Currently, there are four orally active drugs are available to treat ED. These include: sildenafil citrate (Viagra [Pfizer, USA]), vardenafil hydrochloride (Levitra [Bayer, Germany]), tadalafil (Cialis [Eli Lilly, USA]) and avanafil (Stendra, Spedra [Vivus Inc, USA]). These drugs inhibit the enzyme phosphodiesterase type 5 (PDE-5), which is responsible for the hydrolysis of cGMP. PDE-5 inhibitors and cGMP act as effectors of dilation of smooth muscle of cavernosal bodies. PDE-5 inhibitors are contraindicated in patients taking any kind of nitrate therapy for angina, and may not be appropriate for men with certain health conditions, such as severe heart disease, heart failure, history of stroke or heart attack, uncontrolled high blood pressure or diabetes, and patients with pigmental retinopathy. PDE-5 inhibitors are less effective in men with diabetes and men who have been treated for prostate cancer. PDE-5 inhibitors are also not effective in men with retinitis pigmentosa, a genetic disease involving PDE-5 deficiency. The common side effects of PDE-5 inhibitors include gastrointestinal upset, headache, nasal congestion, back pain and dizziness. The PDE-5 inhibitors may interact with other medications including antihypertension drugs. Nonetheless, the PDE-5 inhibitors are generally safe and effective for most men. The primary mechanism of action of these drugs is through the mediation of NO. NO is one of the key molecules involved in ED. It is a short-lived, highly permeable, pleiotropic, gaseous molecule, secreted from the postganglionic cavernosal parasympathetic nerves, endothelium of the cavernosal blood vessels, platelets in the cavernosal sinuses and phagocytic cells (monocytes, macrophages and neutrophils). NO acts on platelets to inhibit platelets adhesion and aggregation. NO causes relaxation of the smooth muscle of the cavernosal blood vessels of the penis, leading to vasodilation, tumescence and stimulation. Release of NO in the corpus cavernosum of the penis during stimulation activates the enzyme guanylate cyclase, which results in increased levels of cGMP, producing smooth muscle relaxation in the corpus cavernosum and resulting in increased blood flow (5). NO is mainly produced from cavernosal nerves, which are nonadrenergic, noncholinergic nerves within the penis, and acting via its second messenger cGMP. It has been suggested that maintaining normal body weight and mild exercise, as well as dietary supplementation of folic acid, zinc, calcium, vitamin C, vitamin E and L-arginine, a precursor of NO, can support the biochemical pathway leading to NO release . NO is an effector molecule that is involved in a number of intracellular functions such as vasorelaxation, endothelial regeneration, inhibition of leukocyte chemotaxis and platelet adhesion . A small proportion of autonomic nerves do not release either Ach or norepinephrine . For example, the cavernous nerves predominantly release NO in the penis. The exact mechanism is not known, but it is believed to be through increased intracellular calcium. Another gaseous molecule produced in the corpora cavernosa is hydrogen sulphide (H2S), which is also known to be involved in erectile function . H2S activates ATP-sensitive potassium channels in smooth muscle cells. Some reports indicate that NO acts in large vessels and H2S in small vessels. A high level of tumour necrosis factor-alpha has been shown in ED patients . Although current ED therapies using PDE-5 inhibitors are safe and effective, approximately 40% of ED patients do not respond to currently available treatment [11,12]. For these patients, herbal therapy may be useful.
W somnifera (ashwagandha), also referred to as winter cherry (family Solanaceae), grows in Africa, the Mediterranean, India, Pakistan, Bangladesh, Afghanistan, South Africa, Egypt, Morocco, Congo and Jordan . The roots of the plant contain steroid alkaloids and steroidal lactone, which are the main constituents of ashwagandha; these compounds are referred to as withanolides. Among the various alkaloids, withnine is the main constituent. The other alkaloids are somniferin, somnine, somniferine, withananine, pseudowithanine, tropine, pseudotropine, cuscohygrine, anferine and anhydrine. Two acyl steryl glucosides (sitoindoside VII and sitoindoside VIII) have been isolated from the root. The withanolides contain a C28 steroidal nucleus with a C9 side chain and six-membered lactone rings. Ashwagandha root also contains flavonoids and many ingredients of the withanolide class. It has several medicinal applications (aphrodisiac, liver tonic, anti-inflammatory agent, astringent), and is used to treat bronchitis, asthma, ulcers, insomnia, senility and dementia. Clinical trials and studies involving animal models support the use of ashwagandha for anxiety, cognitive and neurological disorders, inflammation and Parkinson’s disease. It also provides cryoprotective benefits to patients undergoing radiation and chemotherapy, and shows beneficial effects for nervous exhaustion. W somnifera is used as an aphrodisiac, sedative and rejuvenative, and is also used to treat chronic fatigue, dehydration, bone weakness, muscle weakness, loose teeth, impotency, premature ejaculation, debility, constipation, senility, rheumatism, nervous exhaustion, memory loss, drug withdrawal symptoms, anxiety and arthritis pain in the knee. Extracts from W somnifera inhibit transcription factor nuclear factor kappa B (NF-κB); thus, it acts as an anti-inflammatory agent. This has been attributed to its ability to interact with IKKB, a kinase that is responsible for the nuclear translocation of NF-κB and activation of inflammatory signalling pathways .
Epimedium extract (Horny Goat Weed) (11), (Figure 9): the Chinese refer to this herb as ‘yin yang huo’, which has been loosely translated as ‘licentious goat plant’; hence, its common name is well known as ‘horny goat weed’ by many Western cultures. Scientifically, studies have shown that Epimedium may restore low levels of both testosterone and thyroid hormone, bringing low levels back to their normal levels (5), which may account for some of its benefits in improving sexual libido. Other benefits to Epimedium involve increased muscle mass. Used for fatigue and aging, And vasodilatation effect; thus, most frequently used in treatment of sexual dysfunction in Traditional Chinese Medicine (12). The active substance from horny goat weed was reported by Xin Zhong Cheng at Beijing Medical University as Icarin—acts by increasing sexual activities and ICP levels in castrated rats after long term oral administration. It has no effects on serum testosterone level in castrated rats after long term oral administration. Instead Icariin increases nNOS and iNOS mRNA and protein expression in the corpus cavernosum after long term oral administration and hence may have long term efficacy on erectile dysfunction after oral administration.
A list of 33 medicinal plants both cultivated and wild-harvested generated show that herbal remedies are greatly utilized by men for managing sexual impotence and erectile dysfunction in western Uganda. Erectile dysfunction and sexual impotence are old problem and traditionally the indigenous knowledge had ways of treating or managing these conditions associated with male reproductive system. These plants in the tables we are discussing have been in use for centuries in treating or managing conditions in male reproductive organs.
Penile implants - are generally used if physical damage (like an accident) makes the anatomical parts needed for an erection not work. These are inserted by surgery and can provide a permanent treatment choice if others fail to work. The implants can be semi-rigid or inflatable. They can be pretty expensive and are not usually available on the NHS.
A number of nonprescription products claim to be herbal forms of Viagra. Some of these products contain unknown amounts of ingredients similar to those in prescription medications, which can cause dangerous side effects. Some actually contain the real drug, which should be given by prescription only. Although the Food and Drug Administration has banned many of these products, some potentially dangerous erectile dysfunction remedies remain on the market.