Anti-inflammatory, Antiplatelet Aggregation, and Antiangiogenesis Polyketides from Epicoccum sorghinum: Toward an Understating of Its Biological Activities and Potential Applications

Chi-Ying Li; Ching-Chia Chang; Yi-Hong Tsai; Mohamed El-Shazly; Chin-Chung Wu; Shih-Wei Wang; Tsong-Long Hwang; Chien-Kei Wei; Judit Hohmann; Zih-Jie Yang; Yuan-Bin Cheng; Yang-Chang Wu; Fang-Rong Chang

doi:10.1021/acsomega.0c01000

Anti-inflammatory, Antiplatelet Aggregation, and Antiangiogenesis Polyketides from Epicoccum sorghinum: Toward an Understating of Its Biological Activities and Potential Applications

ACS Omega. 2020 May 6;5(19):11092-11099. doi: 10.1021/acsomega.0c01000. eCollection 2020 May 19.

Authors

Chi-Ying Li¹, Ching-Chia Chang¹, Yi-Hong Tsai¹, Mohamed El-Shazly^{2

3}, Chin-Chung Wu¹, Shih-Wei Wang⁴, Tsong-Long Hwang^{5

6

7}, Chien-Kei Wei¹, Judit Hohmann^{8

9}, Zih-Jie Yang¹, Yuan-Bin Cheng¹, Yang-Chang Wu^{10

11}, Fang-Rong Chang^{1

12

13

14}

Affiliations

¹ Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
² Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Organization of African Unity Street, Abassia, Cairo 11566, Egypt.
³ Department of Pharmaceutical Biology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt.
⁴ Department of Medicine, Mackay Medical College, New Taipei City 252, Taiwan.
⁵ Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
⁶ Research Center for Chinese Herbal Medicine, Research Center for Food and Cosmetic Safety, and Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan.
⁷ Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan.
⁸ Department of Pharmacognosy, Interdisciplinary Excellence Center, University of Szeged, H-6720 Szeged, Hungary.
⁹ Interdisciplinary Centre for Natural Products, University of Szeged, H-6720 Szeged, Hungary.
¹⁰ Graduate Institute of Integrated Medicine, China Medical University, Taichung 404, Taiwan.
¹¹ Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung 404, Taiwan.
¹² Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
¹³ Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
¹⁴ Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 804, Taiwan.

Abstract

The ethyl acetate extract of an endophyte Epicoccum sorghinum exhibited anti-inflammatory activity at a concentration of <10 μg/mL. By bioassay-guided fractionation, one new compound, named epicorepoxydon A (1), and one unusual bioactive compound, 6-(hydroxymethyl)benzene-1,2,4-triol (6), together with six known compounds, were isolated from E. sorghinum. The structures of all isolates were established by spectroscopic analyses. The relative configuration of 1 was deduced by the NOESY spectrum and its absolute configuration was determined by X-ray single-crystal analysis. The biological activities of all isolates were evaluated using four types of bioassays including cytotoxicity, anti-inflammatory, antiplatelet aggregation, and antiangiogenesis activities. Compounds 4 and 6 showed potent anti-inflammatory activity, compound 2 possessed potent antiplatelet aggregation and antiangiogenesis activities, and compound 6 demonstrated antiangiogenesis activity. This fungal species can cause a human hemorrhagic disorder known as onyalai. In this study, we identified the active components with antiplatelet aggregation and antiangiogenesis activities, which may be related to the hemorrhagic disorder caused by this fungus. Moreover, we proposed a biosynthetic pathway of the isolated polyketide secondary metabolites and investigated their structure-activity relationship (SAR). Our results suggested that E. sorghinum is a potent source of biologically active compounds that can be developed as antiplatelet aggregation and anti-inflammatory agents.