Promising role of medicinal plants in the regulation and management of male ED

[madman]

1. Introduction

Male erectile dysfunction (ED) or impotence refers to incompetence to reach and retain adequate penile tumescence for sexual intercourse [1]. Over 152 million men globally suffer from ED [1]. The global issue of ED is anticipated to affect around 322 million males by 2025 [46,47]. Incompetence in accomplishing normal penile erection leads to depression, loss of self-confidence, socialization, and communication with the family [4]. Also, ED leads to conflicts in the relationships that negatively influence the well-being of the couple [5]. ED led men to seek medical care. The fundamental workup for patients with ED includes a detailed history of family, medical, social, and sexual history, helps to disclose the underlying onset of ED. Family history includes diabetes and cardiovascular diseases (CVDs) [6,7]. The medical history includes medications used for depression, mental illness, CVDs, and hypertension [3,41]. Social history should include a history of smoking, drug use, alcohol consumption, diet, and exercise [7]. A detailed sexual history includes open-ended questions that require the patient to elaborate more about sexual performance, previous and current relationships, and sexual health status [6,7].




2. Views on male erectile dysfunction


2.1. Physiology of the penis

The penis is one of the major parts of the male reproductive system. It consists of three erectile (cavernous) tissues, two corpora cavernosa, and corpus spongiosum. The urethra extended inside the penis to the urinary meatus that opens outside. The deep penile artery and glans or head of the penis are covered with foreskin or prepuce [12–15].


2.2. Etiology of male erectile dysfunction

2.2.1. Endocrinopathies induced erectile dysfunction

2.2.2. Neurogenic erectile dysfunction

2.2.3. Vasculogenic erectile dysfunction


2.3. Risk factors for male erectile dysfunction

2.3.1. Diabetes

2.3.2. Hypertension

2.3.3. Obesity

2.3.4. Lack of physical activity

2.3.5. Alcoholism

2.3.6. Cigarette smoking

2.3.7. Drugs induced erectile dysfunction

2.3.8. Psychological factors



3. Sex therapy


3.1. Mechanisms underlying the pathophysiology of erectile dysfunction

3.1.1. Phosphodiesterase 5 enzyme activity

3.1.2. Nitric oxide synthase uncoupling

3.1.3. Insulin signaling pathway

3.1.4. Glucose oxidation-induced superoxide production

3.1.5. Renin-angiotensin system

3.1.6. Acetylcholinesterase pathway



4. Treatment of male erectile dysfunction


4.1. Phosphodiesterase inhibitors

4.2. Alprostadil

4.3. Penile prosthesis surgery

4.4. Gonadotropin replacement therapy



5. Promising medicinal plants for the treatment of male erectile dysfunction


5.1. Animal testing and in vitro studies

5.1.1. Arctium lappa L

5.1.2. Anogeissus leiocarpus

5.1.3. Asteracantha longifolia (L.) nees

5.1.4. Berberine

5.1.5. Bulbine natalensis (Baker)

5.1.6. Camellia sinensi

5.1.7. Cinnamomum cassia

5.1.8. Curcuma longa Linn

5.1.9. Cyperus esculentus L

5.1.10. Epimedium sagittatum

5.1.11. Ficus capensis

5.1.12. Garcinia kola

5.1.13. Ginkgo biloba

5.1.14. Gloriosa superba L

5.1.15. Hunteria umbellata

5.1.16. Massularia acuminata

5.1.17. Microdesmis keayana

5.1.18. Moringa oleifera Lam

5.1.19. Myristica fragnans

5.1.20. Ocimum gratissium linn

5.1.21. Pseudopanax arboreus

5.1.22. Telfairia occidentalis



5.2. Clinical studies

5.2.1. Crocus sativus L. - Saffron

5.2.2. Eurycoma longifolia Jack

5.2.3. Panax ginseng

5.2.4. Tribulus terrestris

5.2.5. Yohimbine

5.2.6. VigRx plus







6. Conclusion

ED is a complex disorder involving several pathophysiologic mechanisms such as nitric oxide synthase, insulin resistance, glucose oxidation-induced superoxide production, renin-angiotensin system, and acetylcholinesterase. Owing to the side effects resulting from usage of PDE inhibitors, alprostadil, penile prosthesis and hormonal replacement therapies excited prompted researchers’ interest to investigate more medicinal plant species and natural active constituents to alleviate and cure ED. Few clinical trials have evaluated the safety and efficacy of medicinal plants for the treatment of ED. According to the results of animal experiments and in vitro studies, medicinal plants have revealed potential therapeutic effects against male ED. Clinical trials on these medicinal plants could help in the development of new and abundant drugs for ED treatment.

 

[madman]

Fig. 1. Phosphodiesterase 5 induces male erectile dysfunction. Abbreviations: L-Arg = L-arginine; O2 = molecular oxygen; NOS = nitric oxide synthase; NO = nitric oxide; GTP = guanosine-5′-triphosphate; cGMP = 3′-5′-cyclic guanosine monophosphate; PKG = cGMP-dependent protein kinase; Protein P = protein phosphorylation; Ca2+ = calcium ion; PDE5 = phosphodiesterase 5.

 

[madman]

Fig. 2. Oxidative stress induces uncoupling nitric oxide synthase and diminished levels of nitric oxide. Abbreviations: L-Arg = L-arginine; O2 = molecular oxygen; BH4 = tetrahydrobiopterin; NO = nitric oxide; BH2 = dihydrobiopterin; O2− = superoxide; ONOO- = peroxynitrite; NO2 = nitrogen dioxide; OH- = hydroxyl radical.

 

[madman]

Fig. 3. Relationship between the insulin signaling pathway and the male erectile response. Normal insulin levels result in nitric oxide production, whereas insulin resistance impairs nitric oxide synthesis. Abbreviations: IRS1 = insulin receptor substrate 1; PI3K = phosphoinositide-3 kinase; Akt = protein kinase B; NOS = nitic oxide synthase; NO = nitric oxide; P = phosphorylation; PKC = protein kinase C; line ⊥ = inhibition.

 

[madman]

Fig. 4. Sequential steps by which high blood sugar levels lead to increased formation of superoxide anions associated with erectile dysfunction. Abbreviations: NADH = nicotinamide adenine dinucleotide; NAD+ = oxidized nicotinamide adenine dinucleotide, H+ = hydrogen ion; FADH2 = flavin adenine dinucleotide; FAD = oxidized flavin adenine dinucleotide; FAD+ = reduced flavin adenine dinucleotide; O2− = superoxide; ↑ = increased.

 

[madman]

Fig. 5. Chronic effect of increasing levels of angiotensin II in the renin-angiotensin system on penile erection. Abbreviations: AT1R = angiotensin type 1 receptor.

 

[madman]

Fig. 6. The effect of acetylcholinesterase on the acetylcholine released by cholinergic nerve leads to contraction of corpus cavernosum smooth muscle compared with the absence of acetylcholinesterase results in adequate production of nitric oxide and relaxation effect. Abbreviations: ACh = acetylcholine; AChE = acetylcholinesterase; L-Arg = L-arginine; O2 = molecular oxygen; NOS = nitric oxide synthase; NO = nitric oxide; ↑↓ = increase or decrease.

 

[madman]

*ED is a complex disorder involving several pathophysiologic mechanisms such as nitric oxide synthase, insulin resistance, glucose oxidation-induced superoxide production, renin-angiotensin system, and acetylcholinesterase.