Filbertone-Induced Nrf2 Activation Ameliorates Neuronal Damage via Increasing BDNF Expression.
Jeong Heon Gong, Chu-Sook Kim, Jeongmin Park, Soeun Kang, Yumi Jang, Min-Seon Kim, Hun Taeg Chung, Yeonsoo Joe, Rina Yu
Author Information
Jeong Heon Gong: College of Korean Medicine, Daegu Haany University, Gyeongsan, 38610, Republic of Korea.
Chu-Sook Kim: Department of Biological Sciences, College of Information and Biotechnology, Ulsan National Institute of Science and Technology, Ulsan, 44919, Republic of Korea.
Jeongmin Park: College of Korean Medicine, Daegu Haany University, Gyeongsan, 38610, Republic of Korea.
Soeun Kang: Department of Food and Nutrition, University of Ulsan, Ulsan, 44610, Republic of Korea.
Yumi Jang: Department of Food and Nutrition, University of Ulsan, Ulsan, 44610, Republic of Korea.
Min-Seon Kim: Division of Endocrinology and Metabolism, Department of Internal Medicine, Diabetes Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea.
Hun Taeg Chung: College of Korean Medicine, Daegu Haany University, Gyeongsan, 38610, Republic of Korea.
Yeonsoo Joe: College of Korean Medicine, Daegu Haany University, Gyeongsan, 38610, Republic of Korea. joeyeonsoo@dhu.ac.kr.
Rina Yu: Department of Food and Nutrition, University of Ulsan, Ulsan, 44610, Republic of Korea. rinayu@ulsan.ac.kr.
Neurotrophic factors are endogenous proteins that promote the survival of various neuronal cells. Increasing evidence has suggested a key role for brain-derived neurotrophic factor (BDNF) in the dopaminergic neurotoxicity associated with Parkinson's Disease (PD). This study explores the therapeutic potential of filbertone, a bioactive compound found in hazelnuts, in neurodegeneration, focusing on its effects on neurotrophic factors and the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. In our study, filbertone markedly elevated the expression of neurotrophic factors, including BDNF, Glial cell line-Derived Neurotrophic Factor (GDNF), and Nerve Growth Factor (NGF), in human neuroblastoma SH-SY5Y cells, mouse astrocyte C8-D1A cells, and mouse hypothalamus mHypoE-N1 cells. Moreover, filbertone effectively countered neuroinflammation and reversed the decline in neurotrophic factors and Nrf2 activation induced by a high-fat diet (HFD) in neurodegeneration models. The neuroprotective effects of filbertone were further validated in models of neurotoxicity induced by palmitic acid (PA) and the neurotoxin MPTP/MPP, where it was observed to counteract PA and MPTP/MPP-induced decreases in cell viability and neuroinflammation, primarily through the activation of Nrf2 and the subsequent upregulation of BDNF and heme oxygenase-1 expression. Nrf2 deficiency negated the neuroprotective effects of filbertone in MPTP-treated mice. Consequently, our finding suggests that filbertone is a novel therapeutic agent for neurodegenerative diseases, enhancing neuronal resilience through the Nrf2 signaling pathway and upregulation of neurotrophic factors.
