**4.1. Behaviour therapy of erectile dysfunction**

When there is no obvious medical etiology for ED, psychosocial factors should be explored. The potential clue that psychosocial factors may be a cause is that a man is able to achieve normal erections and orgasm through masturbation or sexual stimulation with a partner other than the "index case" partner with whom he has ED (e.g., a spouse with whom there is substantial conflict). Group or individual cognitive behaviour therapy, psychosexual therapy, including sensate focus technique and therapy aimed at improving relationship difficulties (couple's theraphy) may help to improve sexual dysfunction in men. In some cases, education about medical and psychosocial etiologies of ED in conjunction with a physician reassurance may prove adequate to restore normal male sexual function [54]. Lifestyle interventions focused on modifiable health behaviours may be a safe strategy to improve ED.

#### **4.2. Pharmacotherapeutic treatment of erectile dysfunction**

Pharmacology of current and future therapies of erectile dysfunction depend on risk factors and conditions associated with it. Different kinds of administration have been proposed such as intracavernosal administration and non intracavernosal administration [55].

Clinical studies and experimental studies have showed positive and negative effects of the different methods of administration [55]. Pharmacotherapy involves locally acting vasoactive drugs such as papaverin and alprostadil [56] and firstline oral therapy for ED includes phosphodiesterase type 5 (PDE-5) inhibitors such as sildenafil, vardenafil, and tadalafil, which inhibit hydrolysis of the second messenger cyclic guanosine monophosphate (cGMP), the production of which is promoted by NO release within the penile smooth cells [57, 58]. Various centrally acting drugs influence sexual behaviour. In particular, the dopaminergic substance apomorphine is a central enhancer that acts in the paraventricular nucleus of the hypothalamus as a dopamine (D2) receptor agonist, inducing and increasing penile erection responses following sexual stimulation via disinhibition [59].

PDE5 inhibitors have had a tremendous impact on the treatment of ED, but are not always effective (e.g., in patients with diabetes) [55]. Common adverse events with PDE inhibitors include headache (10–16%), flushing (5–12%), dyspepsia (4–12%), nasal congestion (1–10%), and dizziness (2–3%) occurring during treatment [60]. The most successful approach to treat ED has been drugs aimed at mechanisms in the target organ. Despite significant progress, the different mechanisms involved in neurotransmission, impulse propagation, and intracellular transduction of neural signals in penile smooth muscles need further investigation. It should be remembered that most of the pharmacological options for ED treatment do not influence the progress of the underlying pathophysiology and do not cure the disease [55].

Testosterone therapy has been shown to normalize serum testosterone levels in patients with hypogonadism. Testosterone therapy was aimed at maintaining or restoring libido and erectile function; improving or maintaining virilization, muscle mass, strength, and bone density; and to alleviate other symptoms related to hypogonadism. There is some evidence that the addition of type 5 phosphodiesterase inhibitor can potentiate the effects of testosterone replacement in some hypogonadal men [8]. If this is unsuccessful, one should consider other treatments for ED. Because there are a wide range of pharmacotherapy options available, it would be desirable, in many instances, to offer patients an alternative to current pharmacotherapy.

#### **4.3. Effects of phytomedicinal plants on erectile dysfunction**

**•** Psychological/behavioural therapy with a trained counsellor aimed at helping people to address feelings of anxiety, fear and guilt that may have an impact on sexual function;

**•** Pharmacological and drug treatments (e.g testosterone replacement therapy for cases of

When there is no obvious medical etiology for ED, psychosocial factors should be explored. The potential clue that psychosocial factors may be a cause is that a man is able to achieve normal erections and orgasm through masturbation or sexual stimulation with a partner other than the "index case" partner with whom he has ED (e.g., a spouse with whom there is substantial conflict). Group or individual cognitive behaviour therapy, psychosexual therapy, including sensate focus technique and therapy aimed at improving relationship difficulties (couple's theraphy) may help to improve sexual dysfunction in men. In some cases, education about medical and psychosocial etiologies of ED in conjunction with a physician reassurance may prove adequate to restore normal male sexual function [54]. Lifestyle interventions

Pharmacology of current and future therapies of erectile dysfunction depend on risk factors and conditions associated with it. Different kinds of administration have been proposed such

Clinical studies and experimental studies have showed positive and negative effects of the different methods of administration [55]. Pharmacotherapy involves locally acting vasoactive drugs such as papaverin and alprostadil [56] and firstline oral therapy for ED includes phosphodiesterase type 5 (PDE-5) inhibitors such as sildenafil, vardenafil, and tadalafil, which inhibit hydrolysis of the second messenger cyclic guanosine monophosphate (cGMP), the production of which is promoted by NO release within the penile smooth cells [57, 58]. Various centrally acting drugs influence sexual behaviour. In particular, the dopaminergic substance apomorphine is a central enhancer that acts in the paraventricular nucleus of the hypothalamus as a dopamine (D2) receptor agonist, inducing and increasing penile erection responses

PDE5 inhibitors have had a tremendous impact on the treatment of ED, but are not always effective (e.g., in patients with diabetes) [55]. Common adverse events with PDE inhibitors include headache (10–16%), flushing (5–12%), dyspepsia (4–12%), nasal congestion (1–10%), and dizziness (2–3%) occurring during treatment [60]. The most successful approach to treat ED has been drugs aimed at mechanisms in the target organ. Despite significant progress, the different mechanisms involved in neurotransmission, impulse propagation, and intracellular transduction of neural signals in penile smooth muscles need further investigation. It should

focused on modifiable health behaviours may be a safe strategy to improve ED.

as intracavernosal administration and non intracavernosal administration [55].

**4.2. Pharmacotherapeutic treatment of erectile dysfunction**

following sexual stimulation via disinhibition [59].

androgen insufficiency

286 Antioxidant-Antidiabetic Agents and Human Health

**•** Phytomedical treatment

**4.1. Behaviour therapy of erectile dysfunction**

**•** Surgical treatment

A wide variety of human disorders is currently being treated with the use of plant materials due to their decreased toxicity levels, cost-effectiveness as well as minimized side effects in order to avoid drug resistance caused by pharmacological agents 61- 63].

Plants and herbs are persistently being studied for the identification of novel therapeutic agents. Among the 250,000 higher plant species on earth, more than 80,000 plants have medicinal values [62]. Herbal medicine is still the mainstay of about 75-80% of the global population, mainly in developing countries, for primary health care because of better cultural acceptability, better compatibility with the human body and lesser side effects. The chemical constituents presenting the herbal medicine or plant are a part of the physiological functions of living flora and hence they are believed to have better compatibility with human body [64].

A traditional system of Indian medicine called Ayurveda deals with the sexual dysfunctions in a special category of treatment under the name "*Vajikarna*" or virilification. The system includes the use of aphrodisiacs for erectile dysfunction, spermatogenesis, semenogenesis, and methods of improving defective semen, causes of infertility, reproduction and sexual satis‐ faction [65].

About 317 phytochemicals are listed for antioxidant potential; 340 plants as aphrodisiac and antioxidants and 40 plants are listed for adaptogenic nature. Ethnobotanical plants contain antioxidant, aphrodisiac and adaptogenic properties [66].

Natural antioxidants are located in different parts of a plant such as wood, bark, stems, pods, leaves, fruit, roots, flowers, pollen, and seeds [67]. Natural products, mainly phytomedicine, or diet ingested by human, are antioxidants capable of terminating the free radical chain reactions [68].

Antioxidant properties in plants are due to the presence of cinnamic acids, coumarins, diterpenes, flavonoids, lignans, monoterpenes, phenylpropanoids, tannins and triterpenes [69]. Phytochemicals like carotenoids, tocopherols, ascorbates and phenols presentin plants are considered strong natural antioxidants and have an important role in health care system. Phenols, a major group with antioxidant properties, comprise subclasses suchphenolic acid, flavonoid, biflavonoid, anthocyanin andisoflavonoid [70]. Adaptogens found in plants modulate response to stress (physical, environmental, or emotional) and help regulate the interconnected endocrine, immune, and nervous systems. This re-regulation of a disordered or highly stressed system is achieved by metabolic regulators such as, catecholamines, glucocorticoids, cortisol, serotonin, nitric oxide (NO), cholecystokinin, corticotrophinreleasing factor (CRF), and sex hormones [71]. *Chlorophytum borivilianum* (Safed Musli) is often referred to as Viagra without the side effects [71]. Safed musli contains saponin and alkaloids which give musli its medicinal properties. Stigmasterol, a form of saponin is very similar in structure to testosterone and consequently can occupy the testosterone receptor sites-door‐ ways to the cells acting like an aphrodisiac. Hecogenin has steroidal-like effects that help to synthesize anabolic hormones. Anabolic hormones allow men to retain nitrogen more readily, which helps form larger more bulging muscle during an erection.

provide them with a sense of a natural erection. Inflatable devices are more expensive than malleable devices with satisfaction rates of 70-87% reported from patients after appropriate

Potentials of Phytotherapeutic Treatment of Erectile Dysfunction

http://dx.doi.org/10.5772/57174

289

Vacuum constriction devices apply negative pressure to the penis in order to draw venous blood into the penis which is then retained by application of a visible constricting band at the base of the penis (a method that seems preferable to older patients) [79]. This method yields a successful erection for intercourse that can be rated as 90%. The satisfaction rates range between 27-94% but about <30% of the patients discontinue use after 2years because of the negative side effects that include penile pain, delayed ejaculation and numbness that occur. Penile prosthesis can go wrong because there are two major complications involved, namely mechanical failure and infection. Infection rate is therefore reduced by the use of antibiotic

Erectile dysfunction is an increasing global the incidence. ED is also indicative of more serious cardiovascular, psychoactive disorders. Therapeutic interventions that are successful in treating ED may be effective in treating the early stages of conditions that include atheroscle‐ rosis, angina, plaque rupture and diabetic angiopathy. One common pathological denomina‐ tor in both CVD and ED is oxidative stress, that is, the overproduction of ROS, in particular, O2- and H2O2.Thus there is direct relationship between oxidative stress, sexual impotency and psychoactive mechanisms that alters nitrogen oxide inhibition mechanisms significantly as stated above. Therefore it is necessary to evaluate potential of natural herbs/ extracts to correct disorders and disabilities evolved in the manifestation of ED. An ideal medicinal plant extract and or natural product will achieve biochemical, physiological, pharmacological responses on erectile dysfunction. However, because of the synergic or antagonistic effects of the contents of the natural plants, herbs or their extract, it would be a worthy to investigate on their bioavailability and properties in order to maximise their use. Moreover, further investigations

, Boitumelo R. Mosito1

1 Department of Biomedical Sciences, Faculty of Health and Wellness, Cape Peninsula Uni‐

2 Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch

, Michelle van der Linde2 and

prophylaxis or by using implants that are impregnated with antibiotics [80].

in the clinical setting and qualify for clinical trials in humans are warranted.

**5. Conclusion and recommendations**

consultation [78].

**Author details**

Stefan S. du Plessis2

Guillaume Aboua1\*, Claudine Manirafasha1

versity of Technology, Bellville, South Africa

University, Tygerberg, South Africa

\*Address all correspondence to: abouay@cput.ac.za

*Tribulus terrestris* is a herb that has been used in the traditional medicine of China and India for centuries. The active compounds in *Tribulus* are called steroidal saponins. The protective effect of *T. terrestris* for Streptozotocin –induced diabetic rats may be mediated by inhibiting oxidative stress [72]. Oral administration of 100 mg/kg of test drug has proven anabolic effect as evidenced by body weight gain in the body and reproductive organs. Improvement in sexual behaviour of male rats was characterized by increased amount and intromission frequency. Penile erection index (PEI) was also considerably enhanced without any noticeable toxicity. The testosterone level and sperm count also significantly increased. The results are comparable to that of standard drug, sidenafil citrate. Findings of the present study validate the traditional use of *T. terrestris* for its role in enhancing sexual behaviour and potential to be used in the treatment of ED [73].

Ginseng is an essential constituent in traditional Chinese medicine for the treatment of sexual impotence. It is likely that this effect reflects the tonic, restorative and adaptogenic properties. It has been shown that ginsenosides relax rabbit corpus cavernosum and this effect is mediated by nitric oxide, released from endothelial or neural cells. These endothelial and neurogenic effects of ginsenosides in inducing relaxation of the corpus cavernosum may account for the aphrodisiac effect of *Panax ginseng* [74].

*Eriosema kraussianum* Zulu indigenous plants are effective remedies for the treatment of ED and/or impotence. Five pyranoisoflavones have been isolated from the rootstock of *Eriosema kraussianum* and were screened for smooth muscle relaxation of rabbit penile muscle*.* The most active of the compounds had an activity of 75% of that found in Viagra. In a test on ED rabbit penile smooth muscle, it showed an activity close to that of Viagra, thus living up to the plant its traditional use [75, 76].

Yohimbine is an alkaloid derived from the African yohimbe tree (*Pausinystalia yohimbe*). It blocks the presynaptic α-2 adrenergic receptors in the brain, leading to reduction of brain and spinal cord norepinephrine levels. Inhibition of sympathetic tone enhances sexual arousal and NO release from penile nerves [77].

#### **4.4. Surgical treatment**

Patients who fail to respond to pharmacotherapy or those who want a permanent solution usually have surgical implantations of penile prosthesis. These prosthetics can either be inflatable or malleable, however most patients prefer the inflatable devices because they provide them with a sense of a natural erection. Inflatable devices are more expensive than malleable devices with satisfaction rates of 70-87% reported from patients after appropriate consultation [78].

Vacuum constriction devices apply negative pressure to the penis in order to draw venous blood into the penis which is then retained by application of a visible constricting band at the base of the penis (a method that seems preferable to older patients) [79]. This method yields a successful erection for intercourse that can be rated as 90%. The satisfaction rates range between 27-94% but about <30% of the patients discontinue use after 2years because of the negative side effects that include penile pain, delayed ejaculation and numbness that occur.

Penile prosthesis can go wrong because there are two major complications involved, namely mechanical failure and infection. Infection rate is therefore reduced by the use of antibiotic prophylaxis or by using implants that are impregnated with antibiotics [80].
