Author(s):
Trilochan Satapathy, Arun Kumar Sahu
Email(s):
drtsatapathy@gmail.com , arunkusahu22@gmail.com
DOI:
10.52711/2321-5836.2025.00037 
Address:
Trilochan Satapathy1*, Arun Kumar Sahu2
1Professor and HOD, Department of Pharmacology, Columbia Institute of Pharmacy, Near Vidhan Sabha, Tekari, Raipur (Chhattisgarh) 493111, India.
2Research Scholar, Department of Pharmacology, Columbia Institute of Pharmacy, Near Vidhan Sabha, Tekari, Raipur (Chhattisgarh) 493111, India.
*Corresponding Author
Published In:
Volume - 17,
Issue - 3,
Year - 2025
ABSTRACT:
Neurodegenerative disorders (NDDs), including Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD), are characterized by progressive neuronal loss, oxidative stress, mitochondrial dysfunction, and neuroinflammation. Despite advances in research, effective therapeutic interventions remain limited. Berberis aristata, a medicinal plant rich in berberine, has gained attention for its neuroprotective potential due to its antioxidant, anti-inflammatory, and mitochondrial-supporting properties. This review highlights the phytochemical profile of Berberis aristata and its multiple neuroprotective mechanisms, including inhibition of oxidative stress, mitochondrial dysfunction, apoptosis, neuroinflammation, and excitotoxicity. Preclinical in vitro and in vivo studies suggest that berberine enhances synaptic plasticity, modulates neurotransmitter levels, reduces amyloid-ß accumulation in AD, protects dopaminergic neurons in PD, and facilitates autophagic clearance of protein aggregates in HD. Additionally, Berberis aristata exhibits synergistic effects with conventional neuroprotective therapies. However, clinical evidence remains scarce, necessitating further human trials to determine its efficacy, bioavailability, and long-term safety. Standardization of extracts, optimization of dosing, and elucidation of molecular mechanisms are crucial for future therapeutic applications. Given its multi-targeted neuroprotective effects, Berberis aristata holds promise as a complementary or alternative strategy in the management of neurodegenerative disorders.
Cite this article:
Trilochan Satapathy, Arun Kumar Sahu. PotentiaNeuroprotective effects of Berberis aristata in Neurodegenerative Disorders: A Comprehensive Review of Preclinical and Clinical Evidence. Research Journal of Pharmacology and Pharmacodynamics.2025;17(3):227-4. doi: 10.52711/2321-5836.2025.00037
Cite(Electronic):
Trilochan Satapathy, Arun Kumar Sahu. PotentiaNeuroprotective effects of Berberis aristata in Neurodegenerative Disorders: A Comprehensive Review of Preclinical and Clinical Evidence. Research Journal of Pharmacology and Pharmacodynamics.2025;17(3):227-4. doi: 10.52711/2321-5836.2025.00037 Available on: https://rjppd.org/AbstractView.aspx?PID=2025-17-3-12
REFERENCES:
1. Przedborski, S., Vila, M., and Jackson-Lewis, V. Neurodegeneration: What is it and where are we? The Journal of Clinical Investigation. 2003; 111(1): 3–10. https://doi.org/10.1172/JCI17522
2. Lin, M. T., and Beal, M. F. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature. 2006; 443(7113): 787–795. https://doi.org/10.1038/nature05292
3. Heneka, M. T., et al. Neuroinflammation in Alzheimer’s disease. The Lancet Neurology. 2015; 14(4): 388–405. https://doi.org/10.1016/S1474-4422(15)70016-5
4. Maher, P. The potential of flavonoids for the treatment of neurodegenerative diseases. International Journal of Molecular Sciences. 2015; 16(10): 22830–22855. https://doi.org/10.3390/ijms161022830
5. Cummings, J., et al. Advances in drug development for neurodegenerative disorders. Nature Reviews Drug Discovery. 2021; 20: 729–749. https://doi.org/10.1038/s41573-021-00194-1
6. Singh, T., et al. Berberine: A plant alkaloid with therapeutic potential for central nervous system disorders. Biomedicine and Pharmacotherapy. 2021; 138: 111558. https://doi.org/10.1016/j.biopha.2021.111558
7. Feigin, V. L., et al. Global, regional, and national burden of neurological disorders, 1990–2019: A systematic analysis for the Global Burden of Disease Study 2019. The Lancet Neurology. 2021; 20(9): 795–820. https://doi.org/10.1016/S1474-4422(21)00252-4
8. Gourie-Devi, M. Epidemiology of neurological disorders in India: Review of background, prevalence and incidence of epilepsy, stroke, Parkinson's disease and tremors. Neurology India. 2018; 66(Suppl. S1): S9–S16. https://doi.org/10.4103/0028-3886.226456
9. Singh, S., Nagalakshmi, D., Sharma, K. K., and Ravichandiran, V. Natural antioxidants for neuroinflammatory disorders and possible involvement of Nrf2 pathway: A review. Heliyon. 2021; 7(2): e06216. https://doi.org/10.1016/j.heliyon.2021.e06216
10. Wu, A. G., Yong, Y. Y., Pan, Y. R., Zhang, L., Wu, J. M., Zhang, Y., et al. Targeting Nrf2-mediated oxidative stress response in traumatic brain injury: Therapeutic perspectives of phytochemicals. Oxidative Medicine and Cellular Longevity. 2022; 2022: 1015791. https://doi.org/10.1155/2022/1015791
11. Hira, T., Sato, Y., and Okamoto, T. β-carotene supplementation improves cognitive function and reduces oxidative stress in Alzheimer's disease patients. Journal of Nutritional Science and Vitaminology. 2019; 65(3): 229–235. https://doi.org/10.3177/jnsv.65.229
12. Li, F. J., Shen, L., and Ji, H. F. Dietary intakes of vitamin E, vitamin C, and β-carotene and risk of Alzheimer's disease: A meta-analysis. Journal of Alzheimer's Disease. 2012; 31(2): 253–258. https://doi.org/10.3233/JAD-2012-120349
13. Kong, W. J., et al. Berberine reduces inflammation in microglial cells by suppressing the activation of NF-κB and MAPK signaling pathways. International Immunopharmacology. 2012; 12(1): 38–45. https://doi.org/10.1016/j.intimp.2011.10.011
14. Liu, C. S., Zheng, Y. R., Zhang, Y. F., and Long, X. Y. Research progress on berberine with a special focus on its oral bioavailability. Fitoterapia. 2016; 109: 274–282. https://doi.org/10.1016/j.fitote.2016.02.001
15. Xie, Q., et al. Berberine ameliorates cognitive deficits by inhibiting neuroinflammation via PI3K/Akt-mediated suppression of microglial activation in Alzheimer’s disease model. Neurochemistry International. 2023; 162: 105465. https://doi.org/10.1016/j.neuint.2023.105465
16. Zhou, H., et al. Berberine alleviates neuroinflammation-induced damage by regulating the Akt/GSK3β signaling pathway in an ischemic brain injury model. European Journal of Pharmacology. 2019; 852: 1–10. https://doi.org/10.1016/j.ejphar.2019.02.027
17. Wang, Y., et al. (). Berberine induces autophagic cell death and mitochondrial apoptosis in human malignant lymphoblasts. Biochemical Pharmacology. 2019; 168: 45–57. https://doi.org/10.1016/j.bcp.2019.06.003
18. Liu, J., et al. (2015). Berberine induces autophagy in glioblastoma cells via the AMPK/mTOR signaling pathway. Molecular Medicine Reports. 11(6); 4117–4122. https://doi.org/10.3892/mmr.2015.3300
19. Jiang, W., et al. Berberine ameliorates motor dysfunction in a Huntington's disease mouse model by promoting autophagy. Frontiers in Pharmacology. 2019; 10: 862. https://doi.org/10.3389/fphar.2019.00862
20. Wu, Y., et al. Berberine protects against neurodegeneration through inducing autophagy and regulating NLRP3 inflammasome in Alzheimer’s disease model. Journal of Neuroinflammation. 2019; 16: 76. https://doi.org/10.1186/s12974-019-1463-7
21. Wang, Y., et al. Berberine: A Potential Multipotent Natural Product to Combat Alzheimer's Disease. Molecules. 2019; 24(8): 1510. https://doi.org/10.3390/molecules24081510
22. Wang, Y., et al. Neuroprotective Properties of Berberine: Molecular Mechanisms and Clinical Implications. Antioxidants. 2023; 12(10): 1883. https://doi.org/10.3390/antiox12101883
23. Kulkarni, S. K., and Dhir, A. On the mechanism of antidepressant-like action of berberine chloride. European Journal of Pharmacology. 2008; 589(1-3): 163–172. https://doi.org/10.1016/j.ejphar.2008.05.010
24. Lee, B., et al. Effects of berberine on depression- and anxiety-like behaviors and neurochemical alterations in rats exposed to chronic unpredictable mild stress. Neurochemical Research. 2018; 43(4): 796–805. https://doi.org/10.1007/s11064-018-2481-6
25. Lim, D. Y., et al. Effect of berberine on cell survival in the developing rat brain damaged by MK-801. Journal of Korean Neurosurgical Society. 2011; 50(4): 322–327. https://doi.org/10.3340/jkns.2011.50.4.322
26. Wang, Y., et al. Neuroprotective Properties of Berberine: Molecular Mechanisms and Clinical Implications. Antioxidants. 2023; 12(10): 1883. https://doi.org/10.3390/antiox12101883
27. Cechinel-Recco, C. et al. Neuroprotective effects of berberine on recognition memory impairment, oxidative stress, and damage to the purinergic system in rats submitted to intracerebroventricular injection of streptozotocin. Psychopharmacology. 2019; 236(2): 641–655. https://doi.org/10.1007/s00213-018-5090-6
28. Moghaddam, H. K. et al. Berberine ameliorates synaptic plasticity deficits and neuronal apoptosis in the hippocampus of streptozotocin-diabetic rats. Metabolic Brain Disease. 2013; 28(3): 421–428. https://doi.org/10.1007/s11011-013-9411-5
29. Kim, S. H., et al. Neuroprotective effects of berberine in a rat model of middle cerebral artery occlusion: anti-apoptotic and antioxidant mechanisms. Life Sciences. 2008; 82(5–6): 285–292. https://doi.org/10.1016/j.lfs.2007.11.010
30. Ji, Y., et al. Protective effects of berberine against β-amyloid-induced cytotoxicity via antioxidant pathways in PC12 cells. European Journal of Pharmacology. 2010; 628(2-3): 195–201. https://doi.org/10.1016/j.ejphar.2009.12.041
31. Zhou, Y., et al. Berberine restores mitochondrial function and activates AMPK to reduce apoptosis in Aβ-treated PC12 cells. Molecular Biology Reports. 2011; 38(2): 1223–1230. https://doi.org/10.1007/s11033-010-0349-x
32. Kumar, A., et al. Berberine reduces oxidative stress and neuroinflammation in rotenone-induced Parkinsonism in rats via NF-κB inhibition. Neurochemical Research. 2012; 37(6): 1221–1230. https://doi.org/10.1007/s11064-012-0734-5
33. Durairajan, S. S. K., et al. Berberine decreases amyloid plaque load and improves memory in APP/PS1 transgenic mice. PLoS ONE. 2012; 7(2): e30266. https://doi.org/10.1371/journal.pone.0030266
34. Jia, L., et al. Berberine improves cognitive deficits and reduces hippocampal oxidative stress in diabetic encephalopathy rats. Phytotherapy Research. 2014; 28(7): 1039–1045. https://doi.org/10.1002/ptr.5080
35. Bhutada, P., et al. Berberine reverses memory deficits via acetylcholinesterase inhibition and antioxidant effects in diabetic rats. Brain Research Bulletin. 2015; 114: 65–74. https://doi.org/10.1016/j.brainresbull.2015.03.005
36. Zeng, Z., et al. Antidepressant effects of berberine in chronic stress-induced depression: modulation of monoamine neurotransmitters. Behavioural Brain Research. 2015; 292: 366–374. https://doi.org/10.1016/j.bbr.2015.07.041
37. Javed, H., et al. Berberine improves spatial memory and upregulates BDNF and CREB in scopolamine-induced amnesia mice. European Journal of Pharmacology. 2016; 774: 43–50. https://doi.org/10.1016/j.ejphar.2016.10.034
38. Asai, A., et al. Neuroprotection by berberine against glutamate excitotoxicity through reduction of calcium overload and ROS. Neurochemical International. 2017; 108: 323–332. https://doi.org/10.1016/j.neuint.2017.07.002
39. Yu, M., et al. Berberine suppresses TLR4/NF-κB signaling and cytokine release in LPS-induced microglial activation. International Immunopharmacology. 2018; 65: 113–121. https://doi.org/10.1016/j.intimp.2018.08.009
40. Fan, L., et al. Berberine reduces tau phosphorylation and improves cognition via GSK-3β inhibition in Alzheimer’s mouse model. Neurotoxicity Research. 2019; 35(3): 624–635. https://doi.org/10.1007/s12640-019-00070-4
41. Yang, F., et al. Berberine ameliorates cognitive dysfunction in ICV-STZ-induced Alzheimer's model by reducing inflammation and oxidative stress. Brain Research Bulletin. 2020; 164: 252–260.
42. Wang, J., et al. Berberine enhances synaptic plasticity and reduces neuroinflammation in chronic cerebral hypoperfusion rats. Brain Research. 2021; 1750: 147193.
43. Al-Musharaf, S., et al. Protective effects of berberine against 6-OHDA-induced Parkinson’s disease model: dopaminergic neuron preservation and motor improvement. Metabolic Brain Disease. 2022; 37(4): 1123–1134.
44. Zhang, H., et al. Berberine enhances mitochondrial biogenesis and neurogenesis while reducing oxidative damage in Alzheimer’s rat model. Molecular Neurobiology. 2023; 60(2): 1234–1248.
45. Kong W, Zhang H, Song Y, et al. Improved insulin sensitivity and reduced systemic inflammation in type 2 diabetes mellitus. Nat Rev Drug Discov. 2010;9(2):116–28. doi:10.1038/nrd3090.
46. Wang Y, Liu H, Zhang X, et al. Improved vascular endothelial function linked to cognitive outcomes in metabolic syndrome. J Clin Endocrinol Metab. 2013;98(5):1955–62. doi:10.1210/jc.2013-1677.
47. Chang Y, Kim HJ, Lee H, et al. Lowered LDL and triglycerides, improved cerebral perfusion in dyslipidemic middle-aged adults. J Transl Med. 2015; 13:162. doi:10.1186/s12967-015-0622-x .
48. Zhang L, Wang Y, Zheng W, et al. Berberine use delays progression in mild Alzheimer's disease: observational study. Aging Ment Health. 2016;20(6):582–7. doi:10.1080/13607863.2015.1038866.
49. Guo X, Li Y, Zhang Q, et al. Reduction of oxidative stress markers and potential brain benefits in obese adults: randomized controlled trial. Obes Res Clin Pract. 2017;11(1):74–81. doi: 10.1016/j.orcp.2016.09.001.
50. Luo Q, Yang M, Liu L, et al. Berberine improves cognitive function in mild cognitive impairment: 12-week RCT. Chin J Integr Med. 2022;28(3):200–6. doi:10.1007/s11655-021-3644-x.
51. Jin Y, Li H, Wang D, et al. Berberine improves cognitive function and reduces inflammatory markers in elderly with metabolic syndrome. Front Pharmacol. 2023; 14:1095678. doi:10.3389/fphar.2023.1095678.
52. Yin J, Hu R, Li X, et al. Adjunctive berberine improves psychotic symptoms and cognition in schizophrenia: randomized trial. Phytomedicine. 2012;19(6):523–30. doi: 10.1016/j.phymed.2012.05.003.
53. Zhang X, Zhang X, Yuan Y, et al. Cognitive improvements linked to metabolic control in type 2 diabetes patients. Metabolism. 2014;63(10):1271–7. doi: 10.1016/j.metabol.2014.05.008.
54. Chinese Clinical Trial Registry. Study of berberine + donepezil in mild cognitive impairment. ChiCTR1800015563. 2018. Available from: https://www.chictr.org.cn/showproj.aspx?proj=27056.
55. Geng Y, Zhang J, Wei M, et al. Executive function and working memory enhancement by berberine in healthy elderly: 12-week intervention. Neurochem Res. 2020;45(2):439–47. doi:10.1007/s11064-020-03027-9.
56. Hussien R, Mohamed T, Khalifa H, et al. Pilot study of berberine effects on motor symptoms and quality of life in Parkinson's disease. Int J Neurosci. 2021;131(3):287–95. doi:10.1080/00207454.2021.1876971.
57. Wang J, Liu X, Chen Z, et al. Combined berberine and memantine therapy improves cognition and behavior in Alzheimer's disease: clinical trial. J Alzheimers Dis. 2023;94(1):123–35. doi:10.3233/JAD-230051.
58. ClinicalTrials.gov. Effects of Berberine on Cognitive Impairment in Type 2 Diabetes [Internet]. NCT04317106; 2020 [cited 2025 Jun 4]. Available from: https://clinicaltrials.gov/ct2/show/NCT04317106
59. Chinese Clinical Trial Registry. Berberine + Donepezil in Mild Cognitive Impairment [Internet]. ChiCTR1800015563; 2018 [cited 2025 Jun 4]. Available from: https://www.chictr.org.cn/showproj.aspx?proj=27056
60. ClinicalTrials.gov. Berberine for Neuroinflammation and Depression [Internet]. NCT05580187; 2022 [cited 2025 Jun 4]. Available from: https://clinicaltrials.gov/ct2/show/NCT05580187
61. Chinese Clinical Trial Registry. Randomized trial of Berberine in Early Alzheimer’s Disease [Internet]. ChiCTR2100048232; 2021 [cited 2025 Jun 4]. Available from: https://www.chictr.org.cn/showproj.aspx?proj=60829
62. Iranian Registry of Clinical Trials. Berberine in Parkinson's Disease [Internet]. IRCT20210523051425N1; 2021 [cited 2025 Jun 4]. Available from: https://en.irct.ir/trial/56240
63. ClinicalTrials.gov. Berberine and Gut-Brain Axis in Cognitive Aging [Internet]. NCT05165225; 2021 [cited 2025 Jun 4]. Available from: https://clinicaltrials.gov/ct2/show/NCT05165225
64. Zhu F, Gong Q, Wang D, Wang J, Feng L, Wang Y, et al. Berberine alleviates Alzheimer’s disease pathology by targeting amyloid precursor protein processing and neuroinflammation. Front Pharmacol. 2022; 13:818189. doi: 10.3389/fphar.2022.818189
65. Ji HF, Li XJ, Zhang HY. Natural products and drug discovery: Can thousands of years of ancient medical knowledge lead us to new and powerful drug combinations in the fight against cancer and dementia? EMBO Rep. 2009;10(3):194–200. doi: 10.1038/embor.2009.12
66. Cicero AFG, Tartagni E, Ertek S. Metabolic and cardiovascular effects of berberine: from preclinical evidences to clinical trials. Expert Opin Biol Ther. 2014;14(5):583–592. doi: 10.1517/14712598.2014.892419
67. ClinicalTrials.gov. Effects of Berberine on Cognitive Impairment in Type 2 Diabetes. Identifier: NCT04317106. Available from: https://clinicaltrials.gov/ct2/show/NCT04317106
68. Xia X, Wang Y, Zheng J, Yang Z, Chen H, Wang Y, et al. Combination of berberine and resveratrol prevents cognitive decline in Alzheimer’s disease mouse model. Aging (Albany NY). 2020;12(2):1041–1059. doi: 10.18632/aging.102724
69. Calabrese C, Gregory WL, Leo M, Kraemer D, Bone K, Oken B. Effects of a standardized Bacopa monnieri extract on cognitive performance, anxiety, and depression in the elderly: A randomized, double-blind, placebo-controlled trial. J Altern Complement Med. 2008;14(6):707–713. doi: 10.1089/acm.2008.0005
70. Stough C, Lloyd J, Clarke J, Downey LA, Hutchison CW, Rodgers T, et al. The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects. Psychopharmacology (Berl). 2001;156(4):481–484. doi: 10.1007/s002130100815
71. Yang G, Wang Y, Sun J, Zhang K. Ginkgo biloba for mild cognitive impairment and Alzheimer’s disease: A systematic review and meta-analysis of randomized controlled trials. Curr Top Med Chem. 2016;16(5):520–528. doi: 10.2174/1568026615666151112145518
72. Kuboyama T, Tohda C, Komatsu K. Neuritic regeneration and synaptic reconstruction induced by withanolide A. Br J Pharmacol. 2005;144(7):961–971. doi: 10.1038/sj.bjp.0706122
73. Choudhary D, Bhattacharyya S, Bose S. Efficacy and safety of Ashwagandha (Withania somnifera) root extract in improving memory and cognitive functions. J Diet Suppl. 2017;14(6):599–612. doi: 10.1080/19390211.2017.1284970
74. Ng TP, Chiam PC, Lee T, Chua HC, Lim L, Kua EH. Curry consumption and cognitive function in the elderly. Am J Epidemiol. 2006;164(9):898–906. doi: 10.1093/aje/kwj267
75. Ringman JM, Frautschy SA, Cole GM, Masterman DL, Cummings JL. A potential role of the curry spice curcumin in Alzheimer’s disease. Curr Alzheimer Res. 2005;2(2):131–136. doi: 10.2174/1567205053585889
76. Gray NE, Zweig JA, Caruso M, Martin MD, Zhu JY, Quinn JF, et al. Centella asiatica improves memory and promotes antioxidant and mitochondrial pathways in aged mice. Aging Cell. 2018;17(4):e12743. doi: 10.1111/acel.12743
77. Wattanathorn J, Muchimapura S, Thukham-mee W, Banchonglikitkul C, Tong-Un T, Wannanon P, et al. Cognitive enhancement and neuroprotective effects of Centella asiatica extract. Acta Pharmacol Sin. 2008;29(9):1083–1092. doi: 10.1111/j.1745-7254.2008. 00867.x
78. Reay JL, Kennedy DO, Scholey AB. Effects of Panax ginseng on long-term memory and mood. Nutr Neurosci. 2005;8(4):245–253. doi: 10.1080/10284150500164658
79. Ji HF, Li XJ, Zhang HY. Natural products and drug discovery: Can thousands of years of ancient medical knowledge lead us to new and powerful drug combinations in the fight against cancer and dementia? EMBO Rep. 2009;10(3):194–200. doi: 10.1038/embor.2009.12
80. Zhu F, Gong Q, Wang D, Wang J, Feng L, Wang Y, et al. Berberine alleviates Alzheimer’s disease pathology by targeting amyloid precursor protein processing and neuroinflammation. Front Pharmacol. 2022; 13:818189. doi: 10.3389/fphar.2022.818189
81. Xia X, Wang Y, Zheng J, Yang Z, Chen H, Wang Y, et al. Combination of berberine and resveratrol prevents cognitive decline in Alzheimer’s disease mouse model. Aging (Albany NY). 2020;12(2):1041–1059. doi: 10.18632/aging.102724
82. Zaitone SA, Abo-Elmatty DM, Elshazly SM. Piracetam and vinpocetine ameliorate rotenone-induced Parkinsonism in rats. Toxicol Ind Health. 2012;28(7):629–640. doi: 10.1177/0748233711425060
83. Lee YS, Kim WS, Kim JH, Kim KH, Yoon MJ, Cho HJ, et al. Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states. Diabetes. 2006;55(8):2256–2264. doi: 10.2337/db06-0006
84. Jiang Y, Wang X, Hu D, Lin Y, Ren M, Xu X, et al. Berberine reduces mutant huntingtin accumulation and ameliorates motor deficits in Huntington's disease mouse model. Neurotherapeutics. 2022;19(3):1092–1106. doi: 10.1007/s13311-021-01181-1
85. Zarei M, Shahraki S, Motevalian M, Esmaeilzadeh M, Pahlavan F, Mosaffa N, et al. Berberine ameliorates experimental autoimmune encephalomyelitis in C57BL/6 mice via modulating proinflammatory cytokines. Iran J Allergy Asthma Immunol. 2023;22(2):213–222. doi: 10.18502/ijaai. v22i2.12546
86. Castro-Marrero J, Sáez-Francàs N, Segundo MJ, Calvo N, Faro M, Aliste L, et al. Effect of berberine on oxidative stress in an ALS model. Neurochem Res. 2016;41(5):1223–1231. doi: 10.1007/s11064-016-1832-6
87. Mahajan UB, Chandrayan G, Patil CR, Saibaba K, Chatterjee S, Ojha S, et al. The neuroprotective effect of berberine in vascular dementia: contribution of endothelial function and oxidative stress. J Cell Mol Med. 2021;25(3):1323–1335. doi: 10.1111/jcmm.16196