Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatry. Apr 19, 2024; 14(4): 563-581
Published online Apr 19, 2024. doi: 10.5498/wjp.v14.i4.563
Tanshinone IIA improves Alzheimer’s disease via RNA nuclear-enriched abundant transcript 1/microRNA-291a-3p/member RAS oncogene family Rab22a axis
Long-Xiu Yang, Man Luo, Sheng-Yu Li
Long-Xiu Yang, Man Luo, Sheng-Yu Li, Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530000, Guangxi Zhuang Autonomous Region, China
Sheng-Yu Li, Department of Neurology, Wuming Hospital of Guangxi Medical University, Nanning 530199, Guangxi Zhuang Autonomous Region, China
Author contributions: Yang LX, Luo M, and Li SY contributed to the study design, experiments, data collection, and manuscript writing; Luo M and Li SY contributed to the visualization; Li SY contributed to the resources; and all authors have read and approved the final manuscript.
Supported by 2020 Guangxi Zhuang Autonomous Region Health Care Commission Self-Financing Research Projects, No. Z20200096; 2023 Guangxi University Young and Middle-Aged Teachers’ Basic Research Ability Improvement Project, No. 2023KY0091; National Natural Science Foundation of China, No. 82260241; and the Natural Science Foundation of Guangxi Province, No. 2015GXNSFAA139171 and No. 2020GXNSFAA259053.
Institutional animal care and use committee statement: All procedures involving animals were approved by the Animal Care and Use Committee of the First Affiliated Hospital of Guangxi Medical University, No. 2021(KY-E-292), and performed in accordance with the Guide for the Care and Use of Laboratory Animals. All surgery and euthanasia were performed under sodium pentobarbital anesthesia (200 mg/kg) by intraperitoneal injection, and all efforts were made to minimize suffering.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Sheng-Yu Li, MD, Doctor, Teacher, Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Qingxiu District, Nanning 530000, Guangxi Zhuang Autonomous Region, China. 15177821212@163.com
Received: October 11, 2023
Peer-review started: October 11, 2023
First decision: December 26, 2023
Revised: January 9, 2024
Accepted: February 28, 2024
Article in press: February 28, 2024
Published online: April 19, 2024
Processing time: 188 Days and 23.7 Hours
Abstract
BACKGROUND

Alzheimer’s disease (AD) is a neurodegenerative condition characterized by oxidative stress and neuroinflammation. Tanshinone IIA (Tan-IIA), a bioactive compound isolated from Salvia miltiorrhiza plants, has shown potential neuroprotective effects; however, the mechanisms underlying such a function remain unclear.

AIM

To investigate potential Tan-IIA neuroprotective effects in AD and to elucidate their underlying mechanisms.

METHODS

Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology. To assess changes in oxidative stress and neuroinflammation, we performed enzyme-linked immunosorbent assay and western blotting. Additionally, the effect of Tan-IIA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Genetic changes related to the long non-coding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1)/microRNA (miRNA, miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction.

RESULTS

In vivo, Tan-IIA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice. In vitro experiments showed that Tan-IIA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability, apoptosis, oxidative stress, and neuroinflammation. In this process, the lncRNA NEAT1 - a potential therapeutic target - is highly expressed in AD mice and downregulated via Tan-IIA treatment. Mechanistically, NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p, which activates nuclear factor kappa-B (NF-κB) signaling, leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein, which exacerbates AD. Tan-IIA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling.

CONCLUSION

This study demonstrates that Tan-IIA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway, serving as a foundation for the development of innovative approaches for AD therapy.

Keywords: Tanshinone IIA; Alzheimer’s disease; Nuclear-enriched abundant transcript 1; Member of RAS oncogene family Rab22a; Reactive oxygen species

Core Tip: Tanshinone IIA (Tan-IIA), a compound isolated from Salvia miltiorrhiza, demonstrates neuroprotective effects against Alzheimer’s disease (AD). This study reveals that Tan-IIA improves neuronal health, reduces oxidative stress and neuroinflammation, and promotes neural stem cell viability. Importantly, it targets the nuclear-enriched abundant transcript 1/microRNA-291a-3p/member RAS oncogene family Rab22a/nuclear factor kappa-B pathway, offering a potential therapeutic avenue for AD.