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Abstract

Erectile dysfunction (ED) is a global public health issue affecting approximately 150 million men of all ages. The ED prevalence in South Africa is 65% of adult males attending a primary care facility. In South Africa, several aphrodisiac plants were traditionally used to treat and manage ED. Therefore, the review sought to scientifically validate the use of aphrodisiac plants in the treatment of ED. Secondary data were extracted from previous articles, which were obtained from Google Scholar, ScienceDirect, and ResearchGate databases. Diverse aphrodisiac plants including S. longepedunculata A. vera, E. capensis, M. oleifera, M. serrata, Z. officinale, M. angustifolia, V. unguiculata, A. sativum, and W. somnifera exhibited many phytonutrients and secondary metabolites. Phytonutrients comprised vitamins (A, B_1-4, B₆, B₉, B₁₂, C, E) and minerals (iron, copper, selenium, potassium, calcium, zinc, magnesium, etc) while secondary metabolites comprised polyphenols, phenols, flavonoids, alkaloids, tannins, and others. Those phytoconstituents exhibited antioxidant, anti-inflammatory, antidiabetic, anti-obesity, vasodilatory, antihyperlipidemic, antiatherosclerosis, antithrombotic, antihyperglycemic, anti-sickling, and antihypertension properties. As explained in the body of text, plant extracts, phytoconstituents, and pharmacological properties demonstrated, through various ways, their commendable potential to stimulate erectile function in animal models by increasing sexual drive, testosterone, and blood flow. But some aphrodisiac plants, E. tirucalli, C. tomentosa, E. lysistemon, A. senegal, S. madagacariensis, R. communis, A. vera, B. natalensis, P. Africana, K. africana, A. sativum, C. edulis, and C. sativa, were found to be toxic when administered to animal models. Overall findings explain the use of those aphrodisiac plants in the treatment and management of ED by local communities. However, these findings are inconclusive because they are mostly based on in vitro and in vivo studies. Therefore, clinical trials are recommended to determine efficacy and safety in terms of standardising optimal dosages for humans with ED.

Keywords

Aphrodisiac plants vascular endothelium erectile function flavonoids pharmacological properties phytonutrients secondary metabolites

Introduction

Erectile dysfunction (ED) is defined as the inability to consistently achieve and maintain an erection sufficient to permit satisfactory sexual intercourse.^1–3 This is a result of the impairment of vascular system supplying blood to the erectile tissues of the penis, which are three cavernous, two corpora cavernosa, and corpus spongiosum.^4,5 It is a worldwide public health problem that affects men of all age groups including under 40 years and above (up to 70 years).^2,3 The prevalence of ED increases with age, rising from 2%-9% in men aged 40 to 49 years to 20%-40% in men aged 60 to 69 years and 50%-100% in men over 70 years.^6,7 At a global scale, approximately 150 million people are affected by this condition, and by 2025, that number is expected to rise to around 320 million.⁶ The ED prevalence in South Africa is 65% of adult males attending a primary care facility.⁸ Although this condition is evidently widespread, it is still undertreated.⁶

The ED condition may be triggered by physiological, psychological, or hormonal (testosterone deficiency) disturbances in the nervous, cardiovascular, endocrine, or reproductive systems.^5,6,9 Baker et al¹⁰ have classified the main causes of ED as vascular, neurological, and hormonal, This condition disrupts sequence of events comprising nerve impulses in the brain, spinal column, area around the penis, and the response in muscles, fibrous tissues, veins, and arteries in and near the corpora cavernosa. The cardiovascular system is at risk of impairment by ageing, chronic diseases (atherosclerosis, heart diseases, atherosclerosis, hypertension, diabetes mellitus, and obesity), and a lifestyle of alcoholism, cigaret smoking, and lack of physical activity.^1,4,11 Between 35% and 50% of men with diabetes have experience ED¹² while 98% of male patients with chronic illnesses in South Africa had ED symptoms.⁸ Ageing and poor lifestyle in particular are associated with metabolic impediments to nitric oxide (NO) production, fewer smooth muscle cells, and increased fibrosis within the corpora cavernosa, which prevent adequate penile engorgement and pressure on the penile veins.¹¹

The phosphodiesterase type-5 (PDE-5) enzyme present in the walls of blood vessels catalyzes the breakdown of the smooth muscle-relaxing agent (cyclic guanosine monophosphate [cGMP]), which is a second messenger of NO.¹³ Consequences of ED are reduced self-esteem, compromised well-being and limited interpersonal relationships, which could result in a loss of emotional and physical intimacy and at times divorce.¹ The inhibition of PDE-5 increases cGMP levels, reduces intracellular calcium (Ca²⁺) and induces vasodilation to promote penile erectile.¹⁴ Blocking PDE-5 causes blood vessels to relax and widen, which increases blood flow to certain areas of the body including penis. Mainstream pharmacological treatments for ED are PDE-5 enzyme inhibitors [sildenafil citrate (Viagra), tadalafil (Cialis), vardenafil (Levitra), avanafil, lodenafil, udenafil, mirodenafil, and vardenafil] as well as intracavernosal injection therapy of vasoactive substances, vacuum erection devices, and penile prosthesis implants.^2,4 Challenges associated with traditional PDE-5 inhibitors are side effects, failure by some patients to respond, addressing only symptoms, and high costs. Inhibitors for ED produce life-threatening toxic effects because PDE-5 gets expressed throughout the entire body.¹⁵

Plant-based aphrodisiacs have been used throughout the history to enhance libido, maintain penile erections, and improve sexual desire and endurance.¹⁵ Africa and other developing nations have been using plant-based aphrodisiacs more than conventional remedies.^6,16 In South Africa alone, over 130 plant species were found to be traditionally used as aphrodisiacs to treat and manage ED or impotence.¹⁷ Plant-based products are preferred to conventional remedies because of easy access, affordability, cultural and spiritual legitimacy, effectiveness, safety (minimal or no side-effects), and understanding of preparations and applications.^2,6 Inadequate accessibility to modern medicines and drugs in middle- and low-income countries, especially in Africa, has largely contributed to the widespread use of traditional medicines especially in poor households.¹⁸ However, there is still dearth of scientific information to validate traditional uses of aphrodisiac plants.^16,19

Therefore, the review sought to scientifically validate the use of aphrodisiac plants used in South Africa for the treatment of ED.

Results and Discussion

Aphrodisiac Plants Traditionally Used to Treat ED

The review study identified about 41 plant species that belonged to 26 families for which there was reasonable amount of information to scientifically validate their use as aphrodisiac (Table 1). Except for exotic and cultivated Citrus sinensis (sweet oranges), Zingiber officinale (ginger), and Allium sativum (garlic), the remaining 38 plant species were native to South Africa. Fabaceae, Euphorbiaceae, Asteraceae or Malvaceae families were represented by seven, four, and two plant species being used as aphrodisiacs for ED, respectively, while most families had one representative each. In another study,²⁰ Fabaceae had the highest number of representative plant species with medicinal value in the sub-Saharan Africa. Furthermore, Fabaceae has an extensive range of distribution across all biomes of the world.²¹ Apart from ED, which is the focus of this review, plant species are also being used to treat 3-15 other ailments (Table 1).

Table 1.

Scientific Validation of Aphrodisiac Plants Traditionally Used for the Treatment of Erectile Dysfunction.

Scientific name	Family	Traditional uses	Parts used and preparations	Phytochemical and pharmacological data	References
Dombeya rotundifolia	Malvaceae	It treats erectile dysfunction, heart problems, nausea in pregnant women, intestinal ulcers, headaches, stomach complaints, hemorrhoids, diarrhoea, and dyspepsia, as well as hasten the onset of labor.	Bark decoction is taken orally as an aphrodisiac to improve sexual performance.	Phytochemicals: tannins, saponins and cardiac glycosides. Pharmacological properties: antioxidant, anti-inflammatory, anti-hypertensive, and acetylcholinesterase properties. Since oxidative stress and inflammation contribute to erectile dysfunction, the anti-inflammatory properties might indirectly support erectile health.	^17,22–24
Erythrina lysistemon	Fabaceae	It treats erectile dysfunction, sores, open wounds, earache, sprains, and toothache.	Bark is boiled, and the decoction drank as an aphrodisiac.	Phytochemicals: flavonoids (flavonols, anthocyanins, isoflavones, quercetin), benzenoids, alkaloids, phenylpropanoids, and tannins. Pharmacological properties: Flavonoids improve blood flow and vascular health for erectile function.	^17,25–27
Annona senegalensis	Annonaceae	It treats erectile dysfunction, male sexual impotence, hernia, snakebite, diabetes, chicken pox, smallpox, yellow fever, tuberculosis, gastricitis.	Root, bark, leaf infusion or decoction is taken orally to treat impotence or erectile dysfunction in Nigeria and Cameroon. The root was also reported for treating erectile dysfunction. Leaf, seed, or bark decoction treats diabetes in Democratic Republic of Congo.	Phytochemicals: polyphenols, alkaloids, phenols, tannins, flavonoids, saponins, glycoside, steroid, and essential oils. Pharmacological properties: anticonvulsant (calming nerves or muscles), anti-inflammatory, antioxidant, antianemic, and spermatogenic activities.	^17,28–31
Adansonia digitata	Malvaceae	It treats diarrhea and dysenter, toothache, oral hydration, gingivitis, diaphoretic, fever.	Crushed bark or roots mixed with honey, taken orally before breakfast to treat erectile dysfunction in Ethiopia and Kenya.	Phytochemicals: flavonoids, catechins, proanthocyanins, saponins, phenols, tannins, and carotenoids. The fruit contains vitamin C, zinc, potassium, magnesium, iron, calcium, and protein. Pharmacological properties: antioxidant, anti-inflammatory, and antidiabetic activities, which could enhance erectile function by ensuring better blood circulation and supply to penile tissues.	^3,32–34
Aloe vera	Asphodelus	It treats headaches, ulcerative colitis, coughs, wounds, ulcers, gastritis, arthritis, cuts (abrasions), burns (sunburns), eczema, pain, inflammation bowel disease, diabetes, cancer.	Raw latex and gel (exudate) can be taken orally as a treatment for erectile dysfunction. These products are also used topically by smearing on a shaft of the penis in Nigeria.	Phytochemicals: aloe-emodin, phenols, aspirin, polysaccharides, anthraquinones, β-sitosterol, lupeol, minerals: calcium, chromium, copper, selenium, magnesium, manganese, potassium, sodium, zinc, vitamins (A, B₄, B₉, B₁₂, C, E). Pharmacological properties: anti-inflammatory, antioxidant, antidiabetic, antibacterial, antiviral, anticancer, wound healing, antiatherosclerosis, and antidiabetic properties. Antioxidant neutralizes free radicals. The intake of the vitamins and minerals present in Aloe stimulates blood saturation, thus guaranteeing better oxygenation and faster expulsion of toxins. As a natural vasodilator, A. vera extract increases the amount of nitrogen produced in the body, which loosens the blood vessels, thereby allowing blood flow to the penis.	^32,34–37
Ekebergia capensis	Meliaceae	It treats fever, malaria, gastrointestinal problems, pain, parasitic worms, reproductive problems in women, respiratory problems, and skin diseases.	Leaf, root and stem decoctions are taken orally to alleviate erectile dysfunction in Uganda and Zimbabwe.	Phytochemicals: saponins and steroid glycosides, tannins, anthraquinones, alkaloids, carotenoids, flavonoids, and anthracyanosides. Pharmacological properties: Extracts fed to mice alleviated sexual dysfunction by increasing the mounting frequency and testosterone levels of male rats.	^21,33,38
Moringa oleifera	Moringaceae	It is used for water purification, animal feed, antidote, antiaging, and the treatment of paralysis, helminthiasis, sores, and skin infections.	Seed and leaf decoction, tea, and condiment are taken orally to treat erectile dysfunction. Seed powder is taken as tea, leaves are eaten as sauce or drunk as decoction (100 mL) in Uganda. Root bark decoction mixed with Grewia plagiophylla is taken orally ie, drink half glass of decoction daily for 10 days. Seed powder can be applied topically on the penis.	Phytochemicals: flavonoids, phenolics glucosinolates, terpenes, sterols, tetraterpenoids (carotenoids), alkaloids, and sterols. Pharmacological properties: antioxidant and anti-inflammatory. Sterols inhibit the secretion of inflammatory factors and reduce the absorption of cholesterol by the intestines (hypocholesterolemic activity).	^17,33,39,40
Morella serrata	Myricaceae	It treats flu, dysmenorrhea, headaches, and erectile dysfunction.	Decoction of the root is taken orally in South Africa.	Phytochemicals: tannins, saponins, flavonoids, terpenoids, and steroids. Pharmacological properties: Feeding extracts to mice increased erection, quick flips, long flips and total penile reflexes in mice. This could be ascribed to antioxidant and adaptogenic constituents.	^21,41,42
Zingiber officinale	Zingiberaceae	It treats headaches, colds, nausea, and emesis.	Rhizome decoction or infusion taken orally in tea, milk, and porridge in Uganda. Rhizome is mixed with honey and taken orally. Rhizomes are also chewed, and the exudates are swallowed in Ethiopia.	Pharmacological properties: essential oils, phenolics, flavonoids, alkaloids, glycosides, steroids, terpenoids, tannin, gingerols, shogaols, paradols, steroids, saponins, protein, unsaturated fat, dietary fibers, carbohydrates, lipids, iron, calcium, magnesium, potassium, phosphorous, and vitamins (B₁, B₂, B₃, C). Pharmacological properties: antioxidant, anti-inflammatory, cardiovascular protective, anti-obesity, and antidiabetic properties. Extracts fed to mice increased gonadal hormones, sequestered free radicals, enhanced production of nitric oxide, decreased serum glucose, cholesterol and triacylglycerol levels in the treated diabetic rats. Rhizome extract reduced the carrageenan – induced rat paw edema in rats. Extracts exhibited good scavenging activity.	^{3,16,32,33,43,44}
Monsonia angustifolia	Geraniaceae	It treats heartburn, diarrhea, eye infections, hemorrhoids, sores, ulcers, flatulence, influenza, dysentery, and minor stomach ailments.	Root decoction is used by indigenous people to increase libido and treat premature ejaculation and erectile dysfunction in males.	Phytochemicals: coumarins, flavonoids, terpenoids, saponins and polyphenols. Pharmacological properties: The animal-based in vivo administration of the extract resulted in a significant increase in mount frequency, intromission frequency, ejaculation frequency, ejaculation latency and serum hormone concentrations. The administration of 300 mg/kg body weight of the aqueous extract produced the best effects in all the parameters (produced pro-sexual stimulatory effect).	^45,46
Ximenia caffra	Olacaceae	It treats wounds, sexually transmitted infections (STIs), infertility, stomachache, fever, eye problems, diarrhoea, bilharzia, menorrhagia, malaria, intestinal worms, impotence, and coughs. Bark and fruits are used by small-scale farmers as ethnoveterinary medicine to treat dermatophilosis, foot rot, saddle sores and control ectoparasites. Oil from X. caffra seed is used as a moisturizer, soap and shampoo for dry, fragile and damaged hair.	Root decoction is taken orally in Botswana and Zimbabwe	Phytochemicals: polyphenols, glycosides phenolic acids, flavonoids, phenols, phytosterols, tannins, and fatty acids. Pharmacological properties: antioxidant and anti-inflammatory. Leaf extract inhibits the mRNA expression of proinflammatory genes (IL-6, iNOS, and TNF-α) by using RT-qPCR, implying its anti-inflammatory effects.	^32,47,48
Dichrostachys cinerea	Fabaceae	It treats many diseases such as dysentery, diuretic, edema, gout, nasopharyngeal infections, anthelmintic, rheumatism, diabetes, kidney disorders, gonorrhea, syphilis, malaria, asthma, coughs, tuberculosis, epilepsy, snake bites, pains, boils, burns, toothache, headache, scabies.	Bark decoction is taken orally for ED in Uganda. Roots used in mixtures with different plants for treatment of erectile dysfunction in South Africa. Bark decoction is taken orally in DR Congo and Uganda. Oral administration of the bark is used in Uganda. In Tanzania, the root is crushed and mixed with maize or taken as a decoction.	Phytochemicals: carbohydrates, proteins, alkaloids, meroterpenes, flavonoids, glycosides, saponins, tannins, amino acids, and terpenoids. Pharmacological properties: antioxidant, anti-inflammatory, anti-analgesic, antidiarrheal, antiviral, antibacterial, antifungal, antimalarial.	^{21,32,33,49–53}
Vigna unguiculata	Fabaceae	It treats neuritis, insomnia, weakness of memory, dyspepsia, indigestion, needles in limbs, sensation of pins, stomatitis, corneal ulcers, and celiac disease.	Leaf decoction taken orally as aphrodisiac.	Phytochemicals: vitamins (A, B_1, B_2, B_3, B_6, C), minerals (iron, zinc, calcium, magnesium, phosphorus, potassium, sodium), and amino acids (arginine, alanine), tannins, phenolic acids, saponins, steroids, glycosides, flavonoids, anthocyanin, flavonoids, alkaloids, terpenoids. Pharmacological properties: antioxidant, anti-atherosclerotic, hypocholesterolemic, hypoglycemic, anti-obesity, anti-anemic, and antidiabetic activities. Anthocyanin and flavonoids that were characterized by anti-sickling and antihyperlipidemic activities, respectively.	^31,33,54,55
Ziziphus mucronata	Rhamnaceae	It treats menorrhagia, infertility of women, body pains, tooth ache, scrofula, sexually transmitted infections including gonorrhea and chlamydia, diarrhoea, body pains, dysentery, fever, rheumatism, respiratory and chest ailments including cough and tuberculosis, snake bites, sores, boils, swelling and diabetes.	Root decoction is taken orally to treat erectile dysfunction.	Phytochemicals: zinc, magnesium, calcium, iron, potassium, sodium, phosphorus, phenolics, flavonoids, quercetin, terpenoids, quinones and alkaloids. Pharmacological properties: antioxidant, anti-inflammatory, antidiabetic, and anti-sickling.	^49,56
Strychnos madagascarensis	Loganiaceae	It treats many ailments such as foot ache, toothache, fever, epilepsy, eye problems, stomach complaints and dysentery, wounds and sores, diarrhoea, diabetes.	Root decoction is taken orally as aphrodisiac.	Phytochemicals: alkaloids, fatty acids, cardiac glycosides, flavonoids, saponins, steroids, tannins, terpenoids, triterpenoids, terpenoids, alkaloids, cardiac glycosides. Pharmacological properties: antidiabetic, antioxidant, and toxicity activities.	^49,57,58
Allium sativum	Amaryllidaceae	It treats indigestion, respiratory and urinary tract infections, cardiac disorders, and erectile dysfunction.	Bulb, leaves, roots and tuber can be chewed directly or be used as a decoction to be taken orally in water, and in food in Uganda.	Phytochemicals: S-allyl cysteine, alliin, allicin, ajoenes, vinyldithiins, and flavonoids, alkaloids, tannins, saponin, cardenolides, and steroids. Pharmacological properties: antioxidant, anti-inflammatory, immunomodulatory, antidiabetic, antihypertension, antithrombosis, antihyperlipidemia, antianemic, and anti-atherosclerosis activities. Allium improves DNA integrity through increment in testosterone level and luteinising hormone, sequestering free radicals and enhanced production of nitric oxide. Extracts administered to rats restored their erectile function.	^{16,21,31–33,59}
Acacia senegal	Fabaceae	It treats cough, diarrhea, dysentery, and urinary tract disorders.	Root decoction is taken orally to treat erectile dysfunction.	Phytochemicals: tannins, saponins glycosides, alkaloids and flavonoids, eicosanoic acid, linoleic.acid. Pharmacological properties: antioxidant activities, which might have reduced hypercholesterolemia by inhibiting HMG-CoA reductase and slowing the progression of atherosclerotic plaque formation in hypercholesterolemic rabbits.	^3,60–62
Momordica foetida	Cucurbitaceae	It treats malaria, flu, cough, tuberculosis, vomiting, stomach-ache, expelling worms, diabetes.	Tuber is ground and taken orally or smeared topically on shaft of the penis.	Pharmacological properties: triterpenoids and flavanones. Pharmacological properties: Antioxidant, antidiabetic, and antihypertension activities.	^17,63
Capparis tomentosa	Capparaceae	It treats rheumatism, madness, snakebite, chest pain, jaundice, malaria, headache, coughs, pneumonia, constipation, infertility, leprosy, tuberculosis, gonorrhea, impotence, and sterility), and asthma.	Roots are used, especially powdered root paste mixed with butter is applied on the glans of penis. Decoction of the root is mixed with roots of Cyperus esculentus and taken orally for impotency.	Phytochemicals: alkaloids, stachydrine, saponin glycosides, phytosterols, terpenoids, tannins, sterol, polyphenols, flavonoids, and anthranoids. Pharmacological properties: anti-inflammatory, antioxidant, and antidiabetic.	^3,16,17,64
Euphorbia tirucalli	Euphorbiaceae	It treats rheumatism, warts, cough, asthma, earache, toothache, neuralgia, cough, gonorrhea, asthma, leprosy, dropsy, dyspepsia, enlarged spleen, colic, jaundice, stone in bladder, syphilis, snakebite, infertility in women, leprosy, and foot paralysis.	Latex is used to treat impotence. Latex / juice is mixed with butter and heated for 5 min after which it gets smeared onto the penis shaft for three days. Latex / juice is used in South Africa and Tanzania.	Phytochemicals: sitosterol, tirucalicine, gallic acids, terpenic alcohol, tannins, linoleic acid. Pharmacological properties: anti-inflammatory, antioxidant, immunomodulatory activities.	^{3,16,21,33,65}
Withania somnifera	Solanaceae	It treats cold and coughs, ulcers, emaciation, diabetes, conjunctivitis, epilepsy, insomnia, senile dementia, leprosy, Parkinson's disease, nervous disorders, rheumatism, arthritis, intestinal infections, bronchitis, asthma, and impotence.	Orally, drink root decoction. The decoction is taken at a dose of one to two tablespoonsful daily.	Phytochemicals and pharmacological properties: alkaloids (relaxant activity), phenols (antioxidant, anti-inflammatory), flavonoids (antioxidant, strengthen capillary walls, improve blood cholesterol levels), saponins (anti-inflammatory, hypoglycemic), tannins (anti-inflammatory), steroids (aphrodisiac, anti-inflammatory, anti-anxiety, reduce cholesterol levels, strengthen immune system).	^{3,16,21,66,67}
Vangueria infausta	Rubiaceae	It treats chest pain, asthma, cold, cough, diarrhoea, stomach problems, epilepsy, fever, headache, hernia, infertility, bloody stool, malaria, vaginal discharge, snakebites, pneumonia.	Leaf and root are boiled, and the decoction is taken orally to treat erectile dysfunction. Macerated root decoction is also taken orally in Kenya and South Africa.	Phytochemicals: fiber, carbohydrates, copper, iron, zinc, calcium, potassium, magnesium, sodium, phosphorus, vitamin C, phenols, tannin, flavonoids, triterpenoids, kaempferol, quercetin, luteolin, glucoside). Pharmacological properties: antioxidant and anti-inflammatory activities.	^49,68
Eriosema kraussianum	Fabaceae	It treats anxiety, skin conditions, diabetes mellitus, kidney and urinary infections, tonsillitis, pneumonia, constipation, stomach and back pains, arthritis, erectile dysfunction, impotence, and urinary complaints in male.	Hot milk infusion of roots and maceration of root bark are drunk to treat erectile dysfunction. Pounded boiled root decoctions of the plant are taken in small doses in the morning and at night in South Africa. In some cases, milk infusions and decoctions of roots are taken two to four hours before sexual intercourse. Effects could last four to six hours.	Phytochemicals: terpenoids, flavonoids. Pharmacological properties: antioxidant, erectile function, hypoglycemic, vasodilatory (vasorelaxant), hypoglycaemic, antidiabetic (extracts reduced fasting blood glucose levels), hypolipidemic, acetylcholinesterase inhibitory. It improved the relaxation of corpus cavernosum smooth muscle.	^{2,13,16,21,69–72}
Artemisia annua	Asteraceae	It treats fevers, bone steaming and heat/fever arising from exhaustion, tuberculosis, lice, wounds, scabies, dysentery fevers due to malaria, hemorrhoids, pain and swelling around tooth, pus in ear, rhinopolyp, eye problems.	Root decoction boiled in water for 20 min is taken orally.	Phytochemicals: terpenoids, artemisinin (antimalarial), flavonoids (antioxidant, anti-inflammatory), coumarins (anti-inflammatory), artemisia ketone, camphor, and phenolics (antioxidant) were the main components of A. annua. Pharmacological properties: antioxidant, anti-inflammatory, immunoregulation, and antimalarial activities.	^{1,17,21,73,74}
Bauhinia galpinii	Fabaceae	It treats diarrhoea, epilepsy, convulsion, amenorrhea.	Root decoction is taken orally to treat erectile dysfunction.	Phytochemicals: flavonoids, tannins, phenolics, and others. Pharmacological properties: antioxidant and anti-inflammatory activities.	^17,74–76
Bulbine natalensis	Asphodelaceae	It treats skin diseases, burns, diarrhoea, and sexually transmitted diseases, stomach ailments, urinary tract infection, viral infections such as HIV, chicken pox and shingles, parasitic infections.	The powder from the stem is mixed with milk and taken orally for the management of male erectile dysfunction.	Phytochemicals: flavonoids, triterpenoids, saponins, cardiac glycoside, tannins, alkaloids and anthraquinones. Pharmacological properties: The administration of the extract at the doses of 25 and 50 mg ⁄ kg body weight resulted in the significant increase in mount frequency, intromission frequency, ejaculatory latency, ejaculation frequency, serum testosterone and luteinizing hormone concentrations, computed indices of sexual behavior, erection, quick flips, long flips and total penile reflexes.	^16,21,77,78
Carica papaya	Caricaceae	It treats skin and hair problems, jaundice, rheumatism, urethritis, gastroenteritis, stomach-ache, ringworm infections, and cancer.	Pounded root taken with soft porridge in South Africa.	Pharmacological properties: quercetin, α-tocopherol, papain, kaempferol, papain, steroids, alkaloids, saponins, carotenoids, antheraxanthin, tyrosine, Tryptophan. Pharmavological properties: reduced production of both the ROS and pro-inflammatory cytokines.	^1,21,31,79
Jatropha curcas	Euphorbiaceae	It treats various ailments such as ulcers, septic gums, cuts, wounds, burns, itched and, blistered skin, ulcer, piles, diarrhoea, urinary infection, intestinal parasites, toothache, pains, healing, gum problems, inflammation, pyorrhea, rheumatism, leprosy, fever, jaundice, gonorrhea.	Root decoction – ie, root is boiled in water for 5 min and the decoction is taken orally.	Phytochemicals: alkaloids, tannins, glycosides, flavonoids, sapogenins. Pharmacological properties: antioxidant, anti-inflammatory activity in mice and rats. Topical application of root powder in paste form in mice and rats has been reported to exhibit anti-inflammatory activity. Root bark extract scavenged hydroxyl in a concentration dependent manner and has a stronger hydroxyl scavenging activity compared with ascorbic acid or vitamin C.	^{1,16,17,21,80}
Peltophorum africanum	Fabaceae	It treats stomatitis, insomnia, skin disorders, constipation, ringworm, dysentery, muscular pains, sores.	Pounded bark taken with warm water. Decoction of root or stem bark is taken orally. The bark may also be pounded and taken orally with warm water.	Phytochemicals: phenolics, coumarins, saponins, tannins, flavonoids, tannins, terpenoids, xanthone, coumarins, amino acids (arginine). Pharmacological properties: Anti-inflammatory, antioxidant, and cardioprotective effects were attributed to phenolic compounds, coumarins, flavonoids, saponins, and tannins.	^{1,16,21,81,82}
Hypoxis hemerocallidea	Hypoxidaceae	It treats tuberculosis, testicular tumors, other cancers, HIV/ acquired immunodeficiency syndrome (AIDS), insanity, barrenness, bad dreams, intestinal parasites, urinary infection, cardiac diseases, headache, dizziness, prostate hypertrophy, burns, and ulcers.	The tuber is boiled in water for 5 min and decoction taken orally.	Phytochemicals: sterols, sterol glycosides, terpenoids, saponins, cardiac glycosides, tannins, reducing sugars. Pharmacological properties: antioxidant, hypoglycaemic, and anti-inflammatory effects. It improves sexual function and fertility parameters and may protect the testes from oxidative damage.	^1,21,83
Catha edulis	Celastraceae	It treats diarrhea, gonorrhea, toothache, gastrointestinal disorders, helminthiasis, toothache, asthma, gonorrhea, influenza, erectile dysfunction, pneumonia, cough, diarrhoea, stomach upset,	Young leaves and stems are chewed in Uganda. Root decoction is boiled for 5 min and is taken orally in South Africa and Uganda.	Phytochemicals: alkaloids terpenoids, flavonoids, sterols, glycosides, tannins, amino acids (arginine), vitamins and minerals.	^21,84,85
Securidaca longepedunculata	Polygalaceae	It treats syphilis, pains, stomach ache and dysentery, constipation, flu, tuberculosis, coughs, fever, pneumonia, epilepsy, tuberculosis, dislocated jaw, headaches, skin cancer, skin infections, malaria, tick, ascariasis, toothache, rheumatism, typhoid, erectile dysfunction (as aphrodisiac).	Leaf and bark decoction is taken orally for ED in Uganda. Bark extracts are dissolved in mageu (traditional beverage made from water and various grains) in South Africa and Nigeria. Leaf infusion is taken orally promptly or within 48 h. Pounded root and bark mixed with pounded root of Zanthoxylum humile taken with soft porridge in South Africa. In Nigeria, the root bark is chopped into pieces and infused in 350 mL of water for 24 h and taken orally. Zimbabweans chew small piece of root, and the infusions, decoctions or macerations of the root is taken orally in other countries. Botswana, Nigeria, South Africa, and Zimbabwe use these products.	Phytochemicals: saponins, tannins, anthroquinones, Sterols, terpenes, alkaloids, xanthones, triterpene, saponins. Pharmacological properties/; Xanthones exhibit activity against erectile dysfunction. Two new xanthones were isolated; and one of them was active against erectile dysfunction by showing potent activity to relax the corpus cavernosal smooth muscle by 97% in comparison to sildenafil (Viagra) at 1.8 × 10⁻⁵ mg/mL. Xanthones stimulate the relaxation of corpus cavernous smooth muscle, which supports the traditional use of its root bark.	^{1,2,16,17,21,33,86,87}
Citrus sinensis	Rutaceae	It treats constipation, cramps, colic, diarrhoea, bronchitis, tuberculosis, cough, cold, obesity, menstrual disorder, angina, hypertension, anxiety, depression and stress, asthma, vomiting, fever, coughs, indigestion, and respiratory disorders.	Root/stem /bark decoction taken orally in a glass 3 times a day for 3 days in Kenya.	Phytochemicals: polyphenols, flavonoids, limonoids, carotenoids, vitamin C. Pharmacological properties: antioxidant and antianemic activities. Oranges and lemons are considered potential sources of antioxidant agents scavenging free radicals and preventing oxidative damage.	^31,33,88,89
Mondia whitei	Apocynaceae	It treats abdominal pains, nausea, fever, bilharzia, malaria, ringworm infestation (anthelmintics), skin diseases, heart diseases, asthma, male infertility, stress and tension, and sexual dysfunction to stimulate appetite as an aphrodisiac.	Roots and root bark can be chewed when raw or dry, or taken orally as a decoction in tea and in food. Root is ingested orally after grinding, chewing or boiling, and can be consumed with food, water, or tea in Cameroon, Uganda, and Kenya.	Phytochemicals: sterols, glycosides, alkaloids. Pharmacological properties: Compounds caused increased sexual arousal, copulatory efficiency, testosterone and luteinising hormone, copulatory efficiency, sexual sensation through the activation or stimulation of nitric oxide synthase activity resulting in the elevation of levels of cyclic guanosine monophosphate. Increased weight of seminal vesicles and epididymides in male rats.	^2,21,33,90
Bidens pilosa	Asteraceae	It treats a diversity of ailments such as stomach-ache, stomach ulcers, headache, dysentery, sore throat, cuts, burns, wounds, snakebites, hemorrhoids, diarrhea or constipation, cold, influenza, cough, yellow fever, skin problems, eye infections, malaria, intestinal worms, and diabetes.	Shoot or flower decoction is taken orally as tea in Kenya and Uganda ie, drinking 500 mL daily for 2 days for erectile dysfunction.	Phytochemicals: aliphatics, terpenoids, alkaloids, phenolics, tannins, glycosides, saponins, sterols, and flavonoids. Pharmacological properties: antioxidant, anti-inflammatory, and immunomodulatory activities.	^33,91–93
Warburgia salutaris	Canellaceae	It treats numerous ailments that include abdominal pains, backache, blood disorders, chest complaints, colds, coughs, febrile complaints, fever, headache, inflammations, influenza, irritations, malaria, respiratory complaints, rheumatism, sores, stomach ulcers, toothache, and venereal diseases.	Bark decoction is used as aphrodisiacs.	Phytochemicals: flavonoids, polyphenols, tannins, warburganal, polygodial, muzigadial, ugandensidial, sesquiterpenoid lactones, mukaadial, salutarisolide, were isolated and identified.	^{16,17,94–96}
Kigelia africana	Boraginaceae	It treats digestive system disorders, leg edemas, dermal irritations and infections, mastitis, retained placenta, brucellosis, and Newcastle disease.	Fruits, root and leaf decoctions are taken orally to treat poor libido, sexual asthenia and impotence in Africa. Fruits, seeds or bark decoction is taken orally in Tanzania. Roasted seeds or fruits are macerated in beer in Ethiopia. Bark, leaves, and roots decoction aphrodisiac is taken orally in tea. ie, 1 spoonful thrice daily or in porridge; 250 mL drunk to treat ED in Uganda and Kenya. Fruit boiled with milk, cooled and taken orally in Botswana and Nigeria.	Phytochemicals: alkaloids, tannins, terpenoids, phenols, flavonoids, phenolics, coumarins, sterols, triterpenes, unsaturated fatty acids. Pharmacological properties: anti-inflammatory activity, antidiabetic, hypoglycemic. Anti-inflammatory inhibits inflammatory cytokines, reduced inflamed hind paw diameter. Antidiabetic activity lower blood glucose. Exhibiting great free radical scavenging properties. Extracts in African catfish increased testicular weight, testosterone levels, sperm count, motility, and fertilization ability.	^{16,17,21,33,97,98}
Cannabis sativa	Cannabaceae	It treats a host of ailments such as diabetes, digestive problems, circulatory problems, genital problems, urinary problems, central nervous system, skin disorders and burns, respiratory diseases, joint pains, nausea and vomiting, loss of appetite in AIDS patients, anxiety, seizure, cancer, arthritis, rheumatic, bloating, cough, dysentery, diarrhoea, fever, gout, and asthma.	Leaves and roots are chewed directly, taken as a decoction orally, or taken as inhaled fumes (smoking). Leaf and seed are also used for circulatory system and blood disorders, hypertension, muscle relaxants, inflammatory.	Phytochemicals: polyphenols, alkaloids, cannabinoids, tocopherols, sterols, terpenes, carotenoids, flavonoids. Pharmacological properties: Anti-inflammatory, antihypertension, antioxidant, antibacterial, anticoagulant, anticancer, and antidiabetic activities. Inhibition of glucosidase suppress carbohydrates digestion to delay glucose absorption and, consequently, reduce blood glucose levels. Compounds also decreased inflammatory cytokines.	^21,33,99
Cleome gynandra	Capparaceae	It treats headaches, sinus infection, chest congestion, fevers, ear diseases, and gastrointestinal disorders including infections.	Leaves, roots, and flowers are used directly (by chewing), or as a decoction orally or as food as aphrodisiac. Roots are chewed and leaves are cooked as food.	Phytochemicals: phosphorous, magnesium, potassium, calcium, sodium, manganese, iron, copper, zinc, vitamins (A, C, E), flavonoids, terpenes, and phenols. Pharmacological properties: vasodilatory, antioxidant, antimicrobial, immunomodulatory, antithrombotic, and anti-inflammatory activities. Extracts significantly reduced rat paw edema. Dose-dependent vasodilatory effect in endothelium intact aortic rings. Extracts stimulated immune system in a dose-dose-dependent manner.	^16,21,33,100
Combretum molle		It treats leprosy, fever, wounds, edema or dropsy, chest disorders, convulsions, abdominal disorders, angina, and HIV/AIDS	Leaves in decoction drink 500 mL (adult) daily for ED in Uganda.	Phytochemicals: alkaloids, polyphenols, flavonoids, phenolic compounds, polyphenols, terpenoids, tannins, coumarins, saponins, triterpene acid, phytosterols, gums, mucilage, lignins, carbohydrates, lipids, fixed oils, amino acids and proteins. Pharmacological properties: antioxidant, cardioprotective, antihypertensive, and anti-inflammatory activities. Polyphenols are involved in the treatment of diabetes and exhibit anti-inflammatory activity.	^33,101
Ricinus communis	Euphorbiaceae	It treats and manages ailments such as dermatitis, ringworm, warts, dandruff, rheumatism, headaches, edema, and labor pain to speed up delivery. Its castor oil is as a purgative or laxative.	Leaf decoction is taken orally for erectile dysfunction. Crushed leaves are mixed with coffee, tea, or milk, and are drunk before copulation. Dried seeds are pounded, mixed with a small quantity of latex from Aloe spp. in water or coffee, and drunk before bedtime for two days in Ethiopia.	Phytochemicals: Flavonoids, flavonoids, saponins, glycosides, alkaloids and steroids. Pharmacological properties: antidiabetic, anti-inflammatory, immunomodulatory, antioxidant, antifertility, lipolytic. There was a decline in lipid profile, decreased levels of serum glucose from 390 mg/dL to 148 mg/dL, indicating a 62% decrease following treatment. Anti-inflammatory reduced edema in mice model. Reduction was more pronounced at 43% and 58% when administered topically at doses of 250 and 500 μg/kg, respectively, for 8 d (0.9 mg/mouse).	^{3,32,33,102,103}

Preparations and Administration of Herbal Medicines

Traditional use of plants to treat ED and other ailments is a common practice in Africa, especially in the Southern (South Africa, Zimbabwe, Botswana), Western (Nigeria), Eastern (Ethiopia, Kenya, Tanzania, Uganda), and Central (Democratic Republic of Congo, Cameroon) Africa (Table 1). Plant parts used for traditional remedies for ED were leaves, shoots, flowers, stems, roots, stem and root bark, bulbs, tubers, rhizomes, seeds, latex (milky substances), and gels. Those remedies were either taken orally either through chewing and swallowing exudates or through drinking decoctions (mix of herbal products with boiled milk or water) and infusions (herbal products soaked in milk or water). Sometimes remedies were taken as inhaled fumes or smokes. In another study,¹⁰⁴ medicinal products are added to or mixed with a traditional beer, porridge, fermented corn, and tea. Crushed root or bark was mixed with honey, porridge or other herbal products, and taken orally before breakfast. Latex and powdered root paste each mixed with butter were applied topically on the shaft and glans of the penis, respectively. Some information on the preparations of herbal remedies was provided for, including periods for boiling decoctions and treatments as well as dosages, which is corroborated by another study on commercialization of herbal products.¹⁰⁴ Although packaging and presentation of those products are modern, they lack scientific safety and quality controls. All this information can be used as a baseline for developing and standardising herbal medicines for African Traditional Medicine (ATM).¹⁰⁵

Phytoconstituents of Aphrodisiac Plants to Alleviate Erectile Dysfunction

This review established some promising phytoconstituents (secondary metabolites or phytochemicals, phytonutrients and pharmacological properties), which could possibly alleviate ED (Table 1). For instance, extracts of almost all the identified plant species including Securidaca longepedunculata Aloe vera, Ekebergia capensis, Moringa oleifera, Morella serrata, Zingiber officinale, Monsonia. angustifolia, Vigna unguiculata, A. sativum, and Withania somnifera exhibited many phytonutrients and secondary metabolites. Phytonutrients included vitamins (A, Bs, C, E) and minerals (iron, copper, selenium, potassium, calcium, zinc, copper, etc) while secondary metabolites comprised polyphenols, phenols, flavonoids, alkaloids, tannins, glycosides, saponins, polysaccharides, xanthones, and terpenoids. Collectively, those phytoconstituents exhibited antioxidant, anti-inflammatory, antidiabetic, anti-obesity, vasodilatory (vasorelaxant), lipolytic (antihyperlipidemic), antiatherosclerosis, antithrombotic, antihyperglycemic, anti-sickling, and antihypertension properties. Those phytoconstituents together with their pharmacological properties have potential to promote blood flow in arteries and veins of the body and penis, and therefore penile erectile. This finding is supported by various studies^21,106–108 citing that secondary metabolites enhance erectile function by ensuring blood circulation and supply to penile tissues. To qualify the finding, mechanisms of action of plant extracts and their phytoconstituents on how they alleviate ED are unpacked below.

Mechanisms of Action of Plants in Treating and Managing Erectile Dysfunction

In several in vitro and in vivo studies, Mondia whitei, Kigelia Africana, E. capensis, M. serrata, Bulbine natalensis, M. angustifolia extracts were fed to rats, mice and African catfish to see if their induced ED could be alleviated (Table 1). Those plant extracts increased sexual activity serum testosterone levels and luteinising hormone, sexual desire (libido), penile reflexes, penile erection, penile ejaculation, intromission, mounting frequency, testicular weight, sperm count, sperm motility, quick flips, long flips, and fertilization ability of mice or rats. Precursors of sexual function such as testosterone level, libido, and penile erection are linked to the presence of aphrodisiac activity of medicinal plants.¹⁰⁹ The abovementioned plant extracts exhibited polyphenols, phenols, flavonoids, alkaloids, tannins, terpenoids, coumarins, sterols, saponins, glycosides, anthraquinones, carotenoids, anthracyanosides, and steroids, which could have played a role in alleviating ED in those animal models. Aphrodisiac action of various plants including Carica papaya were also found to be attributed to the presence of tryptophan, carotenoid, vitamins, flavonoids (quercenin, kaempferol), some minerals, and amino acids (arginine).¹⁰⁹ Minerals such as potassium, calcium, zinc, and magnesium play an important role in the processes that promote penile erection.¹⁰⁹ In some studies,^110,111 minerals (e.g. zinc) and vitamins were found to stimulate the synthesis and release of testosterone by regulating luteinising hormone and testosterone-degrading enzymes in animal models. In other studies,^19,109 phytoconstituents that exhibit antioxidant properties played an important role in enhancing male reproductive function. A. sativum extracts increased sexual behavior of male rats through the activity of phytoconstituents such as steroids, flavonoids, phenolics, and allicin, which increased blood flow to sexual organs through nitric oxide synthase.¹⁰⁹ Erythrina lysistemon flavonoids also improved blood flow and vascular health for erectile function. W. somnifera root extract also improved the production of nitric oxide (NO) signaling the pathway at the penile site in mice.¹¹² M. oleifera extracts were able to alleviate sexual dysfunction via the inhibition of cleaving enzymes monoamine oxidase type B and PDE-5 in male rats. The inhibition of PDE-5 increases the production of cGMP, reduces intracellular calcium (Ca²⁺), and induces vasodilation in the inner walls of blood vessels resulting in increased blood flow to prolong penile erection.^14,15,113 The penis is composed largely of a sponge-like smooth muscle called the corpus cavernosum. During arousal, blood fills the lacunar spaces in the smooth muscle. The result of sexual stimulation is a release of the smooth muscle relaxant property, nitric oxide (NO), from the endothelial cells by the enzyme NO synthase (eNOS) that uses L-arginine as its substrate. NO diffuses into the smooth muscle cells of the corpus cavernosum where it binds to and activates guanylate cyclase. A. sativum (garlic) extracts also activated guanylate cyclase enzyme by increasing the production of cGMP in the body, stimulated sexual desire or libido, and mediated relaxation of smooth muscle cells to dilate or widen blood vessels, which yielded increased blood flow into penile tissues resulting in an erection.¹¹⁴ A. vera also proved to be a natural vasodilator as its extracts fed to rats increased the amount of nitrogen (converted to nitric oxide or NO) produced in the body, which loosened and widened walls of blood vessels, thereby allowing blood flow to the entire body and penile tissues. Furthermore, Allium sativum extracts facilitated the release of endothelial nitric oxide synthase (eNOS) or neuronal NOS (nNOS), which converts L-arginine to L-citrulline to form or synthesise NO in vascular smooth muscle.^115,116 As such, the therapeutic effect of A. sativum extracts on the improvement of erectile function was found to be comparative to or even better than that of Viagra. S. longepedunculata xanthones stimulate the relaxation of corpus cavernosum smooth muscle of the penis by 97% in comparison to Viagra at 1.8 × 10⁻⁵ mg/mL.¹⁰⁹ Annona senegalensis extracts also exhibited anticonvulsant property that could help relax corpus cavernosum smooth muscles. Antimicrobial and immunomodulatory properties of several aphrodisiac plants in Table 1 have enabled the body to treat or prevent pathogenic infections, which also enhances vascular endothelial function to increase blood flow in the body and penile tissues. This augments the immune response to prevent pathogenic infection in states of immunodeficiency, to fight pathogenic infections and to mitigate risks of chronic diseases including cancer. These findings are indicative of pro-sexual stimulatory potential of aphrodisiac plants, which could alleviate ED. Although undertaking clinical trials remain a challenge, Malviya et al¹⁹ have presented several other plants that have scientifically been validated for the management and treatment of ED. The influence of secondary metabolites and pharmacological properties on vascular system (vascular endothelium) and erectile function is unpacked as follows.

Since oxidative stress and inflammation contribute to ED, antioxidant and anti-inflammatory properties might indirectly support erectile health. Free radicals [reactive oxygen species (ROS) and reactive nitrogen species (RNS)] cause cellular oxidative stress and inflammation that damage the inner lining of arteries and veins within the body and penis resulting in vascular endothelial dysfunction and cardiovascular complications such as hypertension and atherosclerosis.^5,115,117 Free radicals linked to inflammation react with NO to form peroxynitrite that increases the degradation of NO, which leads to a reduced NO production and availability.¹¹³ This impairs vasodilation, which increases vascular resistance marked by vasoconstriction (narrowing of the lumen or walls of blood vessels) and conversion to a prothrombotic, atherosclerosis and proinflammatory state.¹¹⁸ Endothelial dysfunction primarily causes ED because of the decreased blood flow to penile tissue and the inability to achieve or maintain an erection.¹¹⁷ It must however be noted that a reduced lumen diameter of the artery could also cause cardiovascular disease such as hypertension (HTN) due to the development of high blood pressure (HBP). Inflammation is also regarded as a major factor in the development of metabolic abnormalities that contribute to ED due the production of pro-inflammatory cytokines (IL-1, IL-6, IL-12, TNF-α), which too damage endothelium. Therefore, antioxidant and anti-inflammatory properties in extracts of many plants in this review were critical as they scavenged free radicals (ROS and RNS) and inhibited the production of pro-inflammatory cytokines, respectively. For instance, extracts of A. vera, E. capensis, B. natalensis, K. africana, M. serrata, Z. officinale, M. angustifolia, A. sativum, and M. whitei fed to male rats sequestered free radicals and inhibited the secretion of proinflammatory factors to boost endothelial cells lining blood vessels to enhance the stimulation of NOS activity to produce NO to increase blood flow. A. vera extracts decreased inflammation by 48% and 37% in a rat adjuvant induced arthritic inflammatory model and croton oil-induced edema, respectively. Ricinus communis extracts exhibiting flavonoids fed to mice reduced induced edema by 26% and 58% due to a good anti-inflammatory activity. Furthermore, R. communis extracts exhibiting flavonoids and tannins, which are strong antioxidants, fed to mice had promising free radical scavenging activity. Cytokine modulation increases the production of NO in Baker et al,¹⁰ which demonstrates the potential therapeutic utility of anti-inflammatory property in the management and prevention of ED. Zhu et al¹¹³ also found that the elevated compound dietary antioxidant Index (CDAI) levels were closely linked with a reduced risk of ED while the CDAI was significantly reduced in ED patients. Antioxidant and anti-inflammatory properties support healthy testosterone levels and protect endothelial cells from oxidative stress by neutralizing free radicals. Antioxidant activity also reduces the injury effect or structural damage and apoptosis (cell death) on the endothelium of capillary and artery by quenching free radicals through bioactive components such as superoxide dismutase (SOD), minerals (zinc²⁺, selenium), vitamins (A, Bs, C, E), secondary metabolites (flavonoids, phenolics, polysaccharides, polyphenols, and saponins).^107,119 In this review study, phenolics, flavonoids, tannins, terpenoids, carotenoids, and anthocyanins, characterized by antioxidant and anti-inflammatory, reduced atherosclerosis formation and risk of developing cardiovascular disease (hypertension or high blood pressure) and decreased inflammatory biomarkers levels. Scavenging free radicals that cause oxidative stress prevent the onset of chronic diseases, which can impair cardiovascular system.¹²⁰ Reduced atherosclerosis activity means a decrease in the buildup of plague, which widens the lumen size of arteries to increase blood flow. Extracts of several other plants in Owaba et al¹⁰⁹ used as aphrodisiacs also exhibited secondary metabolites (flavonoids, xanthones), vitamins (A, B₁, B₂, B₃), and minerals (zinc, iron, potassium, phosphorus, copper) characterized by antioxidant and anti-inflammatory properties, which could protect organs from oxidative stress caused by free radicals and cytokines. Flavonoids of S. longepedunculata, Erythrina lysistemon, and other plant extracts improved vascular health and blood flow, which are crucial for erectile function. Those phytoconstituents and the associated pharmacological properties heightened libido, increased the level of serum testosterone, inhibited lipid peroxidation, stimulated the relaxation of corpus cavernosum smooth muscle, and dilated arteries or blood vessels in the penis. Habitual intake of specific flavonoid-rich foods was also found to be associated with reduced ED incidence.^121,122 Healthy endothelial cells in corpus cavernosa of the penis regulate erectile function by releasing NO and other vasoactive agents to promote vasodilation and relaxation of corpus cavernosum smooth muscle cells to increase blood flow to facilitate penile erection.^7,123 In preclinical and clinical studies,¹¹² natural products rich in polyphenols also exhibited therapeutic potential in ED because of their anti-inflammatory and antioxidant properties that had increased intracavernous blood flow by enabling smooth muscle cell to relax leading to an improvement in erectile function. Another study¹²⁴ had established that antioxidant treatment with α-tocopherol (vitamin E) improved the impairment of relaxation in the corpus cavernosum by enhancing neuronal NO action as well as endothelial function. Furthermore, anti-inflammatory activity in rats normalized the expression of vascular endothelial growth factor and decreased tumor necrosis factor-α (TNF-α) in the lumen of the blood vessels of the organ, which proved effective in preserving erectile function in a rat model of neurogenic ED.¹²⁵ Anti-inflammatory activity treatment before cavernous nerve (CN) injury in rats also improved erectile recovery and vascular regeneration, and preserved the micro-architecture of the corpus cavernosum.¹²⁵ Secondary metabolites and phytonutrients of plants also increase the amount of nitrogen produced in the body to form NO, which loosens and widens blood vessels, thereby allowing more blood flow to the penis. Since oxidative stress was prevalent in ED patients,^126,127 scavenging free radicals may prevent risks of the onset of ED. In a clinical study based on men over 50 years old,⁷ antioxidant supplementation significantly improved erectile function compared to placebo. This is because antioxidant and anti-inflammatory therapy are a useful tool for preventing smooth muscle dysfunction and fibrosis in ED condition.¹²⁸ Most ED patients were found to have high levels of pro-inflammatory cytokines such as tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), and interleukin-8 (IL-8).¹²⁹ Inflammation and diabetes mellitus are linked with ED male patients in various studies.^130–133 Since inflammation is associated with ED,¹³⁰ the above stated anti-inflammatory properties of plant extracts have potential to indirectly support erectile function. Plant-based anti-inflammatory activity of the identified plants promises to prevent the onset of ED condition in men by reducing the production of pro-inflammatory cytokines due to therapeutic effects of sterols, flavonoids, phenolics, alkaloids, some vitamins, and other phytoconstituents. M. oleifera sterols were also found to inhibit the secretion of inflammatory factors. Other botanical drugs showed promising therapeutic effects on ED in clinical studies without significant adverse effects in particular study.¹⁴

Diabetic condition has an influence on vascular system and ED. The presence of hyperglycemia and insulin resistance in diabetes mellitus makes metabolic processes of the endothelial cell undergo excessive oxidative stress, which causes endothelial cell injury and early development of atherosclerosis.¹³⁴ Endothelial cell injury results in endothelial dysfunction, which impairs the availability of NO and therefore vasodilatation that slows or blocks blood flow to the body and penile tissues. Atheroscslerosis also reduces the flow of blood due to a build-up of plague (fats, cholesterols, calcium deposits), which narrows the lumen of vessels. Glycation end-products and ROS derived from a hyperglycemic state also accelerate endothelial dysfunction by lowering NO bioavailability, and the essential stimulus of relaxation on the smooth muscles.¹³⁵ Several aspects of altered metabolism in individuals with type-2 diabetes may compromise the penile vasculature structure and functions, thus exacerbating the imbalance between smooth muscle contractility and relaxation.¹³⁵ This is the reason ED prevalence increases in patients with long-lasting diabetes and of greater severity.^136,137 Diabetic patients are even less responsive to medical therapy than non-diabetic patients both with ED.⁴ Therefore, inhibiting diabetic condition is also likely to prevent the onset of ED. In this review, A. vera, Z. officinale, S. longepedunculata, R. communis, K. africana, and V. unguiculata extracts exhibited great antidiabetic (antihyperglycemic) and antiatherosclerosis properties by lowering serum glucose and build-up of plague (cholesterol and triacylglycerol) under preclinical and clinical trials, respectively. R. communis extracts fed to mice resulted in the elevated level of insulin and better lipid profile, which resulted in the decreased levels of glucose from 390 mg/dL to 148 mg/dL (ie, 62% reduction). Sterols emanating from M. oleifera extracts also reduced the absorption of cholesterol by the intestines. Rats fed with A. vera extracts containing some polysaccharides and vitamin Bs significantly reduced the level of phospholipids along with the elevation in the level of high-density lipoprotein (HDL) known as good cholesterol. A. vera vitamin Bs also help lower the level of lipoprotein cholesterol in the bloodstream. The prevention of the build-up of plague may help to reduce the development of atherosclerosis while widening lumen of arteries and increasing blood flow in the body and penis. As such, lowering of serum cholesterol, which when elevated accelerates the deposition of fatty materials in arteries, including the coronary arteries of the heart, could minimize risks of hypertension and the onset of cardiovascular diseases in humans. Antidiabetic and anti-obesity properties of those plants were attributed to various secondary metabolites such as xanthones, essential oils, polysaccharides, flavonoids, alkaloids, polyphenols, S-allyl cysteine, and carotenoids.^107,108,119 Polyphenolic compound, pycnogenol, improved erectile function in patients with ED and diabetes mellitus (DM) group by 45%, in non-diabetes mellitus (NDM) group by 22%, in lowering of total and low-density lipoprotein cholesterol by 20% and 21% and glycemia by 22% in DM patients.¹³⁸ This compound inhibited arginase, acetylcholinesterase, angiotensin converting enzyme (ACE), rhokinase II; activated endothelial and neuronal nitric oxide synthase (nNOS); decreased synthesis of luteinizing hormone and testosterone reduction; activated silent information regulator 2-related enzymes (sirtuin1) and inhibited free radical/reactive oxygen species.¹³⁹ Essentials oils of certain plants exhibited hypoglycemic properties that hindered glucose production, increased glucose uptake, and improved insulin sensitivity.¹²² Essential oils also increased antioxidant effects by regulating antioxidant enzymes, scavenging ROS, and decreasing lipid peroxidation.¹²² In another study,¹⁴⁰ intake of plant-based polysaccharides was also found to have improved glucose metabolism and reduced bodyweight in animal models of obesity. Glucose- and cholesterol-lowering properties (antiatherosclerosis) of plants improve endothelial dysfunction and preserve endothelial cell viability, which stimulate NO production and the relaxation of vessels to increase blood flow in the body and penis.¹³⁵ A. sativum S-allyl cysteine had enabled restoration of erectile function or reversed ED in diabetic rats by inhibiting ROS formation via modulation of nicotinamide adenine dinucleotide phosphate (NADP) oxidase subunit expression in penile tissue.

As was briefly explained above, a build-up of plague (atherosclerosis) is one of the major causes of ED in men as it clogs the blood vessels. This, in turn, affects the flow of blood into the penile area, resulting in ED. Coronary heart disease (hypertension) associated with build-up plague on the lining of the arteries is still one of the major causes of death in the Western world. In this review, antihyperlipidemic, antihypercholesterolemic, antiatherosclerosis or anti-dyslipidemia property of many plants such as A. sativum, A. vera, V. anguiculata, and Z. officinale in in vitro and in vivo (animals and humans) studies inhibited lipid peroxidation (causing oxidative degradation of lipids) and lowered the build-up of plaque or the accumulation of cholesterol and calcium deposits on inner walls of blood vessels. Continuing feeding plant extracts exhibiting such properties to rats also reduced the absorption of dietary cholesterol to widen walls or lumen of arteries and increase blood flow in the body and penile tissues. Flavonoids, polyphenols, polysaccharides and alkaloids as well as vitamins (B₄, B₉, B₁₂) were found to be responsible for this due to their antiatherosclerosis properties.^107,108 V. unguiculata leaf extracts possessed flavonoids that were characterized by antihyperlipidemic activity. Inhibition of lipid peroxidation prevents overproduction of ROS, which could cause oxidative stress to damage endothelial cell integrity. Antiatherosclerosis activity may also alleviate hypertension by opening clogged arteries (ie, widening the lumen of arteries) to promote blood flow throughout the body and to enable penile erection. This is also likely to reverse vasculogenic ED, which usually occurs when arteries and veins supplying blood to and from corpora cavernosa of the penis are blocked by cholesterol.⁴ A. vera vitamin Bs also helped with lowering the level of lipoprotein cholesterol on inner walls of vessels. Vasodilatory (vasorelaxant) activity of Eriosema kraussianum and Cleome gynandra enabled the relaxation of vascular system to widen walls of vessels to increase blood flow, which could be ascribed to the presence of NO. NO converted from V. unguiculata L-arginine in the body enabled the corpus cavernosum smooth muscles in the penis to relax, which allowed chambers inside the penis to open wide and fill up with blood triggering an erection. Anticonvulsant activity of A. senegalensis is a muscle relaxer that affects smooth muscle cells of mice. Anti-thrombotic activity of C. gynandra and A. sativum also prevented the formation of blood clots in vessels to widen lumen and increase blood flow.

Sickle cell disease (SCD), especially the sickle cell anemia (SCA) is also associated with ED. This is a condition in which red blood cells take a shape of a sickle.¹⁴¹ Those sickle cells are rigid or inflexible and they stack one over another preventing them from flowing in the vessels.^142,143 This condition is associated with overproduction of ROS, which promotes intravascular oxidative stress and inflammation in endothelial cells disrupting NO homeostasis.¹⁴⁴ All this reduces or blocks the flow of blood from vessels to vital organs including penis, which may cause thrombosis.^141,142 This explains why ED is more prevalent among men with this SCD than those without it.¹⁴⁵ In this review, anti-sickling or anti-anemic activity of Ziziphus mucronate, A. vera, V. unguiculata, A. sativum, C. papaya, and Citrus sinensis had alleviated or reversed the anemic condition in mice. This activity is able to prevent the sickling of healthy red blood cells caused by microvascular occlusion.³¹ For instance, 92% of sickle cells in control (in the presence of hydroxyurea) was considerably reduced to 29%, 42%, 33%, 38%, and 48% when treated with Cajanus cajan seed, C. cajan leaf, Zanthoxylum zanthoxyloides leaf, and C. papaya leaf extracts, respectively.¹⁴⁶ Nutritional preparation of C. cajan fruit with proven anti-sickling properties is already being used in the management of sickle cell disease in Nigeria.¹⁴⁷ Additional fruit preparations from Persia americana and C. sinensis in the same country were also found to possess promising anti-sickling properties in an in vitro study. A. sativum (exhibiting S-allyl cysteine and fructosyl arginine compounds),¹⁴⁸ as well as V. unguiculata and A. senegalensis extracts also exhibited great anti-sickling activities.¹⁴⁹ Anti-sickling properties are ascribed to phytoconstituents such as anthocyanin, essential oils, flavonoids, carotenoids and nitrogenous substances.¹⁴⁷ These compounds are also characterized by strong antioxidant activities. Antioxidant activities have potential to be used as therapeutic management of sickle cell disease by providing a shield against lipid peroxidation in red blood cells.^150,151 Overall, anti-sickling property reduces the destruction of red blood cells, which promotes the flow of healthy blood to vital organs including penile tissues.

Safety and Toxicity of Herbal Medicines

About 29 aphrodisiac plants were screened for safety and toxicity in this review (Table 2). The screening studies were largely dominated by animal models (93%) with only 7% representing clinical trials. Of all those plants, 13 or approximately 45% showed varying nature of toxicity while the remaining majority (16 or 56%) did not. Those plants were Euphorbia tirucalli, Capparis tomentosa, E. lysistemon, Acacia senegal, S. madagacariensis, R. communis, A. vera, B. natalensis, Peltophorum Africana, K. africana, A. sativum, Catha edulis, and Cannabis sativa. Strychnos spp. alkaloids (especially tropane, nicotine, pyrrolizidine, lupin) and R. communis ricin and agglutinin were found to be highly toxic in nature and showed severe effects on animal and human health.¹⁰⁶ A. sativum extracts exhibited side effects and toxicity that were found to be less than those of Viagra.¹¹⁴ It is however noted that animal models are poor indicators of drug safety in humans.¹⁵

Table 2.

Safety and Toxicity of Some Aphrodisiac Plants (Data Extracted from Table 1).

Scientific name	Levels of safety and toxicity	Study types
Bidens pilosa	Oral acute and 28-day toxicities of water extract of B. pilosa leaves were evaluated in Wistar rats. An oral dose of 10 g/kg BW showed no obvious mortality or changes in the appearance in rats. The same extract at 0.8 g/kg BW/day, once a day, showed no obvious sub-chronic toxicity in rats over 28 days, as measured by survival rate, body weight, and gross examination of organs.	In vivo
Euphorbia tirucalli	It is cytotoxic at LC₅₀= 23.10 ppm in mice.	In vitro
Capparis tomentosa	Safety studies yielded opposing findings. One study indicated that there were no toxic effects on brine shrimps while the other indicated toxic effects on goats and camels, which died instantly after consuming plant extracts.	In vivo
Erythrina lysistemon	Plant extracts did not show toxicity on human mammary epithelial (non-cancerous) cells. But showed high lethality against brine shrimps (Artemia salina) due to the presence of some alkaloid compounds known to be highly toxic.	In vitro and in vivo
Acacia senegal	Toxicity studies of ethanolic extract from stem bark revealed significant toxicity against brine shrimp (Artemia salina).	In vivo
Strychnos madagacariensis	The extract was toxic exhibiting mortality rate of 68.0% and mutagenic against both Salmonella typhimurium strains due to alkaloids.	In vitro
Ricinus communis	Cytotoxicity - Ricinus communis seed contains two poisonous toxins (ricin and agglutinin) that affect insect, animals and humans severely.	In vivo and clinical
Aloe vera	One group of people in the study advocates that extracts are quite safe for human consumption. The other group warns to use it with caution and utmost care to avoid contamination of aloin from the yellow exudates, as aloin is reported as DNA damaging and causes cancer. Studies in mice revealed no acute toxicity in therapeutic doses but in high doses a decreased central nervous system (CNS) activity was noticed. In chronic treatment, decrease in red cell count and significant sperm damage was noticed.	In vivo
Dichrostachys cinerea	Leaf extracts of up to doses of 2000 mg/kg, 3500 mg/kg, 539 ug/mL, fed to Sprague-Dawley rats, Swiss albino mice, and brine shrimps did not show sign of toxicity or mortality. Leaf butanol extract exhibited LD₅₀ value of 1265 mg/kg indicating that the extract is less toxic. In another study, triterpenoid and flavone had cytotoxic effects towards the 9 tested cancer cell lines of mice with IC₅₀ values below 50 μM. The recorded IC₅₀ values varied from 7.65 μM (towards multidrug-resistant CEM-ADR5000 leukemia cells) to 44.17 μM (against HepG2 hepatocarcinoma cells).	In vivo
Bulbine natalensis	Toxic on liver but not kidney functionality in rats.	In vivo
Peltophorum Africanum	The toxicity of the stem bark extract on normal human liver cell was 82.6 µg/mL lethal dose after 24 h. The leaf, bark and root extracts did not show toxicity on the Vero monkey cell line and the brine shrimp larval mortality assays. Root and leaf nontoxicity were also indicated by inhibition of HelaP4 cell growth at a concentration of 400 µg/mL The bark extracts have lower cytotoxicity against MAGI CCR5 + cells (CC50 > 110 lg/mL). The lack of extracts’ toxicity was further shown on sheep infected with parasites H. contortus and T. colubriformis. But despite this lack of toxicity the extracts rich in phenolic compounds would need to be used carefully as phenolic compounds have useful application as well as toxicity properties.	In vitro and In vivo
Kigelia africana	In some studies toxicity ranged from low to moderate toxic. In another study, at 6400 mg/kg of extracts, mice showed signs of toxicity like jerks and writhes with 60% death. At 12 800 mg/kg, there was 80% death of the animals.	In vivo
Annona senegalensis	A. senegalensis exhibited low cytotoxicity with an IC₅₀ of 28.8 μg/mL. Various fractions of the leaf extracts have shown mild to moderate cytotoxicity in different brine shrimp lethality bioassays.	In vivo
Allium sativum	Bulb extract induced mild alterations at 300 mg/kg in mice, indicating that it is relatively safe. Not toxic up to 2200 mg/kg dosage. But previous in vivo experiments revealed that prolonged feeding of raw garlic in high doses led to weight loss and anemic due to red blood cells (RBCs) lysis, while administration of 5 mL/kg of raw garlic juice resulted in stomach injury that led finally to death.	In vivo
Catha edulis	The main toxic effects include increased blood pressure, tachycardia, insomnia, anorexia, constipation, general malaise, irritability, migraine and impaired sexual potency in men.	Clinical
Cannabis sativa	Cannabidiol in extracts of this species is potentially toxic through the inhibition of hepatic drug metabolism, alterations of in vitro cell viability, reduced fertilization capacity, and decreased activities of p-glycoprotein and other drug transporters. Prolonged use of cannabis can affect several physiological processes.	In vitro
Morella serrata	In one study, there was no toxicity recorded. In another study, cytotoxicity assay revealed potent cytotoxic potential of M. serrata methanol and ethanol root extracts by displaying LC₅₀ of 0.26 and 0.18 μgmL⁻¹, respectively.	In vivo
Cleome gynandra	No toxicity was recorded in brine shrimps.	In vivo
Artemisia annua	The lethal dose (LD₅₀) of the extract was found to be 2750 mg/kg body weight. Overall studies showed low toxicity in short time treatment.	In vivo
Carica papaya	The acute toxicity study of the C. papaya leaf extract revealed that there were no significant toxic effects of C. papaya leaf extract at the concentration of up to 2 g/kg of body weight, which corresponded to 14 times the dose incorporated in traditional medication. Concentration of C. papaya leaf extract below 2 g/kg of body weight posed no significant toxicity and adverse effects when administered orally for a 14-day interval.	In vivo
Eriosema kraussianum	There is no record of toxicity studies of E. kraussianum. But in vivo, acute toxicity carried out with E. chinense, E. laurentii and E. psoraleoides indicated a low toxicity of investigated extracts.	In vitro and in vivo
Mondia whitei	Low toxicity levels in mice fed with the extract for 90 days.	In vivo
Withania somnifera	Nontoxic.	In vivo
Securidaca longepedunculata	Acute toxicity - in vivo and in vitro, revealed that extracts are only toxic at relatively high concentrations.	In vitro and in vivo
Ziziphus mucronata	The in vivo studies show that the plant species is relatively not toxic at low dosages	In vivo
Vangueria infausta	The ethanol extract exhibited LC₅₀ values of 145 µg/mL which was nontoxic in comparison to the LC₅₀ value of 16 µg/mL exhibited by cyclophosphamide, the positive control. In another study, toxicity was the lowest.	In vivo
Monsonia angustifolia	Extracts were found to be nontoxic against Madin-Darby canine kidney (MDCK) cells and VERO monkey kidney (VERO) cells.	In vivo
Zingiber officinale	Ginger is regarded as nontoxic. It did not show any adverse effects when a dose of 0.5-1.0 g of ginger powder was ingested 2-3 times a day from 3 months to 2.5 years. Extract had no toxicity at 5000 mg/kg body weight.	Clinical
Momordica foetida	Extracts exhibited some cytotoxicity (a score of 1 out of a maximum of 4 for toxicity) although details of the toxicity study were not included. Considering the little information on the cytotoxicity of M. foetida and its wide use in folk medicines, it is obvious that the toxicological study of this plant requires more scientific attention. Nevertheless, it has been reported that cucurbitane triterpenoids found in most of the species of the Momordica genus including M. foetida are potentially toxic.	In vivo

Conclusion

Extracts of many aphrodisiac plants traditionally used for the treatment of ED and other ailments in South Africa possessed diverse secondary metabolites, phytonutrients, and pharmacological properties. Those phytoconstituents stimulated erectile function in animal models as a result of the increased sex drive (libido), testosterone, and amount of blood flowing in the penis. Furthermore, about 13 aphrodisiac plants were found to be toxic to the tested animal models. To an extent, these findings justify the use of aphrodisiac plants in the treatment and management of ED by local communities. But efficacy and safety of the phytoconstituents cannot be guaranteed for human consumption because these findings are mostly based on in vitro and animal-based in vivo studies. Therefore, efficacy and safety of those phytoconstituents are to be tested through clinical trials to establish optimal doses to be administered to people suffering from ED. Outcomes of such trials could provide leads for the development of new plant-based drugs for ED treatment and management in South Africa.

Materials and Methods

The review was based on secondary data searched from relevant literature, which was sourced and accessed from electronic databases that included Google Scholar, ScienceDirect, and ResearchGate. The following terms and combinations thereof were used to collect information: aphrodisiac plants OR aphrodisiacs, ED OR sexual impotence AND erectile function, secondary metabolites OR phytochemicals OR bioactive compounds, botanicals OR ethnobotanicals OR ethnomedicinal, pharmacological property OR biological activity, traditional medicine OR herbal medicine, cytotoxicity AND toxicity. Articles that were included in this review were those covering keywords and published in English language from anywhere in the world during the 2000-2024 period. Articles that were excluded comprised those partially accessed (abstract only), with missing author names, covering plants not found in South Africa, and with non-English full text. About 134 articles were selected and searched for information. The required information was packaged in terms of scientific name, family, traditional uses, parts used and preparations as well as phytochemical and pharmacological data (see Table 1). Gathered information and data were analysed manually to yield findings and results as reported in the body of text.

Footnotes

Declaration of Conflicting Interests

The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ethical Approval

Ethical Approval is not applicable for this review manuscript.

Funding

The author received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Thiambi R. Netshiluvhi

Statement of Human and Animal Rights

This review does not contain any studies with human or animal subjects.

Statement of Informed Consent

There are no human subjects in this article and informed consent is not applicable.

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Scientific Validation of South African Aphrodisiac Plants for Erectile Dysfunction: An Exploratory Review

Abstract

Keywords

Introduction

Results and Discussion

Aphrodisiac Plants Traditionally Used to Treat ED

Preparations and Administration of Herbal Medicines

Phytoconstituents of Aphrodisiac Plants to Alleviate Erectile Dysfunction

Mechanisms of Action of Plants in Treating and Managing Erectile Dysfunction

Safety and Toxicity of Herbal Medicines

Conclusion

Materials and Methods

Footnotes

Declaration of Conflicting Interests

Ethical Approval

Funding

ORCID iD

Statement of Human and Animal Rights

Statement of Informed Consent

References