Novel insights on the multi-functional properties of flavonol glucosides from red onion (Allium cepa L) solid waste - In vitro and in silico approach.

Flavonol glucosides was extracted from red onion solid waste (ROSW) and multi-functional properties were determined to develop alternative strategy for therapeutic beneficiation and utilisation as functional food. The major flavonol glucosides extracted from ROSW were confirmed as quercetin-3, 4'-O-diglucoside (QDG), quercetin-3-O-glucoside (isoquercetin), quercetin-4'-O-glucoside (spiraeoside), isorhamnetin- 4'-glucoside (IMG), quercetin glycoside (QG), and quercetin (Q) using a combination of chromatographic, spectroscopic and scientific literature data. The ROSW solvent fractions and extracted flavonol glucosides showed significant antioxidant effect with DPPH, ABTS, FRAP, and ORAC radical scavenging assays. The in vitro and in silico study revealed that the QG, QDG, isoquercetin, and spiraeoside from ROSW exhibited potent α-glucosidase, tyrosinase and xanthine oxidase enzyme inhibitory activity. In addition, QG, QDG, isoquercetin, and spiraeoside showed potent anticancer effect on HeLa cancer lines. Considering these results, the utilization of ROSW and their flavonol glucosides might be helpful for developing potential antioxidant, anticancer and enzyme inhibitory agents.

New insights into antiviral and cytotoxic potential of quercetin and its derivatives - A biochemical perspective.

Quercetin, a potential polyphenolic which possesses several biological effects. The influenza virus polymerase basic 2 (PB2) subunit of RNA polymerase responsible for replication, degree of virus conservation and active target site for designing specific antivirals. The quercetin derivatives downloaded from PubChem were screened using PyRX software configured with Vina Wizard, targeted on cap-binding site of the PB2 of influenza viral RNA polymerase. Among the PubChem library (total 97,585,747 compounds), 410 quercetin derivatives were screened using molecular docking (affinity: <-9.0 kcal) for their drug-likeness and in vitro cytopathic effect by Sulforhodamine B (SRB) assay. Among all quercetin derivatives, quercetin 3'-glucuronide (Q3G) showed strongest binding affinity towards cap-binding site of the PB2 subunit with -9.6 kcal of binding affinity and 0.00054 mM of Ki value, while quercetin 3'-glucuronide (Q7G) was presented highest anti-influenza activity with 2.10 ± 0.05 of IC50 on influenza A/PR/8/34 virus and non-cytotoxic effect as CC50 > 100 µg/mL.

Probing the effect of quercetin 3-glucoside from Dianthus superbus L against influenza virus infection- In vitro and in silico biochemical and toxicological screening.

Investigation of antiviral and cytotoxic effect of quercetin 3-glucoside (Q3G) from Dianthus superbus L over influenza virus infection and replication were studied. Moreover, anti-influenza mechanism was screened by time-dependent antiviral assay, virus-induced symptoms and related gene expressions. The blockade of cap-binding domain of polymerase basic protein subunit were analysed by molecular docking study. The Q3G demonstrated potent antiviral activity showing 4.93, 6.43, 9.94, 8.3, and 7.1 µg/mL of IC50 for A/PR/8/34, A/Victoria/3/75, A/WS/33, B/Maryland/1/59, and B/Lee/40, respectively. The cellular toxicity of Q3G and oseltamivir (control) were tested and >100 µg/mL of CC50 value considered as nontoxic. Influenza A virus infection induced a higher ROS production, however potentially reduced by Q3G treatment and significantly blocked virus infection induced acidic vesicular organelles (AVO). Moreover, Q3G has no inhibitory effect for neuraminidase activity but blocked virus replication through time dependent assay and showed more competitive binding affinity (-8.0 kcal/mal) than GTP (-7.0 kcal/mol) to block polymerase basic protein-2 subunit of influenza virus. Q3G from D. superbus showed potent antiviral activity against influenza A and B viruses with suppressive effect on virus-induced cellular ROS generation and AVO formation. Thus, this study provided a new line of research for Q3G to develop possible natural anti-influenza drug.

Subcritical water extraction of withanosides and withanolides from ashwagandha (Withania somnifera L) and their biological activities.

Subcritical water extraction (SWE) applied to analyses the bioactives from ashwagandha (W. somnifera) at varying temperature (100-200 °C) and extraction time (10-30 min). The effect of temperature and time has been investigated in terms of extraction yield (EY), total phenolic content (TPC), cytotoxicity, antioxidant, and enzyme inhibitory activities. The withanosides and withanolides responsible for various biological effects were quantified using high performance liquid chromatography (HPLC). The HPLC analysis revealed Withanoside V, Withanoside IV, 12-Deoxywithastramonolide, Withanolide A, and Withaferin A as a principle bioactive compounds in SWE, with high in concentration compared to microwave-assisted extraction (MAE), Soxhlet extraction (SE) and maceration (MC). For SWE the highest EY (65.6%; 200 °C for 30 min), TPC (82.5 mg GAE/g DE), antioxidant activity (DPPH: 80.3%, FRAP: 60.5% and ABTS: 78.9), and potent enzyme inhibitory effects were observed. The SWE and Withaferin A showed significant reduction in cell viability of cervical cancer (HeLa) cells, with IC50 values 10 mg/ml and 8.5 µM/ml, respectively but no cytotoxic effect for normal cells (MDCK). Thus, SWE can provide effective extraction for ashwagandha withanosides and withanolides compared MAE, SE and MC to conventional methods, which could be used for extraction of pharmacologically active fractions with therapeutic applications.

Lutein derived from marigold (Tagetes erecta) petals triggers ROS generation and activates Bax and caspase-3 mediated apoptosis of human cervical carcinoma (HeLa) cells.

The present investigation was designed to determine molecular and cellular events involved in anticancer properties of lutein derived from marigold (Tagetes erecta) petals using Human cervical carcinoma (HeLa) cell lines. In vitro experiments demonstrated that lutein at concentration of 10 µM significantly inhibited proliferation of HeLa cells by up to 62.85% after 24 h of treatment and 84.85% after 48 h of treatment. In addition, lutein inhibited proliferation of HeLa cells in a dose-dependent manner by inducing apoptosis. Lutein-treated HeLa cells also showed enhanced accumulation of reactive oxygen species (ROS) correlated with significant downregulation of Bcl-2 (anti-apoptotic) expression and upregulation of Bax (pro-apoptotic) expression. Furthermore, lutein mediated activation of caspase-3 and imbalance between Bax and Bcl-2 expression, causing significant loss of mitochondrial membrane potential of HeLa cells. TUNEL assays revealed significant damage of nuclei DNA in lutein-treated HeLa cells, demonstrating a critical role of lutein in the final stage of apoptosis. Taken together, the results indicate that lutein-induced apoptosis of HeLa cells occurs through enhanced ROS production, interaction with mitochondrial factors, and upregulation of caspase-3-mediated pathway, leading to fragmentation of nuclei DNA. Therefore, lutein could be potentially useful as a chemotherapeutic and/or chemopreventive biomolecule against Human cervical carcinoma.

Authenticating apple cider vinegar's home remedy claims: antibacterial, antifungal, antiviral properties and cytotoxicity aspect.

These are the days when one would go online first seeking home remedies before seeing a doctor. Apple cider vinegar (ACV) is one such popular yet scientifically under-validated remedy. Our results prove the unequivocal antimicrobial activity of ACV to be true at full strength concentrations. However, the activity cannot be generalised because although strong antibacterial activity was observed at 25% concentrations, in terms of antifungal activity, yeasts, especially Candida were found to be less susceptible. The antimicrobial/antioxidant properties are ascertained to the total phenolic contents of ACV, as confirmed by our characterisation of the bioactive compounds and antioxidant activity. When checking for its cytotoxicity, ACV exhibited toxicity even at concentrations as low as 0.7%. These results indicate that there is no question of generalising the idea of ACV usage, instead more in vitro and in vivo validations are necessary in order to precisely weigh the pros and cons of ACV.

Chemopreventive Effect of ß-Cryptoxanthin on Human Cervical Carcinoma (HeLa) Cells Is Modulated through Oxidative Stress-Induced Apoptosis.

The present study was aimed to assess cellular and molecular events involved in the chemopreventive activities of ß-cryptoxanthin derived from mandarin oranges (Citrus unshiu Marc.) on human cervical carcinoma (HeLa) cells. In vitro experiments established that ß-cryptoxanthin significantly inhibited the proliferation of HeLa cells with the IC50 value of 4.5 and 3.7 µM after 24 and 48 h of treatments, respectively. ß-cryptoxanthin-treated HeLa cells exhibited enhanced levels of oxidative stress correlated with significant downregulation of anti-apoptotic Bcl-2, and upregulation of pro-apoptotic Bax mRNA expression. Moreover, ß-cryptoxanthin triggered nuclear condensation and disruption of the integrity of the mitochondrial membrane, upregulated caspase-3, -7, and -9 mRNA, and enhanced activation of caspase-3 proteins, resulting in nuclei DNA damage and apoptosis of HeLa cells. Remarkably, TUNEL assay carried out to detect nuclei DNA damage showed 52% TUNEL-positive cells after treatment with a physiological concentration of ß-cryptoxanthin (1.0 µM), which validates its potential as an anticancer drug of natural origin.

Ultrasound mediated accelerated Anti-influenza activity of Aloe vera.

Aloe vera (AV) is popular and has been commercialized as a beauty product, laxative, herbal medicine, the antimicrobial activity of AV is proven. The antiviral activity of AV however, has not been well documented except for a handful reports. Till date extraction of AV compounds is popularized using organic solvents, since the active components are effectively extracted in methanol. In the current work, we have employed a 5 min ultrasound based extraction for the effective extraction of aloin and aloe-emodin compounds from AV in water. This rapid, one-pot extraction process resulted in enhanced extraction of flavonoids and phenolics and enrichment of the aloin and aloe-emodin moieties in the ulrasonicated water extracts. The extracts were tested for their anti-influenza activity and, the results showed that the ultrasound extraction enabled the water extracts to show excellent anti influenza activity comparable to that seen in the methanolic extracts. Compared to the methanolic extracts which showed high cytotoxicity, the water extracts showed zero cytotoxicity. Spectrophotometric scans of the extracts confirmed the enrichment of the aloin and aloe emodin peaks in the ultrasonicated extracts of AV, suggesting their handiwork behind the anti-influenza activity. The demonstrated technique if appropriately implicated, would lead to promising solutions in the pharmaceutical pursuit against influenza virus.

An efficient one-step scheme for the purification of major xanthophyll carotenoids from lettuce, and assessment of their comparative anticancer potential.

The foremost problem in carotenoid research is the excessive cost and difficulty of maintaining pure carotenoid compounds. This work presents an economical, efficient, and simplified one-step scheme for the purification of four major xanthophyll carotenoids from lettuce by utilizing preparative thin layer chromatography on Hyflo-Super-Cel: MgO (Heavy): calcium sulfate hemihydrate (9:9:2 w/w) based adsorbent. The mobile phase of acetone: hexane (1:1) provided the perfect separation of major xanthophylls, resulting in 95-96% purity after just single-step separation, with no interference from chlorophylls or other minor carotenoids. The identity of carotenoids was confirmed by absorption spectroscopy, chemical tests and APCI+-MS/MS. The proposed scheme can be used to isolate the carotenoids at the analytical and preparative scale. In anticancer studies, among four xanthophylls, 9-Z-neoxanthin was found most potent for reduction of cell viability of cervical (HeLa) and lung cancer (A549) cells, with IC50 values of 3.8 and 7.5 µM, respectively.

The unequivocal preponderance of biocomputation in clinical virology.

Bioinformatics and computer based data simulation and modeling are captivating biological research, delivering great results already and promising to deliver more. As biological research is a complex, intricate, diverse field, any available support is gladly taken. With recent outbreaks and epidemics, pathogens are a constant threat to the global economy and security. Virus related plagues are somehow the most difficult to handle. Biocomputation has provided appreciable help in resolving clinical virology related issues. This review, for the first time, surveys the current status of the role of computation in virus related research. Advances made in the fields of clinical virology, antiviral drug design, viral immunology and viral oncology, through input from biocomputation, have been discussed. The amount of progress made and the software platforms available are consolidated in this review. The limitations of computation based methods are presented. Finally, the challenges facing the future of biocomputation in clinical virology are speculated upon.

Nature nominee quercetin's anti-influenza combat strategy-Demonstrations and remonstrations.

Nature's providences are rather the choicest remedies for human health and welfare. One such is quercetin, which is nature's nominee for cancer cure and recently demonstrated against influenza attack. Quercetin is highly recognized for its anticancer applications. This review emphasizes on yet another gift that this compound has to offer for mankind, which is none other than combating the deadly evasive influenza virus. The chemistry of this natural bioflavonoid and its derivatives and its modus operandi against influenza virus is consolidated into this review. The advancements and achievements made in the anti-influenza clinical history are also documented. Further, the challenges facing the progress of this compound to emerge as a predominant anti-influenza drug are discussed, and the future perspective for breaking its limitations through integration with nanoplatforms is envisioned.

The ethanopharmacological aspect of carbon nanodots in turmeric smoke.

Smoke manifested ever since our ancient's lit fire; today it has evolved to become an environmental concern. However, medicinal smoke is still part of man's natural remedies, religious and cultural practices too. The Asiatic household practice of burning turmeric rhizomes to relieve nose and chest congestion is a well known yet never scientifically authenticated or studied practice. For the first time we investigate the components of these turmeric smudges, validate their antimicrobial and anticancer properties and their cell compatibility. With smoke there is always nanoparticulate carbon and turmeric smoke is no exception. If so, what is the role of the nano carbon (NC) in the turmeric smudge effect? This study isolated, characterized and exposed these secret natural NC undercover agents in turmeric smoke. Their unequivocal role in the ethanopharmocological activity of turmeric smudging has been demonstrated. This work opens a new avenue for use of such nano components of smoke for harnessing the ethanopharmacological property of various medicinal smokes, by excluding the smoke factor, through extracting the nano carbon material in them. This is a possibility to realizing the use of such naturally available nanomaterial, as an eco friendly substitute for the notorious anthropogenic nanomaterials.

Probing the impact of quercetin-7-O-glucoside on influenza virus replication influence.

BACKGROUND: Influenza virus is still at large and seriously affects social welfare and health. Dianthus superbus is a well-known medicinal plant widely used in Mongolian and Chinese traditional medicine for anti-inflammatory purposes. PURPOSE: To investigate the influence of this novel herbal medicinal product over virus infection and virus-induced symptoms METHOD: Quercetin-7-O-glucoside was isolated by bioassay (anti-influenza)-guided fractionation. The structural elucidation was made with 1H-NMR and 13C-NMR. Influenza A/Vic/3/75 (H3N2), A/PR/8/34 (H1N1), B/Maryland/1/59 and B/Lee/40 viruses were used for the evaluation of the antiviral activity. Virus-induced reactive oxygen species and autophagy formation levels were studied. The antiviral mechanism was elucidated via time-dependent, pre-, post-incubation assay methods. The viral RNA replication inhibition of Q7G was analyzed using quantitative RT-PCR method. The blocking of polymerase basic protein subunits of influenza viral RNA polymerase by Q7G was detected by in silico molecular docking assays using AutoDock Vina program with m(7)GTP. Additionally, Q7G was tested against M-MuLV RNA polymerase. RESULTS: Q7G was not cytotoxic (CC50>100µg/ml) in MDCK cells and it showed 3.1µg/ml, 6.61µg/ml, 8.19µg/ml and 5.17µg/ml IC50 values against influenza A/PR/8/34, A/Vic/3/75, B/Lee/40 and B/Maryland/1/59 virus strains, respectively. Treatment of Q7G highly reduced ROS and autophagy formation induced by influenza virus infection. Q7G did not reduce NA activity and did not directly interact with the virus particles. Since viral RNA synthesis was blocked by treatment of Q7G. We targeted viral RNA polymerase for further probing. Interestingly, the binding energy of Q7G on viral PB2 protein was -9.1kcal/mol and was higher than m(7)GTP recorded as -7.5kcal/mol. It also was observe to block M-MuLV RNA polymerase. CONCLUSION: Isolated compound Q7G showed strong inhibition activity against influenza A and B viruses. It also reduced virus-induced ROS and autophagy formation. Q7G does not directly bind to the virus particles and did not affect NA activity. These results indicated that Q7G inhibits viral RNA polymerase, and that it occupies the binding site of m(7)GTP on viral PB2 protein.