Surgical Neurology International OPEN ACCESS Editor-in-Chief:

James I. Ausman, MD, PhD

University of California, Los
For entire Editorial Board visit :
http://www.surgicalneurologyint.com Angeles, CA, USA

Review Article
Natural anti-inflammatory agents for pain relief
Joseph C. Maroon, Jeffrey W. Bost, Adara Maroon1

Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, PA, 1Vanderbilt University, Nashville, TN, USA
E-mail: Joseph C. Maroon - maroonjc@upmc.edu; *Jeffrey W. Bost - bostj@upmc.edu; Adara Maroon - amaroon@sewickley.org
*Corresponding author

Received: 20 October 10 Accepted: 22 October 10 Published: 13 December 10

DOI: 10.4103/2152-7806.73804 Surg Neurol Int 2010, 1:80
This article is available from: http://www.surgicalneurologyint.com/content/1/1/80
Copyright: © 2010 Maroon JC. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and
reproduction in any medium, provided the original author and source are credited.

This article may be cited as:

Maroon JC, Bost JW, Maroon A. Natural anti-inflammatory agents for pain relief Surg Neurol Int 2010;1:80
Available FREE in open access from: http://www.surgicalneurologyint.com/text.asp? 2010/1/73804

Abstract
The use of both over-the-counter and prescription nonsteroidal medications is frequently
recommended in a typical neurosurgical practice. But persistent long-term use safety con-
cerns must be considered when prescribing these medications for chronic and degenerative
pain conditions. This article is a literature review of the biochemical pathways of inflamma-
tory pain, the potentially serious side effects of nonsteroidal drugs and commonly used and
clinically studied natural alternative anti-inflammatory supplements. Although nonsteroidal
medications can be effective, herbs and dietary supplements may offer a safer, and often
an effective, alternative treatment for pain relief, especially for long-term use.
Key Words: Alternative treatments, inflammation, natural anti-inflammatories, pain

INTRODUCTION Table 1: The commonly known and documented side

effects of steroid-based medications[106]
Pain, heat, redness, and swelling (dolor, calor, rubor,
Side effects of steroid-based medications
tumor) are the classic manifestations of the inflammatory
process. Abnormalities of the joints of the spine, Increased risk of infection Impaired wound healing
associated muscles, tendons, ligaments and bone Dermatitis Increased appetite
structural abnormalities can all result in pain and need Fluid retention edema Weight gain
for neurosurgical consultations. Typically, patients will not Fat deposits in face, chest, upper Worsening of previously acquired
back and stomach medical conditions
require immediate surgical intervention, and therefore
Mood change Depression
require treatments to reduce pain and enhance quality of
Hypertension Hyperglycemia
life activities.[71]
Cushingoid-like state Adrenal suppression and crisis
In most cases, the genesis of pain is inflammatory, Stomach ulcers Cataracts
regardless of the etiology. With the elucidation of the Osteoporosis
role of inflammatory cytokines, there is now a clear
understanding of the pathways by which many anti-
inflammatory drugs can alleviate inflammation and NSAID mechanisms are primarily through interaction
relieve pain. with proinflammatory cytokines interleukin (IL)-1a, IL-
1b, IL-6 and tumor necrosis factor (TNF-α). Increased
The use of non-steroidal anti-inflammatory drug (NSAID)
concentrations of TNF-α are believed to cause the
medication is still the mainstay of most classically taught
cardinal signs of inflammation to occur.[44]
clinicians for joint and spine related inflammatory pain,
despite their commonly known side effects [Table 1]. These proinflammatory cytokines result in
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chemoattractant for neutrophils and help them to selectively only blocking COX-2 in order to inhibit the
stick to the endothelial cells for migration. They also inflammatory response and reduce the production of
stimulate white cell phagocytosis and the production of inflammatory prostaglandins and thromboxanes. The
inflammatory lipid prostaglandin E2 (PGE2). NSAIDs’ major push to develop the selective COX-2 inhibitors
ability to interfere with the production of prostaglandin has been the recognition of significant complications
during the inflammatory cascade is the major mechanism associated with the nonselective COX-1 and COX-2
cited for the anti-inflammatory success of these NSAIDs. Nonselective NSAIDs’ major side effects include
medications [Figure 1].[112] significant gastrointestinal upset, gastritis, ulceration,
hemorrhage, and even death. By locking COX-1, which
INFLAMMATORY PATHWAYS also normally acts to protect the gastrointestinal mucosa,
nonselective NSAIDs and aspirin can cause significant
Prostaglandins act as short-lived localized hormones gastric tissue damage.[34,51,78,91,3,101,115]
that can be released by any cell of the body during Various studies have also shown that NSAIDs can delay
tissue, chemical, or traumatic injury, and can induce muscle regeneration and may reduce ligament, tendon,
fever, inflammation, and pain, once they are present in and cartilage healing.[4,13,77] Specifically, NSAIDs are
the intercellular space. Thromboxanes, which are also believed to wipe out the entire inflammatory mediated
hormone activators, can regulate blood vessel tone, proliferative phase of healing associated with WBC
platelet aggregation, and clot formation to increase the actions (days 0–4). A study of the effects of NSAIDs on
inflammatory response.[92,82] The inflammatory pathway is acute hamstring injuries was done in humans by Reynolds
a complex biochemical pathway which, once stimulated et al.,[93] and these investigators concluded that patients
by injury, leads to the production of these and other who used NSAIDs did not experience a greater reduction
inflammatory mediators whose initial effect is pain and of pain and soft-tissue swelling when compared with the
tissue destruction, followed by healing and recovery.[34,51] placebo group. Interestingly enough, the authors noted
A major component of the inflammatory pathway is that the NSAIDs’ group had worse pain associated with
called the arachidonic acid pathway because arachidonic severe injuries compared with the placebo group.
acid is immediately released from traumatized cellular
membranes. Membrane-based arachidonic acid is The NSAIDs are also known to have adverse effects on
transformed into prostaglandins and thromboxanes partly kidney function.[31] Dehydration or preexisting chronic
through the enzymatic action of cyclooxygenase (COX)[34,57]. renal failure or disease, resulting in stimulation of
There are two types of COX enzymes, COX-1 and COX-2. the renin–angiotensin system, may predispose certain
Both the enzymes act similarly, but selective inhibition (as populations to acute renal failure through inhibition of
accomplished by selective COX-2 inhibiting NSAIDs) can prostaglandin synthesis, which can occur when taking
make a difference in terms of side effects. NSAIDs.[31] The National Kidney Foundation asserts that
approximately 10% of kidney failures per year are directly
Acetylsalicylic acid works by irreversibly disabling the correlated to substantial overuse of NSAIDs.
COX enzymes to block the cascade [Figure 1]. NSAIDs
have evolved from blocking both COX-1 and COX-2 to Life-threatening side effects of selective COX-2
NSAIDs
in December 1998, celecoxib (Celebrex) was approved
by the Food and Drug Administration (FDA) as the
first selective COX-2 inhibitor for treatment of arthritis
pain.[92,13,22] Rofecoxib (Vioxx) was approved several
months later, followed by valdecoxib (Bextra).[92,28,67,79]
These NSAIDs were designed to allow continued
production of the gastrointestinally protective
prostaglandins produced through the COX-1 enzyme
system while blocking the COX-2 enzyme that produces
the inflammatory prostaglandins.[34,45,51,89]
Celebrex, Vioxx, and Bextra quickly became the mainstay
Figure 1: Schematic showing that when a cell membrane is injured
the arachidonic acid pathway is activated to initiate the local
for the treatment of chronic pain conditions related
inflammatory response through the production of prostaglandins, to inflammation.[71] Within a few years, an estimated
thromboxanes, and leukotrienes. Their activation requires the 15–20 million people in the US were using selective
enzymes COX and LOX. The NSAIDs can block COX action and COX-2–inhibiting NSAIDs on a long-term basis. These
thereby prevent the formation of the COX-derived inflammatory
mediators. 5-HPETE = 5-hydroperoxyeicosatetraenoic acid; LTC4
drugs became the most commonly used pharmaceutical
= leukotriene C4; PGE2 = prostaglandin E2; PGF2 = prostaglandin agent with more than 70 million NSAID prescriptions
F2; PGI2 = prostacyclin;TXA2 = thromboxane. written each year and 30 billion over-the-counter NSAID
Surgical Neurology International 2010, 1:80 http://www.surgicalneurologyint.com/content/1/1/80

tablets sold annually. It was estimated that 5–10% of synthesis of inflammatory cytokines [Figure 2].
the adult population used NSAIDs, and among the
Aspirin is now believed to target both the NF-kB
elderly (a group at higher risk of nonselective NSAID-
and COX pathways. These agents inhibit the NF-kB
induced gastrointestinal complications), the use of
pathway in endothelial cells and block NF-kB activation
these drugs was as high as 15%. The general acceptance
to inhibit leukocyte recruitment.[114,115,116] NSAIDs have
of these drugs was due to the perceived lack of serious
also been found to inhibit both the COX system and
gastrointestinal side effects that had been associated with
the NF-kB pathway. Immunosuppressant drugs also
the nonselective class of NSAIDs.[26,119]
reduce nuclear expression of NF-kB.[39,70,75] Research now
On September 30, 2004, Merck Research Laboratories indicates that blocking the activation of NF-kB along
announced the global withdrawal of rofecoxib (Vioxx), with other inflammation mediators [Table 2] is the
its primary selective COX-2–inhibiting NSAID.[52,90,122] major mechanism for reducing inflammation by natural
Analysis of the results of the Adenomatous Polyps compounds.
Prevention on Vioxx study (known as the APPROVe
study) showed that there was double the risk of serious
Examples of natural anti-inflammatory
Plant- and animal-derived nutraceutical preparations
thromboembolic events, including myocardial infarction,
have been used for hundreds and even thousands of years
which became apparent after 18 months of Vioxx
to obtain effective pain relief. Herbal medications are
treatment.[26] Selective COX-2 NSAID’s thrombotic
becoming increasingly popular because of their relatively
mechanism of action is based on COX-1’s unopposed
few side effects. Nevertheless, there are problems
action to continued platelet synthesis of thromboxane.
associated with these dietary supplements, and their use
Thromboxane is a thrombogenic and atherogenic
requires knowledge of their biological action, clinical
eicosanoid. Prostacyclin prevents formation of platelet
studies (both affirmative and negative), and potential
clotting. By inhibiting COX-2 that blocks production
interactions with other nutraceutical products and
of prostacyclin (PGI2) there is unopposed thromboxane
prescription medications.
which will increase the clotting risk. Thus, inhibiting
prostacyclin led to the increased risk of thrombotic The evaluation of nutraceutical preparations with
cardiovascular and cerebrovascular events.[5,26,73,123] appropriately designed controlled studies has exploded in
recent years. There is now a greater degree of confidence
Natural compounds for inflammation based on controlled study design and improved quality of
Because of the significant side effect profiles of steroidal the investigators that has strengthened positive findings
and NSAID medications, there is a greater interest in found using natural compounds to treat diseases. It is
natural compounds, such as dietary supplement and important for healthcare practitioners to learn about
herbal remedies, which have been used for centuries to these scientific studies to counsel patients who are taking
reduce pain and inflammation.[94] Many of these natural various dietary supplements, herbs minerals and vitamins
compounds also work by inhibiting the inflammatory for both disease treatment and prevention.
pathways in a similar manner as NSAIDs. In addition
to the COX pathway, many natural compounds act to
inhibit nuclear factor-kB (NF-kB) inflammatory pathways.
NF-kB inflammatory pathways and cytokines
The NF-kB molecule is a transcription factor that controls
the transcription of DNA for the perpetuation of the
inflammatory immune response. It acts as a switch to
turn inflammation on and off in the body. NF-kB has
the ability to detect noxious stimuli, such as infectious
agents, free radicals, and other cellular injuries, and then
directs DNA to produce inflammatory cytokines. The NF-
kB proteins are localized in the cytoplasm of the cell and
are associated with a family of inhibitory proteins known
as inhibitor of kB (IkB).[43,119] The TNF-α, and especially
IL-1b, can also directly stimulate enzymes known as
matrix metalloproteinases, which break down extracellular
collagen matrix, a hallmark of inflammatory joint Figure 2: Schematic showing another inflammatory pathway that
disease.[32,76,77] The IkB proteins are normally bound to NF- is activated by tissue injury. This is the NF-kB activation, in which
once the protein is free as a result of tissue injury, it can enter the
kB and block their nuclear localization signal. A variety of cell nucleus and activate the DNA to enhance the inflammatory
provoking stimuli can degrade the IkB and result in the response further by the production of additional cytokines,
nuclear translocation of NF-kB to be free to activate DNA chemokines, and adhesion molecules (IKKB = IkB kinase)
Surgical Neurology International 2010, 1:80 http://www.surgicalneurologyint.com/content/1/1/80

Table 2: Several examples of inflammation triggering Published studies have shown the effectiveness of O3
factors, pathway mediators and conditions modulated to successfully treat spine-related pain.[71] Capsaicin, oil
by natural compounds of camphor, and other natural topical preparations are
Natural compounds and inflammatory pathway modulation commonly used for muscle soreness and local application
Inflammation triggers for painful traumatic injuries.[12,16,80] The subsequent
Stress Infection sections will review many of these products and discuss
Radiation Allergic immune response
both their efficacy and safety issues. As with any drug or
natural compounds, additional caution should be used
Trauma/injury Arachidonic acid
when considering these treatments for children, pregnant
Inflammatory diet
or lactating mothers or any other clinical or disease
Inflammatory pathways
condition that could increase possible risk of side effect
NF-Kß Leukotrienes
or complication.
IL-1,6 NO
CRP Lipoxygenase Omega-3 EFAs (fish oil)
COX-1 and -2 TNF-α The use of fish oil (in the form of cod liver oil), an
Prostaglandins Adhesion molecules omega-3 EFA, for the treatment of muscular, skeletal,
Thromboxanes Reactive oxygen species (ROS) and discogenic diseases, can be traced back to the
Collagenase/MVP Cytokines late 18th century as detailed by Curtis et al.,[24,25]
Conditions modulated Unfortunately, because of the rapid onset of rancidity of
Pain Atherosclerosis this polyunsaturated oil when exposed to air, and hence
Inflammation Thrombosis
its disconcerting odor, cod liver oil fell out of favor.
With improved extraction techniques, such as using a
Insulin resistance Autoimmune response
protective nitrogen blanket and enhanced oxygen-free
Cancer Neurodegeneration
encapsulation methods, there is less chance of oxidation
during the manufacturing process. The therapeutic
Quality considerations benefits of fish oil can now be realized without the
The processes used to prepare herb-derived compounds regurgitation and odor of previous products caused by
pose complications when it comes to determining the peroxides and rancid tasting fish oil.[14]
quantity and concentration of the products.[30,63,102]
Research has shown that the omega-3 polyunsaturated
The preparation processes are not standardized, and
fatty acids are some of the most effective natural anti-
therefore, the extraction process and the type of plant
inflammatory agents available.[12,23-25,27,50,85] With the
used may affect the true concentration of the product.
discovery that vascular inflammation is the underlying
In addition, there is a lack of uniformity within and
cause of coronary artery disease, fish and fish oil
between manufacturers. Although dietary supplements
supplements are now recommended by the American
are not held to the same rigorous testing and standards
Heart Association for the prevention of this disease.[12,23-
as pharmaceutically derived medications in the US, there 25,27,50,85]
Countries that have the highest fish consumption
are many regulations that still control their manufacture
also have a lower incidence of neurodegenerative disease
because these are food products.
and depression.[12,23-25,27,50,85] The biological basis for the
The US governmental agencies, through the FDA and effectiveness of fish oil in treating arthritis has been
others, routinely inspect the manufacture of vitamins well documented with many positive clinical studies,
or supplements made in this country, as they do for any when compared to traditional pharmaceutical anti-
other food product.[30,63,74] Contaminants, such as the inflammatory agents.[12,23-25,27,50,85]
recently discovered high lead content found in various
The active ingredients in fish oil, eicosapentaenoic acid
Ayurvedic preparations that were made by an Indian
(EPA) and docosahexaenoic acid (DHA), enhance the
manufacturer and imported into the US,[30,61,63,74,102] are
conversion of COX to prostaglandin E3. A natural anti-
generally thought to be uncommon, but can be a concern
inflammatory agent, prostaglandin E3 competitively
when purchasing imported supplements.
inhibits the effects of the arachidonic acid conversion
Some manufacturers inflate nutraceutical products’ claims to prostaglandin E2, a highly inflammatory substance.
and may not cite possible side effects and potential drug Prostaglandin E3 also inhibits the synthesis of TNF-α
interactions. Bleeding complications are associated with and IL-1b, both of which are inflammatory cytokines.
white willow bark, ginger, garlic, and others. Therefore, The EPA and DHA can inhibit the 5-LOX pathway, which
such medicinal preparations are not without risk. converts arachidonic acid to inflammatory leukotrienes,
Products such as omega-3 essential fatty acids (EFAs) by competitive inhibition as well. When EPA and DHA
(O3) do have strong scientific support to be considered are incorporated into articular cartridge chondrocyte cell
as an alternative and/or complementary agent to NSAIDs. membranes, there is a dose-dependent decrease in the
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expression and activity of the proteoglycan-degrading inhibit inflammation by suppressing NF-kB, restricting
aggrecanase enzymes.[12,23-25,27,50,85] various activators of NF-kB as well as stemming its
expression.
Omega-3 EFA, found in fish oil, can directly reduce
the degenerative enzymes, aggrecanase and matrix Curcumin has also been suggested as a treatment for
metalloproteinase, as well as IL-1, TNF-α, and COX- colitis, chronic neurodegenerative diseases, arthritis, and
2, to reduce the inflammation in synovial cartilage. A cancer. In addition, it regulates the activity of several
recent study of 250 patients with cervical and lumbar enzymes and cytokines by inhibiting both COX-1 and
disc disease, who were taking NSAIDs, revealed that 59% COX-2. Most studies to date have been performed in
could substitute fish oil supplements as a natural anti- animals, but given the centuries of use of curcumin,
inflammatory agent for the NSAIDs.[71] The recommended as well as its now demonstrated activity in the NF-kB,
dosage is a total of 1.5–5g of EPA and DHA per day, COX-1, and COX-2 inflammatory pathways, it may be
taken with meals. considered a viable natural alternative to nonsteroidal
agents for the treatment of inflammation.
Rare side effects include steatorrhea and occasional
belching if the supplements are not taken with meals. The usual dosage of standardized turmeric powder is
Typically, persons on a regimen of anticoagulant 400–600 mg taken three times per day.[13] Side effects
medications should not take omega-3 EFAs because of are few, but with extended use, this agent can cause
the possibility of increasing the bleeding potential. stomach upset, and in extreme cases gastric ulcers may
occur at very high doses. Caution should be used if
White willow bark the patient is taking anticoagulant medications or high
Bark from the white willow tree is one of the oldest doses of nonsteroidal drugs. Studies have shown that
herbal remedies for pain and inflammation, dating curcumin may be used in combination with lower doses
back to ancient Egyptian, Roman, Greek, and Indian of nonsteroidal medications.[7-9,11,21,40,87,111,121]
civilizations, as an analgesic and antipyretic agent.
Because of the gastric side effects of aspirin, there has Green tea
been a resurgence in the use of white willow bark for the Green tea has long been recognized to have
treatment of inflammatory syndromes. The mechanism cardiovascular and cancer preventative characteristics due
of action of white willow bark is similar to that of aspirin to its antioxidant properties. Its use in the treatment of
which is a nonselective inhibitor of COX-1 and COX-2, arthritic disease as an anti-inflammatory agent has been
used to block inflammatory prostaglandins.[48] recognized more recently. The constituents of green
tea are polyphenolic compounds called catechins, and
Various randomized, placebo-controlled studies epigallocatechin-3 galate is the most abundant catechin
comparing white willow bark with nonsteroidal agents in green tea.
have shown an efficacy comparable to these agents and
aspirin. Salicin from white willow bark is converted to Epigallocatechin-3 galate inhibits IL-1–induced
salicylic acid by the liver and is considered to have fewer proteoglycan release and type 2 collagen degradation
side effects than aspirin. However, it is costlier than in cartilage explants.[44] In human in vitro models, it
aspirin, and should not be used in children (to avoid also suppresses IL-1b and attenuates activation of the
the risk of Reye’s syndrome), or in patients with peptic transcription factor NF-kB. Green tea also inhibits the
ulcer disease, poorly controlled diabetes, hepatic or renal aggrecanases which degrade cartilage.
disorders, or other conditions in which aspirin would be Green tea research now demonstrates both anti-
contraindicated. The usual dose of white willow bark is inflammatory and chondroprotective effects. Additionally,
240 mg/day.[18,19,33,41,64,69,99,100] green tea research includes the “Asian paradox”, which
theorizes that increased green tea consumption in Asia
Curcumin (turmeric)
may lead to significant cardiovascular, neuroprotective
Curcumin is a naturally occurring yellow pigment derived
and cancer prevention properties.[113] The usual
from turmeric (Curcuma longa), a flowering plant of the
recommendation is 3–4 cups of tea a day. Green tea
ginger family. It has traditionally been used as a coloring
extract has a typical dosage of 300–400 mg. Green tea
and flavoring spice in food products. Curcumin has long
can cause stomach irritation in some, and because of its
been used in both Ayurvedic and Chinese medicines as
caffeine content, a decaffeinated variety is also available;
an anti-inflammatory agent, a treatment for digestive
but the polyphenol content is currently unknown.
disorders, and to enhance wound healing. Several clinical [2,49,53,108,112,117,120]
trials have demonstrated curcumin’s antioxidant, anti-
inflammatory, and antineoplastic effects. Results of a Pycnogenol (maritime pine bark)
study by Zandi and Karin suggested that curcumin might Pycnogenol, like white willow bark, is a nutraceutical
be efficacious in the treatment of cystic fibrosis because material that has been used since ancient times.
of its anti-inflammatory effect.[121] Curcumin is known to Pycnogenol is derived from the bark of the maritime pine
Surgical Neurology International 2010, 1:80 http://www.surgicalneurologyint.com/content/1/1/80

tree (Pinus maritima) and has been used for more than Boswellia typically is given as an extract standardized to
2000 years. It has been considered helpful for wound contain 30–40% boswellic acids (300–500 mg two or three
healing, treating scurvy, healing of ulcers, and reducing times/day). Boswellia has been well tolerated in most
vascular inflammation. It contains a potent blend of studies, although some people may experience stomach
active polyphenols, which includes catechin, taxifolin, discomfort, including nausea, acid reflux, or diarrhea.[1-
procyanidins, and phenolic acids. It is one of the most 10,42,48,56,62,103,104]

potent antioxidant compounds currently known.[17,118]

Resveratrol
Pycnogenol inhibits TNF-α–induced NF-kB activation Resveratrol is a plant-based polyphenol molecule that
as well as adhesion molecule expression in the is found in various concentrations of many different
endothelium. Grimm et al, recently reported that oral plant sources. The plant is called Japanese Knot weed or
intake of pycnogenol inhibited NF-kB activation in Polygonum cuspidatum, and the skins of red wine grapes
lipopolysaccharide-stimulated monocytes as well, thus are believe to have the most concentrated amounts of
decreasing the inflammatory response. It also statistically resveratrol. In plants, resveratrol is generally found in the
significantly inhibited matrix metalloproteinase-9.[46] This plant skin and acts as a phytoalexin to protect the plant
matrix-degrading enzyme is highly expressed at sites of from infection, excessive UV radiation and aide in general
inflammation, and contributes to the pathogenesis of plant defense. Resveratrol has also been found to have
various chronic inflammatory diseases.[96] significant anti-mutation, anti-inflammatory, antoxidant
Studies have shown that pycnogenol is 50–100 times and DNA protective actions, when consumed by animals
more potent than vitamin E in neutralizing free radicals and humans.
and that it helps to recycle and prolong the activity of Most of the active research with resveratrol has been
vitamins C and E. Studies have shown pycnogenol to done in neuro and cardioprotection, but several studies
be effective in reducing blood pressure and reducing are being reported on resveratrol’s use for arthritic joint
the risk of venous thrombosis by its effect on vascular pain. Elmali et al, reported in 2007 using animals that
endothelium. The usual dosage is 100–200 mg daily. Few intra-articular injection of resveratrol protects cartilage
side effects from the use of pine bark extracts have been and reduces the inflammatory reaction in simulated
reported, the most frequent being mild gastrointestinal knee osteoarthritis. The anti-inflammatory properties of
effects such as diarrhea and upset stomach. Pycnogenol resveratrol have also been observed in experimental animal
should not be taken by patients who are being treated models with paw edema, which is attributed to suppression
with immunosuppressants or by those receiving of inflammatory prostaglandin synthesis.[29] Resveratrol
corticosteroid drugs because it can enhance immune is also a potent and specific inhibitor of TNF-α– and
system function and interact with drugs that suppress the IL-1b–induced NF-kB activation. Resveratrol shows the
immune system.[46-84] anti-inflammatory properties as it suppresses COX-2 by
blocking NF-kB activation.
Boswellia serrata resin (Frankincense)
The Boswellia species are trees located in India, Ethiopia, Resveratrol is available commercially as a dietary
Somalia, and the Arabian Peninsula, and they produce supplement capsule, generally from the P. cuspidatum
a gum resin called olibanum, better known in the source. The trans-resveratrol is the active form, and
western world as frankincense. This resin possesses anti- although there is not an established dosing range, the
inflammatory, anti-arthritic, and analgesic properties. typical dose is from 50 to 500 mg daily. Any significant
Boswellia can inhibit the leukotriene biosynthesis side effect or safety issues with resveratrol have not been
in neutrophilic granulocytes by inhibiting 5-LOX, established, but due to an experimentally shown anti-
thus affecting various inflammatory diseases that are platelet effect, caution should be exercised when taking
perpetuated by leukotrienes.[95] Clinically, the substance is other prescription or herbal anti-platelet or coagulation
used in the treatment of degenerative and inflammatory altering products.[29,54,59,68,72,107,109]
joint disorders. It reduces the total white blood cell count
Uncaria tomentosa (cat’s claw)
in joint fluid, and it also inhibits leukocyte elastase,
Uncaria tomentosa and Uncaria guianensis are Peruvian
which is released in rheumatoid arthritis. In one recent
herbs derived from woody vines with small claw-like
study, a statistically significant improvement in arthritis
thorns (hence the vernacular name, cat’s claw) at the base
of the knee was shown after 8 weeks of treatment with
of the leaf, which allow the plant to climb to heights of
333 mg B. serrata extract taken three times a day. The
up to 100 ft. Traditionally, the bark of cat’s claw is used
treatment improved function, but radiographically there
to treat arthritis, bursitis, and intestinal disorders. The
was no change in the affected joints.[62]
active ingredients appear to be polyphenols (flavonoids,
A combination of Boswellia and curcumin showed proanthocyanidins, and tannins), alkaloids, and sterols.
superior efficacy and tolerability compared with Various studies indicate that this Peruvian herb induces
nonsteroidal diclofenac for treating active osteoarthritis. a generalized reduction in proinflammatory mediators.
Surgical Neurology International 2010, 1:80 http://www.surgicalneurologyint.com/content/1/1/80

This herb has been shown to prevent the activation with fewer side effects. We have briefly reviewed several
of the transcriptional factor NF-kB and it directly of the most commonly used plant- and animal-derived
inhibits TNF-α production by up to 65–85%. It inhibits natural compounds that may possess similar effectiveness
the expression of inducible genes associated with in treating the inflammatory reaction seen in both
inflammation, specifically negating the expression of chronic and sub-acute pain syndromes encountered in
inducible nitric oxide synthase, and hence attenuates a typical neurosurgical practice. Ongoing experiments
nitrous oxide production. Side effects may include and clinical trials should be continued to guide and
nausea, although it has shown an impressive protective provide their scientifically based effectiveness to reduce
effect on indomethacin-induced enteritis in laboratory inflammation and promote wellness.
studies.
Disclosures
In general, toxicity and side effects are considered Author #1 is the Chairman of Medical Advisory Board
minimal. Two case reports of acute renal failure in a for GNC and a Shareholder of Herbals USA. Author #2
patient with lupus erythematosus have been recorded. is a Shareholder of Herbals USA.
Cat’s claw can be consumed as a tea (1000 mg root
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