Plectranthus barbatus: A Review of Phytochemistry, Ethnobotanical Uses and Pharmacology – Part 2

Abstract

Plectranthus barbatus Andr. is one of the most important species of the genus Plectranthus L′ Herit. (Lamiaceae), with a wide variety of traditional medicinal uses in Hindu and Ayurvedic traditional medicine as well as in the folk medicine of Brazil, tropical Africa and China. The plant has therefore been an attractive target for intensive chemical and pharmacological studies up to now. This review presents data about the phytochemistry, ethnobotanical uses and pharmacology of Plectranthus barbatus as well as the pharmacology of its constituents. In addition to essential oil, abietane diterpenoids and 8,13-epoxy-labd-14-en-11-one diterpenoids are the main constituents found in Plectranthus barbatus. The major ethnobotanical uses are for intestinal disturbance and liver fatigue, respiratory disorders, heart diseases and certain nervous system disorders. Forskolin as one of the major constituents with its unique adenylyl cyclase activation that underlies the wide range of pharmacological properties could explain the different traditional uses of Plectranthus barbatus. Forskolin is involved in a number of patented pharmaceutical preparations used as over-the-counter drugs for the treatment of several ailments. However, the water-insoluble nature of forskolin limits its clinical usefulness. Forskolin thus served as a prototype for the development of 6-(3-dimethylaminopropionyl)forskolin hydrochloride (NKH477) as a potent water-soluble forskolin derivative that finds use in the therapy for a number of diseases especially of the cardiovascular system.

Key words

Plectranthus barbatus - Lamiaceae - forskolin - phytochemistry - ethnobotanical uses - pharmacology - 6‐(3‐dimethylaminopropionyl)forskolin hydrochloride (NKH477)

References

• 1 Matu E N, van Staden J. Antibacterial and anti-inflammatory activities of some plants used for medicinal purposes in Kenya.  J Ethnopharmacol. 2003;  87 35-41
• 2 Runyoro D K B, Matee M I N, Ngassapa O D, Joseph C C, Mbwambo Z H. Screening of Tanzanian medicinal plants for anti-Candida activity.  BMC Complement Altern Med. 2006;  6 11
• 3 Tamasiro V, Davino S C, Freitas P C D, Barros S B M. In vitro antioxidant activity of Coleus barbatus (Andr.) Benth (false boldo) and Peumus boldo (Molina) (Boldo do Chile): a comparative study.  Rev Farm Bioquim Univ Sao Paulo. 1998;  34 15-17
• 4 Costa M C C D, Nascimento S C. Actividade citotóxica de Plectranthus barbatus Andr. (Lamiaceae).  Acta Farm Bonaer. 2003;  22 155-158
• 5 de Souza N J, Dohadwalla A N, Reden J. Forskolin: a labdane diterpenoid with antihypertensive, positive inotropic, platelet aggregation inhibitory, and adenylate cyclase activating properties.  Med Res Rev. 1983;  3 201-219
• 6 Kelecom A. Isolation, structure determination, and absolute configuration of barbatusol, a new bioactive diterpene with a rearranged abietane skeleton from the labiate Coleus barbatus.  Tetrahedron. 1983;  39 3603-3608
• 7 Bhakuni D S, Dhar M L, Dhar M M, Dhawan B N, Gupta B, Srimal R C. Screening of Indian plants for biological activity.  Indian J Exp Biol. 1971;  9 91
• 8 Staudinger J L, Ding X, Lichti K. Pregnane X receptor and natural products: beyond drug-drug interactions.  Expert Opin Drug Metab Toxicol. 2006;  2 847-857
• 9 Kubo I, Matsumoto T, Tori M, Asakawa Y. Structure of plectrin, an aphid antifeedant diterpene from Plectranthus barbatus.  Chem Lett. 1984;  9 1513-1516
• 10 Zelnik R, Lavie D, Levy E C, Wang A H J, Paul I C. Barbatusin and cyclobutatusin, two novel diterpenoids from Coleus barbatus Bentham.  Tetrahedron. 1977;  33 1457-1467
• 11 Yadava J N S, Gupta S, Ahmad I, Varma N, Tandon J S. Neutralization of enterotoxins of Escherichia coli by coleonol (forskolin) in rabbit and guinea pig ileal loop models.  Indian J Anim Sci. 1995;  65 1177-1181
• 12 Almeida F C, Lemonica I P. The toxic effects of Coleus barbatus B on the different periods of pregnancy in rats.  J Ethnopharmacol. 2000;  73 53-60
• 13 Camara C C, Nascimento N R, Macedo-Filho C L, Almeida F B, Fonteles M C. Antispasmodic effect of the essential oil of Plectranthus barbatus and some major constituents on the guinea-pig ileum.  Planta Med. 2003;  69 1080-1085
• 14 Fischman L A, Skorupa L A, Souccar C, Lapa A J. The water extract of Coleus barbatus Benth decreases gastric secretion in rats.  Mem Inst Oswaldo Cruz. 1991;  86 (Suppl. 2) 141-143
• 15 Schultz C, Bossolani M P, Torres L M B, Lima-Landman M T R, Lapa A J, Souccar C. Inhibition of the gastric H+, K+-ATPase by plectrinone A, a diterpenoid isolated from Plectranthus barbatus Andrews.  J Ethnopharmacol. 2007;  111 1-7
• 16 Battochio A P, Sartori M S, Coelho C A. Water-soluble extract of Coleus barbatus modulates weight gain, energy utilization and lipid metabolism in secondary biliary cirrhosis: an experimental study in young rats.  Acta Cir Bras. 2005;  20 229-236
• 17 Han L K, Morimoto C, Yu R H, Okuda H. Effects of Coleus forskohlii on fat storage in ovariectomized rats.  Yakugaku Zasshi. 2005;  125 449-453
• 18 Zhang R, Kong L, Wang G, Zuo G. Manufacture of dripping pills containing Coleus forskohlii extract. Chinese Patent CN 1682840 A. 2005
• 19 Liu J, Zhang J, Chen Z, Xu Y L, Jin Q D. Chinese medicine composition for treating asthma and cough and its preparation. Chinese Patent CN 1872146 A. 2006
• 20 Jin Q, Chen Z, Zhang G. A Chinese medicinal granule for treating bronchial asthma containing flos colei esquirolii, radix peucedani, and radix glycyrrhizae. Chinese Patent CN 1154861 A. 1997
• 21 Tanaka R. Dentifrice compositions containing taurine and Coleus forskohlii extract. Japanese Patent JP 2003171250 A. 2003
• 22 Godard M P, Johnson B A, Richmond S R. Body composition and hormonal adaptations associated with forskolin consumption in overweight and obese men.  Obes Res. 2005;  13 1335-1343
• 23 Badmaev V, Majeed H. Compositions for physiological increase of male and female hormones with diterpene forskolin and its derivatives. Patent Application No. AU 2007200442 A1. 2007
• 24 Yamashita A, Takashita T, Ishihara T. Antiobesity agents and food, beverage, and medical compositions containing bergenin and forskolin and/or astilbin. Japanese Patent JP 2004091464 A. 2004
• 25 Miura M. Foods containing α-glucosidase inhibitors for restricting calories. Japanese Patent JP 2007195510 A. 2007
• 26 Saito M, Hara M, Hirotsu S. Lipid decomposition promoters and cosmetics containing plant extracts. Japanese Patent JP 2000016916 A. 2000
• 27 Kawakami T. Anti-allergy compositions containing Coleus forskohlii root extract and cinnamon extract. Japanese Patent JP 2003252786 A. 2003
• 28 Bonte F, Meybeck A, Marechal C. Composition based on hydrated lipidic lamellar phases or on liposomes containing at least one derivative of labdane, or a plant extract containing it; cosmetic or pharmaceutical, particularly dermatological composition containing it. US Patent 5891464. 1999
• 29 Adachi H, Ehata S, Hayashi T. Antiaging cosmetics containing Coleus forskohlii root extracts and antioxidants. Japanese Patent JP 08176005 A. 1996
• 30 Majeed M, Prakash S. Composition and methods containing an antimicrobial essential oil extended from Coleus forskohlii. US Patent 6607712 B2. 2003
• 31 Lukhoba C W, Simmonds M S J, Paton A J. Plectranthus: a review of ethnobotanical uses.  J Ethnopharmacol. 2006;  103 1-24
• 32 Seamon K B, Padgett W, Daly J W. Forskolin: unique diterpene activator of adenylate cyclase in membranes and in intact cells.  Proc Natl Acad Sci USA. 1981;  78 3363-3367
• 33 Daly J W, Padgett W, Seamon K B. Activation of cyclic AMP-generating systems in brain membranes and slices by the diterpene forskolin: augmentation of receptormediated responses.  J Neurochem. 1982;  38 532-544
• 34 Fradkin J E, Cook G H, Kilhoffer M C, Wolff J. Forskolin stimulation of thyroid adenylate cyclase and cyclic 3′,5′-adenosine monophosphate accumulation.  Endocrinology. 1982;  111 849-856
• 35 Birnbaumer L, Stengel D, Desmier M, Hanoune J. Forskolin regulation of liver membrane adenylyl cyclase.  Eur J Biochem. 1983;  136 107-112
• 36 Mettauer M, Giesen E M, Imbs J L, Schmidt M, Schwartz J. Forskolin increases cAMP production in a kidney cell line (MDCK).  Libr Compend. 1983;  11 887
• 37 Seamon K B, Daly J W, Metzger H, de Souza N J, Reden J. Structure-activity relationships for activation of adenylate cyclase by the diterpene forskolin and its derivatives.  J Med Chem. 1983;  26 436-439
• 38 Seamon K B, Wetzel B. Interaction of forskolin with dually regulated adenylate cyclase.  Adv Cyclic Nucleotide Protein Phosphorylation Res. 1984;  17 91-99
• 39 Seamon K B. Forskolin and adenylate cyclase: new opportunities in drug design.  Annu Rep Med Chem. 1984;  19 293-302
• 40 Daly J W. Forskolin, adenylate cyclase, and cell physiology: an overview.  Adv Cyclic Nucleotide Protein Phosphorylation Res. 1984;  17 81-89
• 41 Seamon K B. Activation of hormone-sensitive adenylate cyclase by forskolin.  Drug Dev Res. 1985;  6 181-192
• 42 Seamon K B. Forskolin and adenylate cyclase. ISI atlas of science.  Pharmacology. 1987;  1 250-253
• 43 Pfeuffer E, Mollner S, Pfeuffer T. Adenylate cyclase from bovine brain cortex: purification and characterization of the catalytic unit.  EMBO J. 1985;  4 3675-3679
• 44 Smigel M D. Purification of the catalyst of adenylate cyclase.  J Biol Chem. 1986;  261 1976-1982
• 45 Hacker B M, Tomlinson J E, Wayman G A, Sultana R, Chan G, Villacres E, Disteche C, Storm D R. Cloning, chromosomal mapping, and regulatory properties of the human type 9 adenylyl cyclase (ADCY9).  Genomics. 1998;  50 97-104
• 46 Defer N, Best-Belpomme M, Hanoune J. Tissue specificity and physiological relevance of various isoforms of adenylyl cyclase.  Am J Physiol Renal Physiol. 2000;  279 F400-F416
• 47 Dahle M K, Myhre A E, Aasen A O, Wang J E. Effects of forskolin on Kupffer cell production of interleukin-10 and tumor necrosis factor alpha differ from those of endogenous adenylyl cyclase activators: possible role for adenylyl cyclase 9.  Infect Immun. 2005;  73 7290-7296
• 48 Ammon H P, Müller A B. Forskolin: from an ayurvedic remedy to a modern agent.  Planta Med. 1985;  51 473-477
• 49 Bhat S V, Dohadwalla A N, Bajwa B S, Dadkar N K, Dornauer H, de Souza N J. The antihypertensive and positive inotropic diterpene forskolin: effects of structural modifications on its activity.  J Med Chem. 1983;  26 486-492
• 50 Lindner E, Metzger H. The action of forskolin on muscle cells is modified by hormones, calcium ions and calcium antagonists.  Arzneimittelforschung. 1983;  33 1436-1441
• 51 Iwase M, Ishikawa Y, Shen Y T, Shannon R P, Sato N, Ganguly P K, Eki T, Vatner D F, Vatner S F. Neurally mediated cardiac effects of forskolin in conscious dogs.  Am J Physiol. 1996;  271 H1473-H1482
• 52 Abe A, Karaki H. Effect of forskolin on cytosolic Ca⁺⁺ level and contraction in vascular smooth muscle.  J Pharmacol Exp Ther. 1989;  249 895-900
• 53 Rembold C M, Chen X L. Mechanisms responsible for forskolin-induced relaxation of rat tail artery.  Hypertension. 1998;  3 872-877
• 54 White R E, Kryman J P, El-Mowafy A M, Han G, Carrier G O. cAMP-dependent vasodilators cross-activate the cGMP-dependent protein kinase to stimulate BKCa channel activity in coronary artery smooth muscle cells.  Circ Res. 2000;  86 897-905
• 55 Linz W, Wiemer G, Schölkens B A. Effects of colforsin, trequinsin and isoprenaline on norepinephrine-induced contractions and cyclic nucleotide levels of isolated vascular tissue.  Arzneimittelforschung. 1988;  38 240-243
• 56 Bristow M R, Ginsburg R, Strosberg A, Montgomery W, Minobe W. Pharmacology and inotropic potential of forskolin in the human heart.  J Clin Invest. 1984;  74 212-223
• 57 Kramer W, Thormann J, Kindler M, Schlepper M. Effects of forskolin on left ventricular function in dilated cardiomyopathy.  Arzneimittelforschung. 1987;  37 364-367
• 58 Baumann G, Felix S, Sattelberger U, Klein G. Cardiovascular effects of forskolin (HL 362) in patients with idiopathic congestive cardiomyopathy – a comparative study with dobutamine and sodium nitroprusside.  J Cardiovasc Pharmacol. 1990;  16 93-100
• 59 Vaden S L, Adams H R. Inotropic, chronotropic and coronary vasodilator potency of forskolin.  Eur J Pharmacol. 1985;  118 131-137
• 60 Wysham D G, Brotherton A F, Heistad D D. Effects of forskolin on cerebral blood flow: implications for a role of adenylate cyclase.  Stroke. 1986;  17 1299-1303
• 61 Agarwal K C, Zielinski B A, Maitra R S. Significance of plasma adenosine in the antiplatelet activity of forskolin: potentiation by dipyridamole and dilazep.  Thromb Haemost. 1989;  61 106-110
• 62 Graber S E, Hawiger J. Evidence that changes in platelet cyclic AMP levels regulate the fibrinogen receptor on human platelets.  J Biol Chem. 1982;  257 14606-14609
• 63 Kariya T, Morito F, Sakai T, Takahata K, Yamanaka M. Effect of forskolin on platelet deaggregation and cyclic AMP generation.  Naunyn Schmiedebergs Arch Pharmacol. 1985;  331 119-121
• 64 Salim M L D. Effect of aspirin and forskolin on blood platelet function.  Alex J Pharm Sci. 2003;  17 151-155
• 65 de Chaffoy de Courcelles D, Roevens P, Van Belle H. Prostaglandin E1 and forskolin antagonize C-kinase activation in the human platelet.  Biochem J. 1987;  244 93-99
• 66 Doni M G, Deana R, Bertoncello S, Zoccarato F, Alexandre A. Forskolin and prostacyclin inhibit fluoride induced platelet activation and protein kinase C dependent responses.  Biochem Biophys Res Commun. 1988;  156 1316-1323
• 67 Russo I, Doronzo G, Mattiello L, De Salve A, Trovati M, Anfossi G. The activity of constitutive nitric oxide synthase is increased by the pathway cAMP/cAMP-activated protein kinase in human platelets. New insights into the antiaggregating effects of cAMP-elevating agents.  Thromb Res. 2004;  114 265-273
• 68 Wong S, Mok W, Phaneuf S, Katz S, Salari H. Forskolin inhibits platelet-activating factor binding to platelet receptors independently of adenylyl cyclase activation.  Eur J Pharmacol. 1993;  245 55-61
• 69 Agarwal K C, Parks Jr R E. Forskolin: a potential antimetastatic agent.  Int J Cancer. 1983;  32 801-804
• 70 Yoshizawa J, Yoshida K, Fujikawa T, Tanabe A, Sakurai K. Inhibitory effects of forskolin on hepatic metastasis from human colon cancer in nude mice.  Nippon Geka Gakkai Zasshi. 1995;  96 26-30
• 71 Thulesius O, Christenson J T. Methods for preventing thrombosis; and surgical implant having reduced platelet deposition characteristics. US Patent 4909799. 1990
• 72 Siegl A M, Moroff G. Effect of forskolin on the maintenance of platelet properties during storage.  J Lab Clin Med. 1986;  108 354-359
• 73 Chang J, Hand J M, Schwalm S, Dervinis A, Lewis A J. Bronchodilating activity of forskolin in vitro and in vivo.  Eur J Pharmacol. 1984;  101 271-274
• 74 Kreutner W, Chapman R W, Gulbenkian A, Tozzi S. Bronchodilator and antiallergy activity of forskolin.  Eur J Pharmacol. 1985;  111 1-8
• 75 Tsukawaki M, Suzuki K, Suzuki R, Takagi K, Satake T. Relaxant effects of forskolin on guinea pig tracheal smooth muscle.  Lung. 1987;  165 225-237
• 76 Yousif M H M, Thulesius O. A pharmacological study of bronchodilator properties of NKH477, forskolin, and β-agonists on guinea pig and ovine isolated bronchioles.  Drug Dev Res. 2000;  51 169-176
• 77 Yousif M H, Thulesius O. Forskolin reverses tachyphylaxis to the bronchodilator effects of salbutamol: an in-vitro study on isolated guinea-pig trachea.  J Pharm Pharmacol. 1999;  51 181-186
• 78 Kreutner W, Green M J, Shue H-J, Saksena A K. Method for treating allergic reactions with forskolin. US Patent 4782082. 1988
• 79 Lichey I, Friedrich T, Priesnitz M, Biamino G, Usinger P, Huckauf H. Effect of forskolin on methacholine-induced bronchoconstriction in extrinsic asthamtics.  Lancet. 1984;  2 167
• 80 Kaik G, Witte P U. Protective effect of forskolin in acetylcholine provocation in healthy probands. Comparison of 2 doses with fenoterol and placebo.  Wien Med Wochenschr. 1986;  136 637-641
• 81 González-Sánchez R, Trujillo X, Trujillo-Hernández B, Vásquez C, Huerta M, Elizalde A. Forskolin versus sodium cromoglycate for prevention of asthma attacks: a single-blinded clinical trial.  J Int Med Res. 2006;  34 200-207
• 82 Bauer K, Dietersdorfer F, Sertl K, Kaik B, Kaik G. Pharmacodynamic effects of inhaled dry powder formulations of fenoterol and colforsin in asthma.  Clin Pharmacol Ther. 1993;  53 76-83
• 83 Yang C M, Pan S L, Chiu C T, Lin C C, Hsu Y M. Effect of forskolin on endothelin-induced phosphoinositide hydrolysis and calcium mobilization in cultured canine tracheal smooth muscle cells.  J Auton Pharmacol. 1998;  18 213-221
• 84 Schramm C M, Chuang S T, Grunstein M M. cAMP generation inhibits inositol 1,4,5-trisphosphate binding in rabbit tracheal smooth muscle.  Am J Physiol. 1995;  269 L715-L719
• 85 Zhu S, White R E, Barman S A. Effect of PKC isoenzyme inhibition on forskolin-induced activation of BKCa channels in rat pulmonary arterial smooth muscle.  Lung. 2006;  184 89-97
• 86 Bai Y, Sanderson M J. Airway smooth muscle relaxation results from a reduction in the frequency of Ca²⁺ oscillations induced by a cAMP-mediated inhibition of the IP₃ receptor.  Respir Res. 2006;  7 34
• 87 Tajimi M, Hori M, Mitsui M, Ozaki H, Karaki H. Inhibitory effect of forskolin on myosin phosphorylation-dependent and independent contractions in bovine tracheal smooth muscle.  J Smooth Muscle Res. 1995;  31 129-142
• 88 Tolloczko B, Jia Y L, Martin J G. Effects of cAMP on serotonin evoked calcium transients in cultured rat airway smooth muscle cells.  Am J Physiol. 1997;  272 L865-L871
• 89 Sakai J, Oike M, Hirakawa M, Ito Y. Theophylline and cAMP inhibit lysophosphatidic acid-induced hyperresponsiveness of bovine tracheal smooth muscle cells.  J Physiol. 2003;  549 171-180
• 90 Kaur M, Holden N S, Wilson S M, Sukkar M B, Chung K F, Barnes P J, Newton R, Giembycz M A. Effect of beta2-adrenoceptor agonists and other cAMP-elevating agents on inflammatory gene expression in human ASM cells: a role for protein kinase A.  Am J Physiol Lung Cell Mol Physiol. 2008;  295 L505-L514
• 91 Musa N L, Ramakrishnan M, Li J, Kartha S, Liu P, Pestell R G, Hershenson M B. Forskolin inhibits cyclin D1 expression in cultured airway smooth-muscle cells.  Am J Respir Cell Mol Biol. 1999;  20 352-358
• 92 Kassel K M, Wyatt T A, Panettieri Jr R A, Toews M L. Inhibition of human airway smooth muscle cell proliferation by β-2-adrenergic receptors and cAMP is PKA independent: evidence for EPAC involvement.  Am J Physiol Lung Cell Mol Physiol. 2008;  294 L131-L138
• 93 Prostran M, Varagić V M. The effect of forskolin on the isometric contraction of the isolated hemidiaphragm of the rat.  Br J Pharmacol. 1986;  88 791-797
• 94 Takahashi S, Moriwaki K, Himeno S, Kuroshima T, Shinomura Y, Hamabe S, Kurokawa M, Saito R, Kitani T, Tarui S. Forskolin-induced cyclic AMP production and gastric acid secretion in dispersed rabbit parietal cells: novel evidence for a major role of cyclic AMP in acid release.  Life Sci. 1983;  33 1401-1408
• 95 Choquet A, Magous R, Galleyrand J C, Bali J P. Is forskolin a stimulant of gastric secretion?.  C R Seances Soc Biol Fil. 1988;  182 335-343
• 96 Hersey S J, Miller M, Norris S H. Forskolin: a new biochemical tool for studying gastric secretion.  Prog Clin Biol Res. 1983;  126 329-341
• 97 Hersey S J, Owirodu A, Miller M. Forskolin stimulation of acid and pepsinogen secretion by gastric glands.  Biochim Biophys Acta. 1983;  755 293-299
• 98 Modlin I M, Schafer D E, Tyshkov M, Ballantyne G H, Fratesi G R, Roberts J R, Zdon M J. Forskolin (cyclic adenosine monophosphate)-dependent protein phosphorylation in isolated gastric glands.  Arch Surg. 1986;  121 330-337
• 99 Iwatsuki K, Horiuchi A, Yamagishi F, Chiba S. Effects of forskolin on pancreatic exocrine secretion and cyclic nucleotide concentrations of the dog pancreas.  Arch Int Pharmacodyn Ther. 1987;  286 320-328
• 100 Dubey M P, Srimal R C, Nityanand S, Dhawan B N. Pharmacological studies on coleonol, a hypotensive diterpene from Coleus forskohlii.  J Ethnopharmacol. 1981;  3 1-13
• 101 Mimura M. Functional food for the bowel movement improvement. Japanese Patent JP 2007097572 A. 2007
• 102 Morita T, Wheeler M A, Miyagawa I, Kondo S, Weiss R M. Effects of forskolin on contractility and cyclic AMP levels in rabbit detrusor muscle.  Tohoku J Exp Med. 1986;  149 283-285
• 103 Truss M C, Uckert S, Stief C G, Kuczyk M, Schulz-Knappe P, Forssmann W G, Jonas U. Effects of various phosphodiesterase-inhibitors, forskolin, and sodium nitroprusside on porcine detrusor smooth muscle tonic responses to muscarinergic stimulation and cyclic nucleotide levels in vitro.  Neurourol Urodyn. 1996;  15 59-70
• 104 Schwertschlag U, Hackenthal E. Forskolin stimulates renin release from the isolated perfused rat kidney.  Eur J Pharmacol. 1982;  84 111-113
• 105 Bishop B L, Duncan M J, Song J, Li G, Zaas D, Abraham S N. Cyclic AMP-regulated exocytosis of Escherichia coli from infected bladder epithelial cells.  Nat Med. 2007;  13 625-630
• 106 Vedernikov Y P, Syal A S, Okawa T, Saade G R, Garfield R E. Adenylate cyclase and potassium channels are involved in forskolin- and 1,9-dideoxyforskolin-induced inhibition of pregnant rat uterus contractility.  Am J Obstet Gynecol. 2000;  182 620-624
• 107 Tamaki T, Hasui K, Shoji T, Aki Y, Kiyomoto H, Iwao H, Abe Y. Forskolin preferentially dilates the afferent arteriole in the canine kidney.  Jpn J Pharmacol. 1991;  55 161-164
• 108 Caprioli J, Sears M. Forskolin lowers intraocular pressure in rabbits, monkeys, and man.  Lancet. 1983;  1 958-960
• 109 Caprioli J, Sears M, Bausher L, Gregory D, Mead A. Forskolin lowers intraocular pressure by reducing aqueous inflow.  Invest Ophthalmol Vis Sci. 1984;  25 268-277
• 110 Burstein N L, Sears M L, Mead A. Aqueous flow in human eyes is reduced by forskolin, a potent adenylate cyclase activator.  Exp Eye Res. 1984;  39 745-749
• 111 Caprioli J, Sears M. The adenylate cyclase receptor complex and aqueous humor formation.  Yale J Biol Med. 1984;  57 283-300
• 112 Sears M L. Regulation of aqueous flow by the adenylate cyclase receptor complex in the ciliary epithelium.  Am J Ophthalmol. 1985;  100 194-198
• 113 Bartels S P, Lee S R, Neufeld A H. Forskolin stimulates cyclic AMP synthesis, lowers intraocular pressure and increases outflow facility in rabbits.  Curr Eye Res. 1982/1983;  2 673-681
• 114 Ramachandran C, Satpathy M, Mehta D, Srinivas S P. Forskolin induces myosin light chain dephosphorylation in bovine trabecular meshwork cells.  Curr Eye Res. 2008;  33 169-176
• 115 Bartels S P, Lee S R, Neufeld A H. The effects of forskolin on cyclic AMP, intraocular pressure and aqueous humor formation in rabbits.  Curr Eye Res. 1987;  6 307-320
• 116 Lee P Y, Podos S M, Serle J B, Camras C B, Severin C H. Intraocular pressure effects of multiple doses of drugs applied to glaucomatous monkey eyes.  Arch Ophthalmol. 1987;  105 249-252
• 117 Matsumoto S, Yamashita T, Araie M, Kametani S, Hosokawa T, Takase M. The ocular penetration of topical forskolin and its effects on intraocular pressure, aqueous flow rate and cyclic AMP level in the rabbit eye.  Jpn J Ophthalmol. 1990;  34 428-435
• 118 Santana C, Menendez-Pelaez A, Reiter R J, Guerrero J M. Treatment with forskolin for 8 hours during the day increases melatonin synthesis in the Syrian hamster pineal gland in organ culture: the long lag period is required for RNA synthesis.  J Neurosci Res. 1990;  25 545-548
• 119 Michelet J F, Gautier B, Gaillard O, Bernard B A, Benech F. Human hair follicle pigmentary unit as a direct target for modulators of melanogenesis, as studied by [C]-2-thiouracil incorporation.  Exp Dermatol. 2009;  18 414-416
• 120 Nishizawa H, Kono T, Yokoyama D, Masuda M. Effects of forskolin on hair follicular keratinocytes.  Nippon Koshohin Kagakkaishi. 2000;  24 111-114
• 121 Hayashi T. Application of a new botanical ingredient ‘Coleus extract to hair growth products.  Fragr J. 2000;  28 45-49
• 122 Majeed M. Compositions and methods to treat alopecia. US Pat Appl Publ US 2008/0241285 A1. 2008
• 123 Lal B, Blumbach J, Dohadwalla A N, de Souza N J. Pharmaceutical compositions comprising labdane diterpenoid derivatives and pyrimido[6,1-a]isoquinolin-4-one derivatives and their use. US Patent 5141942. 1992
• 124 D'Orazio J A, Nobuhisa T, Cui R, Arya M, Spry M, Wakamatsu K, Igras V, Kunisada T, Granter S R, Nishimura E K, Ito S, Fisher D E. Topical drug rescue strategy and skin protection based on the role of Mc1 r in UV-induced tanning.  Nature. 2006;  443 340-344
• 125 Passeron T, Namiki T, Passeron H J, Le Pape E, Hearing V J. Forskolin protects keratinocytes from UVB-induced apoptosis and increases DNA repair independent of its effects on melanogenesis.  J Invest Dermatol. 2009;  129 162-166
• 126 Majeed M. Compositions and methods to effect enhanced photoprotection against UV A and UV B induced damage of human skin. US Pat Appl Publ US 2008/0226571 A1. 2008
• 127 Halprin K M, Adachi K. Treatment of hyperplastic diseases of the skin with polyoxygenated labdanes. PCT Int Appl WO 8503637 A1. 1985
• 128 Piontek M, Hengels K J, Porschen R, Strohmeyer G. Protein kinase C and adenylate cyclase as targets for growth inhibition of human gastric cancer cells.  J Cancer Res Clin Oncol. 1993;  119 697-699
• 129 Gützkow K B, Naderi S, Blomhoff H K. Forskolin-mediated G1 arrest in acute lymphoblastic leukemia cells: phosphorylated pRB sequesters E2Fs.  J Cell Sci. 2002;  115 1073-1082
• 130 Guan K, Liu H, Tan W. Relationship between expression of Ha-ras and inhibition of proliferation by forskolin in human gastric cancer cell line BGC-823.  Shengwu Huaxue Zazhi. 1995;  11 401-405
• 131 Guan K, Liu H, Tan W. The effect of forskolin on protein kinase C and its subunits in human gastric cancer cell line BGC-823.  Shengwu Huaxue Zazhi. 1995;  11 316-320
• 132 Wang X, Zhang L, Zhao S, Ma L. Effects of forskolin on cell proliferation in human gastric cancer cells.  Zhongliu Fangzhi Zazhi. 2003;  10 928-930
• 133 Neviani P, Santhanam R, Trotta R, Notari M, Blaser B W, Liu S, Mao H, Chang J S, Galietta A, Uttam A, Roy D C, Valtieri M, Bruner-Klisovic R, Caligiuri M A, Bloomfield C D, Marcucci G, Perrotti D. The tumor suppressor PP2A is functionally inactivated in blast crisis CML through the inhibitory activity of the BCR/ABL-regulated SET protein.  Cancer Cell. 2005;  8 355-368
• 134 McEwan D G, Brunton V G, Baillie G S, Leslie N R, Houslay M D, Frame M C. Chemoresistant KM12C colon cancer cells are addicted to low cyclic AMP levels in a phosphodiesterase 4-regulated compartment via effects on phosphoinositide 3-kinase.  Cancer Res. 2007;  67 5248-5257
• 135 Zhang D, Ye C, Wang H. Antitumor composition containing forskolin, theophylline, IBMX and carboxyamidotriazole. Chinese Patent CN 1660434 A. 2005
• 136 García-Bermejo L, Pérez C, Vilaboa N E, de Blas E, Aller P. cAMP increasing agents attenuate the generation of apoptosis by etoposide in promonocytic leukemia cells.  J Cell Sci. 1998;  111 637-644
• 137 Watabe M, Masuda Y, Nakajo S, Yoshida T, Kuroiwa Y, Nakaya M. The cooperative interaction of two different signaling pathways in response to bufalin induces apoptosis in human leukemia U937 cells.  J Biol Chem. 1996;  271 14067-14073
• 138 Wu S I, Ma J, Qi H I, Zhang Y, Zhang X Y, Chen H I. Forskolin up-regulates metastasis-related phenotypes and molecules via protein kinase B, but not PI-3K, in H7721 human hepato-carcinoma cell line.  Mol Cell Biochem. 2003;  254 193-202
• 139 Burns T W, Langley P E, Terry B E, Bylund D B, Forte L R. Alpha-2 adrenergic activation inhibits forskolin-stimulated adenylate cyclase activity and lipolysis in human adipocytes.  Life Sci. 1982;  31 815-821
• 140 Okuda H, Morimoto C, Tsujita T. Relationship between cyclic AMP production and lipolysis induced by forskolin in rat fat cells.  J Lipid Res. 1992;  33 225-231
• 141 Mooney R A, Swicegood C L, Marx R B. Coupling of adenylate cyclase to lipolysis in permeabilized adipocytes: direct evidence that an antilipolytic effect of insulin is independent of adenylate cyclase.  Endocrinology. 1986;  119 2240-2248
• 142 Litosch I, Hudson T H, Mills I, Li S Y, Fain J N. Forskolin as an activator of cyclic AMP accumulation and lipolysis in rat adipocytes.  Mol Pharmacol. 1982;  22 109-115
• 143 Allen D O, Ahmed B, Naseer K. Relationships between cyclic AMP levels and lipolysis in fat cells after isoproterenol and forskolin stimulation.  J Pharmacol Exp Ther. 1986;  238 659-664
• 144 Allen D O, Quesenberry J T. Quantitative differences in the cyclic AMP-lipolysis relationships for isoproterenol and forskolin.  J Pharmacol Exp Ther. 1988;  244 852-858
• 145 Schimmel R J. Stimulation of cAMP accumulation and lipolysis in hamster adipocytes with forskolin.  Am J Physiol. 1984;  246 C63-C68
• 146 Morimoto C, Kameda K, Tsujita T, Okuda H. Relationships between lipolysis induced by various lipolytic agents and hormone-sensitive lipase in rat fat cells.  J Lipid Res. 2001;  42 120-127
• 147 Majeed M, Bammi R K, Sankaran N, Ramanujam R, Kalkunte S S, Prakash S. Method of preparing labdane diterpene composition, preferably isoforskolin and deacetylforskolin from forskolin extract and their use for promoting lean body mass and other applications. US Pat Appl Publ US 2006122261 A1. 2006
• 148 Greenway F L, Bray G A. Regional fat loss from the thigh in obese women after adrenergic modulation.  Clin Ther. 1987;  9 663-669
• 149 Greenway F L, Bray G A, Heber D. Topical fat reduction.  Obes Res. 1995;  3 (Suppl. 4) 561S-568S
• 150 Furukawa Y, Matsumori A, Hirozane T, Matsui S, Sato Y, Ono K, Sasayama S. Immunomodulation by an adenylate cyclase activator, NKH477, in vivo and vitro.  Clin Immunol Immunopathol. 1996;  79 25-35
• 151 Schorlemmer H U, Dickneite G, Sedlacek H H, de Souza N J, Dohadwalla A N. Use of the diterpene derivative forskolin for immunostimulation. US Patent 4578399. 1986
• 152 Curtin B F, Pal N, Gordon R K, Nambiar M P. Forskolin, an inducer of cAMP, upregulates acetylcholinesterase expression and protects against organophosphate exposure in neuro 2A cells.  Mol Cell Biochem. 2006;  290 23-32
• 153 Morazzoni P, Bombardelli E. Use of forskolin or extracts containing it in the manufacture of a medicament for the treatment of alcohol addiction. PCT Int Appl WO 9636332 A1. 1996
• 154 Karaçay B, Li G, Pantazis N J, Bonthius D J. Stimulation of the cAMP pathway protects cultured cerebellar granule neurons against alcohol-induced cell death by activating the neuronal nitric oxide synthase (nNOS) gene.  Brain Res. 2007;  1143 34-45
• 155 Gupta P P, Srimal R C, Verma N, Tandon J S. Passive cutaneous anaphylactic inhibitory and mast cell stabilizing activity of coleonol and its derivative.  Indian J Pharmacol. 1994;  26 150-152
• 156 Marone G, Columbo M, Triggiani M, Cirillo R, Genovese A, Formisano S. Inhibition of IgE-mediated release of histamine and peptide leukotriene from human basophils and mast cells by forskolin.  Biochem Pharmacol. 1987;  36 13-20
• 157 Dohadwalla A N, Mandrekar S S, Dadkar N K, Khandelwal Y, Rupp R H, de Souza N J. Labdane derivatives and their use as drugs. Patent DE 3502686 A1. 1986
• 158 Dohadwalla A N, Mandrekar S S, Dadkar N K, Khandelwal Y, Rupp R H, de Souza N J. Method of treating inflammatory diseases with labdan derivatives. US Patent 4724238. 1988
• 159 Maeda H, Ozawa H, Saito T, Irie T, Takahata N. Potential antidepressant properties of forskolin and a novel water-soluble forskolin (NKH477) in the forced swimming test.  Life Sci. 1997;  61 2435-2442
• 160 Sano M, Seto-Ohshima A, Mizutani A. Forskolin supresses seizures induced by pentylenetetrazole in mice.  Experientia. 1984;  40 1270-1271
• 161 Barraco R A, Phillis J W, Altman H J. Depressant effect of forskolin on spontaneous locomotor activity in mice.  Gen Pharmacol. 1985;  16 521-524
• 162 Bersudsky Y, Kotler M, Shifrin M, Belmaker R H. A preliminary study of possible psychoactive effects of intravenous forskolin in depressed and schizophrenic patients. Short communication.  J Neural Transm. 1996;  103 1463-1467
• 163 Vitolo O V, Sant'Angelo A, Costanzo V, Battaglia F, Arancio O, Shelanski M. Amyloid beta-peptide inhibition of the PKA/CREB pathway and long-term potentiation: reversibility by drugs that enhance cAMP signaling.  Proc Natl Acad Sci USA. 2002;  99 13217-13221
• 164 Wang X, Li X, Wang K, Zhou H, Xue B, Li L, Wang X. Forskolin cooperating with growth factor on generation of dopaminergic neurons from human fetal mesencephalic neural progenitor cells.  Neurosci Lett. 2004;  362 117-121
• 165 Ahmad F, Khan M M, Rastogi A K, Kidwai J R. Insulin and glucagon releasing activity of coleonol (forskolin) and its effect on blood glucose level in normal and alloxan diabetic rats.  Acta Diabetol Lat. 1991;  28 71-77
• 166 Yamamoto S, Nakadate T, Uzumaki H, Kato R. Lipoxygenase inhibitors and cyclic AMP-mediated insulin secretion caused by forskolin, theophylline and dibutyryl cyclic AMP.  J Pharmacol Exp Ther. 1985;  233 176-180
• 167 Leclercq-Meyer V, Malaisse W J. Modulation of gliquidone action by forskolin in the pancreas of normal and GK rats.  Am J Physiol. 1997;  273 E52-E58
• 168 Mulhall J P, Daller M, Traish A M, Gupta S, Park K, Salimpour P, Payton T R, Krane R J, Goldstein I. Intracavernosal forskolin: role in management of vasculogenic impotence resistant to standard 3-agent pharmacotherapy.  J Urol. 1997;  158 1752-1759
• 169 Liu J H, Li Y, Cao Z G, Ye Z Q. Influences of dibutyryl cyclic adenosine monophosphate and forskolin on human sperm motility in vitro.  Asian J Androl. 2003;  5 113-115
• 170 Li Y, Liu J, Ye H, Ye Z. Influence of forskolin on human sperm motility.  Zhongguo Nankexue Zazhi. 2004;  18 23-25
• 171 van Sande J, Cochaux P, Mockel J, Dumont J E. Stimulation by forskolin of the thyroid adenylate cyclase, cyclic AMP accumulation and iodine metabolism.  Mol Cell Endocrinol. 1983;  29 109-119
• 172 Laurenza A, Sutkowski E M, Seamon K B. Forskolin: a specific stimulator of adenylyl cyclase or a diterpene with multiple sites of action?.  Trends Pharmacol Sci. 1989;  10 442-447
• 173 Kashiwagi A, Huecksteadt T P, Foley J E. The regulation of glucose transport by cAMP stimulators via three different mechanisms in rat and human adipocytes.  J Biol Chem. 1983;  258 13685-13692
• 174 Joost H G, Steinfelder H J. Forskolin inhibits insulin-stimulated glucose transport in rat adipose cells by a direct interaction with the glucose transporter.  Mol Pharmacol. 1987;  31 279-283
• 175 Sergeant S, Kim H D. Inhibition of 3-O-methylglucose transport in human erythrocytes by forskolin.  J Biol Chem. 1985;  260 14677-14682
• 176 Kim H D, Sergeant S, Shukla S D. Glucose transport in human platelets and its inhibition by forskolin.  J Pharmacol Exp Ther. 1986;  236 585-589
• 177 Martin G E, Seamon K B, Brown F M, Shanahan M F, Roberts P E, Henderson P J. Forskolin specifically inhibits the bacterial galactose-H⁺ transport protein, GalP.  J Biol Chem. 1994;  269 24870-24877
• 178 Hoshi T, Garber S S, Aldrich R W. Effect of forskolin on voltage-gated K⁺ channels is independent of adenylate cyclase activation.  Science. 1988;  240 1652-1655
• 179 Matthias K, Seifert G, Reinhardt S, Steinhäuser C. Modulation of voltage-gated K(+) channels Kv11 and Kv14 by forskolin.  Neuropharmacology. 2002;  43 444-449
• 180 Ono K, Fozzard H A, Hanck D A. A direct effect of forskolin on sodium channel bursting.  Pflugers Arch. 1995;  429 561-569
• 181 Asai T, Pelzer S, McDonald T F. Cyclic AMP-independent inhibition of cardiac calcium current by forskolin.  Mol Pharmacol. 1996;  50 1262-1272
• 182 Park T J, Kim K T. Cyclic AMP-independent inhibition of voltage-sensitive calcium channels by forskolin in PC12 cells.  J Neurochem. 1996;  66 83-88
• 183 Gandía L, Vitale M L, Villarroya M, Ramirez-Lavergne C, García A G, Trifaró J M. Differential effects of forskolin and 1,9-dideoxyforskolin on nicotinic receptor-and K⁺-induced responses in chromaffin cells.  Eur J Pharmacol. 1997;  329 189-199
• 184 Shi L J, Liu L A, Wang C A. Effect of forskolin on acetylcholine-induced current in rat pheochromocytoma cells.  Acta Pharmacol Sin. 2000;  21 281-285
• 185 Fan P. Antagonism by forskolin of the 5-HT3 receptor-mediated current in nodose ganglion neurons is independent of cyclic AMP.  Brain Res. 1994;  650 16-19
• 186 Oz M, Zhang L, Spivak C E. Direct noncompetitive inhibition of 5-HT3 receptor-mediated responses by forskolin and steroids.  Arch Biochem Biophys. 2002;  404 293-301
• 187 Wadler S, Wiernik P H. Partial reversal of doxorubicin resistance by forskolin and 1,9-dideoxyforskolin in murine sarcoma S180 variants.  Cancer Res. 1988;  48 539-543
• 188 Morris D I, Speicher L A, Ruoho A E, Tew K D, Seamon K B. Interaction of forskolin with the P-glycoprotein multidrug transporter.  Biochemistry. 1991;  30 8371-8379
• 189 Uboldi A D, Savage N. The adenylate cyclase activator forskolin partially protects L929 cells against tumour necrosis factor-alpha-mediated cytotoxicity via a cAMPindependent mechanism.  Cytokine. 2002;  19 250-258
• 190 Sidhu J S, Omiecinski C J. Forskolin-mediated induction of CYP3A1 mRNA expression in primary rat hepatocytes is independent of elevated intracellular cyclic AMP.  J Pharmacol Exp Ther. 1996;  276 238-245
• 191 Dowless M S, Barbee J L, Borchert K M, Bocchinfuso W P, Houck K A. Cyclic AMP-independent activation of CYP3A4 gene expression by forskolin.  Eur J Pharmacol. 2005;  512 9-13
• 192 Li Ping, Yang X L. Forskolin modulation of desensitization at GABAA and glycine receptors is not mediated by cAMP-dependent protein kinase in isolated carp amacrine-like cells.  Pflugers Arch. 2001;  441 739-745
• 193 Middleton P, Jaramillo F, Schuetze S M. Forskolin increases the rate of acetylcholine receptor desensitization at rat soleus endplates.  Proc Natl Acad Sci USA. 1986;  83 4967-4971
• 194 Miles K, Anthony D T, Rubin L L, Greengard P, Huganir R L. Regulation of nicotinic acetylcholine receptor phosphorylation in rat myotubes by forskolin and cAMP.  Proc Natl Acad Sci USA. 1987;  84 6591-6595
• 195 Wagoner P K, Pallotta B S. Modulation of acetylcholine receptor desensitization by forskolin is independent of cAMP.  Science. 1988;  240 1655-1657
• 196 Middleton P, Rubin L L, Schuetze S M. Desensitization of acetylcholine receptors in rat myotubes is enhanced by agents that elevate intracellular cAMP.  J Neurosci. 1988;  8 3405-3412
• 197 Berger C E, Datta H K. Forskolin has a bimodal cAMP-independent effect on superoxide anion generation in isolated osteoclasts.  Exp Physiol. 2000;  85 57-60
• 198 Kreiger N S, Stern P H. Effect of forskolin on bone in organ culture.  Am J Physiol. 1987;  252 E44-E48
• 199 Ding X, Staudinger J L. Induction of drug metabolism by forskolin: the role of the pregnane X receptor and the protein kinase A signal transduction pathway.  J Pharmacol Exp Ther. 2005;  312 849-856
• 200 Putnam W C, Swenson S M, Reif G A, Wallace D P, Helmkamp Jr G M, Grantham J J. Identification of a forskolin-like molecule in human renal cysts.  J Am Soc Nephrol. 2007;  18 934-943
• 201 Yang W, Li X, Chen Z, Nie L, Wang B, Shen Z. Adenylate cyclase stimulation and ocular hypertension inhibition by forskolin analogs.  Yanke Yanjiu. 2001;  19 1-4
• 202 Bhat S V, Bajwa B S, Dornauer H, de Souza N J, Fehlhaber H W. Structures and stereochemistry of new labdane diterpenoids from Coleus forskohlii Briq.  Tetrahedron Lett. 1977;  19 1669-1672
• 203 Tandon J S, Jauhari P K, Singh R S, Dhar M M. Structures of three new diterpenes, coleonol B, coleonol C and deoxycoleonol isolated from Coleus forskohlii.  Indian J Chem Sect B Org Chem Incl Med Chem. 1978;  16 B 341-345
• 204 Shan Y, Xu L, Lu Y, Wang X, Zheng Q, Kong L, Niwa M. Diterpenes from Coleus forskohlii (Willd.) Briq. (Labiatae).  Chem Pharm Bull. 2008;  56 52-56
• 205 Joost H G, Habberfield A D, Simpson I A, Laurenza A, Seamon K B. Activation of adenylate cyclase and inhibition of glucose transport in rat adipocytes by forskolin analogues: structural determinants for distinct sites of action.  Mol Pharmacol. 1988;  33 449-453
• 206 Zerr P, Becherer U, Rodeau J L, Feltz A. Forskolin's structural analog 1,9-dideoxyforskolin has Ca2+ channel blocker-like action in rat cerebellar granule cells.  Eur J Pharmacol. 1996;  303 101-108
• 207 Li Z, Wang J. A forskolin derivative, FSK88, induces apoptosis in human gastric cancer BGC823 cells through caspase activation involving regulation of Bcl-2 family gene expression, dissipation of mitochondrial membrane potential and cytochrome c release.  Cell Biol Int. 2006;  30 940-946
• 208 Tandon J S, Roy R, Balachandran S, Vishwakarma R A. Epi-deoxycoleonol, a new antihypertensive labdane diterpenoid from Coleus forskohlii.  Bioorg Med Chem Lett. 1992;  2 249-254
• 209 Sashidhara K V, Rosaiah J N, Kumar A, Bid H K, Konwar R, Chattopadhyay N. Cell growth inhibitory action of an unusual labdane diterpene, 13-epi-sclareol in breast and uterine cancers in vitro.  Phytother Res. 2007;  21 1105-1108
• 210 Shan Y, Wang X, Zhou X, Kong L, Niwa M. Two minor diterpene glycosides and an eudesman sesquiterpene from Coleus forskohlii.  Chem Pharm Bull. 2007;  55 376-381
• 211 Liu Y, Wu H, Wang X M, Liu J, Xing X. Use of coleon C extracted from Coleus as inhibitor for tumor growth and tumor cell proliferation. Chinese Patent CN 1899273 A. 2007
• 212 Majeed M, Kumar A, Nagabhushanam K, Prakash S. Process for preparing water soluble diterpenes and their applications. US Pat Appl Pub US 2005/0284812 A1. 2005
• 213 Hosono M, Takahira T, Fujita A, Fujihara R, Ishizuka O, Ohoi I, Tatee T, Nakamura K. Cardiovascular effects of NKH477, a novel potent water-soluble forskolin derivative.  Eur J Pharmacol. 1990;  183 2110
• 214 Laurenza A, Khandelwal Y, de Souza N J, Rupp R H, Metzger H, Seamon K B. Stimulation of adenylate cyclase by water-soluble analogues of forskolin.  Mol Pharmacol. 1987;  32 133-139
• 215 Saettone M F, Burgalassi S, Giannaccini B. Preparation and evaluation in rabbits of topical solutions containing forskolin.  J Ocul Pharmacol. 1989;  5 111-118
• 216 Khandelwal Y, Rajeshwari K, Rajagopalan R, Swamy L, Dohadwalla A N, de Souza N J, Rupp R H. Cardiovascular effects of new water-soluble derivatives of forskolin.  J Med Chem. 1988;  31 1872-1879
• 217 Tatee T, Narita A, Narita K, Izumi G, Takahira T, Sakurai M, Fujita A, Hosono M, Yamashita K, Enomoto K, Shiozawa A. Forskolin derivatives. I. Synthesis, and cardiovascular and adenylate cyclase-stimulating activities of water-soluble forskolins.  Chem Pharm Bull (Tokyo). 1996;  44 2274-2279
• 218 Himeta M, Sakashita Y, Fujita A, Hosono M, Nakamura K. Characterization of the vasodilating effects of NKH477, a novel forskolin derivative, in isolated rat aorta, canine arteries and rabbit femoral arteries and veins.  Yakuri To Chiryo. 1998;  26 775-785
• 219 Hosono M. Cardiovascular effects of colforsin daropate hydrochloride, a novel drug for the treatment of acute heart failure.  Nippon Yakurigaku Zasshi. 1999;  114 83-88
• 220 Hirota K, Yoshioka H, Kabara S, Koizumi Y, Abe H, Sato T, Matsuki A. Spasmolytic effects of colforsin daropate on serotonin-induced pulmonary hypertension and bronchoconstriction in dogs.  Acta Anaesthesiol Scand. 2002;  46 297-302
• 221 Ogata J, Minami K, Segawa K, Uezono Y, Shiraishi M, Yamamoto C, Sata T, Sung-Teh K, Shigematsu A. A forskolin derivative, colforsin daropate hydrochloride, inhibits the decrease in cortical renal blood flow induced by noradrenaline or angiotensin II in anesthetized rats.  Nephron Physiol. 2004;  96 59-64
• 222 Uchida M, Iida H, Iida M, Kumazawa M, Sumi K, Takenaka M, Dohi S. Both milrinone and colforsin daropate attenuate the sustained pial arteriolar constriction seen after unclamping of an abdominal aortic cross-clamp in rabbits.  Anesth Analg. 2005;  101 9-16
• 223 Nakashima S, Morikawa M, Komatsu K, Matsuura A, Sato N, Abe T. Antiproliferative effects of NKH477, a forskolin derivative, on cytokine profile in rat lung allografts.  J Heart Lung Transplant. 2005;  24 462-469
• 224 Onda T, Hashimoto Y, Nagai M, Kuramochi H, Saito S, Yamazaki H, Toya Y, Sakai I, Homcy C J, Nishikawa K, Ishikawa Y. Type-specific regulation of adenylyl cyclase. Selective pharmacological stimulation and inhibition of adenylyl cyclase isoforms.  J Biol Chem. 2001;  276 47785-47793
• 225 Toya Y, Schwencke C, Ishikawa Y. Forskolin derivatives with increased selectivity for cardiac adenylyl cyclase.  J Mol Cell Cardiol. 1998;  30 97-108
• 226 Sawaki S, Furukawa Y, Inoue Y, Takayama S, Chiba S. Positive chronotropic and inotropic responses to novel cardiotonics, NKH477 and MCI-154 in isolated, perfused canine heart preparations.  Asia Pac J Pharmacol. 1993;  8 133-140
• 227 Takeuchi M, Takaoka H, Hata K, Mori M, Yamakawa H, Yamaguchi K, Yokoyama M. NKH477: a new inotropic agent.  Cardiovasc Drug Rev. 1995;  13 339-352
• 228 Ishizuka O, Hosono M, Nakamura K. Profile of cardiovascular effects of NKH477, a novel forskolin derivative, assessed in isolated, blood-perfused dog heart preparations: comparison with isoproterenol.  J Cardiovasc Pharmacol. 1992;  20 261-267
• 229 Hosono M, Takahira T, Fujita A, Fujihara R, Ishizuka O, Tatee T, Nakamura K. Cardiovascular and adenylate cyclase stimulant properties of NKH477, a novel water-soluble forskolin derivative.  J Cardiovasc Pharmacol. 1992;  19 625-634
• 230 Takahira T, Hosono M, Sakitama K. Cardiovascular effects of NKH477 in experimental canine heart failure.  Junkan Seigyo. 1995;  16 196-203
• 231 Sanbe A, Takeo S. Effects of NKH477, a water-soluble forskolin derivative, on cardiac function in rats with chronic heart failure after myocardial infarction.  J Pharmacol Exp Ther. 1995;  274 120-126
• 232 Ishizuka O, Fujita A, Kanbe E, Noguchi M, Hosono M, Sakitama K. Effectiveness of NKH477, a novel forskolin derivative, in rat cardiac preparations with desensitized beta-adrenoceptors.  Nippon Yakurigaku Zasshi. 1996;  108 23-30
• 233 Mori M, Takeuchi M, Takaoka H, Hata K, Hayashi Y, Yokoyama M. Effect of NKH477, a new water-soluble forskolin derivative, on arterial-ventricular coupling and mechanical energy transduction in patients with left ventricular systolic dysfunction: comparison with dobutamine.  J Cardiovasc Pharmacol. 1994;  24 310-316
• 234 Hayashida N, Chihara S, Tayama E, Kashikie H, Takaseya T, Hiratsuka R, Kai E, Enomoto N, Kawara T, Aoyagi S. Effects of colforsin daropate hydrochloride in patients undergoing coronary artery bypass surgery.  Kyobu Geka. 2001;  54 391-395
• 235 Iranami H, Okamoto K, Kimoto Y, Maeda H, Kakutani T, Hatano Y. Use of colforsin daropate following cardiac surgery in a neonate.  Anesthesiology. 2002;  97 503-504
• 236 Ogata J, Nakano K, Sakamoto K, Minami K. Preoperative use of colforsin daropate hydrochloride in a patient with severe cardiac function scheduled for Y-graft replacement.  Anesth Analg. 2001;  93 1079-1080
• 237 Hayashida N, Teshima H, Tayama E, Chihara S, Enomoto N, Kawara T, Aoyagi S. Influence of colforsin daropate hydrochloride on internal mammary artery grafts.  Circ J. 2002;  66 372-376
• 238 Hibino N, Kawai A, Uchikawa S, Chikazawa G, Kurihara T, Kihara S, Uebe K, Aomi S, Nishida H, Endo M, Koyanagi H. Cardiovascular effects of colforsin daropate hydrochloride for acute heart failure after open heart surgery.  Kyobu Geka. 2001;  54 1016-1019