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Teng-Fei Li, Nian Gong, Yong-Xiang Wang
Aconitines, including bulleyaconitine A, probably the most bioactive and abundant alkaloids in Aconitum plant, are a group of diester C19-diterpenoid alkaloids with one acetylester group attached to C8 of the diterpenoid skeleton and one benzoylester group to C14. Hydrolysis of both groups is involved in the processing of Aconitum, a traditional Chinese medicinal approach. We recently demonstrated that bulleyaconitine A produced anti-hypersensitivity, which was mediated by stimulation of spinal microglial dynorphin A expression...
2016: Frontiers in Pharmacology
Min Qiu, Yong-He Dong, Feng Han, Jian-Min Qin, Hao-Nan Zhang, Jian-Xi Du, Xin-Min Hao, Yu-Mei Yang
It is well known that various traditional Chinese medicines produce antiarrhythmic actions. The aims of this study were to examine whether total flavones derived from Choerospondias axillaris folium (TFCF) also produced antiarrhythmic effects using a rat model of aconitine-induced arrhythmia and to compare these observations with the effects of total flavones of Choerospondias axillaris fructus (TFC). Wistar rats were orally administered TFC (0.2 g/kg) or TFCF (0.1, 0.2, or 0.4 g/kg) daily for 7 d. Subsequently, aconitine iv at 25 µg/kg was used to induce arrhythmia in these animals...
2016: Journal of Toxicology and Environmental Health. Part A
Fei Wang, Zhenggang Yue, Pei Xie, Li Zhang, Zhen Li, Bei Song, Zhishu Tang, Xiaomei Song
Three new C19-norditerpenoid alkaloids (1-3), along with two known C19-norditerpenoid alkaloids (4-5) have been isolated from Aconitum szechenyianum. Their structures were established by extensive spectroscopic techniques and chemical methods as szechenyianine A (1), szechenyianine B (2), szechenyianine C (3), N-deethyl-3-acetylaconitine (4), and N-deethyldeoxyaconitine (5). Additionally, compounds 1-5 were tested for the inhibition of NO production on LPS-activated RAW264.7 cells with IC50 values of 36.62 ± 6...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Bin Yang, Yanyan Xu, Yuanyuan Wu, Huanyu Wu, Yuan Wang, Lei Yuan, Jiabin Xie, Yubo Li, Yanjun Zhang
A rapid, sensitive and selective ultra-high performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for simultaneous determination of ten Aconitum alkaloids in rat tissues. The tissue samples were prepared by a simple procedure protein precipitation with acetonitrile containing 0.1% acetic acid and separated on an Agilent XDB C18 column (4.6 mm×50mm, 1.8μm) using gradient elution with a mobile phase consisting of water and acetonitrile (both containing 0...
October 15, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Jeffrey Aalders, Shaukat Ali, Tom J de Jong, Michael K Richardson
In previous publications, we described the population incidence of abnormalities in zebrafish larvae exposed to toxicants. Here, we examine the phenomenon of clustering or co-occurrence of abnormalities in individual larva. Our aim is to see how this clustering can be used to assess the specificity and severity of teratogenic effect. A total of 11,214 surviving larvae, exposed continuously from 1 day postfertilization (dpf) to one of 60 toxicants, were scored at 5 dpf for the presence of eight different abnormal phenotypes...
August 25, 2016: Zebrafish
Katsuya Ohbuchi, Chika Miyagi, Yasuyuki Suzuki, Yasuharu Mizuhara, Keita Mizuno, Yuji Omiya, Masahiro Yamamoto, Eiji Warabi, Yuka Sudo, Akinobu Yokoyama, Kanako Miyano, Takatsugu Hirokawa, Yasuhito Uezono
Processed Aconiti tuber (PAT) is used to treat pain associated with various disorders. Although it has been demonstrated that the κ opioid receptor (KOR) signaling pathway is a mediator of the analgesic effect of PAT, active components affecting opioid signaling have not yet been identified. In this study, we explored candidate components of PAT by pharmacokinetic analysis and identified ignavine, which is a different structure from aconitine alkaloids. A receptor binding assay of opioid receptors showed that ignavine specifically binds the μ opioid receptor (MOR), not the KOR...
2016: Scientific Reports
Kevin G M Kou, Beryl X Li, Jack C Lee, Gary M Gallego, Terry P Lebold, Antonio G DiPasquale, Richmond Sarpong
The denudatine-type diterpenoid alkaloids cochlearenine, N-ethyl-1α-hydroxy-17-veratroyldictyzine, and paniculamine have been synthesized for the first time (25, 26, and 26 steps from 16, respectively). These syntheses take advantage of a common intermediate (8) that we have previously employed in preparing aconitine-type natural products. The syntheses reported herein complete the realization of a unified strategy for the preparation of C20, C19, and C18 diterpenoid alkaloids.
August 31, 2016: Journal of the American Chemical Society
Panpan Zhang, Dezhi Kong, Qian Du, Jing Zhao, Qing Li, Jianghua Zhang, Tonghui Li, Leiming Ren
1. A model of aconitine-induced bradycardia and hypotension, which is similar to aconitine poisoning in humans, was constructed in conscious rats by oral administration. 2. Blood pressure (BP) and heart rate (HR) of Sprague-Dawley rats were measured using a volume pressure recording (VPR) system. The pharmacokinetics of toxic doses of aconitine and its metabolites were analyzed using UPLC-MS/MS. 3. The HR was significantly decreased by 29% at 2 h after oral administration of 200 μg/kg aconitine. When the dose was increased to 400 μg/kg, systolic BP and diastolic BP were significantly decreased by 11% and 12% at 2 h after the administration, except when bradycardia occurred at 2 h and 4 h...
July 14, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Ding-Kun Zhang, Rui-Sheng Li, Xue Han, Chun-Yu Li, Zhi-Hao Zhao, Hai-Zhu Zhang, Ming Yang, Jia-Bo Wang, Xiao-He Xiao
Complex chemical composition is an important reason for restricting herbal quality evaluation. Despite the multi-components determination method significantly promoted the progress of herbal quality evaluation, however, which mainly concerned the total amount of multiple components and ignored the activity variation between each one, and did not accurately reflect the biological activity of botanical medicines. In this manuscript, we proposed a toxicity calibrated contents determination method for hyper toxic aconite, called toxic constituents index (TCI)...
2016: Frontiers in Pharmacology
Yan Li, Yun-Xia Li, Meng-Jie Zhao, An Yuan, Xiao-Hong Gong, Meng-Jun Zhao, Cheng Peng
BACKGROUND AND OBJECTIVES: Aconitum carmichaelii Debx. (Fuzi) is usually compatible with Rheum palmatum L. (Dahuang) in clinic. The study is conducted to investigate the influence of Dahuang on the pharmacokinetics of Fuzi. METHODS: Twelve rats were randomly divided into two groups. Fuzi group was orally administered a single dose of 38.4 mg/kg total alkaloids from Fuzi, and Fuzi-Dahuang group was given 38.4 mg/kg total alkaloids from Fuzi and 76.8 mg/kg Dahuang anthraquinones at the same time...
June 29, 2016: European Journal of Drug Metabolism and Pharmacokinetics
Haoran Li, Liang Liu, Shaohua Zhu, Qian Liu
Aconitum species have long been used in key traditional medicines in China, but cases of fatal aconite poisoning have also been reported. This paper presents a review of 40 single and multi-person cases of fatal aconite poisoning. The cases involved 53 victims in mainland China described in 27 case reports published between January 2004 and September 2015. We summarize the details of the case reports in order to highlight the features of fatal aconite-poisoning cases in China, including victims' sex and age, route of intoxication, clinical symptoms, medicolegal autopsy findings, and results of toxicological analysis...
August 2016: Journal of Forensic and Legal Medicine
Yoshitake Nishiyama, Satoshi Yokoshima, Tohru Fukuyama
The total synthesis of (-)-cardiopetaline, an aconitine-type natural product, has been accomplished. Our synthesis involved a Wagner-Meerwein rearrangement of a sulfonyloxirane that enabled, in a single step, the construction of the bicyclo[3.2.1] system in the aconitine skeleton and effective introduction of oxygen functional groups at the appropriate positions.
May 20, 2016: Organic Letters
Jinjun Wu, Na Lin, Fangyuan Li, Guiyu Zhang, Shugui He, Yuanfeng Zhu, Rilan Ou, Na Li, Shuqiang Liu, Lizhi Feng, Liang Liu, Zhongqiu Liu, Linlin Lu
The Aconitum species, which mainly contain bioactive Aconitum alkaloids, are frequently administered concomitantly with other herbal medicines or chemical drugs in clinics. The potential risk of drug-drug interactions (DDIs) arising from co-administration of Aconitum alkaloids and other drugs against specific targets such as P-glycoprotein (P-gp) must be evaluated. This study focused on the effects of three representative Aconitum alkaloids: aconitine (AC), benzoylaconine (BAC), and aconine, on the expression and activity of P-gp...
2016: Scientific Reports
Xingxing Wang, Dian Wang, Xiaojun Yu, Guohong Zhang, Jiayan Wu, Guanghui Zhu, Ruibing Su, Junyao Lv
Lethal ventricular tachyarrhythmia (LVTA) is the predominant underlying mechanism of sudden cardiac death (SCD). The aim of this study is to characterize the metabolic features of myocardia following LVTA, and identify potential biomarkers to diagnose LVTA. We developed two LVTA rat models induced by aconitine injection or coronary artery ligation, which represent cardiac ion channel disease-related and cardiac ischemia-related SCD, respectively. The myocardial metabolic profile was investigated by gas chromatography-mass spectrometry and proton nuclear magnetic resonance-based metabolomics...
June 21, 2016: Molecular BioSystems
Long Yang, Xin Ran, Le Cai, Yucong Li, Hui Zhao, Can-Peng Li
A dual-signalling electrochemical approach has been developed towards aconitine based on competitive host-guest interaction by selecting methylene blue (MB) and p-sulfonated calix[8]arene functionalized single-walled carbon nanohorns (SCX8-SWCNHs) as the "reporter pair". Upon the presence of aconitine to the performed SCX8-SWCNHs·MB complex, the MB molecules are displaced by aconitine. This results in a decreased oxidation peak current of MB and the appearance of an oxidation peak of aconitine, and the changes of these signals correlate linearly with the concentration of aconitine...
September 15, 2016: Biosensors & Bioelectronics
Long Yang, Xiaoguang Xie, Le Cai, Xin Ran, Yucong Li, Tianpeng Yin, Hui Zhao, Can-Peng Li
This work reports a novel method for the determination of aconitine through the competitive host-guest interaction between p-sulfonated calix[8]arene (SCX8) and signal probe/target molecules by using SCX8 functionalized reduced graphene oxide (SCX8-RGO) as a receptor. Three dyes (ST, RhB, BRB) and aconitine were selected as the probe and target molecules, respectively. The formation of SCX8-RGO·ST, SCX8-RGO·RhB, and SCX8-RGO·BRB complexes greatly decreases the fluorescence emission of ST, RhB, and BRB. The aconitine/SCX8 complex possesses a higher binding constant than ST/SCX8, RhB/SCX8, and BRB/SCX8 complexes, thus the dye in the SCX8 cavity can be replaced by aconitine to revert the fluorescence emission of SCX8-RGO·dye, leading to a "switch-on" fluorescence response...
August 15, 2016: Biosensors & Bioelectronics
Na Zhang, Yuelin Song, Qingqing Song, Shepo Shi, Qian Zhang, Yunfang Zhao, Jun Li, Pengfei Tu
Dual roles have been widely disclosed for Aconiti Lateralis Radix Praeparata (Chinese name: Fuzi) by acting as an effective herbal medicine accompanied with high toxicity risk and narrow therapeutic range. Aconite alkaloids, also known as diterpenoid alkaloids (DAs), have been proved to be primary therapeutic as well as toxic material basis of Fuzi. In the present study, we aim to characterize qualitative profile along with quantitative features of DAs in Fuzi, which could benefit the quality control of Fuzi as well as its safe medication in clinic...
July 2016: Journal of Chromatographic Science
Jinjun Li, Zhaoxin Qian, Xiaozhe Xia, Limin Fang, Guilin Xiao
OBJECTIVE: To study the impact of aconitine and Shuang-huang-lian injection on the expression of myocardial ryanodine receptor (RyR2) and to discuss the anti-arrhythmic mechanisms of Shuanghuanglian against aconitine poisoning.
 METHODS: A total of 52 SD rats were randomly divided into 3 groups: aconitine group (group A, n=20), Shuang-huang-lian group (group B, n=20) and control group (group C, n=12). Aconitine at a dose of 0.3 mg/kg was firstly administrated to the rats of group A and group B through gavage...
March 28, 2016: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
Beibei Wang, Jiaojiao Ji, Shuang Zhao, Jie Dong, Peng Tan, Shengsang Na, Yonggang Liu
BACKGROUND: Crude radix Aconitum kusnezoffii (RAK) has great toxicity. Traditional Chinese medicine practice proved that processing may decrease its toxicity. In our previous study, we had established a new method of RAK processing (Paozhi). However, the mechanism is yet not perfect. OBJECTIVE: To explore the related mechanism of processing through comparing the chemical contents. MATERIALS AND METHODS: A new processing method of RAK named stoving (Hong Zhi) was used...
January 2016: Pharmacognosy Magazine
Aimen K Farraj, Fatiha Malik, Najwa Haykal-Coates, Leon Walsh, Darrell Winsett, Dock Terrell, Leslie C Thompson, Wayne E Cascio, Mehdi S Hazari
CONTEXT: Within urban air sheds, specific ambient air pollutants typically peak at predictable times throughout the day. For example, in environments dominated by mobile sources, peak nitrogen dioxide (NO2) levels coincide with morning and afternoon rush hours, while peak levels of ozone (O3), occur in the afternoon. OBJECTIVE: Given that exposure to a single pollutant might sensitize the cardiopulmonary system to the effects of a subsequent exposure to a second pollutant, we hypothesized that a morning exposure to NO2 will exaggerate the cardiovascular effects of an afternoon O3 exposure in rats...
2016: Inhalation Toxicology
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