James South, M.A.
As I reported in the last issue of Vitamin
Research News, chronic, often "silent" inflammation is the new
plague of the 21st century. This inflammation is triggered by aging
and a host of lifestyle factors, including obesity/overweight, too
little exercise, too much high sugar/high starch and overcooked foods,
trans fatty acids, high vegetable oil intake, stress and sleep
This chronic inflammation plays a major role in a variety of diseases,
including cancer, heart disease, Alzheimer's disease, diabetes, obesity,
periodontal disease, allergies, asthma, depression and osteoporosis, to
name just a few.
In my article on inflammation I detailed a series of diet and lifestyle
changes to reduce inflammation. This month I report on some herbal
extracts and nutrients that can effectively reduce various inflammatory
mediators, including interleukin-6 (IL-6), IL-1 beta, TNF-alpha,
prostaglandin E2 and leukotrienes.
Stephania tetrandra is an herb used in China and Korea to treat various
inflammatory conditions, including rheumatoid arthritis, lung silicosis
and hypertension.[2,3] Its main anti-inflammatory components have been
found to be tetrandrine (Tet) and fangchinoline (Fang). Stephania
extracts concentrate these two ingredients so that their combined level
represents 10 to 20 percent of the extract. A Stephania preparation has
shown significant effect in reducing the neutrophil-induced inflammation
in rheumatoid arthritis.
Tet and Fang have been shown to suppress multiple inflammatory cytokines
and mediators. Tet powerfully suppressed nuclear factor kappa Beta (NFkB)
activation in human T cells (immune cells).
NFkB is a multimodal inflammation factor that promotes production of
powerful inflammatory cytokines including IL-1, IL-6, IL-8 and tumor
necrosis factor-alpha. Tet effectively reduced conjunctivitis in mice
exposed to ragweed pollen, reducing inflammatory cytokines IL-1 beta and
IL-5, while also reducing mast cell degranulation (source of
All of these are part of the cause of allergen-triggered red, itchy,
irritated eyes. Tet and Fang powerfully suppressed formation of
thromboxane B2 by human platelets, reducing their tendency to form
unnecessary clots. Tet and Fang reduced by 90 percent the production
of IL-1 and tumor necrosis factor-alpha when human monocytes (white
blood cells) were activated by germs.
Tet showed potent inhibitory effect on leukotriene and prostaglandin
(PG) generation by human monocytes and neutrophils. Tet did not
directly inhibit the cyclooxygenase (COX) enzyme that makes inflammatory
PGs, but rather acted like a corticosteroid to inhibit arachidonic acid
release from cell membranes, thereby depriving the COX enzyme of the raw
material needed to make PGs.
Perhaps most importantly, both Tet and Fang have shown powerful (63 to
86 percent) suppression of IL-6 activity, even at very low
concentrations. IL-6 becomes especially problematic with aging, obesity,
stress and sleep deprivation. IL-6 is the main cause of elevated
blood C-reactive protein, a major risk factor for heart disease.
5-Loxin® is a special extract of boswellic acids from the traditional
East Indian herb frankincense (Boswellia serrata). 5-Loxin contains
approximately 30 percent AKBA (acetyl-II-keto-beta-boswellic acid), due
to a patented process that converts other beta-boswellic acids to AKBA.
AKBA is a selective inhibitor of 5-lipoxygenase (5-Lox).
5-Lox converts arachidonic acid (made within the body from linoleic acid
in vegetable oils) to the highly inflammatory leukotrienes.
Leukotrienes promote cancer, damage the brain, and promote
asthma, arthritis, psoriasis and colitis. They may also promote
atherosclerosis. 5-Lox is activated by stress-released cortisol.
Boswellia extracts have been used successfully to treat ulcerative
colitis, asthma, ileitis and osteoarthritis.
Traditional Boswellia extracts typically contain 2 percent or less AKBA.
Other boswellic acids show little or no 5-Lox inhibition, and some may
even counteract AKBA's inhibition of 5-Lox. Thus 5-Loxin represents
a superior form of Boswellia extract, which works at much lower
potencies than traditional Boswellia extracts.
Luteolin is a flavone (flavonoid) widespread in nature, present in foods
such as celery, green pepper, perilla leaf and seed and chamomile.
According to Kotanidou and colleagues, "Luteolin is...among the most
potent and efficacious flavonoid inhibitors of LPS [germ cell wall
fragment]-induced TNF-[alpha], interleukin-6 production and inducible
nitric oxide expression."
Luteolin possesses strong anti-inflammatory and anti-allergic activity
in vivo (living organism). In mice given LPS to induce sepsis,
luteolin increased the survival rate from 4 percent (untreated) to 48
When compared to other flavonoids, such as quercetin, myricetin, chrysin,
apigenin and taxifolin, only luteolin successfully inhibited TNF-alpha
production and reduced several forms of inflammatory edema when given
orally to test animals.
Luteolin inhibited mast cell release of histamine in rats challenged
with IgE (allergy) antibodies. In studies with human colon cells,
luteolin effectively suppressed TNF-alpha and IL-8 production.
Luteolin also inhibited the release of histamine, leukotrienes and PGD2
from cultured human mast cells sensitized with IgE antibody.
Unlike many flavonoids, luteolin has been shown to be well-absorbed
orally by animals and humans, and to be highly bioavailable (taken up by
body cells).[21-23,27,28] Luteolin has been shown effective even at low
levels.[21-23] Luteolin, along with Stephania, may be one of the most
broad-spectrum anti-inflammatory "nutrients."
Stinging Nettle Leaf
Stinging Nettle (Urtica dioica) is an herb that grows throughout the
temperate zones of Europe and America. It has been used as a medicine
since ancient times and has been used to treat inflammatory conditions
such as asthma, eczema and rheumatic conditions. In Germany a nettle
leaf extract is approved as adjuvant therapy of rheumatic diseases
(joint or musculoskeletal inflammatory conditions).
Nettle leaf extract (NLE) has been shown to reduce IL-2 and
interferon-gamma release by monocytes, which "may inhibit the
inflammatory cascade in autoimmune diseases like rheumatoid
arthritis." NLE was shown to reduce secretion of TNF-alpha by human
dendritic cells, leading to reduced T cell-mediated inflammatory
response. Mice suffering colitis treated with NLE exhibited fewer
signs of colitis than untreated mice. The treated mice also had
significantly lower levels of IL-1 beta and TNF-alpha than untreated
Monocyte proliferation (which promotes inflammation) after LPS
stimulation was also less in treated mice. When 20 healthy humans
ingested NLE for 21 days, there was an 80 percent reduction in TNF-alpha
and a 99 percent reduction in IL-1 beta when blood samples were
stimulated with LPS ex vivo (outside the body). NLE has also been
shown to inhibit NFkB activation. NLE thus exhibits multimodal
Holy basil (Ocimum sanctum) is an East Indian herb highly esteemed in
Ayurvedic medicine. Newmark and Schulick report holy basil leaf
extract (HBE) to be an inhibitor of both cyclooxygenase-2 (COX-2) and
5-lipoxygenase. Kelm and colleagues found various compounds in holy
basil leaves to be effective COX-2 inhibitors. A key constituent of
HBE is ursolic acid. Ringbom and associates reported ursolic acid to
be an effective COX-2 inhibitor.
Godhwani and coworkers tested HBE in rats and found that it was about 60
percent as effective as sodium salicylate (an aspirin-related compound)
in reducing inflammation in various tests. HBE has also been shown
to reduce corticosterone release in response to noise stress in
This is a novel anti-inflammatory property of HBE, given that noise
stress is ubiquitous in the modern world, that noise stress can increase
cortisol release in humans, and that cortisol activates 5-lipoxygenase,
producing inflammatory leukotrienes. As a COX-2 inhibitor (not as
powerful, and thus safer, than the prescription COX-2 inhibitors that
have made recent headlines), HBE represents an important herbal
Green Tea Polyphenols
Dona and colleagues stated, "Green tea is rich in flavonoids and indeed
epidemiological, in vitro, and animal-model studies have associated
green tea consumption with health benefits, including decreased
inflammation." The researchers found both EGCG (the most important
green tea polyphenol) and green tea extract (GTE) inhibited neutrophil-mediated
angiogenesis in an in vivo inflammatory angiogenesis model.
Inflammation-induced angiogenesis (growing new blood vessels) helps
tumors create the massive blood supply they need for growth. Researchers
also found that oral GTE enhanced resolution in a mouse lung
inflammation model, significantly reducing subsequent fibrosis.
Ahmed and associates found EGCG reduced expression and activity of COX-2
in human chondrocytes (cartilage-producing cells) from osteoarthritis
cartilage. They also found GTE reduced inflammatory PGE2 production
when the chondrocytes were stimulated with IL-1 beta.
Kundu and coworkers found that mice pretreated with oral GTE had reduced
COX-2 expression when stimulated by a tumor promoter. Wheeler and
associates found that EGCG inhibited NFkB activation in human lung
epithelial cells treated with IL-1 beta, which is a powerful activator
of NFkB. The same researchers had also previously shown that EGCG
inhibits TNF-alpha activation of super inflammatory NFkB.
Aktas and colleagues found that EGCG reduced the severity of
experimental autoimmune encephalomyelitis (inflammatory brain disease)
when mice were orally pretreated with EGCG. They also found that
EGCG significantly reduced TNF-alpha production in the mice.
Hussain and coworkers found that EGCG inhibited COX-2 without inhibiting
COX-1 expression (COX-1 is important for intestinal and kidney health)
in several different types of human prostate cancer cells.
Varilek and associates found that GTE attenuated chronic inflammation in
mice suffering inflammatory bowel disease, demonstrating lower
interferon-gamma and TNF-alpha levels than control mice with colitis
that were not given EGCG. Thus EGCG-rich green tea extract also
qualifies as a broad-spectrum anti-inflammatory agent.
Ginger (Zingiber officinalis) has been used throughout the world for
thousands of years as a medicine. It is called the "universal medicine"
in East Indian Ayurvedic medicine. Ginger root contains a veritable
cornucopia of natural anti-inflammatory compounds. The USDA
Phytochemical Database reported as of 1999 that ginger has more
5-lipoxygenase inhibitors than any other botanical source.
Dr. Srivastava reported excellent results with ginger root in 56
patients with various rheumatic complaints, with over 75 percent getting
relief in pain and swelling. He suggested that ginger inhibits both
inflammatory prostaglandin (COX-2) synthesis and leukotriene
Newmark and Schulick note: "Ginger has multiple constituents that
inhibit COX-2 and inhibit the 5-lipoxygenase metabolism of arachidonic
acid...Ginger inhibits the creation of prostaglandin PGE2, which [gives
ginger] strong anti-pyretic (or anti-heat) producing effects. It
balances production of inflammatory prostaglandins [PGE2] and PGI2,
which also regulates the production of compounds that dilate the
arteries. Ginger's constituents safely restore healthy platelet function
by inhibiting the formation of...thromboxanes.... Ginger reduces
prostaglandins that sensitize pain receptors at nerve endings...; [and]
has significant anti-ulcer effects [which shows that ginger does not
suppress intestine-essential COX-1 while suppressing COX-2]...."
Jalad and colleagues reported that "Most of the [ginger root] fractions
containing gingerols and/or gingerol derivatives showed excellent
inhibition of LPS-induced PGE2 production." Park and associates
found that topical gingerol "suppressed TPA-induced...[skin] inflammation"
Given its balanced anti-COX-2 and anti-5-lipoxygenase activity, ginger
root extract provides useful, yet safe anti-inflammatory activity.
To help support those who struggle with long-term chronic inflammation,
we have developed two products, Inflammation Control and Advanced
Advanced Inflammation Control is a four-capsule-daily formula,
containing Stephania tetrandra extract; 5-Loxin, luteolin, stinging
nettle leaf extract, green tea extract and ginger extract. It is a
synergistic, state-of-the-art, inflammation-modulating formula.
For those desiring a more basic formula, we also offer Inflammation
Control, a combination of Stephania and luteolin.
Chronic silent inflammation is probably the most insidious yet pervasive
health problem in America today. Now, well-researched, high-tech herbal
nutrition can be used to douse the hidden fires of inflammation.
source of nutrients and supplements.
did we qualify them ?
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