Research & Reviews: A Journal of Pharmaceutical Science

ISSN: 2229-7006(online)
Volume 6, Issue 3
www.stmjournals.com

Herbal Coxibs: Natures Aspirin

Rajgopal Nidamboor1*, Jawahar R. Nidamboor2
1
Wellness Physician and Independent Researcher, Mumbai, Maharashtra, India
2
Alumnus,Vivekanand Education Society's College of Pharmacy, Mumbai, Maharashtra, India

Abstract
Pain is part and parcel of most health conditions from joint disorders to cancer. This explains
why several researchers were hooked on to unraveling the deep puzzle behind the pain
mechanism and finding a better way to relieving it with medicines that went far beyond killing
pain alone. When a landmark outcome emerged and identified prostaglandins, the bodys
chemical messengers, as the cause of inflammation, or pain, and that they could be blocked, it
catapulted research to a new frontier. The result: a novel pain-and-inflammation-relieving
medicinal assembly line called non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs are
a large group of medications. There are several types of NSAIDs, and aspirin is the most
familiar. Other examples of NSAIDs are ibuprofen, naproxen, piroxicam, nabumetone, and so
on. NSAIDs were predictably hailed as magic bullets to quash pain. Slowly, however, it
dawned that NSAIDs were effective, all right, but caused unwanted side-effects, some of them
serious. This prompted researchers to think of alternatives, medicines that had all the good
qualities of NSAIDs in the treatment of pain, but without their dangerous side-effects. The
emergence of cyclooxygenase-2 (COX-2) inhibitors, or coxibs, a new class of medications,
provided the means to that end, if not the end to a means. Besides, the arrival of coxibs that
work by inhibiting the enzyme, COX-2, which triggers the release of prostaglandins, one
thought, was a boon, until clinicians warned people with heart problems to exert caution and
avoid their use. COX-2 inhibitors were said to be superior to NSAIDs, in several ways.
Labelled super aspirins, COX-2 inhibitors were found to be as effective as the wonder
drug aspirin is in relieving arthritic pain, for instance, in clinical and patients trials and
treatment outcomes; they also had comparatively less tummy, or gastrointestinal, side-
effects in comparison to medications, like NSAIDs [1]. Besides, they were thought to provide
equivalent pain reducing and anti-inflammatory benefits associated with traditional NSAID
use but, without the inherent side-effects or platelet-related (blood-thinning) problems of
conventional NSAID agents. In addition, some researchers were of the opinion that they could
be useful agents in the management of a host of general and specific ailments, including
prevention and/or treatment of cancer. This brings us to the foundation of this review. Is there
something better than conventional COX-2 inhibitors?

Keywords: Pain, pain relief, COX inhibitors, arthritis, cancer, NSAIDs, herbs, natures
aspirin, ginger, turmeric, holy basil, green tea, conventional medicine, Ayurveda

*Author for Correspondence E-mail: wordoscope@gmail.com

INTRODUCTION Call it the herbal aspirin effect, or what you

Research evidences that a natural herb, or
herbs, selected carefully, and in sufficient
concentrations, can offer substantial relief
from the fury of COX-2 inflammation and
other related diseases, without the diverse
side-effects of conventional, synthetic, or
prescription COX-2 inhibitors [2]. Also, the
best part is: natural herbs come from nature.
They inhibit the COX-2 enzyme, and
powerfully balance platelet aggregation. They
kill pain and inflammation; they heal ulcers;
they also prevent clotting and heart attacks.
may, and this comes without the solemn side-
effects of conventional NSAIDs and/or COX-2
inhibitors. Besides, herbs offer us the added
benefit, which is not confined only to relieving
pain, or distress. They provide us with a
holistic medical tool-kit, not just for
inflammatory relief, but also maintenance of
optimal health and wellness. More so, because
revamping healthy articular cartilage holds
the key to restoring healthy, pain-free joint
function. Pain is relative. It is also specific.
Pain can emanate from previous illness and

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Herbal Coxibs as Natural Aspirin
trauma, or from certain underlying causes,
such as arthritis. In certain cases, there is no
obvious cause of pain, or, one may
erroneously attribute pain to a recent activity
rather than a serious causal effect. Besides, it
is not uncommon for people to assume aches
as being caused, for example, by a recent
sports activity, or hard work. In addition, most
people would not know that aches might be
symptomatic of a heart ailment, or a sign of
stomach cancer [3].
Most individuals bogged down by pain reach
by way of reflex for a bottle of pain-killers, or
soothing balm to control, or get over pain. It
works. But, when the pain begins to stay, or
leaves its visiting card in their body, or
joints, they sense there is something wrong.
They visit a physician or therapist to find out
whats gone wrong. The rest, as the clich
goes, is elementary, nay alimentary. They
are put on medication, most often a NSAID for
pain relief. Soon enough, they get over their
pain syndrome, and also forget about it. They
are lucky.
However, in certain instances, the pain only
expands in its intensity and, over a period of
time, it becomes firmly established. When this
happens, they are at their wits end, not
because the NSAID medication they had
begun to take dutifully has given them relief,
but because it has slowly led to some
unpleasant side-effects; in certain cases,
sombre side-effects.
Its, therefore, not without reason that
researchers were at their wits end and for long
deliberated on a more acceptable line of
treatment, with less side-effects. In the course
of time, like most scientific endeavours, their
sustained work paid dividends. As they
stumbled upon a group of novel medications,
they found that they not only provided better
pain relief, but were also relatively free of
side-effects.
Their identity: herbal COX-2 inhibitors. There
are essentially two types of enzymes involved
in prostaglandins production: COX-1 and
COX-2. Prostaglandins are substances
responsible for pain as well as many other
body functions, which also include protection
of the stomach lining. COX-2, in essence,
RRJoPS (2015) 13-22 STM Journals 2015. All Rights Reserved
Nidamboor and Nidamboor
plays a key role in the creation of
prostaglandins involved in pain and
inflammation. COX-2 inhibitors hamper the
activity of specific COX enzymes, which
release prostaglandins. On the other hand,
COX-1 produces prostaglandins that protect
the digestive system from its own erosive
acids. So, it is important that the enzyme is
best left to itself, and not interfered with [4].
COX is an enzyme naturally present in our
body. COX-1 enzymes are produced
abundantly throughout the body. These
enzymes are involved in the regulation of day-
to-day cellular and metabolic activities
maintaining stomach lining stability,
regulating blood flow within the kidneys, and
balancing platelet function. COX-1 should be
present in the body always; also, it would not
be the right thing for us to impede it. COX-2
enzymes, like COX-1 enzymes, are essential
for inducing pain. But, unlike the COX-1
enzyme, COX-2 enzyme is present in our body
within a restricted area. Also, factors such as
diet, stress, and injury can affect its formation.
So, when COX-2 is produced on a constant
basis, persistent pain follows. The implication:
obstructing COX-2 is a choice wed rely upon
for joint and muscular pain relief and
management, among other things. COX-1
enzyme, as in vivo studies suggest, produces
prostaglandins that help maintain the
capability of the gastroduodenal mucosa, while
COX-2 enzymes form prostaglandins at sites
of tissue inflammation, or injury, which trigger
pain and swelling. To highlight one example;
aspirin and the other NSAIDs inhibit both
COX-1 and COX-2. They often cause
gastrointestinal bleeding and ulcers. On the
other hand, herbal COX-2 inhibitors
selectively inhibit COX-2, while sparing
COX-1. Hence, they cause relatively less
gastrointestinal side-effects [5]. Prostaglandins
are natural chemicals, they are key elements
involved in inflammation. Prostaglandins
perform a variety of functions within the body,
including the control of inflammation and
blood vessel permeability, regulation of
hormones, stomach acid secretion, body
temperature, and smooth muscle contraction.
The enzyme responsible for prostaglandins
synthesis is, as already cited, COX. This is
precisely the spoor vis--vis the COX
enzymes significance. To go back to
NSAIDs; NSAIDs reduce inflammation by
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Research & Reviews: A Journal of Pharmaceutical Science
Volume 6, Issue 3
ISSN: 2229-7006(online)
thwarting the bodys production of
prostaglandins. In the process, they disturb the
production of certain prostaglandins that play a
critical role in protecting the stomach from
acidic effects as well as maintaining the
natural, healthy condition of the belly lining.
This disturbed effect can lead to gastric
ulcers and bleeding. When researchers first
observed that dexamethasone, a synthetic
adrenal corticosteroid, inhibited increased
COX activity, which is induced in the
macrophages, but had no effect on basal
production of prostaglandins, it was proposed
that there were two enzymes, COX-1 and
COX-2. Soon enough, the molecular function
and protein structure of the COX forms were
rapidly identified. This led to the development
of selective COX-2 inhibitors. These drugs
provide the same efficacy as non-selective
NSAIDs, with fewer gastrointestinal adverse
reactions.
COX-2 inhibitor selectively blocks the COX-2
enzyme. Blocking this enzyme stalls the
production of prostaglandins that cause pain
and swelling, for example, arthritic
inflammation. COX-2 inhibitors may not pose
as great a risk of injuring the stomach, or
intestines, as COX-1 inhibitors, but they may
not be totally safe, as was discussed earlier.
Interestingly, we have something that is safe
and easy to use from the herbal medicine front,
wonder herbs from our kitchen. To name a
few major COX-2 herbs: turmeric, ginger,
holy basil, green tea, rosemary, and oregano,
among others.
The COX-2 enzyme, as you know, is turned
on during inflammation and tissue repair. It
also has a significant physiological role to play
in reproduction and renal function.
1. COX-1 is involved in normal
physiological functions, including the
production of protective prostaglandins in
the stomach;
2. COX-2 is induced by inflammation;
3. COX-1 and COX-2 enzymes are inhibited
by NSAIDs;
4. COX-2 inhibitors have little effect on
COX-1 activity; they also do not inhibit
prostaglandins synthesis, hence, their
buffer value.
RRJoPS (2015) 13-22 STM Journals 2015. All Rights Reserved
The COX-1 enzyme, as research suggests,
seems to have a primarily housekeeping
role, serving normal physiological functions in
the gut and kidney, besides being involved in
platelet activation.
NSAIDs are commonly prescribed
medications for inflammatory symptoms, or
arthritis, a major joint disorder. Common side-
effects of NSAIDs include: abdominal pain,
diarrhoea, bloating, heartburn, and dyspepsia.
Long-term NSAID treatment may lead to
ulceration of the stomach and duodenum, in
15 per cent of patients. Though most patients
are asymptomatic, or not aware of their ulcers,
they are at risk, no less, of developing serious
ulcer complications, including bleeding or
perforation of the stomach, especially with
long-term NSAID use.
A huge population of patients with pain
syndromes takes NSAIDs regularly:
approximately 30 million Americans, for
example, according to reports, are currently on
NSAID treatment, everyday [6]. At the same
time, some estimates suggest that the annual
risk of serious complications is 24 per cent
with continual NSAID treatment. The risk
increases substantially in elderly patients;
especially in people suffering from rheumatoid
arthritis, patients taking blood-thinning
medications (e.g., heparin), or prednisone, a
cortisone medication, and individuals with a
prior history of bleeding ulcers and/or affected
by heart disease.
It is also reported that nearly 2,500 people, in
the UK, die from stomach bleeding, each year,
a well-known side-effect of NSAIDs, like
aspirin and ibuprofen. It is estimated that a
quarter of patients, in other parts of the globe,
using conventional NSAIDs, such as aspirin
and ibuprofen, experience some kind of side-
effects, and about 45 per cent of them
develop gastrointestinal bleeding and kidney
dysfunction. The reason is simple; both COX-
1 and COX-2 enzymes are subdued to varying
degrees by conventional, or first generation,
NSAIDs, such as aspirin, diclofenac,
ibuprofen, indomethacin, naprosyn, piroxicam,
and others. While scientific studies maintain
the fact that such adverse side-effects are due
to the inhibition of COX-1 enzymes, it is an
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Herbal Coxibs as Natural Aspirin
acknowledged piece of evidence that NSAIDs
anti-inflammatory effects are also due to the
inhibition of COX-2 enzymes, not to mention
their side-effects.
Besides, the action of conventional NSAIDs
for COX-1 and COX-2 enzymes differs
substantially. Some NSAIDs (e.g., ketoprofen)
are relatively COX-1 selective, while drugs
like ibuprofen and naproxen are fundamentally
non-selective. Also, drugs like diclofenac
are relatively COX-2 selective. Besides, what
is often referred to as COX-2-selective-
NSAIDs continue to possess ample anti-COX-
1 enzyme activity. The result: they greatly
inhibit gastric prostaglandins. This clearly
explains why none of the conventional, first-
generation NSAIDs, in its curative or
therapeutic concentration, or form, shows
mercy to gastric COX-1 activity. Hence, they
cause side-effects, some of them serious.
As is well known, traditional NSAIDs are
frequently used as first-line therapy for
patients with rheumatoid arthritis and for
patients with osteoarthritis, who are not
responsive to the conventional medication,
acetaminophen, for e.g., paracetamol, which is
commonly used for headache and pain. In fact,
an estimated 30 million people take traditional
NSAIDs regularly, and more than 90 million
prescriptions are filled and 40 billion over-the-
counter (OTC) NSAID tablets are sold
annually worldwide. The inference is obvious;
long-term NSAID use can lead to
gastrointestinal bleeding, peptic ulcer, and
other complications. Besides, some clinicians
also underline the fact that NSAIDs are the
primary and major source of serious or adverse
drug reactions.
It is also estimated that 30 per cent of patients
taking traditional NSAIDs develop persistent
gastrointestinal symptoms; more than 10 per
cent discontinue treatment because of this
unfavourable side-effect. Figures estimate that
gastrointestinal bleeding and other
complications from long-term use of
conventional NSAIDs account for at least
100,000 hospitalisations and 16,000 deaths in
the US alone, on a yearly basis [7]. Though
side-effects and adverse reactions have
dropped somewhat by the use of selective
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Nidamboor and Nidamboor
NSAIDs, in the recent past, a lurking danger
still looms large.
The term, COX-2, relates to a clue why the
enzyme works. COX has a specific job:
oxidising, or burning, a fat in the body called
arachidonic acid. This fat is an omega-6 fatty
acid, which occurs naturally in our cell
membranes, or walls. Omega-6 acids, found in
soybean, safflower, sunflower oil etc., are
essential fats in our nutrition. They are
fundamental for managing chronic
inflammatory conditions, thanks to their ability
to alter prostaglandins production and also
yield to measurable changes in certain disease
parameters, especially osteoarthritis.
One could think of the COX-2 enzyme as a
switch that turns on the fat and transforms
inflammatory substances. In other words, the
enzyme is the source of power, the fat being
the electrical current, or cooking medium
and, the end result being inflammation. We all
need the power of the COX-2 enzyme to fight
bodily invasions, and react to trauma and
injury. However, when the power switch goes
out of control, we may fall a victim to
friendly fire, like it sometimes happens in
warfare. Result: we may develop some forms
of arthritis and cancer, and even certain
disorders that affect the brain. The situation
today, unlike before, is not desperate, or
hopeless, thanks to the availability of herbal
COX-2 inhibitor drugs, natural medicines that
can help beat the COX-2 inflammation.
The first in the list of conventional drugs,
which initiated new research, has, of course,
been the wonder drug, aspirin, which not only
inhibits the COX-2 enzyme, but also reduces
the gumminess of our blood platelets. In so
doing, aspirin helps ward-off heart attacks and
strokes. But, this effect comes with a hidden
cost. Aspirin and other NSAIDs cause adverse
side-effects, from time to time: severe
gastrointestinal bleeding and kidney problems.
Agreed that such anomalies have been
somewhat corrected with the introduction of
modified, or safer, forms of aspirin. But, the
problem is, the newer versions of the wonder
drug lack the protective effect, or anti-
coagulant properties of their traditional
cousin [8].
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Volume 6, Issue 3
ISSN: 2229-7006(online)
Also, with the emergence of COX-2 inhibitors
such as celebrex, which were yanked off the
market, for their possible unpleasant
cardiovascular effects, it now looks like one
celebrated too soon. Because, conventional
COX-2 inhibitors work on a different plane,
not something through which our body
regulates inflammation and they also have
somewhat unpleasant side-effects? Possibly,
yes. So, it would do us all a world of good if
we go back to the basics again, and review
joint affections and other disorders, with a
holistic approach, and, in the process, examine
the biochemical pathways that often lead to
inflammation.
This simple approach has a definite advantage.
It will help us understand the complexities of
COX-2 inhibitors better and also show how we
can circumnavigate the pain pathway with
good effect by the use of their herbal
cousins: natural, or herbal, COX-2
inhibitors.
Scientists have (re)discovered several
traditional herbs that can safely inhibit the
COX-2 enzyme. These herbs are ginger,
turmeric, holy basil, green tea, rosemary,
skullcap, oregano, Chinese goldthread, and so
on. To begin with, lets explore what herbal
COX-2 inhibitors hold for us; a mirror to the
future of pain relief gently, and purposefully,
and without the troubled side-effect profile
of conventional, or synthetic, COX-2
medications; in other words, the safe and
effective alternative mode for pain relief and
physical, physiological, and emotional
wellness.
It may come as no surprise that more and more
people are disillusioned with the unwanted
side-effects of conventional, or palliative,
therapies, and have turned, or now turn, to
natural herbs and plants to relieve discomfort
and promote healing. As we all know,
conventional therapies often include NSAIDs
such as aspirin and ibuprofen or even steroids.
NSAIDs work by inhibiting COX-1 and COX-
2 enzymes, which cause inflammation. Long-
term use of NSAIDs, however, can produce
unwanted side-effects, including
gastrointestinal ulceration, or bleeding, and
peptic ulcers. They can also lead to kidney
RRJoPS (2015) 13-22 STM Journals 2015. All Rights Reserved
dysfunction or liver damage (Note: Some
physicians use steroids, which are strong anti-
inflammatory agents. They relieve pain
quickly, but at a cost; they often diminish
white blood cell build-up at the location of
infection or injury and, in so doing, slow down
the process of healing itself).
Besides, the fact remains that more and more
consumers in a growingly health-conscious
world are becoming increasingly aware of the
harmful effects of NSAIDs. Also, their
numbers are expanding and for good reasons.
It would, therefore, be heartening for us to
know about the enormous benefits that
natures natural pharmacy: our herbs and
plants hold as extremely effective and safe
pain relievers, and also help us treat a host of
other disorders, from arthritic pain, obesity and
common cold to cancer. As a matter of fact,
traditional herbs like green tea, turmeric,
ginger, holy basil, oregano etc., used in pain
treatment work similarly to NSAIDs, and
COX-2 inhibitors, but without their
disagreeable side-effects.
As Jill Hoppe, a certified nutritional herbalist
puts it, Turmeric is a really good anti-
inflammatory with few side-effects, and it
doesnt cause the gastric ulceration that aspirin
does. Heres evidence: in a double-blind
study, arthritis patients who were given
turmeric reported decreased inflammation and
pain. The studys researchers, in a report
published in Carcinogenesis, attributed this
effect to curcumin, a natural COX-2 inhibitor
which is also turmerics active constituent [9].
Hoppe recommends 400 mg of turmeric daily
to reduce pain from swelling, or inflammation.
She also says that ginger and boswellia, an
ancient Ayurvedic remedy, may be taken to
reduce pain from inflammation. Hoppe
recommends chamomile too, as a mild anti-
inflammatory. Turmeric and ginger, she
says, are both hot stimulating herbs.
Chamomile is good for someone with mild
inflammation. She says chamomile is also
effective either as a poultice or tea.
It may safely be said that herbs can help
relieve pain, but it is important to look at the
basic causes of pain and its discomfort.
Besides, it may also be said that natural
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Herbal Coxibs as Natural Aspirin
remedies dont characteristically relieve pain
as swiftly as conventional medications do, but
it would only be sensible for us to stand by
them with patience; because they are safe and
also sure to cure pain from the root with
relatively less, or no, side-effects.
There is, of course, no need to have the
patience to move mountains but a little
patience with herbs can bring us huge
dividends in terms of safety and long-lasting
relief. You know that this also comes with an
added bonus: reduced reliance on
conventional drugs that dont actually go to
the source of pain, but often generate
serious, long-term side-effects.
Pain is our bodys natural response to disease,
injury, or other conditions that could harm
health. We often experience pain as a result of
the activation of specialised nerve endings
called nociceptors, which are found in most
tissues in the body. These nerve endings excite
the feeling of pain in answer to:
1. any type of stimulus that causes tissue
damage, pressure, heat, cold;
2. swelling, or excessive stretching of a
structure;
3. extended muscular contraction, or spasm;
4. insufficient blood flow to an organ; and,
5. the presence of certain chemicals.
In addition, any injury or irritation of tissues
can incite the nociceptors. Besides, pain can
continue long after the injury or irritation has
occurred, because the chemicals that influence
the nociceptors hang on at the site of the injury
even after the distress is well-entrenched.
Inflammation is also a natural response to
pain, disease, or injury. The process is
characterised by redness, pain, swelling and
warmth. In some cases, there may be loss of
function. The suffix itis refers to the process
of inflammation. For example: arthritis
signifies the inflammation of the joints;
appendicitis relates to the inflammation of the
appendix. However, it may be said that one
can have pain without inflammation, although
inflammation without pain is uncommon.
Also, both pain and inflammation can be acute
(sudden onset, with shorter duration), or
chronic (slow onset, and long-lasting).
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Nidamboor and Nidamboor
It is obvious that there is a pathway to pain,
the channel of pain. So, let us look at what this
inflammatory pathway is all about and how
COX-2 inhibition works on it. COX forms
the bodys inflammatory pathway. Aspirin and
other NSAIDs obstruct COX in both its forms:
COX-1 and COX-2. COX-2 produces
prostaglandins, which, as already cited, are
powerful triggers of pain and inflammation.
COX-1 is essential for stomach lining
protection. Interfering with its activity can lead
to gastric smarting from minor discomfort to
bleeding ulcers. It is precisely for this reason
that new COX-2 inhibitors, which block COX-
2 selectively, and not COX-1, zoomed into
prominence.
While it is agreed that COX-2 inhibition
relieves pain symptoms, new research admits
that it has little or no effect on any underlying
degenerative process. To recall the words of
scientists that discovered COX, The short-
term effects of COX-2 inhibitors on pain and
swelling of inflammation and arthritis may be
achieved at the cost of an increased propensity
to long-term tissue damage with which these
cytokines, or non-antibody proteins, have been
associated with [10]. To recall another
observation, Tumor necrosis factor (TNF)
and interleukin-1 (IL-1) are considered to be
master cytokines in chronic, destructive
arthritis. The reason is simple. The cytokine
TNF-alpha figures more significantly in
prompting inflammation, while IL-1 beta is
more involved in the destruction of cartilage
and bone. The inference: it is important to
inhibit TNF-alpha and IL-1 beta just as well
when using a COX-2 inhibitor.
This is the bright prospect herbal COX-2
inhibitors hold for us without the side-effects
of conventional medications. Our body has
two inflammatory pathways, both evolving
from arachidonic acid, the inflammatory
precursor. So, it is obvious that blocking one
pathway while sparing the other isnt good
medicine. This was reason enough for
pharmaceutical companies to embark on the
development of drugs that blocked both
branches of the inflammatory pathway.
However, the pitfall for such conventional
(NSAID) drugs has been, they block both
forms of COX (COX-1, and COX-2), and they
also lead to a persistent rebound effect on
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ISSN: 2229-7006(online)
pro-inflammatory factors. In a study,
published in Chemical and Pharmaceutical
Bulletin (Tokyo; 1992; 40(2): 387391p.),
researchers reported that after two weeks
following the termination of daily aspirin or
ibuprofen, the cytokine, or non-antibody
protein-stimulated production of TNF-alpha
and IL-1 beta increased from 270 to 538 per
cent; not a happy equation. The end result was
also frustrating: expanded cartilage destruction
and inflammatory progression in arthritis.
You could just as well guess another aspect.
For balanced selective inhibition of COX-2,
combined with the inhibition of TNF-alpha
and IL-1 beta, to work, scientists suggest that
it is essential to block the additional
inflammatory pathway, 5-lipoxygenase (5-
LOX), which produces pro-inflammatory
leukotrienes. They are products of arachidonic
acid metabolism; they have been implicated as
mediators of inflammation. Research also
reports that an herbal inhibitor of 5-LOX has
proved to be valuable in the treatment of
arthritis. The medication (5-Loxin) is derived
from Boswellia serrata (referred to earlier), a
tree native to India, whose aromatic gum
resins have been used in the ancient Ayurvedic
system of medicine to treat arthritis. As a
matter of fact, laboratory analysis of the
gummy resin from Boswellia serrata shows
one component -boswellic acid that acts as a
specific inhibitor of 5-LOX. With its isolation,
it is now possible to derive the benefits of 5-
LOX inhibition without resorting to the use of
large amounts of ordinary Boswellia serrata
extracts for treatment.
A Japanese pharmaceutical company Shionogi
has one such medicinal candidate under
extension.The remedy illustrates the
potential of the dual-inflammatory pathway
blockade. Called S-2474, the medication is a
potential dual-inhibitor of COX-2 and 5-LOX.
In clinical studies, S-2474 significantly
inhibited experimentally induced arthritis and
oedema, while suppressing inflammatory
activity, all without the mandatory
gastrointestinal ulcer/bleeding or side-effect
profile of NSAIDs [11]. It has also been
reported in patient trials that S-2474 protects
brain cells from senile plaque which is
characteristic of Alzheimers disease, a
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progressive brain disorder. It would be more
than interesting to note that ginger (root), a
common herb, contains gingerols that also
obstruct both the COX-2 and lipoxygenase
pathways, including the production of
prostaglandins and leukotrienes. The inference
is palpable when COX-2 and 5-LOX inhibitors
are used together, in the form of an herbal
preparation, such as S-2474, where both
inflammatory leukotrienes and prostaglandins
are suppressed equally. In the process, their
balance is also restored with the added benefit
of safety. This illustrates yet another
advantage of herbal COX-2 inhibitors.
The revolutionary promise of COX-2
enzymatic inhibition has been hailed as a
landmark event in the annals of preventative
medicine. Studies are a dime-a-dozen on how
COX-2 inhibition reduces arthritic
inflammation and menstrual pain, and, in so
doing, prevents certain cancers; most
notably of the colon.
You may now want to quiz why inhibition of
COX-2 enzyme is so important, and why it
needs to be carefully cowed down and put on
hold. A naturally occurring enzyme, COX-2
controls the creation of prostaglandins in our
body. This inflammatory process is not just
confined to the knee or shoulder, but also
inflammation throughout the body, including
the brain. This has also given scientists
tangible evidence that any no-holds-barred
activity of the enzyme could be one of the
most likely causes for some forms of arthritis,
Alzheimers disease, and cancer.
Like all discoveries, the emergence of the
COX-2 enzyme has given the medical world a
shot in the arm. It has also given the key to the
fundamental cause of some of our most
devastating diseases. No wonder, conventional
drug companies have jumped on to the
bandwagon for newer remedies and produced
pharmaceutical substances that inhibit the
enzymes dreadful effects. The best part is;
research has also had a happy dual effect.
When scientists synthesised COX-2 inhibitors,
a hugely beneficial, and grossly unexpected,
side-benefit also resulted from their efforts; the
motivation to find herbs and plant compounds
to synthetically copy, or mimic, the former. In
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Herbal Coxibs as Natural Aspirin
so doing, researchers have identified several
traditional herbs that contain natural and safe
COX-2 inhibitors. So, from one, it is two
today, the creation of synthetic COX-2
prescription drugs has led to the (re)discovery
of herbal alternatives that are naturally
available and, whats more important, without
prescription. Also, all of this with their natural
ease of use, economics of scale, and relatively
fewer, or minimal, or negligible side-effects in
comparison to conventional coxib
medications.
Conventional COX-2 inhibitors, researchers
acknowledge, have a lower potential to cause
stomach ulcers; but, they do not rule out the
possibility of ulcers in certain patients. As a
safety measure, labels for celecoxib and
rofecoxib, for instance, clearly advice patients
to be vigilant for heart concerns, gastric
ulceration and bleeding that can occur without
warning, and report them to their physician. In
addition, conventional COX-2 inhibitors can
also increase blood pressure, cause leg
swelling and alter, or aggravate, kidney
function, like their cousins, traditional
NSAIDs, in certain patients. Whats more, as
with new drugs, previously undetermined risks
may emerge down the line with conventional
coxibs. It is, therefore, imperative that further
research is needed to determine if conventional
coxibs are reliable enough to replace
traditional NSAIDs as first-line agents.
It is, again, in situations such as these, that
herbal COX-2 inhibitors offer us a far better
advantage, primarily because they are
natural. Hence, they are less likely to cause
unwanted side-effects, including gastric
distress.Now, a bit of the fundamentals; this is
also the dull part. Cyclooxygenases catalyse
the conversion of arachidonic acid. This leads
to biologically active prostaglandins, which
have a plethora of functional roles to perform,
management of the inflammatory process and
protection of the gastrointestinal tract,
including the regulation of our inner biological
clock.
It may be acknowledged that the two
cyclooxygenase forms (COX-1 and COX-2)
also differ in their pattern of tissue expression
and regulation. COX-1 is constitutively
expressed in virtually all tissues, most notably
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Nidamboor and Nidamboor
platelets, endothelial cells, gastrointestinal
tract, the kidneys, and collecting ducts. Its
expression can increase 2-4-fold under
stimulatory conditions. COX-2, on the other
hand, is almost undetectable in most tissues,
but its expression in many cell types, including
macrophages, fibroblasts, chondrocytes,
epithelial and endothelial cells, is amplified
1080 fold upon stimulation with
inflammatory cytokines, growth factors, or
endotoxins. The inference? COX-1, as already
cited, functions as a housekeeping gene in
the regulation of normal functions, such as
maintaining gastric mucosal integrity, platelet
function, and renal blood flow. COX-2, on the
other hand, is rapidly induced and tightly
regulated. It, therefore, plays a critical role in
inflammatory and pathological disease
processes.
The inference is herbal COX-2 is a good
choice. Why? The analogy is simple. The
beneficial actions of NSAIDs, to go back a bit
in our narrative, are associated with the
inhibition of COX-2, just as much as their
adverse effects are related to the inhibition of
COX-1. This is yet another important reason
why the ground swell of opinion in favour of
herbal COX-2 remedies is expanding: that they
are as effective as NSAIDs because they
hamper COX-2 enzymes that mediate pain.
They are also not harmful, because they do
not hamper COX-1 enzymes.
It is a well-known fact that, for ages, natural
remedies such as white willow bark (Salix
alba) and myrtle (Myrtus communis) have
provided pain relief for millions of people.
Willow bark, an ancient remedy, which is used
to treat fevers and arthritic complaints, has
often been referred to as natures aspirin.
Salicin is its active ingredient. Several human
studies have evaluated and confirmed the
remedys ability to rapidly relieve pain and, in
the process, reduce inflammation.
Myrtle has also, for long, been used as a
stimulant, astringent, emetic, anti-spasmodic,
expectorant, diaphoretic, and tonic. It finds
reference in ancient Egyptian and Greek
manuscripts. Evidence also supports the fact
that it was prescribed by Hippocrates, father of
modern medicine, to combat pain and fevers.
What was not known for centuries was the
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Research & Reviews: A Journal of Pharmaceutical Science
Volume 6, Issue 3
ISSN: 2229-7006(online)
exact mechanism of its action. Salicin, as
studies now report, does not cause stomach
upset, or gastric bleeding, as aspirin does. It
lowers your bodys levels of prostaglandins
and has been known to have long-lasting
effects. It has a noticeable action on acute and
chronic pain, including back and neck pain,
muscle and menstrual cramps. A large number
of arthritis sufferers have experienced reduced
swelling and inflammation and eventually
increased mobility in the back, knees, hips,
and other joints, with its use.
CONCLUSION
The quest for an herbal analgesic, or anti-
inflammatory agent, which could provide
therapeutic efficacy equivalent to that of
traditional NSAIDs, but without their
gastrointestinal toxicity, has spurred on
research efforts, as already cited, and from
these forays statistics has also emerged. New
data correspond to a natural drug that inhibits
COX-2 without affecting COX-1. This has led
to the emergence of a truly new era, the
development of natural COX-2 inhibitors.
From the thorough testing of such COX-2
inhibitors which began with in vivo animal
studies, a model for pain has been established
by injecting the polysaccharide, carrageenan,
derived from red seaweed too, into the footpad
of rats to create inflammation [12]. Following
this, an oral COX-2 inhibitor was
administered, which produced both anti-
inflammatory and anti-analgesic effects
without gastric distress. The positive results
established the benefits of herbal COX-2
inhibitors for pain and inflammatory
conditions. Picture this: the downside of new
conventional COX-2 medications. The fact is
they are almost ten times more expensive than
traditional NSAIDs both in terms of
comparison and daily dosage patterns,
although, as proponents argue, they offer
some advantage by way of their
comparatively less side-effects. Think of
natures bounty and human ingenuity. Today,
there is evidence that natural, herbal COX-2
inhibitors obstruct the production of pain and
inflammation and help treat other health
affections, in a more friendly, gentle manner
and, also safely, efficaciously and cost-
effectively.
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The real advance, therefore, is natural or
herbal coxibs, wonder medicines, derived from
nature, that have proved their worth for
thousands of years. Besides, they are easily
affordable in terms of cost and ease of use.
Whats more, COX-2 inhibition would have
been apparent with several common and
widely recognised natural products, from the
time our ancients first used them. It is a
different narrative that it was not known for
long why actual healing benefits resulted from
their use, until scientists isolated the COX
enzymes responsible for such a function.
This is, of course, the opening, not the
concluding, part of the story, because until
each of natures herbal coxibs, or newer
medications, is systematically tested, verified,
and replicated for scientific and beneficial
activity, there wont be a standard to measure
actual clinical effects. The best part is, the
probability, at the present time, seems to
usefully support natural compounds, or herbal
coxibs, serving us as natures original
modulators of pain and as curative
medications. This also bids fair to the future of
safe, natural and effective pain relief.
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AUTHOR BIBLIOGRAPHIES
Rajgopal Nidamboor, PhD, is a board-
certified wellness physician, Fellow of the
College of Chest Physicians (FCCP), Member
of the Centre of Applied Medicine (M-CAM),
writer-editor, commentator, critic, columnist,
RRJoPS (2015) 13-22 STM Journals 2015. All Rights Reserved
Nidamboor and Nidamboor
author, and publisher. His special interests
include natural health and wellness, mind-
body/integrative medicine, and nutritional
medicine. His focus areas also encompass
contemporary independent research and
dissemination of dependable information for
all people concerned about their health. He
feels that it is increasingly gratifying to see
most people, including physicians thinking
outside the box; especially in areas such as
natural health, where the body knows best to
heal itself from the inside out. His published
work includes hundreds of newspaper,
magazine, web articles; four books on natural
health, two coffee-table books, a handful of e-
books, and a primer on therapeutics.
Jawahar R. Nidamboor, BPharm, is a post-
graduate student in industrial pharmaceutics in
the UK.
Cite this Article
Rajgopal Nidamboor, Nidamboor
Jawahar R. Herbal Coxibs: Natures
Aspirin. Research & Reviews: A Journal
of Pharmaceutical Science. 2015; 6(3):
1322p.
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