Studies find that Palo Azul’s can treat cavities, bad breath and E. coli!
The health benefits of this magical tea don’t seem to ever run out do they?
…Apparently not! A study tested 47 different plants for the treatment of dental diseases such as toothache, dental caries, periodontal disease and gingivitis.
As it turns out, Palo Azul was among the plants that showed the highest inhibitory effect against certain bacterial diseases! For this reason, it was among the plants most frequently used for treating tooth pain, gum diseases, cavities, and bad breath!
Heck, another study even found that it “showed good antimicrobial effects in E. coli!”
How can palo azul protect against viruses and bacteria?
The answer is simple: Flavonoids.
In case you’ve never heard of flavonoids before, they’re natural products commonly found in vegetables, fruits, plants, bark, flowers, wine and tea such as Palo Azul.
There’s a ton of studies that have found numerous health benefits in flavonoids and these are are attributed to their anti-oxidative, anti-inflammatory, anti-diabetic, anti-aging, anti-hypertensive, anti-bacterial, anti-mutagenic, anti-viral and anti-carcinogenic properties.
In fact, a medical review that analyzed the results of 161 studies mentioned that flavonoids proved to be potent antimicrobial and viral inhibitors.
Therefore, they are found to be effective against many infectious diseases (bacterial and viral) such as E. coli.
* Here is an interesting finding!
“Flavonoids are known to be synthesized by plants in response to microbial infection; thus it should not be surprising that they have been found in vitro to be effective antimicrobial substances against a wide array of microorganisms.”
Another medical review which reviewed 166 studies mentions the following about flavonoids:
“It is due to their potent antibacterial, antimicrobial and antiviral activity that flavonoids “show inhibitory activity against E. coli.”
This same medical review also found that “many flavonoids show activity against several types of virus including HSV, respiratory syncytial virus, polio virus and Sindbis virus [135].”
* Here is another interesting finding!
One study mentioned that flavonoids “are an important source for the discovery and the development of novel antiviral drugs.”
One study concluded the following:
“Flavonoids have also been recognised for their antimicrobial activity and many researchers have isolated and identified the structures of flavonoids having properties of antifungal, antiviral and antibacterial activity.”
Due to this property, “many flavonoids are now being used extensively in the fields of nutrition, food safety and health.”
What types of viruses can flavonoids block?
Recently, we found a study published in 2020 which found that “flavonoids block attachment and entry of viruses into cells, interfere with various stages of viral replication processes or translation and polyprotein processing to prevent the release of the viruses to infect other cells.”
The researchers mention that “flavonoids are natural biomolecules that are known to be effective antivirals” and that “these biomolecules can act at different stages of viral infection, particularly at the molecular level to inhibit viral growth.”
* What's really interesting though, is that they found that flavovonoids' inhibitory effects were found to block the entry of Ebola, herpes, HIV, Influenza and coronaviruses!
Coronavirus
The researchers found that "a flavonoid derivative, luteolin, was found to interfere with the entry of influenza A virus and severe acute respiratory syndrome coronavirus (SARS-CoV) by interacting with the hemagglutinins of influenza A virus and the S2 protein of SARS-CoV viruses."
In addition, the scientists reported "that another flavonoid derivative, kaempferol, also inhibited coronavirus channel 3a and blocked the release of the virus' progeny."
The way that Coronaviruses attack our bodies is that they use the DNA in our cells to send out RNA signals that replicate the virus.
* This is why the next finding is very important!
"Plant flavonoids serve as a vast reservoir of therapeutically active compounds that have been explored as potential antiviral candidates against RNA and DNA viruses. RNA and DNA viruses (such as COVID-19) attach to our own cells and send RNA signals across our cell membranes to replicate.
In other words, RNA and DNA viruses use our own cells to multiply and attack our bodies.
Read our full article here: Palo Azul & Flavonoids vs Coronavirus
Moreover, we read a FOX news article which stated that “quercetin (flavonoid) is presently being studied in China as a drug treatment for COVID-19, based on research initiated at McGill University.”
Lastly, a study published recently on April 9, 2020 concluded the following:
“Our findings suggest that all of these compounds (flavonoids) have the potential to inhibit SARS- CoV-2 and should be explored further as preventive therapeutics for COVID-19.”
HIV
“In a similar manner, sulfated rutin (flavonoid derivative) was shown to block the entry of human immunodeficiency virus (HIV)-1.” In fact, the researchers mentioned revealed that “sulfated rutin could drastically inhibit HIV-1 infection.”
Moreover, they found that “flavonoids were reported to inhibit assembly and release of HIV and influenza A virus, respectively.”
Influenza
The researchers from this study found that “tea catechins (flavonoids) were also reported to inhibit the influenza A virus by binding to the hemagglutinins and restricted virus adsorption, preventing the penetration of the virus into the cells.”
Moreover, another flavonoid derivitave, quercetins, were “found to inhibit the initial stage of viral replication of the influenza A virus, evident by a decrease in mRNA synthesis of the virus.”
Another group of flavonoids, viz. methoxyflavone, isoscutellarein, and 8-methoxy-isoscutellarein, were reported to inhibit early replication of influenza A virus by reduction of sialidase activity, inhibition of lysosomal fusion and RNA polymerase activity."
Herpes and Ebola
Quercetin, a flavonoid derivative, “also blocked viral binding and entry of herpes simplex virus (HSV)-1.”
“Another flavonoid derivative, 3-β-O-d-glucoside, was able to protect mice from Ebola virus infection when given prior to virus challenge.”
Lastly, the researchers mention that due to flavonoids’ ability to target various stages of viral infection, they are “becoming a more focused topic to explore their potential as antivirals in the current era.”
Below, we’ve shared all the key points we found from medical studies on the anti-bacterial and anti-viral effects of Palo Azul and flavonoids.
Key findings from medical studies
• One study tested 47 plants and concluded the following: “Our study demonstrated that most of the medicinal plants showed an antibacterial effect in vitro, and justified at least in part their use in traditional medicine.” The same study mentioned that “the most frequent uses were to treat tooth pain, gum diseases, bad breath and cavities.”
• “Naturally occurring flavonoids with antiviral activity have been recognized since the 1940s and many reports on the antiviral activity of various flavonoids are available.”
• “The antiviral effect of flavonoids has been shown by Wang et al.(,142), particularly in therapy for viral infection.”
• “Inhibition of viral polymerase and binding of viral nucleic acid or viral capsid proteins have been proposed as antiviral mechanisms of action [139].”
• “Flavonoids have also been recognised for their antimicrobial activity and many researchers have isolated and identified the structures of flavonoids having properties of antifungal, antiviral and antibacterial activity.”
• “These compounds (flavonoids) are reported for their in vitro antibacterial activity against Vibrio cholerae, Streptococcus mutans, Shigella, and other bacteria.”
• A study found that Palo Azul “showed good antimicrobial effects in E. coli” and concluded the following: “The results here presented corroborate the folk medicinal use of Eysenhardtia polystachya (Palo Azul) in the treatment of infections, diarrhea, inflammation, and pain.”
• Many studies have suggested “protective effects of flavonoids against many infectious (bacterial and viral diseases) and degenerative diseases such as cardiovascular diseases, cancers, and other age-related diseases.”
Medical Studies
* Palo Azul is commonly referred to by its scientific name: Eysenhardtia polystachya / E. polystachya / E.P - Cyclolepis genistoides / C. genistoides - kidney wood - palo dulce
Eysenhardtia polystachya is used for the empirical treatment of cancer, infections, diarrhea, inflammation, and pain. This study identified, using GC-MS, the main chemical components in an ethanol extract of E. polystachya branches and leaves (EPE) and tested its cytotoxic, antimicrobial, anti-diarrheal, anti-inflammatory, and antinociceptive effects.
Conclusion: EPE exerted in vitro anti-inflammatory effects, mainly, by the decrease in the production of H2O2 (IC50 = 43.9 ± 3.8 µg/ml), and IL-6 (73.3 ± 6.9 µg/ml). EPE (ED50 =7.5 ± 0.9 mg/kg) and D-pinitol (ED50 = 0.1 ± 0.03 mg/kg) showed antidiarrheal activity, and antinociceptive effects in the acetic acid test with ED50 = 117 ± 14.5 mg/kg for EPE and 33 ± 3.2 mg/kg for D-pinitol. EPE showed also antinociceptive activity in the phase 2 of the formalin test (ED50 = 48.9 ± 3.9 mg/kg), without inducing hypnotic effects or altering the locomotor activity in mice. Furthermore, EPE lacked cytotoxic activity (IC50 > 300 µg/ml) on human cancer cells, but showed good antimicrobial effects in E. coli (MIC=1.56 µg/ml) and S. aureus (MIC = 0.78 µg/ml). The results here presented corroborate the folk medicinal use of Eysenhardtia polystachya in the treatment of infections, diarrhea, inflammation, and pain. D-pinitol, the main metabolite of EPE, showed antinociceptive and antidiarrheal effects with similar potency compared to standard drugs.
The ethnobotanical survey conducted in this study showed 47 plant species used in the Altiplane region of Mexico for the treatment of dental diseases such as toothache, dental caries, periodontal disease and gingivitis. The most frequent uses were to treat tooth pain, gum diseases, bad breath and cavities. Infusions were the most frequently prepared formulation.
The ethanolic extracts of Bursera simaruba, Cedrela odorata and Rhus standleyi (12.5–65.0 μg/mL) as well as water extracts of Haematoxylon brasiletto, Punica granatum, Iostephane heterophyla, Amphipterygium adstringens, Argemone mexicana, Eysenhardtia polystachya (Palo Azul), Persea americana, Syzygium aromaticum, Cinnamomun zeylanicum, Cnidoscolus multilobus and Rhus standleyi (10.5–78.0 μg/mL) showed the highest inhibitory effect against Streptococcus mutans and Porphyromonas gingivalis.
Conclusion: Many plants are used in the Mexican traditional medicine to treat oral bacterial diseases by the healers or patients. Our study demonstrated that most of the medicinal plants showed an antibacterial effect in vitro, and justified at least in part their use in traditional medicine. These results encourage further investigations to extract and identify the active chemical compounds responsible for the antibacterial effect observed.
(2009) Chapter 18 - Flavonoids and Cardiovascular Health
More than 8000 compounds with flavonoids structure have been identified, many of which are responsible for the attractive colors of flowers, fruits and leaves. In plants, these compounds afford protection against ultraviolet radiation, pathogens, and herbivores [1, 2].
Studies have indicated the protective effects of flavonoids in cardiovascular diseases and these chemicals possess the bioactivity to positively affect against cardiovascular risk factors such as lipoprotein oxidation, dyslipidemia and endothelial dysfunction. Flavonoids have strong antioxidant properties and so can reduce oxidative stress related to cardiovascular disease. The cardioprotective role of tea is reported to be due to antioxidant effect of the flavonoids, which act as scavengers for free radicals.
Epidemiological, clinical and animal studies reveal that flavonoids may exert protective effects against various disease conditions including cardiovascular disease and cancer. Flavonoids also possess antibacterial, antiviral, and anti-inflammatory effects. Population studies have shown that flavonoid intake is inversely correlated with mortality from cardiovascular disease [3–6]. Flavonoids have been reported to beneficially impact parameters associated with atherosclerosis, including lipoprotein oxidation, blood platelet aggregation, and vascular reactivity. Antioxidant, antithrombotic, anti-inflammatory, and hypolipidemic properties are illustrated to play a significant role in the lower cardiovascular mortality observed with higher flavonoid intake [4, 5, 7]. Continued studies of the mechanisms underlying the biological effects of plant flavonoids may provide new strategies for the prevention and treatment of cardiovascular disease.
ACTIVIDAD ANTIMICROBIANA DE LOS EXTRACTOS DE Eysenhardtia polystachya texana
Objective: to evaluate the antimicrobial activity of extracts of Eysenhardtia polystachya and E. texana, against microorganisms of medical importance.
Conclusions: the extract of E. polystachya presented activity against E. aerogenes, P. vulgaris, S. aureus and S. epidermidis, presents flavonoids, sesquiterpenlactones, unsaturations, phenolic oxhydrils
(2016, Dec 29) (Medical Review: 161 studies) Flavonoids: an overview
Flavonoids, a group of natural substances with variable phenolic structures, are found in fruits, vegetables, grains, bark, roots, stems, flowers, tea and wine. These natural products are well known for their beneficial effects on health and efforts are being made to isolate the ingredients so called flavonoids. Flavonoids are now considered as an indispensable component in a variety of nutraceutical, pharmaceutical, medicinal and cosmetic applications. This is attributed to their anti-oxidative, anti-inflammatory, anti-mutagenic and anti-carcinogenic properties coupled with their capacity to modulate key cellular enzyme function. Research on flavonoids received an added impulse with the discovery of the low cardiovascular mortality rate and also prevention of CHD.
The recent studies on different plant metabolites have shown that flavonoids may perform a key role in enzyme and receptor systems of the brain, exerting significant effects on the central nervous system, like prevention of the neurodegeneration associated with AD and Parkinson's disease(,15,119).
They have miscellaneous favourable biochemical and antioxidant effects associated with various diseases such as cancer, Alzheimer's disease (AD), atherosclerosis, etc. Flavonoids have several subgroups, which include chalcones, flavones, flavonols and isoflavones. These subgroups have unique major sources. For example, onions and tea are major dietary sources of flavonols and flavones. A number of flavonoids were studied to lower Alzheimer's Aβ production using molecular docking studies.
Lee et al.(,81), while working on the known flavonoid inhibitors of β-KAS III against the methicillin-resistant bacteria Staphylococcus aureus, found that flavonoids such as naringenin (5,7,4′-trihydroxyflavanone) and eriodictyol (5,7,3′,4′-tetrahydroxyflavanone) are potent antimicrobial inhibitors of Staphylococcus aureus KAS III. Ganugapati et al.(,82) worked on in silico modelling and docking studies of a superbug enzyme, namely New Delhi metallo-β-lactamase-1 (NDM-1), which is an enzyme found in Escherichia coli.
Lu & Chong(,85) carried out the computational work to predict the binding modes of flavonoid derivatives with the neuraminidase of the 2009 haemagglutinin 1 neuraminidase (H1N1) influenza virus. They employed molecular dynamics simulation techniques to optimise the 2009 H1N1 influenza neuraminidase X-ray crystal structure. All the twenty flavonoid derivatives were found to be satisfactory in binding and inhibiting the activity of the virus. These findings may help to develop a potential drug form of the flavonoid derivatives for the treatment of H1N1 influenza disease.
Kim et al.(,87) reported that a flavonoid-rich diet is associated with a reduced risk of CVD (cardiovascular disease). The study focused on individual as well as total flavonoid diet effects. Higher flavonoid intake was found to be associated with the improved CVD risk factors.
The observational studies done by Hügel et al.(,89) indicated that dietary flavonoids are associated with a decreased risk of hypertension and CVD. A diet rich in all flavonoid classes through herbs and beverages improves vascular health leading to a reduced risk of diseases. It has been observed that the consumption of them is associated with improvement in endothelial function via vascular endothelial nitric oxide synthase and protein kinase B (Akt) activation. The effect of regular quercitin intake on blood pressure in overweight and obese patients with pre-hypertension and stage I hypertension was studied in seventy patients. Ambulatory blood pressure and office blood pressure were measured. It was observed that the blood pressure level was reduced in patients with hypertension(,90).
Paris et al.(,97) worked on flavonoids which lower Alzheimer's amyloid protein (Aβ) production via a nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB)-dependent mechanism. It is well known that AD is due to the accumulation of Aβ peptides and the presence of neurofibrillary tangles in the brain(,98,99). Aβ is believed to play an important role in AD and it has been shown that certain flavonoids such as genistein, quercetin, taxifolin, kaemferol, luteolin, apigenin, daidzein, aminogeneistein, and α- and β-napthofalvone can affect Aβ production. Recently, it was suggested that the Aβ-lowering properties of flavonoids are mediated by a direct inhibition of β active site cleavage enzyme-1 (BACE-1) activity, the rate-limiting enzyme responsible for the production of Aβ peptides(,97). It has been reported that a strong correlation exists between the inhibition of NF-κB activation by flavonoids and their Aβ-lowering properties, suggesting that flavonoids inhibit Aβ production in whole cells via NF-κB-related mechanisms.
Flavonoids can prevent injury caused by free radicals in various ways and one way is the direct scavenging of free radicals. Flavonoids are oxidised by radicals, resulting in a more stable, less-reactive radical. In other words, flavonoids stabilise the reactive oxygen species by reacting with the reactive compound of the radical. Because of the high reactivity of the hydroxyl group of the flavonoids, radicals are made inactive, as explained in the following equation as given by Korkina & Afanasev(,108): They further mentioned that this action protects the LDL particles and, theoretically, flavonoids may have preventive action against atherosclerosis.
Antioxidants are compounds that protect the cells against the oxidative effect of reactive oxygen species, and the impaired balance between these reactive oxygen species and antioxidants results in oxidative stress. The oxidative stress may lead to cellular damage which is related to various health ailments such as diabetes, cancer, CVD, neurodegenerative disorders and ageing. Oxidative stress can also damage many biological molecules and proteins and DNA molecules are significant targets of cellular injury. Antioxidants interfere with radical-producing systems and increase the function of endogenous antioxidants, protecting the cells from damage by these free radicals
Anticancer effects of flavonoids such as tangeritin, 3-hydroxyflavone, 3′,4′-dihydroxyflavone, 2′,3′-dihydroxyflavone, fisetin, apigenin, luteolin daidzein and genistein have been carried out by a number of researchers(,151–154). Ren et al.(,130) and Huang et al.(,155), while working on natural phenolic compounds and their potential use for cancer prevention, reported that various flavonoids such as tannins, stilbenes, curcuminoids, coumarins, lignans, quinones and other flavonoids have chemopreventive properties and also contribute to induce apoptosis by arresting the cell cycle, regulating carcinogen metabolism and ontogenesis expression. While explaining the possible mechanism of flavonoids in cancer prevention they further mentioned that the flavonoids have complementary and overlapping mechanisms of action including antioxidant activity and scavenging free radicals, modulation of carcinogen metabolism, regulation of gene expression on oncogenes and tumour-suppressor genes in cell proliferation and differentiation, induction of cell cycle arrest and apoptosis, modulation of enzyme activities in detoxification, oxidation and reduction, anti-inflammatory properties and action on other possible targets.
Flavonoids have also been recognised for their antimicrobial activity and many researchers have isolated and identified the structures of flavonoids having properties of antifungal, antiviral and antibacterial activity. Because of this property, many flavonoids are now being used extensively in the fields of nutrition, food safety and health. The antiviral effect of flavonoids has been shown by Wang et al.(,142), particularly in therapy for viral infection.
Flavonoids, like flavonols, are associated with lower population rates of dementia(,156). Similarly, Hwang & Yen(,157) and Jager & Saaby(,119) suggested that citrus flavanones such as hesperidin, hesperetin and naringenin could traverse the blood–brain barrier and may play an effective role in the intervention for neurodegenerative diseases. The role of flavonoids in antidiabetic activity and anti-ageing has also been reported(,158–161).
Fruits and vegetables are the main dietary sources of flavonoids for humans, along with tea and wine.
Many flavonoids are shown to have antioxidative activity, free radical scavenging capacity, coronary heart disease prevention, hepatoprotective, anti-inflammatory, and anticancer activities, while some flavonoids exhibit potential antiviral activities. In plant systems, flavonoids help in combating oxidative stress and act as growth regulators.
The number of studies has suggested protective effects of flavonoids against many infectious (bacterial and viral diseases) and degenerative diseases such as cardiovascular diseases, cancers, and other age-related diseases. Flavonoids also act as a secondary antioxidant defense system in plant tissues exposed to different abiotic and biotic stresses.
Flavonoids found in the highest amounts in the human diet include the soy isoflavones, flavonols, and the flavones.
Oxidative modification of LDL cholesterol is thought to play a key role during atherosclerosis. The isoflavan glabridin, a major polyphenolic compound found in Glycyrrhiza glabra (Fabaceae), inhibits LDL oxidation via a mechanism involving scavenging of free radicals [52]. Several epidemiological studies have suggested that drinking either green or black tea may lower blood cholesterol concentrations and blood pressure, thereby providing some protection against cardiovascular disease. Flavonoids contained in berries may have a positive effect against Parkinson's disease and may help to improve memory in elderly people. Antihypertensive effect has been observed in total flavonoid fraction of Astragalus complanatus in hypertensive rats [55]. Intake of antioxidant flavonoids has been inversely related to the risk of incidence of dementia.
Flavonoids possess many biochemical properties, but the best described property of almost every group of flavonoids is their capacity to act as antioxidants. The antioxidant activity of flavonoids depends upon the arrangement of functional groups about the nuclear structure. The configuration, substitution, and total number of hydroxyl groups substantially influence several mechanisms of antioxidant activity such as radical scavenging and metal ion chelation ability
Hepatoprotective activities were observed in flavonoids isolated from Laggera alata against carbon-tetrachloride (CCl4-) induced injury in primary cultured neonatal rat hepatocytes and in rats with hepatic damage. Several clinical investigations have shown the efficacy and safety of flavonoids in the treatment of hepatobiliary dysfunction and digestive complaints, such as sensation of fullness, loss of appetite, nausea, and abdominal pain.
Flavonoids are known to be synthesized by plants in response to microbial infection; thus it should not be surprising that they have been found in vitro to be effective antimicrobial substances against a wide array of microorganisms. Flavonoid rich plant extracts from different species have been reported to possess antibacterial activity [70, 72, 89, 90]. Several flavonoids including apigenin, galangin, flavone and flavonol glycosides, isoflavones, flavanones, and chalcones have been shown to possess potent antibacterial activity [91]. These compounds are reported for their in vitro antibacterial activity against Vibrio cholerae, Streptococcus mutans, Shigella, and other bacteria [94, 95]. Another study demonstrated inhibitory activity of quercetin, apigenin, and 3,6,7,3′,4′-pentahydroxyflavone against Escherichia coli DNA gyrase [98].
Inflammation is a normal biological process in response to tissue injury, microbial pathogen infection, and chemical irritation. Inflammation is initiated by migration of immune cells from blood vessels and release of mediators at the site of damage. This process is followed by recruitment of inflammatory cells, release of ROS, RNS, and proinflammatory cytokines to eliminate foreign pathogens, and repairing injured tissues. In general, normal inflammation is rapid and self-limiting, but aberrant resolution and prolonged inflammation cause various chronic disorders [106]. A number of flavonoids such as hesperidin, apigenin, luteolin, and quercetin are reported to possess anti-inflammatory and analgesic effects. It has been reported that flavonoids are able to inhibit expression of isoforms of inducible nitric oxide synthase, cyclooxygenase, and lipooxygenase, which are responsible for the production of a great amount of nitric oxide, prostanoids, leukotrienes, and other mediators of the inflammatory process such as cytokines, chemokines, or adhesion molecules [110]. Much of the anti-inflammatory effect of flavonoid is on the biosynthesis of protein cytokines that mediate adhesion of circulating leukocytes to sites of injury. Certain flavonoids are potent inhibitors of the production of prostaglandins, a group of powerful proinflammatory signaling molecules [111].’
Dietary factors play an important role in the prevention of cancers. Fruits and vegetables having flavonoids have been reported as cancer chemopreventive agents [72, 115]. Consumption of onions and/or apples, two major sources of the flavonol quercetin, is inversely associated with the incidence of cancer of the prostate, lung, stomach, and breast. In addition, moderate wine drinkers also seem to have a lower risk to develop cancer of the lung, endometrium, esophagus, stomach, and colon [116]. The critical relationship of fruit and vegetable intake and cancer prevention has been thoroughly documented. It has been suggested that major public health benefits could be achieved by substantially increasing consumption of these foods [117]. Flavonoids are known to inhibit production of heat shock proteins in several malignant cell lines, including breast cancer, leukemia, and colon cancer [119].
Higher consumption of phytoestrogens, including isoflavones and other flavonoids, has been shown to provide protection against prostate cancer risk [132]. It is well known that due to oxidative stress cancer initiation may take place and thus potent antioxidants show potential to combat progression of carcinogenesis. Potential of antioxidant as an anticancer agent depends on its competence as an oxygen radical inactivator and inhibitor [70, 72, 133]. Therefore diets rich in radical scavengers would diminish the cancer-promoting action of some radicals [134].
Natural compounds are an important source for the discovery and the development of novel antiviral drugs because of their availability and expected low side effects. Naturally occurring flavonoids with antiviral activity have been recognized since the 1940s and many reports on the antiviral activity of various flavonoids are available. Many flavonoids, namely, dihydroquercetin, dihydrofisetin, leucocyanidin, pelargonidin chloride, and catechin, show activity against several types of virus including HSV, respiratory syncytial virus, polio virus and Sindbis virus [135]. Inhibition of viral polymerase and binding of viral nucleic acid or viral capsid proteins have been proposed as antiviral mechanisms of action [139].
Flavonoids have long been reported as serving multiple functions in plants [140]. Various abiotic and biotic factors helps in the generation of ROS in plants leading to oxidative stress. Flavonoids have been suggested as representing a secondary antioxidant defense system in plant tissues exposed to different stresses [141].
Prevention and cure of diseases using phytochemicals especially flavonoids are well known. Fruits and vegetables are natural sources of flavonoids. Variety of flavonoids found in the nature possesses their own physical, chemical, and physiological properties. Structure function relationship of flavonoids is epitome of major biological activities. Medicinal efficacy of many flavonoids as antibacterial, hepatoprotective, anti-inflammatory, anticancer, and antiviral agents is well established. Further achievements will provide newer insights and will certainly lead to a new era of flavonoid based pharmaceutical agents for the treatment of many infectious and degenerative diseases.
The healthy properties of flavonoids may be derived from their antioxidative characteristics as free-radical neutralizers. However, some more specific functions have been reported, including their effect on cancer prevention, antiinflammatory and antiviral activities, and their positive effect on capillary fragility and vascular protection.
(2020) Flavonoids as Antiviral Agents for Enterovirus A71 (EV-A71)
Flavonoids are natural biomolecules that are known to be effective antivirals. These biomolecules can act at different stages of viral infection, particularly at the molecular level to inhibit viral growth. Pharmacological properties of flavonoids include antioxidant, anti-inflammatory, anticancer, antimicrobial and immunomodulatory functions. Due to a wide range of biological activities being exhibited by flavonoids, they have become molecules of interest for natural drug discovery research.
They can block attachment and entry of viruses into cells, interfere with various stages of viral replication processes or translation and polyprotein processing to prevent the release of the viruses to infect other cells. Different flavonoids have been found to inhibit the virus through various mechanisms. Based on antiviral mechanisms of action, flavonoids can be prophylactic inhibitors, therapeutic inhibitors or indirect inhibitors by interaction with the immune system.
Quercetin (flavonoid derivative) also blocked viral binding and entry of herpes simplex virus (HSV)-1, HSV-2, and drug-resistant HSV-1 to Madin–Darby canine kidney NBL-2 (MDCK) cells [6]. Another flavonoid derivative, 3-β-O-d-glucoside, was able to protect mice from Ebola virus infection when given prior to virus challenge.
In a similar manner, sulfated rutin (flavonoid derivative) was shown to block the entry of human immunodeficiency virus (HIV)-1 without interactions with the host cell membrane. Cell fusion and entry assays revealed that sulfated rutin could drastically inhibit HIV-1 infection when cells were treated during the early adsorption phase. The probable mechanism proposed by investigators was the inhibition of HIV glycoprotein-mediated cell-cell fusion step [11].
Flavonoids, genistein and ginkgetin, were reported to inhibit assembly and release of HIV and influenza A virus, respectively.
Flavonoids, with their ability to target various stages of viral infection, are becoming a more focused topic to explore their potential as antivirals in the current era. Apart from their classical antioxidant properties, some flavonoids have been shown to inhibit viruses at the molecular level both in vitro and in vivo.
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