Microbial Transformation and Biological Activities of the Prenylated Aromatic Compounds from Broussonetia kazinoki.

Euna Choi,Jisu Park,Ik-Soo Lee,Fubo Han

doi:10.3390/molecules27061879

Abstract

Broussonetia kazinoki has been used as a traditional medicine for the treatment of burns and acne, and its extracts have been found to show tyrosinase inhibitory and anticancer activities. In this study, the tyrosinase inhibitory and cytotoxic activities of B. kazinoki were explored, leading to the isolation of kazinol C (1), kazinol E (2), kazinol F (3), broussonol N (4), and kazinol X (5), of which the compounds 4 and 5 have not been previously reported. Microbial transformation has been recognized as an efficient tool to generate more active metabolites. Microbial transformation of the major compounds 1 and 3 was conducted with Mucor hiemalis, where four glucosylated metabolites (6–9) were produced from 1, while one hydroxylated (10) and one glucosylated (11) metabolites were obtained from 3. Structures of the isolated metabolites were determined by extensive spectroscopic analyses. All compounds were evaluated for their tyrosinase inhibitory and cytotoxic activities. Compound 3 and its metabolites, kazinol Y (10) and kazinol F-4″-O-β-d-glucopyranoside (11), exhibited the most potent tyrosinase inhibitory activities with the IC50 values ranging from 0.71 to 3.36 µM. Meanwhile, none of the metabolites, except for kazinol C-2′,3″-di-O-β-d-glucopyranoside (7), showed moderate cytotoxic activities (IC50 17.80 to 24.22 µM) against A375P, B16F10 and B16F1 cell lines.

Highlights

Broussonetia kazinoki, a deciduous shrub tree belonging to the family Moraceae, is widely distributed throughout Korea, China, and Japan [1–3]
The extract of B. kazinoki has been registered as a skin-whitening agent by the Korea Food and Drug Administration (KFDA) due to its potent tyrosinase inhibitory and anti-melanogenic effects [5,8]
2Cl2 fraction of the extract showed promising tyrosinase inhibitory effects, and the subsequent activity-guided extract showed promising tyrosinase inhibitory effects, and the subsequent activityfractionation led to the isolation of five prenylated polyphenols 1–5 (Figure 1)

Summary

Introduction

Broussonetia kazinoki, a deciduous shrub tree belonging to the family Moraceae, is widely distributed throughout Korea, China, and Japan [1–3]. Its leaves, branches, roots and fruits have been used for various therapeutic purposes including the amelioration of vision, and suppression of edema [1–4]. It has been traditionally used for dermatologic diseases such as burns and acne in Korea according to the Principles and Practice of Eastern Medicine, an encyclopedia of medical knowledge [5,6]. Previous biological investigations have demonstrated that B. kazinoki exhibited a variety of pharmacological effects, such as antioxidant, anti-inflammatory, anticancer, anti-allergic, anti-diabetic, and anti-hyperglycemic activities [2–7]. The extract of B. kazinoki has been registered as a skin-whitening agent by the Korea Food and Drug Administration (KFDA) due to its potent tyrosinase inhibitory and anti-melanogenic effects [5,8]. A series of prenylated polyphenols including kazinol F and broussonin C isolated from

Methods

Results

Conclusion