Berberine Attenuates Brain Aging via Stabilizing Redox Homeostasis and Inflammation in an Accelerated Senescence Model of Wistar Rats
Abstract
Aging is a multifaceted and progressive physiological change of the organism categorized by the accumulation of deteriorating processes, which ultimately compromise the biological functions. The objective of this study was to investigate the anti-aging potential of berberine (BBR) in D-galactose (D-Gal) induced aging in rat models. In this study, male Wistar rats were divided into four groups: The control group was given only vehicle, the BBR group was treated with berberine orally, the D-Gal group was treated with D-galactose subcutaneously and the BBR + D-Gal group was treated with D-galactose and berberine simultaneously. D-galactose exposure elevated the pro-oxidants such as malondialdehyde (MDA) level, protein carbonyl and advanced oxidation protein products (AOPP) in the brain. It decreased the anti-oxidants such as reduced glutathione (GSH) and ferric reducing antioxidant potential (FRAP) in the brain. D-galactose treatment also reduced the mitochondrial complexes (I, II, III and IV) activities and elevated the inflammatory markers such as interleukine-6 (IL-6), tumor necrosis factor- α (TNF-α) and C-reactive protein (CRP). The mRNA expressions of IL-6 and TNF-α in the brain were upregulated following D-galactose exposure. Berberine co-treatment in D-galactose induced aging rat model prevented the alteration of pro-oxidant and anti-oxidant in the brain. Berberine treatment restored the mitochondrial complex activities in the brain and also normalized the inflammatory markers. Based on these findings we conclude that berberine treatment has the potential to mitigate brain aging in rats via stabilizing the redox equilibrium and neuroinflammation.
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In aging rodent models, berberine restored mitochondrial complex activities, balanced redox homeostasis, and reduced neuroinflammation.
“In aging rodent models, berberine restored mitochondrial complex activities, balanced redox homeostasis, and reduced neuroinflammation, thus supporting its role in mitigating brain aging”
From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [109]
Cites
The Ferric Reducing Ability of Plasma (FRAP) as a Measure of “Antioxidant Power”: The FRAP Assay
Benzie, I. F. F., & Strain, J. (1996) · Analytical Biochemistry · doi:10.1006/abio.1996.0292 · Cited by 23,027 · see citing works
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982 · see citing works
Free radicals and antioxidants in normal physiological functions and human disease
Valko, M., Leibfritz, D., Moncol, J., Cronin, M. T. D., Mazur, M., & Telser, J. (2007) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2006.07.001 · Cited by 14,269 · see citing works
Hallmarks of aging: An expanding universe
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2023) · Cell · doi:10.1016/j.cell.2022.11.001 · Cited by 6,549 · see citing works
Chronic inflammation in the etiology of disease across the life span
Furman, D., Campisi, J., Verdin, E., Carrera-Bastos, P., Targ, S., Franceschi, C., Ferrucci, L., Gilroy, D. W., Fasano, A., Miller, G. W., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0675-0 · Cited by 4,915 · see citing works
Advanced oxidation protein products as a novel marker of oxidative stress in uremia
Witko‐Sarsat, V., Friedlander, M. A., Capeillère‐Blandin, C., Nguyen‐Khoa, T., Nguyen, A., Zingraff, J., Jungers, P., & Descamps‐Latscha, B. (1996) · Kidney International · doi:10.1038/ki.1996.186 · Cited by 2,000 · see citing works
Reactive Oxygen-Mediated Protein Oxidation in Aging and Disease
Stadtman, E. R., & Berlett, B. S. (1998) · Drug Metabolism Reviews · doi:10.3109/03602539808996310 · Cited by 892 · see citing works
Witko‐Sarsat, V., Friedlander, M. A., Nguyen‐Khoa, T., Capeillère‐Blandin, C., Nguyen, A., Canteloup, S., Dayer, J., Jungers, P., Drüeke, T. B., & Descamps‐Latscha, B. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.5.2524 · Cited by 879 · see citing works
Bonnard, C., Durand, A., Peyrol, S., Chanseaume, E., Chauvin, M.-A., Morio, B., Vidal, H., & Rieusset, J. (2008) · Journal of Clinical Investigation · doi:10.1172/jci32601 · Cited by 819 · see citing works
Role of Mitochondrial Ca2+ in the Regulation of Cellular Energetics
Glancy, B. C., & Balaban, R. S. (2012) · Biochemistry · doi:10.1021/bi2018909 · Cited by 649 · see citing works
Metabolic Syndrome, Aging and Involvement of Oxidative Stress
Bonomini, F., Rodella, L. F., & Rezzani, R. (2015) · Aging and Disease · doi:10.14336/ad.2014.0305 · Cited by 599 · see citing works
Berberine: a plant alkaloid with therapeutic potential for central nervous system disorders
Kulkarni, S. K., & Dhir, A. (2009) · Phytotherapy Research · doi:10.1002/ptr.2968 · Cited by 367 · see citing works
Mitochondrial biogenesis in neurodegeneration
Li, P. A., Hou, X., & Hao, S. (2017) · Journal of Neuroscience Research · doi:10.1002/jnr.24042 · Cited by 353 · see citing works
Role of D-galactose-induced brain aging and its potential used for therapeutic interventions
Shwe, T., Pratchayasakul, W., Chattipakorn, N., & Chattipakorn, S. C. (2017) · Experimental Gerontology · doi:10.1016/j.exger.2017.10.029 · Cited by 334 · see citing works
Mitochondrial dysfunction in brain aging: Role of oxidative stress and cardiolipin
Paradies, G., Petrosillo, G., Paradies, V., & Ruggiero, F. M. (2011) · Neurochemistry International · doi:10.1016/j.neuint.2010.12.016 · Cited by 220 · see citing works
Navarro, A., Gómez, C., Sánchez-Pino, M.-J., González, H., Bández, M. J., Boveris, A. D., & Boveris, A. (2005) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00834.2004 · Cited by 209 · see citing works
Qin, X., Jiang, M., Zhao, Y., Gong, J., Su, H., Yuan, F., Fang, K., Yuan, X., Yu, X., Dong, H., et al. (2019) · British Journal of Pharmacology · doi:10.1111/bph.14935 · Cited by 192 · see citing works
Hussien, H. M., Abd-Elmegied, A., Ghareeb, D. A., Hafez, H. S., Ahmed, H. E. A., & Moneam, N. M. A. E. (2017) · Food and Chemical Toxicology · doi:10.1016/j.fct.2017.11.025 · Cited by 176 · see citing works
Lu, D., Tang, C., Chen, Y., & Wei, I. (2010) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22580 · Cited by 151 · see citing works
Sadigh‐Eteghad, S., Majdi, A., McCann, S., Mahmoudi, J., Vafaee, M. S., & Macleod, M. R. (2017) · PLoS ONE · doi:10.1371/journal.pone.0184122 · Cited by 148 · see citing works
Antiaging Effect of Metformin on Brain in Naturally Aged and Accelerated Senescence Model of Rat
Garg, G., Singh, S., Singh, A. K., & Rizvi, S. I. (2016) · Rejuvenation Research · doi:10.1089/rej.2016.1883 · Cited by 116 · see citing works
Self-citationBerberine Attenuates Experimental Autoimmune Encephalomyelitis in C57 BL/6 Mice
Ma, X., Jiang, Y., Wu, A., Chen, X., Pi, R., Liu, M., & Liu, Y. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013489 · Cited by 110 · see citing works
Bektas, A., Schurman, S. H., Franceschi, C., & Ferrucci, L. (2020) · Immunity & Ageing · doi:10.1186/s12979-020-00196-8 · Cited by 102 · see citing works
Chen, C.-C., Hung, T.-H., Lee, C.-Y., Wang, L., Wu, C.-H., Ke, C.-H., & Chen, S.-F. (2014) · PLoS ONE · doi:10.1371/journal.pone.0115694 · Cited by 101 · see citing works
Berberine: A novel therapeutic strategy for cancer
Samadi, P., Sarvarian, P., Gholipour, E., Asenjan, K. S., Maleki, L. A., Motavalli, R., Hojjat‐Farsangi, M., & Yousefi, M. (2020) · IUBMB Life · doi:10.1002/iub.2350 · Cited by 101 · see citing works
Protein and DNA Oxidation in Different Anatomic Regions of Rat Brain in a Mimetic Ageing Model
Yanar, K., Aydın, S., Çakatay, U., Mengi, M., Büyükpınarbaşılı, N., Atukeren, P., Sitar, M. E., Sönmez, A., & Uslu, E. (2011) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/j.1742-7843.2011.00756.x · Cited by 84 · see citing works
Berberine: A Plant-derived Alkaloid with Therapeutic Potential to Combat Alzheimer’s disease
Singh, A. K., Singh, S. K., Nandi, M. K., Mishra, G., Maurya, A., Rai, A., Rai, G. K., Awasthi, R., Sharma, B., & Kulkarni, G. T. (2019) · Central Nervous System Agents in Medicinal Chemistry · doi:10.2174/1871524919666190820160053 · Cited by 79 · see citing works
Self-citationEl‐Shiekh, R. A., Ashour, R. M. S., El-Haleim, E. A. A., Ahmed, K. A., & Abdel-Sattar, E. A. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110303 · Cited by 78 · see citing works
Bioactive Phytochemicals with Anti-Aging and Lifespan Extending Potentials in Caenorhabditis elegans
Okoro, N. O., Odiba, A. S., Osadebe, P. O., Omeje, E. O., Liao, G., Fang, W., Jin, C., & Wang, B. (2021) · Molecules · doi:10.3390/molecules26237323 · Cited by 73 · see citing works
Research progress on the pharmacological effects of berberine targeting mitochondria
Fang, X., Wu, H., Wei, J., Miao, R., Zhang, Y., & Tian, J. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.982145 · Cited by 72 · see citing works
Berberine suppresses gero-conversion from cell cycle arrest to senescence
Zhao, H., Halicka, H. D., Li, J., & Darżynkiewicz, Z. (2013) · Aging · doi:10.18632/aging.100593 · Cited by 70 · see citing works
Long, J., Wang, X., Gao, H., Liu, Z., Liu, C., Miao, M., Cui, X., Packer, L., & Liu, J. (2007) · Biogerontology · doi:10.1007/s10522-007-9081-y · Cited by 67 · see citing works
Lipid lowering agents of natural origin: An account of some promising chemotypes
Singh, S. P., & Sashidhara, K. V. (2017) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2017.09.020 · Cited by 66 · see citing works
Mitochondrial alterations in aging rat brain: effective role of (−)‐epigallo catechin gallate
Srividhya, R., Žarković, K., Štroser, M., Waeg, G., Žarković, N., & Kalaiselvi, P. (2009) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2009.01.003 · Cited by 55 · see citing works
Chronic D-galactose administration induces natural aging characteristics, in rat’s brain and heart
Pantiya, P., Thonusin, C., Ongnok, B., Chunchai, T., Kongkaew, A., Nawara, W., Arunsak, B., Chattipakorn, N., & Chattipakorn, S. C. (2023) · Toxicology · doi:10.1016/j.tox.2023.153553 · Cited by 44 · see citing works
Pretreatment with berberine protects against cisplatin-induced renal injury in male Wistar rats
Allameh, H., Fatemi, I., Malayeri, A., Nesari, A., Mehrzadi, S., & Goudarzi, M. (2020) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-020-01877-3 · Cited by 40 · see citing works
Sadigh‐Eteghad, S., Majdi, A., McCann, S., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0190328 · Cited by 39 · see citing works
Song, B., Tang, X., Wang, X., Huang, X., Ye, Y., Lu, X., Wei, X., & Zeng, Y. (2012) · Cellular Immunology · doi:10.1016/j.cellimm.2012.04.006 · Cited by 34 · see citing works
Zhuang, J., Chen, X., Cai, G., Wu, D.-Z., Tu, C., Zhu, S., Huang, Y., Xu, P., & Zhong, Z. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-04441-w · Cited by 29 · see citing works
Gendy, A. M., Soubh, A. A., Elnagar, M. R., Hamza, E., Ahmed, K. A., Aglan, A., El-Haddad, A. E., Farag, M. A., & El-Sadek, H. M. (2023) · Food and Chemical Toxicology · doi:10.1016/j.fct.2023.113721 · Cited by 29 · see citing works
Ji, Z.-H., Liu, C., Hong, Z., et al. (2014) · Journal of Molecular Neuroscience · doi:10.1007/s12031-014-0407-3 · Cited by 27 · see citing works
Zych, M., Wojnar, W., Kielanowska, M., Folwarczna, J., & Kaczmarczyk‐Sedlak, I. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124278 · Cited by 26 · see citing works
Seth, E., Ahsan, A. U., Kaushal, S., et al. (2021) · Pesticide Biochemistry and Physiology · doi:10.1016/j.pestbp.2021.104977 · Cited by 25 · see citing works
El‐Horany, H. E., Gaballah, H. H., & Helal, D. S. (2018) · Archives of Physiology and Biochemistry · doi:10.1080/13813455.2018.1499117 · Cited by 24 · see citing works
Liu, B., Xie, Y., Chen, J., et al. (2021) · Journal of Inflammation Research · doi:10.2147/jir.s332286 · Cited by 24 · see citing works
Singh, A. K., Singh, S., Garg, G., & Rizvi, S. I. (2017) · Archives of Physiology and Biochemistry · doi:10.1080/13813455.2017.1359629 · Cited by 23 · see citing works
Self-citationDsbA-L ameliorates renal aging and renal fibrosis by maintaining mitochondrial homeostasis
Yang, M., Liu, Y., Luo, S., Liu, C., Jiang, N., Li, C., Zhao, H., Han, Y., Chen, W., Li, L., et al. (2024) · Acta Pharmacologica Sinica · doi:10.1038/s41401-023-01216-1 · Cited by 23 · see citing works
d-galactose induced inflammation lipid peroxidation and platelet activation in rats
Hadzi‐Petrushev, N., Stojkovski, V., Mitrov, D., et al. (2014) · Cytokine · doi:10.1016/j.cyto.2014.05.006 · Cited by 21 · see citing works
Li, F., Huang, H. Y., Wu, Y., Lu, Z., Zhou, X., Tan, F., & Zhao, X. (2021) · Food & Function · doi:10.1039/d1fo00982f · Cited by 21 · see citing works
Liu, J., Chen, H., Yu, T., Fu, X., Qian, C., & Feng, X. (2023) · Aging · doi:10.18632/aging.204642 · Cited by 20 · see citing works
Entropy Meets Physiology: Should We Translate Aging as Disorder?
Tatullo, M. (2023) · Stem Cells · doi:10.1093/stmcls/sxad084 · Cited by 16 · see citing works
Biochemical and metabolomic insights into antifungal mechanism of berberine against Candida glabrata
Gupta, P., Gupta, H., Tripathi, S., et al. (2023) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-023-12714-x · Cited by 15 · see citing works
Can Berberine Serve as a New Therapy for Parkinson’s Disease?
Dadgostar, E., Moghanlou, M., Parvaresh, M., Mohammadi, S., Khandan, M., Aschner, M., Mirzaei, H., & Tamtaji, O. R. (2022) · Neurotoxicity Research · doi:10.1007/s12640-022-00526-2 · Cited by 13 · see citing works
Comparative effects of berberine and piperine on the neuroprotective potential of neostigmine
Adefegha, S. A., Oboh, G., & Okeke, B. M. (2021) · Journal of Complementary and Integrative Medicine · doi:10.1515/jcim-2020-0055 · Cited by 9 · see citing works
Wang, P., Wang, X., Wang, Q., Jiao, Y., Wang, X., Chen, C., Chen, H., & Song, T. (2023) · Brain Research · doi:10.1016/j.brainres.2023.148372 · Cited by 9 · see citing works
Chitosan Displays a Potent Caloric Restriction Mimetic Effect in Senescent Rats
Kumar, R., Kumar, M., & Rizvi, S. I. (2021) · Rejuvenation Research · doi:10.1089/rej.2021.0010 · Cited by 8 · see citing works
Self-citationBerberine may provide redox homeostasis during aging in rats
Yadawa, A. K., Srivastava, P., Singh, A. L., et al. (2023) · Zeitschrift für Naturforschung C · doi:10.1515/znc-2022-0213 · Cited by 8 · see citing works
Self-citationTong, T., Guo, J., Wu, Y., Sharma, D., Sangar, M., Sangpreecha, N., Song, D., Unno, T., Ham, K., & Kang, S. (2023) · Journal of the Science of Food and Agriculture · doi:10.1002/jsfa.12958 · Cited by 8 · see citing works
The microRNA-mediated gene regulatory network in the hippocampus and hypothalamus of the aging mouse
Munkhzul, C., Yi, S. S., Kim, J., Lee, S., Kim, H.-T., Moon, J., & Lee, M. (2023) · PLoS ONE · doi:10.1371/journal.pone.0291943 · Cited by 4 · see citing works
Luo, H., Kou, T., Su, Y., et al. (2023) · Cardiovascular Diagnosis and Therapy · doi:10.21037/cdt-22-464 · Cited by 1 · see citing works
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Tero-Vescan, A., Degens, H., Matsakas, A., Ștefănescu, R., Ősz, B. E., & Slevin, M. (2025) · Pharmaceuticals · doi:10.3390/ph18081222 · Cited by 44 · see citing works
“In aging rodent models, berberine restored mitochondrial complex activities, balanced redox homeostasis, and reduced neuroinflammation, thus supporting its role in mitigating brain aging [109].”
- Authors
- Yadawa, A. K., Srivastava, P., Singh, A., Kumar, R., Arya, J. K., & Rizvi, S. I.
- Affiliations
- University of Allahabad (IN)
- Corresponding author
- Yadawa, Arun Kumar
- Srivastava, Parisha
- Singh, Akanksha
- Kumar, Raushan
- Arya, Jitendra Kumar
- Rizvi, Syed Ibrahim
- ORCID
- Venue
- Metabolic Brain Disease
- Published
- 2024-05-10
- Volume
- 39
- Issue
- 5
- Pages
- 649-659
- ISSN
- 0885-7490 (ISSN-L)
- 1573-7365
- OpenAlex
- W4396805293
- Cited by
- 10
- References
- 60
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 1
- FWCI
- 1.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Metabolic Brain Disease (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Antioxidants, Aging, Portulaca oleracea
- Health Sciences › Medicine › Pharmacology › Berberine and alkaloids research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- berberine, brain aging, D-galactose-induced aging, redox homeostasis, oxidative stress, neuroinflammation, mitochondrial complex activity, advanced oxidation protein products, malondialdehyde, interleukin-6, TNF-α, C-reactive protein, anti-aging
- MeSH terms
- Aging, Animals, Antioxidants, Berberine, Brain, Galactose, Homeostasis, Inflammation, Male, Oxidation-Reduction, Rats, Wistar, Oxidative Stress, Rats
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