Page 256 - 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-73

Phellinus linteus, a traditional medicinal mushroom, confers Nrf2-dependent

neuroprotection against blue light-induced retinopathy

5
４
3
1,2
Yi-Chien Liu, 1,2 Yueh-Hsiung Kuo, Liang-Huan Wu, Jau-Der Ho, Ching-Hao Li,
6
Ahmad Dzulfikri Nurhan, Y u -Wen Cheng,* ,1,7 George Hsiao* ,1,2

1 Ph.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei
Medical University, Taipei 110, Taiwan
2 Graduate Institute of Medical Sciences and Department of Pharmacology, School of Medicine,
College of Medicine, Taipei Medical University, Taipei 110, Taiwan
3 Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College
of Chinese Medicine, China Medical University, Taichung 404, Taiwan
4 Department of Ophthalmology, Taipei Medical University Hospital, Taipei 110, Taiwan
5 Department of Physiology, School of Medicine, College of Medicine, Taipei Medical
University, Taipei 110, Taiwan
6 School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan
7 Department of Pharmaceutical Sciences, School of Pharmacy, College of Pharmacy, Taipei
Medical University, Taipei 110, Taiwan

* E-mail: ywcheng@tmu.edu.tw (Y u -Wen Cheng); geohsiao@tmu.edu.tw (George Hsiao)

Abstract
Blue light, a high-energy visible radiation, penetrates the retina; prolonged exposure triggers
oxidative stress, inflammation, and apoptosis, ultimately leading to retinal degeneration.
Oxidative stress from reactive oxygen species (ROS) accumulation damages cellular
components and activates pro-apoptotic pathways. This study explores a natural fungal
compound, 3,4-dihydroxybenzalacetone (DBA), from Phellinus linteus as a protective agent
against retinal injury using complementary in vitro and in vivo models. Its protective effects
were first investigated in 661W photoreceptor cells against blue light- and tert-butyl
hydroperoxide (t-BHP)-induced cytotoxicity, establishing its rationale for in vivo efficacy.
Furthermore, DBA promoted photoreceptor survival by reducing ROS, upregulating BCL-2,
suppressing pro-apoptotic BAX and caspase-3, and inhibiting the activation of JNK and c-Jun.
It also activated pro-survival AKT and ERK in Nrf2/HO-1 signaling, thereby promoting
photoreceptor survival. The cytoprotective effect was confirmed to be Nrf2-dependent, as
siRNA-mediated knockdown abolished its activity. DBA also regulated LC3-II and p62,
restoring autophagic flux and preventing dysregulation of autophagy–apoptosis crosstalk. In
the animal model, DBA restored the electroretinogram (a- and b-wave) and improved chromatic
pupillary light response (CPLR) and visual evoked potential (VEP). It exerted potent anti-
inflammatory effects by downregulating TNF-α and MMP-9, and suppressed the oxidative
stress marker nitrotyrosine. Furthermore, DBA reduced photoreceptor apoptosis, preserved
IS/OS integrity, and normalized opsin expression, reinforcing retinal structural protection. In
conclusion, DBA protects retinal cells by mitigating oxidative stress and inflammation while
regulating the autophagy–apoptosis balance through Nrf2 activation, highlighting its
therapeutic potential for blue light-induced retinal degeneration.

Keywords: Oxidative stress; Phellinus linteus; Retinal protection; Blue light damage; Apoptosis;
Nrf2