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Abstract

To evaluate the phytochemical constituents and the aphrodisiac potential of the aqueous extract of Fadogia agrestis (Rubiaceae) stem in male albino rats. The aqueous stem extract of the plant was screened for phytochemical constituents. Male rats were orally dosed with 18 mg/kg, 50 mg/kg and 100 mg/kg body weight, respectively, of the extract at 24 h intervals and their sexual behavior parameters and serum testosterone concentration were evaluated at days 1, 3 and 5. Phytochemical screening revealed the presence of alkaloids and saponins while anthraquinones and flavonoids are weakly present. All the doses resulted in significant increase in mount frequency, intromission frequency and significantly prolonged the ejaculatory latency (P 0.05) and reduced mount and intromission latency (P 0.05). There was also a significant increase in serum testosterone concentrations in all the groups in a manner suggestive of dose-dependence (P 0.05). The aqueous extract of Fadogia agrestis stem increased the blood testosterone concentrations and this may be the mechanism responsible for its aphrodisiac effects and various masculine behaviors. It may be used to modify impaired sexual functions in animals, especially those arising from hypotestosteronemia.
Asian J Androl 2005; 7 (4): 399-404
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- Complementary Medicine -
Aphrodisiac potentials of the aqueous extract of Fadogia agrestis (Schweinf. Ex Hiern) stem in
male albino rats
M. T. Yakubu, M. A. Akanji, A. T. Oladiji
Medicinal Plants Research Laboratory, Department of Biochemistry, University of Ilorin, PMB 1515, Ilorin, Nigeria
Abstract
Aim: To evaluate the phytochemical constituents and the aphrodisiac potential of the aqueous extract of Fadogia
agrestis (Rubiaceae) stem in male albino rats. Methods: The aqueous stem extract of the plant was screened for
phytochemical constituents. Male rats were orally dosed with 18 mg/kg, 50 mg/kg and 100 mg/kg body weight,
respectively, of the extract at 24 h intervals and their sexual behavior parameters and serum testosterone concentration
were evaluated at days 1, 3 and 5. Results: Phytochemical screening revealed the presence of alkaloids and saponins
while anthraquinones and flavonoids are weakly present. All the doses resulted in significant increase in mount
frequency, intromission frequency and significantly prolonged the ejaculatory latency (P < 0.05) and reduced mount and
intromission latency (P < 0.05). There was also a significant increase in serum testosterone concentrations in all the
groups in a manner suggestive of dose-dependence (P < 0.05). Conclusion: The aqueous extract of Fadogia agrestis
stem increased the blood testosterone concentrations and this may be the mechanism responsible for its aphrodisiac
effects and various masculine behaviors. It may be used to modify impaired sexual functions in animals, especially
those arising from hypotestosteronemia. (Asian J Androl 2005 Dec; 7: 399-404)
Keywords: Fadogia agrestis; aphrodisiacs; sexual behavior; testosterone; erectile dysfunction
Correspondence to: Dr M. T. Yakubu, Medicinal Plants Research Laboratory, Department of Biochemistry, University of
Ilorin, PMB 1515, Ilorin, Nigeria.
Tel: +234-803-3578-658, Fax: +234-31-221-593
E-mail: tomuyak@yahoo.com
Received 2004-09-24 Accepted 2005-03-21
DOI: 10.1111/j.1745-7262.2005.00052.x
1 Introduction
Male impotence or erectile dysfunction (ED) is a significant problem that may contribute to infertility [1]. There has been
a worldwide increase in the incidence of ED, probably due to aging populations and other risk factors such as the
presence of chronic illnesses (e.g. heart disease, hypertension, diabetes mellitus), smoking, stress, alcohol, drug abuse
and sedentary lifestyles. ED is defined as the consistent inability to achieve an erection sufficient for the purpose of
satisfactory sexual intercourse, or the inability to ejaculate, or both [2]. Management therapies include the use of
psychotherapy, vacuum devices, surgery, penile implants and drugs [2]. Some of these are too expensive and not
easily affordable.
In many localities in Nigeria, Fadogia agrestis, a shrub with a yellowish stem and leaves, 1-3 feet high, is one of several
plants commonly used in the management of ED [3].
However, the validity of the claimed aphrodisiac activity (the ability to arouse sexual desire [4]) has not been proven
scientifically. This study was carried out to provide information on its acclaimed aphrodisiac properties. Previous
workers [5, 6] had shown that male sexual behavior parameters (mount frequency, mount latency, intromission
frequency, intromission latency and ejaculatory latency) and serum testosterone levels could be used to assess the
aphrodisiac potential of the plant extract, hence these indices were used in the present study.
2 Material and methods
2.1 Animals and reagents
Healthy, sexually experienced, white male albino rats (Rattus novergicus) weighing 270 g-300 g, aged 5-5.5 months
and female albino rats weighing 150 g-180 g, aged 3.5-4 months were obtained from the Small Animal Holding Unit of
the Department of Biochemistry, University of Ilorin, Ilorin, Nigeria. They were kept in well-ventilated house conditions
(temperature: 28 °C-31 °C; photoperiod: 12 h natural light and 12 h dark; humidity: 50 %-55 %) with free access to rat
pellets (Bendel Feeds and Flour Mills Ltd., Ewu, Nigeria) and tap water. Estradiol benzoate was purchased from Sigma
Chemical (St. Louis, USA) and progesterone from Shalina Laboratories (Mumbai, India). The testosterone assay kit was
procured from Immunometrics (London, UK).
2.2 Plant authentication, preparation of plant extract and phytochemical analysis
The plant sample bought from the herb sellers at Kulende Market, Ilorin, Nigeria was authenticated at the Department of
Horticulture and Landscape Technology, Federal School of Forestry, Jos, Nigeria with a voucher number 2:108. The
plant stem was cut into pieces, oven-dried at 40 °C to a constant weight. The dried pieces were then pulverized using
an electric blender (Blender/Miller III, model MS-223, Taiwan, China) and the powder obtained was stocked in a plastic
container from which varying amounts were taken and extracted in distilled water for 48 h at room temperature (26 °C-
28 °C). This was then filtered using filter paper (Whatman No. 1). The filtrate was then concentrated in stem bath and
the resulting brownish black residue was reconstituted in distilled water to give the equivalent dose of 18 mg/kg body
weight (value originated from ethnobotanical survey), while higher doses of 50 mg/kg body weight and 100 mg/kg body
weight were also used in this study. The reconstituted aqueous extract was administered orally using plastic syringes to
all animals in different groups. The aqueous extract was subjected to chemical tests for the qualitative and quantitative
analyses of alkaloids, tannins, phlobatannins, anthraquinones, cardiac glycosides, saponins, cardenolides and
dienolides, phenolics, flavonoids, caffeine, triterpenes and steroids [7, 8].
2.3 Evaluation of male sexual behavior
A total of 60 male rats of proven fertility were housed individually in metabolic cages of dimensions 33.0 cm × 20.5 cm ×
19.0 cm, with cleaning of the cages done once daily. The rats were randomly divided into four groups (A, B, C and D) of
15 animals each. Rats in groups A, B and C were administered with the plant extract (1mL) once daily at 24 h intervals
at the dose of 18 mg/kg, 50 mg/kg and 100 mg/kg body weight respectively. Group D served as the control and
received appropriate volume (1mL) of the vehicle (distilled water) in a similar manner. Five rats from each of the groups
were monitored for sexual behavior after 1, 3 and 5 daily doses respectively.
Sixty female rats were brought to oestrus by the se quential administration of estradiol benzoate (10 µg/100 g) and
progesterone (0.5 mg/100 g) through subcutaneous injections, 48 h and 4 h respectively prior to pairing [9]. Sexual
behavior studies were monitored in a separate room for 2 h following the administration and were given 20 min
adaptation period, after which a primed female was placed in the same cage with the male. On days 1, 3 and 5, sexual
behaviors were monitored, including:
· Mount frequency (MF): the number of mounts without intromission from the time of introduction of the female until
ejaculation.
· Intromission frequency (IF): the number of intromissions from the time of introduction of the female until ejaculation.
· Mount latency: the time interval between the introduction of the female to the first mount by the male.
· Intromission latency: the interval from the time of introduction of the female to the first intromission by the male.
· Ejaculatory latency: the time interval between the first intromission and ejaculation. This is characterized by longer,
deeper pelvic thrusting and slow dismount followed by a period of inactivity [6].
All sexual behavior studies were carried out between 13:00 and 16:00 at room temperature 26 °C-28 °C.
2.4 Testosterone assay
The same set of animals used for sexual behavior parameters were also used for the testosterone assay; the animals
were sacrificed 24 h after the extract dosing. Under ether anesthesia, the neck areas were quickly cleared of fur and
skin to expose the jugular veins. The jugular veins were slightly displaced from the neck region (to prevent
contamination of the blood with interstitial fluid) and then cut with a sharp sterile blade. The rats were made to bleed
into clean, dry corked centrifuge tubes which were left at room temperature for 10 min. After that, the tubes were
centrifuged at 33.5 × g for 15 min using uniscope Laboratory Centrifuge (model SM800B, Surgifriend Medicals,
England).
The sera were thereafter collected using Pasteur pipettes into clean, dry, sample bottles and were then stored frozen
overnight [1] before being used for the testosterone assay.
The serum testosterone concentration was quantitatively determined using the direct human serum testosterone
enzyme immunoassay kit as outlined in the manu- facturer’s protocol. The determination was based on the principle of
direct assay of a limited (competitive) type following the general antibody-antigen reaction based on enzyme linked
immunoabsorbent assay as described by Tietz [10] using Serozyme IÔ Serono (Diagnostics, Freiburg, Germany). The
serum testosterone concentration was then interpolated from a standard calibration curve.
2.6 Statistical analysis
Data were presented as the mean ± SD (n = 5). Statistical analyses used one-way analysis of variance (ANOVA) to
account for the different treatments and were complemented with unpaired t-test. Differences were considered
statistically significant at P < 0.05 [11].
3 Results
3.1 Phytochemical analysis
Phytochemical screening of the aqueous extract of Fadogia agrestis stem showed the presence of alkaloids and
saponins, while anthraquinones and flavonoids are present in a small amount (Table 1). All other phytoche-micals
analyzed were not detected.
3.2 Male sexual behavior
Increase in the sexual vigor of MF (Figure 1) and IF (Figure 2) were observed in all three dosed groups (namely 18
mg/kg, 50 mg/kg and 100 mg/kg body weight) in a dose dependent manner that was statistically significant (P < 0.05)
when compared with the control. By the last day of the experimental period (day 5) in the highest dosed group
(100mg/kg), both MF and IF had increased to 3.7 times of their respective control values. In addition, pre-copulatory
behavior such as anogenital sniffing and nosing were less prominent with the 100 mg/kg body weight group while
chasing was more pronounced. In contrast, the mount latency (Figure 3) and intromission latency (Figure 4) decreased
significantly with the doses and as the experimental period increased (P < 0.05). There was also statistically significant
prolongation of ejaculatory latency (P < 0.05) following the administration of various doses of the plant stem extract
(Figure 5).
3.3 Serum testosterone
The administration of various doses of the plant extract resulted in a significant increase in serum testosterone
concentration throughout the period of administration (P < 0.05). The various doses (18 mg/kg, 50 mg/kg and 100
mg/kg body weight) produced two-, three- and six-fold increases compared with the control by the end of the
experimental period (Figure 6).
4 Discussion
Since many people are now relying on herbal medicines for health care [12], possibly because the other treatment
options available are becoming more expensive and often carry serious side effects, there should be scientific
dissemination of information on the therapeutic efficacy of these plants. The aqueous extract of Fadogia agrestis stem
has been in use by many people in our local population as a means of treating sexual inadequacy and stimulating
sexual vigor even without recourse to the scientific validity of the claim. Aphrodisiacs are substances that enhance sex
drive and/or sexual pleasure or can arouse sexual desire or libido [4]. They are also agents that can be used to modify
impaired sexual functions.
Phytochemical screening can help to reveal the chemical constituents of the plant extract and the one that
predominates over the others. It may also be used to search for bioactive agents for starting products used in the partial
synthesis of some useful drugs [13]. Phytochemical screening of the plant stem showed the presence of major
metabolites of alkaloids and saponins, while anthraquinones and flavonoids are weakly present (Table 1). Saponins
have been implicated as possible bioactive agent responsible for the aphrodisiac effect in Tribulus terrestris extract [6].
The significant increase in the indices of sexual vigor (i.e. mount and intromission frequency [Figures 1, 2]) and the
significant decrease in mount and intromission latencies (Figures 3, 4) are indications of the aphrodisiac potential of
Fadogia agrestis stem extract. In this study, the marked effects on the sexual behavior parameters, compared with the
control, are indications of stimulation in the desire component of sexuality. Apart from the desire that is essential for
initiation of sex, penile tumescence and rigidity as well as the accessory muscles that help in providing additional penile
rigidity and ejaculation are dependent on testosterone for normal sexual activity [6]. Such increase in the frequency of
mount and intromission suggests that libido, sexual vigor and sexual performance were unimpaired [5]. The prolonged
ejaculatory latency indicates enhancement of sexual function and suggests an aphrodisiac action.
It has been documented previously that sexual behavior and erection are dependent on an androgen that may be acting
both centrally and peripherally [14]. Testosterone supplementation has previously been shown to improve sexual
function and libido [15], in addition to the intensity of orgasm and ejaculations which might also be expected to improve
[16]. The continued administration of the plant extract for five days at various doses which led to the significant increase
in serum testosterone may be responsible for the marked effect on sexual behavior indices of the male rats. Increase in
testosterone levels in the present study may thus account for the observed masculine behavior.
Studies have implicated the saponin component of plants in enhancing aphrodisiac properties due to its androgen
increasing property [6]. Saponins present in the aqueous extract of this plant might have assisted in stimulating an
increase in the body natural endogenous testosterone levels by raising the level of leutinizing hormones (LH). This LH
released normally by the pituitary gland helps to maintain testosterone levels; as LH increases, so does the
testosterone [6]. The increase in testosterone seemed to have translated into the male sexual competence observed in
this study. Furthermore, this study suggests that the aphrodisiac action may be mediated through a change in the blood
testosterone level.
In conclusion, results of this study have provided evidence to support the acclaimed role of Fadogia agrestis as an
aphrodisiacs in traditional medicine. It has also provided scientific evidence as to its purported aphrodisiac effect. The
aqueous extract of the Fadogia agrestis stem may be adduced to increase in the testosterone level of the blood, which
may be due to its saponin component. Theaqueous extract of the Fadogia agrestis stem may thus be used to modify
impaired sexual functions in animals, especially those arising from hypotestoster-onemia.
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... These hormonal imbalances may be caused by numerous chemical agents contained in plant extracts. Phytochemical screening has revealed many bioactive as well as toxic chemical substances of plant extracts that can adversely affect the regulation of menstrual/estrous cycle, conception and reproduction of kinds in both humans and animals respectively [27,28]. Alkaloids and flavonoids have been shown to have effect on plasma concentrations of LH, estradiol and FSH [29,30], because they interact with the hormones and alter their activities in various ways. ...
... [37] opined that estrogenic compound (stigmasterol) has an affinity for estrogen receptors and thus leads to infertility in animals. Plants with estrogenic property can directly influence pituitary action by peripheral of LH and FSH, decreasing secretion of these hormones and blocking ovulation [27]. Thus, the decrease in the serum concentration of estradiol may be attributed to a process initiated by aromatase activity or substrate supplementation during estrogen synthesis [38]. ...
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... When measured against sexual carving, these factors decrease. Any elevation of these markers indicates a decline in sexual desire or appetite (Yakubu et al., 2005). The in-vivo studies demonstrated the dose-dependent aphrodisiac effect of AG and improved sexual performance in rats at 150 and 300 mg/kg body wt. ...
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Ethnopharmacological relevance: Processing cow ghee (clarified butterfat) with therapeutic herbs, i.e. ghrita, is recognized for augmenting the therapeutic efficacy of plant materials. Ashwagandha ghrita (AG) is an effective Ayurvedic formulation consisting of Indian ginseng, i.e., Withania somnifera (L.) Dunal is the main constituent used to treat infertility, weakness, gynaecological disorders, and general debility. Objectives: The present investigation was undertaken to corroborate the ethnopharmacological claim of AG as ‘Vajikarana Rasayana’ for its aphrodisiac potential using bioinformatics (in-silico) and experimental (in-vitro and in-vivo) approaches. Methods: AG was formulated as per the methods reported in Ayurved sarsangraha. AG was further subjected to HPLC, GCMS analysis, and biological (acute toxicity and aphrodisiac) assessment per the standard procedures. Thirty-eight bioactives of Indian ginseng were subjected to computational studies (molecular docking and network pharmacology) to confirm the plausible mechanism. Results: AG was found to be safe up to 2000 mg/kg body wt., and it showed dose-dependent upsurge (p<0.01 and p<0.05, wherever necessary) in mount and intromission frequency, genital grooming, and anogenital sniffing at 150 and 300 mg/kg body weight suggesting aphrodisiac activity. In-vitro studies demonstrated significant relaxation of the Corpus Cavernosal Smooth Muscle at all concentrations in a dose-dependent manner. Furthermore, the results of molecular modelling studies were in aggregate with the biological activity and showed interaction with phosphodiesterase-5 as a possible target. Conclusion: AG exhibited an aphrodisiac effect and substantiated the traditional claim of Indian ginseng-based ghrita formulation as ‘Vajikarana Rasayana’.
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The seeds of M. pruriens are widely used for treating male sexual dysfunction in Tibb-e-Unani (Unani Medicine), the traditional system of medicine of Indo-Pak sub-continent. The effect of the powdered seeds on general mating behaviour, libido and potency, was studied in sexually normal male rats. The drug produced a striking and sustained increase of sexual activity.
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The search for an effective aphrodisiac has been a perennial pursuit of most societies throughout history. In the past decade, attention has focused increasingly on the prosexual effects of oral pharmacological agents with central neurotransmitter actions. The role of various dopaminergic, adrenergic, and serotonergic agents, in particular, has been intensively investigated in both human and animal studies. Some of these drugs have been considered for their potential role in the treatment of sexual dysfunction, while others have contributed to our understanding of basic neurophysiological processes in sexual arousal. This review provides a critical evaluation of current laboratory and clinical research on the "new aphrodisiacs," including studies in both patient populations and normal volunteers. Several conceptual and methodological problems are addressed, such as the definition and measurement of sexual response, the need to separate specific and nonspecific drug effects on sexual response, and the lack of studies in women. Although no single drug has proven to be clinically safe and reliably effective for human use, several promising candidates have been identified. Overall, research on prosexual drugs has contributed significantly to our understanding of basic mechanisms in sexual response, as well as providing new treatment options for common sexual disorders.
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While it is generally accepted that the erectile response in mammals is regulated by androgens, the extent of in- volvement and the precise role of these steroids remains to be established. A number of neurotransmitters have been identified that may mediate erectile function, and several research groups are actively investigating how an- drogens may affect the synthesis and action of these agents. This article reviews what is known about the role of androgens in erectile function, the effects of these ste- roid hormones on the activity of some of the neurotrans- mitters that are thought to be involved, and it cites dif- ferent experimental designs and animal models used in the study of erectile physiology. Also discussed is the question of why castration in men is not always followed by the immediate and rapid loss of erectile capacity.
Article
To evaluate the aphrodisiac potential of Tenminalia catappa Linn. seeds using a suspension of its kernel (SS) in 1% methyl cellulose in rats. Male rats were orally treated with 1,500 mg/kg or 3,000 mg/kg SS or vehicle, and their sexual behaviour was monitored 3 h later using a receptive female. Another group of rats was orally treated with either 3,000 mg/kg SS or vehicle for 7 consecutive days. Their sexual behaviour and fertility were evaluated on days 1, 4 and 7 of treatment and day 7 post-treatment by pairing overnight with a pro-oestrous female. The 1,500 mg/kg dose, had a marked aphrodisiac action (prolongation of ejaculation latency) but no effect on libido (% mounting, % intromission and % ejaculation), sexual vigour (mounting-and-intromission frequency), or sexual performance (intercopulatory interval). In contrast, the higher dose (3,000 mg/kg) reversibly inhibited all the parameters of sexual behaviour other than mounting-and-intromission frequency and copulatory efficiency. The effects of high dose SS were not due to general toxicity, liver toxicity, haemotoxicity, stress, muscle deficiency, muscle incoordination, analgesia, hypoglycaemia or reduction in blood testosterone level. They were due to marked sedation. The kernel of T. catappa seeds has aphrodisiac activity and may be useful in the treatment of certain forms of sexual inadequacies, such as premature ejaculation.