Phenols, alkaloids and terpenes from medicinal plants with antihypertensive and vasorelaxant activities. a review of natural products as leads to potential therapeutic agents

Natural Product Communications

Volumn 8, Issue 4, 2013, Pages 539-544

  Maione, Francesco ^a   Cicala, Carla ^a   Musciacco, Giulia ^a   De Feo, Vincenzo ^b   Amat, Anibal G ^c   Ialenti, Armando ^a   Mascolo, Nicola ^a  

^a UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^b UNIVERSITY OF SALERNO   (Italy)

^c UNIVERSIDAD NACIONAL DE MISIONES   (Argentina)

Author keywords

Alkaloids; Cardiovascular diseases; Drug discovery; Hypertension; Phenols; Terpenes

Indexed keywords

ACTEOSIDE; ALKALOID; APIGENIN; ARTEMETIN; ASTRAGALIN; CAFFEOYLQUINIC ACID; CALCIUM CHANNEL BLOCKING AGENT; CHRYSIN; CISTANOSIDE F; CLEOMISCOSIN A; CLEOMISCOSIN C; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ECHINACOSIDE; HESPERETIN; HYDROXYDERRICIN; ISOQUERCITRIN; KAEMPFEROL; KANKANOSE; KANKANOSIDE F; LEUCOSCEPTOSIDE; LUTEOLIN; MARTYNOSIDE; OSTHOLE; PHENOL DERIVATIVE; QUERCETIN; SCOPOLETIN; TERPENE DERIVATIVE; TILIANIN; UNCLASSIFIED DRUG; UNINDEXED DRUG; XANTHOANGELOL;

ACER NIKOENSE; ACHILLEA; AEGLE MARMELOS; AGASTACHE MEXICANA; AILANTHUS EXCELSA; ALEPIDEA AMATYMBICA; ANDROGRAPHIS PANICULATA; ANGELICA KEISKEI; ANNONA CHERIMOLA; ANTIHYPERTENSIVE ACTIVITY; CALYCOTOME VILLOSA; CARDIOVASCULAR EFFECT; CARROT; CASSYTHA FILIFORMIS; CISTANCHE TUBULOSA; CLERODENDRON TRICHOTOMUM; CNIDIUM MONNIERI; COLEUS FORSKOHLII; CORYDALIS RACEMOSA; CROTON CAJUCARA; CUSCUTA JAPONICA; DIOCLEA GRANDIFLORA; ERYTHROXYLUM GONOCLADUM; EUPHORIA LONGANA; FRITILLARIA USURIENSIS; GENTIANA KOCHIANA; GEUM JAPONICUM; GINGER; HIBISCUS SABDARIFFA; HUMAN; HYPERTENSION; ILLIGERA LUZONENSIS; LEPECHINIA CAULESCENS; LIGUSTICUM WALLICHII; LIGUSTRUM PURPURASCENS; LINDERA MEGAPHYLLA; MAGNOLIA FARGESII; MAHONIA AQUIFOLIUM; MARRUBIUM VULGARE; MEDICINAL PLANT; MENTHA VILLOSA; MOLDENHAWERA NUTANS; NONHUMAN; OCIMUM GRATISSIMUM; PAEONIA MOUTAN; PERSIMMON; PETASITES FORMOSANUS; PHYLLANTHUS NIRURI; PHYLLANTHUS URINARIA; PLANT IDENTIFICATION; PLATYCAPNOS SPICATUS; POLYALTHIA LONGIFOLIA; REVIEW; SALVIA MILTIORRHIZA; SEDUM SARMENTOSUM; SELAGINELLA TAMARISCINA; STEPHANIA GLABRA; STEPHANIA TETRANDRA; STEVIA; SWEET ORANGE; TETRADIUM RUTICARPUM; TROPAEOLUM MAJUS; UNCARIA RHYNCHOPHYLLA; VALIDATION STUDY; VASODILATATION; VERBESINA CARACASANA; VIGUIERA ARENARIA; XYLOPIA AETHIOPICA;

EID: 84876231944     PISSN: 1934578X     EISSN: 15559475     Source Type: Journal    
DOI: 10.1177/1934578x1300800434     Document Type: Review

References (84)

1. Mascolo N, Borrelli F, Capasso R, Capasso F, Di Carlo G, Izzo AA, Pinto L, Castaldo S, Longo R (1998) Natural products and cardiovascular disturbances. Phytotherapy Research, 12, 121-123.
2. Harvey AL. (2008) Natural products in drug discovery. Drug Discovery Today, 19-20, 894-901.
3. Capasso F, De Pasquale R, Grandolini G, Mascolo N. (Eds) (2000) In Farmacognosia, Springer-Verlag, Italy, Milano. 1-189.
4. Iizuka T, Nagumo S, Yotsumoto H, Moriyama H, Nagai M. (2007) Vasorelaxant effects of Acer nikoense extract and isolated coumarinolignans on rat aortic rings. Biological and Pharmaceutical Bulletin, 6, 1164-1166.
5. de Souza P, Gasparotto A Jr, Crestani S, Stefanello MÉ, Marques MC, da Silva-Santos JE, Kassuya CA. (2011) Hypotensive mechanism of the extracts and artemetin isolated from Achillea millefolium L. (Asteraceae) in rats. Phytomedicine, 10, 819-825.
6. Hernández-Abreu O, Castillo-España P, León-Rivera I, Ibarra-Barajas M, Villalobos-Molina R, González-Christen J, Vergara-Galicia J, Estrada- Soto S. (2009) Antihypertensive and vasorelaxant effects of tilianin isolated from Agastache mexicana are mediated by NO/cGMP pathway and potassium channel opening. Biochemical Pharmacology, 1, 54-61.
7. Kim TJ, Kim JH, Jin YR, Yun YP. (2006) The inhibitory effect and mechanism of luteolin-7-glucoside on rat aortic vascular smooth muscle cell proliferation. Archive of Pharmacal Research, 1, 67-72.
8. Sanchez M, Lodi F, Vera R, Villar IC, Cogolludo A, Jimenez R, Moreno L, Romero M, Tamargo J, Perez-Vizcaino F, Duarte J. (2007) Quercetin and isorhamnetin prevent endothelial dysfunction, superoxide production, and overexpression of p47phox induced by angiotensin II in rat aorta. Journal of Nutrition, 4, 910-915.
9. Loizzo MR, Said A, Tundis R, Rashed K, Statti GA, Hufner A, Menichini F. (2007) Inhibition of angiotensin converting enzyme (ACE) by flavonoids isolated from Ailanthus excelsa (Roxb) (Simaroubaceae). Phytotherapy Research, 1, 32-36.
10. Rodrigo R, Gil D, Miranda-Merchak A, Kalantzidis G. (2012) Antihypertensive role of polyphenols. Advances in Clinical Chemistry, 58, 225-254.
11. Matsuura M, Kimura Y, Nakata K, Baba K, Okuda H. (2001) Artery relaxation by chalcones isolated from the roots of Angelica keiskei. Planta Medica, 3, 230-235.
12. Ogawa H, Ohno M, Baba K. (2005) Hypotensive and lipid regulatory actions of 4-hydroxyderricin, a chalcone from Angelica keiskei, in strokeprone spontaneously hypertensive rats. Clinical and Experimental Pharmacology and Physiology, 1-2, 19-23.
13. Cherkaoui-Tangi K, Lachkar M, Wibo M, Morel N, Gilani AH, Lyoussi B. (2008) Pharmacological studies on hypotensive, diuretic and vasodilator activities of chrysin glucoside from Calycotome villosa in rats. Phytotherapy Research, 3, 356-361.
14. Fusi F, Sgaragli G, Hale M, Cuong NM, Saponara S. (2012) Mechanism of osthole inhibition of vascular Ca(v)1.2 current. European Journal of Pharmacology, 1-3, 22-27.
15. Orallo F, Alvarez E, Basaran H, Lugnier C. (2004) Comparative study of the vasorelaxant activity, superoxide-scavenging ability and cyclic nucleotide phosphodiesterase-inhibitory effects of hesperetin and hesperidin. Naunyn Schmiedeberg's Archives of Pharmacology, 6, 452-463.
16. Yoshikawa M, Matsuda H, Morikawa T, Xie H, Nakamura S, Muraoka O. (2006) Phenylethanoid oligoglycosides and acylated oligosugars with vasorelaxant activity from Cistanche tubulosa. Bioorganic & Medicinal Chemistry, 22, 7468-7475.
17. Xie H, Morikawa T, Matsuda H, Nakamura S, Muraoka O, Yoshikawa M. (2006) Monoterpene constituents from Cistanche tubulosa-chemical structures of kankanosides A-E and kankanol. Chemical and Pharmaceutical Bulletin, 5, 669-675.
18. Kang DG, Lee YS, Kim HJ, Lee YM, Lee HS. (2003) Angiotensin converting enzyme inhibitory phenylpropanoid glycosides from Clerodendron trichotomum. Journal of Ethnopharmacology, 1, 151-154.
19. Liu JC, Hsu FL, Tsai JC, Chan P, Liu JY, Thomas GN, Tomlinson B, Lo MY, Lin JY. (2003) Antihypertensive effects of tannins isolated from traditional Chinese herbs as non-specific inhibitors of angiontensin converting enzyme. Life Sciences, 12, 1543-1555.
20. Mishima S, Yoshida C, Akino S, Sakamoto T. (2005) Antihypertensive effects of Brazilian propolis: identification of caffeoylquinic acids as constituents involved in the hypotension in spontaneously hypertensive rats. Biological and Pharmaceutical Bulletin, 10, 1909-1914.
21. Gilani AH, Shaheen E, Saeed SA, Bibi S, Irfanullah, Sadiq M, Faizi S. (2000) Hypotensive action of coumarin glycosides from Daucus carota. Phytomedicine, 7, 423-426.
22. Trigueiro F, Cortes SF, Almeida RN, Lemos VS. (2000) Endothelium- independent vasorelaxant effect of dioclein, a new flavonoid isolated from Dioclea grandiflora, in the rat aorta. Journal of Pharmacy and Pharmacology, 11, 1431-1434.
23. Côrtes SF, Rezende BA, Corriu C, Medeiros IA, Teixeira MM, Lopes MJ, Lemos VS. (2001) Pharmacological evidence for the activation of potassium channels as the mechanism involved in the hypotensive and vasorelaxant effect of dioclein in rat small resistance arteries. British Journal of Pharmacology, 6, 849-858.
24. Loizzo MR, Tundis R, Menichini F, Statti GA, Menichini F. (2008) Hypotensive natural products: current status. Mini Review in Medicinal Chemistry, 8, 828-855.
25. Lucas-Filho MD, Silva GC, Cortes SF, Mares-Guia TR, Perpétua Ferraz V, Serra CP, Braga FC. (2010) ACE inhibition by astilbin isolated from Erythroxylum gonocladum (Mart.) O.E. Schulz. Phytomedicine, 5, 383-387.
26. Cheng JT, Lin TC, Hsu FL. (1995) Antihypertensive effect of corilagin in the rat. Canadian Journal of Physiology and Pharmacology, 73, 1425- 1429.
27. Chericoni S, Testai L, Calderone V, Flamini G, Nieri P, Morelli I, Martinotti E. (2003) The xanthones gentiacaulein and gentiakochianin are responsible for the vasodilator action of the roots of Gentiana kochiana. Planta Medica, 8, 770-772.
28. Kang DG, Kim YC, Sohn EJ, Lee YM, Lee AS, Yin MH, Lee HS. (2003) Hypotensive effect of butein via the inhibition of angiotensin converting enzyme. Biological and Pharmaceutical Bulletin, 9, 1345-1347.
29. Xie YW, Xu HX, Dong H, Fiscus RR, But PP. (2007) Role of nitric oxide in the vasorelaxant and hypotensive effects of extracts and purified tannins from Geum japonicum. Journal of Ethnopharmacology, 1, 128-133.
30. Magos GA, Mateos JC, Páez E, Fernández G, Lobato C, Márquez C, Enríquez RG. (2008) Hypotensive and vasorelaxant effects of the procyanidin fraction from Guazuma ulmifolia bark in normotensive and hypertensive rats. Journal of Ethnopharmacology, 1, 58-68.
31. Ojeda D, Jiménez-Ferrer E, Zamilpa A, Herrera-Arellano A, Tortoriello J, Alvarez L. (2010) Inhibition of angiotensin convertin enzyme (ACE) activity by the anthocyanins delphinidin- and cyanidin-3-O-sambubiosides from Hibiscus sabdariffa. Journal of Ethnopharmacology, 1, 7-10.
32. Aguirre-Crespo F, Vergara-Galicia J, Villalobos-Molina R, Javier López-Guerrero J, Navarrete-Vázquez G, Estrada-Soto S. (2006) Ursolic acid mediates the vasorelaxant activity of Lepechinia caulescens via NO release in isolated rat thoracic aorta. Life Sciences, 11, 1062-1068.
33. Pang PK, Shan JJ, Chiu KW. (1996) Tetramethylpyrazine, a calcium antagonist. Planta Medica, 5, 431-435.
34. Yu SM, Hsu SY, Ko FN, Chen CC, Huang YL, Huang TF, Teng CM. (1992) Haemodynamic effects of dicentrine, a novel alpha 1-adrenoceptor antagonist: comparison with prazosin in spontaneously hypertensive and normotensive Wistar-Kyoto rats. British Journal of Pharmacology, 4, 797-801.
35. Yoo MY, Lee BH, Choi YH, Lee JW, Seo JH, Oh KS, Koo HN, Seo HW, Yon GH, Kwon DY, Kim YS, Ryu SY (2006) Vasorelaxant effect of the rootbark extract of Paeonia moutan on isolated rat thoracic aorta. Planta Medica, 14, 1338-1341.
36. Iizuka T, Moriyama H, Nagai M. (2006) Vasorelaxant effects of methyl brevifolincarboxylate from the leaves of Phyllanthus niruri. Biological and Pharmaceutical Bulletin, 1, 177-179.
37. Lin SY, Wang CC, Lu YL, Wu WC, Hou WC. (2008) Antioxidant, anti-semicarbazide-sensitive amine oxidase, and anti-hypertensive activities of geraniin isolated from Phyllanthus urinaria. Food and Chemical Toxicology, 7, 2485-2492.
38. Gao XP, Xu DY, Deng YL, Zhang Y. (2004) Screening of angiotensin converting enzyme inhibitors from Salvia miltiorrhizae. Zhongguo Zhong Yao Za Zhi, 4, 359-362.
39. Nagai M, Noguchi M, Iizuka T, Otani K, Kamata K. (1996) Vasodilator effects of des(alpha-carboxy-3, 4-dihydroxyphenethyl)lithospermic acid (8- epiblechnic acid), a derivative of lithospermic acids in Salvia miltiorrhizae radix. Biological and Pharmaceutical Bulletin, 2, 228-232.
40. Wang W, Hu GY, Wang YP. (2006) Selective modulation of L-type calcium current by magnesium lithospermate B in guinea-pig ventricular myocytes. Life Sciences, 26, 2989-2997.
41. Oh H, Kang DG, Kwon JW, Kwon TO, Lee SY, Lee DB, Lee HS. (2004) Isolation of angiotensin converting enzyme (ACE) inhibitory flavonoids from Sedum sarmentosum. Biological and Pharmaceutical Bulletin, 12, 2035-2037.
42. Kang DG, Yin MH, Oh H, Lee DH, Lee HS. (2004) Vasorelaxation by amentoflavone isolated from Selaginella tamariscina. Planta Medica, 8, 718-722.
43. Gasparotto Junior A, Gasparotto FM, Lourenço EL, Crestani S, Stefanello ME, Salvador MJ, da Silva-Santos JE, Marques MC, Kassuya CA. (2011) Antihypertensive effects of isoquercitrin and extracts from Tropaeolum majus L.: evidence for the inhibition of angiotensin converting enzyme. Journal of Ethnopharmacology, 2, 363-372.
44. Tabassum N, Ahmad F. (2011) Role of natural herbs in the treatment of hypertension. Pharmacognosy Reviews, 9, 30-40.
45. Tirapelli CR, Ambrosio SR, da Costa FB, de Oliveira AM. (2008) Diterpenes: a therapeutic promise for cardiovascular diseases. Recent Patents on Cardiovascular Drug Discovery, 1, 1-8.
46. Hsich MH, Chan P, Sue YM, Liu JC, Liang TH, Huang TY, Tomlinson B, Sun Chow MS, Kao PF, Chen YJ. (2003) Efficacy and tolerability of oral stevioside in patients with mild essential hypertension: a two-year, randomized, placebo-controlled study. Clinical Therapeutics, 11, 2797-2808.
47. Chuliá S, Ivorra MD, Cavé A, Cortés D, Noguera MA, D'Ocón MP. (1995) Relaxant activity of three aporphine alkaloids from Annona cherimolia on isolated aorta of rat. Journal of Pharmacy and Pharmacology, 8, 647-650.
48. Valiente M, D'Ocon P, Noguera MA, Cassels BK, Lugnier C, Ivorra MD. (2004) Vascular activity of (-)-anonaine, (-)-roemerine and (-)-pukateine, three natural 6a(R)-1, 2-methylenedioxyaporphines with different affinities for alpha1-adrenoceptor subtypes. Planta Medica, 7, 603-609.
49. Chang CW, Ko FN, Su MJ, Wu YC, Teng CM. (1997) Pharmacological evaluation of ocoteine, isolated from Cassytha filiformis, as an alpha 1- adrenoceptor antagonist in rat thoracic aorta. Japanese Journal of Pharmacology, 3, 207-214.
50. Chueh FY, Hsieh MT, Chen CF, Lin MT. (1995) Hypotensive and bradycardic effects of dl-tetrahydropalmatine mediated by decrease in hypothalamic serotonin release in the rat. Japanese Journal of Pharmacology, 2, 177-180.
51. Lin MT, Chueh FY, Hsieh MT, Chen CF. (1996) Antihypertensive effect of DL-tetrahydropalmatine: an active principle isolated from Corydalis. Clinical and Experimental Pharmacology and Physiology, 8, 738-742.
52. Chiou WF, Shum AY, Liao JF, Chen CF. (1997) Studies of the cellular mechanisms underlying the vasorelaxant effects of rutaecarpine, a bioactive component extracted from an herbal drug. Journal of Cardiovascular Pharmacology, 4, 490-498.
53. Wang GJ, Wu XC, Chen CF, Lin LC, Huang YT, Shan J, Pang PK. (1999) Vasorelaxing action of rutaecarpine: effects of rutaecarpine on calcium channel activities in vascular endothelial and smooth muscle cells. Journal of Pharmacology and Experimental Therapeutics, 3, 1237-1244.
54. Oh H, Kang DG, Lee S, Lee Y, Lee HS. (2003) Angiotensin converting enzyme (ACE) inhibitory alkaloids from Fritillaria ussuriensis. Planta Medica, 6, 564-565.
55. Guh JH, Ko FN, Yu SM, Wu YC, Teng CM. (1995) Evaluation of N-methyl-actinodaphnine, a new vascular alpha-adrenoceptor antagonist, isolated from Illigera luzonensis. European Journal of Pharmacology, 1, 33-41.
56. Tsai CC, Lai TY, Huang WC, Liu IM, Cheng JT. (2002) Inhibitory effects of potassium channel blockers on tetramethylpyrazine-induced relaxation of rat aortic strip in vitro. Life Sciences, 11, 1321-1330.
57. Yu SM, Kang YF, Chen CC, Teng CM. (1993) Effects of dicentrine on haemodynamic, plasma lipid, lipoprotein level and vascular reactivity in hyperlipidaemic rats. British Journal of Pharmacology, 4, 1055-1061.
58. Yu SM, Chen CC, Huang YL, Tsai CW, Lin CH, Huang TF, Teng CM. (1990) Vasorelaxing effect in rat thoracic aorta caused by denudatin B, isolated from the Chinese herb, Magnolia fargesii. European Journal of Pharmacology, 1, 39-47.
59. Sotníková R, Kost'álová D, Vaverková S. (1994) Effect of bisbenzylisoquinoline alkaloids from Mahonia aquifolium on the isolated rat aorta. General Pharmacology, 7, 1405-1410.
60. Kawashima K, Hayakawa T, Miwa Y, Oohata H, Suzuki T, Fujimoto K, Ogino T, Chen ZX. (1990) Structure and hypotensive activity relationships of tetrandrine derivatives in stroke-prone spontaneously hypertensive rats. General Pharmacology, 3, 343-347.
61. Kim HS, Zhang YH, Oh KW, Ahn HY. (1997) Vasodilating and hypotensive effects of fangchinoline and tetrandrine on the rat aorta and the stroke-prone spontaneously hypertensive rat. Journal of Ethnopharmacology, 2, 117-123.
62. Zhang WB, Chen CX, Sim SM, Kwan CY. (2004) In vitro vasodilator mechanisms of the indole alkaloids rhynchophylline and isorhynchophylline, isolated from the hook of Uncaria rhynchophylla (Miquel). Naunyn Schmiedebergs Archives of Pharmacology, 2, 232-238.
63. Carmignani M, Volpe AR, Delle Monache F, Botta B, Espinal R, De Bonnevaux SC, De Luca C, Botta M, Corelli F, Tafi A, Ripanti G, Monache GD. (1999) Novel hypotensive agents from Verbesina caracasana. 6. Synthesis and pharmacology of caracasandiamide. Journal of Medicinal Chemistry, 16, 3116-3125.
64. Chen CX, Kwan CY. (2001) Endothelium-independent vasorelaxation by leonurine, a plant alkaloid purified from Chinese motherwort. Life Sciences, 8, 953-960.
65. Kakiyuchi, N., Senaratne, R.E., Huang, S., Yang, X., Hattori, M., Pilapitiya, U., Namba, T. (1991) Effects on constituents of Beli (Aegle marmelos) on spontaneous beating and calcium-paradox of myocardial cells. Planta Medica, 57, 43-46.
66. Somova LI, Shode FO, Moodley K, Govender Y. (2001) Cardiovascular and diuretic activity of kaurene derivatives of Xylopia aethiopica and Alepidea amatymbica. Journal of Ethnopharmacology, 2, 165-174.
67. Zhang C, Kuroyangi M, Tan BK. (1998) Cardiovascular activity of 14-deoxy-11, 12 didehydroandrographolide in the anaesthetized rat and isolated right atria. Pharmacological Research, 6, 413-417.
68. Tirapelli CR, Ambrosio SR, de Oliveira AM, Tostes RC. (2010) Hypotensive action of naturally occurring diterpenes: a therapeutic promise for the treatment of hypertension. Fitoterapia, 7, 690-702.
69. Silva RM, Oliveira FA, Cunha KM, Maia JL, Maciel MA, Pinto AC, Nascimento NR, Santos FA, Rao VS (2005) Cardiovascular effects of transdehydrocrotonin, a diterpene from Croton cajucara in rats. Vascular Pharmacology, 1, 11-18.
70. El-Bardai S, Wibo M, Hamaide MC, Lyoussi B, Quetin-Leclercq J, Morel N. (2003) Characterisation of marrubenol, a diterpene extracted from Marrubium vulgare, as an L-type calcium channel blocker. British Journal of Pharmacology, 7, 1211-1216.
71. Guedes DN, Silva DF, Barbosa-Filho JM, Medeiros IA. (2004) Calcium antagonism and the vasorelaxation of the rat aorta induced by rotundifolone. Brazilian Journal of Medicinal and Biological Research. 12, 1881-1887.
72. Lahlou S, De Barros Correia CA, Dos Santos VM, David JM, David JP, Duarte GP, Magalhaes PJ (2007) Mechanisms underlying the cardiovascular effects of a labdenic diterpene isolated from Moldenhawera nutans in normotensive rats. Vascular Pharmacology, 1, 60-66.
73. Lahlou S, Figueiredo AF, Magalhães PJ, Leal-Cardoso JH, Gloria PD. (2004) Cardiovascular effects of methyleugenol, a natural constituent of many plant essential oils, in normotensive rats. Life Sciences, 19, 2401-2412.
74. Interaminense LF, Leal-Cardoso JH, Magalhães PJ, Duarte GP, Lahlou S. (2005) Enhanced hypotensive effects of the essential oil of Ocimum gratissimum leaves and its main constituent, eugenol, in DOCA-salt hypertensive conscious rats. Planta Medica, 4, 376-378.
75. Soares PM, Lima RF, de Freitas Pires A, Souza EP, Assreuy AM, Criddle DN. (2007) Effects of anethole and structural analogues on the contractility of rat isolated aorta: Involvement of voltage-dependent Ca2+-channels. Life Sciences, 13, 1085-1093.
76. Esberg LB, Wang GJ, Lin YL, Ren J. (2003) Iso-S-petasin, a hypotensive sesquiterpene from Petasites formosanus, depresses cardiac contraction and intracellular Ca2+ transients in adult rat ventricular myocytes. Journal of Pharmacy and Pharmacology, 1, 103-107.
77. Lee CN, Wong KL, Liu JC, Chen YJ, Cheng JT, Chan P. (1991) Inhibitory effect of stevioside on calcium influx to produce antihypertension. Planta Medica, 9, 796-799.
78. Melis MS, Sainati AR. (1991) Participation of prostaglandins in the effect of stevioside on rat renal function and arterial pressure. Brazilian Journal of Medicinal and Biological Research, 12, 1269-1276.
79. Melis MS. (1992) Stevioside effect on renal function of normal and hypertensive rats. Journal of Ethnopharmacology, 3, 213-217.
80. Liu JC, Kao PK, Chan P, Hsu YH, Hou CC, Lien GS, Hsieh MH, Chen YJ, Cheng JT. (2003) Mechanism of the antihypertensive effect of stevioside in anesthetized dogs. Pharmacology, 1, 14-20.
81. Ambrosio SR, Tirapelli CR, Bonaventura D, De Oliveira AM, Da Costa FB. (2002) Pimarane diterpene from Viguiera arenaria (Asteraceae) inhibit rat carotid contraction. Fitoterapia, 6, 484-489.
82. Tirapelli CR, Ambrosio SR, da Costa FB, de Oliveira AM. (2004) Evidence for the mechanisms underlying the effects of pimaradienoic acid isolated from the roots of Viguiera arenaria on rat aorta. Pharmacology, 1, 31-38.
83. Somova LI, Shode FO, Moodley K, Govender Y. (2001) Cardiovascular and diuretic activity of kaurene derivatives of Xylopia aethiopica and Alepidea amatymbica. Journal of Ethnopharmacology, 2-3, 165-174.
84. Bonito MC, Cicala C, Marcotullio MC, Maione F, Mascolo N. (2011) Biological activity of bicyclic and tricyclic diterpenoids from Salvia species of immediate pharmacological and pharmaceutical interest. Natural Product Communications, 8, 1205-1215.