Running head: Anti- inflammatory Bioflavonoids 1

Bioflavonoids and Anti-Inflammatory Effects

Kimmer Collison-Ris

MSN, FNP-C, WOCN

Herb 503

January 19, 2014

Bioflavonoids reduce inflammation 2

Abstract

Many health conditions such as cardiovascular, endocrine, obesity, ADD/ADHD, diabetes,

and possibly ASD can be linked to chronic inflammation. Obesity, pollution, allergies, chronic

illness, and a westernized diet have been implicated in causing chronic body inflammation (Wiel,

2013). Researchers believe that decreasing exposure to toxins/allergens, making lifestyle

changes that include a healthier diet and exercise, and weight reduction will help decrease whole

body inflammation (Weil, 2013; Wong, 2004; Pick, 2013). The study of phytotherapy is helping

to bring about a whole new range of anti-inflammatory agents that more effectively target the

inflammatory cascade, well upstream of where conventional NSAID’s and COX-2 inhibitors

cause their damaging and unwanted side effects (Pick, 2013). There are some specific anti-

inflammatory compounds found in foods and botanicals sources that could be incorporated into a

lifestyle regimen that may help reverse chronic inflammation; among these are the bioflavonoids.

Bioflavonoids are a class of over 5000 plant chemicals that our bodies metabolize in a way that

offers strong anti-oxidant, anti-cancer, anti-allergenic, and anti-inflammatory effects (Pick, 2013;

Yao, Jiang, Shi, Tomás-Barberán, Datta, Singanusong, and Chen 2004). Bioflavonoids can be

useful therapeutic agents in treating many inflammatory, autoimmune, and cardiovascular

diseases based on its diverse action mechanisms. This paper seeks to discuss this class of

compounds to suggest they could play a vital role in helping to treat chronic inflammation,

potentially decreasing the above named health conditions (Cho, Yun, Packer, and Chunga,

2001).

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Introduction

Botanicals are used worldwide and some have been determined to be effective at calming

inflammatory conditions within the body. Inflammation is a key contributor of many chronic

health conditions. There is a clear connection between higher blood levels of certain nutrients

and lower risk of health conditions caused by inflammation like arthritis, cardiovascular disease,

and insulin resistance (Weil, 2013). The study of phytotherapy is helping to provide specific anti-

inflammatory agents to target and treat the inflammatory cascade; many of these are comparative

to current NSAID’s and COX-2 inhibitors available on the market that often cause unwanted side

effects (Pick, 2013). By reducing chronic inflammation — also known as low-grade or systemic

inflammation — it may be possible to reverse this by boosting the immune system against

several major health conditions (Wong, 2013). Many traditional medicinal foods, herbs, and

spices, utilized for centuries, have been found to help lower chronic low grade inflammation,

among those substances, bioflavonoids appear to be a key constituent and help decrease

inflammatory mediators in the body (Pick, 2013). Researchers have found a clear connection

between higher blood levels of certain nutrients and lower risk of health conditions caused by

inflammation like arthritis, cardiovascular disease, and insulin resistance (Maroon, Bost, and

Maroon, 2010; Weil, 2013; Wong, 2013).

Methods

A systematic search of existing literature was conducted using PubMed

(http://www.ncbi.nlm.nih.gov/pubmed/), BioMed Central (http://www.biomedcentral.com/,

LIRN and Google Scholar. The search terms used were various combinations of inflammation

and bioflavonoids, flavonoids, causes of inflammation, reduction of inflammation, bioflavonoids

and diet, bioflavonoids and botanicals, and bioflavonoids and herbs. Articles were screened on

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the basis of whether they discussed and addressed reducing inflammation or bioflavonoids

(flavonoid) positive impact upon the body (human and/or animals).

Discussion

Causes of Inflammation

Increased concentrations of TNF-α are believed to cause the cardinal signs of inflammation to

occur (Maroon et al, 2010). Arachidonic acid pathway plays a key role in inflammation because

arachidonic acid is immediately released from traumatized cellular membranes. Membrane-based

arachidonic acid is transformed into prostaglandins and thromboxanes partly through the

enzymatic action of cyclooxygenase (COX). Prostaglandins act as short-lived localized

hormones that can be released by any cell of the body during tissue, chemical, or traumatic

injury, and can induce fever, inflammation, and pain, once they are present in the intercellular

space. Thromboxanes, which are also hormone activators, can regulate blood vessel tone,

platelet aggregation, and clot formation to increase the inflammatory response (Pick, 2013).

Inflammation occurs when the immune system continually releases those inflammatory

chemicals -- even when there are no foreign invaders to fight off (Wong, 2004). Researchers

have found there is a link between higher blood levels of certain nutrients and lower risk of

health conditions caused by inflammation like arthritis, cardiovascular disease, and insulin

resistance (Pick, 2013). Because of the significant side effect profiles of steroidal and NSAID

medications, there is a greater interest in natural compounds, such as dietary supplement and

herbal remedies, which have been used for centuries to reduce pain and inflammation (Maroon et

al, 2013). The damaging effects of inflammation can be prevented and reversed by making

healthy dietary changes today (Pick, 2013; Weil, 2013; Wong, 2013).

Because of the significant side effect profiles of steroidal and NSAID medications, there is a

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greater interest in natural botanicals, like those containing bioflavonoids, some of which have

been used for centuries to reduce pain and inflammation (Maroon et al. 2010). Many of these

natural compounds work by inhibiting the inflammatory pathways in a similar manner as

NSAIDs.

Anti-inflammatory Diet

Epidemiological studies reveal that the Mediterranean diet, saturate in flavonoid-rich foods

(Allium and Brassica vegetables, and red wine), correlates with the increased longevity and

decreased incidence of cardiovascular disease (Weil, 2013) seen in the French people. The most

frequently studied flavonoid, quercetin, has been shown to have biological properties consistent

with its sparing effect on the cardiovascular system. Quercetin and other flavonoids demonstrate

modified eicosanoid biosynthesis and anti-inflammatory responses, prevent atherosclerotic

plaque formation, have antithrombic effects, and promote relaxation of cardiovascular smooth

muscle leading to antihypertensive and antiarrhythmic effects (Formica and Regelson, 1995).

Bioflavonoids

Bioflavonoids are one class of constituents found in some botanicals that comprises over 5000

plant chemicals offering strong anti-oxidant, anti-cancer, anti-allergenic, and anti-inflammatory

effects in the human body (Maroon et al. 2013). Flavonoids are widely distributed in plants and

flavonoids are the most important plant pigments for flower coloration producing yellow or

red/blue pigmentation in petals designed to attract pollinator animals (NewsMedical.net, 2014).

Flavonoids (or bioflavonoids), also known as “Vitamin P and citrin”, are a class of plant

secondary metabolites. According to the IUPAC nomenclature, they can be classified into:

flavonoids, derived from 2-phenylchromen-4-one (2-phenyl-1,4-benzopyrone) structure

(examples: quercetin, rutin), isoflavonoids, derived from 3-phenylchromen-4-one (3-phenyl-1,4-

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benzopyrone) structure, and neoflavonoids, derived from 4-phenylcoumarine (4-phenyl-1,2-

benzopyrone) structure (NewsMedical.net, 2014). The body metabolizes these as natural anti-

inflammatory agents; bioflavonoids include compounds such as quercetin, epicatechin, and

oligomeric proanthocyanidins (OPC’s) many occurring abundantly in our daily food and drink,

such as in citrus fruits, vegetables, tea, cocoa and wine. Among the best for soothing the

inflammatory cascade are quercetin, rutin, and procyanidins (OPC’s) such as those found in pine

bark extract (Pycnogenol) and grape seed extract (Maroon et al, 2013; Wong, 2004; Pick, 2013).

Bioflavonoids are considered "nature's biological response modifiers" because they modify

the body's reaction to allergens, viruses, and carcinogens. The name Bioflavonoid (or flavinoid),

is from the Latin word flavus meaning yellow; it is a class of plant secondary metabolites. They

are widely distributed in plants and are considered the most important plant pigments for flower

coloration (yellow or red/blue pigmentation) in petals designed to attract pollinator animals. In

higher plants, flavonoids are involved in UV filtration, symbiotic nitrogen fixation and floral

pigmentation. a class of molecules found in several types of plants, including fruits and

vegetables of most kinds. These molecules are present in many everyday foods and beverages,

including coffee and tea, as well as green tea, citrus fruits, grapes and many others. These

substances are thought to help promote health, prevent premature aging and reduce the risk of

degenerative diseases. (Wise Geek, 2013).

Scientists believe they act as chemical messengers, physiological regulators, and cell cycle

inhibitors (Wikipedia, 2013). Bioflavonoids include four categories of compounds,

Proanthocyanidins (PCO’s), Quercetin, Citrus Bioflavonoids, and Green Tea polyphenols

(Painter, 2013). They are powerful antioxidants conferring protection versus oxidative and free

radical damage and functioning to prevent the formation of oxidized cholesterol through

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antioxidant effects. Researchers note the bioflavonoids have greater antioxidant effects than

Vitamins C, E, Selenium, and Zinc (Painter, 1998).

How Bioflavonoids reduce inflammation

Studies indicate that flavonoids may affect anti-inflammatory mechanisms via their ability to

inhibit reactive oxygen or nitrogen compounds. Flavonoids have also been proposed to inhibit

the pro-inflammatory activity of enzymes involved in free radical production, such as

cyclooxygenase, lipoxygenase or inducible nitric oxide synthase, and to modify intracellular

signaling pathways in immune cells (Shaik, Castellani, Perrella, Conti, Salini, Madhappan,

Vecchiet, Lutiis, Caraffa, and Cerulli, 2006). Procyanidins, a class of flavonoids, have been

shown in preliminary research to have anti-inflammatory mechanisms including modulation of

the arachidonic acid pathway, inhibition of gene transcription, protein expression and activity of

inflammatory enzymes, as well as secretion of anti-inflammatory mediators (Maroon et al 2010).

Obese adipose tissue is characterized by an enhanced infiltra tion of macrophages. It is

considered that the paracrine loop involving monocyte chemoattractant protein (MCP)-1 and

tumor necrosis factor (TNF)-α between adipocytes and macrophages establishes a vicious cycle

that augments the inflammatory changes and insulin resistance in obese adipose tissue.

Polyphenols, which are widely distributed in fruit and vegetables, can act as antioxidants and

some of them are also reported to have anti-inflammatory properties. Tomato is one of the most

popular and extensively consumed vegetable crops worldwide, which also contains many

flavonoids, mainly naringenin chalcone. Researchers have discovered that naringenin chalcone

exhibits anti-inflammatory properties by inhibiting the production of proinflammatory cytokines

in the interaction between adipocytes and macrophages; naringenin chalcone may be a useful

flavonoid for reducing inflammation found in obese adipose tissue (Hirai, Kim, Goto, Kang,

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Yoshimura, Obata, Yu, and Kawada, 2007).

Quercetin, is a bioflavonoid found in red wine, grapefruit, onions, apples, black tea, and leafy

green vegetables and beans; possessing antioxidant and anti-inflammatory activity. This natural

compound blocks substances causing allergies and acts as an inhibitor of mast cell secretion,

resulting in decreases in the release of tryptase, MCP-1 and IL-6 and the down-regulation of

histidine decarboxylase (HDC) mRNA from mast cell lines. This flavonoid is a safe, natural

therapy that could serve as either primary therapy or in conjunction with other treatments in

fighting inflammation (Shaik, Castellani, Perrella, Conti, Salini, Madhappan, Vecchiet, Lutiis,

Caraffa, and Cerulli, 2006).

Bioflavonoid Rich Botanicals

Pycnogenol is considered 50–100 times more potent than vitamin E in neutralizing free

radicals and that it helps to recycle and prolong the activity of vitamins C and E. Scientists

report it is effective in reducing blood pressure and reducing the risk of venous thrombosis by its

effect on vascular endothelium. The usual dosage is 100–200 mg daily. Few side effects from the

use of pine bark extracts have been reported, the most frequent being mild gastrointestinal effects

such as diarrhea and upset stomach (Pick, 2013). Grape-seed extract is rich in flavonoids and

demonstrates antioxidant activity in in vivo studies with rats, protecting their gastrointestinal

mucosa against the reactive oxygen species generated by acute and chronic stress (Maroon et al.

Table 1 Suggested Flavonoid Dosages

Preventive and antioxidant=50 mg/day of grape seed extract or pine bark extract.

Therapeutic purposes dose=150-300 mg/day of either extract

Quercetin: 200-400 mg taken 20 minutes before meals three times a day

Citrus Bioflavonoids: 2000-6000 mg/day

Green Tea Polyphenols:

For green tea extract standardized for 80% polyphenols and 55 % epigallocatechin gallate, the dose=300-400 mg/day

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2010).

Uncaria tomentosa (cat’s claw) Peruvian herbs derived from woody vines with small claw-

like thorns (hence the vernacular name, cat’s claw) at the base of the leaf, which allow the plant

to climb to heights of up to 100 ft. The active ingredients appear to be polyphenols (flavonoids,

proanthocyanidins, and tannins), alkaloids, and sterols. Various studies indicate that this

Peruvian herb induces a generalized reduction in pro-inflammatory mediators. Researchers

report it prevents the activation of the transcriptional factor NF-kB and it directly inhibits TNF-α

production by up to 65-85%. It inhibits the expression of inducible genes associated with

inflammation, specifically negating the expression of inducible nitric oxide synthase, and hence

attenuates nitrous oxide production. Side effects may include nausea, although it has shown an

impressive protective effect on indomethacin- induced enteritis in laboratory studies (Maroon et

al. 2010).

Conclusion

Botanicals are becoming increasingly popular because of their relatively few side effects.

Nevertheless, there are problems associated with these dietary supplements, and their use

requires knowledge of their biological action, clinical studies (both affirmative and negative),

and potential interactions with other nutraceutical products and prescription medications. As with

any drug or natural compounds, additional caution should be used when considering these

treatments for children, pregnant or lactating mothers or any other clinical or disease condition

that could increase possible risk of side effect or complication (Maroon et al. 2010).

Bioflavonoids occur abundantly in many food sources such as citrus fruits, vegetables, tea,

cocoa and wine as well as botanical substances. This class of over 5000 plant chemicals assists in

body metabolism; some exhibit potential for anti-human immunodeficiency virus functions;

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many flavonoids demonstrate antioxidative activity, free-radical scavenging capacity, coronary

heart disease prevention, anticancer activity, anti-allergenic capabilities, and anti-inflammatory

effects. Due to their availability and abundance, they offer ease of access for a natural anti-

inflammatory regimen for various health conditions. As research progresses, further

achievements will certainly lead to a greater emphasis on the importance of consuming

flavonoid-rich foods and botanical substances. Future research needs to investigate appropriate

models for precise assessment of intake of flavonoids and dosing regimens to treat various health

conditions.

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