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APHRODISIAC DRUGS FOR WOMEN AND ITS CORRELATION WITH SEROTONIN

Authors:
  • Regional Ayurveda Research Institute Ranikhet

Abstract

Effect of PGE1 (0.4 mg/kg i p ) and Drugs affecting serotonin and Prostaglandin metabolism including aphrodisiac plants on the serotonin level in rat uterus in estrus, and pregnant state were taken up in the present study. Female aphrodisiac an upcoming branch became a thrust area after the discovery of Sildenfil. Some known aphrodisiac plants and natural products showed to increase uterine 5-HT level. The 5-HT response in rat's uterus is different in estrus and non-estrus state .The uterine 5-HT content increase three fold in estrus in comparison to non-estrus state. Drugs like l-tryptophan increase 5-HT synthesis and projected 5-HT concentration in uterine tissue. Monoamine oxidase inhibitor (MAOI) pargyline also increased uterine tissue 5-HT. PGE1 like brain and intestine increased in uterine 5-HT. Indomethacin and diclofenac sodium known to block prostaglandin synthesis by inhibiting prostaglandin synthetase like pCPA reduced the 5-HT content. In pregnant uterus 5-HT content increased while Prostaglandin treatment both in estrus and nonestrus condition also increased 5-HT content more than three fold. Herbs with known aphrodisiac activity contain 5-HT showed significant increase in uterine 5-HT content significantly. The results such obtained show a silvelining in future study of these drugs for therapeutic use.
137
INTRODUCTION
India bears a longstanding Medicare system
with rich heritage evolved on a continuous
process of experience- based scientific research.
Silajit a mountain exuded was under use as to
vitalize, loaded with gold and other minerals.
To change gold into fine powder for
consumption as rejuvenator by Amla also known
as gold making juice. In the later period, an
initial form of chemistry together with
APHRODISIAC DRUGS FOR WOMEN AND ITS CORRELATION
WITH SEROTONIN
P.K. Debnath*1, Tapas Sur2, Anjan Adhikari3 , Achintya Mitra4 ,
S.K. Bandopadhyay5 , Dipankar Bhattacharya6
ABSTRACT: Effect of PGE1 (0.4 mg/kg i p ) and Drugs affecting serotonin and Prostaglandin
metabolism including aphrodisiac plants on the serotonin level in rat uterus in estrus, and pregnant
state were taken up in the present study. Female aphrodisiac an upcoming branch became a thrust
area after the discovery of Sildenfil. Some known aphrodisiac plants and natural products showed to
increase uterine 5-HT level. The 5-HT response in rat's uterus is different in estrus and non-estrus
state .The uterine 5-HT content increase three fold in estrus in comparison to non-estrus state. Drugs
like l-tryptophan increase 5-HT synthesis and projected 5-HT concentration in uterine tissue.
Monoamine oxidase inhibitor (MAOI) pargyline also increased uterine tissue 5-HT. PGE1 like brain
and intestine increased in uterine 5-HT. Indomethacin and diclofenac sodium known to block
prostaglandin synthesis by inhibiting prostaglandin synthetase like pCPA reduced the 5-HT content.
In pregnant uterus 5-HT content increased while Prostaglandin treatment both in estrus and non-
estrus condition also increased 5-HT content more than three fold. Herbs with known aphrodisiac
activity contain 5-HT showed significant increase in uterine 5-HT content significantly. The results
such obtained show a silvelining in future study of these drugs for therapeutic use.
Key word: Female aphrodisiac, Herbal aphrodisiac, 5-HT.
1 Gananath Sen Institute of Ayurvidya and Research , Kolkata, West Bengal, India.
2Department of Pharmacology, Institute of Post Graduate Medical Education and Research, Kolkata,
West Bengal, India.
3 Department of Pharmacology, R G Kar Medical College, Kolkata, West Bengal, India.
4 National Research Institute of Ayurvedic Drug Development, Kolkata, West Bengal, India.
5 Director of Medical Education, Govt. of West Bengal, West Bengal, India.
6 Principal, Kalyani Medical College, Kalyani, Nadia, West Bengal, India.
*Corresponding author
Explor. Anim. Med. Res., Vol.2, Issue - II, 2012, p. 137-145 ISSN 2277- 470X (Print)
ISSN 2319-247X (Online)
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Exploratory Animal and Medical Research, Vol.2, Issue -II, December, 2012
philosophical and magical association the
Alchemy appeared. (Mehedihasan 2002).
Studies on a female aphrodisiac an upcoming
branch needs attention to increase the state of
arousal. In order to accomplish these
phenomena, a substance or activity would
require impacting the libido in women. While
in age old, Ayurveda dating back to 5000 years
deals with the rejuvenating drugs in Vajikarana
specialty (Debnath 2002) may be nomenclature
as aphrodisiac with detail description for
males(Charaka Samhita, chi 2). On evaluation
the food and natural products described as
aphrodisiac (vajikaran) known to have serotonin
content.
Serotonin plays an important role in sex cycle
but its involvement in the aphrodisiac activity
leading to orgasm is not fully elucidated. Some
known aphrodisiac plants and natural products
showed to increase uterine 5-HT effect and so
also increases uterine 5-HT level. Yohimbe is
also popular as a female aphrodisiac that
increases sexual desire in women having low
sex drive (Meston et al. 1996 ).
Serotonin is widely distributed biogenic
amine present in animal and plant kingdom with
complete synthesizing and degradation enzyme
system and stored, in the tissue, being
synthesized for specific function ( Fozard 1989).
Serotonin's role in the majority of peripheral
processes is similar in males and females. The
female genital tract is innervated by the pelvic
splanchnic, hypogastric and pudendal nerves
(Grey 1966) In women, contractions in the
smooth muscles of the genital organs entail
orgasm, which are characterized by rhythmic,
synchronized vaginal, anal and uterine
contraction (Bohlen et al. 1982, Fox 1976)
One of the primary functions of peripheral
serotonin is the regulation of vascular tone and
blood flow (Meston et al. 1996). Serotonin
administration produces contractions in the rat
and human uterus (Wrigglesworth 1983) The
5-HT antagonists and ketaserine inhibits 5-HT
induced contractions of the rat uterus in vitro.
Serotonin produced contractions in human
myometrial smooth muscle obtained from
cesarean section. The contractile effect of 5-HT
in genital tissues as agent is more potent than
noradrenalin, prostaglandins F2α and E2
(Maigaard et al. 1986).
Similarly prostaglandins are also a strong
contender to designate important transmitters in
parturition and labour like 5-HT( Acharya et al.
1989 ) .In our earlier studies, we has postulated
interrelationship of PGs and 5-HT in brain and
GIT ( Debnath et al. 1978). In uterine tissue,
existence of such correlation is questionable. To
substantiate the role of male aphrodisiac drugs
on uterine tissue 5-HT and to correlate with
female aphrodisiac activity are essential. In
Ayurveda, drugs with aphrodisiac (vajikarana)
initiator were known for their use especially in
males but not for females.
The physiological changes that occurs in
different female reproductive organs were first
recorded by Sintchak and Geer in 1975 photo
plethysmo graphically with introduction of a
probe to record the vaginal blood flow. That was
the first practical and reliable measurement
device for vaginal blood flow recording . This
evidence drawn attention to the scientists as the
starting point to record physiological changes
with evidence before the role of aphrodisiac on
female to yield orgasm was less known.
Research in late 1970s and early 1980s had
provided ample information about the female
sex physiology. The psycho physiological
assessment of female sexual function has
relatively short history in sexology (Rosen and
Beck 1988). In post Sildenafil era, attempts are
being made to search for a suitable replica for
139
female aphrodisiac with limited success (Terrett
et al. 1996) . The incidence of female sexual
dysfunction including libido is of great concern
not only in India but also in abroad. The female
sexual arousal is associated with
neurotransmitter mediated vascular smooth
muscle relaxation, which stimulate vaginal
lubrication, vaginal wall engorgement and
increased clitoral vaso-congestion. Thus,
women with atherosclerotic vascular disease
experience decrease response of vascular
smooth muscle relaxation and orgasm (Park and
Colleagues 1997).
Different reproductive functioning centers
concerning infertility mainly focus in and around
ovarian function and general gynecological
health issues concentrating on the reproductive
potential of a male. Knowing full well female
sexual dysfunction but the sexual implications
per se is hardly addressed. In the present study
effect of 5-HT synthesis and metabolizing drugs
along with some rejuvenating and aphrodisiac
drugs are evaluated on serotonin content in rat
uterus in different condition explore female
aphrodisiac.
MATERIALS AND METHODS
The study was conducted on female Wistar
albino rats (120-150 g). The rats were
maintained on standard Hind Lever diet and
were housed in an air cooled room (25OC) in
colony cages. Animals were fasted overnight but
water was allowed ad lib. before
experimentation. Different drugs were
administered at different times shown in Table
1 and rats were killed by decapitation between
9 and 11 am to take out uterine tissue in frozen
condition. Uterine tissue serotonin was
estimated by the method of Snyder et al. (1965)
in non-estrus and estrus state. Artificial estrus
was produced by injection of stilbesterol,
described in detail ( Debnath 1977) . Statistical
analysis of data was done by Student's 't' test.
The choice of the dose and route of
administration was based on earlier reports
(Debnath et al. 1978, Bhattacharya et al. 1975
& 1976). All the drugs were purchased from
Sigma except PGE1 gifted by The Upjohn
Company, USA. The study protocol was
approved by Institutional Animal Ethics
Committee.
RESULTS AND DISCUSSION
The response of 5-HT in rat's uterus is
different in estrus and non-estrus state .The
uterine 5-HT content increase three fold in estrus
in comparison to non-estrus state. Drugs like
l-tryptophan precursor amino acid pre-treatment
increase 5-HT synthesis and projected 5-HT
concentration in uterine tissue. Monoamine
oxidase inhibitor (MAOI) pargyline block the
degradation of 5-HT to 5-HIAA also increased
uterine 5-HT. PGE1 increased uterine 5-HT like
brain and intestine. Indomethacin and diclofenac
sodium known to block prostaglandin synthesis
by inhibiting prostaglandin synthetase like pCPA
reduced the 5-HT content. In pregnant uterus
5-HT content increased while Prostaglandin
treatment both in estrus and non-estrus condition
also increased 5-HT content more than three
fold. Herbs with known aphrodisiac activity
contain 5-HT which showed significant increase
in uterine 5-HT content significantly. The results
are summarized in Table 1.
In the present study 5-HT content in rats
uterine tissue showed changes depending upon
the synthesis and degradation enzyme acting
drug response similar to GIT and brain. The
prostaglandin E1 increased 5-HT level in uterus.
Moreover, increased the 5-HT synthesis in brain,
peripheral tissue and stomach established
interrelationship of PGE1 and 5-HT (Debnath
Aphrodisiac drugs for women and its correlation with Serotonin
140
Exploratory Animal and Medical Research, Vol.2, Issue -II, December, 2012
et al. 1978). Prostaglandin relationship further
strengthens on the effect of indomethacin, PGE1
increased 5-HT synthesis rate while
indomethacin decreased the synthesis rate point
towards further involvement of PGE1 in 5-HT
response. It is well known that indomethacin,
aspirin are being used clinically in the pregnancy
for threatened abortion (Acharya et al. 1989,
Debnath et al. 1994) Aphrodisiac drugs used
usually for males also showed increased 5-HT
in uterine tissue in rats.
Aphrodisiacs typically magical substance
contains chemical properties or involves
activities that stimulate hormonal responses to
achieve this task. A female aphrodisiac, to work,
needs to increase the state of arousal would also
need to impact the libido in women. Natural
female aphrodisiacs are not well proven. Many
have supporting clinical studies showing that
the hormones or chemical properties in them
could actually generate positive results. In the
present study aphrodisiac drugs were employed
Withania somnifera, Asperagus recemosus,
Mucuna prurians and Musa paradisiac
(vegetable banana). All of them showed
increased uterine 5-HT in comparison to control
non-oestrus rats. There are reports that besides
those drugs Crocus sativa, Glyceriza glabra,
black tea or Camellia senesis, Tribulus teristics
showed aphrodisiac activity (Dutta et al. 2002,
Gupta and Shaw 2011).
In Sri Lankan traditional medicine black tea
brew (BTB) of Camellia sinensis is claimed to
have male sexual stimulant activity. Although
Table 1: Effect of PGE1 (0.4 mg/kg i p ) and Drugs affecting serotonin and Prostaglandin
metabolism including Aphrodisiac plants on the serotonin level in Rat Uterus.
Values are Mean ± S E, n= sample size , p< 0.01
141
this claim is not scientifically tested and proven,
(Ratnasooriya and Fernando 2008) Another
natural herbal aphrodisiac Withania Somnifera
(Ashwagandha), an herbal miracle that works
mainly on the reproductive and nervous systems
as a sexual and an energy tonic with a
rejuvenating effect increases brain 5-HT. Herbal
drug preparation containing Aswagandha,
Satavari, Gokshura increase brain 5-HT,
melatonin and histamine (Upadhyay et al. 1988).
Withania somnifera reduces increases the blood
sugar level, reduces glucose tolerance, impairs
cognitive performance, triggers gastric
ulceration, suppresses immunity, reduces libido
and stimulates corticosterone secretion and
exhibiting anti-stress effect in chronically
stressed rats. (Bhattacharya and Muruganandam
2003).
Tribulus can be helpful for menopause,
decreased libido or sex drive, impotence and
male and female infertility. Tribulus terristis
increase brain 5-HT and improve sexual
dysfunction in men and women due to an
increase up-regulating androgen receptor
expression and nitrogen oxide synthetase
neurons in the regions of the brain that regulate
sexual behavior and desire function (Kerry and
Lovell 2001).
Myristica fragrance (Nutmeg) natural herbal
aphrodisiac effect widely used to improve the
natural aroma and flavor of food (Sonavane et
al. 2001). Asparagus racemosus is used as a
nutritive tonic, natural herbal aphrodisiac, and
as an, galactogue, and also used as
antispasmodic and in epilepsy, depression and
hysteria. Shatavari roots promote breast milk
production and are used to treat low sex drive
and infertility and decrease the menopausal
symptoms by the improvement in vaginal
dryness associated with menopause (Dutta et al.
2002). M. pruriens is widely used as male and
female aphrodisiac. Recent study reveals that
M. pruriens showed antimicrobial activity
(against gram positive, gram negative and spore
forming bacteria and also fungi) on the methanol
leaf extract and 5-HT was detected in the seed
(Salau 2007).
The effect of Crocus sativus (saffron) was
studied on male erectile dysfunction(ED). It is
presumed that Crocus sativus may replace
phosphodiesterase 5-inhibitors as aphrodisiac
(Ali et al. 2009). Aphrodisiac activity of
Glycyrrhiza glabra in male Wistar rats
exhibiting the greatest efficacy in delaying
ejaculation like re-uptake inhibitors (SSRIs)
.The brain area most associated with sexual
behavior is the limbic system. Indicates a
relationship between brain dopamine, 5-HT and
sexual behavior (Singh and Mukherjee 1968)
Both dopamine and 5-HT are implicated in
depression are known to effect libido, erection,
ejaculation and orgasm. It is also suspected that
monoamines play a crucial role in the regulation
of sexual behavior (Sudhir et al. 2012).
Vegetable banana contain 5-HT and proved
to have antiulcer effect. Ethanol extract of
banana (BE) was reported to increase the
accumulation of eicosonoids like prostaglandin
E and I2 (PGE and PGI2) and leukotrienes B4,
and C4/ D4 (LTB4, C4/ D4) in the human gastric
and colonic mucosal incubates.( Goel et al.
1989, Travares et al. 1990, Goel and Maity
1992). Aqueous extracts of onion, garlic and
ginger on platelet aggregation and metabolism
of arachidonic acid in the blood vascular system
are known (Srivastava 1984).
Research on the relationship between
aphrodisiac effect of herbal drugs in female and
correlation with serotonin and sexual
functioning has focused primarily on Central
Nervous System (CNS) activity. In animal
experiments, to evaluate the mechanism directly
Aphrodisiac drugs for women and its correlation with Serotonin
142
Exploratory Animal and Medical Research, Vol.2, Issue -II, December, 2012
drug could be injected into the CNS, or into the
periphery and subsequently examine sexual
responding to map relationship between sexual
activity and specific serotonin receptor activity
in serotonin rich brain regions. In human, such
direct examination for ethical reasons cannot be
conducted. Only possible to depends on the
indirect research to link between serotonin and
sexual behavior that too focused primarily on
centrally mediated events. Antidepressant, anti-
psychotic, or other serotonergic drugs have been
discussed almost exclusively in terms of
serotonin receptor subtype activation or
inhibition in the CNS. Clearly, serotonin may
mediate some aspects of sexual functioning
almost entirely within CNS. Evidence suggests
that hypothalamic serotonin activity can produce
lordosis response in rats (Uphouse et al. 1996).
However, the vast majority of serotonin
receptors are located in the periphery of the
body, with only 5% in the CNS (Prichard and
Smith 1990) Particular artery may constrict or
dilate when exposed to serotonin depending
upon whether it was relaxed or constricted prior
to serotonin exposure (Yang and Mehta 1994).
Serotonin may also act synergistically with other
substances to affect vasoconstriction or
dilatation( Yildiz et al. 1998).
Sexual difficulties often accompany certain
disorders that are characterized by abnormalities
in peripheral serotonin. It is possible that these
sexual difficulties result at least in part, from
deregulation. For example, depression, which
has been traditionally viewed as a psychological
disease, is characterized by changes in sexual
functioning and the evidences suggests that
peripheral serotonin as measured by platelet
serotonin level, is lower in depressed individuals
as compared to non-depressed (Takahashi 1976).
Platelet serotonin levels may be inversely related
to severity of depression (Mann et al. 1992)
143
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Ahlman H, Dahlstrom A, Kewenter J and
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Ali S, Hossein H, Mahmood M,
Mohammad TS and Omid R.(2009).
Evaluation of Crocus sativus L. (saffron) on
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Bhattacharya, SK Raddy PKSP, Debnath
PK and Sanyal AK.(1975). Potentiation of
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Bhattacharya SK, Mukhopadhyay SN,
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5-Hydroxytryptamine in Prostaglandin E1
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Bhattacharya SK and Muruganandam
AV.(2003). Adaptogenic activity of Withania
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Caraka Samhita ed. by Vaidya Jadavaji
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Debnath PK, Sanyal AK, Bhattacharya
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Acharya SB.(1994). Effect of PGE1 on Blood
Aphrodisiac drugs for women and its correlation with Serotonin
Adrenergic stimulation has been reported to
produce an increased release of 5-HT from the
enterochromaffin cells of the gastrointestinal
tract and in women(Ahlman et al. 1976),
adrenergic activity facilitate sexual arousal
(Menston & Gorzalka 1996). It is feasible that
increased adrenergic activity during sexual
stimulation in women produces an acute increase
in 5-HT. In myometrial preparations,
Prostaglandin F2α (PGF2α), Prostaglandin E2
(PGE2), Noradrenaline (NA) and Serotonin
(5-HT) all caused concentration-related
contractions (Miaigaard et al. 1986), while
oxytocic activity of both 5-HT and PGs was
reported in rats (Acharya et al. 1985).
Premature ejaculation (PE), whose
pathophysiology is still not clearly identified, is
the most common male sexual dysfunction, yet
it remains under diagnosed and undertreated.
Pharmacologic manipulation of the serotonergic
system has been performed in rats, with the
selective serotonin mediated antidepressant
(Giuliano et al. 2006). Retrospective analysis of
the data indicated that fibers may be more
sensitive to uterine stimulation when rats are in
vaginal estrus/proestrus than in diestrus/
metestrus. The hypothesis of an implication of
brain 5-HT in the mechanism of psychogenic
sexual deficiency and the possibility of a
therapeutic approach with drugs interfering with
5-HT turnover (Debnath et al. 1978) may be
rational to improve female sexual dysfunction.
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Aphrodisiac drugs for women and its correlation with Serotonin
... Mucuna pruriens L. & Asparagus racemosus (Shatavari) increase brain 5-HT & Melatonin. Therefore widely used as male and female aphrodisiacs [22]. Milk decoction of Asparagus racemosus enhance penile erection and sexual behavior [23]. ...
... And also it is consider as scientifically proven herb that improve libido and spermatogenesis [23,24]. Glycyrrhiza glabra (Madhuyashti) modulate the serotonin level that plays an important role in sex cycle [22]. Formulation made from roots of Glycyrrhiza glabra and Sida cordifolia (Bala) has showed significant therapeutic efficacy in male sexual disorders by inhibition of primary and secondary symptoms while enhancement in hormonal and seminal parameters validating its spermatogenesis effect without any toxic or adverse effect [25]. ...
Article
Background: Vājīkarana - Aphrodisiacs / Virilification Therapy is one branch of Ashtanga Ayurveda. It deals with preservation and promotion of sexual potency of a healthy man, conception of healthy progeny, and management of sexual and reproductive ailments. Vājīkarana drugs have been selected for the present review due to high prevalence of reproductive disorders among young people below age 40 years, recorded neonatal death caused by congenital anomalies and the urgency of effective medicines in the community. Objectives: To identify Vājīkarana drugs mentioned in Bhaisajya Rathnavali and analyze the pharmacodynamics properties of commonly used Vājīkarana drugs. Methodology: The review was mainly based on Vājīkarana drugs mentioned in Bhaisajya Rathnavali by Acharya Govinda Das Sen and commonly used and mostly available drugs have been analyzed according to their pharmacodynamics properties. Collected pharmacodynamics properties from authentic texts and journal articles were tabulated and analysis was done by using SPSS. Results: Out of 67 Vājīkarana formulae, 208 single drugs were identified which included 83.65% of herbal origin drugs and 74.6% of drug formulae were used to increase the sexual power. 37.3% of the formulae were prepared as Churna (Powder) and most frequently used Anupana (Vehicle) was cow’s milk. Among frequently used & commonly available 10 drugs, Maricha - Piper nigrum has been used in majority of formulae (26.8%). Pharmacodynamics analysis revealed that 80% of drugs were Madhura rasa (sweet in taste), 70% were Guru guna (heavy in property), 70% were Shita virya (cold in potency) and 80% were Madhura vipaka (sweet in post digestive action). Based on modern science, 60% of the drugs had tonic action. Conclusion: Vājīkarana formulae mentioned in Bhaisajya Rathnavali were mainly used to increase the sexual power of man. Madhura rasa, Guru guna, Shita virya and Madhura vipaka were the pharmacodynamics properties of commonly used drugs in the formulae.
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A sensitive and specific method for the estimation of serotonin in biological materials is described. In this method, serotonin is reacted with ninhydrin to form a product whose fluorescence is eight times more intense than the native fluorescence of serotonin in strong acid solution. With this method it is possible to measure serotonin in organs in which endogenous serotonin had not been previously detected and to study the subcellular distribution of this amine in the rat pineal and adrenal glands.
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Extracts of plantain banana (Musa sapientum Linn var. paradisiaca) were studied on the accumulation of eicosanoids in incubates of human gastric and colonic mucosa. The ethanolic extract caused a concentration-dependent increase in the eicosanoid accumulation but the water extract was ineffective. Since all the eicosanoids studied tended to increase, banana may act by increasing the availability of arachidonate. In control tissues the accumulation of PGE and TXB2 in the incubates decreased with time while that of 6-keto-PGF1 alpha increased (colon only, studied).