Aconitum kusnezoffii,Aconitum carmichaelii,Delphinium giraldii
Soluble in Chloroform,Dichloromethane,Ethyl Acetate,DMSO,Acetone,etc.
695.0±55.0 °C at 760 mmHg
HS Code Reference
Personal Projective Equipment
For Reference Standard and R&D, Not for Human Use Directly.
provides coniferyl ferulate(CAS#:2752-64-9) MSDS, density, melting point, boiling point, structure, formula, molecular weight etc. Articles of coniferyl ferulate are included as well.>> amp version: coniferyl ferulate
Background: Therapeutic applications of Fuzi (lateral root of Aconitum carmichaeli Debx) are seriously concerned with its toxic effects. Strategies and approaches to reducing toxicity are of great interest.
Purpose: We aimed to characterize the diurnal rhythm of Fuzi toxicity, and to determine the role of metabolism and pharmacokinetics in generating toxicity rhythmicity.
Methods: Toxicity was determined based on assessment of heart injury and animal survival after dosing mice with Fuzi decoction at different circadian time points. Circadian clock control of pharmacokinetics and toxicity was investigated using Bmal1-deficient (Bmal1-/-) mice.
Results: Fuzi exhibited a diurnal rhythmicity in cardiotoxicity (reflected by plasma CK-MB and LDH levels). The highest level of toxicity was observed at ZT10 (5 PM), while the lowest level of toxicity occurred at ZT22 (5 AM). Also, a higher mortality rate was observed at ZT10 and lower mortality rates at other times of the day. ZT10 dosing of Fuzi generated higher systemic exposures of three toxic alkaloid ingredients aconitine (AC), hypaconitine (HA) and mesaconitine (MA) compared to ZT22. This was accompanied by reduced the formation of the metabolites (N-deethyl-AC, didemethyl-HA and 2‑hydroxyl‑MA) at ZT10. Bmal1 ablation resulted in an increased level of Fuzi toxicity at ZT22, while having no influences when drug was dosed at ZT10. As a consequence, circadian time-dependent toxicity of Fuzi was lost in Bmal1-deficient mice. In addition, Bmal1 ablation increased the plasma concentrations of AC, HA and MA in mice after oral gavage of Fuzi, and reduced formation of their metabolites (N-deethyl-AC, didemethyl-HA and 2‑hydroxyl‑MA). Moreover, Fuzi metabolism in wild-type liver microsomes was more extensive at ZT22 than at ZT10. Bmal1 ablation abrogated circadian time-dependency of hepatic Fuzi metabolism.
Conclusions: Fuzi chronotoxicity in mice was attributed to time-varying hepatic metabolism and systemic exposure regulated by circadian clock. The findings may have implications in reducing Fuzi toxicity with a chronotherapeutic approach
Aconitine; Chronotherapeutics; Chronotoxicity; Circadian clock; Fuzi.
Zemin Yang 1, Yanke Lin 1, Lu Gao 1, Ziyue Zhou 1, Shuai Wang 1, Dong Dong 2, Baojian Wu 3
The unintentional ingestion of toxic compounds in herbs is not uncommon in many parts of the world. To provide timely and life-saving care in the emergency department, it is essential to develop a point-of-care analytical method that can rapidly identify these toxins in herbs. Since electrospray laser desorption ionization mass spectrometry (ELDI/MS) has been successfully used to characterize non-volatile chemical compounds without sample preparation, it was used to identify toxic herbal compounds in this study. The herbal toxins were collected either by sweeping a metallic probe across the surface of a freshly cut herb section or by directly sampling extracts of ground herbal powder. The analytes on the probe were then desorbed, ionized and detected using ELDI/MS, wherein analysis of the herbal toxins was completed within 30 s. This approach allows for the rapid morphological recognition of herbs and early point-of-care identification of herbal toxins for emergency management and is promising in providing important toxicological information to ensure appropriate medical treatment.
Electrospray laser desorption ionization mass spectrometry; Emergency management; Herbal toxins; Point-of-care.
Rapid identification of herbal toxins using electrospray laser desorption ionization mass spectrometry for emergency care
Hung Su 1, Kuan-Ting Liu 2, Bai-Hsiun Chen 3, Yen-Ping Lin 1, Yu-Min Jiang 1, Yi-Hong Tsai 4, Fang-Rong Chang 5, Jentaie Shiea 6, Chi-Wei Lee 7
Over-representation together with deep sequencing can dramatically shorten the discovery process, distinguish aptamers having a wide range of affinity for the target, allow an exhaustive search of the sequence space within a simplified library, reduce the quantity of the target required, eliminate cycling artifacts, and should allow multiplexing of sequencing experiments and targets.
Yougui pill; liquid chromatography; mass spectrometry; pharmacokinetics; traditional Chinese medicine.
Simultaneous high-performance liquid chromatography with tandem mass spectrometry quantification of six bioactive components in rat plasma after oral administration of Yougui pill
Haolong Liu 1 2, Feng Qiu 1, Haiyu Zhao 3, Baolin Bian 3, Lei Wang 1
Mesaconitine-induced relaxation in rat aorta: involvement of Ca2+ influx and nitric-oxide synthase in the endothelium. PUMID/DOI：11858801 Eur J Pharmacol. 2002 Feb 2;436(3):217-25. The effect of Mesaconitine was dependent on external Ca2+ concentrations. The relaxation induced by Mesaconitine was abolished by N(omega)-nitro-L-arginine methyl ester (0.1 mM, an inhibitor of nitric-oxide synthase), as well as the relaxation induced by acetylcholine. Acetylcholine induced relaxation in two phases in our conditions; the initial phase was transient and external Ca2+ -independent, and the second phase was sustained and external Ca2+ -dependent. Treatment with 100 nM thapsigargin, which depleted intracellular Ca2+ stores, inhibited acetylcholine-induced, but not Mesaconitine-induced, relaxation. Mesaconitine increased the [Ca2+]i level in endothelial cells by influx of Ca2+ from extracellular spaces. These findings suggest that Mesaconitine-induced Ca2+ influx and activation of nitric-oxide synthase in endothelial cells and, thus, induced vasorelaxation in rat aorta. Inhibition of stimulus-triggered and spontaneous epileptiform activity in rat hippocampal slices by the Aconitum alkaloid mesaconitine. PUMID/DOI：9548384 Eur J Pharmacol. 1998 Jan 26;342(2-3):183-91. The aim of the present study was to investigate if the plant alkaloid, Mesaconitine, which has been reported to have antinociceptive effects via stimulation of the noradrenergic system, inhibits epileptiform field potentials. The experiments were performed as extracellular recordings on rat hippocampal slices. Epileptiform activity was induced by omission of Mg2+ from the bathing medium or by addition of bicuculline and stimulus-evoked population bursts were recorded in the CA1 region. Spontaneous epileptiform activity was elicited by perfusing a nominally Mg2+-free bathing medium with high K+ concentration (5 mM). Both stimulus-triggered and spontaneous epileptiform activity was attenuated in a concentration-dependent manner by Mesaconitine (30 nM-1 microM). The inhibitory effect was rather variable in appearance when lower concentrations (30 and 100 nM) of Mesaconitine were applied. Pretreatment of the slices with the alpha-adrenoceptor antagonist yohimbine (1 microM) prevented the effect of Mesaconitine. It is concluded that the inhibitory action of Mesaconitine at low concentration is mediated via alpha-adrenoceptors. Mechanism of inhibitory action of mesaconitine in acute inflammations. PUMID/DOI：6127222 Eur J Pharmacol. 1982 Aug 13;82(1-2):65-71. Mesaconitine (MA) inhibited carrageenin-induced hind-paw edema in sham-operated mice as well as adrenalectomized mice. Hind-paw edema produced by subplantar injection of histamine, serotonin and prostaglandin E1 was suppressed by MA, indicating that it elicits the antiinflammatory activity at the early exudative stage of inflammations. However, MA did not affect the biosynthesis of the prostaglandins. Trazoline and propranolol had no effect on the inhibitory activity of MA on carrageenin-induced hind-paw edema. MA when administered i.c. at the doses where it shows marked analgesic activity produced dose-dependent antiinflammatory responses on paw edema produced by carrageenin and on vascular permeability accelerated by acetic acid and agar. The inhibitory activity of morphine on carrageenin-induced paw edema failed to be potentiated by the concurrent administration of MA, demonstrating that the mechanism of the antiinflammatory activity of MA involves the central nervous system.