Epimedium Icariin

Fitoterápico no tratamento da libido masculina

DESCRIÇÃO

Extrato seco obtido das folhas de Epimedium sagittatum, que contém flavonoides (icariin), polissacarídeos, ligninas, sesquiterpenos, esteróis e alcaloides, entre outros componentes, usado na medicina popular chinesa .

MECANISMO DE AÇÃO

O óxido nítrico (NO) promove o fluxo sanguíneo por ligação à enzima guanilato ciclase, que catalisa a conversão de guanosina trifosfato (GTP) para 3,5-cíclico de guanosina (cGMP), produzindo relaxamento da musculatura lisa dos corpos cavernosos e permitindo o influxo de sangue. O Epimedium icariin inibe a fosfodiesterase-5 (PDE-5), enzima responsável pela degradação de GMPc, o que eleva potencialmente o efeito do NO endógeno liberado localmente no corpo cavernoso em função da estimulação sexual, onde inclusive alguns materiais científicos relatam também o fato dele estimular os nervos sensitivos, restaurando o desejo sexual. Estudos recentes comprovam que o icariin foi inibitório para as três isoformas PDE5 com valores de IC50 semelhantes, as quais eram aproximadamente três vezes maiores do que aqueles para o zaprinaste, demonstrando que o fitoterápico foi capaz de aumentar os níveis de cGMP em células musculares lisas cavernosos tratados com SNP.

INDICAÇÕES

 Disfunção erétil;  Diminuição da libido;  Aumentar as sensações sexuais.

DOSE USUAL

Recomendação oral de 1000mg de Epimedium icariin, fracionado em 2 ou 3 doses.

SUGESTÕES DE FÓRMULAS

Epimedium icariin (5% icariin ext. seco)....250mg Epimedium icariin (5% icariin ext. seco)..150mg Ácido D-aspártico ...... 50mg Modo de Uso: 1 dose, 2 vezes ao dia. Panax ginseng Ext. seco...... 100mg Indicação: disfunção erétil. Modo de Uso: 1 dose, 2 vezes ao dia. Indicação: diminuição da libido.

PRINCIPAIS REFERÊNCIAS

BATISTUZZO, J. A O; ITAYA, M.; ETO, Y. Formulário Médico-Farmacêutico. 5ª ed. São Paulo: Pharmabooks, 2015.

NING, H. et.al. Effects of icariin on phosphodiesterase-5 activity in vitro and cyclic guanosine monophosphate level in cavernous smooth muscle cells. Urology. V. 68, n.6, p. 1350-1354, Dec. 2006. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/17169663>. Acesso em: 22 de dezembro de 2015, às 16:37.

http://aformulabr.com.br/qrcode/zeaxantinafv01.pdf

EPIMEDIUM ICARIIN

ESTUDOS CLÍNICOS

Effects of icariin on phosphodiesterase-5 activity in vitro and cyclic guanosine monophosphate level in cavernous smooth muscle cells. OBJECTIVES:To investigate the effect of icariin on the cyclic guanosine monophosphate (cGMP)-hydrolytic activity of phosphodiesterase-5 (PDE5) isoforms and the cGMP levels in cavernous smooth muscle cells treated with sodium nitroprusside (SNP).METHODS:PDE5 isoforms (PDE5A1, A2, and A3) were isolated from sf9 insect cells infected with baculoviruses carrying PDE5 isoform cDNA. Icariin was isolated from Epimedii herba. Varying amounts (10(-6) to 10(-11) M) of icariin or zaprinast were added to reaction mixtures containing PDE5 isoforms and cGMP. The inhibitory effects of icariin and zaprinast were analyzed by GraphPad Software and are expressed as concentration that inhibits 50% (IC50) values. Cavernous smooth muscle cells were isolated from 3-month-old rats, treated with icariin (100 and 200 microM) or zaprinast (200 microM) for 15 minutes, and then with 10 microM SNP for 30, 60, 120, 240, and 360 minutes. The cells were then analyzed for the cGMP concentration using an enzyme immunoassay system.RESULTS:Icariin inhibited PDE5A1, A2, and A3 with an IC50 value of 1.0, 0.75, and 1.1 microM, respectively. The corresponding IC50 values for zaprinast were 0.33, 0.23, and 0.32 microM. Icariin consistently outperformed the control (SNP-only treatment) in maintaining greater cGMP levels, particularly at the greater concentration of 200 microM. In contrast, zaprinast at 200 microM did better than the control only at 60 and 360 minutes.CONCLUSIONS: Icariin was inhibitory to all three PDE5 isoforms with similar IC50 values, which were approximately three times greater than those for zaprinast. Icariin was able to enhance cGMP levels in SNP-treated cavernous smooth muscle cells.

Effects of icariin on cGMP-specific PDE5 and cAMP-specific PDE4 activities AIM:To clarify the mechanism of the therapeutic action of icariin on erectile dysfunction (ED).METHODS: PDE5 was isolated from the human platelet and PDE4 from the rat liver tissue using the FPLC system (Pharmacia, Milton Keynes, UK) and the Mono Q column. The inhibitory effects of icariin on PDE5 and PDE4 activities were investigated by the two-step radioisotope procedure with [(3)H]-cGMP/[(3)H]-cAMP. Papaverine served as the control drug.RESULTS:Icariin and papaverine showed dose-dependent inhibitory effects on PDE5 and PDE4 activities. The IC(50) of Icariin and papaverine on PDE5 were 0.432 micromol/L and 0.680 micromol/L, respectively and those on PDE4, 73.50 micromol/L and 3.07 micromol/L, respectively. The potencies of selectivity of icariin and papaverine on PDE5 (PDE4/PDE5 of IC(50)) were 167.67 times and 4.54 times, respectively.CONCLUSION:Icariin is a cGMP- specific PDE5 inhibitor that may be developed into an oral effective agent for the treatment of ED.

Effect of icariin on cyclic GMP levels and on the mRNA expression of cGMP-binding cGMP-specific phosphodiesterase (PDE5) in penile cavernosum To further investigate the mechanisms of action of icariin (ICA), we assessed the effects of ICA on the in vitro formation of cGMP and cAMP in isolated rabbit corpus cavernosum. Isolated segments of rabbit corpus cavernosum were exposed to increasing concentrations of ICA and the dose-dependent accumulation of cGMP and cAMP was determined in the tissues samples by means of 125I radioimmunoassay. Responses of the isolated tissues preparations to ICA were compared with those obtained with the reference compounds sildenafil (Sild). Furthermore, the effects of ICA on the mRNA expression of specific cGMP-binding phosphodiesterase type V (PDE5) in rat penis were also observed. After incubation with ICA for 6 h or 14 h respectively, the levels of PDE5 mRNA were examined by reverse transcriptase polymerase chain reaction (RT-PCR). The results showed that ICA increased cGMP concentrations directly (P < 0.05), but there was no significant effect on cAMP concentrations (P > 0.05). In the presence of sodium nitroprusside (SNP), a stimulatory agent of cGMP, both ICA and Sild increased cGMP concentrations with increasing dose (P < 0.01). Their EC50 was 4.62 (ICA) and 0.42 (Sild) micromol/L respectively. Under the same condition, ICA and Sild unaltered cAMP level significantly (P > 0.05). There were PDE5A1 and PDE5A2 mRNA expressions in rat corpus cavernosum with PDE5A2 being the dominant isoform. ICA could obviously inhibit these two isoforms mRNA expression in rat penis, and decrease PDE5A1 more pronouncedly (P < 0.01). The present study indicated that the aphrodisiac mechanisms of icariin involved the NO-cGMP signal transduction pathway, with increasing cGMP levels in the corpus cavernosum smooth muscle. The inhibitory effect of icariin on PDE5 mRNA expression, especially on PDE5A1, might account for its molecular mechanisms for its long-term activity.

Icariin on relaxation effect of corpus cavernosum smooth muscle

NO-cGMP pathway in penile corpus cavernosal smooth muscle plays an important role in penile erection. The level of cGMP is regulated by a balance between the rate of synthesis by guanylate cyclase and the rate of hydrolytic breakdown to guanosine 5′ monophosphate (GMP) by phosphodiesterase 5(PDE5). Icariin is isolated from natural drug Epimedii herba, it is shown to have the relaxation effect on corpus cavernosal smooth muscle of rabbit (IC50: 4×10−4 mol/L), and the mechanism of the relaxation effect of Icariin on corpus cavernosum believed to have the inhibiting effect on PDE5 and activation of NO-cGMP pathway to enhancing penile erection.

REFERÊNCIAS

XIN, Z.C. et. al. Effects of icariin on cGMP-specific PDE5 and cAMP-specific PDE4 activities. Asian J Androl.v. 5, n.1, p; 15-18, Mar 2003. Disponível em: http://www.ncbi.nlm.nih.gov/pubmed/12646997. Acesso em: 22 de dezembro de 2015, às 16:53.

JIANG, Z. et. al. Effect of icariin on cyclic GMP levels and on the mRNA expression of cGMP-binding cGMP-specific phosphodiesterase (PDE5) in penilecavernosum.J Huazhong Univ Sci Technolog Med Sci. V. 26, n.4 ,p.460- 462 ,2006 . Disponível em : < http : // www .ncbi .nlm. nih. gov/ pubmed/17120748>. Acesso em: 22 de dezembro de 2015, às 17:06.

ZHONGCHENG, XIN. Et. al. Icariin on relaxation effect of corpus cavernosum smooth muscle. Chinese Science Bulletin. V. 46, n. 14, p. 1186-1190, Jul 2001. Disponível em: . Acesso em: 22 de dezembro às 17:19.