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Authors

Hao-Chun Hu, Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Taiwan
Szu-Yin Yu, Institute of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, Hungary
Xiao-Shan Hung, Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Taiwan
Chun-Han Su, Agricultural Biotechology Research Center, Academia Sinica, Taiwan
Yu-Liang Yang, Biotechnology Center in Southern Taiwan, Academia Sinica, Taiwan
Chien-Kei Wei, Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Taiwan
Yuan-Bin Cheng, Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Taiwan
Yang-Chang Wu, Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Taiwan
Chia-Hung Yen, Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Taiwan
Tsong-Long Hwang, Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taiwan
Shu-Li Chen, Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Taiwan
István Szatmári, Institute of Pharmaceutical Chemistry and ELKH-MTA-SZTE Stereochemistry Research Group, Hungarian Academy of Sciences, University of Szeged, Hungary
Attila Hunyadi, Institute of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, Hungary
Yi-Hong Tsai, Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Taiwan
Fang-Rong Chang, Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, TaiwanFollow

Abstract

The jelly from achenes of Ficus pumila var. awkeotsang (FPAA) is a famous beverage ingredient in Taiwan. In this work, ficumarin (1), a new compound was obtained from its twigs (FPAT) and elucidated with comprehensive spectroscopic data. The biosynthetic origin was proposed from the p‐coumaroyl‐CoA pathway. Alloxanthoxyletin, betulinic acid, and catechin were identified as the major and active constituents responsible for relieving neutrophilic inflammation by FPAT. Among them, the most potent alloxanthoxyletin was found to interact with PRO350 and GLU377 of human INOSOX. Further, Nrf2 activating capacity of the FPAT fraction and its coumarins was confirmed. With the analysis of LC-MS/MS data and feature-based molecular networking, coumarins were found as the dominant and responsible components. Notably, alloxanthoxyletin increased Nrf2 expression by up to 816.8±58% due to the interacting with the VAL561, THR560 and VAL420 residues of 5FNQ protein. COVID-19 Docking Server simulation indicated that pyranocoumarins would promisingly interfere with the life cycle of SARS-CoV-2. FPAT was proven to exert anti-inflammatory activity on neutrophils and to activate Nrf2, and may likely be developed as a complementary supplement in the treatment of COVID-19 patients.

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Supporting information.pdf (829 kB)
Supporting information

Research highlights_9.pdf (91 kB)
Research highlights_9

Graphical Abstract_9.jpg (539 kB)
Graphical Abstract_9

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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