Assessment of the Aromatase Inhibitory Activity of Ma-Huang-Tang (MHT) and Its Active Compounds.

Dong Ho Jung,Song Yi Yu,Joo Tae Hwang,Bo-Jeong Pyun,Byoung Seob Ko

doi:10.1155/2019/4809846

Dong Ho Jung, Song Yi Yu + Show 3 more

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https://doi.org/10.1155/2019/4809846

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Abstract

Aromatase, a cytochrome P450 enzyme that converts androgens into estrogens, is an important drug target for hormone-dependent diseases. The purpose of this study was to elucidate the aromatase inhibitory effects of Ma-Huang-Tang (MHT), a traditional Korean herbal medicine prescription, and to identify its active ingredients. In this study, the inhibitory effect of MHT on aromatase activity was observed using dibenzylfluorescein (DBF) and KGN cells, and the dose-dependent effect of MHT was verified (IC50 values of 251 μg/mL and 246 μg/mL as determined by the two methods, respectively). Furthermore, among the six herbal medicines that constitute MHT, Ephedrae Herba, Cinnamomi Ramulus, and Glycyrrhizae Radix et Rhizoma showed the most potent inhibition of aromatase activity. Furthermore, upon identification of the active MHT compounds, three markers from Glycyrrhizae Radix et Rhizoma, liquiritin (5), liquiritin apioside (6), and liquiritigenin (7), were verified (IC50 values of 530 μM, 508 μM, and 1.611 mM and 499 μM, 522 μM, and 1.41 mM as determined by the two methods, respectively). In addition, their contents were confirmed to be 15.58, 19.80, and 2.22 mg/g, respectively, by HPLC/DAD analysis. These results indicate that the aromatase inhibitory effect of MHT results from the synergistic action of its active components and that MHT has potential as a preventive agent against aromatase activity.

Highlights

Aromatase (CYP19) is a major cytochrome P450 (CYP) steroidogenic enzyme that catalyzes the rate-limiting aromatization step of converting androgens, including testosterone and androstenedione, into estrogens such as estrone and 17βestradiol [1, 2]
We investigated the effects of eight typical index compounds from the three MHT hydrothermal extract herbal medicine components identified as inhibiting aromatase activity: ephedrine (1) from Ephedrae Herba [29]; coumarin (2), cinnamic acid (3), and cinnamaldehyde (4) from Cinnamomi Ramulus [30]; and liquiritin (5), liquiritin apioside (6), liquiritigenin (7), and glycyrrhizin (8) from Glycyrrhizae Radix et Rhizoma [31]
The IC50 values of liquiritin (5), liquiritin apioside (6), and liquiritigenin (7), the three major compounds in MHT, were determined to be 499 μM, 522 μM, and 1.41 mM, respectively (Table 3). These results demonstrate that MHT and its main compounds exhibited IC50 values in the cell-based assay similar to those observed in the fluorescence assays using human recombinant microsomes and showed an inhibitory effect on aromatase

Summary

Introduction

Aromatase (CYP19) is a major cytochrome P450 (CYP) steroidogenic enzyme that catalyzes the rate-limiting aromatization step of converting androgens, including testosterone and androstenedione, into estrogens such as estrone and 17βestradiol [1, 2]. Aromatase enzymatically removes C19 using C19 androgens as substrates and forms a phenolic A ring in the steroid [3, 4]. Through these actions, the androgen/estrogen ratio is controlled to maintain the endocrine balance. The main uses of aromatase inhibitors (AIs) include preventing the recurrence of estrogen-specific receptor-positive breast cancer and reducing the risk of adjuvant treatment [8]. Positive effects of AIs on cognition were reported [12], and AIs were reported to be effective in treating male breast cancer [13]

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