The DOI matches its Crossref record; 70 of the 71 references it cites were found in a registry or an index.
Mitigation of honokiol on fluoride-induced mitochondrial oxidative stress, mitochondrial dysfunction, and cognitive deficits through activating AMPK/PGC-1α/Sirt3
Abstract
Oxidative stress and mitochondrial dysfunction contribute greatly to fluoride-induced cognitive impairment and behavioural disorders. Honokiol, a natural biphenolic compound, possesses antioxidant and mitochondrial protective properties. The present study investigated the protective actions of honokiol on NaF-elicited cognitive deficits and elucidated the possible mechanism of honokiol-mediated protection. The results demonstrated that honokiol administration markedly attenuated fluoride-induced cognitive impairments and neural/synaptic injury in mice. Moreover, honokiol elevated the activity and expression of SOD2 and promoted mtROS scavenging through Sirt3 activation in NaF-treated mice and SH-SY5Y cell lines. Meanwhile, honokiol substantially lowered mtROS production by enhancing Sirt3-mediated mitochondrial DNA (mtDNA) transcription, thereby leading to significant increases in ATP synthesis and complex I activity. Further studies revealed that honokiol activated AMPK and upregulated the PGC-1α and Sirt3 protein expression in vivo and in vitro. Intriguingly, the protective actions of honokiol on oxidative stress and mitochondrial dysfunction were abolished by AMPK shRNA or Sirt3 shRNA. Notably, AMPK knockdown prevented the increase in PGC-1α and Sirt3 expression induced by honokiol, while Sirt3 shRNA suppressed Sirt3 signaling without significant effects on p-AMPK and PGC-1α expression. In conclusion, our findings indicate that honokiol mitigates NaF-induced oxidative stress and mitochondrial dysfunction by regulating mtROS homeostasis, partly via the AMPK/PGC-1α/Sirt3 pathway, which ultimately contributes to neuronal/synaptic injury and cognitive deficits.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“intestinal AMPK, which can directly or indirectly interact with SOD2 [24, 25]”
From Healthy Human Fecal Microbiota Transplantation into Mice Attenuates MPTP-Induced Neurotoxicity via AMPK/SOD2 Pathway (2023) · cites this paper as [25]
Citations
Cites
Mitochondrial free radical generation, oxidative stress, and aging
Cadenas, E., & Davies, K. J. A. (2000) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(00)00317-8 · Cited by 3,010
AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α
Jäger, S., Handschin, C., St.-Pierre, J., & Spiegelman, B. M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705070104 · Cited by 2,491
Superoxide Dismutases: Role in Redox Signaling, Vascular Function, and Diseases
Fukai, T., & Ushio‐Fukai, M. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2011.3999 · Cited by 2,074
A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis
Ahn, B.-H., Kim, H.-S., Song, S., Lee, I. H., Liu, J., Vassilopoulos, A., Deng, C.-X., & Finkel, T. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0803790105 · Cited by 1,291
Brand, M. D. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.04.001 · Cited by 1,063
Sundaresan, N. R., Gupta, M., Gene, K., Rajamohan, S. B., Isbatan, A., & Gupta, M. P. (2009) · Journal of Clinical Investigation · doi:10.1172/jci39162 · Cited by 1,006
Mitochondrial transport in neurons: impact on synaptic homeostasis and neurodegeneration
Sheng, Z., & Cai, Q. (2012) · Nature reviews. Neuroscience · doi:10.1038/nrn3156 · Cited by 940
Tao, R., Coleman, M. C., Pennington, J. D., Ozden, O., Park, S.-H., Jiang, H., Kim, H.-S., Flynn, C. R., Hill, S., Hayes McDonald, W., et al. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.12.013 · Cited by 899
Redox Homeostasis and Mitochondrial Dynamics
Willems, P. H. G. M., Rossignol, R., Dieteren, C. E. J., Murphy, M. P., & Koopman, W. J. H. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.06.006 · Cited by 876
Chen, M., Zhu, X., Ran, L., Lang, H., Yi, L., & Mi, M. (2017) · Journal of the American Heart Association · doi:10.1161/jaha.117.006347 · Cited by 600
Tumour suppressor SIRT3 deacetylates and activates manganese superoxide dismutase to scavenge ROS
Chen, Y., Zhang, J., Lin, Y., Lei, Q., Guan, K., Zhao, S., & Xiong, Y. (2011) · The EMBO Reports · doi:10.1038/embor.2011.65 · Cited by 572
Rabinovitch, R. C., Samborska, B., Faubert, B., Ma, E. H., Gravel, S.-P., Andrzejewski, S., Raissi, T. C., Pause, A., St.-Pierre, J., & Jones, R. G. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.09.026 · Cited by 543
Developmental Fluoride Neurotoxicity: A Systematic Review and Meta-Analysis
Choi, A. L., Sun, G., Zhang, Y., & Grandjean, P. (2012) · Environmental Health Perspectives · doi:10.1289/ehp.1104912 · Cited by 469
SIRT3 deacetylates FOXO3 to protect mitochondria against oxidative damage
Tseng, A. H.-H., Shieh, S.-S., & Wang, D. L. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.05.002 · Cited by 458
Self-citationHonokiol blocks and reverses cardiac hypertrophy in mice by activating mitochondrial Sirt3
Pillai, V. B., Samant, S. A., Sundaresan, N. R., Raghuraman, H., Kim, G. H., Bonner, M. Y., Arbiser, J. L., Walker, D. I., Jones, D. P., Gius, D. R., et al. (2015) · Nature Communications · doi:10.1038/ncomms7656 · Cited by 453
A cannabinoid link between mitochondria and memory
Hebert-Chatelain, E., Desprez, T., Serrat, R., Bellocchio, L., Soria-Gomez, E., Busquets-Garcia, A., Pagano Zottola, A. C., Delamarre, A., Cannich, A., Vincent, P., et al. (2016) · Nature · doi:10.1038/nature20127 · Cited by 434
Dikalova, A., Pandey, A. K., Xiao, L., Arslanbaeva, L. R., Sidorova, T. N., Lopez, M. G., Billings, F. T., Verdin, E. M., Auwerx, J. H., Harrison, D. G., et al. (2019) · Circulation Research · doi:10.1161/circresaha.119.315767 · Cited by 379
SIRT3-SOD2-mROS-dependent autophagy in cadmium-induced hepatotoxicity and salvage by melatonin
Pi, H., Xu, S., Reiter, R. J., Guo, P., Zhang, L., Li, Y., Li, M., Cao, Z., Tian, L., Xie, J., et al. (2015) · Autophagy · doi:10.1080/15548627.2015.1052208 · Cited by 363
Zhai, M., Li, B., Duan, W., Jing, L., Zhang, B., Zhang, M., Yu, L., Liu, Z., Yu, B., Ren, K., et al. (2017) · Journal of Pineal Research · doi:10.1111/jpi.12419 · Cited by 354
Mitochondrial reactive oxygen species production and elimination
Nickel, A. G., Kohlhaas, M., & Maack, C. (2014) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2014.03.011 · Cited by 334
Ansari, A., Rahman, M. S., Saha, S. K., Saikot, F. K., Deep, A., & Kim, K. (2016) · Aging Cell · doi:10.1111/acel.12538 · Cited by 315
SIRT3 regulation of mitochondrial oxidative stress
Bause, A. S., & Haigis, M. C. (2013) · Experimental Gerontology · doi:10.1016/j.exger.2012.08.007 · Cited by 311
Han, X., Tai, H., Wang, X., Wang, Z., Zhou, J., Wei, X., Ding, Y., Gong, H., Mo, C., Zhang, J., et al. (2016) · Aging Cell · doi:10.1111/acel.12446 · Cited by 302
Self-citationFOXO3a from the Nucleus to the Mitochondria: A Round Trip in Cellular Stress Response
Fasano, C., Disciglio, V., Bertora, S., Signorile, M. L., & Simone, C. (2019) · Cells · doi:10.3390/cells8091110 · Cited by 251
Dysfunctional Mitochondria and Mitophagy as Drivers of Alzheimer’s Disease Pathogenesis
Chakravorty, A., Jetto, C. T., & Manjithaya, R. R. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00311 · Cited by 225
Fluoride induces oxidative damage and SIRT1/autophagy through ROS-mediated JNK signaling
Suzuki, M., Bandoski, C., & Bartlett, J. D. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.08.015 · Cited by 216
Mitochondrial Dysfunction and Synaptic Transmission Failure in Alzheimer’s Disease
Guo, L., Tian, J., & Du, H. (2017) · Journal of Alzheimer’s Disease · doi:10.3233/jad-160702 · Cited by 211
Zhou, X., Chen, M., Zeng, X., Yang, J., Deng, H., Yi, L., & Mt, M. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.530 · Cited by 208
Self-citationCritical role of AMPK in redox regulation under glucose starvation
Ren, Y., & Shen, H. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101154 · Cited by 201
Zheng, J., Shi, L., Liang, F., Xu, W., Li, T., Gao, L., Sun, Z., Yu, J., & Zhang, J. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00414 · Cited by 173
SOD2 and Sirt3 Control Osteoclastogenesis by Regulating Mitochondrial ROS
Kim, H., Lee, Y. D., Kim, H. J., Lee, Z. H., & Kim, H. (2016) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2974 · Cited by 153
Hung, C. H.-L., Cheng, S. S., Cheung, Y.-T., Wuwongse, S., Zhang, N. Q., Ho, J. Y. S., Lee, S. M., & Chang, R. C. (2017) · Redox Biology · doi:10.1016/j.redox.2017.08.010 · Cited by 147
Wang, X., Duan, X., Yang, G., Zhang, X., Deng, L., Zheng, H., Deng, C., Wen, J., Wang, N., Peng, C. Y., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018490 · Cited by 138
Neuro-Modulating Effects of Honokiol: A Review
Woodbury, A., Yu, S. P., Wei, L., & García, P. S. (2013) · Frontiers in Neurology · doi:10.3389/fneur.2013.00130 · Cited by 133
Fluoride exposure impairs glucose tolerance via decreased insulin expression and oxidative stress
García-Montalvo, E. A., Reyes-Pérez, H., & Razo, L. M. D. (2009) · Toxicology · doi:10.1016/j.tox.2009.06.008 · Cited by 127
Zhao, Q., Tian, Z., Zhou, G., Niu, Q., Chen, J., Li, P., Dong, L., Xia, T., Zhang, S., & Wang, A. (2020) · Theranostics · doi:10.7150/thno.42387 · Cited by 127
Traba, J., Geiger, S. S., Osei, M. A., Han, K., Ra, O. H., Siegel, R. M., Gius, D. R., & Sack, M. N. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.791715 · Cited by 120
LIN, J., Chen, J.-T., Hong, C.-Y., Lin, Y., Wang, K., Yao, C., Lai, G., & Chen, R.-M. (2012) · Neuro-Oncology · doi:10.1093/neuonc/nor217 · Cited by 118
Studying synapses in human brain with array tomography and electron microscopy
Kay, K. R., Smith, C., Wright, A. K., Serrano-Pozo, A., Pooler, A. M., Koffie, R., Bastin, M. E., Bak, T. H., Abrahams, S., Kopeikina, K. J., et al. (2013) · Nature Protocols · doi:10.1038/nprot.2013.078 · Cited by 116
Baj, G., Patrizio, A., Montalbano, A., Sciancalepore, M., & Tongiorgi, E. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00018 · Cited by 99
Divya, S. P., Pratheeshkumar, P., Son, Y., Roy, R. V., Hitron, J. A., Kim, D., Dai, J., Wang, L., Asha, P., Huang, B., et al. (2015) · Toxicological Sciences · doi:10.1093/toxsci/kfv089 · Cited by 98
N europrotective effects of honokiol: from chemistry to medicine
Talarek, S., Listos, J., Barreca, D., Tellone, E., Sureda, A., Nabavi, S. F., Braidy, N., & Nabavi, S. M. (2017) · BioFactors · doi:10.1002/biof.1385 · Cited by 94
Jiang, Q., Fan, L., Yang, G., Guo, W., Hou, W.-L., Chen, L., & Wei, Y.-Q. (2008) · BMC Cancer · doi:10.1186/1471-2407-8-242 · Cited by 87
Song, C., Fu, B., Zhang, J., Zhao, J., Yuan, M., Peng, W., Zhang, Y., & Wu, H. (2017) · Scientific Reports · doi:10.1038/s41598-017-00796-3 · Cited by 86
Guo, X., Jiang, Q., Tuccitto, A., Chan, D. W.-H., Alqawlaq, S., Won, G.-J., & Sivak, J. M. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.02.004 · Cited by 85
Song, C., Zhao, J., Fu, B., Li, D., Mao, T., Peng, W., Wu, H., & Zhang, Y. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.09.005 · Cited by 77
Psychopharmacology of fluoride
Spittle, B. J. (1994) · International Clinical Psychopharmacology · doi:10.1097/00004850-199400920-00002 · Cited by 76
Liu, X., Zhang, L., Wang, P., Li, X., Qiu, D., Li, L., Zhang, J., Hou, X., Han, L., Ge, J., et al. (2017) · Cell Cycle · doi:10.1080/15384101.2017.1320004 · Cited by 76
Li, H., Jia, J., Wang, W., Hou, T., Tian, Y., Wu, Q., Xu, L., Wei, Y., & Wang, X. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180126 · Cited by 71
Wang, H., Zhang, Y., Tan, P., Jia, L.-S., Chen, Y., & Zhou, B.-H. (2019) · Environmental Pollution · doi:10.1016/j.envpol.2019.113359 · Cited by 69
Tsai, T., Chou, C., Cheng, F.-C., & Chen, C.-F. (1994) · Journal of Chromatography B Biomedical Sciences and Applications · doi:10.1016/0378-4347(94)00031-x · Cited by 65
Wang, X., Cai, L., Zhang, X.-Y., Deng, L., Zheng, H., Deng, C., Wen, J., Zhao, X., Wei, Y.-Q., & Chen, L. (2011) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2011.03.003 · Cited by 61
Liu, S.-G., Wang, Y.-M., Zhang, Y., He, X., Ma, T., Song, W., & Zhang, Y. (2017) · Neurochemistry International · doi:10.1016/j.neuint.2017.04.005 · Cited by 53
Wang, H., Liu, J., Wei, S.-S., Zhao, W., Zhu, S.-Q., & Zhou, B.-H. (2019) · Chemosphere · doi:10.1016/j.chemosphere.2019.125099 · Cited by 53
Wang, D., Dong, X., & Wang, C. (2018) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.118.248674 · Cited by 47
Self-citationZhou, G., Tang, S., Yang, L., Niu, Q., Chen, J., Xia, T., Wang, S., Wang, M., Zhao, Q., Liu, L., et al. (2019) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2019.114608 · Cited by 44
Sirt3-mediated mitochondrial dysfunction is involved in fluoride-induced cognitive deficits
Wang, D., Cao, L., Pan, S., Wang, G., Wang, L., Cao, N., & Hao, X. (2021) · Food and Chemical Toxicology · doi:10.1016/j.fct.2021.112665 · Cited by 43
Self-citationBasha, P. M., & Saumya, S. M. (2013) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-013-9912-0 · Cited by 41
Cao, K., Xiang, J., Dong, Y., Xu, Y., Li, Y., Song, H., Zeng, X.-X., Ran, L., Hong, W., & Guan, Z.-Z. (2019) · Alzheimer s Research & Therapy · doi:10.1186/s13195-019-0490-3 · Cited by 40
Zhou, G., Yang, L., Luo, C., Liu, H., Li, P., Cui, Y., Liu, L., Yu, X., Zeng, Q., Chen, J., et al. (2019) · Environment International · doi:10.1016/j.envint.2019.03.033 · Cited by 37
Liu, H.-T., Wang, T., Hsu, Y.-T., Chou, C., Huang, K., Hsu, C., Liang, H., Chang, H., Lee, T., & Tsai, P. (2019) · Antioxidants · doi:10.3390/antiox8100466 · Cited by 35
The Pharmacokinetics and Tissue Distribution of Honokiol and its Metabolites in Rats
Wang, J., Xiao-lei, M., Jing-ya, C., & Chen, Y. (2015) · European Journal of Drug Metabolism and Pharmacokinetics · doi:10.1007/s13318-015-0281-6 · Cited by 34
Wang, D., Dong, X., Wang, B., Liu, Y., & Li, S. (2019) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.9b03977 · Cited by 34
Self-citationMa, L., Kong, F., Dong, Z., Xin, K., Wang, X., Sun, A., Zou, Y., & Ge, J. (2021) · Cell Proliferation · doi:10.1111/cpr.13051 · Cited by 30
Chauhan, S. S., Mahmood, A., & Ojha, S. (2013) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-013-1804-6 · Cited by 26
Guo, S., Xu, J., Wei, N., Han, J., Xue, R., Xu, P., & Gao, C. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190324 · Cited by 24
Acute fluoride exposure alters myocardial redox and inflammatory markers in rats
Panneerselvam, L., Raghunath, A., Sundarraj, K., & Perumal, E. (2019) · Molecular Biology Reports · doi:10.1007/s11033-019-05050-9 · Cited by 20
Treatment effects of Cardiotrophin-1 (CT-1) on streptozotocin-induced memory deficits in mice
Wang, D., Liu, X., Liu, Y., Shen, G., Zhu, X., & Li, S. (2017) · Experimental Gerontology · doi:10.1016/j.exger.2017.03.007 · Cited by 16
Self-citationZhuang, Q., Pan, R., Liu, X., Xu, W., Wang, H., Zhang, X., Lai, X., Wang, H., Zhang, L., & Jiang, J. (2019) · Bioanalysis · doi:10.4155/bio-2019-0030 · Cited by 10
Liang, Y., Cui, G., Wang, X., Zhang, W., An, Q., Lin, Z., Wang, H., & Chen, S. (2014) · Biomedical Chromatography · doi:10.1002/bmc.3179 · Cited by 9
Cited by
Sorted by citations
The sirtuin family in health and disease
Wu, Q., Zhang, T., Chen, H., Yu, X., Lv, J.-L., Liu, Y., Liu, Y., Zheng, G., Zhao, J.-Q., Wei, Y., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01257-8 · Cited by 928
New insights into the role of mitochondrial dynamics in oxidative stress-induced diseases
Chen, S., Li, Q., Shi, H., Li, F., Duan, Y., & Guo, Q. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117084 · Cited by 250
Xie, Z., Zhang, M., Luo, Y., Jin, D., Guo, X., Yang, W., Zheng, J., Zhang, H., Zhang, L., Deng, C., et al. (2023) · Aging and disease · doi:10.14336/ad.2023.0309 · Cited by 80
“Intriguingly, intestinal AMPK, which can directly or indirectly interact with SOD2 [24, 25], was discovered to be modulated by microbiota [26].”
He, W., Tang, P., & Lv, H. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1571576 · Cited by 67
Wang, D., Yin, K., Zhang, Y., Lu, H., Hou, L., Zhao, H., & Xing, M. (2023) · Environmental Pollution · doi:10.1016/j.envpol.2023.121847 · Cited by 57
Self-citation
Metadata
- Authors
- Wang, D., Cao, L., Zhou, X., Wang, G., Ma, Y., Hao, X., & Fan, H.
- Affiliations
- Henan University of Science and Technology (CN)
- First Affiliated Hospital of Henan University of Science and Technology (CN)
- Corresponding author
- Wang, Dongmei
- Fan, Hua
- Venue
- Journal of Hazardous Materials
- Publisher
- Elsevier BV
- Published
- 2022-09
- Volume
- 437
- Pages
- 129381
- ISSN
- 0304-3894 (ISSN-L)
- OpenAlex
- W4283010307
- Cited by
- 186
- References
- 71
- Citations by year
- 2026: 59 · 2025: 53 · 2024: 53 · 2023: 19 · 2022: 2
- FWCI
- 10.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Journal of Hazardous Materials (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Physical Sciences › Environmental Science › Water Science and Technology › Fluoride Effects and Removal
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Magnolia and Illicium research
- Keywords
- honokiol, fluoride toxicity, sodium fluoride, mitochondrial oxidative stress, mitochondrial dysfunction, cognitive impairment, AMPK, PGC-1α, SIRT3, mitochondrial reactive oxygen species, manganese superoxide dismutase, mitochondrial transcription, ATP production, complex I activity, neuronal injury, synaptic injury, neuroprotection
- MeSH terms
- Allyl Compounds, Animals, Biphenyl Compounds, Cognition, DNA, Mitochondrial, Fluorides, Humans, Mitochondria, Neuroblastoma, Phenols, Lignans, Oxidative Stress, RNA, Small Interfering, Mice, AMP-Activated Protein Kinases, Sirtuin 3, Cognitive Dysfunction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review