Meroterpenoids From Ganoderma lucidum Mushrooms and Their Biological Roles in Insulin Resistance and Triple-Negative Breast Cancer

Jiao-Jiao Zhang; Dai-Wei Wang; Dan Cai; Qing Lu; Yong-Xian Cheng

doi:10.3389/fchem.2021.772740

Meroterpenoids From Ganoderma lucidum Mushrooms and Their Biological Roles in Insulin Resistance and Triple-Negative Breast Cancer

Front Chem. 2021 Nov 3:9:772740. doi: 10.3389/fchem.2021.772740. eCollection 2021.

Authors

Jiao-Jiao Zhang^{1

2}, Dai-Wei Wang¹, Dan Cai¹, Qing Lu^{1

3}, Yong-Xian Cheng^{1

3}

Affiliations

¹ Institute for Inheritance-Based Innovation of Chinese Medicine, School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, China.
² Institute of Microscale Optoelectronics, Shenzhen University, Shenzhen, China.
³ Guangdong Key Laboratory for Functional Substances in Medicinal Edible Resources and Healthcare Products, School of Life Sciences and Food Engineering, Hanshan Normal University, Chaozhou, China.

Abstract

Ganoderma fungi as popular raw materials of numerous functional foods have been extensively investigated. In this study, five pairs of meroterpenoid enantiomers beyond well-known triterpenoids and polysaccharides, dayaolingzhiols I-M (1-5), were characterized from Ganoderma lucidum. Their structures were identified using spectroscopic and computational methods. Structurally, compound 1 features a novel dioxabicyclo[2.2.2]octan-3-one motif in the side chain. Ethnoknowledge-derived biological evaluation found that (+)-5 could activate Akt and AMPK phosphorylation in insulin-stimulated C2C12 cells, and (+)-5 could activate glucose uptake dose dependently in C2C12 cells. Furthermore, we found that (+)-1 (+)-4, and (-)-4 could significantly inhibit cell migration of the MDA-MB-231 cell line, of which (+)-4 showed significant inhibitory effects against cell migration of the MDA-MB-231 cell line in a dose-dependent manner. These findings revealed the meroterpenoidal composition of G. lucidum and its roles in the prevention of chronic diseases such as diabetes mellitus and triple-negative breast cancer.

Keywords: AMPK phosphorylation; Akt phosphorylation; Ganoderma lucidum; cell migration; glucose uptake; meroterpenoids.