Sesamin and sesamol attenuate H₂O₂-induced oxidative stress on human neuronal cells via the SIRT1-SIRT3-FOXO3a signaling pathway

ABSTRACT

Background: An imbalance of free radicals and antioxidant defense systems in physiological processes can result in protein/DNA damage, inflammation, and cellular apoptosis leading to neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD). Sesamin and sesamol, compounds derived from sesame seeds and oil, have been reported to exert various pharmacological effects, especially antioxidant activity. However, their molecular mechanisms against the oxidative stress induced by exogenous hydrogen peroxide (H₂O₂) remain to be elucidated.

Aim: In this study, neuroprotective effects of sesamin and sesamol on H₂O₂-induced human neuroblastoma (SH-SY5Y) cell death and possible signaling pathways in the cells were explored.

Methods: MTT assay and flow cytometry were conducted to determine cell viability and apoptotic profiles of neuronal cells treated with sesamin and sesamol. Carboxy-DCFDA assay was used to measure reactive oxygen species (ROS). Moreover, Western blot analysis was performed to investigate protein profiles associated with neuroprotection.

Results: Pretreatment of the cells with 1 µM of sesamin and sesamol remarkably reduced the SH-SY5Y cell death induced by 400 µM H₂O₂ as well as the intracellular ROS production. Moreover, the molecular mechanisms underlying neuroprotection of the compounds were associated with activating SIRT1-SIRT3-FOXO3a expression, inhibiting BAX (proapoptotic protein), and upregulating BCL-2 (anti-apoptotic protein).

Conclusion: The findings suggest that sesamin and sesamol are compounds that potentially protect neuronal cells against oxidative stress similar to that of the resveratrol, the reference compound. These antioxidants are thus of interest for further investigation in in vivo models of neuroprotection.

KEYWORDS:

• Sesamin
• sesamol
• antioxidant
• antiapoptosis
• oxidative stress
• sirtuin
• neurodegenerative diseases

Disclosure statement

No potential conflict of interest was reported by the authors.

Notes on contributors

Waralee Ruankham completed her B.Sc. and M.Sc. in Medical Technology, Mahidol University, Thailand. Currently, she is pursuing PhD in Medical Technology, Faculty of Medical Technology, Mahidol University. Her research areas include natural and synthetic bioactive compounds for neuroprotection including Alzheimer’s disease and molecular docking analysis.

Wilasinee Suwanjang completed her B.Sc. in Conservation Biology, Faculty of Science and her Ph.D. in Neuroscience from the Institute of Molecular Biosciences, Mahidol University, Thailand. Currently, she is a lecturer at the Center of Research and Innovation and an Assistant Dean for Holistic Health and Wellness Development and Safety Regulation, Faculty of Medical Technology, Mahidol University. Her current research focuses on the cellular mechanisms of neurodegeneration in Alzheimer’s disease and the role of mitochondria, reactive oxygen species (ROS), and calcium signaling. Her research interests also include natural treatments in the fields of neurodegenerative diseases and depression.

Prapimpun Wongchitrat obtained her Ph.D. in Molecular Biology from the Faculty of Medicine, Srinakharinwirot University, Thailand. She is currently a lecturer at the Faculty of Medical Technology, Mahidol University. Her research focuses on the neurobiology of rhythms, neurophysiology of the brain, and molecular mechanisms of several age-related diseases such as Alzheimer’s disease, diabetes, obesity, and viral infections.

Verapong Prachayasittikul received his B.Sc. in Medical Technology, Mahidol University, and M.Sc. Pharmacology from Mahidol University, Thailand. In addition, he completed his Ph.D. in Microbiology from the University of Health Science/The Chicago Medical School, the United States of America and Doctor of Technology (Honoris Causa) from Lund University, Sweden. Currently, he is a professor at the Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Thailand. His major research areas include Medical Microbiology, Pharmacology, Medical technology, and Computer-aided drug design for therapeutic applications including anticancer, antioxidant, and antimalarial agents.

Supaluk Prachayasittikul obtained her B.Sc. in Chemistry, Faculty of Science, Kasetsart University, Thailand, her M.Sc. in Organic Chemistry, Faculty of Science, Mahidol University, Thailand, and her Ph.D. in Medicinal Chemistry from the University of Illinois at Chicago (Health Science Center), the United States of America. She is presently serving as a professor at the Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Thailand. Her research interests include Organic-Medicinal Chemistry, QSAR, Molecular Docking, natural and synthetic bioactive compounds for therapeutic applications.

Kamonrat Phopin received her B.Sc. in Medical Technology, Faculty of Medical Technology, Mahidol University, Thailand, her M.Sc. in Medical Microbiology from Chulalongkorn University, Thailand, and her Ph.D. in Molecular Biology from Lehigh University, the United States of America. She is presently a lecturer and researcher at the Faculty of Medical Technology, Mahidol University. Her main research interests include biological evaluation of synthetic and natural bioactive compounds for treatment of neurodegenerative diseases including Alzheimer’s disease, and investigates the signaling pathways that are involved in neurodegenerative disorders. Additionally, she also performs computational analysis for the prediction of binding interactions between bioactive compounds and target proteins for drug development.

Additional information

Funding

This work was supported by the Office of the Higher Education Commission, Mahidol University under the National Research Universities Initiative.