11,12-Diacetyl-carnosol Protects SH-SY5Y Cells from Hydrogen Peroxide Damage through the Nrf2/HO-1 Pathway

Qingyi Luo; Weiyan Hu; Haofei Yu; Rongping Zhang; Xinglong Chen

doi:10.1155/2022/4376812

11,12-Diacetyl-carnosol Protects SH-SY5Y Cells from Hydrogen Peroxide Damage through the Nrf2/HO-1 Pathway

Evid Based Complement Alternat Med. 2022 May 17:2022:4376812. doi: 10.1155/2022/4376812. eCollection 2022.

Authors

Qingyi Luo^{1

2

3}, Weiyan Hu³, Haofei Yu³, Rongping Zhang⁴, Xinglong Chen⁴

Affiliations

¹ Department of Imaging, Yanan Hospital of Kunming City, The Affiliated Hospital of Kunming Medical University, Kunming 650051, Yunnan Province, China.
² Yunnan Province Key Laboratory of Cardiovascular Diseases, Kunming 650051, Yunnan Province, China.
³ School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China.
⁴ College of Chinese Materia Medica and Yunnan Key Laboratory of Southern Medicine Utilization, Yunnan University of Chinese Medicine, Kunming 650500, China.

Abstract

Background: Oxidative stress-induced neurotoxicity plays a key role in Alzheimer's disease (AD). 11,12-Diacetyl-carnosol (NO.20), an acetylated derivative of carnosol extracted from rosemary, displays a high antioxidative effect in vitro.

Purpose: We investigated the neuroprotective effect of NO.20 on H₂O₂-induced neurotoxicity in human neuroblastoma SH-SY5Y cells and its possible mechanism.

Results: We found that NO.20 pretreatment (1 μM for 1 h) had cytoprotective effects and weakened H₂O₂-induced damage in SH-SY5Y cells by reducing viability loss, apoptotic rate, and reactive oxygen species production. In addition, NO.20 inhibited H₂O₂-induced mitochondrial dysfunctions: it alleviated mitochondrial membrane potential loss and cytochrome c release, decreased the Bax/Bcl-2 ratio, and reduced caspase-3 expression. NO.20 also downregulated malondialdehyde and upregulated glutathione. Furthermore, NO.20 pretreatment caused the nuclear translocation of the transcription factor NF-E2-related factor 2 (Nrf2), increasing heme oxygenase-1 (HO-1) expression in SH-SY5Y cells. Notably, we found that silencing Nrf2 using small interfering RNA (siRNA) suppressed the NO.20-induced HO-1 expression and abolished the neuroprotective effect of NO.20.

Conclusion: These results demonstrate that NO.20 protects SH-SY5Y cells from H₂O₂-induced neurotoxicity by activating the Nrf2/HO-1 pathway. Thus, the neuroprotective and antioxidative stress effects of NO.20 may make it a promising neuroprotective compound for AD treatment.