Dynamic Changes of Endogenic or Exogenic β-Carboline Alkaloid Harmine in Different Mammals and Human in vivo at Developmental and Physiological States.

Ning Cao,Xiaoguang Zou,Changhong Wang,Zunji Ke,Shuping Li,Aimin Xu,Manlin Li,Gang Deng,Xuemei Cheng

doi:10.3389/fnagi.2021.773638

Ning Cao, Xiaoguang Zou + Show 7 more

Open Access

https://doi.org/10.3389/fnagi.2021.773638

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Abstract

ObjectiveSeveral 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.MethodsThe 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.ResultsResults 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.ConclusionThe 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.

Highlights

The β-carboline alkaloids, such as harmine, harmaline, harmane, and nor-harmane, are active components of Peganum harmala (Li et al, 2017a)
This study focused on the exposure rules of harmine, harmaline, harmane, and nor-harmane in plasma of non-Alzheimer’s disease (AD) patients with different ages, genders, and races
Harmaline β-Carboline Alkaloid Harmine could turn to harmine in vivo with the presence of heme peroxidase (Wang et al, 2021), which might explain the contents of harmine were higher than that of harmaline under normal conditions

Summary

Introduction

The β-carboline alkaloids (βCBs), such as harmine, harmaline, harmane, and nor-harmane, are active components of Peganum harmala (Li et al, 2017a). P. harmala is used to treat diseases, such as cough, asthma, rheumatoid arthritis, and swelling pain in regions such as the Middle East, central Asia, and South America (Zhao et al, 2012) Such βCBs show various pharmacological effects, including hypoglycemic effect, antineoplastic activity, and acetylcholinesterase (AChE) inhibitory activity (Li et al, 2017a). These βCBs are present in other plants, including Banisteriopsis caapi, Tribulus terrestris, and Ayahuasca (Li et al, 2016) Such βCBs can be found in common foodstuffs, such as plant-derived foods (e.g., grapes, rice, corn, barely, bean, and rye), processed foods (e.g., wine, beer, whiskey, brandy, sake, coffee, vinegar, and tobacco), and meat products (e.g., barbecue, smoked fish, and smoked sausages) (Xie et al, 2021). Whether harmine, harmaline, harmane, and norharmane are endogenous or exogenous in mammalian tissues and plasma, and whether such βCBs in mammals are useless or functional, remain unclear

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