aconitine and talatisamine

A new denudatine-type C

Topics: Aconitine; Aconitum; Alkaloids; Diterpenes; Molecular Structure; Plant Extracts; Spectrum Analysis

To investigate the chemical constituents of the processed products of Aconitum Vilmorinian Radix.. The constituents were isolated by repeated column chromatography over silica gel, alumina and RP-C18 as well as recrystallization. The structures were elucidated on the basis of spectral analysis and physicochemical properties.. Ten compounds were obtained from the methanol extract, and they were identified as yunaconitine (1), 8-deacetyl-yunaconitine (2), geniculatine C (3), vilmorrianine B (4), vilmorrianine C(5), vilmorrianine D (6), talatisamine (7), β-sitosterol (8), β-daucosterol (9) and β-sitosterol acetate (10).. All compounds are obtained from the processed products of Aconitum Vilmoriniani Radix for the first time.

Topics: Aconitine; Aconitum; Phytochemicals; Plant Roots; Sitosterols

Loss of cytosolic K(+) through up-regulated delayed rectifier K(+) channels play an important role in beta-amyloid (Aβ) induced neurotoxicity. Potent K(+) channel blocker, particular specific for I(K) channels has been suggested as an attractive candidate for the treatment of Alzheimer's disease (AD). Talatisamine is a novel I(K) channel blocker discovered by virtual screening and electrophysiological characterization. In the present study, we examined the neuroprotective effect of talatisamine against Aβ oligomers induced cytotoxicity in primarily cultured cortical neurons. The neurotoxicity related to K(+) loss caused by Aβ40 oligomers included enhanced I(K) density, increased cell membrane permeability, reduced cell viability, and impaired mitochondrial transmembrane potential. Decreased Bcl-2 and increased Bax level, activation of Caspase-3 and Caspase-9 were also observed after Aβ40 oligomers incubation. Talatisamine (120 μM) and TEA (5mM) inhibited the enhanced I(K) caused by Aβ40 oligomers, attenuated cytotoxicity of Aβ oligomers by restoring cell viability and suppressing K(+) loss related apoptotic response. Our results suggested that talatisamine may become a leading compound as I(K) channel blocker for neuroprotection.

Topics: Aconitine; Amyloid beta-Peptides; Animals; Apoptosis; Blotting, Western; Cell Survival; Cells, Cultured; Cerebral Cortex; Fluorescent Antibody Technique; Neurons; Neuroprotective Agents; Patch-Clamp Techniques; Potassium Channel Blockers; Rats; Rats, Sprague-Dawley

Blocking specific K+ channels has been proposed as a promising strategy for the treatment of neurodegenerative diseases. Using a computational virtual screening approach and electrophysiological testing, we found four Aconitum alkaloids are potent blockers of the delayed rectifier K+ channel in rat hippocampal neurons. In the present study, we first tested the action of the four alkaloids on the voltage-gated K+, Na+ and Ca2+ currents in rat hippocampal neurons, and then identified that talatisamine is a specific blocker for the delayed rectifier K+ channel. External application of talatisamine reversibly inhibited the delayed rectifier K+ current (IK) with an IC50 value of 146.0+/-5.8 microM in a voltage-dependent manner, but exhibited very slight blocking effect on the voltage-gated Na+ and Ca2+ currents even at the high concentration of 1-3 mM. Moreover, talatisamine exerted a significant hyperpolarizing shift of the steady-state activation, but did not influence the steady state inactivation of IK and its recovery from inactivation, suggesting that talatisamine had no allosteric action on IK channel and was a pure blocker binding to the external pore entry of the channel. Our present study made the first discovery of potent and specific IK channel blocker from Aconitum alkaloids. It has been argued that suppressing K+ efflux by blocking IK channel may be favorable for Alzheimer's disease therapy. Talatisamine can therefore be considered as a leading compound worthy of further investigations.

Topics: Aconitine; Alkaloids; Animals; Calcium Channels; Delayed Rectifier Potassium Channels; Drugs, Chinese Herbal; Hippocampus; Ion Channel Gating; Kinetics; Membrane Potentials; Patch-Clamp Techniques; Potassium Channel Blockers; Pyramidal Cells; Rats; Rats, Sprague-Dawley; Sodium Channels

Seven new C19-diterpenoid alkaloids, circinasines A-G (1-7), together with six known compounds, talatisamine, yunaconitine, senbusine A, sachaconitine, hemsleyanisine, and isohemsleyanisine, were isolated from the roots of Aconitum hemsleyanum var. circinatum. The structures of 1-7 were determined by the interpretation of spectroscopic data and by the single-crystal X-ray crystallographic analysis of 6 and the acetonide derivative of 1. In addition, the structures of hemsleyanisine and isohemsleyanisine were revised from 8 and 9 to 10 and 11, respectively.

Topics: Aconitine; Aconitum; Alkaloids; Crystallography, X-Ray; Diterpenes; Drugs, Chinese Herbal; Molecular Conformation; Molecular Structure; Plant Roots

Two new C(19)-diterpenoid alkaloids, piepunensine A (1) and 18-acetylcammaconine (2), have been isolated from the roots of Aconitum piepunense together with five known alkaloids pengshenine B (3), talatisamine (4), aconosine (5), yunaconitine (6), and talatizidine (7). The structures of the new alkaloids were established on the basis of spectral data (1D- and 2D-NMR, HR-MS).

Topics: Aconitine; Aconitum; Alkaloids; Diterpenes; Drugs, Chinese Herbal; Nuclear Magnetic Resonance, Biomolecular; Plant Roots; Spectrometry, Mass, Electrospray Ionization

Two new norditerpenoid alkaloids, 8-acetyl-14-p-methoxybenzoate of talatisamine (1) and 14-p-methoxybenzoate of talatisamine (2), were isolated from Aconitum bulleyanum Diels. The structures were elucidated on the basis of spectroscopic and chemical studies.

Topics: Aconitine; Aconitum; Alkaloids; Diterpenes; Magnetic Resonance Spectroscopy; Molecular Structure; Plant Extracts

By means of HPLC method, yunaconitine and talatisamine contained in 10 samples of folk drug Caowu (aconite) have been analysed. The result shows that in 3 species both yunaconitine and talalisamine are present, and in 7 species only yunaconitine is found. The contents and HPLC chromatograms of these alkaloids vary with the samples.

Topics: Aconitine; Aconitum; Drugs, Chinese Herbal