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Lijun Zhu, Jinjun Wu, Min Zhao, Wenjie Song, Xiaoxiao Qi, Ying Wang, Linlin Lu, Zhongqiu Liu
Aconitine (AC) is the primary bioactive/toxic alkaloid in plants of the Aconitum species. Our previous study demonstrated that Mdr1 was involved in efflux of AC. However, the mechanism by which Mdr1 regulates the efficacy/toxicity of AC in vivo remains unclear. The present study aimed to determine the effects of Mdr1a on the efficacy/toxicity and pharmacokinetics of AC in wild-type and Mdr1a(-/-) FVB mice. After oral administration of AC, significantly higher analgesic effect was observed in Mdr1a(-/-) mice (49% to 105%) compared to wild-type mice (P<0...
February 10, 2017: Toxicology and Applied Pharmacology
Jihong Nie, Fang Wang, Tengfei Ji, Jun Zhao, Feicui Zhao
Aconitum leucostomum Worosch is a traditional Chinese medicine (TCM) and has a broad spectrum of health effects, but with a narrow therapeutic window. It is important to identify both the therapeutic ingredients and the toxic components to better utilize this TCM. The present study investigated the cardiotoxicity of the selected compounds in Aconitum leucostomum Worosch. The effects of extract of A. leucostomum Worosch and the isolated compounds on cardiocardiomyocytes were evaluated in vitro. Five known compounds in this TCM, including three C18-diterpene alkaloids, lappaconitine (2), N-deacetyllappaconitine (3), and ranaconitine (5), and two C19-diterpene alkaloids, delvestidine (1) and anthranoyllycoctonine (4), were isolated from A...
January 3, 2017: Journal of Pharmaceutical and Biomedical Analysis
Ye Bai, Shaohui Du, Fei Li, Fengyuan Huang, Rudong Deng, Jianhong Zhou, Dongfeng Chen
Hypaconitine is an active component of Aconitum carmichaelii Debx, a Chinese medicinal herb for the treatment of cardiovascular diseases, but the mechanism underlying its effect remains elusive. In this study, we found that hypaconitine, rather than aconitum alkaloids in A. carmichaelii (e.g. aconitine, mesaconitine and benzoylaconitine), prevented endothelial cells from damage due to oxidized low-density lipoprotein (oxLDL) challenge. Cleaved caspase 3 expression in endothelial cells was up-regulated by oxLDL and markedly attenuated by hypaconitine, suggesting that hypaconitine inhibited the oxLDL-induced cell apoptosis...
January 1, 2017: Experimental Biology and Medicine
Jianjun Wu, Xiangchong Wang, Ying Ying Chung, Cai Hong Koh, Zhenfeng Liu, Huicai Guo, Qiang Yuan, Chuan Wang, Suwen Su, Heming Wei
Aconitine (ACO) is well-known for causing lethal ventricular tachyarrhythmias. While cardiac Na+ channel opening during repolarization has long been documented in animal cardiac myocytes, the cellular effects and mechanism of ACO in human remain unexplored. This study aimed to assess the proarrhythmic effects of ACO in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). ACO concentration-dependently (0.3 ~ 3.0 μM) shortened the action potentials (AP) durations (APD) in ventricular-like hiPSC-CMs by > 40% and induced delayed after-depolarization...
2017: PloS One
Sen Sun, Qingshan Chen, Jiyun Ge, Xiang Liu, Xinxia Wang, Qi Zhan, Hai Zhang, Guoqing Zhang
This study aimed to investigate the pharmacokinetic interaction of the three ingredients in a traditional Chinese herbal formulation, Sini Decoction, and provide evidence for its compatibility mechanism. Firstly, the effect of liquiritin and 6-gingerol on the pharmacokinetic parameters of aconitine were investigated in rats by using a sensitive and reliable LC-MS/MS method. Then the Caco-2 cell monolayer model and Rhodamine-123 uptake assay were used to investigate the effect of liquiritin and 6-gingerol on the absorption of aconitine and the activity of P-gp...
January 4, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Tapasree Basu, Sourav Panja, Nikhil Baban Ghate, Dipankar Chaudhuri, Nripendranath Mandal
Terminalia belerica Roxb. fruits have been previously reported against diabetes, ulcer, microbial problems and hepatotoxicity. The present study was aimed to investigate antioxidant and anticancer potential of sequentially fractionated hexane (TBHE), chloroform (TBCE), ethyl acetate (TBEE), butanol (TBBE) and water (TBWE) extracts from the 70% methanolic extract of T. belerica fruits. TBCE, TBEE, TBBE and TBWE showed excellent ROS (reactive oxygen species) and RNS (reactive nitrogen species) scavenging activities which was investigated using 11 different assays for various free radicals...
December 21, 2016: Cytotechnology
B-L Ji, L-P Xia, F-X Zhou, G-Z Mao, L-X Xu
OBJECTIVE: Pancreatic cancer is one of the leading causes of death from cancer in European countries and the United States. This study sought to investigate the effects of aconitine, a well-known aconitum plant-produced toxin, on pancreatic cancer cell growth and apoptosis and to explore the potential mechanisms. MATERIALS AND METHODS: In this study, pancreatic cancer cell lines Miacapa-2 and PANC-1 were cultured, and cell viability was examined in these two cells treated with different doses of aconitine...
December 2016: European Review for Medical and Pharmacological Sciences
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...
September 3, 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...
December 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
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