Dual antioxidant activity and the related mechanisms of a novel pentapeptide GLP4 from the fermented mycelia of Ganoderma lingzhi

Ping Huang; Fei-Jun Luo; You-Chu Ma; Si-Xian Wang; Jia Huang; Dan-Dan Qin; Fei-Fei Xue; Bi-Yang Liu; Qiang Wu; Xiao-Ling Wang; Gao-Qiang Liu

doi:10.1039/D2FO01572B

Dual antioxidant activity and the related mechanisms of a novel pentapeptide GLP4 from the fermented mycelia of Ganoderma lingzhi†

Ping Huang,‡^ab Fei-Jun Luo,‡^c You-Chu Ma,^ab Si-Xian Wang,^ab Jia Huang,^ab Dan-Dan Qin,^c Fei-Fei Xue,^ab Bi-Yang Liu,^ab Qiang Wu,^ab Xiao-Ling Wang*^ab and Gao-Qiang Liu

*^ab

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* Corresponding authors

^a Hunan Provincial Key Laboratory of Forestry Biotechnology & International Cooperation Base of Science and Technology Innovation on Forest Resource Biotechnology, Central South University of Forestry and Technology, Changsha 410004, China
E-mail: wxlcsedu@163.com, gaoliuedu@csuft.edu.cn
Fax: +86-731-8562-3132
Tel: +86-731-8562-3132

^b Microbial Variety Creation Center, Yuelushan National Laboratory of Seed Industry, Changsha 410004, China

^c Laboratory of Molecular Nutrition, National Engineering Research Center for Rice and Byproducts, Central South University of Forestry and Technology, Changsha 410004, China

Abstract

Oxidative stress causes chronic inflammation, and mediates various diseases. The discovery of antioxidants from natural sources is important to research. Here we identified a novel antioxidant peptide (GLP4) from Ganoderma lingzhi mycelium and investigated its antioxidant type and potential protective mechanisms. Through free radical scavenging assay, active site shielding validation, superoxide dismutase (SOD) activity assay, and lipid peroxidation assay, we demonstrated that GLP4 was a novel protective agent with both direct and indirect antioxidant activities. GLP4 could directly enter human umbilical vein endothelial cells (HUVECs) as an exogenous substance. Meanwhile, GLP4 promoted the nuclear translocation of nuclear factor erythroid-2-related factor 2 (Nrf2) and activated the Nrf2/antioxidant response element (ARE) signaling pathway, exhibiting antioxidant and anti-apoptotic cytoprotective effects on hydrogen peroxide (H₂O₂)-induced HUVECs. Pull-down experiments of GLP4 target proteins, bioinformatics analysis and molecular docking further revealed that GLP4 mediated Nrf2 activation through binding to phosphoglycerate mutase 5 (PGAM5). The results suggested that GLP4 is a novel peptide with dual antioxidant activity and has promising potential as a protective agent in preventing oxidative stress-related diseases.

Food & Function

Dual antioxidant activity and the related mechanisms of a novel pentapeptide GLP4 from the fermented mycelia of Ganoderma lingzhi†

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