Rosmarinic Acid Inhibits Mitochondrial Damage by Alleviating Unfolded Protein Response

Guoen Cai; Fabin Lin; Dihang Wu; Chenxin Lin; Huiyun Chen; Yicong Wei; Huidan Weng; Zhiting Chen; Minxia Wu; En Huang; Zucheng Ye; Qinyong Ye

doi:10.3389/fphar.2022.859978

Rosmarinic Acid Inhibits Mitochondrial Damage by Alleviating Unfolded Protein Response

Front Pharmacol. 2022 May 16:13:859978. doi: 10.3389/fphar.2022.859978. eCollection 2022.

Authors

Guoen Cai¹, Fabin Lin^{1

2}, Dihang Wu^{1

2}, Chenxin Lin^{1

2}, Huiyun Chen³, Yicong Wei⁴, Huidan Weng¹, Zhiting Chen¹, Minxia Wu⁵, En Huang⁶, Zucheng Ye⁶, Qinyong Ye¹

Affiliations

¹ Department of Neurology, Fujian Medical University Union Hospital, Fujian Key Laboratory of Molecular Neurology, Institute of Clinical Neurology, Institute of Neuroscience, Fujian Medical University, Fuzhou, China.
² Department of Clinical Medicine, Fujian Medical University, Fuzhou, China.
³ Fujian Province Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, China.
⁴ College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China.
⁵ Public Technology Service Center, Fujian Medical University, Fuzhou, China.
⁶ Fujian Key Laboratory of Brain Aging and Neurodegenerative Diseases, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.

Abstract

Mitochondria are essential organelles that perform important roles in cell biologies such as ATP synthesis, metabolic regulation, immunomodulatory, and apoptosis. Parkinson's disease (PD) is connected with mitochondrial neuronal damage related to mitochondrial unfolded protein response (mtUPR). Rosmarinic acid (RA) is a naturally occurring hydroxylated polyphenolic chemical found in the Boraginaceae and the Labiatae subfamily Nepetoideae. This study looked into RA's protective effect against mitochondrial loss in the substantia nigra (SN) caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the underlying mechanism associated with the mtUPR. Pretreatment with RA reduced motor impairments and dopaminergic neuronal degeneration in the SN of a mouse model injected with MPTP. Pretreatment of SH-SY5Y cells from cell viability loss, morphological damage, and oxidative stress. Furthermore, RA pre-injection suppressed MPTP-induced mtUPR, lowered the expression of HSPA9, HSPE1, CLPP, LONP1, and SIRT 4, and protected the MPTP-mice and SH-SY5Y cells from mitochondrial failure. These findings imply that RA can prevent Parkinson's disease by preventing mitochondrial damage in dopaminergic neurons in Parkinson's disease via alleviating mitochondrial unfolded protein response.

Keywords: immunlogy; mitochondrial damage; mtUPR; rosmarinic acid; substantia nigra.