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Garlic-potential substitute to synthetic aphrodisiacs for erectile dysfunction

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Journal of Pharmacy Research Vol.3.Issue 12. December 2010
Parveen Bansal et al. / Journal of Pharmacy Research 2010, 3(12),3072-3074
3072-3074
Review Article
ISSN: 0974-6943 Available online through
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*Corresponding author.
Dr.Parveen Bansal
Department of Biochemistry, PGIMER, Chandigarh, India
Tel.: + 91-9814135703
E-mail:bansal66@yahoo.com
INTRODUCTION
The Science of aphrodisiacs is one of the important chapters of the ‘Ayurveda’
under “Vajikaran”. Unlike the modern system of medicine the approach to
achieve aphrodisiac effects is, through the improvement in total health i.e.
physical mental and spiritual. This very concept was developed, keeping in
mind the existing norms and values of the society. Sexual dysfunction (SD) and
infertility is a major area from socio-economical point of view. One of the
major causes of SD is attributable to socio-educational conditions that prevail
in our country. SD is indeed observed in both male & female. However, male
Erectile Dysfunction (ED) is less highlighted in India. WHO has conducted
survey which shows male infertility is a major factor in 50% of the six
thousand infertile couples. The cause and effect relationship of sexual dys-
function and infertility has not been adequately established1 however male SD
is due to impairment in erectile function and premature ejaculation.
The arrival of the synthetic “love drug preparations”, has, not only, capti-
vated the public imagination, but has led to a flurry of activity to re-assess
“old” natural products for their use as agents to combat impotence, and,
unearth a new natural product which can truly compete with available market
preparations2. There are several aphrodisiac drugs flooded in the market place
but they suffer from the drawback of lack of pre-clinical & clinical evaluation,
cost effectiveness and shyness in demand. As due to change in life style and
stress, impotence is an increasing problem worldwide, the pharmaceutical
industry has initiated efforts to tackle the grave situation and yielded a few
important drug molecules. To date the “natural” equivalent is not in existence
but several pure compounds from nature, e.g., Yohimbine, Citrulline, two
pyrano-isoflavones, berberine, forskolin and others, have either been re-ex-
amined or are new potential candidates. Intense activity exists in the area of
testing semi-purified plant extracts for erectile dysfunction activity. 2
The
reports on adulteration of herbal formulations with synthetic
phosphodiaesterase-5 (PDE-5) inhibitors and its independent use have been
most common in recent past. The three approved inhibitors for the treatment
of penile erectile dysfunction (ED) sildenafil citrate, tadalafil and vardenafil
hydrochloride have many documented side effects and are required to be used
under medical supervision. 3
Around 60–70% cases of ED occur in patients
with hypertension and ischemic heart disease, and unfortunately PDE-5 in-
hibitors show negative pharmacodynamic interactions with the drugs indi-
cated for these diseases, e.g. nitroglycerine, doxazosin and terazosin. 4 Hence
these ED drugs are not advised for such patients. Unfortunately, those using
herbal formulations may be at risk, if there is clandestine adulteration with
synthetic PDE-5 inhibitors. In Ayurvedic Materia Medica (AMM), the men-
tion of multi-ingredient formulation has been made as aphrodisiac medication
Garlic-potential substitute to synthetic aphrodisiacs for erectile dysfunction
Parveen Bansal 1*, Vikas Gupta2, M.V.Acharya 3, Harinder Kaur 4, Renu Bansal5, Savita Sharma 6
1 Department of Biochemistry, PGIMER, Chandigarh, India
2University Centre of Excellence in Research, BFUHS, Faridkot, India
3 National Research Institute of Ayurveda Drug Development, Bhuvaneshwar. Orrisa, India.
4 Department of Biochemistry, Dental College, Sunam (Pb), India
5Department of Microbiology, Govt. Medical College, Faridkot, India
6 Regional Research Institute, Nagpur, India
Received on: 15-06-2010; Revised on: 18-08-2010; Accepted on:13-09-2010
ABSTRACT
The aim of this compilation is to put the pros and cons of market preparation as well as garlic for use in erectile dysfunction at a single platform and make the
researchers as well as the end users aware about hidden potentials and health benefits of garlic. Results have been obtained using comparative study of few parameters
indicated in table.1 and indicate that garlic can be good substitute for certain nitric oxide based market preparations for use in erectile dysfunction. Garlic can prove
to be an economical, safe, easily available, substitute to market preparations and unstandardised adulterated herbal formulations. Further research work in the
direction of standardization, therapeutic level determination and pharmacological studies on an odorless garlic based preparation may lead to a better formulation.
Key words: Garlic, erectile dysfunction, aphrodisiacs, substitute
of garlic use would qualify it as a folk medicine or as an alternative or comple-
mentary medicine. Garlic is mentioned in the Bible and the Talmud. Even fifth
century Sanskrit medical documents found in India mention garlic as treat-
ment for a variety of diseases. In many cultures, garlic was administered to
provide strength and increase work capacity for laborers. Hippocrates, the
revered physician, prescribed garlic for a variety of conditions. Garlic was
given to the original Olympic athletes in Greece, as perhaps one of the earliest
cultures that developed without contact with one another came to similar
conclusions about the efficacy of garlic. Modern science is tending to confirm
many of his beliefs of ancient cultures regarding garlic, defining mechanisms
of action and exploring garlic’s potential for disease prevention and treat-
ment. 4, 6 Garlic a versatile food and spice with major constituents Alliin, Allicin
and Ajoene6, 7 is often used as ingredient in many dishes for flavour, aroma and
taste enhancement8 thus accepted by Chinese, French, Thai, Gajun, Italian
cuisines. These functional effects could be of great importance for their use in
the prevention and treatment of several diseases.9-11 It is endowed with at least
23 sulphur compounds with organosulphurs and flavonoids as bioactive com-
ponents.12,13
Nitric oxide (NO) and erection
Nitric oxide (NO) has significant effects on many physiological processes,
pathology of diseases and plays a role in inflammation, immune response,
neurotransmission in the brain and functioning of the cardiovascular system.14,
15 Dysfunction in the NO pathway is associated with many diseases such as
atherosclerosis, coronary artery disease (CAD), diabetes, hypertension, erec-
tile dysfunction, and stroke. Many pharmaceuticals, nutrients, supplements,
and diet are being investigated and prescribed to modulate NO activity. NO is
synthesized by combining L-arginine with oxygen with enzyme nitric oxide
synthase (NOS), which is found in three forms. 16 There are a series of reactions
involved in the erection of muscles, in which NO is utilized. Corpora Cavernousa
is the erectile tissue which along with Corpus Spongiosum makes up the body
of the penis and erection consists of dilation of arteries of the penis and blood
in turn flows and fills the spaces in the erectile tissue. NO is the principal
vasodilator in the penis. NO activates Guanylyl Cyclase, present in the cell
membrane, resulting in an increase in the level of Cyclic Guanosine Mono
Phosphate (cGMP) leading to the relaxation of smooth muscles of the Cor-
pora Cavernousa, thus allowing inflow of blood. 17,18 Tadalafil, vardenafil and
having beneficial psychological and physiological effects. 5 The major combi-
nations and preparations described in Ayurveda and Charak-Samhita for en-
hancing or maintaining sexual ability includes some to the most commonly
occurring natural drugs of plant origin. Many of these drugs have been used
from centuries and garlic is one of them. The word ‘Allium sativum ’ is derived
from two sources, the Celtic word allium, meaning “hot or burning.” And the
Latin second name sativum meaning “cultivated”. Garlic has been used medici-
nally since antiquity. Almost in every early civilization known, such as ancient
India, Egypt, Rome, China, and Japan, garlic was part of the therapeutic
regimen for a variety of maladies. Therefore, the ancient medicinal tradition
Journal of Pharmacy Research Vol.3.Issue 12. December 2010
Parveen Bansal et al. / Journal of Pharmacy Research 2010, 3(12),3072-3074
3072-3074
Sr. No.
Parameter Market preparations Garlic
1.
Nature Synthetic Herbal
2.
Main active constituents Sildenafil citrate, Tadalafil, Vardenafil hydrochloride Many organo-sulfur and some other compounds
3.
Economy Costly Abundant
4.
Onset of action One-hour-Tablet, 15 Minutes-Spray Dose dependent
5.
Degradation By cytochome P-450 Mainly by sulfur detoxication pathway
6.
Metabolism Hepatic Hepatic
7.
Abuse-potential High No
8.
Side-effects Very toxic at high doses, Visual impairment, Headache, Dyspepsia, Mild and transient,
9.
Indigestion, Painful and prolonged erection, Death. Not used in woman, Contact dermatitis,
Negative pharmacodynamic interactions with the drugs indicated for Inflammation of GIT, Asthma
these diseases, e.g., nitroglycerine, doxazosin and terazosin. Equally effective in women
10.
Warning & contraindications Patient’s having cardiac diseases, with vasodilators, with nitrate No
containing drug, with CYP- Inhibitors (sustained erection)
11.
Dose As directed by the Physician Maximum tolerable dose-25ml. of fresh aqueous
garlic extract, further research required for
therapeutic level determination
12.
Uses For erectile-dysfunction Wide range of therapeutic uses including use in
erectile dysfunction
Table 1: Comparison between garlic and market preparations on the basis of medicinal potential and social aspects
sildenafil commonly prescribed for erectile dysfunction are phosphodiesterase
inhibitors that cause vasodilation and hypotension but contraindicated for
patients taking nitrates because NO increases cGMP by activating the enzyme
guanyl cyclase and phosphodiesterase metabolize cGMP. In other words, the
inhibition of NO by pharmaceuticals may potentiate the effects of the ni-
trates. So it is prudent to use these pharmaceuticals cautiously, especially with
patients who have leukemia, sickle-cell anemia, and other underlying health
conditions.
Garlic and Nitric Oxide production
Along with several uses of garlic, its cloves are used as a vegetable to treat
preliminary stages of impotency. Traditionally ‘Lasun Chatni’ or ‘Lasun Dal’
along with ghee is taken to increase sexual power. Garlic extract can stimulate
NO release by peritoneal macrophages in response to leishmania promastogote.
19, 20 Garlic is reported to exert some of its therapeutic properties by increasing
NO production in the body. At present, two distinct types of enzymes that
catalyze NO production are known as Ca++ requiring constitutive enzyme or
cNOS and Ca++ independent inducible enzymes or iNOS. At least two isoforms
of cNOS exist, eNOS present in endothelial cells and nNOS present in neuronal
cell and garlic has also shown to increase the activity of NOS in cell free
system which is probably an effect on cNOS. Analysis of garlic powder showed
the presence of arginine at the highest concentration that raises the possibil-
ity that arginine present in garlic may be responsible for its activation of NOS
seen in cell-free homogenates of platelets.
All the NOS-isoenzymes catalyse five electron oxidation of L-arginine to NO
and citruline using reduced nicotinamide adenine dinucleotide phosphate
(NADPH) as the source of the electrons and the cofactor terahydrobiopeterin
(TBH), flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN) and
protoprophyrin IX (Heme). The process incorporates molecular oxygen into
NO and citruline. The linkage between garlic and L-arginine-Nitric oxide has
been reported. 21 The L-arginine-NO pathway was originally identified in vas-
cular endothelial cells. The significant relation between NOS and cellular
polyamine was also established.22 Since NO and polyamines are both products
of L-arginine metabolism and there is a link between garlic, L-arginine and NO
pathway, there is a probability of relation of polyamines with the production
of NO by garlic also.23, 24 It was reported that garlic increase the activity of
GTP-Cyclohydrolase-I enzyme, which is responsible for the synthesis of TBH
by GTP. The ability of garlic to increase both NOS and the production of one
of the essential cofactors-TBH for the enzyme, adds support to the claim that
garlic can exert some of its therapeutic properties by increasing NO produc-
tion in the body. The dose dependent increase in NOS activity by garlic
without having effect of arginine on NOS has been reported.21 This raises the
possibility that a substrate other than arginine is responsible for the NOS
activation by garlic. The beneficial effects of garlic on vasodilation were
reported. These results indicate that AGE increased NO production by activat-
ing cNOS, but not iNOS. The arginine contained in AGE was not responsible
for the effect. AGE may be a useful tool for the prevention of cardiovascular
disease.25 It has been reported that fresh garlic powder increased cNOS activity
but the equivalent quantity of arginine to that found in fresh garlic powder did
not affect cNOS activity.26-27 Garlic contains many other amino acids, and Das
et al. speculated that any of these might be responsible for the increase in NOS
activity in response to fresh garlic powder.27 Generally, many other reports
have shown that garlic contributes to an increase in NOS activity in vivo or in
vitro.26-28 The vascular endothelium has a primary regulatory role to keep the
blood vessels dilated and NO is continuously released by vascular endothelial
cells and regulates the blood flow and vasodilatation. This release of NO
appears to be shear stress and tone dependent and this constitutes a local
vascular reflex mechanism to sustain regional blood flow into vascular beds in
the presence of intense sympathetic vasoconstriction18. Studies have sug-
gested that garlic increases NO production. One study on rats showed that
arterial hypertension caused by N omega-nitro-L-arginine-methyl ester, which
inhibits NOS, is prevented by garlic supplementation. Additionally, NO me-
tabolites were measurably higher in the group treated with garlic, suggesting
increased NO production.28
RESULT AND DISCUSSION
Rasayana’ and ‘Vajikaran’ are the important chapters in the ‘Ayurveda’ and
drugs mentioned are even dispensed to healthy individuals for the improve-
ment of sexual desire and sometimes as preventive medicine to prolong life.
Garlic is one of the most constantly featured natural drugs in these combina-
tions. Comparison between garlic and market preparations on the basis of
medicinal potential and social aspects is given (Table-1). The results show
that as far as therapeutic effects of market preparations in erectile dysfunc-
tions is concerned; garlic also has more or less similar effects and mode of
action. The only step that differs is that most of the market preparations
increase blood GMP level by inhibiting its degrading enzyme phsphodiesterase-
5, while garlic acts by activation of guanalyl cyclase enzyme and thus by
increasing production of GMP in body. It is also observed that garlic has mild
side effects and toxicity. No abuse potential and contraindications of garlic
have been reported in comparison to market preparations. On the basis of
above inferences, it can be concluded that garlic can be used as an economical,
easily available, natural, socially accepted and probably better substitute of
synthetic drugs for erectile dysfunction with minimal side effects. This can be
a good substitute in illiterate people who are frequent buyers of branded drugs
but unaware of the contraindications and side effects. However further re-
search work in the direction of standardization, therapeutic level determina-
tion and pharmacological studies on an odorless garlic based preparation may
lead to a better formulation.
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Journal of Pharmacy Research Vol.3.Issue 12. December 2010
Parveen Bansal et al. / Journal of Pharmacy Research 2010, 3(12),3072-3074
3072-3074
Source of support: Nil, Conflict of interest: None Declared
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... NOS are of two types iNOS and cNOS [100,101]. cNOS is calcium dependent and it has two isoforms i.e. eNOS (endothelial) and nNOS (neuronal) [102]. Nitric oxide synthases are responsible for the synthesis of nitric oxide from L-arginine [103]. ...
... NOS are of two types iNOS and cNOS[100, 101]. cNOS is calcium dependent and it has two isoforms i.e. eNOS (endothelial) and nNOS (neuronal) [102]. Nitric oxide synthases are responsible for the synthesis of nitric oxide from L-arginine[103]. ...
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