Pentacyclic triterpenoids and ceramide mediate the vasorelaxant activity of Vitex cienkowskii via involvement of NO/cGMP pathway in isolated rat aortic rings

Dongmo, Alain Bertrand; Azebaze, Anatole Guy Blaise; Donfack, Flaure Metchi; Dimo, Théophile; Nkeng-Efouet, Pepin Alango; Devkota, Krishna Prasad; Sontia, Bruno; Wagner, Hildebert; Sewald, Norbert; Vierling, W.

doi:10.1016/j.jep.2010.09.033

Cited by 22 publications

(15 citation statements)

References 48 publications

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“…The present study shows that OA and synthetic derivatives do not decrease but rather increase myocyte shortening in cells isolated from normotensive rats but not in cells isolated from hypertensive animals. The study also confirms previous observations that OA possesses vasorelaxant properties in the aorta and in mesenteric arteries [ 13 , 14 ], and extend these properties to the two synthetic derivatives, Br-OA and Me-OA.…”

Section: Discussionsupporting

confidence: 90%

Vascular Endothelium-Dependent and Independent Actions of Oleanolic Acid and Its Synthetic Oleanane Derivatives as Possible Mechanisms for Hypotensive Effects

Madlala¹,

Metzinger²,

Heerden³

et al. 2016

PLoS ONE

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PurposePlant-derived oleanolic acid (OA) and its related synthetic derivatives (Br-OA and Me-OA) possess antihypertensive effects in experimental animals. The present study investigated possible underlying mechanisms in rat isolated single ventricular myocytes and in vascular smooth muscles superfused at 37°C.MethodsCell shortening was assessed at 1 Hz using a video-based edge-detection system and the L-type Ca2+ current (ICaL) was measured using the whole-cell patch-clamp technique in single ventricular myocytes. Isometric tension was measured using force transducer in isolated aortic rings and in mesenteric arteries. Vascular effects were measured in endothelium-intact and denuded vessels in the presence of various enzyme or channel inhibitors.ResultsOA and its derivatives increased cell shortening in cardiomyocytes isolated from normotensive rats but had no effect in those isolated from hypertensive animals. These triterpenes also caused relaxation in aortic rings and in mesenteric arteries pre-contracted with either phenylephrine or KCl-enriched solution. The relaxation was only partially inhibited by endothelium denudation, and also partly inhibited by the cyclooxygenase (COX) inhibitor indomethacin, with no additional inhibitory effect of the NO synthase inhibitor, N-ω-Nitro-L-arginine. A combination of both ATP-dependent channel inhibition by glibenclaminde and voltage-dependent K+ channel inhibition by 4-aminopyridine was necessary to fully inhibit the relaxation.ConclusionThese data indicate that the effects of OA and its derivatives are mediated via both endothelium-dependent and independent mechanisms suggesting the involvement of COX in the endothelium-dependent effects and of vascular muscle K+ channels in the endothelium-independent effects. Finally, our results support the view that the antihypertensive action of OA and its derivatives is due to a decrease of vascular resistance with no negative inotropic effect on the heart.

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Section: Discussionsupporting

confidence: 90%

Vascular Endothelium-Dependent and Independent Actions of Oleanolic Acid and Its Synthetic Oleanane Derivatives as Possible Mechanisms for Hypotensive Effects

Madlala¹,

Metzinger²,

Heerden³

et al. 2016

PLoS ONE

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“…The steady-state activation curve of I h in the presence of GTs was shifted along voltage axis toward the less depolarized potential. The IC 50 value (i.e., 11.7 µg/mL) required for GTs-mediated inhibition of I h observed in GH 3 cells is similar to that used for anti-oxidative or neuroprotective properties [2,3,4,15,16,17,46,47]. Such intriguing actions could be of pharmacological relevance and appear to be upstream of its effects on oxidative stress occurring inside the cell.…”

Section: Resultsmentioning

confidence: 68%

Evidence for Effective Inhibitory Actions on Hyperpolarization-Activated Cation Current Caused by Ganoderma Triterpenoids, the Main Active Constitutents of Ganoderma Spores

Chang

Gao

et al. 2019

Molecules

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The triterpenoid fraction of Ganoderma (Ganoderma triterpenoids, GTs) has been increasingly demonstrated to provide effective antioxidant, neuroprotective or cardioprotective activities. However, whether GTs is capable of perturbing the transmembrane ionic currents existing in electrically excitable cells is not thoroughly investigated. In this study, an attempt was made to study whether GTs could modify hyperpolarization-activated cation currents (Ih) in pituitary tumor (GH3) cells and in HL-1 atrial cardiomyocytes. In whole-cell current recordings, the addition of GTs produced a dose-dependent reduction in the amplitude of Ih in GH3 cells with an IC50 value of 11.7 µg/mL, in combination with a lengthening in activation time constant of the current. GTs (10 µg/mL) also caused a conceivable shift in the steady-state activation curve of Ih along the voltage axis to a more negative potential by approximately 11 mV. Subsequent addition of neither 8-cyclopentyl-1,3-dipropylxanthine nor 8-(p-sulfophenyl)theophylline, still in the presence of GTs, could attenuate GTs-mediated inhibition of Ih. In current-clamp voltage recordings, GTs diminished the firing frequency of spontaneous action potentials in GH3 cells, and it also decreased the amplitude of sag potential in response to hyperpolarizing current stimuli. In murine HL-1 cardiomyocytes, the GTs addition also suppressed the amplitude of Ih effectively. In DPCPX (1 µM)-treated HL-1 cells, the inhibitory effect of GTs on Ih remained efficacious. Collectively, the inhibition of Ih caused by GTs is independent of its possible binding to adenosine receptors and it might have profound influence in electrical behaviors of different types of electrically excitable cells (e.g., pituitary and heart cells) if similar in vitro or in vivo findings occur.

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“…This compound indicated a pronounced tumor reducing activity (96.64%) in potato disk tumor induction assay and also showed interesting inhibitory properties against human DU-145 and hepatocarcinoma Hep G2 cells with > 70% inhibition at 50 μg/mL [94]. At the same time, the ceramide tanacetamide (113), with an interesting vasorelaxant property, was isolated along with salvin A and maslinic acid from Vitex cienkowskii , thus validating the use of the plant in the treatment of cardiovascular diseases [100]. The antidiabetic property of Terminalia superba has been verified by the isolation of 3,4’-di- O -methylellagic acid 3’- O -β-D-xylopyranoside (45) and 4’- O -galloy-3,3’-di- O -methylellagic acid 4- O -β-D-xylopyrano-side (46), which both exhibited good α-glucosidase inhibition [80], while the antioxidant properties of the compounds isolated from Symphonia globulifera could also be used to validate the use of the plant in the preparation of tonics for pregnant women [65].…”

Section: Resultsmentioning

confidence: 99%

Cameroonian medicinal plants: a bioactivity versus ethnobotanical survey and chemotaxonomic classification

Ntie‐Kang

Lifongo

Mbaze

et al. 2013

BMC Complement Altern Med

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BackgroundIn Cameroon herbs are traditionally used to meet health care needs and plans are on the way to integrate traditional medicine in the health care system, even though the plans have not been put into action yet. The country however has a rich biodiversity, with ~8,620 plant species, some of which are commonly used in the treatment of several microbial infections and a range of diseases (malaria, trypanosomiasis, leishmaniasis, diabetes and tuberculosis).MethodsOur survey consisted in collecting published data from the literature sources, mainly from PhD theses in Cameroonian university libraries and also using the author queries in major natural product and medicinal chemistry journals. The collected data includes plant sources, uses of plant material in traditional medicine, plant families, region of collection of plant material, isolated metabolites and type (e.g. flavonoid, terpenoid, etc.), measured biological activities of isolated compounds, and any comments on significance of isolated metabolites on the chemotaxonomic classification of the plant species. This data was compiled on a excel sheet and analysed.ResultsIn this study, a literature survey led to the collection of data on 2,700 secondary metabolites, which have been previously isolated or derived from Cameroonian medicinal plants. This represents distinct phytochemicals derived from 312 plant species belonging to 67 plant families. The plant species are investigated in terms of chemical composition with respect to the various plant families. A correlation between the known biological activities of isolated compounds and the ethnobotanical uses of the plants is also attempted. Insight into future direction for natural product search within the Cameroonian forest and Savanna is provided.ConclusionsIt can be verified that a phytochemical search of active secondary metabolites, which is inspired by knowledge from the ethnobotanical uses of medicinal plants could be very vital in a drug discovery program from plant-derived bioactive compounds.

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Pentacyclic triterpenoids and ceramide mediate the vasorelaxant activity of Vitex cienkowskii via involvement of NO/cGMP pathway in isolated rat aortic rings

Cited by 22 publications

References 48 publications

Vascular Endothelium-Dependent and Independent Actions of Oleanolic Acid and Its Synthetic Oleanane Derivatives as Possible Mechanisms for Hypotensive Effects

Vascular Endothelium-Dependent and Independent Actions of Oleanolic Acid and Its Synthetic Oleanane Derivatives as Possible Mechanisms for Hypotensive Effects

Evidence for Effective Inhibitory Actions on Hyperpolarization-Activated Cation Current Caused by Ganoderma Triterpenoids, the Main Active Constitutents of Ganoderma Spores

Cameroonian medicinal plants: a bioactivity versus ethnobotanical survey and chemotaxonomic classification

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