Page 193 - 2025中醫藥與天然藥物聯合學術研討會-中醫藥與天然藥物的挑戰Ｘ機遇與未來大會手冊

PP-11

Citrus peel flavonoids as potential inhibitors of the IDI1/IDI2–GPP–NDRG1

axis in ovarian cancer chemoresistance

2,3
1
1
Pei-Yun Wang, Wan-Ting Liao, Shang-Ming Huang, Lu-Hai Wang,* ,4,5 Hsiang-Cheng
,4,6
Chi*

1 Department of Nutrition, China Medical University, Taichung, Taiwan
2 Chinese Medicine Department, Show Chwan Memorial Hospital, Changhua, Taiwan
3 Graduate Institute of Chinese Medicine and Drug Development, National Chung Hsing
University, Taiwan
4 Chinese Medicine Research Center, China Medical University, Taichung, Taiwan
5 Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
6 Institute of Biochemistry and Molecular Biology, China Medical University, Taichung,
Taiwan
* E-mail:luhaiwang@mail.cmu.edu.tw; hcchi@cmu.edu.tw

Abstract
Citrus peel (Chenpi), widely used in traditional Chinese medicine, contains a variety of
natural flavonoids with potential health benefits. From this phytochemical diversity, we selected
six representative compounds—hesperetin, hesperidin, naringin, narirutin, nobiletin, and
tangeretin—for further analysis. These flavonoids are known for their metabolic regulatory
activities and have been suggested to exert anticancer effects. Platinum resistance is a critical
challenge in epithelial ovarian cancer (EOC). Our recent work implicates the mevalonate (MVA)
pathway, particularly the IDI1/IDI2–GPP–NDRG1 axis, in promoting chemoresistance. To
explore whether citrus peel flavonoids may interact with this pathway, we performed molecular
docking simulations using RosettaLigand. Docking results predicted favorable binding of all
six compounds to the IDI1 cofactor-binding pocket. Among them, polymethoxyflavones
(nobiletin, tangeretin) formed stable hydrogen-bonding and π–π stacking interactions with key
residues, suggesting a potential inhibitory effect on IDI1 activity. Although further experimental
validation is needed, these findings provide a structural rationale that citrus peel flavonoids
could modulate the MVA pathway and serve as promising candidates for future development
against chemoresistance in EOC.

Keywords: Citrus peel flavonoids; Epithelial ovarian cancer; Chemoresistance; Mevalonate
pathway