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ORIGINAL RESEARCH article

Front. Cell. Neurosci.

Sec. Cellular Neuropathology

Volume 19 - 2025 | doi: 10.3389/fncel.2025.1625362

This article is part of the Research TopicIntercellular communication in chronic neuroinflammatory diseasesView all 5 articles

Neuroprotective Effects of Saikosaponin-A in Ethanol-induced Glia-mediated Neuroinflammation, Oxidative Stress via RAGE/TLR4/NFkB Signaling

Provisionally accepted
Waqar AliWaqar Ali1Kyonghwan ChoeKyonghwan Choe1,2Min Hwa KangMin Hwa Kang1Jawad AliJawad Ali1Hyun Young ParkHyun Young Park2,3Abubakar AtiqAbubakar Atiq1Sareer AhmadSareer Ahmad1Tae Ju ParkTae Ju Park4*Myeong Ok KimMyeong Ok Kim1,5*
  • 1Gyeongsang National University, Jinju, Republic of Korea
  • 2Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Maastricht University, 6229 ER Mastricht, The Netherlands., Maastricht, Netherlands
  • 3Department of Pediatrics, Maastricht University Medical Center (MUMC+), 6202 AZ Maastricht, The Netherlands, Maastricht, Netherlands
  • 4Haemato-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, United Kingdom
  • 5Alz-Dementia Korea Co., Jinju 52828, Republic of Korea., Jinju, Republic of Korea

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Chronic use of ethanol leads to psychological and physiological dependence followed by neurodegeneration via glia-mediated neuroinflammation, and oxidative stress. The current study is aimed at the neuroprotective effects of saikosaponin-A against ethanol-induced neurodegeneration.Here, saikosaponin-A 10mg/kg i.p., for seven days was used against the ethanol (5g/kg i.p., for six weeks) induced neuroinflammation via RAGE/TLR4 signaling in mouse neurodegenerative model.The immunoblotting and immunofluorescences microscopy results showed that, ethanol activates the glial cells at the level of mice brain. The relative expression of Toll like receptor (TLR4), receptor for advance glycation end product (RAGE), ionized calcium binding adaptor molecules 1 (Iba-1), glial fibrillary acidic protein (GFAP) was upregulated in ethanol-treated mice group. However, expression level of inflammatory biomarkers were downregulated in ethanol+SSA co-treated group. Similarly, our finding revealed that SSA significantly reduced the protein expression level of Phospo c-Jun N-Terminal Kinase (p-JNK), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and downstream signaling targets in ethanol+SSA co-treated group. SSA also regulates the elevated ethanol-induced oxidative stress via NRF2 and HO-1 proteins. Finally, we analyzed the synaptic and behavioral alteration that was reversed in SSA treated group. Taken together, we concluded that SSA exhibits anti-inflammatory and antioxidant effects against ethanol-induced neurodegeneration.

Keywords: alcohol1, neurodegeneration2, Gliosis3, Oxidative Stress4, Saikosaponin-A5

Received: 08 May 2025; Accepted: 05 Aug 2025.

Copyright: © 2025 Ali, Choe, Kang, Ali, Park, Atiq, Ahmad, 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:
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, United Kingdom
Myeong Ok Kim, Gyeongsang National University, Jinju, Republic of Korea

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material