic component of Salvia miltiorrhiza extract. Tan IIA shares a history of high repute in Traditional Chinese Medicine. Reckoning with these, the present review collates the pharmacological properties of Tan IIA with a special emphasis on its therapeutic potential against diverse diseases including cardiovascular diseases, cerebrovascular diseases, cancer, diabetes, obesity and neurogenerative diseases. Further, possible applications of various therapeutic preparations of Tan IIA were discussed with special emphasis on nano-based drug delivery formulations. Considering the tremendous advancement in the field of nanomedicine and the therapeutic potential of Tan IIA, the convergence of these two aspects can be foreseen with great promise in clinical application.

Biogenic Gold Nanoparticles as Potent Antibacterial and Antibiofilm Nano-Antibiotics against Pseudomonas aeruginosa.

Abstract: Plant-based synthesis of eco-friendly nanoparticles has widespread applications in many fields, including medicine. Biofilm-a shield for pathogenic microorganisms-once formed, is difficult to destroy with antibiotics, making the pathogen resistant. Here, we synthesized gold nanoparticles (AuNPs) using the stem of an Ayurvedic medicinal plant, Tinospora cordifolia, and studied the action of AuNPs against Pseudomonas aeruginosa PAO1 biofilm. The synthesized AuNPs were characterized by techniques such as ultraviolet-visible spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, energy-dispersive X-ray diffraction, X-ray diffraction, scanning electron microscopy (SEM), and transmission electron microscopy. The AuNPs were spherically shaped with an average size of 16.1 nm. Further, the subminimum inhibitory concentrations (MICs) of AuNPs (50, 100, and 150 µg/mL) greatly affected the biofilm-forming ability of P. aeruginosa, as observed by crystal violet assay and SEM, which showed a decrease in the number of biofilm-forming cells with increasing AuNP concentration. This was further justified by confocal laser scanning microscopy (CLSM), which showed irregularities in the structure of the biofilm at the sub-MIC of AuNPs. Further, the interaction of AuNPs with PAO1 at the highest sub-MIC (150 µg/mL) showed the internalization of the nanoparticles, probably affecting the tendency of PAO1 to colonize on the surface of the nanoparticles. This study suggests that green-synthesized AuNPs can be used as effective nano-antibiotics against biofilm-related infections caused by P. aeruginosa.

Cinnamomum verum Bark Extract Mediated Green Synthesis of ZnO Nanoparticles and Their Antibacterial Potentiality.

Cinnamomum verum plant extract mediated propellant chemistry route was used for the green synthesis of zinc oxide nanoparticles. Prepared samples were confirmed for their nano regime using advanced characterization techniques such as powder X-ray diffraction and microscopic techniques such as scanning electron microscopy and transmission electron microscopy. The energy band gap of the green synthesized zinc oxide (ZnO)-nanoparticles (NPs) were found between 3.25-3.28 eV. Fourier transmission infrared spectroscopy shows the presence of Zn-O bond within the wave number of 500 cm-1. SEM images show the specific agglomeration of particles which was also confirmed by TEM studies. The green synthesized ZnO-NPs inhibited the growth of Escherichia coli and Staphylococcus aureus with a minimum inhibitory concentration (MIC) of 125 µg mL-1 and 62.5 µg mL-1, respectively. The results indicate the prepared ZnO-NPs can be used as a potential antimicrobial agent against harmful pathogens.

Recent Nano-based Therapeutic Intervention of Bioactive Sesquiterpenes: Prospects in Cancer Therapeutics.

In the recent scenario, nanotechnology-based therapeutics intervention has gained tremendous impetus all across the globe. Nano-based pharmacological intervention of various bioactive compounds has been explored on an increasing scale. Sesquiterpenes are major constituents of essential oils (EOs) present in various plant species which possess intriguing therapeutic potentials. However, owing to their poor physicochemical properties; they have pharmacological limitations. Recent advances in nano-based therapeutic interventions offer various avenues to improve their therapeutic applicability. Reckoning with these, the present review collates various nano-based therapeutic intervention of sesquiterpenes with prospective potential against various debilitating diseases especially cancer. In our viewpoint, considering the burgeoning advancement in the field of nanomedicine; in the near future, the clinical applicability of these nano-formulated sesquiterpenes can be foreseen with great enthusiasm.

A Computational Study of Natural Compounds from Bacopa monnieri in the Treatment of Alzheimer's Disease.

Keeping in view the public health-related issues of Alzheimer's disease (AD), its unpredictable occurrence and progression indicate the needs for best treatment options. The present bioinformatics study explores the binding pattern and molecular interactions between human acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes with natural compounds from Bacopa monnieri. The docking analysis between natural compounds as a ligand and AChE, BuChE as a receptor was completed using MGL tools Autodock 4.2 module. The analysis of the hydrophobic interactions, inhibition constants, and hydrogen bonds may indicates that they play a significant role in finding out the interacting position at the active site. However, after analyzing the binding energy (ΔG), the documented data shows that bacoside X, bacoside A, 3-beta-D-glucosylstigmasterol and daucosterol could be good inhibitors in the inhibition of AChE and BuChE activities. Therefore, our study indicates that the inhibition constants of the aforesaid natural compounds of Bacopa can be utilized for the development of inhibitors.

One-Pot Facile Green Synthesis of Silver Nanoparticles Using Seed Extract of Phoenix dactylifera and Their Bactericidal Potential against MRSA.

Due to the great economic, health, and medicinal importance, Phoenix dactylifera seeds were chosen for the synthesis of silver nanoparticles (AgNPs) because of their ecofriendly, nonhazardous, cost effectiveness advancement over physical and chemical methods, as green methods are safe, one step, and simple and did not require any chemical reducing and stabilizing agents. The green synthesized AgNPs were characterized by UV-Vis spectroscopy, SEM, HR-TEM, and DLS. Further, the bactericidal activity of synthesized AgNPs against Methicillin-resistant Staphylococcus aureus (MRSA) was investigated by determining MIC/MBC, agar diffusion methods, and electron microscopy. TEM images of the so-formed AgNPs revealed that the NPs were spherical in shape, with a size range of 14-30 nm. The MIC and MBC of AgNPs for MRSA were found to be 10.67±0.94 and 17.33±1.89 µg/ml, respectively. The antibacterial activities were found to be increased with the increasing concentration of AgNPs. The zone of inhibition was greater (24mm) at highest concentrations (500µg/ml) of AgNPs, while smaller (11mm) at lowest concentrations (7.8µg/ml). The SEM images of treated MRSA cells showed wrinkled and damaged cell wall, indicating the disruption and disorganization of membrane. HR-TEM analysis exhibits extensive injury and complete disintegration of cell wall and membrane. Large translucent zones have been seen in the cytoplasm, due to either localized or complete separation of the cell membrane from the cell wall. Overall, these results indicate that green synthesized AgNPs should be considered as an effective treatment and prevention option for the medical devises related infections caused by deadly MRSA and other drug resistant pathogens.

Therapeutics Role of Azadirachta indica (Neem) and Their Active Constituents in Diseases Prevention and Treatment.

Neem (Azadirachta indica) is a member of the Meliaceae family and its role as health-promoting effect is attributed because it is rich source of antioxidant. It has been widely used in Chinese, Ayurvedic, and Unani medicines worldwide especially in Indian Subcontinent in the treatment and prevention of various diseases. Earlier finding confirmed that neem and its constituents play role in the scavenging of free radical generation and prevention of disease pathogenesis. The studies based on animal model established that neem and its chief constituents play pivotal role in anticancer management through the modulation of various molecular pathways including p53, pTEN, NF-κB, PI3K/Akt, Bcl-2, and VEGF. It is considered as safe medicinal plants and modulates the numerous biological processes without any adverse effect. In this review, I summarize the role of Azadirachta indica in the prevention and treatment of diseases via the regulation of various biological and physiological pathways.

In Silico Analysis of Green Tea Polyphenols as Inhibitors of AChE and BChE Enzymes in Alzheimer's Disease Treatment.

Alzheimer's disease (AD) is the most frequent cause of dementia, especially in the elderly. AD is the most common progressive neurodegenerative disorder, which involves the loss of structure and function of cholinergic neurons. Moreover, if these neuronal changes cannot be compensated, this may ultimately lead to neurodegenerative processes. Therefore, most of the drug therapies are based on the cholinergic hypothesis, which suggests that AD begins as a deficiency in the production of the neurotransmitter acetylcholine. In this context, many inhibitors play an important role in AD treatment among which acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) have more potential in the treatment process of AD. In this study, we selected tea polyphenols of green tea which are reported as AChE and BChE inhibitors used in the treatment of AD. The molecular docking results revealed that polyphenols exhibit interactions and inhibit by binding with AChE and BChE. The amount of energy to bind with AChE and BChE needed by Epigallocatechin-3-gallate was lowest at about -14.45 and -13.30 kcal/mol, respectively. All compounds showed binding energy values ranging between -14.45 to -9.75 kcal/mol for both types of enzymes. The present docking study suggests that tea polyphenols inhibit AChE as well as BChE and enhance the cholinergic neurotransmission by prolonging the time. However, AChE molecules remain in the synaptic cleft. In consideration to these findings, cholinesterase inhibitors are suggested as the standard drugs for the treatment of AD.

Green synthesis of Al2O3 nanoparticles and their bactericidal potential against clinical isolates of multi-drug resistant Pseudomonas aeruginosa.

The high prevalence of extended-spectrum ß-lactamases (76.3 %) and metallo-ß-lactamases (7.3 %) amongst the bacteria Pseudomonas aeruginosa is a critical problem that has set forth an enormous therapeutic challenge. The suggested role of nanoparticles as next generation antibiotics, and inadequate information on antibacterial activity of aluminium oxide nanoparticles has led us to investigate the green synthesis of aluminium oxide nanoparticles (Al2O3 NPs) using leaf extracts of lemongrass and its antibacterial activity against extended-spectrum ß-lactamases and metallo-ß-lactamases clinical isolates of P. aeruginosa. The synthesized Al2O3-NPs were characterized by scanning electron microcopy, high resolution-transmission electron microscopy, atomic force microscopy, X-ray diffraction, Zeta potential, and differential light scattering techniques. The X-ray diffraction data revealed the average size of the spherical Al2O3-NPs as 34.5 nm. The hydrodynamic size in Milli Q water and Zeta potential were determined to be 254 nm and +52.2 mV, respectively. The minimal inhibitory concentration of Al2O3-NPs was found to be in the range of 1,600-3,200 µg/ml. Treatment at concentrations >2,000 µg/ml, resulted in complete growth inhibition of extended-spectrum ß-lactamases and metallo-ß-lactamases isolates. Scanning electron microcopy analysis revealed the clusters of nanoparticles attached to the bacterial cell surface, causing structural deformities in treated cells. High resolution-transmission electron microscopy analysis confirmed that nanoparticles crossed the cell membrane to become intracellular. The interaction of nanoparticles with the cell membrane eventually triggered the loss of membrane integrity, most likely due to intracellular oxidative stress. The data explicitly suggested that the synthesized Al2O3-NPs can be exploited as an effective bactericidal agent against extended-spectrum ß-lactamases, non-extended-spectrum ß-lactamases and metallo-ß-lactamases strains of P. aeruginosa, regardless of their drug resistance patterns and mechanisms. The results elucidated the clinical significance of Al2O3-NPs in developing an effective antibacterial therapeutic regimen against the multi-drug resistant bacterial infections. The use of leaf extract of lemongrass for the synthesis of Al2O3-NPs appears to be cost effective, nontoxic, eco-friendly and its strong antibacterial activity against multi-drug resistant strains of P. aeruginosa offers compatibility for pharmaceutical and other biomedical applications.

Therapeutic Implications of Black Seed and Its Constituent Thymoquinone in the Prevention of Cancer through Inactivation and Activation of Molecular Pathways.

The cancer is probably the most dreaded disease in both men and women and also major health problem worldwide. Despite its high prevalence, the exact molecular mechanisms of the development and progression are not fully understood. The current chemotherapy/radiotherapy regime used to treat cancer shows adverse side effect and may alter gene functions. Natural products are generally safe, effective, and less expensive substitutes of anticancer chemotherapeutics. Based on previous studies of their potential therapeutic uses, Nigella sativa and its constituents may be proved as good therapeutic options in the prevention of cancer. Black seeds are used as staple food in the Middle Eastern Countries for thousands of years and also in the treatment of diseases. Earlier studies have shown that N. sativa and its constituent thymoquinone (TQ) have important roles in the prevention and treatment of cancer by modulating cell signaling pathways. In this review, we summarize the role of N. sativa and its constituents TQ in the prevention of cancer through the activation or inactivation of molecular cell signaling pathways.

Azadirachta indica ethanolic extract protects neurons from apoptosis and mitigates brain swelling in experimental cerebral malaria.

BACKGROUND: Cerebral malaria is a rapidly developing encephalopathy caused by the apicomplexan parasite Plasmodium falciparum. Drugs currently in use are associated with poor outcome in an increasing number of cases and new drugs are urgently needed. The potential of the medicinal plant Azadirachta indica (Neem) for the treatment of experimental cerebral malaria was evaluated in mice. METHODS: Experimental cerebral malaria was induced in mice by infection with Plasmodium berghei ANKA. Infected mice were administered with Azadirachta indica ethanolic extract at doses of 300, 500, or 1000 mg/kg intraperitoneally (i.p.) in experimental groups, or with the anti-malarial drugs chloroquine (12 mg/kg, i.p.) or artemether (1.6 mg/kg, i.p.), in the positive control groups. Treatment was initiated at the onset of signs of brain involvement and pursued for five days on a daily basis. Mice brains were dissected out and processed for the study of the effects of the extract on pyramidal cells' fate and on markers of neuroinflammation and apoptosis, in the medial temporal lobe. RESULTS: Azadirachta indica ethanolic extract mitigated neuroinflammation, decreased the severity of brain oedema, and protected pyramidal neurons from apoptosis, particularly at the highest dose used, comparable to chloroquine and artemether. CONCLUSIONS: The present findings suggest that Azadirachta indica ethanolic extract has protective effects on neuronal populations in the inflamed central nervous system, and justify at least in part its use in African and Asian folk medicine and practices.

Effect of chronic unpredictable stress on short term dietary restriction and its modulation by multivitamin-mineral supplementation.

Dietary restriction (DR) lowers steady-state levels of oxidative stress and alters behavioral, physiological and biochemical responses in mammals. However, various factors effect its application in humans like socio-cultural, appetite and the daily life stress. Physiological and psychological stress owing to fast-paced lifestyles, translates into oxidative stress. In this work, the role of chronic unpredictable stress (CUS) on the effects of short term DR in mice in terms of biochemical and oxidative stress parameters was investigated. Further, the modulatory role of multivitamin-mineral supplement (MVM) on CUS and DR induced biochemical changes was studied to delineate the role of micronutrient supplementation. DR treatment increased the antioxidant status in the circulation and liver of mice but in the presence of chronic stressors there was a significant shift towards the pro-oxidant state. A decrease was found in the activities of antioxidant enzymes superoxide dismutase, catalase, and glutathione-S-transferase and glutathione reductase in the rats exposed to CUS with DR (CUS+DR), with an increased malondialdehyde and a decreased glutathione (GSH) levels as compared to the controls. Liver function enzymes-glutamate oxaloacetate transaminase and glutamate pyruvate transaminase were increased and a significant DNA damage was observed. Oral MVM supplement significantly improved this oxidative deterioration. Hence, MVM supplementation appears to potentially offer an effective intervention in the DR regimen to combat daily life physical and mental stress.