Page 241 - 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-58

Characterization of neuroprotective mechanism of several marine pigments

against cell death pathways in HT-22 cells

2
2
2
Nguyen DT,* ,1,2 Serive B, Ruchaud S, Bach S

1 Department of Analytical Chemistry and Drug Quality Control, School of Pharmacy,
University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
2 UMR8227 & FR2424, Sorbonne Université, CNRS, Station Biologique de Roscoff,
Roscoff, France
* Email : ntndung@ump.edu.vn

Abstract
The mouse hippocampal neuronal cell line HT22 is frequently used for the study of
neurotoxicity. This study aimed to evaluate the in vivo neuroprotective activity of several
marine pigments in HT-22 cells, by regulating different cell death pathways. The study focuses
on the modulation of cell death pathways induced by glutamate, a neurotoxic molecule, in the
HT-22 neuronal cell model. To modulate cell death, a panel of commercial inhibitors, such as
Z-VAD-FMK, Nec-1, Nec-1-s, Fer-1, 3-MA, NAC, was used. The protection of marine
pigments on HT-22 cells, whose death is induced by a high dose of glutamate or by erastin, was
also evaluated. The commercial inhibitors protected HT-22 cells against the toxic effect of
glutamate, with a significant restoration of cell viability. This observation highlights the
involvement of multiple death pathways, including ferroptosis, autophagy and oxidative stress.
The negative results of Z-VAD-FMK and Nec-1-s proved that glutamate-induced cell death
does not result from apoptosis or necroptosis. On the other hand, in the presence of glutamate,
almost all pigments tested significantly restored the viability of HT-22 cells. By evaluating the
relationship between the effectiveness of these molecules and their toxicity, three pigments as
diadinoxanthin, lutein and violaxanthin were chosen to carry out in the next step. The EC50s
(median effective concentration) of these pigments, determined from the dose-response curves,
are respectively 22 μM, 34 µM and 28 µM for diadinoxanthin, lutein and violaxanthin.
Diadinoxanthin, lutein and violaxanthin present the in vitro neuroprotective activity in HT-22
cells. These three marine pigments effectively inhibit glutamate-induced death pathways
(autophagy, ferroptosis and oxidative stress).

Keywords: Marine pigments; Inhibitors; Cell death pathway; Neuroprotection;
Neurodegenerative disease