HYPNOTIC (Ultimate Sleep Formula)

May 20, 2020

AUTONOMOUS (Nootropic Tour De Force)

September 18, 2020

VICTORIOUS (Science Based Anti-Viral Formula)

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$275.00

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introducing

INTERSTELLAR blend

“victorious”

SCIENCE BASED INGREDIENTS

THE MOST COMPREHENSIVE ALL NATURAL ANTIVIRAL FORMULA EVER CREATED

Featuring: 1-Dehydrogingerdione – Zingiber Officinale (Ginger)• 3,2᾿Dihydroxyflavone (3,2᾿Dhf) & 3,4᾿Dihydroxyflavone (3,4᾿Dhf) – Trifolium Repens L. • 6-Gingerol – Zingiber Officinale (Ginger)• Acidicheteroglucan – Tremella Fuciformis • Aconitum Carmichaelii Debx • Ailanthus Altissima Stem Bark • Allantoin – Glyoxylic Acid • Alphitonia Philippinensis Stems • Amygdalin – Semen Armeniacae Amarum • Anemarrhena Asphodeloides • Angelica Sinensis (Oliv.) Diels • Apigenin – Celery • Arctigerin, Arctin – Burdock (Arctium Lappa) • Artemisinin – Artemisia Annua • Aspalathin – Rooibos Tea • Atractylodin ,Β-Eudesmol, Hinesol, Hydroxy-Atractylo – Rhizoma Areactylodis Lanceae • Baicalein – Scutellaria Baicalensis Georgi • Benzaldehyde – Laurus Nobilis Leaves • Berberine – Coptis Chinensis • Beta-Sitosterol – Rice Bran Oil • Betulinic Acid – Betula Platyphylla Suk Bark • Bisdemethoxycurcumin – Turmeric Rhizome • Brachyamide B – Piper Boehmeriaefolium (Miq.) C. Dc • Bulbocapnine – Corydalis Decumbens(Thunb.) • Caffeic Acid – Cimicifuga Simplex (Dc.) Wormsk. Ex Turcz.Root • Calanolide A – Calophyllum Lanigerum • Campesterol – Rapeseed Oil • Carvacrol – Oregano • Chavicine – Black Pepper • Chelidimerine – Chelidonium Majus • Chlorogenic Acid – Green Coffee Bean • Chrysin – Pinus Mon-Ticola Dougl • Cinanserin – Cinnamic Acid • Cinnamomum Cassia Presl Dried Bark • Cirsilineol – Cirsium Lineare (Thunb.) Sch. • Cirsimaritin – Rabdosia Eriocalyx • Cis-Capsaicin (Civamide) – • Colchicine – Colchicum Autumnale L. • Cordifolioside A – Viola Verecunda • Crategolic Acid – Hawthorn • Curcumin – Turmeric Root • Cycloastragenol – Astragalus Membranaceus • Cyclocurcumin – Turmeric Root • Demethoxycurcumin – Turmeric Root • Dianthus Caryophyllus Seed – Carnation • Dioscin, Diosgenin – Wild Yam （Dioscorea Oppositae Thunb）• Douchi (Semen Sojae Praepatum) – Semen Sojae Praepatum • Egcg – Green Tea • Emodin – Rhubarb • Eriodictyol – Lemon • Eugenitin – Clove • Ferruginol – Podocarpus Ferruginea • Fisetin – Rhus Succedanea L • Flavonol Glucoside – Trichilia Connaroides Leaves • Forskolin – Coleus Forskohlii • Fructus Perillae – Perillafrutescens • Fumarophycine – Laptopyrum Reichb • Galangin – Alpinia Officinarum Hance Root • Gallic Acid – Rheumpalmatum L.Root • Genistein – Genista Tinctoria Linn Root • Glycyrrhizic Acid – Licorice Root • Gossypol – Cotton Seed • Guineensine – Piper Longum L. • Gypsum Fibrosum – Gypsum • Hawthorn Flavone – Crataegus Pinnatifida Bunge • Herba Dendrobii – Dendrobium Nobile Lindl • Herbacetin – Flaxseed • Hesperetin – Citrus Aurantium • –Hesperidin Nobiletin B-Phellandrene – Pericarpium Citri Reticulatae • Himachalol – Cupressus Funebris Endl. • Honokiol – Magnolia Officinalis • Houttuynia Cordata – Houttuynia Cordata Thunb • Hypericin Pseudohypericin Protohypericin – Forsythia Suspensa • Isochavicine – Pepper • Isoliquiritigenin – Glycyrrhiza Uralensisfisch Root • Isopiperine – Pepper • Isothymonin – Kaempferia Galanga L • Jatrorrhizine – Phellodendron Amurense Rupr. • Jujuboside A+B – Jujube • Kaempferol – Kaempferol Galanga L • Kaempferol 3-O-Robinobioside – Robinia Pseudoacacia L. • Leachianone – Morus Alba Root Bark • Lepidium Meyenii (Maca ) • Lily – Lilium Auratum • Luteoforol (A Flavan-4-Ol) – Peanut Shell • Luteolin – Peanut Shell • Lycoris Radiata – Lycoris Radiata (L’her.) Herb. • Macaranga Barteri Leaves • Maclura Cochinchinensis (Loureiro) Corner Root • Magnoflorine – Thalictrum Aquilegifolium Root • Marrubium Peregrinum L (Lamiaceae) • Meliacine – Melia Azedarach L • Mint – Mentha Haplocalyx Briq.• Morroniside,7-0-Methylmorroniside, Sweroside, Loganin, Cornus-Tannin 1,2,3 – Cornus Officinalis (Fructus Corni) • Morroniside,Cornus-Tannin 1,2,3 – Fructus Corni • Myricetin – Black Bayberry Fruit • N-Acetylcysteine ethyl ester (NACET) • Naringenin – Amacardi-Um Occidentale L.) • Ndoxyl-Β-Glucoside Uridine, Salicylic Acid,Daucosterol, Β-Sitostero – Radix Isatidis P.E (Satis Tinctoria L. Isatis Indigotica Fort.) • Nothofagin – Aspalathus Linearis • Oleanolic Acid – Olea Europaea L.Leaves • Olomoucine Ii – • Ophiocarpine – Corydalis Ophiocarpa Hook. F. Et Thoms • Ophiopogonin A B C D – Ophiopogon Root • Orientin – Globeflower • Oxypeucedanin Stiamasterol Β-Sitosterol Β-Daucosterin – Angelica Dahurica • Paeoniflorin – Radix Paeoniae Rubra • Patrinia Villosa Juss. – Patrinia Villosa (Thunb. ) Juss. • Peach Kernel – Emen Persicae • Pectolinarin – Linaria Vulgaris Hill Subsp. • Pelargonium Sidoides – Pelargonium Peltatum (L.) Ait. • Pentadienoylpiperidine – Pepper • Phragmitescommunis Trin – Phragmites Australis (Cav.) Trin. Ex Steud • Phyllanthus Orbicularis – Phyllanthus Orbicularis Kunth • Pinusolidic Acid – Vanillin & Malonic Acid • Piperettine – Pepper • Pipericide – Pepper • Piperine – Pepper • Piperolein B – Pepper • Poria Cocos Polysaccharide – Poria Cocos(Schw.)Wolf. • Protocatechuic Acid – Stenoloma Chusanum(L.) Ching Leaves • Protopine – Corydalis Yanhusuo W.T.Wang • Quercetin – Sophora Japonica • Quercetin-3-B-Galactoside – St. John’s Wort • Quercetin-3,7-O-Α-L-Dirhamnoside （Quercitrin） – Sabina Pingii Var. Wilsonii • Quinic Acid – Cinchona Bark • Radix Codonopsis Root • Radix Glehniae – Coasiai Giehnia Root • Radix　Platycodonis Platycodigenin, Polygalacic Acid – Platycodon Grandiflorum Root • Radix Scrophulariae Root • Reserpine – Rauvolfia Verticillata (Lour.) Baill. • Resveratrol – Polygonum Cuspidatum • Retrofractamide A – Black Pepper • Rhamnetin – Syzygium Aromaticum • Rhizoma Atractylodis Macrocephalae Root • Rhizoma Pinelliae – Pinellia Ternata (Thunb.) Breit • Rhoifolin – Turpinia Arguya Seem Leaves • Rosmarinic Acid – Rosemary • Rupestonic Acid – Artemisia Rupestris L. • Rutin – Ruta Graveolens L. • Saikosapoins A B C D – Bupleurum (Radix Stellariae) • Salicin – Salix Babylonical Bark • Salidroside, Rosavine, Rosin，Rosarin，Rhodiolin – Rhodiola Rosea • Samarangenin B – Limonium Bicolor (Bag.) Kuntze • Saposhnikovia Divaricata (Trucz.) Schischk Root • Savinin • Schisandrin, Deoxyschisandrin, Neoschisandrin – Schisandra Chinensis • Schizonepeta Tenusfolia Briq Dried Flower • Selaginella Moellendorfii Hieron • Semen Lepidii Semen Descurainiae – Eruca Sativa Mill • Silibinin – Milk Thistle • Silymarin – Milk Thistle • Solanum Rantonnetii Aerial Parts Extact – Lycianthes Rantonnetii Bitter • Somniferine – Ashwagandha/Ajagandha/Kanaje • Stigmasterol – Soybean • Synephrine – Citrus Aurantium Powde • Taxillus Sutchuenensis – Taxillus Sutchuenensis (Lecomte ) Danser • Tinocordifolin – Tinospora Cordifolia • Tinocordifolioside – Tinospora Cordifolia • Tinosporide – Tinospora Cordifolia • Trichostachine – Piper Hancei Maxim • Triterpenoid Saponins – Trichosanthes Kirilowii (Mongolian Snakegourd Fruit) • Umbelliferone – Ruta Graveolens L. • Ursolic Acid – Loquat Leaf • Valinomycin – Bacterium Streptomyces • Verbascum Thapsus L – Mullein • Vicenin – Desmodium Styracifolium • Vincamine – Catharanthus Roseus （L.）G. Don • Vitex Polygama – Vitex Negundo L. Var. Cannabifolia (Sieb. Et Zucc.) Hand.-Mazz • Withaferin A – Ashwagandha • Withanolide – Ashwagandha • Withanolide B – Ashwagandha • Withanone – Ashwaganda • Wogonin – Scutellaria Baicalensis （Radix Scutellariae） • Wrinkled Giant hyssop – Agastache Rugosa (Fisch. Et Mey.) O. Ktze. • Yohimbine – Yohimbe Bark

200:1 CONCENTRATION

very potent

300 1/8 tsp servings per 100g bag.

Take 1/8 – 1/4 serving 2-4 times a day.

ANTIVIRAL EFFECTS OF FLAVONOIDS AND POLYPHENOLS (THOUSANDS OF STUDIES – CLICK TO READ)

May Polyphenols Have a Role Against Coronavirus Infection? An Overview of the Evidence

Overall, this evidence suggests that polyphenols may exert a marked and well-demonstrated activity against coronaviruses, at least in vitro, in addition to the previously demonstrated antiviral activity in vivo. Studies available in the literature agree in establishing that the reduction of virus titer and the inhibition of nucleocapsid protein expression are their main general mechanisms of action at the base of this promising effect of polyphenols. These elucidated mechanisms are of great interest, since nowadays no effective treatments have been licensed, and the development of novel synthetic drugs against specific coronavirus molecular targets are still far from being achieved.

Antiviral effect of flavonoids on human viruses

The effect of several naturally occurring dietary flavonoids including quercetin, naringin, hesperetin, and catechin on the infectivity and replication of herpes simplex virus type 1 (HSV-1), polio-virus type 1, parainfluenza virus type 3 (Pf-3), and respiratory syncytial virus (RSV) was studied in vitro in cell culture monolayers employing the technique of viral plaque reduction. Quercetin caused a concentration-dependent reduction in the infectivity of each virus. In addition, it reduced intracellular replication of each virus when monolayers were infected and subsequently cultured in medium containing quercetin. Preincubation of tissue culture cell monolayers with quercetin did not affect the ability of the viruses to infect or replicate in the tissue culture monolayers. Hesperetin had no effect on infectivity but it reduced intracellular replication of each of the viruses. Catechin inhibited the infectivity but not the replication of RSV and HSV-1 and had negligible effects on the other viruses. Naringin had no effect on either the infectivity or the replication of any of the viruses studied. Thus, naturally occurring flavonoids possess a variable spectrum of antiviral activity against certain RNA (RSV, Pf-3, polio) and DNA (HSV-1) viruses acting to inhibit infectivity and/or replication.

Discovery of anti-2019-nCoV agents toward respiratory diseases via docking screening

The 2019 novel coronavirus (2019-nCoV) causes novel coronavirus pneumonia (NCP). Given that approved drug repurposing becomes a common strategy to quickly find antiviral treatments, a collection of FDA-approved drugs can be powerful resources for new anti-NCP indication discoveries. In addition to synthetic compounds, Chinese Patent Drugs (CPD), also play a key role in the treatment of virus related infections diseases in China. Here we compiled major components from 38 CPDs that are commonly used in the respiratory diseases and docked them against two drug targets, ACE2 receptor and viral main protease. According to our docking screening, 10 antiviral components, including hesperidin, saikosaponin A, rutin, corosolic acid, verbascoside, baicalin, glycyrrhizin, mulberroside A, cynaroside, and bilirubin, can directly bind to both host cell target ACE2 receptor and viral target main protease. In combination of the docking results, the natural abundance of the substances, and botanical knowledge, we proposed that artemisinin, rutin, glycyrrhizin, cholic acid, hyodeoxycholic acid, puerarin, oleanic acid, andrographolide, matrine, codeine, morphine, chlorogenic acid, and baicalin (or Yinhuang Injection containing chlorogenic acid and baicalin) might be of value for clinical trials during a 2019-nCov outbreak.

Antiviral potential of phytoligands against chymotrypsin-like protease of COVID‐19 virus using molecular docking studies: An optimistic approach

A recent outbreak of the novel coronavirus, COVID‐19, in the city of Wuhan, Hubei province, China and its ensuing worldwide spread have resulted in lakhs of infections and thousands of deaths. As of now, there are no registered therapies for treating the contagious COVID‐19 infections, henceforth drug repositioning may provide a fast way out. In the present study, a total of thirty-five compounds including commonly used anti-viral drugs were screened against chymotrypsin-like protease (3CLpro) using SwissDock. Interaction between amino acid of targeted protein and ligands was visualized by UCSF Chimera. Docking studies revealed that the phytochemicals such as cordifolin, anisofolin A, apigenin 7-glucoside, luteolin, laballenic acid, quercetin, luteolin-4-glucoside exhibited significant binding energy with the enzyme viz. – 8.77, -8.72, -8.36, -8.35, -8.13, -8.04 and -7.87 Kcal/Mol respectively. Therefore, new lead compounds can be used for drug development against SARS‐CoV‐2 infections.

Identification of potent COVID-19 main protease (Mpro) inhibitors from natural polyphenols: An in silico strategy unveils a hope against CORONA

COVID-19, a rapidly spreading new strain of coronavirus, has affected more than 150 countries and received worldwide attention. The lack of efficacious drugs or vaccines against SARS-CoV-2 has further worsened the situation. Thus, there is an urgent need to boost up research for the development of effective therapeutics and affordable diagnostic against COVID-19. The crystallized form of SARS-CoV-2 main protease (Mpro) was demonstrated by a Chinese researcher Liu et al. (2020) which is a novel therapeutic drug target.

This study was conducted to evaluate the efficacy of medicinal plant-based bioactive compounds against COVID-19 Mpro by molecular docking study. Molecular docking investigations were performed by using Molegro Virtual Docker 7 to analyze the inhibition probability of these compounds against COVID-19. COVID-19 Mpro was docked with 80 flavonoid compounds and the binding energies were obtained from the docking of (PDB ID: 6LU7: Resolution 2.16 Å) with the native ligand. According to obtained results, hesperidin, rutin, diosmin, apiin, diacetylcurcumin, (E)-1-(2-Hydroxy-4-methoxyphenyl)-3-[3-[(E)-3-(2-hydroxy-4- methoxyphenyl)-3-oxoprop-1-enyl]phenyl]prop-2-en-1-one, and beta,beta’-(4-Methoxy-1,3- phenylene)bis(2′-hydroxy-4′,6′-dimethoxyacrylophenone have been found as more effective on COVID-19 than nelfinavir. So, this study will pave a way for doing advanced experimental research to evaluate the real medicinal potential of these compounds to cure COVID-19.

Potential of Flavonoid-Inspired Phytomedicines against COVID-19

Flavonoids are widely used as phytomedicines. Here, we report on flavonoid phytomedicines with potential for development into prophylactics or therapeutics against coronavirus disease 2019 (COVID-19). These flavonoid-based phytomedicines include: caflanone, Equivir, hesperetin, myricetin, and Linebacker. Our in silico studies show that these flavonoid-based molecules can bind with high affinity to the spike protein, helicase, and protease sites on the ACE2 receptor used by the severe acute respiratory syndrome coronavirus 2 to infect cells and cause COVID-19. Meanwhile, in vitro studies show potential of caflanone to inhibit virus entry factors including, ABL-2, cathepsin L, cytokines (IL-1β, IL-6, IL-8, Mip-1α, TNF-α), and PI4Kiiiβ as well as AXL-2, which facilitates mother-to-fetus transmission of coronavirus.

Recognition of Natural Products as Potential Inhibitors of COVID-19 Main Protease (Mpro): In-Silico Evidences

Since most of the drug candidates presently available for COVID-19 substantially act on viral main protease, by using molecular docking analysis, we have predicted the protease inhibitor activity of several natural products that can emerge as potential drug candidates inhibiting viral protease. A promising binding of natural products with the COVID-19 main protease was revealed by docking analysis. Among the several natural products screened by docking analysis, glycyrrhizin, tryptanthrine, rhein, and berberine were found to exhibit a higher degree of interaction with the viral protease accompanied by lowest binding energy with favorable drug-like properties. Thus these natural products may emerge as potential COVID-19 main protease inhibitor. However, additional exploration is inevitable for the investigation of the inherent use of the herbs containing these natural products and their in-vivo activity.

Targeting SARS-CoV-2 Spike Protein of COVID-19 with Naturally Occurring Phytochemicals

Spike glycoprotein found on the surface of SARS-CoV-2 (SARS-CoV-2S) is a class I fusion protein which helps the virus in its initial attachment with human Angiotensin converting enzyme 2 (ACE2) receptor and its consecutive fusion with the host cells. The attachment is mediated by the S1 subunit of the protein via its receptor binding domain. Upon binding with the receptor the protein changes its conformation from a pre-fusion to a post-fusion form. The membrane fusion and internalization of the virus is brought about by the S2 domain of the spike protein. From ancient times people have relied on naturally occurring substances like phytochemicals to fight against diseases and infection. Among these phytochemicals, flavonoids and non-flavonoids have been found to be the active source of different anti-microbial agents. Recently, studies have shown that these phytochemicals have essential anti-viral activities. We performed a molecular docking study using 10 potential naturally occurring flavonoids/non-flavonoids against the SARS-CoV-2 spike protein and compared their affinity with the FDA approved drug hydroxychloroquine (HCQ). Interestingly, the docking analysis suggested that C-terminal of S1 domain and S2 domain of the spike protein are important for binding with these compounds.

Kamferol, curcumin, pterostilbene, and HCQ interact with the C-terminal of S1 domain with binding energies of -7.4, -7.1, -6.7 and -5.6 Kcal/mol, respectively. Fisetin, quercetin, isorhamnetin, genistein, luteolin, resveratrol and apigenin on the other hand, interact with the S2 domain of spike protein with the binding energies of -8.5, -8.5, -8.3, -8.2, -8.2, -7.9, -7.7 Kcal/mol, respectively. Our study suggested that, these flavonoid and non-flavonoid moieties have significantly high binding affinity for the two main important domains of the spike protein which is responsible for the attachment and internalization of the virus in the host cell and their binding affinities are much higher compared to that of HCQ. In addition, ADME (absorption, distribution, metabolism and excretion) analysis also suggested that these compounds consist of drug likeness property which may help for further explore as anti-SARS-CoV-2 agents. Further, in vitro and in vivo study of these compounds will provide a clear path for the development of novel compounds that would most likely prevent the receptor binding or internalization of the SARS-CoV-2 spike protein and therefore could be used as drugs for COVID-19 therapy.

Roles of flavonoids against coronavirus infection

In terms of public health, the 21st century has been characterized by coronavirus pandemics: in 2002-03 the virus SARS-CoV caused SARS; in 2012 MERS-CoV emerged and in 2019 a new human betacoronavirus strain, called SARS-CoV-2, caused the unprecedented COVID-19 outbreak. During the course of the current epidemic, medical challenges to save lives and scientific research aimed to reveal the genetic evolution and the biochemistry of the vital cycle of the new pathogen could lead to new preventive and therapeutic strategies against SARS-CoV-2. Up to now, there is no cure for COVID-19 and waiting for an efficacious vaccine, the development of “savage” protocols, based on “old” anti-inflammatory and anti-viral drugs represents a valid and alternative therapeutic approach. As an alternative or additional therapeutic/preventive option, different in silico and in vitro studies demonstrated that small natural molecules, belonging to polyphenols family, can interfere with various stages of coronavirus entry and replication cycle.

Here, we reviewed the capacity of well-known (e.g. quercetin, baicalin, luteolin, hesperetin, gallocatechin gallate, epigallocatechin gallate) and uncommon (e.g. scutellarein, amentoflavone, papyriflavonol A) flavonoids, secondary metabolites widely present in plant tissues with antioxidant and anti-microbial functions, to inhibit key proteins involved in coronavirus infective cycle, such as PL^pro, 3CL^pro, NTPase/helicase. Due to their pleiotropic activities and lack of systemic toxicity, flavonoids and their derivative may represent target compounds to be tested in future clinical trials to enrich the drug arsenal against coronavirus infections.

In conclusion, the interest of scientists for the antiviral capacity of flavonoids against human coronavirus infections can benefit of the enormous amount of resources that governments, health agencies, and private companies are pouring in the field, searching for a cure against SARS-CoV-2. This situation barely resembles what happened in the eighties-nineties following the AIDS pandemic, when the basic knowledge in the immunological mechanisms controlling the response to HIV infection underwent amazing and unpredictable progresses. Waiting for a valuable vaccine against COVID-19, the pharmacological approach remains a priority and flavonoids may contribute to it. In this scenario, the “pleiotropic” properties of flavonoids that we mentioned at the beginning of this review, risks to become the passepartout to counteract coronaviruses since they can be effective on both sides, viral and host cells, to inhibit infection. In fact, recent works hypothesized that flavonoids can inhibit both TMPRSS2 and Furin, which cleave the SARS-CoV-2 Spike protein facilitating SARS-CoV-2 infectivity. Molecular docking-based screening and in vitro assays using recombinant proteins indicated that (−)-epicatechin 3-O-(3′-O-methyl) gallate for TMPRSS2 [⁸⁴] and baicalein and oroxylin A glycoside for Furin [⁸⁵] can bind and inhibit their respective proteases blocking virus propagation.

INGREDIENTS & studies

3,2᾿dihydroxyflavone (Trifolium repens L.)

Antiviral activity of 3,4′-dihydroxyflavone on influenza a virus

Influenza virus infection causes thousands of deaths and millions of hospitalizations worldwide every year and the emergence of resistance to anti-influenza drugs has prompted scientists to seek new natural antiviral materials. In this study, we screened 13 different flavonoids from various flavonoid groups to identify the most potent antiviral flavonoid against human influenza A/PR/8/34 (H1N1). The 3-hydroxyl group flavonoids, including 3,2᾿dihydroxyflavone (3,2᾿DHF) and 3,4᾿dihydroxyflavone (3,4᾿DHF), showed potent anti-influenza activity. They inhibited viral neuraminidase activity and viral adsorption onto cells. To confirm the anti-influenza activity of these flavonoids, we used an in vivo mouse model.

In mice infected with human influenza, oral administration of 3,4᾿DHF significantly decreased virus titers and pathological changes in the lung and reduced body weight loss and death. Our data suggest that 3-hydroxyl group flavonoids, particularly 3,4᾿DHF, have potent antiviral activity against human influenza A/PR/8/34 (H1N1) in vitro and in vivo. Further clinical studies are needed to investigate the therapeutic and prophylactic potential of the 3-hydroxyl group flavonoids in treating influenza pandemics.

6-gingerol (ginger extract)

Acidicheterogluca (Tremella fuciformis)

Structure, bioactivities and applications of the polysaccharides from Tremella fuciformis mushroom: A review

Tremella fuciformis is an important edible mushroom that has been widely cultivated and used as food and medicinal ingredient in traditional Chinese medicine. In the past decades, many researchers have reported that T. fuciformis polysaccharides (TPS) possess various bioactivities, including anti-tumor, immunomodulatory, anti-oxidation, anti-aging, repairing brain memory impairment, anti-inflammatory, hypoglycemic and hypocholesterolemic. The structural characteristic of TPS has also been extensively investigated using advanced modern analytical technologies such as NMR, GC–MS, LC-MS and FT-IR to dissect the structure-activity relationship (SAR) of the TPS biomacromolecule. This article reviews the recent progress in the extraction, purification, structural characterization and applications of TPS.

Antitumor and immunomodulatory

In recent years, studies on the mechanism of polysaccharides have shown that polysaccharides have an immunosuppressive activity protecting against tumor growth. TPS exerts anti-tumor activity by promoting the host’s natural immune defenses. These polysaccharides can modulate the body’s immune functions by regulating immune organs, immune cells and immune molecules, and their immune activity without significant side effects [34]. TPS also has the effect of regulating body immunity and inhibiting tumor growth. Its inhibitory effect on tumors is achieved through the intermediate host effect, that is, by enhancing the body’s immune function to a tumor. TPS can inhibit the growth of Hep G22 cells and at concentrations of 50 mg/ml, the antitumor activity can reach 92% [12]. TPS can reduce side effects during treatment of tumors and can enable patients to rebuild their own immune system improving their cancer resistance [35]. Polysaccharides mainly play an immune function through macrophages, and macrophages can respond to infections, tumors and inflammation.

Macrophages directly kill pathogens through phagocytosis and present antigens to elicit an immune response [36]. Macrophages produce a large number of biologically active molecules, including nitric oxide (NO), reactive oxygen species (ROS), and cytokines including tumor necrosis factor TNF-α, interleukin (IL)-1α, IL-1β, for defense of IL-6, IL-10 [37]. TPS can reverse the effect of proliferation and polarization of CD4+ T cells in Pseudomonas aeruginosa infected scald mice, resulting in a decline in the level of IL-10 [38]. TPS can inhibit modulate cyclophosphamide-induced mouse leukopenia. Leukocytes increase in a dose-dependent fashion [39]. Cyclophosphamide significantly reduces the mRNA expression of IL-1β, IL-4 and IL-12 in liver and spleen, and significantly increases the expression of TGF-β in liver and spleen. CY significantly reduces serum immune organ index and serum cytokine levels (IL-2, IL-12, INF-γ, and Ig G) and increases serum TGF-β levels. These results suggest that low-dose TPS has no obvious effect,

Aconitum carmichaelii

Antiviral activity of aconite alkaloids from Aconitum carmichaelii Debx

Four diterpenoid alkaloids, namely, (a) hypaconitine, (b) songorine, (c) mesaconitine and (d) aconitine, were isolated from the ethanol root extract of Aconitum carmichaelii Debx. The antiviral activities of these alkaloids against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) were evaluated. Antiviral activity test in vivo showed that compounds a and c, which were C19-diterpenoid alkaloids, showed inactivation efficacy values of 82.4 and 85.6% against TMV at 500 μg/mL, respectively.

By contrast, compound c presented inactivation activity of 52.1% against CMV at 500 μg/mL, which was almost equal to that of the commercial Ningnanmycin (87.1% inactivation activity against TMV and 53.8% inactivation activity against CMV). C19-Diterpenoid alkaloids displayed moderate to high antiviral activity against TMV and CMV at 500 μg/mL, dosage plays an important role in antiviral activities. This paper is the first report on the evolution of aconite diterpenoid alkaloids for antiviral activity against CMV.

Ailanthus altissima

Virus-Cell Fusion Inhibitory Compounds from Ailanthus altissima Swingle

In order to search for the anti-HIV agents from natural products, eighty MeOH extracts of medicinal plants were applied to a syncytia formation inhibition assay which is based on the interaction between the HIV-1 envelope glycoprotein gp120/gp41 and the cellular membrane protein CD4 of T lymphocytes. Among them, Ailanthus altissima showed a potent virus-cell fusion inhibitory activity.

allantoin (Glyoxylic acid)

Alphitonia philippinensis

Flavonol glycosides derived from the stems of Alphitonia philippinensis have been reported to inhibit the replication of HSV-1.

Three new flavonol glycosides, namely, isorhamnetin 3-O-(6″-O-(Z)-p-coumaroyl)-β-d-glucopyranoside, quercetin 3-O-α-l-rhamnopyranosyl(1-2)-α-l-arabinopyranosyl(1-2)-α-l-rhamnopyranoside, and quercetin 3-O-α-l-arabinopyranosyl(1-2)-α-l-rhamnopyranoside, were isolated from the stems of Alphitonia philippinensis collected from Hainan Island, China. Some of the isolated triterpenoids and flavonoid glycosides showed cytotoxicity against human PC-3 cells and hepatoma HA22T cells, and the inhibition of replication on HSV-1 (131). Viral diseases, especially of skin, can be treated with a virucide encapsulated in multilamellar phospholipid liposomes. Rosmarinic acid (70), incorporated in phospholipid mixture demonstrated effectiveness in humans afflicted with HSV (132). Flavonol glycosides (from quercetin and isorhamnetin) derived from the stems of Alphitonia philippinensis have been reported to inhibit the replication of HSV-1.

Amygdalin (Semen Armeniacae Amarum)

Amygdalin could Inhibit IFN-γ, NF-κB and NLRP3 signaling pathways so as to reduce the inflammatory response (Paoletti et al., 2013; Zhang et al., 2017). These reports provided the scientific ground of integrating TCM therapy from the aspects of their compositions’ potential targeting proteins and signaling pathways in the treatment of COVID-19.

Anemarrhena asphodeloides

Anti-respiratory syncytial virus (RSV) activity of timosaponin A-III from the rhizomes of Anemarrhena asphodeloides

Two known steroidal saponins, timosaponin A-III (1) and anemarsaponin B (2) were isolated from the BuOH fraction of the rhizomes of Anemarrhena asphodeloides Bunge (Liliaceae) together with the xanthone derivatives, mangiferin (3) and neomangiferin (4). Structures of the isolates were identified using 1D and 2D NMR techniques and by comparison with the published values. Timosaponin A-III (1) exhibited potent inhibitory effects on the respiratory syncytial virus (RSV), with an IC₅₀ value of 1.00 µM.

Angelica sinensis

Angelica sinensis may provide protection against human immunodeficiency virus infection

Increased oxidative stress and disturbed glutathione redox system play an important role in the pathogenesis of human immunodeficiency virus (HIV) infection. Depletion in intracellular levels of reduced glutathione (GSH) contributes to an increment in tumor necrosis factor α (TNF-α)-stimulated-HIV-1-transcription, activation of HIV-1-replication, sensitivity to TNF-α-induced cell death, and impairment of CD4+ cell function and survival. Therefore, several studies have investigated the effect of GSH-enhancer agents such as N-acetyl cystein in the treatment of patients with HIV infection. With regard to the beneficial effects of Angelica sinensis, a Chinese medicinal herb, on GSH redox system and the pathogenic role of GSH depletion in HIV infection and the immunomodulator effects of active ingredients of this herb, we postulated that Angelica sinensis may be of value in the treatment of HIV-infected patients.

Apigenin (celery extract)

Targeting SARS-CoV-2 Spike Protein of COVID-19 with Naturally Occurring Phytochemicals

Apigenin has shown potent antiviral activity against hepatitis B virus, adenoviruses, african swine fever virus and some RNA viruses in vitro.

arctigeNin, arctin (Arctium Lappa)

Therapeutic effect of arctiin and arctigenin in immunocompetent and immunocompromised mice infected with influenza A virus

Arctiin and its aglucone, arctigenin from the fruits of Arctium lappa L. showed potent in vitro antiviral activities against influenza A virus (A/NWS/33, H1N1) (IFV). Based on the data from time-of-addition experiments and on release tests of progeny viruses, arctigenin was assumed to interfere with early event(s) of viral replication after viral penetration into cells, and to suppress the release of progeny viruses from the host cells. Arctiin was orally effective against either IFV-inoculated normal or 5-fluorouracil (5-FU)-treated mice, being less effective as compared with oseltamivir.

Noticeably, arctiin produced a larger amount of virus-specific antibody than those of control and oseltamivir in sera collected from 5-FU-treated mice. Furthermore, oral treatment of 5-FU-treated mice with arctiin did not induce any resistant viruses, although the same treatment with oseltamivir induced resistant viruses at a 50% frequency. When the combination of arctiin and oseltamivir was administered to normal mice infected with IFV, the virus yields in both bronchoalveolar lavage fluids and lungs were significantly reduced relative to those in the mice treated with arctiin or oseltamivir alone. Thus, monotherapy of arctiin or combined therapy of arctiin with oseltamivir would be another treatment option for influenza.

artemisinin (Artemisia annua)

Discuss about the application of Artemisia annua prescriptions in the treatment of COVID-19

The applications of traditional Chinese medicine (TCM) have been playing an important role in treating the epidemics of Coronavirus Disease 2019 (COVID-19), which is now prevalent all over the world. Exploring the mechanisms of TCM compound prescriptions might be difficult though, pharmacological studies on elucidating the effective components of TCM could serve as the experimental basis in the application of TCM compound prescription in treating COVID-19. As the critical active ingredients of Qinghao (Artemisia annua), artemisinin was initially used as antimalaria drug.

Artemisia annua prescriptions take significant effect against pneumonia. Sharing similarities in pharmacology with artemisinin, chloroquine has been confirmed effective in inhibiting Severe Acute Respiratory Syndrome coronavirus 2 (SARS-Cov-2) both in vitro and practically. In this context, we discussed the application of Artemisia annua prescriptions against COVID-19 along with the antiviral effect of chloroquine.

Conclusion

With similar pharmacological effects between chloroquine and artemisinin in treating infectious diseases, this paper discusses the modern scientific basis for the application of Artemisia annua prescriptions in COVID-19. Except for antimalarial, most of the other pharmacological studies on artemisinin and its derivatives are still on the bench or at animal level, with only a few in clinical trials. Artemisinin treatment on COVID-19 has not been reported yet. As a treasure of TCM, compound prescription has played an important role in plagues in history. The main cause of COVID-19 in Wuhan is damp-heat according to TCM theory. The prescription for clearing heat and eliminating dampness based on Artemisia annua is widely used in this epidemic. Based on the antiviral and anti-inflammatory effects of artemisinin and its derivatives, Artemisia annua prescriptions have great value to dig into and are promising to be used in more infectious diseases. But more in vitro experiments need to be carried out to provide more evidence, such as the influence of Artemisia or Artemisia annua prescriptions on inflammatory factors express

aspalathin

Aspalathus Linearis (Burm.f.) R. Dahlrgen (Rooibos)

Aspalathin and nothofagin extracted from Rooibos have been shown to effectively inhibit LPS-induced release of HMGB1, and suppressed HMGB1-mediated septic responses, such as hyperpermeability, adhesion and migration of leukocytes, and expression of cell adhesion molecules [124]. These molecules, as part of ethanol and alkaline extracts of the Rooibos plant, have also been shown to reduce Influenza A viral load at a late stage of the infection in vitro [125].

atractylodin (Areactylodis Lanceae)

Antiviral activities of atractylon from Atractylodis Rhizoma

Atractylodis Rhizoma is a traditional medicinal herb, which has antibacterial, antiviral, anti-inflammatory and anti-allergic, anticancer, gastroprotective and neuroprotective activities. It is widely used for treating fever, cold, phlegm, edema and arthralgia syndrome in South-East Asian nations. In this study, 6 chemical compositions of Atractylodis Rhizoma were characterized by spectral analysis and their antiviral activities were evaluated in vitro and in vivo. Among them, atractylon showed most significant antiviral activities. Atractylon treatment at doses of 10–40 mg/kg for 5 days attenuated influenza A virus (IAV)-induced pulmonary injury and decreased the serum levels of interleukin (IL)-6, tumor necrosis factor-α and IL-1β, but increased interferon-β (IFN-β) levels.

Atractylon treatment upregulated the expression of Toll-like receptor 7 (TLR7), MyD88, tumor necrosis factor receptor-associated factor 6 and IFN-β mRNA but downregulated nuclear factor-κB p65 protein expression in the lung tissues of IAV-infected mice. These results demonstrated that atractylon significantly alleviated IAV-induced lung injury via regulating the TLR7 signaling pathway, and may warrant further evaluation as a possible agent for IAV treatment.

Baicalein (Scutellaria baicalensis)

benzaldehyde (Laurus nobilis)

Berberine (Coptis chinensis)

Beta-sitosterol

BS has been shown to act as a powerful immune modulator [134]. BS exhibits immune-modulating activities in HIV-infected patients [135]. It has also been reported that BS targets specific T-helper (Th) lymphocytes, increasing Th1 activity and improving T-lymphocyte and natural killer (NK) cell activity [135,136]. In another study it was observed that BS maintains stable CD 4 cell counts in AIDS, declines apoptosis of CD 4 lymphocytes slightly, thereby slowing HIV. A significant decrease in IL-6 levels in the same study leads to a further claim that there is slowing down of viral replication rates in infected cells thereby decreasing viral load [137]. Neurath et al. (2005) proposes BS as an envelope virus neutralizing compound (EVNC) and thus acting as an HIV-1 entry inhibitor [138].

This claim has been substantiated by the fact that the EVNCs in the body fluid neutralize viruses in the blood stream and elicit an immune response to the neutralized authentically folded virus particle [139,140]. Even though the effect of BS on entry and exit out of the cell is not available, it is evident that BS facilitates the development of a potentially protective immunity against HIV. However, further study for considering BS as potential therapeutic agent has not progressed. Therefore, extensive study is suggested.

Betulinic acid (Betula platyphylla)

Bisdemethoxycurcumin (turmeric)

Brachyamide B (Piper boehmeriaefolium)

Broussonetia papyrifera

Identification of polyphenols from Broussonetia papyrifera as SARS CoV-2 main protease inhibitors using in silico docking and molecular dynamics simulation approaches

bulbocapnine (Corydalis decumbens)

caffeic acid

Calanolide A (Calophyllum lanigerum)

Campesterol (Rapeseed oil)

Carvacrol (Oregano)

Antiviral activity of the Lippia graveolens (Mexican oregano) essential oil and its main compound carvacrol against human and animal viruses

Mexican oregano (Lippia graveolens) is a plant found in Mexico and Central America that is traditionally used as a medicinal herb. In the present study, we investigated the antiviral activity of the essential oil of Mexican oregano and its major component, carvacrol, against different human and animal viruses. The MTT test (3–4,5-dimethythiazol-2yl)-2,5-diphenyl tetrazolium bromide) was conducted to determine the selectivity index (SI) of the essential oil, which was equal to 13.1, 7.4, 10.8, 9.7, and 7.2 for acyclovir-resistant herpes simplex virus type 1 (ACVR-HHV-1), acyclovir-sensitive HHV-1, human respiratory syncytial virus (HRSV), bovine herpesvirus type 2 (BoHV-2), and bovine viral diarrhoea virus (BVDV), respectively.

The human rotavirus (RV) and BoHV-1 and 5 were not inhibited by the essential oil. Carvacrol alone exhibited high antiviral activity against RV with a SI of 33, but it was less efficient than the oil for the other viruses. Thus, Mexican oregano oil and its main component, carvacrol, are able to inhibit different human and animal viruses in vitro. Specifically, the antiviral effects of Mexican oregano oil on ACVR-HHV-1 and HRSV and of carvacrol on RV justify more detailed studies.

Chavicine (black pepper)

chelidimerine (Chelidonium majus)

chlorogenic acid

Chrysin (Pinus monticola)

Cinnamomum cassia bark

Cirsilineol (Cirsium lineare)

Cirsimaritin (Rabdosia eriocalyx)

cis-capsaicin (civamide)

colchicine (Colchicum autumnale)

Cordifolioside A (Viola verecunda)

Crategolic acid (Loquat leaf)

Curcumin (Turmeric Root)

Cycloastragenol (Astragalus membranaceus)

dehydrogingerdione (ginger extract)

Dendrobium nobile

Demethoxycurcumin

Dianthus caryophyllus

Dioscin (Dioscorea oppositae)

Douchi (Sojae Praepatum)

Egcg (green tea extract)

Emodin (Rhubarb extract)

Eriodictyol (lemon extract)

Eugenitin (clove extract)

ferruginol (PodocarpuS ferruginea)

Fisetin (Rhus succedanea)

Flavonol glucoside (Trichilia connaroides)

forskolin (Coleus Forskohlii)

Fructus Perillae

fumarophycine (Laptopyrum Reichb)

galangin (Alpinia officinarum)

gallic acid (Rheumpalmatum)

Genistein (Genista tinctoria)

Glycyrrhizic acid (licorice root)

gossypol (cotton seed)

Guineensine (Piper longum)

GYPSUM FIBROSUM extract

Hawthorn Extract

herbacetin (flaxseed)

Hesperetin (Citrus Aurantium)

hesperidin
(Pericarpium Citri Reticulatae Extract)

SARS-CoV-2 or COVID-19 is representing the major global burden that implicated more than 4.7 million infected cases and 310 thousand deaths worldwide in less than 6 months. The prevalence of this pandemic disease is expected to rise every day. The challenge is to control its rapid spread meanwhile looking for a specific treatment to improve patient outcomes. Hesperidin is a classical herbal medicine used worldwide for a long time with an excellent safety profile. Hesperidin is a well-known herbal medication used as an antioxidant and anti-inflammatory agent. Available shreds of evidence support the promising use of hesperidin in prophylaxis and treatment of COVID 19.

Herein, we discuss the possible prophylactic and treatment mechanisms of hesperidin based on previous and recent findings. Hesperidin can block coronavirus from entering host cells through ACE2 receptors which can prevent the infection. Anti-viral activity of hesperidin might constitute a treatment option for COVID-19 through improving host cellular immunity against infection and its good anti-inflammatory activity may help in controlling cytokine storm. Hesperidin mixture with diosmin co-administrated with heparin protect against venous thromboembolism which may prevent disease progression. Based on that, hesperidin might be used as a meaningful prophylactic agent and a promising adjuvant treatment option against SARS-CoV-2 infection.

Hesperidin and SARS-CoV-2: New Light on the Healthy Functions of Citrus Fruit

Among the many approaches to COVID-19 prevention, the possible role of diet has so far been somewhat marginal. Nutrition is very rich in substances with a potential beneficial effect on health and some of these could have an antiviral action or in any case be important in modulating the immune system and in defending cells from the oxidative stress associated with infection. This short review draws the attention on some components of Citrus fruits and especially of the orange (Citrus sinensis), well known for its vitamin content, but less for the function of its flavonoids. Among the latter, hesperidin has recently attracted the attention of researchers, because it binds to the key proteins of the SARS-CoV-2 virus.

Several computational methods, independently applied by different researchers, showed that hesperidin has a low binding energy both with the coronavirus “spike” protein, and with the main protease that transforms the early proteins of the virus (pp1a and ppa1b) into the complex responsible for viral replication. The affinity of hesperidin for these proteins is comparable if not superior to that of common chemical antivirals. The preventive efficacy of vitamin C, at dosage attainable by diet, against viral infections is controversial, but recent reviews suggest that this substance may be useful in case of increased stress on the immune system. Finally, the reasons that suggest undertaking appropriate research on the Citrus fruits addition in the diet, as a complementary prevention and treatment of COVID-19, are discussed.

himachalol (Cupressus funebris)

honokiol (Magnolia officinalis)

houttuynia cordata

Hypericin (Forsythia suspensa)

isoliquiritigenin (glycyrrhiza uralensisfisch)

Isopiperine (pepper extract)

Isothymonin (Kaempferia galanga)

Jatrorrhizine (Phellodendron amurense)

Jujuboside A+B (Jujube extract)

Kaempferol (kaempferol galanga)

Kaempferol 3-O-robinobiosid

leachianone (Morus alba)

Lepidium meyenii (maca extract)

Lily Extract (Lilium auratum)

luteoforol (a flavan-4-ol

Luteolin

LUTeolin specifically binds to the surface spike protein of SARS‐Cov‐2 and inhibits entry of the virus into host cells.

The new coronavirus (severe acute pulmonary syndrome [SARS]‐CoV‐2) originated in China, where it spread rapidly,1 and has reached pandemic proportions because of its high rate of infectivity as well as high morbidity and mortality, associated with COVID‐19.2 This coronavirus infects by first binding to the ectoenzyme angiotensin‐converting enzyme 2 (ACE₂),3, 4 a serine protease acting as the receptor, while another serine protease is necessary for priming the viral “S” protein required for entering the cells.5 Defense against the virus apparently does not involve inflammatory cytokines,6 but pulmonary infection and its serious sequelae result from the release of multiple chemokines and cytokines that damage the lungs.

A recent report correlated coronaviruses infection with activation of mast cells and subsequent cytokine storms in the lungs.7Mast cells are known to be triggered by viruses.8 Mast cells are unique immune cells that are ubiquitous in the body, especially the lungs,9 and are critical for allergic and pulmonary diseases,10 including mastocytosis11 by secreting histamine, leukotrienes, and proteases. Mast cells are also involved in the development of inflammation12 via release of multiple pro‐inflammatory cytokines and chemokines.13, 14

Mast cells contain the serine protease ACE₂, which can convert angiotensin I into angiotensin II.15 In addition to the bronchoconstrictive action of mast cell‐derived leukotrienes, mast cells cause further bronchoconstriction via an active renin‐angiotensin generating system in the lungs.16Moreover, mast cells express a number of serine proteases,17 especially the mast cell‐serine protease tryptase,18 which are necessary for infection by SARS‐CoV‐2. A serine protease inhibitor, camostat mesylate, was recently shown to prevent entry of the virus into the lung cells of SARS‐CoV‐2‐infected patients.19 It would be important to not only inhibit entry of SARS‐CoV‐2 but also prevent SARS associated with COVID‐19.

The possible use of nonsteroidal anti‐inflammatory agents has come into question for possibly aggravating pulmonary symptoms,20 while broad‐spectrum immune suppressors, such as corticosteroids,21 would not be advisable given that an intact immune system is necessary to fight the infection and it may even lead to increased plasma viral load.22

Inhibition of mast cell‐associated inflammation could be accomplished with natural molecules, especially the polyphenolic flavonoids.23 The flavone luteolin (not lutein, which is a carotenoid) has been shown to have broad antiviral properties.24–26 Luteolin specifically binds to the surface spike protein of SARS‐Cov‐2 and inhibits entry of the virus into host cells.27 Furthermore, luteolin inhibits serine proteases,28 including the SARS‐CoV 3CL protease29 required for viral infectivity.

Moreover, luteolin inhibits mast cells30, 31and has anti‐inflammatory properties.32 A novel luteolin analogue, tetramethoxyluteolin, is even more potent32 and can also inhibit secretion of the pro‐inflammatory cytokines TNF and IL‐1β,33, 34 as well as the chemokines CCL2 and CCL535 from human mast cells.