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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Neuropharmacology
Volume 15 - 2024 |
doi: 10.3389/fphar.2024.1443552
This article is part of the Research Topic Microglia and the Neuronal Cytoskeleton: Druggable Targets in Neurodegeneration View all articles
Kojic Acid Rescue LPS-Induced Neuroinflammation and Cognitive Impairment by Regulating TLR4/NF-κB signaling pathway
Provisionally accepted
Waqar Ali
1*
Kyonghwan Choe
1,2*
Jun Sung Park
1*
Riaz Ahmad
1
Hyun Young Park
2,3*
Min Hwa Kang
1*
Tae Ju Park
4*
Myeong Ok Kim
1*- 1 Division of Life Science and Applied Life Science (BK 21 Four), College of Natural Sciences, Gyeongsang National University, Jinju, 52828, Republic of Korea, Gyeongsang National University, Jinju, Republic of Korea
- 2 Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Maastricht University, Maastricht 6229ER, the Netherlands, Maastricht University Medical Centre, Maastricht, Limburg, Netherlands
- 3 Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Maastricht University, 6229 ER Mastricht, The Netherlands, UMC Maastricht and Integral Care Department, Maastricht, Netherlands, Netherlands
- 4 Haemato-oncology/Systems Medicine Group, Paul O’Gorman Leukaemia Research Centre, Institute of Cancer Sciences, College of Medical, Veterinary & Life Sciences (MVLS), University of Glasgow, Glasgow G12 0ZD, United Kingdom, University of Glasgow, Glasgow, Scotland, United Kingdom
Intense neuroinflammation contributes in neurodegenerative diseases, such as Alzheimer's diseases and Parkinson's disease. Lipopolysaccharide (LPS) is an integral part of cell wall of gram-negative bacteria act as PAMPs and potentially activates immune system of Central Nervous System (CNS).Microglial cells are the local macrophages of CNS and having potential to induce and control neuroinflammation. This study is aimed to evaluate the anti-inflammatory and antioxidant effect of kojic acid against the toxic effect of LPS, such as neuroinflammation induced neurodegeneration and cognitive decline. The C57BL/6N mice were subjected to LPS injection for two weeks on an alternate day (each mouse received 0.25 mg/kg/i.p. for a total of seven doses), and kojic acid was administered orally for three weeks consecutively (50 mg/kg/mouse, p.o). Bacterial endotoxins, LPS directly attached to TLR4 surface receptors of microglia and astrocytes, which alter the cellular metabolism of immune cells. Intraperitoneal injection of LPS trigger the Toll-Like Receptor 4 (TLR4), phospho-nuclear factor kappa B (p-NFκB), and phospho-c-Jun n-terminal kinase (p-JNK) proteins expressions in LPS treated group which was significantly downregulated in LPS+KA treated mice brain. Prolong neuroinflammation leads to generation of ROS followed by decrease in nuclear factor erythroid-2-related factor 2 (Nrf2) and the enzyme hemeoxygenase 1 (HO-1) expression in LPS subjected mouse brain. But interestingly, the level of both Nrf-2 and HO-1 were increase in LPS+KA treated mice group. In addition, kojic acid inhibited LPS-induced TNF-α and IL-1β production in mouse brain. These results indicated that kojic acid may suppress LPS-induced neuroinflammation and oxidative stress in male wild type mice brain (both in cortex and hippocampus) by regulating TLR4/NF-κB signaling pathway.
Keywords: LPS 1, Neuroinflammation 2, Oxidative stress 3, Neurodegeneration 4, cognitive
Received: 04 Jun 2024; Accepted: 22 Jul 2024.
Copyright: © 2024 Ali, Choe, Park, Ahmad, Park, Kang, Park and Kim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Waqar Ali, Division of Life Science and Applied Life Science (BK 21 Four), College of Natural Sciences, Gyeongsang National University, Jinju, 52828, Republic of Korea, Gyeongsang National University, Jinju, Republic of Korea
Kyonghwan Choe, Division of Life Science and Applied Life Science (BK 21 Four), College of Natural Sciences, Gyeongsang National University, Jinju, 52828, Republic of Korea, Gyeongsang National University, Jinju, Republic of Korea
Jun Sung Park, Division of Life Science and Applied Life Science (BK 21 Four), College of Natural Sciences, Gyeongsang National University, Jinju, 52828, Republic of Korea, Gyeongsang National University, Jinju, Republic of Korea
Hyun Young Park, Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Maastricht University, Maastricht 6229ER, the Netherlands, Maastricht University Medical Centre, Maastricht, 6229 HX, Limburg, Netherlands
Min Hwa Kang, Division of Life Science and Applied Life Science (BK 21 Four), College of Natural Sciences, Gyeongsang National University, Jinju, 52828, Republic of Korea, Gyeongsang National University, Jinju, Republic of Korea
Tae Ju Park, Haemato-oncology/Systems Medicine Group, Paul O’Gorman Leukaemia Research Centre, Institute of Cancer Sciences, College of Medical, Veterinary & Life Sciences (MVLS), University of Glasgow, Glasgow G12 0ZD, United Kingdom, University of Glasgow, Glasgow, G12 8QQ, Scotland, United Kingdom
Myeong Ok Kim, Division of Life Science and Applied Life Science (BK 21 Four), College of Natural Sciences, Gyeongsang National University, Jinju, 52828, Republic of Korea, Gyeongsang National University, Jinju, Republic of Korea
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