Pikraconitin/Picraconitine/enzoylaconitine/Aconitane-3,8,13,14,15-pentol, 20-ethyl-1,6,16-trimethoxy-4-(methoxymethyl)-, 14-benzoate, (1α,3α,6α,14α,15α,16β)-/8-O-deacetylaconitine/Isaconitine/14-O-Benzoylaconine/benzoylaconine/Benzoylaconitine/(1α,3α,6α,14α,15α,16β)-20-Ethyl-3,8,13,15-tetrahydroxy-1,6,16-trimethoxy-4-(methoxymethyl)aconitan-14-yl benzoate/Aconine 14-benzoate
Benzoylaconine(Isaconitine; Pikraconitin) is an alkaloid in the Chinese traditional medicine Radix Aconiti Lateralis Preparata (Fuzi).
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A selective and simple colorimetric method is presented for the estimation of aconitine in drugs in the presence of aconine and benzoylaconine. The method is based on the formation of an iron hydroxamate complex through the acetate ester group to which the biological activity is due. The color is measured at 530 nm (5–250 microgram/ml). Under the experimental conditions, neither the benzoyl group of benzoylaconine nor aconine is involved in the process of hydroxylaminolysis.
Selective Estimation of Aconitine in Presence of Aconine and Benzoylaconine
M S Karawya, A M Diab
The traditional Chinese medicine “Fuzi” (Aconiti Lateralis Radix Praeparata) and its three representative alkaloids, aconitine (AC), benzoylaconine (BAC), and aconine, have been shown to increase mitochondrial mass. Whether Fuzi has effect on mitochondrial biogenesis and the underlying mechanisms remain unclear. In the present study, we focused on the effect of BAC on mitochondrial biogenesis and the underlying mechanisms. We demonstrated that Fuzi extract and its three components AC, BAC, and aconine at a concentration of 50 μM significantly increased mitochondrial mass in HepG2 cells. BAC (25, 50, 75 μM) dose-dependently promoted mitochondrial mass, mtDNA copy number, cellular ATP production, and the expression of proteins related to the oxidative phosphorylation (OXPHOS) complexes in HepG2 cells. Moreover, BAC dose-dependently increased the expression of proteins involved in AMPK signaling cascade; blocking AMPK signaling abolished BAC-induced mitochondrial biogenesis. We further revealed that BAC treatment increased the cell viability but not the cell proliferation in HepG2 cells. These in vitro results were verified in mice treated with BAC (10 mg/kg per day, ip) for 7 days. We showed that BAC administration increased oxygen consumption rate in mice, but had no significant effect on intrascapular temperature. Meanwhile, BAC administration increased mtDNA copy number and OXPHOS-related protein expression and activated AMPK signaling in the heart, liver, and muscle. These results suggest that BAC induces mitochondrial biogenesis in mice through activating AMPK signaling cascade. BAC may have the potential to be developed as a novel remedy for some diseases associated with mitochondrial dysfunction.
Benzoylaconine Induces Mitochondrial Biogenesis in Mice via Activating AMPK Signaling Cascade
Xiao-Hong Deng 1 2 , Jing-Jing Liu 1 2 , Xian-Jun Sun 1 2 , Jing-Cheng Dong 3 4 , Jian-Hua Huang 5
Aconitine (AC), benzoylaconine (BAC), and aconine (ACN) are three representative alkaloids in Aconitum tubers. Knowing that the drug disposal process in vivo is closely related to the toxicity and efficacy of a drug, it is important to classify the disposal properties of these alkaloids. In this study, the pharmacokinetics of the three alkaloids was investigated. The results showed that the three alkaloids could be quickly absorbed, especially BAC, whose Tmax was 0.31 ± 0.17 h. Their Cmax was 10.99, 3.99, and 4.29 ng·mL(-1) respectively, indicating that AC had better absorption than BAC and ACN. Subsequently, we further investigated their absorption mechanism using the Caco-2 cell monolayer model in vitro. The results showed that they were poorly absorbed, and the absorption of AC and BAC was inhibited by P-gp, while the absorption of ACN was in a form of passive diffusion. The t1/2 of AC, BAC and ACN was 1.41, 9.49, and 3.32 h, respectively, indicating that the metabolic or excretion rate of AC was quicker than that of BAC and ACN. Therefore, their metabolic stability was further investigated by using rat liver microsomes in vitro, which showed that AC was easier to be metabolized than BAC and ACN. The excretion experiments showed that AC and ACN were primarily excreted in urine, while BAC was excreted in faeces. In addition, the results of tissue distribution experiments showed that the three alkaloids distributed throughout all the organs, although the distribution rate of AC was slower than that of BAC and ACN. Copyright © 2015 John Wiley & Sons, Ltd.
LC-MS/MS; absorption; alkaloids; metabolic rate; pharmacokinetics.
Biological Activities and Pharmacokinetics of Aconitine, Benzoylaconine, and Aconine After Oral Administration in Rats
Hai Zhang 1 2 , Sen Sun 1 , Wen Zhang 1 , Xiangqun Xie 3 , Zhenyu Zhu 2 , Yifeng Chai 2 , Guoqing Zhang 1