Many of the current chronic disease conditions including cardiovascular disease, Diabetes, hyperlipidemia, ADD, ADHD, Arthritis, and other chronic conditions implicate chronic inflammation as the main disease culprit. Much of our western diet and lifestyle is to blame for this increase. Bioflavinoids contained in whole foods plant based diets show promise in reducing whole body inflammation. This novel paper discusses it possible role in reimaging and treating patients suffering from chronic inflammation to improve their health.

1. Running head: Anti-inflammatory Bioflavonoids 1
Bioflavonoids and Anti-Inflammatory Effects
Kimmer Collison-Ris
MSN, FNP-C, WOCN
Herb 503
January 19, 2014

2. 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).

3. Bioflavonoids reduce inflammation 3
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

4. Bioflavonoids reduce inflammation 4
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

5. Bioflavonoids reduce inflammation 5
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-

6. Bioflavonoids reduce inflammation 6
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

7. Bioflavonoids reduce inflammation 7
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 infiltration 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,

8. Bioflavonoids reduce inflammation 8
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 SuggestedFlavonoid 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

9. Bioflavonoids reduce inflammation 9
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-kBand 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;

10. Bioflavonoids reduce inflammation 10
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.

11. Bioflavonoids reduce inflammation 11
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