Potential antidepressant properties of forskolin and a novel water-soluble forskolin (NKH477) in the forced swimming test

Maeda, Hideo; Ozawa, Hiroki; Saito, Toshikazu; Irie, Tsuyoshi; Takahata, Naohiko

doi:10.1016/s0024-3205(97)00978-8

Cited by 14 publications

(5 citation statements)

References 19 publications

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“…The results of the present study provide additional support for the hypothesis that NKH477 has antidepressant properties. This possibility is also supported by a recent study dem- onstrating that NKH477 is effective in behavioral models (Maeda et al, 1997). Moreover, preclinical studies indicate that BDNF can promote the survival and sprouting of serotonergic axons in both normal and pathological conditions (Mamounas et al, 1995) and that BDNF potentiates 5-hydroxytryptamine (serotonin)-mediated signal transduction in rat brain (Martin-Iverson et al, 1994).…”

Section: Discussionmentioning

confidence: 83%

“…Clinical trials with NKH477 indicate that this drug is useful and safe in the treatment of acute heart failure (Hosoda et al, 1995). In addition, NKH477 has been reported to penetrate the blood-brain barrier after peripheral administration and can thereby be used to activate adenylyl cyclase in the CNS (Maeda et al, 1997). Moreover, NKH477 is reported to have antidepressant efficacy in the forced swim test (Maeda et al, 1997).…”

Section: Nkh477 Induces Bdnf and Trkb Mrna Expressionmentioning

confidence: 99%

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Stimulation of Adenylyl Cyclase and Induction of Brain‐Derived Neurotrophic Factor and TrkB mRNA by NKH477, a Novel and Potent Forskolin Derivative

Morinobu

Fujimaki

Okuyama

et al. 1999

Journal of Neurochemistry

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Abstract:The present study was undertaken to examine whether NKH477, a novel and potent water-soluble forskolin derivative, stimulates adenylyl cyclase and regulates brain-derived neurotrophic factor (BDNF) and TrkB expression in the rat brain. Administration of NKH477 at a dose of 1 .O mg/kg, but not 0.1 mg/kg, increased levels of cyclic AMP (CAMP) in a time-dependent manner in frontal cortex and hippocampus. Repeated administration of NKH477 (1.0 mg/kg) for 7 or 14 days also increased levels of cAMP in these two brain regions, indicating that the response does not desensitize with chronic treatment. In addition, administration of NKH477 at the 1 mg/kg dose increased the expression of BDNF and TrkB mRNA in frontal cortex and hippocampus. This effect was observed after single, as well as repeated (7 or 14 days), administration of NKH477. These results demonstrate that NKH477 administration rapidly increases cAMP levels in brain and provides evidence that stimulation of this second messenger system increases the expression of BDNF and TrkB mRNA. Key Words: Adenylyl cyclase-Brain-derived neurotrophic factor-Cyclic AM P-Forskolin-N KH477-TrkB.J. Neurochem. 72,2198-2205 (1 999).

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Section: Discussionmentioning

confidence: 83%

Section: Nkh477 Induces Bdnf and Trkb Mrna Expressionmentioning

confidence: 99%

Stimulation of Adenylyl Cyclase and Induction of Brain‐Derived Neurotrophic Factor and TrkB mRNA by NKH477, a Novel and Potent Forskolin Derivative

Morinobu

Fujimaki

Okuyama

et al. 1999

Journal of Neurochemistry

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“…23-27 % inhibition of developing and established arthritis) respectively, [157,158]. As reported by Maeda et al [159], forskolin (0.01 mg/kg) displayed a potential antidepressant effect, stronger (150 times) than that produced by amitriptyline (15 mg/kg) in the forced swimming test. At a high dose (1.0 mg/kg) of forskolin, the duration of immobility was returned to control level.…”

Section: Miscellaneous Pharmacological Activitiesmentioning

confidence: 87%

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

Alasbahi

Melzig²

2010

Planta Med

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Pharmacology ! Plectranthus barbatusStudies on several extracts with various polarities obtained from different parts of P. barbatus revealed a number of pharmacological properties that may justify most of the traditional uses of P. barbatus, for example, organic extracts were reported to possess anti-inflammatory, antimicrobial [1, 2], antioxidant [3], cytotoxic [4], hypotensive [5,6], spasmolytic [7], hepatoprotective [8] and antifeedant [9] activities as well as activity against Ehrlichʼs ascites tumor in mice [10]. An alcoholic extract of the P. barbatus roots was shown to exhibit marked inhibitory action against Escherichia coli toxin-induced secretory response in rabbits and guinea pig ileal loops [11]. It has been shown that a hydroalcoholic extract of P. barbatus (880 mg/kg/day) exerted a variety of toxic effects on the different periods of pregnancy in rats; for example, in the period before embryo implantation, it caused a delay in fetal development and anti-implantation and, after embryo implantation, a delay in the development associated with maternal toxicity [12]. The water extract of P. barbatus leaves was found to exert hypoglycemic, hypotensive and antispasmodic activities [13]. It has been demonstrated that the water extract (WE) of the stems and leaves, at a dose of 1 g/kg p. o., shortened the sleeping time induced by pentobarbital by 37 %, and at a dose of 2 g/kg p. o. enhanced the intestinal transit of charcoal by 30% in mice. The WE (2 g/kg/intraduodenal) also reduced the gastric secretions (3.9 ± 1.0 to 0.5 ± 0.2 mL/4 h), and total acid secretion (34.4 ± 11.0 to 2.7 ± 0.5 mEq/L) and raised gastric pH (2.2 ± 0.3 to 6.5 ± 0.8) in rats. The treatment with WE (2 g/ kg p. o.) was also found to protect against lesions induced by ethanol or cold-restraint stress, in pylorus-ligated rats [14]. Similar results were obtained by Schultz et al. [15] who reported that the WE of the leaves (0.5-0.1 g/kg) injected into the duodenal lumen decreased the volume (62 and 76 %) and total acidity (23 and 50%) of gastric 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 pharmacologic...

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“…For control injections, rats were administered either saline (vehicle for dbcAMP) and IBMX or 0.02% dimethyl sulfoxide (vehicle for forskolin) and IBMX. Doses of dbcAMP, fsk, and IBMX used in this study were obtained from a review of relevant previous literature (Palmer and Doukas, 1984;Maeda et al, 1997;Tumer et al, 1997) and from preliminary experiments. Using this approach, rats were administered treatments once every hour for 5 h. One hour after the final injection (6 h total) rats were euthanized (1.7 ml/kg euthanyl), and the aorta and femoral arteries were removed and processed as described below.…”

Section: General Reagents Radioactive Chemicals [mentioning

confidence: 99%

Vascular Smooth Muscle Cell Phosphodiesterase (PDE) 3 and PDE4 Activities and Levels are Regulated by Cyclic AMP in Vivo

Tilley

Maurice

2002

Mol Pharmacol

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Prolonged incubation of several cell types, including cultured vascular smooth muscle cells (VSMC), with cyclic AMP-elevating agents increases cAMP phosphodiesterase (PDE) activity and levels. In this work, we describe for the first time an increase in arterial VSMC cAMP PDE activity and levels caused by cAMP-elevating agents when these agents are administered to rats in vivo. Injections of rats with dibutyryl cAMP (dbcAMP) or forskolin increased both PDE3 and PDE4 activities in aortic and femoral artery VSMC. Consistent with the idea that cAMPelevating agents increased PDE3 and PDE4 activities by acting directly on VSMC, local delivery of dbcAMP or forskolin to femoral arteries using a pluronic gel-based approach increased femoral artery VSMC PDE3 and PDE4 activities to levels similar to those observed after injection of these agents. Consistent with a role for de novo mRNA and protein synthesis in the cAMP-elevating agent induced increase in PDE3 and PDE4, 1) systemic administration of forskolin increased PDE3A, PDE3B, and PDE4D mRNA levels in aortic VSMC and femoral artery VSMC, 2) local delivery of dbcAMP increased PDE3A, PDE3B, and PDE4D3 protein levels in femoral artery VSMC, and 3) local administration of either actinomycin D or cycloheximide attenuated the effect of dbcAMP. In addition, our results indicate that the PDE3 and PDE4 variants increased by cAMP-elevating agents in arterial VSMC in situ were distinct from those elevated by these agents in cultured arterial VSMC. Consistent with the effect of increased VSMC cAMP PDE on blood vessel function, inhibition of PDE3 and PDE4 activities potentiated the relaxant effect of forskolin in dbcAMP-treated femoral artery rings to a greater extent than in untreated control blood vessels. We propose that our findings are consistent with the concept that cAMP regulates VSMC cAMP PDE activity and levels in vivo and that VSMC phenotype influences the choice of cAMP PDE variant that is elevated. Our findings are discussed in the context that agents aimed at specific PDE3 or PDE4 variants could perhaps allow greater control of cAMP-mediated regulation of VSMC behaviors that are phenotype-dependent.

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Potential antidepressant properties of forskolin and a novel water-soluble forskolin (NKH477) in the forced swimming test

Cited by 14 publications

References 19 publications

Stimulation of Adenylyl Cyclase and Induction of Brain‐Derived Neurotrophic Factor and TrkB mRNA by NKH477, a Novel and Potent Forskolin Derivative

Stimulation of Adenylyl Cyclase and Induction of Brain‐Derived Neurotrophic Factor and TrkB mRNA by NKH477, a Novel and Potent Forskolin Derivative

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

Vascular Smooth Muscle Cell Phosphodiesterase (PDE) 3 and PDE4 Activities and Levels are Regulated by Cyclic AMP in Vivo

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