Mitigating Effects of Liriope platyphylla on Nicotine-Induced Behavioral Sensitization and Quality Control of Compounds

Dahye Yoon,Woo Cheol Shin,Hyoung-Geun Kim,Minhan Ka,Dae Young Lee,Joung-Wook Seo,Eun Young Jang,Young-Seob Lee,In Soo Ryu,Oc-Hee Kim

doi:10.3390/brainsci10090654

Abstract

In this study we investigated the mitigating effects of Liriope platyphylla Wang et Tang extract on behavioral sensitization and the quantification of its major compounds. The extract of L. platyphylla reduces the expression of tyrosine hydroxylase (TH) protein, which is increased by nicotine, back to normal levels, and increases the expression of dopamine transporter (DAT) protein, which is reduced by nicotine, back to normal levels in PC12 cells. In this study, rats received nicotine (0.4 mg/kg, subcutaneously) only for seven days and then received extract of L. platyphylla (200 or 400 mg/kg, oral) 1 h prior to nicotine administration for an additional seven days. The extract of L. platyphylla reduced locomotor activity compared to the nicotine control group in rats. The extract of L. platyphylla significantly attenuated the repeated nicotine-induced DAT protein expression in the nucleus accumbens (NAc), but there was no effect on increased TH protein expression in the dorsal striatum. These findings suggest that L. platyphylla extract has a mitigating effect on nicotine-induced behavioral sensitization by modulating DAT protein expression in the NAc. For quality control of L. plathyphylla, spicatoside A and D, which are saponin compounds, were quantified in the L. platyphylla extract. The amounts of spicatoside A and D in L. platyphylla extract obtained from ultra-high-performance liquid chromatography with tandem mass spectrometry were 0.148 and 0.272 mg/g, respectively. The identification of these compounds in L. platyphylla, which can be used for quality control, provides important information for the development of drugs to treat nicotine dependence.

Highlights

Cigarette smoking is one of the major global public health problems
Fractionation was performed because we found low intensities of overall compounds in the extract
Pretreatment with L. platyphylla extract did not mitigate the repeated nicotine-induced increase in Tyrosine hydroxylase (TH) protein expression in the dorsal striatum (dSTR). These findings suggest that the major saponin compounds in L. platyphylla extracts—spicatoside A and spicatoside D—may pharmacologically act on the dopaminergic system, mitigating the nicotine-induced behavioral sensitization through regulation of dopamine transporter (DAT) protein expression in the nucleus accumbens (NAc)

Summary

Introduction

Brain Sci. 2020, 10, 654 the dopaminergic neurotransmission of the mesolimbic reward system [1,2], leading to behavioral sensitization [2,3]. The dorsal striatum (dSTR) and nucleus accumbens (NAc) are major integration regions of the basal ganglia circuitry which receive a large variety of projections including dopaminergic inputs from the substantia nigra and ventral tegmental area, respectively [4]. The dSTR and NAc play important roles in nicotine-induced behavioral sensitization [4,5]. Tyrosine hydroxylase (TH) and dopamine transporter (DAT) are well-known modulators of dopamine concentrations in the reward system [6,7]. Previous investigations demonstrated that total ginseng saponin attenuates nicotine-induced alternations in dopaminergic neurotransmission in the reward system of the brain and mitigates nicotine-induced behavioral changes such as behavioral sensitization [2,5,8]

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Discussion

Conclusion