Anti-inflammatory

woman with sciatic nerve pain

Studies show that Palo Azul can reduce sciatic nerve pain, arthritis and strengthen joints!

This is one of Palo Azul’s most beneficial health properties! Considering that it is responsible for improving your sciatic nerve health, reducing back pain and arthritis pain.

Results from 6 different studies concluded in their results that Palo Azul induced a significant inhibition of inflammation and/or showed anti-inflammatory activity.

Also, several studies show that methanol, ethanol, or flavonoids in Palo Azul act as anti-inflammatory agents

omega 3 antiinflammatory and flavonoids

How can anti-inflammatories help you?

Reduce sciatic nerve pain

woman healing sciatic nerve pain

One of the lesser known benefits of Palo Azul is that it can improve sciatic nerve health. The main reason for this is that sciatic nerve pain is commonly caused by an accumulation of uric acid in the blood, and Palo Azul is an active reducer of uric acid levels.

palo azul sciatic nerve

Inflammation is another common cause of sciatic nerve pain and many studies have proven Palo Azul’s powerful anti-inflammatory activity. For these 2 reasons, Palo Azul has been traditionally used to cure sciatic nerve pain for centuries!

This are some of the most antiinflammatory foods: vegetables, fruits, nuts, seeds, fatty fish, olive oil, turmuric, cocoa and teas such as palo azul

palo azul and antiinflammatory foods

Uric Acid Reducer

One study mentions that “the plant (palo azul) has been used in traditional treatments of nephrolithiasis or urolithiasis [2], lumbalgia, arthritis, rheumatism, sciatica, and as blood depurative because it eliminates uric acid, of which application the palo azul derives its diuretic and antirheumatic fame.”

Another study found that uric acid indices were significantly higher in the group of diabetic mice that did not receive the blue stick extracts compared to the control group.

This same study concluded the following:

Groups treated with 25, 50, and 100 mg/kg of the dihydrochalcone (palo azul extract) showed a significantly decreased (p < 0.05) uric acid.”


Ant-iinflammatory

Results from 6 different studies concluded in their results that Palo Azul induced a significant inhibition of inflammation and/or showed anti-inflammatory activity.

Moreover, several studies show that “methanol, ethanol, or flavonoids in Palo Azul act as anti-inflammatory agents.”

One medical study concluded the following: The inhibition (of inflammation) leads to a reduction in pain behavior and inflammation following chronic constriction injury (CCI) of the sciatic nerve.

palo azul strengthen joints

Another medical article mentions that “any cause of irritation or inflammation of the sciatic nerve can produce the symptoms of sciatica.”

Hundreds of studies have shown that Palo Azul and its flavonoids are powerful anti-inflammatories and because of this property, their ability to calm joint pain has been demonstrated.

Flavonoids

But that's not all!...In addition to the palo azul's ability to inhibit inflammation and reduce uric acid levels, it also contains some of the healthiest compounds in the world!

palo azul flavonoids

You can learn all about Flavonoids here, but for now just know that there are hundreds of studies that have shown that they have anti-inflammatory, anti-oxidant, anti-aging properties, etc.

In fact, one study found that flavonoids (found in vegetables, fruits and teas like palo azul) “have the most potential of dietary components for promotion of bone health beyond calcium and vitamin D.”

This finding is supported by population studies which have shown “flavonoid consumption to have a stronger association with bone than general fruit and vegetable consumption.”

These are the MOST flavonoid-rich foods: apples, pears, onions, strawberries, blueberries, celery, peppers, and teas such as palo azul

applepearsonionsstrawberries and blueberriescelerypalo azul tea

Reduce back pain and arthritis

woman with back pain

Several studies have found that flavonoids and the anti-inflammatory capacities of palo azul are effective for treating arthritis and pain management.

One study which found that “the ethanol extract of Palo Azul and its flavonoids-rich fractions “inhibited secondary inflammatory reactions in arthritic rats” also concluded that “many plant constituents, including flavonoids, have proven effective against arthritis.”

Another study mentions that many plant constituents, including flavonoids, have proven effective against arthritis by reducing cartilage degradation, diminishing leukocyte infiltration in the synovial space, decreasing serum cytokine levels, and other mechanisms (9).”

Lastly, a study concluded the following:

“Our findings support the use of Eysenhardtia polystachya bark for the treatment of rheumatoid arthritis and pain management.”


Reduce joint pain

woman with arthritis

A common cause of joint pain is due to inflammation, and as we’ve discovered...many studies have shown palo azul’s powerful anti-inflammatory activity.

On top of this, one study found that flavonoids (found in vegetables, fruits and teas like palo azul) “have the most potential of dietary components for promotion of bone health beyond calcium and vitamin D.”

This finding is supported by population studies whichecent have shown “flavonoid consumption to have a stronger association with bone than general fruit and vegetable consumption.”

palo azul strengthens joint health

This is precisely why palo azul has been used effectively for treating ailments such as arthritis, rheumatism, lumbago, gout and sciatica.

Below, we have summarized the key points of ALL the medical studies we have analyzed and also cited all the scientific literature.

Enjoy! :)

...And don't forget to help your friends and family by sharing MagickTea Palo Azul with them!

book with palo azul benefits and studies

Key findings (Sciatica)

• “Medications used in the treatment of sciatica include pain relievers, muscle relaxants, anti-inflammatories, and antidepressants.”

• “Groups treated with 25, 50, and 100 mg/kg of the dihydrochalcone (palo azul extract) showed a significantly decreased (p < 0.05) uric acid.”

    Key findings (Arthritis)

    • One study found that “the ethanol extract of Palo Azul and its flavonoids-rich fractions “inhibited secondary inflammatory reactions in arthritic rats” and that “many plant constituents, including flavonoids, have proven effective against arthritis.”

    • “PAM (Palo Azul) possesses significantly dose-related antiarthritic activity in M. tuberculosis-induced adjuvant arthritis test in rat, which is considered close to simulating human rheumatoid arthritis.”

    • “Our findings support the use of Eysenhardtia polystachya bark for the treatment of rheumatoid arthritis and pain management.”



      Key points (Joints)

      • “Recent epidemiological studies show flavonoid consumption to have a stronger association with bone than general fruit and vegetable consumption.”

      • Flavonoids “have been reported to enhance bone formation and to inhibit bone resorption through their action on cell signaling pathways that influence osteoblast and osteoclast differentiation.”


      This is why you should be eating vegetables, fruits and drinking Palo Azul every day!
      Now do you see why we call it MagickTea?
      Try Palo Azul and you'll feel its radiant taste and all its magical benefits!


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      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

      (Winter 2018) The Ethanolic Extract of Eysenhardtia polystachya (Ort.) Sarg. Bark and Its Fractions Delay the Progression of Rheumatoid Arthritis and Show Antinociceptive Activity in Murine Models

      Eysenhardtia polystachya is widely used in folk medicine as an anti-rheumatic and analgesic agent, but no systematic study of its effects on several markers associated with rheumatoid arthritis and its ethnomedical use as analgesic agent has been performed. We evaluated the anti-arthritic and antinociceptive properties of an ethanolic extract of E. polystachya (EE) bark and its rich-flavonoids fractions in murine models. Many plant constituents, including flavonoids, have proven effective against arthritis by reducing cartilage degradation, diminishing leukocyte infiltration in the synovial space, decreasing serum cytokine levels, and other mechanisms (9). Phytochemical studies indicate that E. polystachya contains polyphenols, and previous chemical examination of this species led to the isolation and structural elucidation of several flavonoids (11, 12). The methanol-water extract showed antidiabetic and anti-hyperlipidemic activities, an ability to reduce the formation of advanced glycation end products, and an antioxidant capacity in-vitro (12).


      Conclusion: EE and its rich-flavonoids fractions inhibited secondary inflammatory reactions, diminished the specific histopathological alterations in the joint capsule and reduced the serum concentrations of the pro-inflammatory cytokines IL-6, TNF-α, and GM-CSF in arthritic rats. EE also reduced the number of writhes produced by acetic acid and increased the response time on the hot plate for mice. Our findings support the use of Eysenhardtia polystachya bark for the treatment of rheumatoid arthritis and pain management.

      In conclusion, the ethanolic extract of Eysenhardtia polystachya bark and its rich-flavonoids fractions inhibited secondary inflammatory reactions in arthritic rats and delayed histopathological alterations of joint capsules. Eysenhardtia polystachya also decreased the serum levels of pro-inflammatory cytokines IL-6, TNF-α, and GM-CSF and showed antinociceptive activity at the peripheral and central levels, which suggests that this plant has an effect on the cellular immune response. These findings support the use of Eysenhardtia polystachya in Mexican folk medicine for treating rheumatoid arthritis and pain management.


      (2013, Dec 29) (Medical review: 166 studies) Chemistry and Biological Activities of Flavonoids: An Overview

      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.



      (2010) Transgenic inhibition of glial NF-kappa B reduces pain behavior and inflammation after peripheral nerve injury

      We utilized a transgenic mouse model (GFAP-IκBα-dn) where the classical NF-κB pathway is inactivated by overexpression of a dominant negative (dn) form of the inhibitor of kappa B (IκBα) in glial fibrillary acidic protein (GFAP)-expressing cells, which include astrocytes, Schwann cells, and satellite cells of the dorsal root ganglion (DRG) and sought to determine whether glial NF-κB inhibition leads to a reduction in pain behavior and inflammation following chronic constriction injury (CCI) of the sciatic nerve.

      We can therefore conclude that transgenic inhibition of NF-κB in GFAP-expressing glial cells attenuated pain and inflammation after peripheral nerve injury. These findings suggest that targeting the inflammatory response in Schwann cells and satellite cells may be important in treating neuropathic pain.


      (2019) Sciatica Nerve Pain

      While sciatica is most commonly a result of a lumbar disc herniation directly pressing on the nerve, any cause of irritation or inflammation of the sciatic nerve can produce the symptoms of sciatica. This irritation of nerves as a result of an abnormal intervertebral disc is referred to as radiculopathy.

      Medications used in the treatment of sciatica include pain relievers, muscle relaxants, anti-inflammatories, and antidepressants.


      The duration of sciatica is critically dependent on its cause. A herniated disc, back sprain, shingles, and degenerative lumbar spine can all cause temporary forms of sciatica, lasting from days to weeks. Each can also cause chronic sciatica. Sometimes degeneration of the lumbar spine and discs can cause chronic sciatica that persists unless a surgical intervention is performed.


      Keys to the management of acute sciatica include relief of pain and relaxing associated muscle spasms. Home remedies include heat and cold pack topical administration, over-the-counter pain medications such as acetaminophen (Tylenol), non-steroidal anti-inflammatory drugs like naproxen (Aleve), ibuprofen (Advil, Motrin), and aspirin, and physical therapy that incorporates gradual exercises and stretching. Exercises and stretching can sometimes best be guided by physical therapists.



      (2008) Development of a capillary electrophoresis method for the characterization of “palo azul” (Eysenhardtia polystachya)

      The plant has been used in traditional treatments of nephrolithiasis or urolithiasis [2], lumbalgia, arthritis, rheumatism, sciatica, and as blood depurative because it eliminates uric acid, of which application the palo azul derives its diuretic and antirheumatic fame. For inges- tion purposes, the wood chips are brought to boil in water to produce a golden-colored liquor having a light blue fluorescence, from which the sick can take two or three cups a day [3].

      Among the E. polystachya components, there can be found polyphenol compounds, tannins, or flavonoid compounds [5, 6], which are a variable and complex mix- ture of bitter, astringent chemicals, although in general these are esters from one kind of sugar having a variable number of phenol acids [7].

      (May 25, 2011) Anti-inflammatory properties from isolated compounds of Cyclolepis genistoides

      Phytochemical studies of the aqueous extract of C. genistoides showed the presence of saponins, flavonoids, tannins, and anthraquinones. Instead, oleanolic acid (1) and the sesquiterpene lactone deacylcynaropicrin (2), which have been previously reported in this plant (De Heluani et. al., 1997), were isolated from the ethyl acetate extract. Compound 1 exhibited significant activity at 1, 3, 5, and 7 h, while compound 2 showed significant inhibition at 3 and 5 h.


      Conclusions: From the results obtained in this work, we can conclude that the intraperitoneal administration of both isolated compounds from C. genistoides showed a significant inhibition of the carrageenan-induced inflammation at doses of 75 and 100 mg/kg, while the dose of 40 mg/kg did not produce a significant anti-inflammatory effect. Considering that compounds 1 and 2 were isolated from aerial parts of C. genistoides, these results give support to the use of this plant as an anti-inflammatory in traditional medicine.

      (Feb 29, 2015) Evolution of anti-inflammatory activity of the bark of Eysenhardtia polystachia in experimental animal models

      Our data indicate that PAM exhibited significant anti-inflammatory activity in all the trials of paw and ear edema induced exhibiting also anti-arthritic activity. PAM could also markedly inhibit production of pro inflammatory cytokines, especially TNF(alpha), IL-1(beta), PGE(2) and LTB(4). These effects resulted in an attenuation of the inflammatory cytokines and ultimately suppression of the edema. The extras also inhibited lipoxygenase and xanthine-oxidase. It was seen that PAM is effective on chronic inflammation and acute inflammation.

      The methanol extract (PAM) exhibited significant (p<0.05) anti-inflammatory activity in all assays, instead hexane and chloroform extracts showed no anti-inflammatory activity.


      PAM possess significantly dose-related antiarthritic activity in M. tuberculosis-induced adjuvant arthritis test in rat, which is considered close to simulating human rheumatoid arthritis.

      The results of this study demonstrated that methanol extract of the bark of E.poystachya acts as an anti-inflammatory agent. It also can be a good source of effective crude inhibitors for XO and LOX. The finding presented in this study are encouraging an substantiate the search for newer pharmacophores in palo azul behind the anti-inflammatory effect.


      (2012) Flavonoid intake and bone health

      Flavonoids, found in a wide diversity of plant foods from fruits and vegetables, herbs and spices, essential oils, and beverages, have the most potential of dietary components for promotion of bone health beyond calcium and vitamin D. Recent epidemiological studies show flavonoid consumption to have a stronger association with bone than general fruit and vegetable consumption. Bioactive flavonoids are being assessed for properties beyond their chemical antioxidant capacity, including anti-inflammatory actions. Some have been reported to enhance bone formation and to inhibit bone resorption through their action on cell signaling pathways that influence osteoblast and osteoclast differentiation.


      (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.


      (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(,151154). 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(,158161).



      (Dec 1, 2011) SEPARACIÓN Y EVALUACIÓN DEL EFECTO ANTIINFLAMATORIO Y ANTIOXIDANTE DE LOS FLAVONOIDES DE Eysenhardtia polystachya (Ort.) Sarg.

      Flavonoids exhibited strong antioxidant activity and other properties that are capable of inhibiting the inflammatory process by different mechanisms of action in vitro and in vivo. Recent research in our laboratory demonstrated the presence of flavonoids in Eysenhardtia polystachya (Ort.) Sarg. (sweet wood) a tree widely distributed in Mexico, as well as anti-inflammatory activity of leaves and bark after the administration of infusion and decoction at a dose of 200 mg/kg (bw) and ethanol extract at doses of 50 and 100 mg/kg (bw) in a murine model of chronic granulomatous inflammation. Therefore, the aim of this study was to separate the flavonoid-rich fraction of Eysenhardtia polystachya (Ort.) Sarg. and evaluate its anti-inflammatory and antioxidant effects.

      Final and dry weights of the granulomas obtained from rats treated with fractions rich in flavonoids and indomethacin significantly decreased as compared to the control group.


      Conclusion: The results of this research show that the fractions rich in flavonoids induce an anti-inflammatory effect in chronic inflammation, probably produced by its selective inhibition of COX-2



      (Oct, 2018) Pharmacological and toxicological study of a chemical-standardized ethanol extract of the branches and leaves from Eysenhardtia polystachya (Ortega) Sarg. (Fabaceae)

      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. 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.



      (2013, Dec 29) (Medical review: 166 studies) Chemistry and Biological Activities of Flavonoids: An Overview

      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.



      (2003) Lupin

      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.



      (2014) Chapter 23 - The Role of Direct and Indirect Polyphenolic Antioxidants in Protection Against Oxidative Stress

      The electrophilic properties of flavonoid quinones make them very reactive towards thiols in protein Cys residues to form cysteinyl flavonoid adducts, which may to a large extent explain their anti-inflammatory and anticancer effects among others.

      A series of exogenous compounds (flavonoids) are able to protect against oxidative stress by induction of phase 2 enzymes (cytoprotective proteins) through activation of the redox sensitive Keap1-Nrf2-ARE regulatory pathway. Inducers of cytoprotective proteins are, for example, found among polyphenols of which many are present in our daily diet.


      Polyphenols are direct antioxidants in vitro, but nevertheless seem to exert their antioxidant effect more by induction of cytoprotective proteins that are involved in a variety of antioxidant actions from reduction of oxidants to the production of endogenous direct antioxidants (e.g., glutathione). Therefore the protection against oxidative stress of polyphenols in vivo is mainly due to their indirect antioxidant effect.



      (2014) Chapter 32 - Anti-Inflammatory and Immunomodulatory Properties of Dietary Flavonoids

      Flavonoids are the most common group of polyphenolic compounds in the human diet and are found ubiquitously in fruits, vegetables, nuts and plant-derived beverages, such as tea and wine. These compounds have been reported to possess a wide range of activities in the prevention of common diseases, including coronary heart disease, cancer, neurodegenerative diseases, gastrointestinal disorders, and others.

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