Antinociceptive Mechanism of the Actonitine Alkaloids Mesaconitine and Benzoylmesaconine

Suzuki, Yoshito; Oyama, Tsutomu; Ishige, Atsushi; Isono, Tomoko; Asami, Akitoshi; Ikeda, Yoshiki; Noguchi, Masamichi; Omiya, Yuji

doi:10.1055/s-2006-959516

Cited by 64 publications

(40 citation statements)

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“…31) It has been considered that the analgesic properties of aconite root are attributed to the presence of aconitinetype alkaloids, which act via the opioid k receptor. 12,14) However, the analgesic effect of aconite root was greatly reduced by heat processing that hydrolyzed the ester linkage in aconitine-type alkaloids. 13) Rats with chronic constriction injury exhibited a reduced threshold to mechanical and thermal pain stimulus and augmentations of pain-related behaviors when reared in a decreased temperature condition by 7°C, 32) suggesting that hypothermia would be involved in the symptoms, including allodynia, hyperalgesia, and spontaneous pain.…”

Section: Discussionmentioning

confidence: 99%

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Processed Aconite Root Prevents Cold-Stress-Induced Hypothermia and Immuno-Suppression in Mice

Makino

Kato

Mizukami

2009

Biological & Pharmaceutical Bulletin

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Processed aconite root (PA) is a crude drug used in traditional Chinese or Japanese medicine to generate heat in interior body and dispel cold. We evaluated the effects of PA on hypothermia and reduction in the activity of natural killer (NK) cells in mice exposed to chronic cold stress. Male mice were reared at 4°C, and powdered PA was administered for 10 d as a food additive. Core body temperature of mice significantly decreased by approximately 1°C after rearing in a cold environment, and PA administration significantly restored the reduction in core body temperature in a dose-dependent manner. After 10 d, splenic NK-cell activity of cold-stressed mice was significantly reduced, and the reduction was dose-dependently recovered by PA administration. An aconitine-type alkaloid fraction prepared from PA was ineffective when administered to cold-stressed mice, and the thermogenic effect on hypothermic mice was present in the fraction containing low-molecular-weight compounds without alkaloids. In cold-stressed mice, the weight of brown adipose tissue (BAT) and uncoupling protein (UCP)-1 level in BAT increased, whereas the weight of white adipose tissue decreased. The increase in UCP-1 level in BAT of cold-stressed mice was further augmented by PA treatment. These results indicate that PA exhibited a thermogenic effect on hypothermia induced by cold stress in mice by additional upregulation of UCP-1 level in BAT, which was already enhanced by hypothermia, and that the active ingredients present in PA are nonalkaloidal low-molecular-weight compounds.

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Section: Discussionmentioning

confidence: 99%

“…[11][12][13][14] However, the thermogenic effects of PA and its active ingredients have yet to be evaluated, and thus may lead to discovery of novel drugs that can be used in hypothermia treatment.…”

mentioning

confidence: 99%

Processed Aconite Root Prevents Cold-Stress-Induced Hypothermia and Immuno-Suppression in Mice

Makino

Kato

Mizukami

2009

Biological & Pharmaceutical Bulletin

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“…The toxicity of DDAs is much higher than that of MDAs and ADAs, and its efficacy is also stronger than that of the other two. [16,17] In the decoction process of the Aconitum tuber, DDAs may transform to MDAs, and further to ADAs. It is common knowledge that the toxicity and efficacy of a drug can be affected by the drug disposal process in vivo, and therefore it is very important to classify the disposal properties of the drug in vivo.…”

Section: Introductionmentioning

confidence: 99%

Biological activities and pharmacokinetics of aconitine, benzoylaconine, and aconine after oral administration in rats

Hai

Sun

Zhang

et al. 2015

Drug Testing and Analysis

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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.

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“…It has been reported to be widely used for analgetic, cardiotonic, diuretics and antirheumatism treatment [1][2][3]. Chuanwu basically contains three types of aconitum alkaloids, diester-diterpenoid alkaloids (DDAs), monoesterditerpenoid alkaloids (MDAs) and lipo-diterpenoid alkaloids (LDAs).…”

Section: Introductionmentioning

confidence: 99%

CE‐electrochemiluminescence with ionic liquid for the facile separation and determination of diester‐diterpenoid aconitum alkaloids in traditional Chinese herbal medicine

Bao

Yang

2011

Electrophoresis

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A CE-electrochemiluminescence(CE-ECL) detection system, CE/tris(2,2'-bipyridyl) ruthenium(II)ECL with ionic liquid, was established for the determination of diester-diterpenoid aconitum alkaloids (aconitine (AC), mesaconitine (MA) and hypaconitine (HA)) in traditional Chinese herbal medicine. Running buffer containing 25 mM borax-20 mM 1-ethyl-3-methylimidazolium tetrafluoroborate at pH 9.15 was used, which resulted in significant changes in separation and obvious enhancement in ECL intensity for AC, MA and HA with similar structures. End-column detection was achieved in 50 mM phosphate buffer with 5 mM Ru(bpy)₃²⁺ (pH 9.15) at applied detection voltage of 1.20 V when the distance between the Pt working electrode and outlet of capillary (50 cm × 25 μm id) was set at 150 μm. One single quantitative analysis of three alkaloids was achieved at a separation voltage of 15 kV within 10 min. Moreover, two extraction processes (ethanol extraction and ethyl ether extraction after basification) were investigated. The result showed that ethanol extraction process has higher extraction efficiency than ethyl ether extraction process. Under the optimized conditions, the detection limits of AC, MA and HA were 5.62 × 10(-8) , 2.78 × 10(-8) and 3.50 × 10(-9) mol/L (S/N=3), respectively. The method was successfully applied to determine the amounts of AC, MA and HA in the aconitum herbal samples.

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Antinociceptive Mechanism of the Actonitine Alkaloids Mesaconitine and Benzoylmesaconine

Cited by 64 publications

References 0 publications

Processed Aconite Root Prevents Cold-Stress-Induced Hypothermia and Immuno-Suppression in Mice

Processed Aconite Root Prevents Cold-Stress-Induced Hypothermia and Immuno-Suppression in Mice

Biological activities and pharmacokinetics of aconitine, benzoylaconine, and aconine after oral administration in rats

CE‐electrochemiluminescence with ionic liquid for the facile separation and determination of diester‐diterpenoid aconitum alkaloids in traditional Chinese herbal medicine

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