PMID- 36873166 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230307 IS - 2211-3835 (Print) IS - 2211-3843 (Electronic) IS - 2211-3835 (Linking) VI - 13 IP - 2 DP - 2023 Feb TI - Honokiol alleviated neurodegeneration by reducing oxidative stress and improving mitochondrial function in mutant SOD1 cellular and mouse models of amyotrophic lateral sclerosis. PG - 577-597 LID - 10.1016/j.apsb.2022.07.019 [doi] AB - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting both upper and lower motor neurons (MNs) with large unmet medical needs. Multiple pathological mechanisms are considered to contribute to the progression of ALS, including neuronal oxidative stress and mitochondrial dysfunction. Honokiol (HNK) has been reported to exert therapeutic effects in several neurologic disease models including ischemia stroke, Alzheimer's disease and Parkinson's disease. Here we found that honokiol also exhibited protective effects in ALS disease models both in vitro and in vivo. Honokiol improved the viability of NSC-34 motor neuron-like cells that expressed the mutant G93A SOD1 proteins (SOD1-G93A cells for short). Mechanistical studies revealed that honokiol alleviated cellular oxidative stress by enhancing glutathione (GSH) synthesis and activating the nuclear factor erythroid 2-related factor 2 (NRF2)-antioxidant response element (ARE) pathway. Also, honokiol improved both mitochondrial function and morphology via fine-tuning mitochondrial dynamics in SOD1-G93A cells. Importantly, honokiol extended the lifespan of the SOD1-G93A transgenic mice and improved the motor function. The improvement of antioxidant capacity and mitochondrial function was further confirmed in the spinal cord and gastrocnemius muscle in mice. Overall, honokiol showed promising preclinical potential as a multiple target drug for ALS treatment. CI - (c) 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. FAU - Zhou, Yujun AU - Zhou Y AD - State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. FAU - Tang, Jingshu AU - Tang J AD - State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. FAU - Lan, Jiaqi AU - Lan J AD - State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. FAU - Zhang, Yong AU - Zhang Y AD - State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. FAU - Wang, Hongyue AU - Wang H AD - State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. FAU - Chen, Qiuyu AU - Chen Q AD - State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. FAU - Kang, Yuying AU - Kang Y AD - State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. FAU - Sun, Yang AU - Sun Y AD - Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. FAU - Feng, Xinhong AU - Feng X AD - Department of Neurology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China. FAU - Wu, Lei AU - Wu L AD - State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. FAU - Jin, Hongtao AU - Jin H AD - New Drug Safety Evaluation Center, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. AD - NMPA Key Laboratory for Safety Research and Evaluation of Innovative Drug, Beijing 100050, China. FAU - Chen, Shizhong AU - Chen S AD - Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. FAU - Peng, Ying AU - Peng Y AD - State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. LA - eng PT - Journal Article DEP - 20220810 PL - Netherlands TA - Acta Pharm Sin B JT - Acta pharmaceutica Sinica. B JID - 101600560 PMC - PMC9979194 OTO - NOTNLM OT - Amyotrophic lateral sclerosis OT - Glutathione OT - Honokiol OT - Mitochondrial biogenesis OT - Mitochondrial dynamics OT - NRF2 OT - Oxidative stress OT - SOD1-G93A EDAT- 2023/03/07 06:00 MHDA- 2023/03/07 06:01 PMCR- 2022/08/10 CRDT- 2023/03/06 03:38 PHST- 2022/04/17 00:00 [received] PHST- 2022/06/12 00:00 [revised] PHST- 2022/06/16 00:00 [accepted] PHST- 2023/03/06 03:38 [entrez] PHST- 2023/03/07 06:00 [pubmed] PHST- 2023/03/07 06:01 [medline] PHST- 2022/08/10 00:00 [pmc-release] AID - S2211-3835(22)00333-1 [pii] AID - 10.1016/j.apsb.2022.07.019 [doi] PST - ppublish SO - Acta Pharm Sin B. 2023 Feb;13(2):577-597. doi: 10.1016/j.apsb.2022.07.019. Epub 2022 Aug 10.