**Jia-Hao Lee 1, Hui-Ching Mei 2, I-Chih Kuo 3, Tzong-Huei Lee 4, Yu-Hsin Chen <sup>5</sup> and Ching-Kuo Lee 1,\***


Academic Editor: Ping-Chung Kuo

<sup>4</sup> Institute of Fisheries Science, National Taiwan University, Taipei 10617, Taiwan

Received: 20 August 2019; Accepted: 8 September 2019; Published: 10 September 2019



**Abstract:** In this study, an in vitro tyrosinase inhibition assay in combination with ultra performance liquid chromatography-orbitrap mass spectrometry (UPLC-orbitrap-MS) was developed for the rapid screening and identification of tyrosinase modulators from roots of *Angelica keiskei*. Of the 15 candidates considered, nine chalcones, xanthoangelols (**1**), B (**2**), D (**3**), E (**4**), G (**5**), H (**6**), 4-hydroxyderricin (**7**), xanthokeismin B (**8**) and (2*E*)-1-[4-hydroxy-2-(2-hydroxy-2-propanyl)-2,3-dihydro-1- benzofuran-7-yl]- 3-(4-hydroxyphenyl)-2-propen-1-one (**9**), five coumarins, umbelliferone (**10**), selinidin (**11**), isopimpinellin (**12**), phellopterin (**13**) and xanthyletin (**14**), and one other compound, ashitabaol A (**15**), were distinguished between the test samples and the controls with statistical significance, and the structure of each compound was determined by comparing with in-house standards and the literature. Among these, six compounds, xanthoangelol (**1**), xanthoangelol D (**3**), xanthoangelol H (**6**), 4-hydroxyderricin (**7**), laserpitin (**16**) and isolaserpitin (**17**), were isolated from roots of *A. keiskei*. Of the compounds isolated, compounds **1**, **7** and **16** were subjected to tyrosinase inhibitory assay, and the IC50 values were 15.87 ± 1.21, 60.14 ± 2.29 and >100 μM, respectively. The present study indicated that the combination of in vitro tyrosinase inhibition assay coupled with UPLC-MS/MS

could be widely applied to the rapid screening of active substances from various natural resources.

**Keywords:** *Angelica keiskei*; tyrosinase; UPLC-MS/MS; chalcone; coumarins
