Ethnopharmacokinetic- and Activity-Guided Isolation of a New Antidepressive Compound from Fructus Aurantii Found in the Traditional Chinese Medicine Chaihu-Shugan-San: A New Approach and Its Application

Rong Fan,Xiao Chen,Xinjian Qiu,Lan Fan,Lichen Gao,Wei Huang,Yang Wang,Ying Xie,Zhaoqian Liu,Yingjin Zhang,Xi Huang,Honghao Zhou,Ping Ren,Hui Ji

doi:10.1155/2012/607584

Abstract

Aims. We aimed to identify an antidepressive compound found in traditional Chinese medicine (TCM) by a new approach called ethnopharmacokinetic- and activity-guided isolation (EAGI). Methods. The new approach targets an unknown chromatographic peak produced by an absorbed compound found in oral Chaihu-Shugan-San (CSS) taken by patients with depression. Once the compound was isolated from Fructus Aurantii (FA), spectral data was employed to identify the compound. The effects of this compound, FA, and CSS on depressive behaviors were investigated. Results. The identified compound was merazin hydrate (MH) according to the new approach. MH, FA, and CSS significantly reduced immobility time and increased locomotor activity. The effects of MH, FA and CSS were similar to Fluoxetine at high doses. Conclusion. MH, a compound whose antidepressive effect is similar to FA and CSS, was isolated for the first time from FA via targeting its corresponding unknown chromatographic peak, and its antidepressive effect was compared with FA or CSS. These findings highlight the potential for drug R&D and pharmacological research of ∼100,000 TCMs.

Highlights

Drug R&D is highly challenging for scientific and economical reasons because of the high rate of failure, massive spending, and lengthy research period (1960s) [1]
We aimed to identify an antidepressive compound found in traditional Chinese medicine (TCM) by a new approach called ethnopharmacokinetic- and activity-guided isolation (EAGI)
merazin hydrate (MH), a compound whose antidepressive effect is similar to Fructus Aurantii (FA) and CSS, was isolated for the first time from FA via targeting its corresponding unknown chromatographic peak, and its antidepressive effect was compared with FA or CSS

Summary

Introduction

Drug R&D is highly challenging for scientific and economical reasons because of the high rate of failure, massive spending, and lengthy research period (1960s) [1]. Unknown chromatographic peaks in the blood and urine obtained from subjects who orally consumed TCMs provided the first leads [5]. An unknown chromatographic peak appeared in blood samples 30 min after patients had been dosed with Chaihu-ShuganSan (CSS), a famous TCM which has been used for several centuries to improve some symptoms similar to depression. Our goal was to isolate the pharmacokinetic compound corresponding to the unknown chromatographic peak and determine the parent herb.

Experimental

Targeting an Unknown Chromatographic Peak in Patient

Isolation and Identification of the Unknown Compound

Results

Discussion