Dynamic Changes of Endogenic or Exogenic β-Carboline Alkaloid Harmine in Different Mammals and Human in vivo at Developmental and Physiological States.
Dynamic Changes of Endogenic or Exogenic β-Carboline Alkaloid Harmine in Different Mammals and Human in vivo at Developmental and Physiological States.
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DOI：
10.3389/fnagi.2021.773638
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发表时间：
2021
影响因子：
4.8
通讯作者：
Wang C
中科院分区：
文献类型：
--
作者：
Cao N;Li S;Xu A;Li M;Zou X;Ke Z;Deng G;Cheng X;Wang C
几种 β-咔啉生物碱 (βCB)，例如骆驼蓬碱、骆驼蓬碱、骆驼蓬烷和去甲骆驼蓬烷，对阿尔茨海默病小鼠模型有效。它们存在于一些植物、常见食品和各种哺乳动物的空白血浆中。然而，哺乳动物中的这些化合物是外源性还是内源性仍不清楚。采用UPLC-MS/MS检测幼鼠、老龄大鼠、不同生理状态小鼠和健康志愿者血浆和组织中βCBs和神经递质的暴露水平。采集110只29日龄以下新生大鼠11个采样点的血浆和组织样本并进行分析，以确定新生大鼠发育阶段βCBs的浓度变化。采用2～18月龄大鼠血浆检测βCBs及部分神经递质的变化趋势。采集正常C57BL/6小鼠、APP/PS1双转基因小鼠和东莨菪碱诱导记忆障碍小鼠的血浆样本进行分析，比较不同生理状态下βCBs的差异。对550名健康志愿者血浆中去氢骆驼蓬碱、骆驼蓬碱、哈马烷等βCBs的暴露水平进行了检测，并按性别、种族、年龄进行分析。结果表明，去氢骆驼蓬碱是在大鼠、小鼠和人类体内发现的主要化合物，无需任何外源消耗即可在新生大鼠血浆（0.16±0.03 ng/ml）和大脑（0.33±0.14 ng/g）中检测到。大鼠血浆中去氢骆驼蓬碱浓度在18个月的生长期呈现与5-羟色胺、氯化乙酰胆碱、谷氨酸、酪氨酸、苯丙氨酸等神经递质暴露水平相似的下降趋势。大鼠和人类的去氢骆驼蓬碱暴露表明对生理和病理状态（如衰老、性别和种族）的高度依赖性。不同动物和人类体内、发育和生理状态下去氢骆驼蓬碱暴露量的动态变化表明，去氢骆驼蓬碱是一种天然、广泛分布于不同哺乳动物和人类体内的内源性物质。除外源摄入外，自发合成可能是哺乳动物体内去氢骆驼蓬碱的另一个重要来源，尚需进一步实验验证。
Several β-carboline alkaloids (βCBs), such as harmine, harmaline, harmane, and nor-harmane, are effective for Alzheimer’s disease mouse models. They can be found in some plants, common foodstuffs, and blank plasma of various mammals. However, whether these compounds in mammals are exogenous or endogenous remain unclear. The exposure levels of βCBs and of neurotransmitters in plasma and tissues of pup rats, aging rats, mice of different physiological states, and healthy volunteers were detected by using UPLC-MS/MS. Plasma and tissue samples from 110 newborn rats up to 29 days old at 11 sampling points were collected and were analyzed to determine the concentration variation of βCBs in the developmental phase of newborn rats. The plasma of rats aged 2 to 18 months was used to detect the variation trend of βCBs and with some neurotransmitters. The plasma samples of normal C57BL/6 mice, APP/PS1 double transgenic mice, and scopolamine-induced memory impairment mice were collected and were analyzed to compare the difference of βCBs in different physiological states. The exposure levels of βCBs such as harmine, harmaline, and harmane in plasma of 550 healthy volunteers were also detected and analyzed on the basis of gender, race, and age. Results showed that harmine was the main compound found in rats, mice, and human, which can be detected in a newborn rat plasma (0.16 ± 0.03 ng/ml) and brain (0.33 ± 0.14 ng/g) without any exogenous consumption. The concentration of harmine in rat plasma showed a decreasing trend similar to the exposure levels of neurotransmitters such as 5-hydroxytryptamine, acetylcholine chloride, glutamic acid, tyrosine, and phenylalanine during the growth period of 18 months. The harmine exposure in rats and human indicates high dependence on the physiological and pathological status such as aging, gender, and race. The dynamic changes of harmine exposure in different animals and human, in vivo, at developmental and physiological states indicate that harmine is a naturally and widely distributed endogenous substance in different mammals and human. In addition to exogenous ingestion, spontaneous synthesis might be another important source of harmine in mammals, which should be verified by further experiment.
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影响因子：
2.7
作者：
Hargis KE;Blalock EM
通讯作者：
Blalock EM
影响因子：
11.4
作者：
Granold M;Moosmann B;Staib-Lasarzik I;Arendt T;Del Rey A;Engelhard K;Behl C;Hajieva P
通讯作者：
Hajieva P
影响因子：
5
作者：
He, Dandan;Wu, Hui;Wang, Changhong
通讯作者：
Wang, Changhong
DOI：
10.1006/bbrc.2000.2598
发表时间：
2000-04-29
影响因子：
3.1
作者：
Fabbri, M;Delp, G;Theopold, U
通讯作者：
Theopold, U
影响因子：
1.9
作者：
Lopes, Guilherme S.;Bielinski, Suzette J.;St Sauver, Jennifer L.
通讯作者：
St Sauver, Jennifer L.