Planta Med 2018; 84(15): 1134-1140
DOI: 10.1055/a-0619-5547
Natural Product Chemistry and Analytical Studies
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Phosphodiesterase 5 Inhibitors from Derris scandens

Nattiya Chaichamnong
1   Bioscreening Unit, Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand
,
Prapapan Temkitthawon
1   Bioscreening Unit, Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand
,
Nantaka Khorana
1   Bioscreening Unit, Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand
,
Prompan Pitpakdeeanan
1   Bioscreening Unit, Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand
,
Pornnarin Taepavarapruk
2   Center for Animal Research and Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok, Thailand
,
Nitra Nuengchamnong
3   Science Laboratory Center, Faculty of Science, Naresuan University, Phitsanulok, Thailand
,
Yuthana Siriwattanasathien
4   Department of Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok, Thailand
,
Apichart Suksamrarn
4   Department of Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok, Thailand
,
Kornkanok Ingkaninan
1   Bioscreening Unit, Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand
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Weitere Informationen

Publikationsverlauf

received 03. Januar 2018
revised 10. April 2018

accepted 19. April 2018

Publikationsdatum:
27. April 2018 (online)

Abstract

Phosphodiesterase 5 inhibitors have been used as a first-line medicine for the treatment of erectile dysfunction. In the search for new phosphodiesterase 5 inhibitors from natural sources, we found that the 95% ethanol extract of Derris scandens stem showed phosphodiesterase 5 inhibitory activity with an IC50 value of about 7 µg/mL. Seven isoflavones and a coumarin constituent isolated from this plant were investigated for phosphodiesterase 5 inhibitory activity. The results showed that osajin (8), 4′,5,7-trihydroxybiprenylisoflavone (4), and derrisisoflavone A (2) had the ability to inhibit phosphodiesterase 5 with IC50 values of 4, 8, and 9 µM, respectively. These compounds exhibited selectivity on phosphodiesterase 5 over phosphodiesterase 1, however, the selectivity on phosphodiesterase 5 over phosphodiesterase 6 was low. In order to quantitatively determine these bioactive constituents in D. scandens extract, LC-QTOF-MS method has been developed and validated. The limit of quantitation values in the range of 0.1 – 5 µg/mL were obtained. The assay showed satisfactory precision and accuracy. The results from our method showed that the 95% ethanol extract of D. scandens stem was comprised of all eight compounds, with derrisisoflavone A (2) and lupalbigenin (3) presenting as the major constituents.

Supporting Information

 
  • References

  • 1 Bender AT, Beavo JA. Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. Pharmacol Rev 2006; 58: 488
  • 2 Lin CS. Tissue expression, distribution, and regulation of PDE5. Int J Impot Res 2004; 16: S8-S10
  • 3 Beavo JA, Francis SH, Houslay MD. Cyclic Nucleotide Phosphodiesterases in Health and Disease. In: Francis SH, Zoraghi R, Kotera J, Ke H, Bessay EP, Blount MA, Corbin JD. eds. Phosphodiesterase-5: molecular Characteristics relating to Structure, Function, and Regulation. Boca Raton, London: CRC Press/Taylor & Francis; 2007: 131-164
  • 4 Corbin JD, Francis SH, Webb DJ. Phosphodiesterase type 5 as a pharmacologic target in erectile dysfunction. Urology 2002; 60: 4-11
  • 5 Rybalkin SD, Yan C, Bornfeldt KE, Beavo JA. Cyclic GMP phosphodiesterases and regulation of smooth muscle function. Circ Res 2003; 93: 280
  • 6 Federal Drug Administration. Viagra (Sildenafil), prescribing Information, January 2010 ed. New York: Pfizer; 2010
  • 7 Federal Drug Administration. Cialis (Tadalafil), prescribing Information, October 2011 ed. Indianapolis, Indiana: Eli Lilly and Company; 2011
  • 8 Bischoff E. Potency, selectivity, and consequences of nonselectivity of PDE inhibition. Int J Impot Res 2004; 16 (Suppl. 01) S11-S14
  • 9 Ferguson JE, Carson CC. Phosphodiesterase type 5 inhibitors as a treatment for erectile dysfunction: current information and new horizons. Arab J Urol 2013; 11: 222-229
  • 10 Huang SA, Lie JD. Phosphodiesterase-5 (PDE5) inhibitors In the management of erectile dysfunction. P T 2013; 38: 407-419
  • 11 Maunwongyathi P, Supatwanich P. Pharmacognostic study of Derris scandens Benth. MU J Pharm 1981; 8: 57-64
  • 12 Department for Development of Thai Traditional and Alternative Medicine, Ministry of Public Health. Monographs of selected Thai Material Medica, Volume 1. Bangkok: Amarin Publishing Services; 2009
  • 13 National Drug System Development Committee. National List of essential Medicine of Thailand. Bangkok, Thailand: Ministry of Public Health; 2015
  • 14 Mahabusarakam W, Deachathai S, Phongpaichit S, Jansakul C, Taylor WC. A benzil and isoflavone derivatives from Derris scandens Benth. Phytochemistry 2004; 65: 1185-1191
  • 15 Sreelatha T, Hymavathi A, Rama Subba Rao V, Devanand P, Usha Rani P, Madhusudana Rao J, Suresh Babu K. A new benzil derivative from Derris scandens: structure-insecticidal activity study. Bioorganic Med Chem Lett 2010; 20: 549-553
  • 16 Rao SA, Srinivas PV, Tiwari AK, Vanka UMS, Rao RVS, Dasari KR, Rao MJ. Isolation, characterization and chemobiological quantification of α-glucosidase enzyme inhibitory and free radical scavenging constituents from Derris scandens Benth. J Chromatogr B 2007; 855: 166-172
  • 17 Hussain H, Al-Harrasi A, Krohn K, Kouam SF, Abbas G, Shah A, Raees MA, Ullah R, Aziz S, Schulz B. Phytochemical investigation and antimicrobial activity of Derris scandens . J King Saud Univ 2015; 27: 375-378
  • 18 Sekine T, Inagaki M, Ikegami F, Fujii Y, Ruangrungsi N. Six diprenylisoflavones, derrisisoflavones A–F, from Derris scandens . Phytochemistry 1999; 52: 87-94
  • 19 Rukachaisirikul V, Sukpondma Y, Jansakul C, Taylor WC. Isoflavone glycosides from Derris scandens . Phytochemistry 2002; 60: 827-834
  • 20 Laupattarakasem P, Houghton P, Robin S, Hoult J. Anti-inflammatory isoflavonoids from the stems of Derris scandens . Planta Med 2004; 70: 496-501
  • 21 Kuptniratsaikul V, Pinthong T, Bunjob M, Thanakhumtorn S, Chinswangwatanakul P, Thamlikitkul V. Efficacy and safety of Derris scandens Benth extracts in patients with knee osteoarthritis. J Altern Complement Med 2011; 17: 147-153
  • 22 Srimongkol Y, Warachit P, Chavalittumrong P. A study of the efficacy of Derris scandens benth extract compared with diclofenac for the alleviation of low back pain. J Thai Tradit Altern Med 2007; 5: 17-23
  • 23 Panche AN, Diwan AD, Chandra SR. Flavonoids: an overview. J Nutr 2016; 5: e47
  • 24 Huang D, Hinds TR, Martinez SE, Doneanu C, Beavo JA. Molecular determinants of cGMP binding to chicken cone photoreceptor phosphodiesterase. J Biol Chem 2004; 279: 48143-48151
  • 25 Ribaudo G, Pagano MA, Pavan V, Redaelli M, Zorzan M, Pezzani R, Mucignat-Caretta C, Vendrame T, Bova S, Zagotto G. Semi-synthetic derivatives of natural isoflavones from Maclura pomifera as a novel class of PDE-5A inhibitors. Fitoterapia 2015; 105: 132-138
  • 26 Ko WC, Shih CM, Lai YH, Chen JH, Huang HL. Inhibitory effects of flavonoids on phosphodiesterase isozymes from guinea pig and their structure-activity relationships. Biochem Pharmacol 2004; 68: 2087-2094
  • 27 DellʼAgli M, Galli GV, Dal Cero E, Belluti F, Matera R, Zironi E, Pagliuca G, Bosisio E. Potent inhibition of human phosphodiesterase-5 by icariin derivatives. J Nat Prod 2008; 71: 1513-1517
  • 28 Shin HJ, Kim HJ, Kwak JH, Chun HO, Kim JH, Park H, Kim DH, Lee YS. A prenylated flavonol, sophoflavescenol: a potent and selective inhibitor of cGMP phosphodiesterase 5. Bioorg Med Chem Lett 2002; 12: 2313-2316
  • 29 Sonnenburg WK, Rybalkin SD, Bornfeldt KE, Kwak KS, Rybalkina IG, Beavo JA. Identification, quantitation, and cellular localization of PDE1 calmodulin-stimulated cyclic nucleotide phosphodiesterases. Methods 1998; 14: 3-19