Skip to main content

Advertisement

SpringerLink
Log in

Neuroprotective Potential of Berberine Against Doxorubicin-Induced Toxicity in Rat’s Brain

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Chemotherapy-associated neurotoxicity is one of the principal side-effects for doxorubicin (DOX)-treated cancer patients. Despite its poor-penetration across the blood–brain barrier (BBB), DOX is linked to the induction of oxidative stress and neuroinflammation. Berberine (BEB) is a natural polyphenolic alkaloid, which exhibits unique antioxidant activity and anti-inflammatory potential. The present study was performed to investigate the neuroprotective potential of BEB in a rodent model of DOX-induced neurotoxicity. Neurotoxicity was induced in rats via a single acute dose of DOX (20 mg/kg/week, i.p.). BEB was administered at 50 mg/kg/day orally for 10 days before and 4 days after DOX administration. Brain acetylcholinesterase (AChE) activities were evaluated. Oxidative stress was investigated via the colorimetric determination of lipid peroxides, glutathione reduced (GSH) contents and catalase (CAT) activities in the brain tissue. In addition, DOX-induced genotoxicity was evaluated using comet assay. DOX produced a significant elevation in AChE activities. Additionally, DOX provoked oxidative stress as evidenced from the significant elevation in lipid peroxidation along with depletion in GSH contents and CAT activities. Moreover, DOX resulted in neuroinflammation as indicated by the elevation of pro-inflammatory mediator glial fibrillary acid protein (GFAP), as well as, the pro-apoptotic nuclear factor kappa B (NF-κB) and caspase-3 in brain tissue. Co-treatment with BEB significantly counteracted DOX-induced oxidative stress, neuroinflammation and genotoxicity. Histopathological and immunohistochemical examination supported the biochemical results. BEB demonstrated neuroprotective potential through exerting cholinergic, anti-oxidative, genoprotective, anti-inflammatory, and anti-apoptotic activities. Our findings present BEB as a promising “pre-clinical” neuroprotective agent against DOX-induced neurotoxicity during anti-neoplastic therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

Data Availability

All data generated or analyzed during this study are included in this published article.

Abbreviations

DOX:

Doxorubicin

BBB:

Blood–brain barrier

BEB:

Berberine

AChE:

Acetylcholinesterase

GSH:

Glutathione reduced

CAT:

Catalase

GFAP:

Glial fibrillary acid protein

NF-κB:

Nuclear factor kappa B

ROS:

Reactive oxygen species

PUFAs:

Polyunsaturated fatty acids

References

  1. Schultz L, Zurich MG, Culot M, da Costa A, Landry C et al (2015) Evaluation of drug-induced neurotoxicity based on metabolomics, proteomics and electrical activity measurements in complementary CNS in vitro models. Toxicol In Vitro 30(1):138–165

    Article  CAS  PubMed  Google Scholar 

  2. Borai IH, Ezz MK, Rizk MZ, Aly HF, El-Sherbiny M, Matloub AA, Fouad GI (2017) Therapeutic impact of grape leaves polyphenols on certain biochemical and neurological markers in AlCl3-induced Alzheimer’s disease. Biomed Pharmacother 93:837–851

    Article  CAS  PubMed  Google Scholar 

  3. Ibrahim Fouad G (2021) The neuropathological impact of COVID-19: a review. Bull Natl Res Cent 45(1):1–9

    Article  Google Scholar 

  4. Ibrahim Fouad G (2020) Combination of omega 3 and coenzyme Q10 exerts neuroprotective potential against hypercholesterolemia-induced Alzheimer’s-like disease in rats. Neurochem Res 45(5):1142–1155. https://doi.org/10.1007/s11064-020-02996-2

    Article  CAS  PubMed  Google Scholar 

  5. Jordan B, Margulies A, Cardoso F, Cavaletti G, Haugnes HS et al (2020) Systemic anticancer therapy-induced peripheral and central neurotoxicity: ESMO–EONS–EANO Clinical Practice Guidelines for diagnosis, prevention, treatment and follow-up. Ann Oncol 31(10):1306–1319

    Article  CAS  PubMed  Google Scholar 

  6. Loghin ME, Kleiman A (2020) Medication-induced neurotoxicity in critically Ill cancer patients. In: Nates J, Price K (eds) Oncologic critical care. Springer, Cham, pp 319–334. https://doi.org/10.1007/978-3-319-74588-6_32

    Chapter  Google Scholar 

  7. Cavaletti G (2014) Chemotherapy-induced peripheral neurotoxicity (CIPN): what we need and what we know. J Peripher Nerv Syst 19(2):66–76. https://doi.org/10.1111/jns5.12073

    Article  PubMed  Google Scholar 

  8. Prša P, Karademir B, Biçim G et al (2020) The potential use of natural products to negate hepatic, renal and neuronal toxicity induced by cancer therapeutics. Biochem Pharmacol 173:113551

    Article  PubMed  CAS  Google Scholar 

  9. Eide S, Feng ZP (2020) Doxorubicin chemotherapy-induced “chemo-brain”: Meta-analysis. Eur J Pharmacol 881:173078

    Article  CAS  PubMed  Google Scholar 

  10. Cavaletti G, Alberti P, Marmiroli P (2015) Chemotherapy-induced peripheral neurotoxicity in cancer survivors: an underdiagnosed clinical entity? Am Soc Clin Oncol Educ Book. https://doi.org/10.14694/EdBook_AM.2015.35.e553

    Article  PubMed  Google Scholar 

  11. Aluise CD, Sultana R, Tangpong J et al (2010) Chemo brain (chemo fog) as a potential side effect of doxorubicin administration: role of cytokine-induced, oxidative/nitrosative stress in cognitive dysfunction. Chemo Fog 678:147–156

    Article  CAS  Google Scholar 

  12. Hayslip J, Dressler EV, Weiss H et al (2015) Plasma TNF-α and soluble TNF receptor levels after doxorubicin with or without co-administration of mesna—a randomized, cross-over clinical study. PloS One 10(4):e0124988

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Sinha BK, Mason RP (2015) Is metabolic activation of topoisomerase II poisons important in the mechanism of cytotoxicity? J Drug Metab Toxicol 6(3):186

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Aluise CD, Miriyala S, Noel T et al (2011) 2-Mercaptoethane sulfonate prevents doxorubicin-induced plasma protein oxidation and TNF-α release: implications for the reactive oxygen species-mediated mechanisms of chemobrain. Free Radic Biol Med 50(11):1630–1638

    Article  CAS  PubMed  Google Scholar 

  15. Brantley-Finley C, Lyle CS, Du L et al (2003) The JNK, ERK and p53 pathways play distinct roles in apoptosis mediated by the antitumor agents vinblastine, doxorubicin, and etoposide. Biochem Pharmacol 66(3):459–469

    Article  CAS  PubMed  Google Scholar 

  16. Cardinale D, Colombo A, Bacchiani G et al (2015) Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation 131(22):1981–1988

    Article  CAS  PubMed  Google Scholar 

  17. Heeba GH, Mahmoud ME (2016) Dual effects of quercetin in doxorubicin-induced nephrotoxicity in rats and its modulation of the cytotoxic activity of doxorubicin on human carcinoma cells. Environ Toxicol 31(5):624–636

    CAS  PubMed  Google Scholar 

  18. Guzel EE, Tektemur NK, Tektemur A (2021) Alpha-lipoic acid may ameliorate testicular damage by targeting dox-induced altered antioxidant parameters, mitofusin-2 and apoptotic gene expression. Andrologia 53:e13990

    Google Scholar 

  19. Liu X, Qiu Y, Liu Y et al (2021) Citronellal ameliorates doxorubicin-induced hepatotoxicity via antioxidative stress, antiapoptosis, and proangiogenesis in rats. Biochem Mol Toxicol 35(2):e22639

    Article  CAS  Google Scholar 

  20. Wang S, Konorev EA, Kotamraju S, Joseph J et al (2004) Doxorubicin induces apoptosis in normal and tumor cells via distinctly different mechanisms: intermediacy of H2O2-and p53-dependent pathways. Biol Chem 279(24):25535–25543

    Article  CAS  Google Scholar 

  21. Rashid S, Ali N, Nafees S et al (2013) Alleviation of doxorubicin-induced nephrotoxicity and hepatotoxicity by chrysin in Wistar rats. Toxicol Mech Method 23(5):337–345

    Article  CAS  Google Scholar 

  22. Kuzu M, Kandemir FM, Yildirim S, Kucukler S et al (2018) Morin attenuates doxorubicin-induced heart and brain damage by reducing oxidative stress, inflammation and apoptosis. Biomed Pharmacother 106:443–453

    Article  CAS  PubMed  Google Scholar 

  23. Silverman DH, Dy CJ, Castellon SA, Lai J, Pio BS, Abraham L et al (2007) Altered frontocortical, cerebellar, and basal ganglia activity in adjuvant-treated breast cancer survivors 5–10 years after chemotherapy. Breast Cancer Res Treat 103(3):303–311

    Article  CAS  PubMed  Google Scholar 

  24. Salas-Ramirez KY, Bagnall C, Frias L et al (2015) Doxorubicin and cyclophosphamide induce cognitive dysfunction and activate the ERK and AKT signaling pathways. Behav Brain Res 292:133–141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Keeney JT, Ren X, Warrier G, Noel T et al (2018) Doxorubicin-induced elevated oxidative stress and neurochemical alterations in brain and cognitive decline: protection by MESNA and insights into mechanisms of chemotherapy-induced cognitive impairment (“chemobrain”). Oncotarget 9(54):30324

    Article  PubMed  PubMed Central  Google Scholar 

  26. Merzoug S, Toumi ML, Boukhris N et al (2011) Adriamycin-related anxiety-like behavior, brain oxidative stress and myelotoxicity in male Wistar rats. Pharmacol Biochem Behav 99(4):639–647

    Article  CAS  PubMed  Google Scholar 

  27. Allen BD, Apodaca LA, Syage AR et al (2019) Attenuation of neuroinflammation reverses Adriamycin-induced cognitive impairments. Acta Neuropathol Commun 7(1):1–15

    Article  CAS  Google Scholar 

  28. Janelsins MC, Kesler SR, Ahles TA, Morrow GR (2014) Prevalence, mechanisms, and management of cancer-related cognitive impairment. Int Rev Psychiatry 26(1):102–113

    Article  PubMed  PubMed Central  Google Scholar 

  29. Sardi I, la Marca G, Cardellicchio S, Giunti L, Malvagia S, Genitori L et al (2013) Pharmacological modulation of blood–brain barrier increases permeability of doxorubicin into the rat brain. Am J Cancer Res 3(4):424

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Carrasco R, Ramirez MC, Nes K et al (2020) Prevention of doxorubicin-induced cardiotoxicity by pharmacological non-hypoxic myocardial preconditioning based on docosahexaenoic acid (DHA) and carvedilol direct antioxidant effects: study protocol for a pilot, randomized, double-blind, controlled trial (CarDHA trial). Trials 21(1):137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Sergazy S, Shulgau Z, Fedotovskikh G, Chulenbayeva L et al (2020) Cardioprotective effect of grape polyphenol extract against doxorubicin induced cardiotoxicity. Sci Rep 10(1):1–12

    Article  CAS  Google Scholar 

  32. Mohamed RH, Karam RA, Amer MGMG (2011) Epicatechin attenuates doxorubicin-induced brain toxicity: critical role of TNF-α, iNOS and NF-κB. Brain Res Bull 86(1–2):22–28

    Article  CAS  PubMed  Google Scholar 

  33. Stankovic JSK, Selakovic D, Mihailovic V, Rosic G (2020) Antioxidant supplementation in the treatment of neurotoxicity induced by platinum-based chemotherapeutics—a review. Int J Mol Sci 21(20):7753

    Article  CAS  PubMed Central  Google Scholar 

  34. Mohammed A, Janakiram NB, Pant S, Rao CV (2015) Molecular targeted intervention for pancreatic cancer. Cancers 7(3):1499–1542

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Yue Q, Gao G, Zou G, Yu H, Zheng X (2017) Natural products as adjunctive treatment for pancreatic cancer: recent trends and advancements. Biomed Res Int 2017:8412508

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Li L, Leung PS (2014) Use of herbal medicines and natural products: an alternative approach to overcoming the apoptotic resistance of pancreatic cancer. Int J Biochem Cell Biol 53:224–236

    Article  CAS  PubMed  Google Scholar 

  37. Li B, Gan R, Yang Q, Huang J, Chen P, Wan L, Guo C (2015) Chinese herbal medicines as an adjunctive therapy for unresectable pancreatic cancer: a systematic review and meta-analysis. Evid-Based Complement Alter Med. https://doi.org/10.1155/2015/350730

    Article  Google Scholar 

  38. Arayne MS, Sultana N, Bahadur SS (2007) The berberis story: Berberis vulgaris in therapeutics. Pak J Pharm Sci 20(1):83–92

    CAS  PubMed  Google Scholar 

  39. Singh IP, Mahajan S (2013) Berberine and its derivatives: a patent review (2009–2012). Expert Opin Ther Pat 23(2):215–231

    Article  CAS  PubMed  Google Scholar 

  40. Abd El-Wahab AE, Ghareeb DA, Sarhan EE, Abu-Serie MM, El Demellawy MA (2013) In vitro biological assessment of Berberis vulgaris and its active constituent, berberine: antioxidants, anti-acetylcholinesterase, anti-diabetic and anticancer effects. BMC Complement Altern Med 13(1):1–12

    Article  Google Scholar 

  41. Ghareeb DA, Khalil S, Hafez HS, Bajorath J, Ahmed HE et al (2015) Berberine reduces neurotoxicity related to nonalcoholic steatohepatitis in rats. Evid-Based Complement Altern Med. https://doi.org/10.1155/2015/361847

    Article  Google Scholar 

  42. Ahmad S, Hussain A, Hussain A, Abdullah I, Ali MS et al (2019) Quantification of berberine in Berberis vulgaris L. root extract and its curative and prophylactic role in cisplatin-induced in vivo toxicity and in vitro cytotoxicity. Antioxidants 8(6):185

    Article  CAS  PubMed Central  Google Scholar 

  43. Chen X, Zhang Y, Zhu Z, Liu H, Guo H et al (2016) Protective effect of berberine on doxorubicin-induced acute hepatorenal toxicity in rats. Mol Med Rep 13(5):3953–3960

    Article  CAS  PubMed  Google Scholar 

  44. Colvin LA (2019) Chemotherapy-induced peripheral neuropathy (CIPN): where are we now? Pain 160(Suppl 1):S1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Hajra S, Patra AR, Basu A, Bhattacharya S (2018) Prevention of doxorubicin (DOX)-induced genotoxicity and cardiotoxicity: effect of plant derived small molecule indole-3-carbinol (I3C) on oxidative stress and inflammation. Biomed Pharmacother 101:228–243

    Article  CAS  PubMed  Google Scholar 

  46. Verma T, Mallik SB, Ramalingayya GV, Nayak PG et al (2017) Sodium valproate enhances doxorubicin-induced cognitive dysfunction in Wistar rats. Biomed Pharmacother 96:736–741

    Article  CAS  PubMed  Google Scholar 

  47. Mohammed HS, Hosny EN, Khadrawy YA, Magdy M et al (1866) (2020) Protective effect of curcumin nanoparticles against cardiotoxicity induced by doxorubicin in rat. Biochim et Biophys Acta (BBA)-Mol Basis Dis 5:165665

    Google Scholar 

  48. Sadraie S, Kiasalari Z, Razavian M et al (2019) Berberine ameliorates lipopolysaccharide-induced learning and memory deficit in the rat: insights into underlying molecular mechanisms. Metab Brain Dis 34:245–255. https://doi.org/10.1007/s11011-018-0349-5

    Article  CAS  PubMed  Google Scholar 

  49. Ohkawa H et al (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95(2):351–358

    Article  CAS  PubMed  Google Scholar 

  50. Beutler E, Duron O, Kelly BM (1963) An improved method for the determination of blood glutathione. J Lab Clin Med 61:882–888

    CAS  PubMed  Google Scholar 

  51. Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126. https://doi.org/10.1016/s0076-6879(84)05016-3

    Article  CAS  PubMed  Google Scholar 

  52. Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175(1):184–191

    Article  CAS  PubMed  Google Scholar 

  53. Suvarna KS, Layton C, Bancroft JD (eds) (2018) Bancroft’s theory and practice of histological techniques E-Book. Elsevier Health Sciences, London

    Google Scholar 

  54. El-Shiekh RA, Ashour RM, Abd El-Haleim EA et al (2020) A potent natural neuroprotective agent for the prevention of streptozotocin-induced Alzheimer’s disease in mice. Biomed Pharmacother 128:110303

    Article  CAS  PubMed  Google Scholar 

  55. Park OK, Choi JH, Park JH, Kim IH, Yan BC, Ahn JH, Kwon SH, Lee JC, Kim YS, Kim M, Kang IJ, Kim JD, Lee YL, Won MH (2012) Comparison of neuroprotective effects of five major lipophilic diterpenoids from Danshen extract against experimentally induced transient cerebral ischemic damage. Fitoterapia 83:1666–1674

    Article  CAS  PubMed  Google Scholar 

  56. Youssef S, Abd-El-Aty OA, Mossalam M (2011) Effects of prenatal phenytoin toxicity on the expression of glial fibrillary acidic protein (GFAP) in the developing rat cerebellum. J Am Sci 7(8):139–152

    Google Scholar 

  57. Matsushita K, Wu Y, Qiu J, Lang-Lazdunski L et al (2000) Fas receptor and neuronal cell death after spinal cord ischemia. J Neurosci 20(18):6879–6887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Chin M, Yokoyama R, Sumi M, Okita H et al (2020) Multimodal treatment including standard chemotherapy with vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide for the Ewing sarcoma family of tumors in Japan: results of the Japan Ewing Sarcoma Study 04. Pediatr Blood Cancer 67(5):e28194

    Article  PubMed  Google Scholar 

  59. Leung WS, Kuo WW, Ju DT, Wang TD et al (2020) Protective effects of diallyl trisulfide (DATS) against doxorubicin-induced inflammation and oxidative stress in the brain of rats. Free Radic Biol Med 160:141–148

    Article  CAS  PubMed  Google Scholar 

  60. Pal S, Ahir M, Sil PC (2012) Doxorubicin-induced neurotoxicity is attenuated by a 43-kD protein from the leaves of Cajanus indicus L. via NF-κB and mitochondria dependent pathways. Free Radic Res 46(6):785–798

    Article  CAS  PubMed  Google Scholar 

  61. Khadrawy YA, Hosny EN, Mohammed HS (2021) Protective effect of nanocurcumin against neurotoxicity induced by doxorubicin in rat’s brain. NeuroToxicology 85:1

    Article  CAS  PubMed  Google Scholar 

  62. Patil S, Tawari S, Mundhada D, Nadeem S (2015) Protective effect of berberine, an isoquinoline alkaloid ameliorates ethanol-induced oxidative stress and memory dysfunction in rats. Pharmacol Biochem Behav 136:13–20

    Article  CAS  PubMed  Google Scholar 

  63. Hussien HM, Abd-Elmegied A, Ghareeb DA, Hafez HS et al (2018) Neuroprotective effect of berberine against environmental heavy metals-induced neurotoxicity and Alzheimer’s-like disease in rats. Food Chem Toxicol 111:432–444

    Article  CAS  PubMed  Google Scholar 

  64. Ji HF, Shen L (2012) Molecular basis of inhibitory activities of berberine against pathogenic enzymes in Alzheimer’s disease. Sci World J 2012:823201

    Article  CAS  Google Scholar 

  65. Patel M (2016) Targeting oxidative stress in central nervous system disorders. Trends Pharmacol Sci 37(9):768–778

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Islam MT (2017) Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders. Neurol Res 39(1):73–82

    Article  CAS  PubMed  Google Scholar 

  67. Shaker FH, El-Derany MO, Wahdan SA, El-Demerdash E, El-Mesallamy HO (2021) Berberine ameliorates doxorubicin-induced cognitive impairment (chemobrain) in rats. Life Sci 269:119078

    Article  CAS  PubMed  Google Scholar 

  68. Tangpong J, Cole MP, Sultana R et al (2007) Adriamycin-mediated nitration of manganese superoxide dismutase in the central nervous system: insight into the mechanism of chemobrain. Neurochemistry 100(1):191–201

    Article  CAS  Google Scholar 

  69. Mayer CA, Brunkhorst R, Niessner M, Pfeilschifter W et al (2013) Blood levels of glial fibrillary acidic protein (GFAP) in patients with neurological diseases. PloS ONE 8(4):e62101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Lei J, Gao G, Feng J, Jin Y et al (2015) Glial fibrillary acidic protein as a biomarker in severe traumatic brain injury patients: a prospective cohort study. Crit Care 19(1):1–12

    Article  Google Scholar 

  71. Sofroniew MV (2015) Astrocyte barriers to neurotoxic inflammation. Nat Rev Neurosci 16(5):249–263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Siracusa R, Fusco R, Cuzzocrea S (2019) Astrocytes: role and functions in brain pathologies. Front Pharmacol 10:1114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Cardoso CV, de Barros MP, Bachi ALL, Bernardi MM et al (2020) Chemobrain in rats: behavioral, morphological, oxidative and inflammatory effects of doxorubicin administration. Behav Brain Res 378:112233

    Article  CAS  PubMed  Google Scholar 

  74. Ali MA, Menze ET, Tadros MG, Tolba MF (2020) Caffeic acid phenethyl ester counteracts doxorubicin-induced chemobrain in Sprague-Dawley rats: emphasis on the modulation of oxidative stress and neuroinflammation. Neuropharmacology 181:108334

    Article  CAS  PubMed  Google Scholar 

  75. Rizk HA, Masoud MA, Maher OW (2017) Prophylactic effects of ellagic acid and rosmarinic acid on doxorubicin-induced neurotoxicity in rats. J Biochem Mol Toxicol 31(12):e21977

    Article  CAS  Google Scholar 

  76. Alhowail AH, Bloemer J, Majrashi M, Pinky PD et al (2019) Doxorubicin-induced neurotoxicity is associated with acute alterations in synaptic plasticity, apoptosis, and lipid peroxidation. Toxicol Mech Method 29(6):457–466

    Article  CAS  Google Scholar 

  77. Quiles JL, Huertas JR, Batino M, Mataix J, Ramirez-Tortosa MC (2002) Antioxidants nutrients and adriamycin toxicity. Toxicology 180:79–95

    Article  CAS  PubMed  Google Scholar 

  78. Choi SS, Lee HJ, Lim I, Satoh JI, Kim SU (2014) Human astrocytes: secretome profiles of cytokines and chemokines. PloS One 9(4):e92325

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Liu T, Zhang L, Joo D, Sun SC (2017) NF-κB signaling in inflammation. Signal Transduct Target Ther 2(1):1–9

    CAS  Google Scholar 

  80. Mattson MP, Kroemer G (2003) Mitochondria in cell death: novel targets for neuroprotection and cardioprotection. Trends Mol Med 9:196–205

    Article  CAS  PubMed  Google Scholar 

  81. Ongnok B, Chattipakorn N, Chattipakorn SC (2020) Doxorubicin and cisplatin induced cognitive impairment: the possible mechanisms and interventions. Exp Neurol 324:113118

    Article  CAS  PubMed  Google Scholar 

  82. Moneim AEA (2015) The neuroprotective effect of berberine in mercury-induced neurotoxicity in rats. Metab Brain Dis 30(4):935–942

    Article  PubMed  CAS  Google Scholar 

  83. Sadeghnia HR, Kolangikhah M, Asadpour E, Forouzanfar F et al (2017) Berberine protects against glutamate-induced oxidative stress and apoptosis in PC12 and N2a cells. Iran J Basic Med Sci 20(5):594

    PubMed  PubMed Central  Google Scholar 

  84. Zhang Z, Li X, Li FL (2016) An, Berberine alleviates postoperative cognitive dysfunction by suppressing neuroinflammation in aged mice. Int Immunopharmacol 38:426–433

    Article  CAS  PubMed  Google Scholar 

  85. Ren Z, He H, Zuo Z, Xu Z, Wei Z, Deng J (2019) The role of different SIRT1-mediated signaling pathways in toxic injury. Cell Mol Biol Lett 24:36

    Article  PubMed  PubMed Central  Google Scholar 

  86. Zhang Q, Qian Z, Pan L, Li H, Zhu H (2012) Hypoxia-inducible factor 1 mediates the anti-apoptosis of berberine in neurons during hypoxia/ischemia. Acta Physiol Hung 99(3):311–323

    Article  CAS  PubMed  Google Scholar 

  87. Wu YZ, Zhang L, Wu ZX, Shan TT, Xiong C (2019) Berberine ameliorates doxorubicin-induced cardiotoxicity via a SIRT1/p66Shc-mediated pathway. Oxid Med Cell Longev 2019:2150394

    Article  PubMed  PubMed Central  Google Scholar 

  88. Wang J, Zhang Y (2018) Neuroprotective effect of berberine agonist against impairment of learning and memory skills in severe traumatic brain injury via Sirt1/p38 MAPK expression. Mol Med Rep 17(5):6881–6886

    CAS  PubMed  Google Scholar 

  89. Rausch CR, Jabbour EJ, Kantarjian HM, Kadia TM (2020) Optimizing the use of the hyperCVAD regimen: clinical vignettes and practical management. Cancer 126(6):1152–1160

    Article  PubMed  Google Scholar 

Download references

Funding

No funding was received to assist with the preparation of this manuscript.

Author information

Authors and Affiliations

  1. Department of Therapeutic Chemistry, National Research Centre, 33 El-Bohouth St., Dokki, Cairo, 12622, Egypt

    Ghadha Ibrahim Fouad

  2. Pathology Department, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt

    Kawkab A. Ahmed

Authors
  1. Ghadha Ibrahim Fouad
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kawkab A. Ahmed
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

GIF conceived and designed the research proposal, performed experiments, analyzed biochemical data, and wrote the original manuscript. KAA was responsible for methodology and writing of histopathological and immunohistochemical investigations and review of the original manuscript.

Corresponding author

Correspondence to Ghadha Ibrahim Fouad.

Ethics declarations

Conflict of interest

The authors have no conflict of interest to declare that are relevant to the content of this article.

Ethical Approval

The animal protocol was adopted in accordance with the National Research Council’s Guide for the Care and Use of Laboratory Animals (NIH Publications No. 8023, revised 1978), and experimental procedures were approved by the Ethical Committee, National Research Centre (NRC), Egypt (Approval no. 19–313).

Consent to Participate

All authors gave their consent to participate in the present study.

Consent for Publication

All authors gave approval to publish the present study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ibrahim Fouad, G., Ahmed, K.A. Neuroprotective Potential of Berberine Against Doxorubicin-Induced Toxicity in Rat’s Brain. Neurochem Res 46, 3247–3263 (2021). https://doi.org/10.1007/s11064-021-03428-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-021-03428-5

Keywords

Search

Navigation