Mediterranean Journal of Pharmacy & Pharmaceutical Sciences

www.medjpps.com ISSN: 2789-1895 online ISSN: 2958-3101 print

Original article

Aqueous extract of Hybanthus enneaspermus exhibited aphrodisiac potentials in

fluoxetine-induced sexually-impaired female rats
Muhammad A. Dikwa 1 , Muhammed R. Asinmi 2 , Mansurat B. Falana 3 ,
2*
Quadri O. Nurudeen and Musbau A. Akanji 4
1
Department of Microbiology and Biotechnology, Federal University, Dutse, Nigeria
2
Department of Biological Sciences (Biochemistry Unit), Al-Hikmah University, Ilorin, Nigeria
3
Department of Biological Sciences (Microbiology Unit), Al-Hikmah University, Ilorin, Nigeria
4
Department of Biochemistry, Kwara State University, Malete, Nigeria
*
Author to whom correspondence should be addressed

Received: 20-11-2023, Revised: 04-12-2023, Accepted: 08-12-2023, Published: 31-12-2023

Copyright © 2023 Dikwa et al. This is an open-access article distributed under the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

HOW TO CITE THIS

Dikwa et al. (2023) Aqueous extract of Hybanthus enneaspermus exhibited aphrodisiac potentials in fluoxetine-induced
sexually-impaired female rats. Mediterr J Pharm Pharm Sci. 3 (4): 61-72.
https://doi.org/10.5281/zenodo.10288519

Keywords: Aphrodisiac, fluoxetine, Hybanthus enneaspermus, sexual dysfunction, tadalafil

Abstract: Hybanthus enneaspermus, traditionally used as an aphrodisiac was investigated for its potential to
reverse antidepressant-induced sexual dysfunction in female rats. The aqueous extract was evaluated for
secondary metabolite, amino acid and mineral constituents. Alkaloids, tannins, flavonoids, anthraquinones,
steroids, terpenoids, phenolics, calcium, potassium, sodium, glutamine and leucine are some of its notable
constituents. 60 healthy, sexually responsive female albino rats (144.7±5.9 gm) were divided into six groups (A-
F) of 10 rats each; of which 50 were induced into sexual dysfunction. Rats in group A were administered distilled
water throughout the experimental period and served as a control group, while rats induced into sexual
dysfunction (Groups B-F) by fluoxetine were given water, the reference medication (Tadalafil) and oral doses of
the extract (250, 500, and 1000 mg/kg body weight) once daily for seven days, respectively. When administered
to sexually active rats, fluoxetine significantly decreased the frequency of darting, hopping, lordosis, genital
grooming, and licking behavior by 57.4%, 42.5%, 43.9%, 64.0%, and 41.8%, respectively. However, the latency
of darting, hopping and lordosis were significantly increased by 50.6%, 47.7%, and 54.9%, respectively.
Hybanthus enneaspermus aqueous extract administered at doses of 250, 500, and 1000 mg/kg significantly
reversed fluoxetine-mediated changes in all sexual behavior parameters. The extract's ability to reverse the
characteristics of sexual behavior at 1000 mg/kg was comparable to those of tadalafil-treated rats. Additionally,
all the extract dosages reversed the levels of blood luteinizing hormone, follicle-stimulating hormone,
progesterone, prolactin and estrogen after it has significantly been altered by fluoxetine. The results indicated that
the aqueous extract of Hybanthus enneaspermus improved the proceptive, receptive and orientational behavior of
rats. The extract also enhanced reproductive hormone concentration by restoring sexual competence in sexually-
impaired female rats. The findings of this study provide further evidence in favor of Hybanthus enneaspermus
widespread usage in the management of female sexual dysfunction.

Dikwa et al. (2023) Mediterr J Pharm Pharm Sci. 3(4): 61-72. 61-72
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www.medjpps.com ISSN: 2789-1895 online ISSN: 2958-3101 print

Introduction proportion of the population suffers from sexual

dysfunction [12]. Disorders in sexual desire and
Aphrodisiacs are medicines or herbs that are used to
psychophysiological alterations connected to the
enhance libido, sexual attraction, desire, enjoyment,
sexual response cycle impact around 35.0% of men
behavior and orgasm [1]. Pharmaceutical
and 45.0% of women [13]. Many women turn to
prescriptions such as flibanserin and bremelanotide,
herbal remedies like H. enneaspermus for sexual
which are exclusively authorized for use in
dysfunction because taking medications can be
premenopausal women, are among the several forms
difficult. This predilection stems from several
of aphrodisiac pills that are sold [1]. Varieties of
variables, including affordability, availability, and
lotions and oils that contain components including
the perception that botanicals have few or no
honey, ripe tamarind fruit, black pepper, camphor,
negative effects. There is noticeable lack of scientific
long pepper, and brown jiggery are also used as
experimental support for H. enneaspermus purported
aphrodisiacs [2]. An increase in virility, sexual
aphrodisiac benefits on female libido in the literature,
vigour, and the quality of offspring is acknowledged
despite plethora of research examining the chemical
to be possible with aphrodisiac medications [1].
makeup and pharmacological effects of the plant.
Hybanthus enneaspermus (H. enneaspermus) Linn
F. Muell, commonly called ewe abiwere among the
Yoruba-speaking people of Nigeria, is a traditional Materials and methods
medicinal herb that belongs to the Violaceae plant Plant material and authentication: H. enneaspermus
family [3, 4]. Its native range extends over tropical leaves were obtained from a local market in Ilorin
and subtropical parts of the world, encompassing West local government, Kwara State, Nigeria. At the
Africa, Australia, and Asia, with a concentration in University of Ilorin Herbarium in Ilorin, Nigeria, a
the sultry regions of India. H. enneaspermus is a botanist carried out identification and authentication
perennial plant with hairy twigs, solitary pink spade- to guarantee correctness, while a voucher sample was
shaped flowers, linear-lanceolate leaves, and a deposited under a reference number (UIH 001/1092).
wooden base for the stem. Many commercial Animals: Sixty healthy and in-bred, sexually active,
products made from H. enneaspermus are sold in female Wistar rats (Rattus norvegicus) were obtained
powder or pill form and are natural libido boosters from the local Animal Holding Unit of the
designed to increase female desire and arousal. This Department of Biochemistry, University of Ilorin,
plant possesses a wide range of medicinal properties.
Ilorin, Nigeria. Rats weighed 144.7±5.90 g. The rats
It has been reported to possess anticonvulsant and were housed in clean, well-maintained cages in an
free radical scavenger [5], nephroprotective [6], Animal House at a controlled room temperature (26-
antiarthritic [7], larvicidal [8], hepatoprotective [9], 28°C). They were fed rat pellets and allowed
and male aphrodisiac [10] properties. H. enneas- unlimited access to tap water. The European
permus has also been reported to contain some amino Convention for the Use of Laboratory Animals for
acids and phytochemicals such as flavonoids, Scientific Purposes (ETS-123) and the National
alkaloids, steroids, carbohydrates, saponins, volatile Institutes of Health's (NIH Publication No. 80-23)
oil, and terpenoids [11]. rules were scrupulously followed during the
Fluoxetine (selective serotonin reuptake inhibitor, investigation. The animal care and usage rules of the
SSRI) is a popularly used antidepressant known to institution were strictly adhered to guarantee the
have a high frequency of undesirable sexual effects. animals' welfare and proper treatment during the
Since these adverse effects frequently cause patients investigation.
to stop taking their drug too soon, their depression Preparation of the extract: After thoroughly washing
symptoms are not relieved [12]. A considerable the leaves under running water, they were dried for

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48 hr at 40°C in an oven. The dried leaves were then Treatment protocol: A total of 60 female rats that had
crushed in an electric blender and put into an airtight been acclimated for 2 weeks were split into 6 groups
container for storage. An aqueous solvent was used (A-F), each with 10 rats, in a randomized design. The
to macerate 100 g of the powdered material grouping is as follows; Group A: rats that received
throughout 48 hrs at 27°C. The maceration process 0.5 ml of distilled water, group B: rats induced into
involved frequent shaking and was filtered using sexual dysfunction and administered 0.5 ml of
cheesecloth. A sticky residue was produced after the distilled water, group C: rats induced into sexual
filtrate was subjected to evaporation in a rotary dysfunction and administered 0.5 ml of 20 mg/kg of
evaporator [14]. This residue was reconstituted in tadalafil, group D: rats induced into sexual
distilled water to get the necessary doses of 250, 500, dysfunction and administered 0.5 ml of 250 mg/kg of
and 1000 mg/kg body weight. Information gathered the extract, group E: rats induced into sexual
from an ethnobotanical survey was used to calculate dysfunction and administered 0.5 ml of 500 mg/kg of
the dosages, and 500 mg/kg was used as the most the extract and group F: rats induced into sexual
commonly stated amount. The dosages of 250 and dysfunction and administered 0.5 ml of 1000 mg/kg
1000 mg/kg were chosen to be half and twice the 500 of the extract. The different rat groups were treated
mg/kg estimated dose, respectively, [15]. as described above once daily for seven days using a
plastic oropharyngeal cannula. Observations of
Screening of secondary metabolites: Following the
female sexual behaviour parameters were made
guidelines provided previously [16-20], 5 g of H.
between 17:00 and 21:00 hrs on days 1, 3, and 7.30
enneaspermus extract was diluted in 40 ml of
min. After treatment, the results were recorded in
distilled water. To find out if there were any steroids,
dim light at room temperature.
flavonoids, phenols, tannins, saponins, alkaloids,
terpenoids, cardenolides, and anthraquinones, Preparation of serum: To prepare the serum, the
phytochemical screening. Following identification, procedure as described by Yakubu et al. [32] adhered
the secondary metabolites were subjected to to diethyl ether fumes and was used to anaesthetize
quantitative analysis using established methods for the rats. After cutting their jugular veins, 5 ml of
the quantification of phenols, alkaloids, flavonoids, blood was extracted and put into dry, sterile
terpenoids, steroids, and anthraquinones [21-27]. centrifuge tubes. To give the blood time to coagulate,
the samples were left at room temperature for 15 min.
Induction of sexual dysfunction in female rats and
After centrifuging using the Uniscope Laboratory
assessment of sexual behaviour indices: Following
Centrifuge, for 10 min at 503 × g, a Pasteur pipette
the protocol described by Sarkar et al. [28], fifty
was then used to obtain clear serum. The sera were
female rats were given an oral dosage of fluoxetine
refrigerated before the various hormone tests were
(15 mg/kg, prepared daily in distilled water) to
performed.
induce sexual dysfunction [28, 29]. The rats were
given fluoxetine for 14 days. The male and female Determination of reproductive hormones: The tube-
rats were placed in separate rectangular hardwood based serum enzyme immunoassay (EIA) method
cages with wire mesh tops on the 15th day. For 30 was used to measure the amounts of progesterone
min, mating behaviours were monitored by the (P), follicle-stimulating hormone (FSH), luteinizing
previous guidelines [30-31]. The sexual impairments hormone (LH), estrogen (E), and prolactin (Pl) in the
in female rats were defined as a least 25.0% decrease serum. The method was carried out in full
in the frequency of lordosis, darting, hopping, licking compliance with the manufacturer's instructions
behaviour, and genital grooming and a minimum (Elabscience Biotechnology Company Limited,
25.0% increase in the latency of darting and hopping. Texas, USA).
These rats were then divided into several groups.

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Statistical analysis: After calculating the mean and Table 2: Amino acid composition of H. enneaspermus
standard error of the mean from 10 replicated data Amino acids Conc. (g/100 ml)
points, a one-way analysis of variance (ANOVA) Alanine 6.20
was performed, followed by Dunnett's test to Arginine 5.78
compare every mean of the group with the mean of Asparagine 7.90
Cysteine 4.55
the control using GraphPad Prism version 8.0. Glutamine 10.25
Statistical significance was ascertained, and p < 0.05 Glycine 6.10
was used as the threshold for differences to be Histidine 2.54
deemed significant. Isoleucine 5.75
Leucine 11.88
Lysine 5.03
Results Methionine 1.60
The results of the phytochemical screening of the Phenylalanine 6.40
Proline 4.65
aqueous extract of H. enneaspermus revealed the
Serine 5.35
presence of flavonoids, tannins, phenols, steroids, Threonine 5.45
terpenoids, anthraquinones and alkaloids (Table 1). Tyrosine 4.42
Tannins are the most abundant secondary metabolite Valine 6.15
detected while anthraquinones are the least abundant.
Table 3: Mineral contents H. enneaspermus leaves
Aqueous extract of the H. enneaspermus leaves
contained 17 amino acids with leucine having the Minerals Conc. (mg/100 ml)
highest concentration followed by glutamine, while Calcium 375.00±5.67
methionine was the least abundant in the plant leaf. Chromium 8.30±0.09
Copper 10.75±0.19
In Table 2, further amino acids found include Iron 30.74±21.26
alanine, arginine, asparagine, cysteine, glycine, Argon 5.32±0.02
histidine, isoleucine, lysine, phenylalanine, proline, Magnesium 80.91±1.42
Manganese 18.50±0.38
serine, threonine, tyrosine and valine. Analysis of the Phosphorus 30.24±1.23
mineral constituents of the aqueous extract of H. Potassium 257.51±3.78
enneaspermus leaves revealed the presence of Sodium 160.79±3.07
calcium, chromium, copper, iron, magnesium, Zinc 10.23±0.55
Lead 3.32±0.03
manganese, phosphorus, potassium, sodium and zinc Cadmium Not detected
(Table 3). Calcium was the most abundant whereas Nickel Not detected
Lead was the least abundant. Data are mean±SEM.

Table 1: Secondary metabolites of H. enneaspermus In Table 4, the administration of fluoxetine to

sexually active female rats significantly decreased
Secondary Concentration the darting frequency (DF), hopping frequency (HF),
metabolite (mg/g)
Alkaloids 10.50±0.98 lordosis frequency (LF), genital grooming (GG) and
Tannins 22.70±0.31 licking behavior (LB) by 57.4%, 42.5%, 43.9%,
Flavonoids 20.60±0.71 64.0%, and 41.8% respectively. Whereas, the darting
Anthraquinones 2.80±0.23
latency (DL), hopping latency (HL), and lordosis
Steroids 15.40±0.52
Terpenoids 8.30±0.11 latency (LL) were significantly increased by 50.6%
Phenolics 12.66±0.63 and 47.7%, and 54.9%, respectively. In all the cases,
Saponins Not detected
Cardenolides Not detected the percentage of change was higher than the 25.0%
Cardiac Glycosides Not detected baseline, which suggests that the animals have been
Data are mean±SEM. induced into sexual dysfunction (Table 4).

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Table 4: Sexual behavior parameters of female rats administered fluoxetine

Parameters Control group Fluoxetine-treated rats Percentage change

Darting frequency 9.85±0.12a 4.20±0.09b 57.36#
Hopping frequency 4.35±0.28a 2.50±0.19 b 42.53#
Lordosis frequency 2.85±0.03a 1.60±0.05b 43.86#
Genital grooming 16.25±0.29a 5.75±0.37b 64.00#
Licking behavior 9.10±0.15a 5.30±0.11b 41.76#
Darting latency* 812.15±27.49 a 1222.80±41.67b 50.55+
Hopping latency* 955.20±39.62a 1411.45±29.83b 47.65+
Lordosis Latency* 970.75±73.28a 1505.60±92.15b 54.94+
Data are mean±SEM. Test values with superscripts different from the control down the group for each day and parameter are
significantly different. a is assigned as the mean of the control group while b shows that the mean (of the test group) is significantly
different from the mean of the control), # means percentage reduction in parameter, + means percentage increase in parameters

In Table 5, the administration of fluoxetine the rats throughout the exposure period (Table 6).
significantly decreased the DL, HL and LF of the rats The extract at all doses (250, 500 and 1000 mg/kg)
throughout the exposure period. On the first and third produced a significant increase in the GG and of the
days of treatment, there was no significant difference fluoxetine-treated animals when compared with the
in the DF, HF and LF of the fluoxetine-induced control sexual dysfunction female rats (Table 6). On
sexual dysfunction female rats when compared with day 3 of treatment, the extract at all the doses
the group given 250 mg/kg and 500 mg/kg, however, evaluated (250, 500 and 1000 mg/kg) produced a
there was a significant increase at 1000 mg/kg significant increase in the GG and LB of the
dosage. In contrast, on day 7 of treatment, the extract fluoxetine-induced sexual dysfunction in female rats,
at all the doses evaluated (250, 500, and 1000 mg/kg) while the significant increase by the extract was more
produced a significant increase in the DF, HF and LF profound on day 7 of treatment when compared with
of the fluoxetine-induced sexual dysfunction female the distilled water-treated fluoxetine-induced sexual
rats. Furthermore, treatment of the animals induced dysfunction female rats (Table 6). Furthermore,
into sexual dysfunction with 1000 mg/kg of extract treatment of the rats induced into sexual dysfunction
on day 7 resulted in DF, HF and LF that compared with 1000 mg/kg of extract on day 7 resulted in GG
favorably with the reference drug (tadalafil) and the and LB that compared favorably with the reference
control animals (Table 5). The administration of drug (tadalafil) and the control rats.
fluoxetine significantly decreased the GG and LB of

Table 5: Darting, hopping and lordosis frequencies of female rats induced into sexual dysfunction
by fluoxetine following the administration of H. enneaspermus

Treatments Darting frequency Hopping frequency Lordosis frequency

Day 1 Day 3 Day 7 Day 1 Day 3 Day 7 Day 1 Day 3 Day 7

Control 9.10±0.12a 9.70±0.11a 9.30±0.13a 4.10±0.03a 3.95±0.07a 4.05±0.02a 2.95±0.02a 2.85±0.03a 3.00±0.06a
Fluoxetine-treated 4.90±0.05b 5.50±0.06b 5.20±0.05b 2.30±0.07b 2.20±0.04b 2.40±0.10b 1.75±0.05b 1.95±0.08b 1.95±0.03b
Fluoxetine+tadalafil 6.40±0.06c 7.00±0.07c 8.50±0.08a 2.70±0.10b 3.10±0.05c 4.00±0.03a 2.00±0.07b 2.80±0.02a 3.05±0.07a
Fluoxetin+250 extr. 5.10±0.04b 5.90±0.06b 6.40±0.05c 2.30±0.13b 2.50±0.12b 2.60±0.05b 1.80±0.03b 1.85±0.07b 2.05±0.09b
Fluoxetine+500 extr. 5.20±0.04b 5.80±0.05b 6.60±0.08c 2.40±0.06b 2.70±0.11b 3.10±0.09c 1.95±0.09b 1.90±0.02b 2.50±0.11c
Fluoxetine+1000 extr. 6.15±0.03c 7.35±0.07c 8.90±0.10a 2.90±0.02b 3.25±0.13c 3.75±0.03a 2.05±0.02b 2.70±0.02a 3.10±0.05a
Data are mean±SEM. Test values with superscripts different from the control down the group for each day and parameter are
significantly different. a is assigned as the mean of the control group while b and c showed that the mean (of the test groups) are
significantly different from the mean of the control.

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www.medjpps.com ISSN: 2789-1895 online ISSN: 2958-3101 print

Table 6: Genital grooming and licking behavior of female rats induced into
sexual dysfunction by fluoxetine following intake of H. enneaspermus
Treatments Genital grooming Licking behavior
Day 1 Day 3 Day 7 Day 1 Day 3 Day 7

Control 16.20±0.29a 14.90±0.24a 16.40±0.31a 9.40±0.12a 9.70±0.14a 9.10±0.09a

Fluoxetine-treated 5.70±0.05b 5.30±0.08b 5.60±0.06b 5.20±0.03b 5.80±0.04b 5.60±0.04b
Fluoxetine+Tadalafil 9.50±0.06c 11.70±0.08c 15.10±0.17a 5.50±0.03b 7.60±0.04c 9.70±0.08a
Fluoxetin+250 extr. 7.00±0.05d 8.80±0.06d 11.10±0.08c 5.30±0.05b 6.10±0.03b 7.40±0.06c
Fluoxetine+500 extr. 7.90±0.05d 10.10±0.06c 13.10±0.13c 5.50±0.04b 7.30±0.05c 8.70±0.05c
Fluoxetine+1000 extr. 10.30±0.06c 12.60±0.15c 16.70±0.23a 5.30±0.03b 7.30±0.04c 9.00±0.06a

Data are mean± SEM. Test values with superscripts different from the control down the group for each day and parameter are
significantly different. a is assigned as the mean of the control group, while b and c showed that the mean (of the test groups)
are significantly different from the mean of the control.

In Table 7, the administration of fluoxetine extract at all the doses evaluated (250, 500 and 1000
significantly increased the DL and HL of the animals, mg/kg) produced a significant decrease in the DL and
when compared with the control rats. On day one of HL of the sexual dysfunction female rats, when
treatment, the doses of 500 and 1000 mg/kg produced compared with the distilled water-treated fluoxetine-
a significant decrease in the DL and HL of the induced sexual dysfunction female rats. The decrease
animals induced into sexual dysfunction by produced by 1000 mg/kg at day 7 compares
fluoxetine when compared with the distilled water- favorably with the reference drug (tadalafil) as well
treated fluoxetine-induced sexual dysfunction female as the control rats.
rats. Furthermore, on days 3 and 7 of treatment, the

Table 7: Darting and hopping latencies of female rats induced into sexual dysfunction
by fluoxetine following the administration of H. enneaspermus
Treatments Darting latency Hopping latency
Day 1 Day 3 Day 7 Day 1 Day 3 Day 7
Control 855.80±14.76a 878.20 ±15.62a 861.40±13.89 a 913.40±11.24a 941.70±11.35a 934.20±11.02a
Fluoxetine-treated 1289.60±22.03b 1275.20±21.28b 1247.30±20.15b 1443.70±18.01b 1481.90±17.05b 1439.50±16.83b
Fluoxetine+tadalafil 1132.50± 18.74c 980.90±17.46c 899.20±15.75a 1131.40±16.38c 1093.20±14.12c 946.80±12.16a
Fluoxetin+250 extr. 1275.40±20.31b 1115.70±16.84d 1041.80±14.22c 1352.60±17.44b 1265.80±15.23d 1136.90±14.68c
Fluoxetine+500 extr. 1178.00±18.61c 1082.50±14.92d 967.30±12.21c 1315.60±17.28b 1148.90±15.31d 1024.60±13.36c
Fluoxetine+1000 extr. 1029.60±16.13c 966.90±12.49c 892.10±11.34a 1124.50±16.82c 1039.40±11.89c 954.70±10.98a
Data are mean±SEM. Test values with superscripts different from the control down the group for each day and parameter are
significantly different. a is assigned as the mean of the control group, while b, c and d showed that the mean (of the test groups)
are significantly different from the mean of the control.

In Table 8, administration of fluoxetine to sexually group administered 1000 mg/kg of the extract, and
active female rats significantly reduced the levels of compared favorably, both with those administered
P, FSH, LH, and E by 25.4%, 33.6%, 41.3%, and the reference drug (tadalafil) and those of the control
39.5%, respectively, while the levels of Pl increased group. The elevated level of prolactin in the
significantly by 58.6% when compared with the fluoxetine-treated animals was significantly
distilled water treated rats. The reduced levels of the decreased following the administration of all the
hormones in the fluoxetine-treated animals were doses (250, 500 and 1000 mg/kg) of the aqueous
significantly increased following the administration extract of H. enneaspermus, when compared with the
of the aqueous extract of H. enneaspermus, and the distilled water-treated fluoxetine-induced sexual
significant increase was more pronounced in the dysfunction female rats.

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Table 8: Concentrations of reproductive hormones of female rats induced into sexual dysfunction
by fluoxetine following the administration of H. enneaspermus
Treatment Progesterone Follicle Stimulating Luteinizing Hormone Estrogen Prolactin
(nmol/L) Hormone (mIU/mL) (mIU/mL)
Control 47.28±0.74a 1.28±0.03a 7.92±0.21a 20.12±0.68a 1.57±0.04a
Fluoxetine-treated 35.24±1.15b 0.85±0.02b 4.65±0.05b 12.09±0.8b 2.49±0.02b
(25.42%) (33.59%) (41.25%) (39.85%) (58.60%)
Fluoxetine+tadalafil 45.35±1.09a 1.31±0.05a 6.18±0.12a 19.79±0.07a 1.69±0.07a
Fluoxetin+250 extr. 37.42±0.19b 1.07±0.03c 5.71±0.28c 15.82±0.76c 2.10±0.02c
Fluoxetine+500 extr. 40.56±1.34c 1.19±0.05a 6.78±0.57c 16.75±0.42c 1.68±0.14a
Fluoxetine+1000 extr. 46.32±1.39a 1.29±0.05a 7.20±0.32a 19.35±0.47a 1.50±0.06a
Data are mean±SEM. Test values with superscripts different from the control down the group for each hormone are significantly
different. a is assigned as the mean of the control group, while b and c show that the mean (of the test groups)
are significantly different from the mean of the control.

Discussion limonene are perhaps the most well-known

compounds that have been linked to increased libido
Numerous plants are proven to increase libido,
and sex drive [39]. Numerous chemicals, including
sexual potency, and/or sexual pleasure, which may
resveratrol and lignans, are phenolic compounds and
have an impact on sexual functioning [33].
can have an impact on sexual functions [40].
Secondary metabolites produced by plants act
Resveratrol is a polyphenol found in red wine,
peripherally by increasing nonadrenergic/nonchol-
grapes, and berries that has been shown to improve
inergic neurotransmitters, such as nitric oxide (NO)
sexual function [41]. Other phenolic-rich extracts
and vasoactive intestinal polypeptide, which are
have been reported to enhance sexual function in
involved in smooth muscle relaxation and improved
animal studies [42]. Phenolics support healthy blood
genital blood flow [34]. Alkaloids as yohimbine, can
vessel dilation and sexual function by avoiding
function as α-2 adrenergic receptor antagonists and
oxidative damage to the NO molecule, which helps
stimulate norepinephrine release, enhancing the
sustain NO. Some phenolics have the potential to
female rats' arousal and sexual desire. Some
behave as phytoestrogens, which can affect
alkaloids cause vasodilation, which relaxes blood
hormonal balance and improve sexual function [42].
vessels in the vaginal region and improves blood
flow to this crucial part of the female rats' copulatory Protein (amino acids) makes up a sizable component
system [35]. Antioxidants named tannins help to of our body's cells, muscles, and reproductive system
maintain NO, which is necessary for healthy vaginal tissues [43]. When arginine is converted to citrulline
blood flow and appropriate blood vessel dilatation by NO synthase, NO, an active free radical, is
for erotic enjoyment and performance [36]. Although created. Arginine can boost sexual desire and
flavonoids are known for their antioxidant qualities, improve sensitivity to sexual stimulation by boosting
they improve sexual health. They can prevent free blood flow to the reproductive area [44]. These
radicals from degrading NO, maintain sustained NO improve the sense of sexual stimulation and increase
for effective vascular relaxation, and enable regular desire with the potential of reaching orgasm [45]. In
vaginal lubrication and sexual performance [37]. By addition, it has been reported to enhance healthy
altering the balance of sex hormones (testosterone uterine function during implantation, boost cervical
and estrogen), several plant steroids can affect sexual mucus, and support endometrial secretions [46].
function through hormonal control, potentially Protein synthesis requires asparagine, especially for
enhancing sexual desire and performance [38]. producing structural proteins which are essential for
Certain terpenoids can affect neurotransmitters, preserving the structural and functional integrity of
thereby, enhancing mood and mental arousal and reproductive tissues and organs [47]. Dietary
enhancing sexual pleasure. The terpenes, linalool and minerals work as supplements and are essential for a

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variety of complex biological processes, including difficulty in eliciting orgasm, and diminished sexual
hormonal, enzymatic, and neurological responses enjoyment, can occur when fluoxetine upsets this
that are necessary for a healthy sex life [48]. The equilibrium by raising serotonin levels while
contraction of muscles, particularly the muscles decreasing other neurotransmitters [52]. The
utilized for sexual activity, depends critically on reduction in GG, HF, LF, DL, and HL, as well as the
calcium. It directly impacts the muscular contraction increase DL and HL may be signs that the rats have
apparatus and causes muscle contraction by its been induced by sexual dysfunction. The proceptive
interaction with regulatory proteins, including the phase, which is characterized by actions like DL and
troponin system [49]. Muscle contraction, HL, is the initial behavior of a female rat to initiate
particularly those of the muscles used for sexual sexual interaction, whereas the receptive phase,
activity, depends on calcium and potassium. It assists which is characterized by lordosis is a useful
in the rhythmic contractions that take place during indicator in the assessment of libido, sexual vigor,
orgasm and sexual desire. arousability, performance, and motivation [52].
Following the administration of fluoxetine, female
Fluoxetine is commonly prescribed to treat bulimia,
rats' sexual behaviors were reduced, which is a sign
premenstrual dysphoric, and major depressive
of lower libido. This decline is probably due to the
disorders. Fluoxetine has antidepressant action in
neurotransmitter systems being affected by
mice by a significant reduction in the duration of the
fluoxetine. The balance of serotonin is frequently
immobility time and enhanced swimming [50]. It
disturbed by fluoxetine. Because fluoxetine
aids in the restoration of a more balanced
indirectly reduces the mesolimbic dopaminergic
neurotransmitter profile, which can lessen the signs
pathway, which is essential for motivation and
and symptoms of depression by boosting the
reward. In addition, serotonin's inactivity effect on
availability of serotonin [51]. More than one-third of
norepinephrine neurotransmission mediated by 5-
women using fluoxetine for therapeutic purposes
HT1A receptors might also contribute to decreased
may experience sexual dysfunction as a result of
arousal and libido, which together impair sexual
consuming fluoxetine, thus, may experience libido
desire and responsiveness in female animals [53].
loss, anorgasmia, and/or decreased vaginal
When compared to rats treated with fluoxetine, the
lubrication. Although the mechanisms underlying
observed reversal of sexual behavior indices in
drug-induced sexual dysfunction in females are still
female rats after extract intake suggested that the
unclear, it is thought to be connected to the complex
effects of the extract gradually improved sexual
neural and endocrine loops in the female
behavior. This improvement might be a result of the
reproductive cycle. Elevated serotonin can affect
extract's capacity to control the mesolimbic
sexual function by inhibiting some
dopaminergic system's dopamine. This might be
neurotransmitters. Sensations of arousal and desire
accomplished either by boosting dopamine uptake or
are known to be correlated with dopamine and
by antagonistically interacting with serotonin
norepinephrine. Overproduction of serotonin can
subtype-2 receptors, which would then enable the
diminish norepinephrine and dopamine, hence
suppression of the serotonin-induced drop in
lowering desire and sexual arousal, thus, noted to
dopamine downstream. The reduction of NO
lessen genital sensation. This loss of sensation might
generation in female genital tissue in fluoxetine-
make it difficult to have orgasms and sexual pleasure.
treated rats may result in poor vaginal smooth muscle
A crucial chemical in sexual response is NO. NO,
relaxation, affecting genital sensitivity and arousal
which helps with blood flow to the vaginal region can
[54]. The ability of the extract to reduce significantly
be inhibited by high levels of serotonin making it
the HL and DL in female rats with sexual dysfunction
difficult to establish and maintain arousal. A variety
showed that it improves sexual arousability,
of sexual side effects, including lower libido,

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 Mediterranean Journal of Pharmacy & Pharmaceutical Sciences
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enthusiasm, vigor, and receptivity. The fact that the It might help the release of eggs from ovarian
extract was able to enhance the quantity of genital follicles, which would aid in ovulation or begin the
licking and grooming behaviors in female rats with process of transforming the remaining ovarian
sexual dysfunction suggests that they had increased follicles into corpus luteum organs. The corpus
propensity and responsiveness. luteum generates progesterone, which is crucial for
preparing the uterine lining for potential implantation
Hormonal indicators of female sexual behavior
[56]. On the other side, increased Pl has been linked
include P, LH, FSH, E, and Pl [55]. The effect of
to lower levels of reproductive hormones, possibly as
fluoxetine on the hypothalamic-pituitary-gonadal
a result of dopamine, a neurotransmitter that plays a
(HPG) axis may explain the marked decrease in
role in sexual excitement, being partially
reproductive hormones that were observed in
counteracted. This explains why fluoxetine-induced
fluoxetine-induced sexual dysfunction in female rats.
sexual dysfunction in female rats increased Pl. The
Fluoxetine's impact on the serotonergic system
significant decrease in Pl that occurred after the
interferes with the hypothalamic release of
administration of H. enneaspermus may help to
gonadotropin-releasing hormone, which in turn
improve female sexual behavior by releasing
affects the HPG axis causing reduced secretion of the
gonadotropin-releasing hormone, stimulating the
pituitary hormones, which are crucial for controlling
pituitary gland to secrete more sex hormones, and
the generation of sex hormones. The gonads may be
possibly resuming normal reproductive function.
directly impacted by the disruption of this hormonal
balance, which would also result in less P and E
Conclusion: The findings revealed that the aqueous
being produced. The subsequent reversal in serum P
extract of H. enneaspermus can improve various
and E levels in sexually dysfunctional female rats
aspects of sexual behavior, including proceptive,
treated with H. enneaspermus extract may be due to
receptive, and orientation behaviors. This result
the extract's possible modulatory actions on the HPG
compares favorably with the reference drug used in
axis. By possibly altering the expression of E
the study, highlighting the extract's potential as a
receptors, improving vaginal lubrication, and easing
management option for sexual dysfunction in
the transition of the uterine lining to a receptive state,
females. It is noteworthy that the extract's
these actions may help to restore normal hormonal
effectiveness in reversing sexual impairment in
levels and therefore increase female sexual
fluoxetine-treated female rats was most pronounced
receptivity. Following treatment with H.
at the highest dose. Thus, it presents evidence to
enneaspermus leaves, LH and FSH increased in
support the traditional usage of H. enneaspermus for
sexually dysfunctional animals. These changes might
the management of female sexual inadequacies.
have a variety of impacts on the reproductive system.

Acknowledgments: The authors are grateful to Mr. Dele Aiyepeku (Phytomedicine, Toxicology & Reproductive Biochemistry
Research Laboratory, Department of Biochemistry, University of Ilorin, Ilorin 24003, Nigeria) for the technical assistance provided
during this study.
Author contribution: QON and MAA conceptualized the work and drafted the manuscript. MAD, MRA and MBF carried out
the experiment and data analysis. All authors participated in the preparation as well as the revision of the manuscript. All authors
approved the final version for publication.
Conflict of interest: The authors declare the absence of any commercial or financial relationships that could be construed as a
potential conflict of interest.
Ethical issues: Including plagiarism, informed consent, data fabrication or falsification, and double publication or submission have
completely been observed by authors.
Data availability statement: The raw data that support the findings of this article are available from the corresponding author upon
reasonable request.
Author declarations: The authors confirm that all relevant ethical guidelines have been followed and any necessary IRB and/or
ethics committee approvals have been obtained.

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www.medjpps.com ISSN: 2789-1895 online ISSN: 2958-3101 print

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