15 Phytochemistry of some Brazilian Plants with Aphrodisiac Activity Cinara V. da Silva, Fernanda M. Borges and Eudes S. Velozo Federal University of Bahia, Brazil 1. Introduction Since time immemorial man has used various parts of plants in the treatment and prevention of many ailments, including sexual impotence (Ayyanar & Ignacimuthu, 2009 as cited in Chah et al., 2006). Ancient people knew about herbal and animal aphrodisiacs, used in combinations like potions to mystical rites to infertility, to increase sexual performance, desire and pleasure (Malviya et al., 2011). One of the first mentions of aphrodisiacs is in the Egyptian papyruses from 2300 to 1700 B.C. In the papyrus of Ebers, mandragora, garlic, onion and blue lotus were found as plants with aphrodisiac activity (Zanolari, 2003). The tomb of Tutankhamon contain a gold plated shrine decorated with a bas-relief of a pharaoh holding a blue lotus and two mandragoras in his left hand, since the Egyptians believed in sexual life after death (Bertol et al., 2004). Hindu poems dating from 2000 to 1000 B.C. and the Kama Sutra had already reported to the use of some products to enhance the sex (Zanolari, 2003). The traditional Chinese Medicine uses with aphrodisiac purpose, among others, ginseng, Chinese chive and parts of animals for example: dogs, rhino, bear and tiger penis and testicles (Still, 2003). On this basis, the legendary love potions, such as Spanish fly, glandular products from musk deer and civet cats, varieties of natural oats (Avena sativa), ginseng, belladonna, and erotic foods like fish and oysters, are known aphrodisiacs (Drewes et al., 2003 as cited in Choudhary & Ur-Rahman, 1997). The word aphrodisiac has its origin in Greek Mythology, most precisely from the goddess of love, Aphrodite. It has been used to define the products applied with proposal of increasing desire and drive associated with sexual instinct. Besides they have represented a passion of man, since historically, in all cultures, the sexual potency is considered as a significant part of the male ego and the anxiety and humiliation is frequently associated with a declining sexual ability (Malviya et al., 2011; Zanolari, 2003). An aphrodisiac includes any food or drug that arouses the sexual instinct, induces venereal desire and increases pleasure and performance. There are two main types of aphrodisiacs: psychophysiological stimuli (visual, tactile, olfactory and aural) preparations and internal preparations (food, alcoholic drinks and love potion) (Malviya et al., 2011). www.intechopen.com 308 Phytochemicals – A Global Perspective of Their Role in Nutrition and Health Currently, the increase in life expectancy of human beings has increased the demand for substances capable of improving quality of this longevity. Among these are products that enhance sexual performance, treat impotence or erectile dysfunction. Brazil is the country with around 55,000 species of higher plants about a quarter of all known and greatest biodiversity in the world (Velozo et al., 2002). Many of these plants are used in folk medicine to aphrodisiac purposes in the form of teas, mixed with alcohol and other beverages. Some of them are belonging to the families like Anacardiaceae, Fabaceae, Sapindaceae, Amarantaceae, Amaryllidaceae, Aristolochiaceae, Bignoniaceae, Erythroxylaceae, Oleaceae, Asteraceae, Sapindaceae, Annonaceae and Dilleniaceae. Several phytochemical studies, with species from these families above cited, have enabled the isolation of secondary metabolites possibly related to its pharmacological activity, such as alkaloids, flavonoids and saponins. This chapter is a review on the chemical composition of Brazilian plants most used by the population for aphrodisiac purpose, searching rationalization between the chemical structure and biological activity (SAR). 2. Erectile dysfunction and aphrodisiac products Erectile dysfunction (ED) is experienced at least some of the time by the most of men who have reached 45 years of age, and it is projected to affect 322 million men worldwide by 2025. This prevalence is high in men of all ages but increases greatly in the elderly (Seftel et al., 2002). Sexual dysfunction, erectile dysfunction or male impotence is characterized by the inability to develop or maintain an erection of the penis and can be caused by psychological disorders like anxiety, stress and depression, physical disorders like chronic diseases: diabetes and hypertension; hormonal problems or sedentary life-style, alcohol and smoking abuses (Malviya et al., 2011; Sumalatha et al., 2010). Drugs play a significant role in the pathogenesis of ED, altering hormonal or vascular mechanics needed for erection. Alterations in penile vessels can be observed in the elderly and in particular, lack of androgens may lead to a reduction of smooth muscle cells content in the penis and an increase in the caliber of vascular spaces (Vignera et al., 2011 as cited in Galiano et al., 2010). An erection is a hemodynamic balance between inflow and outflow of blood within two chambers named corpus cavernosum and it starts with sensory and mental stimulation. There is a relaxation of the smooth muscles and arterioles which allows blood supply to flow in the sinusoidal space. The increased flow of blood, compress venules between sinusoids and the tunica albuginea of the corpus cavernosum. The lack of the distension of tunica albuginea results in venous occlusion, which increases the intracavernosal pressure, generating and sustaining a full erection (Zanolari, 2003). The erection ends when the muscles of penis contract, opening outflow channels. The relaxation of cavernous smooth muscle is mediated by Nitric Oxide (NO) via cyclic guanosine monophosphate (cGMP). After sexual stimulation, nitric oxide is released by nerve endings and endothelial cells. Nitric oxide (NO) stimulates GMP cyclase to produce cGMP, which www.intechopen.com Phytochemistry of some Brazilian Plants with Aphrodisiac Activity 309 leads to relaxation of smooth muscle. The erection ceases after a while because cGMP is hydrolysed by phosphodiesterase enzime into inactive GMP. Five types of phosphodiesterases are known to cause hydrolysis in cGMP. In the penis, phosphodiesterase is type V. Thus, a drug that inhibits the phosphodiesterase type V (cGMP-specific) should accelerate the action of nitric oxide and cGMP in erection (Drewes et al., 2003). Fig. 1. Penis anatomy diagram 2.1 Male dysfunction therapies The treatment with a psychotherapeutic approach is indicated to patients with psychological disorders. To patients with physical disorders, current treatments include oral medication, intracavernosal injection, vacuum pumps and penile prosthesis. Some oral medications are available and well-established for ED treatment, among of them, two natural products: Cantharidin (Spanish fly) and Yohimbine, besides synthetic selective inhibitors, such as sildenafil (Viagra®), vardenafil (Levitra®), tadalafil (Cialis®), lodenafil (Helleva®) and udenafil (Zydena®) (see fig.2). The PDE-5 inhibitors have shown efficacy compared to placebo, in addition to present similar form of action and side effects like headache, flushing, dyspepsia and nasal congestion (Matheus et al., 2009; Wang et al., 2008). The cantharidin is a lactone found in Spanish flies (also called Cantharides), beetles that have been cited in most of Asian and European Pharmacopoeias and have been used in dried form in internal preparations to impotence. Cantharides acts causing irritation of the urethra with vascular congestion, and inflammation of the erectile tissue. The Spanish flies are fallen into disuse due to their toxic effects (Zanolari, 2003). Yohimbine is an indole alkaloid with a 2-adrenergic blocking activity. It comes from the bark of the African tree Corynanthe yohimbe, its first isolation was in the early 1930s and remained on the African market until 1973 like a drug marketed Aphrodex. Renewed www.intechopen.com 310 Phytochemicals – A Global Perspective of Their Role in Nutrition and Health interest in yohimbine for ED has prompted several new investigative trials; however, there are indications of side-effects such as hypertension, anxiety, manic symptoms and interactions with used medications (Drewes et al., 2003). Some natural products act like non-selective PDE inhibitors as the methylxanthines caffeine and theophylline, but others show similar effects to PDE-5 inhibitors, for example: flavonoids and derivatives (quercetin from Allium cepa, pyrano-isoflavones from Eriosema kraussianum - Kraussianone 1 and 2); alkaloids (Neferin from Nelumbo nucifera, Berberine from Berberis aristata, Papaverine from Papaver somniferum – used in association with Prostaglandin-E1 to injections intracavernosal), saponins (Steroidal saponins from Allium tuberosum), coumarins (Osthole from Angelica pubescens) and terpenes (Forskolin from Coleus forskohlii) (Drewes et al., 2003; Guohua et al., 2009; Rahimi et al., 2009; Sumalatha et al., 2010; Zanolari, 2003). O O O O O EtO HN N NN EtO HN N N N O HN N NN EtO HN N NN N N N H O O2S N O2S N O2S NH O2S N N N N O O Sildenafil Vardenafil Udenafil Lodenafil OH Tadalafil N Fig. 2. Selective inhibitors of PDE-5 MeO O N O N OH O MeO N O O O OMe H OH O MeO O OMe O OH Cantharidin Papaverine Yohimbine Forskolin O O HO O O + O N OH OHO O OH OHO O OMe Kraussianone 1 Kraussianone 2 Berberine OMe Fig. 3. Examples of natural products with aphrodisiac effect 2.2 Chemical of some Brazilian aphrodisiacs species and rationalization between structure and activity The success of PDE-5 inhibitors, particularly of Viagra, the first inhibitor that has been marketed, the aging of the population and the quest for improved quality of life led to the search for new drugs with fewer side effects. As sources of research, plants used as aphrodisiacs have turned to folk medicine in whole world. www.intechopen.com Phytochemistry of some Brazilian Plants with Aphrodisiac Activity 311 There are many herbal drugs that have been used by men with ED with varying degrees of success. Most potent aphrodisiacs herbal are available and have few side effects (Malviya et al., 2011). Some of the genera and species listed in this work in in vitro tests showed satisfactory answers to such an aphrodisiac effect like Turnera diffusa (Estrada-Reyes et al., 2009), Pfaffia paniculata (Arletti et al., 1999), Passiflora (Patel et al. 2009), Mucuna pruriens (Suresh et al., 2009), Mimosa pudica (Pande & Pathak, 2009), Mimosa tenuiflora (Souza et al., 2008), Achyrocline satureioides (Hnatyszyn et al, 2004; Simões et al., 1986) and Anemopaegma arvense (Chieregatto, 2005). The effects of the Brazilian herbal medicine Catuama® and each of its plant constituents (Paullinia cupana, Trichilia catigua, Zingiber officinalis and Ptychopetalum olacoides) were investigated on rabbit corpus cavernosum. Catuama® induced relaxations, but P. cupana was the most effective, increased the cAMP levels by 200% indicating that it is the main extract responsible for the relaxing effect (Antunes et al., 2001). Specie (Family) Part used Popular Name Achyrocline satureioides(Asteraceae) Inflorescence Macela do campo Macela Anacardium Ocidentale (Anacardiaceae) Nut Caju Pseudo-fruit Anemopaegma arvense (Bignoniaceae) Stem bark Catuaba verdadeira Roots Marapuama Alecrim do campo Aristolochia cymbifera(Aristolochiaceae) Stem Cipó mil homens Arrabidaea chica (Bignoniaceae) Leaves Cipó cruz Carajiru Artocarpus integrifolia(Moraceae) Seeds Jaca Davilla rugosa (Dilleniaceae) Stem , Leaves Cipó caboclo Erythroxylum viceniifolium(Erythroxylaceae) Stem bark Catuaba Hippeastrum psittacinum(Amaryllidaceae) Bulbs Alho-bravo Alho-do-mato Açucena-do-campo Mimosa pudica (Fabaceae) Stem bark Dormideira Mimosa tenuiflora(Fabaceae) Stem bark Jurema preta Mucuna pruriensis(Fabaceae) Seeds Pó-de-mico Mucuna preta Nymphaea ampla (Nymphaeaceae) Whole plant Ninfa branca Passiflora sp. (P. edulis, P. alata and P. caerulea) Leaves Maracujá (Passifloraceae) Paulinia cupana (Sapindaceae) Seeds Guaraná Pfaffia paniculata (Amarantaceae) Roots Ginseng brasileiro Ptychopetalum olacoides(Oleaceae) Bark Marapuama Schinus terebinthifolius(Anarcadiaceae) Bark Aroeira vermelha Trichilia catigua (Meliaceae) Bark , Leaves Catuaba Turnera diffusa (Turneraceae) Leaves Damiana Table 1. Main Brazilian species with aphrodisiac activity www.intechopen.com 312 Phytochemicals – A Global Perspective of Their Role in Nutrition and Health 2.2.1 Aphrodisiacs chemical classes The classes of substances discussed were those with proven aphrodisiac activity or with this possible action. The compounds were separated in three main groups, according to structures similarities: flavonoids and others phenolics compounds; alkaloids, xanthins and others amines; and saponins. 2.2.1.1 Flavonoids and other phenolic compounds Flavonoids are polyphenols with a diphenylpropane core. According to the chemical and biosynthetic routes, flavonoids are separated into different classes: chalcones, flavonols, flavones, dihydroflavonoids, anthocyanidins, isoflavones, aurones, pterocarpanes, neoflavonoids, bioflavonoids and are presents in all flowering plants. The major classes are flavones, flavonols, anthocyanins, isoflavones and the flavan-3-ol derivatives (catechin and tannins) (Miean & Mohamed, 2001). The flavonoids are widely distributed in gymnosperms and angiosperms with therapeutic potential because of their antioxidant, anti-inflammatory, hepatoprotective, cardio protective, antiulcer, anticancer, antimutagenic, antispasmodic, anti-allergic and antiviral activities, besides to show inhibit xanthine oxidase, protein kinase C and PDE (Rahimi et al., 2009; Ko et al., 2004). Miean & Mohamed (2001) studied 62 tropical species to presence of flavonoids and observed that flavonol quercetin and derivatives, mainly quercetin glycosides, had major occurrence, however glycosides of kaempferol, luteolin and apigenin were also present. In fruits contained almost exclusively quercetin glycosides. In plants surveyed, in addition to flavonoids, other phenols were found such as caffeic and chlorogenic acid in Achyrocline satureioides (Desmarchelier et al., 2000) and chlorogenic acid in Trichilia catigua (Lagos, 2006), besides anacardic acid in Anacardium ocidentale (Kubo et al., 1994). 1,3-Diphenylpropane p-Hydroxycinnamoyl CoA Chalcone Dihydrochalcone (3) Malonyl CoA Flavan Flavanone Flavone Dihydroflavonol Flavonol Flavan 3-ol & -3,4-diol Fig. 4. Biosynthetic relationship among classes of flavonoids (Barron & Ibrahim, 1996) www.intechopen.com Phytochemistry of some Brazilian Plants with Aphrodisiac Activity 313 3' OH 2' 4' O 2 5' HO OH 7 6 5 O OH O O O Flavone Chalcone Dihydrochalcone O O O O Flavanone OH OH O O Flavonol Flavan Dihydroflavonol R OH OH OH + O HO O HO O R1 OH OH O OH OH Catechin Anthocyanidin Isoflavone Fig. 5. Basic Structures of Flavonoids OH O O O OH OH HO O OH COOH OH HO HO HO OH C H 15 31 Caffeic Acid Chlorogenic Acid Anacardic Acid Fig. 6. Phenolic substances Studies conducted by Ko and colleagues (2004) in flavonoids as inhibitors of PDE have suggested that C-4’ and C-5’ hydroxyl groups is not important for PDE-5 inhibition. The replacement of the hydroxyl by a methoxyl did not alter its inhibitory effect and it deletion resulted in no effect on PDE-5 inhibition. However, the C-7 hydroxyl group is very important for PDE-5 inhibition. C-7-glucoside showed no inhibition of the enzyme, being possible that the bulky glycosyl residues may hinder its binding to active site. Also, the C-3- hydroxyl group of flavonols seems difficult the binding with the PDE-5. The luteolin showed more potent than other flavonoids, indicating that the presence of a double bond between C-2 and C-3 is important for PDE-5 inhibition. Between a flavon and an isoflavone, it may be easier for isoflavones than flavones to bind to the moiety of PDE-5. The removal of the C-5 hydroxyl group promoted the loss of inhibition of PDE, proposing that the hydroxyl group is vital for PDE-5 inhibition (Ko et al., 2004). www.intechopen.com 314 Phytochemicals – A Global Perspective of Their Role in Nutrition and Health Specie (Family) Flavonoids and phenols Achyrocline OH OH OH OH satureioides OH OH HO O (Asteraceae) HO O HO O OH OCH3 OH O OH O OH O Luteolin Quercetin 3-O-Metil Quercetin And Caffeic, chlorogenic and isochlorogenic acids (Desmarchelier et al., 2000). Anacardium OH OH Ocidentale (Anacardiaceae) HO O OH OH OH O Myricetin And Quercetin, Anacardic Acids and derivatives (Kubo et al., 1994; Miean & Mohamed, 2001). Anemopaegma OH OH arvense OH OH O OH (Bignoniaceae) HO OOMe OH OH O OH OH O O OH OH O O O O OH OH OH HO O OH OH OH OH OH R OH Catuabine A Cinchonain Ia R = O H Cinchonain IIa R= O H KandelinAl (Tabanca et al.,2007) Arrabidaea chica OH O HO (Bignoniaceae) OH OH HO O O OH HO HO O OH HO O HO OH O HO O OMeO Carajuruflavone Acacetin OH HO OH OVicenin-A (Takemura et al., 1995) (Zorn et al., 2001) OH (Barbosa et al., 2008) OH OH R1 HO O OR MeO O HO O+ OH OMe OH O O HO Kaempferol OCH3 4'-hydroxi-3,7-dimethoxiflavone (Barbosa et al., 2008) R1= H; R = CH3 - Carajurin (Barbosa et al., 2008) R1= OH; R= H - 6,7,3',4'-tetrahydroxy-5-methoxyflavylium R1= H; R= H - 6,7,4'-trihydroxy-5- methoxyflavylium (Zorn et al., 2001) www.intechopen.com Phytochemistry of some Brazilian Plants with Aphrodisiac Activity 315 Specie (Family) Flavonoids and phenols Davilla rugosa OH OH OMe (Dilleniaceae) HO O HO O OH OH O OH O Narigenin 4'-O-methyltaxifolin Quercetin (David et al, 2006) Mimosa tenuiflora R (Fabaceae) HO O O R1 HO R OR2 MeO OH O OH O R= O Me - Kukulkan A R= O Me; R1= OH; R2= Me - Tenuiflorin A R= OH - Kukulkan B R= R1= OMe; R2= H - Tenuiflorin B R= H; R1= OH; R2= Me - Tenuiflorin C R= H; R1= H; R2= H - 6-Dimethoxycapilarisin R= H; R1= H; R2= Me - 6-Dimethoxy-4'-O-methylcapilarisin (Souza et al., 2008) Nymphaea ampla Quercetin derivatives (glycosides) (Marquina et al., 2005) (Nymphaeaceae) Passiflora sp. OMe OH (Passifloraceae) Glu OH Glu OH OH HO O HO O HO O Glu OH O OH O OH O Vitexin Scoparin Isoorientin OH OH OH Glu HO O HO O HO O Glu OH O OH O OH O Isovitexin Chrysin Orientin (P. Caeruleae) Dhwan et al., 2002) Apigenin and luteolin derivatives (P. edulis) (Ferreres et al., 2007) Flavonoids above (P. alata)(Doyama et al, 2005) Paulinia cupana Epicathechins, Cathechins (Ushirobira et al., 2007) (Sapindaceae) Schinus Quercetin, myricetin, Kaempferol and derivatives terebinthifolius (Ceruks et al., 2007; Johann et al., 2010) (Anarcadiaceae) Trichilia catigua Chlorogenic acid, catechin and epicatechin (Lagos, 2006) (Meliaceae) www.intechopen.com 316 Phytochemicals – A Global Perspective of Their Role in Nutrition and Health Specie (Family) Flavonoids and phenols Turnera diffusa HO (Turneraceae) OMe OMe O OH OH O OH HO O HO O OMe GlucO O OH O OH O Tricin Chrysoeriol OH O Echinacin Luteolin, apigenin, quercetin, orientin and vitexin derivatives (Zhao et al., 2007) Table 2. Aphrodisiacs plants, their flavonoids and phenols 2.2.1.2 Alkaloids, xanthines and others amines In broad sense, the alkaloids are natural nitrogen-containing secondary metabolites mostly derived from amino acids and found in about 20% of flowering plants. They are not limited to plants but also occur in marine organisms, insects, microorganisms and some animals (Rahimi et al., 2009). Until 2005, 150,000 compounds were known and 14% these have been alkaloids. They are special interesting due to the heterogeneity of the group and the great bioactive potential particularly as inhibitors of PDE (Silva, 2006). Many of them have been used as a basis for design and development of new and more selective drugs with reduced side effects. The methylxanthines are purine bases and have structural similarity with the cAMP and cGMP, therefore bind competitively to the sites of the various PDEs. They are considered non-selective inhibitors, such as caffeine found in Paullinia cupana seeds, theobromine and adenine from Ptychopetalum olacoides, which validate its aphrodisiac effect. Introducing achiral cyclopenthyl and hexylamines moiety in xanthines analogues enhanced inhibitory activity. The ethyl group at the N-1 and N-3 positions showed the highest effect in PDE-5 (Wang et al., 2002). Aporphines alkaloids act as dopamine agonists, due to their structural similarity. They improve central pro-erectile mechanisms by binding to receptors in the paraventricular nucleus of the hypothalamus. In clinical trials, apomorphine was found to be effective in patients with ED of various aetiologies and levels of severity, albeit with substantially less efficacy than any of the PDE-5 inhibitors (Seftel, 2002). Other plants that seem to act this way are: Mimosa tenuiflora, Mimosa pudica and Mucuna pruriens, but they need more studies to investigation their aphrodisiac activities. While many β-carbolines have effect as a selective inhibitor of PDE-5, the alkaloids of Passiflora seems to have effect as serotonin uptake inhibitors and therefore act with antidepressants. Recently, harmine and numerous related β-carboline derivatives were found as potent and specific inhibitors of cyclin-dependent kinases (CDKs), and the structure activity relationships (SARs) analysis demonstrated that the degree of aromaticity www.intechopen.com