ERECTILE DYSFUNCTION: THERAPEUTIC POTENTIALS OF HERBAL

PHOSPHODIESTERASE V INHIBITORS

BY

TOLUSE KEHINDE PEACE

MATRIC.NO: 16BC1051

A SEMINAR WORK SUBMITTED TO THE DEPARTMENT OF

BIOCHEMISTRY, KOGI STATE UNIVERSITY,
ANYIGBA, KOGI STATE.

IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE AWARD OF

BARCHELOR IN SCIENCES (BS.C) DEGREE IN BIOCHEMISTRY

SEPTEMBER 2019

SUPERVISOR: MR IDAKWOJI P.A

 CERTIFICATION
This is to certify that this Seminar work titled: ‘ERECTILE DYSFUNCTION:
THERAPEUTIC POTENTIAL OF HERBAL PHOSPHODIESTERASE V INHIBITORS’
was carried out by TOLUSE KEHINDE PEACE with the matriculation number: 16BC1051
meets in partial fulfillment of the requirements for the award of Bachelor of Science (B.Sc)
degree in Biochemistry, Natural Sciences, Kogi State University, Anyigba and is approved for its
contribution to knowledge and literary presentation.

Mr. Idakwoji P.A …………………………

(Seminar Supervisor) Signature/ Date

…………………………
(Seminar Coordinator) Signature/ Date

Prof . Eniola .J. Olajide …………………………

(Head of Department) Signature/ Date
 DECLARATION
I hereby declare that this project work was carried out by me: TOLUSE KEHINDE PEACE with
Matric No: 16BC1051 and supervised by Mr. IDAKWOJI P.A for the award of Bachelor in
Sciences Degree (BS.c) Biochemistry, Kogi State University, Anyigba, Kogi State.

------------------------------ ------------------------------
Sign Date
 DEDICATION
This seminar work is dedicated to Almighty God, who has been the reason for my successful
academic pursuit and also to my parents and siblings for their moral, financial and spiritual
support.
 ACKNOWLEDGEMENT
This seminar work was done in partial fulfillment of the requirements for the award of bachelor
in sciences (BS.c) degree in biochemistry
. Therefore, I deem it necessary to acknowledge and appreciate some persons that have
contributed in one way or the other to the success of this seminar work.
My profound gratitude goes to Almighty God for his faithfulness, grace and favour.
I wish to sincerely express my profound gratitude to my able supervisor, Mr Idakwoji P.A for his
constant availability in supervising this work. My sincere gratitude goes to my HOD, Dr. Eniola
J. Olajide and to all my lecturers for their tireless effort.
I must acknowledge the effort of my parents, Mr. and Mrs. Emmanuel Toluse whose spiritual,
financial and moral support I have enjoyed in the period of my study. And I appreciate the effort
of my siblings for their support.
My profound gratitude also goes to the following persons who were of great help and support to
me Dr Yemisi Alepa and her family, Major and Mrs. Adama.
I also appreciate my friends Kehinde Oluwatobi and Owoloja Mary to mention a few.
I will like to appreciate my course mates and the entire members of the department of
biochemistry.
 ABSTRACT
This study was carried out to determine therapeutic potentials of herbal phosphodiesterase V
inhibitors on erectile dysfunction.
The use of plants or plant-based products to stimulate sexual desire and to enhance performance
and enjoyment is almost as old as the human race itself. The present paper reviews the active,
natural principles of plants which have been useful in treating erectile dysfunction, having
potential for improving sexual behaviour and performance, and are helpful in spermatogenesis
and reproduction. The present paper provides an overview of herbs and their active molecule
with claims for improvement of sexual behaviour .
Aphrodisiacs are required to improve male sexual function under stressful conditions.
Phosphodiesterase inhibitors (PDEIs) are a class of drugs that are widely used because of their
various pharmacological properties including cardiotonic, vasodilators, smooth muscle relaxant,
antidepressants, antithrombotic, bronchodilator, antiflammatory and enhancer of cognitive
function. In recent years, interest in drugs of plant origin has been progressively increased. Some
pharmacologically active substances that come from plants demonstrate PDEI activity. They
mainly belong to alkaloids, flavonoids, and saponins. In this present paper, studies on herbal
PDEI were reviewed and their possible therapeutic applications were discussed.
TABLE OF CONTENT
Title page
Certification
Declaration
Dedication
Acknowledgement
Abstract
Table of content
CHAPTER ONE
1.0 Introduction
1.1 Signs and symptoms of erectile dysfunction
1.2 Phosphodiesterase: Potential therapeutic applications and recent progress in drug
development.
CHAPTER TWO
2.0 Brief history and discussion on phosphodiesterase V enzymes.
2.1 Phosphodiesterase V inhibitors as vasodilators.
2.2 Herbal phosphodiesterase V inhibitors:
2.2.1 Allium sativum (Garlic)
2.2.2 Tribulus terrestris (Goat head)
2.2.3 Ocium gratissimum (Scent leaf)
2.2.4 Moringa oleifera (Moringa)
2.2.5 Hibiscus sabdariffa (Roselle)
CHAPTER THREE
3.0 Contraindications of phosphodiesterase V inhibitors.
3.1 Precautions
CHAPTER FOUR
4.0 Conclusion
4.1 Recommendation
REFERENCES

CHAPTER ONE

1.0 INTRODUCTION
Erectile dysfunction (ED) is a common sexual-arousal disorder primarily affecting men
over the age of 40 years. ED is clinically defined as the inability to attain or maintain a penile
erection sufficient for sexual intercourse.
Studies have suggested that men often underreport ED because of embarrassment or lack of
awareness of medical causes. Therefore, optimal nonpharmacologic and or pharmacological
treatment for ED is necessary.
Phosphodiesterase inhibitors block one or more of the five subtypes of the enzyme
phosphodiesterase (PDE), thereby preventing the inactivation of the intracellular second
messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate
(cGMP) by the respective PDE subtype(s). During a normal erection, parasympathetic
stimulations leads to nitric oxide (NO) release from endothelial cells within the penis.
After sexual stimulations, NO concentration is significantly increased and contributes to
the conversion of guanosine triphosphate to cyclic guanosine monophosphate (cGMP).
Downstream cGMP decreases intracellular Ca2+ (calcium ions) in the cavernosal smooth
muscles, leading to smooth-muscle relaxation. Once relaxed, the smooth muscle collapses the
veins, which causes reduced drainage of arterial blood, thus sustaining an erection. Given the
complexity and regulated coordination of this process, multiple aetiologies may contribute to the
inability to attain or maintain a penile erection sufficient for intercourse.

1.1 SIGNS AND SYMPTOMS OF ERECTILE DYSFUNCTION

 Trouble getting an erection
 Reduced sexual desire
 Trouble keeping an erection
PHYSICAL CAUSES OF ERECTILE DYSFUNCTION
 Heart disease
  Obesity
 Surgeries or injuries that affect the pelvic area or spinal cord
 Clogged blood vessel (Atherosclerosis)
 High cholesterol
 Alcoholism
 High blood pressure
 Sleep disorder
 Diabetes
 Tobacco use
 Metabolic syndrome
 Parkinson’s disease
 Peyronie’s disease

PHYSIOLOGICAL CAUSES OF ERECTILE DYSFUNCTION

 Depression
 Stress
 Anxiety or other medical health conditions.
PREVENTION
The best way to prevent erectile dysfunction is to make healthy lifestyle choices and to manage
any existing health conditions. For example:
Work with your doctor to manage diabetes, heart disease or other chronic health conditions.
See your doctor for regular check-ups and medical screening tests.
Stop smoking, limit or avoid alcohol, and don’t use illegal drugs.
Exercise regularly.
Take steps to reduce stress.
Get help for anxiety, depression or other mental health concerns.
MEDICATION SUMMARY
A growing array of medication are available to assist in the management of erectile dysfunction
(ED). An ideal agent would be rapidly effective, easy to administer, affordable, applicable to a
wide range of patients, and minimally toxic. The types of medication can be divided, into oral,
tropical, injectable, and intraurethrally inserted.
Phosphodiesterase type 5 (PDE5) inhibitors are the principal oral agents used in erectile
dysfunction.
1.2 PHOSPHODIESTERASE:POTENTITIAL THERAPEUTIC APPLICATIONS AND
RECENT PROGRESS IN DRUG DEVELOPMENT.
Phosphodiesterase (PDEs) are essential regulators of cyclic nucleotide signalling with
diverse physiological functions, they are a super family of enzymes that degrade cyclic
adenosine monophosphate (cAMP) and cyclic guanine monophosphate (cGMP)
PDEs have become recognized as important drug targets for the treatment of various diseases,
such as heart failure, depression, asthma, inflammation and erectile dysfunction. Because of their
great market potential and therapeutic importance, PDEs inhibitors became recognized as
important therapeutic agents in the treatment of various diseases.
Three-dimensional (3D) structures of catalytic domains of PDE 1, -3, -4, -5 and -9 in the
presence of their inhibitors are now available, and are utilized for rational drug design.
As the intracellular concentration of the cyclic nucleotides rise, they bind to and activate
their target enzymes, protein kinase A (PKA) and protein kinase G (PKG). This protein kinase
phosphorylate substrates such as ion channels, contractile potential and transcription factors,
which regulate key cellular functions, Phosphorylation alters the activity of these substrates and
thus change cellular activity. Obviously, altering the rate of cyclic nucleotide formation or
degradation will change the activation state of these pathways.
CHAPTER TWO
2.O BRIEF HISTORY AND DISCUSSION ON PHOSPHODIESTERASE V ENZYME
INHIBITORS
In the mid-1980s, the association between NO and the PDE family sparked an increase in
drug innovation. The numerous physiological effects of NO had dramatic implications for a
number of diseases. The PDE enzyme is ubiquitous in the body, with 11 distinct recognized
isoenzymes expressed in different concentrations in various tissues. The PDE enzyme is
widespread but more prevalent in penile tissue. Nonselective PDE inhibitors e.g theophylline
were used prior to the discovery of the link between NO and PDEs, but selective PDE inhibitors
were not yet developed.
Since then, a number of selective PDE inhibitors have been approved to treat a variety of
disorders ranging from ED to pulmonary hypertension. Sildenafil (VIAGRA) was first studied in
clinical trials for coronary heart disease in 1991, but the drug serendipitously had favourable
effects on penile erection. By 1998, Viagra was FDA-approved as the first oral treatment of ED.
As realization of the market potential for oral PDE5 inhibitors dawned, pharmaceutical
companies set out to make new products and improvements. Different potencies, duration of
action, and onsets of action played into the creation of alternative PDE5 inhibitor therapies,
resulting in the approval of Cialis, Levitra, and Stendra for treatment of ED. In 2008, Cialis
earned the first market approval for once-daily dosing, which may appeal to individuals desiring
more spontaneity. Although Viagra’s patent was extended to 2020, Pfizer entered the agreement
with a generic manufacturer to the market sildenafil in 2017, making this drug the first generic
PDE5 inhibitors. Generic versions of both Cialis and Levitra were introduced in 2018.
Oral PDE5 inhibitors remain a first-line pharmacological treatment.
The figure below illustrates the general course of therapy of ED which begins with a curable
aetiology, such as primary testicular failure or secondary pituitary\hypothalamic causes.
 Beyond the curable causes of ED, lifestyle modification through risk-factor reduction and
education remains paramount. In addition to these nopharmacologic standards, the use of PDE5

inhibitor is the standard medical treatment following shared decision-making agreement.

Assessment of treatment options includes a patient-focused discussion incorporating information
about risk factors and lifestyle needs. Treatment options should be tailored to patient and partner
satisfaction, quality of life factors, and treatment
2.1 PHOSPHODIESTERASE V INHIBITORS AS VASODILATORS
Some agents injected directly into the penis exert their relaxant effect directly on the
smooth muscle of the corpora cavernosa. They can be used alone or in combination with other
medications.
The most commonly used agents are alprostadil (prostagladins E1) {PGE1}, papaverin, and
phentolamine. The optimal dosages and the most effective combination of these agents must be
determined on a case-by-case basis. These medications can be obtained as commercial
preparations or can be formulated according to the physician’s request by compounding
pharmacies. Patients can be supplied with vials of a single agent or a combination of agents
mixed in a single vial and instructed in the proper technique for administration.
PDE5 is cGMP-specific and is a major cGMP-hydrolysing enzyme in the vascular
smooth muscle of the penis. PDE5 inhibitors rely on the role of nitric acid (NO) in inducing
vasodilation. NO relaxes the smooth muscle of the corpora cavernosa peripherally by stimulating
guanylyl cyclase activity, which results in increased cGMP levels; inhibition of PDE5 increases
intracellular concentrations of cGMP , which in turn induces vasodilation.
Available PDE5 inhibitors include sildenafil, vardenafil, tadalafil, and avanafil. These agents do
not directly cause penile erections but affect instead the response to sexual stimulations.
Sildenafil was the first to be approved, avanafil the most recent. Although all of these agents
inhibit PDE5, the newer drugs in the class are significantly more selective in their inhibition.
2.2 HERBAL PHOSPHODIESTERASE V INHIBITORS
2.2.1 Allium sativum (Garlic)
Garlic is a herb which belongs to lily family. Although garlic powder (mixed with salt) is
considered as spice. All parts of a garlic plant like the bulb, root, leaf and flowers have herbal
quality and used as medicine for several remedies. Garlic is used in treating diabetes, high blood
pressure and prevention of hardening and narrowing of the arteries which is one of the causes of
Erectile dysfunction, garlic also reduces blood sugar level and blood cholesterol levels which are
the direct causes of Erectile dysfunction if not checked.
As people get older, the arteries in the body begin to lose their ability to dilate, which can impede
blood flow. This is due, in part, to a reduction in the production of an enzyme known as nitric
oxide synthase, or NOS. Garlic contains nitric oxide synthase, an enzyme that plays a big role
the mechanism of an erection, and garlic has been shown to stimulate nitric oxide synthase
production, notes Health Guidance. The evidence however is sparse and more studies should be
conducted to verify the effectiveness of nitric oxide synthase from garlic and its effect on
impotence in humans. Polysulfides, which are the compounds in garlic boost H2S production.
Garlic’s ability to relax blood vessels improves circulation, which indirectly contributes to
lessening impotence.
Despite the long tradition of using garlic as a medicinal herb, pharmacists only started to
investigate its constituents in the 20th century. Agarwal (1996) reported a description of Allium
sativum exhibiting antithrombotic actions which include: alliin, ajoene, amino acid glycosides,
adenosine, adenosine deaminase inhibitor and cyclic AMP phosphodiesterase inhibitor.

2.2.2 Goat head (Tribulus terrestris)

Tribulus terrestris is a flowering plant in the family Zygophyllaceae. It is commonly
called devil’s thorn, puncture vine, caltrop, yellow vine and goat head. It is a common herb in
Nigeria. Tribulus terrestris is a plant that has been used for a variety of potential health benefits
for many years. It is popular as a general health supplement and as an ingredient in testosterone
booster supplements. Many of today's popular dietary supplements come from plants that have
been used medicinally since ancient times.
One of the health benefits of Tribulus terrestris includes altered hormone levels and increased
sexual function and libido, It grows in many places, including parts of Europe, Asia, Africa and
the Middle east. Both the root and fruit of the plant have been used medicinally in Traditional
Chinese Medicine and Indian Ayurveda.
 Today, Tribulus terrestris is widely used as a general health supplement, as well as in
supplements that claim to increase testosterone levels .
Summary: Tribulus terrestris is a plant that has been used for a variety of potential health
benefits for many years. It is popular as a general health supplement and as an ingredient in
testosterone booster supplements although it may affect heart health and blood sugar level.
Although people often take Tribulus terrestris for its potential effects on sexual function and
testosterone, it has also been studied for other important effects, animal studies have also shown
that Tribulus terrestris may reduce blood sugar levels, help protect against blood vessel damage
and help prevent increases in blood cholesterol, a quick online search for Tribulus terrestris
supplements shows that many products made with the plant are focused on boosting testosterone.
Tribulus Terrestris may enhance libido, even though this supplement may not increase
testosterone, it may boost libido some researchers found that when men with reduced sex drives
consumed 750–1,500 mg of Tribulus terrestris daily for two months, their sexual desire increased
by 79% also, 67% of women with very low libidos experienced increased sexual desire after they
took supplements of 500–1,500 mg for 90 days. However, studies in men with erectile
dysfunction have yielded mixed results some research shows that taking 800 mg of this
supplement per day may not effectively treat erectile dysfunction however, other reports showed
significant improvements in erections and sexual satisfaction with a dose of 1,500 mg per day
While it seems that Tribulus terrestris may improve libido in women and men, more research is
needed to clarify the extent of the sexual effects of this supplement. This may be partly due to
the herb’s reputation as a testosterone enhancer, though research shows it may not actually live
up to these claims.
Studies investigating its potential blood sugar-lowering effect used 1,000 mg per day,
while research examining libido enhancement used doses from 250–1,500 mg per day, Other
studies prescribed dosages relative to body weight. For example, several studies have used doses
of 4.5–9 mg per pound (10–20 mg per kg) of body weights, so if you weighed about 155 pounds
(70 kg), you might take a dose of 700–1,400 mg per day.
Saponins are chemical compounds found in Tribulus terrestris, and they are thought to be
responsible for its health benefits. Many supplements list the dose along with the percentage of
saponins, which refers to the amount of the supplement that is made up of these compounds, It is
common for Tribulus terrestris supplements to contain 45–60% saponins. Importantly, a higher
percentage of saponins mean that a lower dose should be used, as the supplement is more
concentrated.
Administration of Tribulus terrestris (TT) to humans and animals improves libido and
spermatogenesis ( Neychev et al.) he investigated the influence of Tribulus terrestris extract on
androgen metabolism in young males. The finding of the study predicts that T. terrestris steroid
saponins possess neither direct or indirect androgen increasing properties. It is found to increase
the levels of testosterone, leutinizing hormone, dehydroepiandrosterone sulfate.
Tribulus terrestris works by delivering increasing blood-flow to the new chambers of the penis
called the Corpus Carvernous. This effect aids in the expansion of the penis. It also acts as libido
enhancer and testosterone booster. The role of tribulus terrestris is to synergize (combine) its
testosterone-boosting capabilities with other testosterone boosters in the formula. Furthermore,
tribulus terrestris enhances endurance which helps to stay hardened for longer period.
On October 1st 2017 Relias media issued a short report titled: Tribulus: An RCT Supporting Its
Use for Erectile Dysfunction which discussed a double-blind, randomized, controlled trial in 180
men that showed that a standardized extract of Tribulus terrestris improved erectile function
after 12 weeks of treatment.

2.2.3 Ocium gratissimum (Scent leaf)

Ocimum gratissimum L. is a medicinal plant widely grown in tropical and subtropical
regions with the leaf decoction usually taken in folk medicine to enhance erectile performance in
men although the probable mechanism of actions remains undetermined.
I will be discussing the therapeutic potential of Ocimum gratissimum based on the article:
Ocimum gratissimum Linn. Leaves reduce the key enzymes activities relevant to erectile
dysfunction in isolated penile and testicular tissues of rats by: Oluwafemi Adeleke Ojo, Adebola
Busola Ojo, Babatunji Emmanuel Oyinloye, Basiru Olaitan Ajiboye, Omosola Olufisayo
Anifowose, Ayodeji Akawa, Oluranti Esther Olaiya, Oluwaseun Ruth Olasehinde & Abidemi
Paul Kappo
This study examined the inhibitory potentials of Ocimum gratissimum leaves on some key
enzymes associated with erectile dysfunction in penile and testicular tissues of the rat.
Method:
Inhibitory effect of aqueous extract (1:10 w/v) of O. gratissimum leaves on the activities of
phosphodiesterase-5 (PDE-5), arginase, angiotensin I –converting enzyme (ACE), and acetyl
cholinesterase (AChE) in penile and testicular tissues were assessed. Also, the extract was
investigated for ferric reducing antioxidant property (FRAP) and 1,1-diphenyl-2-picryl-hydrazil
(DPPH) radical scavenging abilities.
Results:
The extract showed higher PDE-5 (IC50 = 43.19 μg/mL), ACE (IC50 = 44.23 μg/mL), AChE (IC50 
= 55.51 μg/mL) and arginase inhibitory activity in the penile tissue than PDE-5 (IC 50 = 44.67 
μg/mL), ACE (IC50 = 53.99 μg/mL), AChE (IC50 = 60.03 μg/mL) and arginase (IC50  = 49.12 
μg/mL) inhibitory activity in the testicular tissue homogenate. Furthermore, the extract
scavenged free radicals and in a dose-dependent manner.
Conclusion:
The enzyme activities displayed might be associated with the bioactive compounds present in the
extract which could possibly explain its use in the management of erectile dysfunction (ED).

Phosphodiesterase-5 (PDE-5) inhibitory activity:

The ability of the extracts to inhibit PDE-5 activity was evaluated by (Adebayo AA, Ademosun
AO, Oboh G, Boligon AA et al. 2017) . The assay solution containing 5 mM of the substrate (p-
nitrophenyl phenyl phosphonate), 100 μl of tissue (penile and testicular) supernatant, 20 mM
Tris-HCL (pH 8.0) and the aqueous extracts of O. gratissimum (20–100 μg/ml) were incubated at
37 °C for 10 min. The amount of p-nitrophenol produced was read as a change in absorbance
after 5 min at 400 nm. The control experiment was performed without the extracts and sildenafil.
PDE-5 inhibitory enzyme activity was expressed as percentage inhibition:
PDE−5 inhibition (%)=[(Abscontrol−Abssamples)/Abscontrol]×100….(1)
where Abs control is the absorbance without the extract and Abs samples are the absorbance with
extract.
Phosphodiesterase-5 activities (PDE-5) of aqueous extract of O. gratissmum in penile and
testicular tissue homogenates were evaluated the result showed that the aqueous extract of O.
gratissmum inhibited PDE-5 enzymes. Taking into consideration the IC50 (lower IC50 value
means stronger enzyme inhibition) showing that the extract had a greater inhibitory activity on
penile phosphodiesterase-5. The mechanisms or actions of cGMP are mainly decreased by the
phosphodiesterase-5 enzyme in diverse parts of corpus cavernosum. PDE-5, an important
enzyme of the NO/cGMP signaling pathway, that performs a key function in corpus cavernosum
weakness, inhibition of nitric oxide-induced cGMP-mediated vasodilation and repairing basal
smooth muscle tone and penile detumescence. Thus, the rate of synthesis of cGMP by guanylate
cyclase and its degradation by PDEs determines the amount of cGMP within the corpus
cavernosum . A protein kinase that decreases cytosolic calcium levels, boosts smooth muscle
relaxation leading to penile erection is activated by cGMP. Sildenafil, tadalafil, and vardenafil;
these PDE-5 inhibitor drugs have negative effects such as nasal congestion, headache, visual
aberrations’ dyspepsia. Furthermore, previous studies have shown that phenolic compounds in
plant exhibit PDE-5 inhibition hence, the result showed that the extract inhibited PDE-5 activity,
this may be due to the presence of phenolic compounds particularly flavonoids, that functions as
an endothelium-independent relaxer.
The inhibition of the enzyme in penile and testicular tissue homogenates suggests that O.
gratissimum could be a promising plant with beneficial potentials for the management of ED.
2.2.4 Moringa oleifera
Moringa (Moringa oleifera Lam.) is a multipurpose tropical tree. It is mainly used for
food and has numerous industrial, medicinal and agricultural uses, including animal feeding.
Nutritious, fast-growing and drought-tolerant, this traditional plant was rediscovered in the 1990s
and its cultivation has since become increasingly popular in Asia and Africa, where it is among
the most economically valuable crops. It has been dubbed the "miracle tree" or "tree of life" by
the media Morphology
Moringa is a small to medium evergreen or deciduous tree that can grow to a height of 10-12 m.
It has a spreading open crown, typically umbrella-shaped. The roots are deep. The bole is
crooked, generally one-stemmed but sometimes forked from the base. The bark is corky and
grey. The branches are fragile and drooping, with a feathery foliage. Young twigs and shoots are
covered in short dense hairs, purplish or greenish white in colour
It was hypothesized that moringa oleifera leaves might improve male sexual dysfunction
induced by stress and also suppresses PDE-5 activity, Moringa consumption results in the
improvement of blood circulation and the healing oxidants that are buzzing through the body are
known to improve the sexual function of men, However moringa can help to combat sexual
dysfunction by suppressing hormones and neurochemicals that leads to erectile dysfunction. The
antioxidants in the leaves help combat the oxidative stress that comes with environmental and
life stressors. As the body grows tired it is stripped of its ability to perform sexually. The
moringa leaf properties then come in and counteract the stressors thereby eliminating the
dysfunction, the boost in heart function and anti-inflammatory response then allows proper blood
flow during sexual activities, giving men an all natural, all safe way to support their overall
sexual function.
2.2.5 Hibiscus sabdariffa
Hibiscus sabdariffa commonly named as “red sorrel” or “roselle” is a member of
malvaceae family. It is a medicinal plant with a worldwide fame and has more than three
hundred species which are distributed in tropical and subtropical regions around the world.
Roselle can adapt to a variety of soil in a warmer and more humid climate. Roselle is rich in
organic acids including citric, malic, tartaric and allo-hydroxycitric acids. The plant is also
known for its Beta carotene, vitamin C, protein and total sugar. Roselle, having various
medically important compounds called photochemical, is well known for its nutritional and
medicinal properties. Many parts of Roselle including seeds, leaves, fruits and roots are used in
various foods as well as in herbal medicine as a potential non-pharmacological treatment.
Different extracts from Roselle plays a crucial role in treating different medical problems. The
plant also act as an anti oxidant, There is a big argument about the origin of Roselle among
different scholars. Cobley suggested Roselle is a native plant of West Africa and from there it
was carried to other parts of the world such as Asia and America, whereas in others opinion,
Roselle was originated from India and Saudi Arabia.
Hibiscus can also help treat ED by lowering blood pressure as a result, not enough blood
flows to the penis needed to get and maintain erections. By effectively lowering blood pressure
with hibiscus tea you can expect to see an improvement in your erectile function (Raphael
Nyarkotey Obu. 2017)
Erections are all about your arteries - nitric oxide in your arteries and nice low blood pressure
levels (which indicates higher blood flow), Increased eNOS (Endothelial nitric oxide synthase)
Activity and Nitric Oxide. We get most of our arterial nitric oxide from the endothelium and this
is governed by the eNOS enzyme. It turns out that the polyphenols in hibiscus tea activate this
enzyme and cause your endothelium to produce more nitric oxide.
The endothelium is the thin layer of cells on the inside of your arteries that are
responsible for controlling their expansion and contraction and the nitric oxide that governs the
process. Researchers refer to this ability to relax the arteries as "endothelial function," and,
generally speaking, endothelial function governs how well and how fast your erections are.
(There are exceptions, of course, as low dopamine, venous leakage and other systems can
negatively impact erections as well.)
CHAPTER THREE
3.0 CONTRAINDICATIONS OF PDE5 INHIBITORS.
Patients with poor general condition, e.g, severe cardiovascular disease, for whom sexual
activity may be risky should not be given ED treatment. In patients receiving nitrate or NO-
donors, treatment with PDE5 inhibitors is contraindicated because they act via the same
NO/cGMP mechanism and concomitant treatment with a PDE5 inhibitor can lead to severe
hypotension and shock.
However some of the patients with stable coronary heart disease and erectile dysfunction
currently taking oral long-acting nitrates can be withdrawn from this treatment without facing
disadvantages and can then be successfully treated with a PDE5 inhibitor.
Rare reports of sudden loss of vision due to non-arteritic anterior ischemic optic
neuropathy (NAION) led the FDA to update the labels of all three products. The labels now
advise doctors to stop PDE5 inhibitor therapy in the event of sudden loss of vision in one or both
eyes and to discuss the increased risk of NAION in patients who have already experienced
NAION. At present, however, it is not possible to determine whether these events were related to
PDE5 inhibitors or to other factors. Conditions predisposing to NAION are: age >50, heart
disease, diabetes, hypertension, high cholesterol, smoking and certain eye problems.
There are certain precautions when using PDE5 inhibitors in patients taking α-blockers due to
the possibility of symptomatic hypotension with concomitant use.
3.1 PRECAUTIONS
All PDE5 inhibitors have precautions in the following cardiovascular categories:
Myocardial infarction, stroke, or life-threatening arrhythmia, resting hypotension (blood pressure
{BP} <90\50 mmHg) or hypertension (BP >170\100 mmHg)
Unstable angina or angina during sexual intercourse or congestive heart failure.

Cardiovascular Considerations:

Physicians should discuss with patients the potential cardiac risk of sexual activity in patients
with pre-existing cardiovascular risk factors. Patients who experience symptoms (e.g., angina
pectoris, dizziness, nausea) upon initiation of sexual activity should be advised to refrain from
further activity and should discuss the episode with their doctor.

CHAPTER FOUR
4.0 CONCLUSION
There is a dire need to develop some of the existing potent, African traditional remedies
for erectile dysfunction into scientifically acceptable natural medicines. With the financial and
goodwill support of governments, non-governmental organisations and philanthropic individuals,
coupled with the cooperation of multinational pharmaceutical companies such as Pfizer and
others, it should be possible to develop some of the currently available African traditional
remedies for ED into acceptable, potent natural medicines in the foreseeable future. Such
existing remedies should be subjected to rigorous scientific scrutiny experimentally (in
laboratory animals) and clinically (in humans), in order to establish their safety, efficacy, quality,
mechanisms of action, side effects, and possibly also, their contra-indications.
The goals of medicines, whether allopathic, traditional or complementary, are the same,
namely, to benefit patients therapeutically and improve their quality of life. Based on these
assumptions, one can look forward to a near future of integrated orthodox and traditional
medicines, and hope that experimental and clinical research in traditional, complementary and
alternative medicines will help to develop affordable, safe and effective natural medicines for
erectile dysfunction, rather than criticising and marginalising unorthodox medicines,
ethnomedical claims and traditional findings.
With traditional health practitioners, pharmacists, orthodox medical practitioners, nurses,
botanists, chemists, pharmacologists, toxicologists and other scientists working together
collaboratively for a common purpose, the future of scientifically developed, affordable, safe and
effective natural medicines for ED will certainly be in sight. Now is the time to ensure that future
availability of scientifically formulated, safe and effective traditional medicines for the treatment
of erectile dysfunction is not an elusive dream, but an imminent reality.
4.1 RECOMMENDATION
A lot of men associate advancing age with declining sexual function and an overall
decreased quality of life. Erectile dysfunction affects up to one third of men throughout their
lives, and the incidence increases with age, First line therapy for erectile dysfunction should
consist of oral phosphodiesterase V inhibitors although synthetic PDE V inhibitors has few and
similar side effects which includes include dyspepsia, headache, and to a lesser extent, myalgia,
flushing, low-back pain, and rhinitis in this case I would recommend herbal phosphodiesterase 5
inhibitors which have little or no side effects when taken in the right quantity, all the herbs
discussed above have potent antioxidants which protect nitric oxide (NO) in its continuing battle
against oxidative stress, and it thereby has the potential to enhance the effect of NO on certain
biologic systems and the result of an intact NO-cyclic guanosine monophosphate (cGMP)
pathway within the cavernosal nerve and cavernosal smooth muscle cells of the penis aids an
erection.
Phosphodiesterase V inhibitors are most effective in the treatment of erectile dysfunction
but the efficacy of synthetic phosphodiesterase V inhibitors in patients with severe diabetic
complications is not proven.

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