Unraveling Berberine's Molecular Mechanisms in Neuroprotection Against Neurodegeneration

Unraveling Berberine's Molecular Mechanisms in Neuroprotection Against Neurodegeneration Md. Zamshed Alam Begh Department of Pharmacy, Faculty of Health and Life Sciences Daffodil International University Dhaka Bangladesh https://orcid.org/0009-0002-6512-3872 Md Al Amin Department of Pharmacy, Faculty of Health and Life Sciences Daffodil International University Dhaka Bangladesh Mst Maharunnasa Shatu Department of Botany Bangabandhu Sheikh Mujibur Rahman Science and Technology University Gopalganj Bangladesh Sherouk Hussein Sweilam Department of Pharmacognosy College of Pharmacy, Prince Sattam Bin Abdulaziz University Al‐Kharj Saudi Arabia Department of Pharmacognosy, Faculty of Pharmacy Egyptian Russian University Badr City Egypt Sachin Puri School of Pharmacy & Technology Management, SVKM's Narsee Monjee Institute of Management Studies (NMIMS) Deemed‐to‐University Hyderabad India Rathod Bhagyashri Ramesh School of Pharmacy & Technology Management, SVKM's Narsee Monjee Institute of Management Studies (NMIMS) Deemed‐to‐University Hyderabad India Uppuluri Varuna Naga Venkata Arjun Department of Pharmaceutics School of Pharmaceutical Sciences, Vels Institute of Science, Technology and Advanced Studies (VISTAS) Chennai India Thukani Sathanantham Shanmugarajan Department of Pharmaceutics School of Pharmaceutical Sciences, Vels Institute of Science, Technology and Advanced Studies (VISTAS) Chennai India Nagaveni Pommala S. V. U. College of Pharmaceutical Sciences, Sri Venkateswara University Tirupati India Akiladevi Durairaj Department of Pharmaceutics School of Pharmaceutical Sciences, Vels Institute of Science, Technology and Advanced Studies (VISTAS) Chennai India Susithra Ethiraj S. V. U. College of Pharmaceutical Sciences, Sri Venkateswara University Tirupati India Nagarajan Shenbakadurai Department of Pharmaceutics School of Pharmaceutical Sciences, Vels Institute of Science, Technology and Advanced Studies (VISTAS) Chennai India Irfan Ahmad Department of Clinical Laboratory Sciences College of Applied Medical Science, King Khalid University Abha Saudi Arabia Talha Bin Emran Department of Pharmacy, Faculty of Health and Life Sciences Daffodil International University Dhaka Bangladesh Department of Pathology and Laboratory Medicine Warren Alpert Medical School, Brown University Providence Rhode Island USA ABSTRACT

Neurodegenerative diseases (NDs) exhibit significant global public health challenges due to the lack of effective treatments. Berberine (BBR), a natural alkaloid compound in various plants, has been recognized for its potential neuroprotective properties. This review explores the current understanding of BBR's mechanisms of action and its therapeutic potential in preventing and treating NDs such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. BBR's neuroprotective properties are attributed to its multifaceted actions, including anti‐inflammatory, antioxidant, antiapoptotic, and neurotrophic effects. In addition, BBR can influence many signaling pathways involved in neurodegeneration, including AMP‐activated protein kinase (AMPK), nuclear factor erythroid 2‐related factor 2, and brain‐derived neurotrophic factor pathways. Furthermore, BBR targets vital signaling pathways, including AMPK, PI3K/Akt, and MAPK, which are essential for developing NDs. In addition, BBR's efficacy in reducing neurodegenerative pathology and improving cognitive function has been demonstrated through preclinical studies using cellular and animal models. Clinical trials demonstrating BBR's therapeutic potential in NDs have yielded promising results, but further research is needed to confirm its safety and efficacy in humans.
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L. 459 18 2019 10.1016/S1474-4422(18)30499-X Global, Regional, and National Burden of Neurological Disorders, 1990–2016: A Systematic Analysis for the Global Burden of Disease Study 2016 Neuroepidemiology Feigin V. L. 1 52 2019 10.1159/000495197 Global Burden of Neurological Disorders: From Global Burden of Disease Estimates to Actions Frontiers in Neurology Onohuean H. 1024004 13 2022 10.3389/fneur.2022.1024004 Epidemiology of Neurodegenerative Diseases in the East African Region: A Meta‐Analysis Folia Neuropathologica Armstrong R. 93 58 2020 10.5114/fn.2020.96707 What Causes Neurodegenerative Disease? Biomolecules Chen D. 1158 10 2020 10.3390/biom10081158 Cellular Mechanisms of Melatonin: Insight From Neurodegenerative Diseases BMC Public Health Lekoubou A. 653 14 2014 10.1186/1471-2458-14-653 Epidemiology of Neurodegenerative Diseases in Sub‐Saharan Africa: A Systematic Review Nature Gammon K. 299 515 2014 10.1038/nj7526-299a Neurodegenerative Disease: Brain Windfall International Journal of Molecular Sciences Iskusnykh I. Y. 1018 25 2024 10.3390/ijms25021018 Aging, Neurodegenerative Disorders, and Cerebellum Cells Cohen J. 511 13 2024 10.3390/cells13060511 Recent Research Trends in Neuroinflammatory and Neurodegenerative Disorders Pharmacological Reports Ahmed T. 970 67 2015 10.1016/j.pharep.2015.03.002 Berberine and Neurodegeneration: A Review of Literature Science China Life Sciences Jiang W. 564 58 2015 10.1007/s11427-015-4829-0 Therapeutic Potential of Berberine Against Neurodegenerative Diseases Frontiers in Pharmacology Cheng Z. 845591 13 2022 10.3389/fphar.2022.845591 Berberine: A Promising Treatment for Neurodegenerative Diseases Journal of Food Biochemistry Akbar M. e13936 45 2021 10.1111/jfbc.13936 Neuroprotective Potential of Berberine in Modulating Alzheimer's Disease via Multiple Signaling Pathways Oxidative Stress and Dietary Antioxidants in Neurological Diseases Imenshahidi M. 199 2020 10.1016/B978-0-12-817780-8.00014-1 Antioxidants Tian E. 1883 12 2023 10.3390/antiox12101883 Neuroprotective Properties of Berberine: Molecular Mechanisms and Clinical Implications Neuropsychiatric Disease and Treatment Cai Z. 2509 12 2016 10.2147/NDT.S114846 Role of Berberine in Alzheimer's Disease Current Pharmaceutical Design Qin S. 5054 26 2020 10.2174/1381612826666200523172334 AMPK and Its Activator Berberine in the Treatment of Neurodegenerative Diseases Combinatorial Chemistry & High Throughput Screening Mohi‐Ud‐Din R. 616 25 2022 10.2174/1386207324666210804122539 Berberine in the Treatment of Neurodegenerative Diseases and Nanotechnology Enabled Targeted Delivery European Neurology Mangoni A. 100 31 1991 10.1159/000116655 Effects of a MAO‐B Inhibitor in the Treatment of Alzheimer Disease Clinical Neuropharmacology Rabey J. 324 23 2000 10.1097/00002826-200011000-00005 Rasagiline Mesylate, a New Mao‐B Inhibitor for the Treatment of Parkinson's Disease: A Double‐Blind Study as Adjunctive Therapy to Levodopa FASEB Journal Caspersen C. 2040 19 2005 10.1096/fj.05-3735fje Mitochondrial Aβ: A Potential Focal Point for Neuronal Metabolic Dysfunction in Alzheimer's Disease Trends in Pharmacological Sciences Poprac P. 592 38 2017 10.1016/j.tips.2017.04.005 Targeting Free Radicals in Oxidative Stress‐Related Human Diseases Cellular and Molecular Neurobiology Li Z. 587 40 2020 10.1007/s10571-019-00756-7 Berberine Attenuated the Cytotoxicity Induced by T‐BHP via Inhibiting Oxidative Stress and Mitochondria Dysfunction in PC‐12 Cells Iranian Journal of Basic Medical Sciences Sadeghnia H. R. 594 20 2017 Berberine Protects Against Glutamate‐Induced Oxidative Stress and Apoptosis in PC12 and N2a Cells International Journal of Molecular Sciences Lee D.‐H. 11783 13 2012 10.3390/ijms130911783 Mechanisms of Oxidative Damage in Multiple Sclerosis and Neurodegenerative Diseases: Therapeutic Modulation via Fumaric Acid Esters Psychopharmacology Oliveira J. S. 641 236 2019 10.1007/s00213-018-5090-6 Neuroprotective Effects of berberine on Recognition Memory Impairment, Oxidative Stress, and Damage to the Purinergic System in Rats Submitted to Intracerebroventricular Injection of Streptozotocin International Immunopharmacology Chen J.‐H. 94 12 2012 10.1016/j.intimp.2011.10.019 Berberine Induces Heme Oxygenase‐1 Up‐Regulation Through Phosphatidylinositol 3‐Kinase/AKT and NF‐E2‐Related Factor‐2 Signaling Pathway in Astrocytes Molecules and Cells Bae J. 151 35 2013 10.1007/s10059-013-2298-5 Berberine Protects 6‐Hydroxydopamine‐Induced Human Dopaminergic Neuronal Cell Death Through the Induction of Heme Oxygenase‐1 Molecular and Cellular Biochemistry Chen M. 285 474 2020 10.1007/s11010-020-03852-1 Berberine Attenuates Aβ‐Induced Neuronal Damage Through Regulating miR‐188/NOS1 in Alzheimer's Disease Journal of Pharmacy and Pharmacology Ye M. 831 61 2009 10.1211/jpp.61.07.0001 Neuropharmacological and Pharmacokinetic Properties of berberine: A Review of Recent Research Sheng Li Xue Bao:[Acta Physiologica Sinica] Zhang C.‐C. 301 70 2018 [Research Progress of Histone Deacetylase 6 Inhibitors in the Therapy of Ischemic Stroke] Brain Research Pires E. N. S. 26 1557 2014 10.1016/j.brainres.2014.02.021 Berberine Was Neuroprotective Against an In Vitro Model of Brain Ischemia: Survival and Apoptosis Pathways Involved International Journal of Molecular Medicine Kim M. 870 33 2014 10.3892/ijmm.2014.1656 Berberine Prevents Nigrostriatal Dopaminergic Neuronal Loss and Suppresses Hippocampal Apoptosis in Mice With Parkinson's disease Experimental Gerontology Huang M. 25 91 2017 10.1016/j.exger.2017.02.004 Berberine Improves Cognitive Impairment by Promoting Autophagic Clearance and Inhibiting Production of β‐Amyloid in APP/Tau/PS1 Mouse Model of Alzheimer's Disease Molecular Medicine Reports Zhang H. N. 5030 18 2018 Berberine Promotes Nerve Regeneration Through IGFR‑Mediated JNK‑AKT Signal Pathway Phytotherapy Research Campisi A. 816 25 2011 10.1002/ptr.3340 Effect of Berberine and Berberis aetnensis C. Presl. Alkaloid Extract on Glutamate‐Evoked Tissue Transglutaminase Up‐Regulation in Astroglial Cell Cultures ACS Chemical Neuroscience Liang Y. 1894 12 2021 10.1021/acschemneuro.0c00808 Berberine Improves Behavioral and Cognitive Deficits in a Mouse Model of Alzheimer's Disease via Regulation of β‐Amyloid Production and Endoplasmic Reticulum Stress Neurochemical Research Lin L. 1130 45 2020 10.1007/s11064-020-02992-6 Synergic Effects of Berberine and Curcumin on Improving Cognitive Function in an Alzheimer's Disease Mouse Model Current Reviews in Clinical and Experimental Pharmacology Singh A. 182 18 2023 10.2174/2772432816666210910104306 Investigating Neuroprotective Potential of Berberine, Levetiracetam and Their Combination in the Management of Alzheimer's Disease Utilizing Drug Repurposing Strategy Redox Biology Zhang C. 1 11 2017 10.1016/j.redox.2016.10.019 Berberine Protects Against 6‐OHDA‐Induced Neurotoxicity in PC12 Cells and Zebrafish Through Hormetic Mechanisms Involving PI3K/AKT/Bcl‐2 and Nrf2/HO‐1 Pathways Acta Pharmacologica Sinica Zhu J.‐R. 1706 39 2018 10.1038/s41401-018-0160-1 Berberine Attenuates Ischemia–Reperfusion Injury Through Inhibiting HMGB1 Release and NF‐κB Nuclear Translocation BMC Neuroscience Zhu F. 7 2006 Berberine Chloride Can Ameliorate the Spatial Memory Impairment and Increase the Expression of Interleukin‐1beta and Inducible Nitric Oxide Synthase in the Rat Model of Alzheimer's Disease Food and Chemical Toxicology Hussien H. M. 432 111 2018 10.1016/j.fct.2017.11.025 Neuroprotective Effect of Berberine Against Environmental Heavy Metals‐Induced Neurotoxicity and Alzheimer's‐Like Disease in Rats Journal of Cellular Biochemistry Lu D. Y. 697 110 2010 10.1002/jcb.22580 Berberine Suppresses Neuroinflammatory Responses Through AMP‐Activated Protein Kinase Activation in BV‐2 Microglia Metabolic Brain Disease Sadraie S. 245 34 2019 10.1007/s11011-018-0349-5 Berberine Ameliorates Lipopolysaccharide‐Induced Learning and Memory Deficit in the Rat: Insights Into Underlying Molecular Mechanisms Food & Function Deng H. 8366 12 2021 10.1039/D1FO01360B Protective Effects of Berberine Against MPTP‐Induced Dopaminergic Neuron Injury Through Promoting Autophagy in Mice Biochemical and Biophysical Research Communications Luo J. 927 490 2017 10.1016/j.bbrc.2017.06.142 The Effects of Berberine on a Murine Model of Multiple Sclerosis and the SPHK1/S1P Signaling Pathway Neuropharmacology Do T. M. 311 81 2014 10.1016/j.neuropharm.2014.02.010 Altered Cerebral Vascular Volumes and Solute Transport at the Blood–Brain Barriers of Two Transgenic Mouse Models of Alzheimer's Disease Journal of Neurochemistry Matuszyk M. M. 434 160 2022 10.1111/jnc.15538 Biological and Methodological Complexities of Beta‐Amyloid Peptide: Implications for Alzheimer's Disease Research Cells Ye C. 1161 10 2021 10.3390/cells10051161 Berberine Improves Cognitive Impairment by Simultaneously Impacting Cerebral Blood Flow and β‐Amyloid Accumulation in an APP/Tau/PS1 Mouse Model of Alzheimer's Disease Molecular Neurobiology Moghaddam H. K. 820 49 2014 10.1007/s12035-013-8559-7 Berberine Ameliorate Oxidative Stress and Astrogliosis in the Hippocampus of STZ‐Induced Diabetic Rats Neurochemical Research Ibrahim Fouad G. 3247 46 2021 10.1007/s11064-021-03428-5 Neuroprotective Potential of Berberine Against Doxorubicin‐Induced Toxicity in Rat's Brain Biomedicine & Pharmacotherapy Chen Y. 109670 121 2020 10.1016/j.biopha.2019.109670 Berberine Mitigates Cognitive Decline in an Alzheimer's Disease Mouse Model by Targeting Both Tau Hyperphosphorylation and Autophagic Clearance Neurobiology of Aging Durairajan S. S. K. 2903 33 2012 10.1016/j.neurobiolaging.2012.02.016 Berberine Ameliorates β‐Amyloid Pathology, Gliosis, and Cognitive Impairment in an Alzheimer's Disease Transgenic Mouse Model Current Reviews in Clinical and Experimental Pharmacology Saleh S. R. 139 16 2021 10.2174/27724336MTA31NzQh0 Berberine Nanoencapsulation Attenuates Hallmarks of Scoplomine Induced Alzheimer's‐Like Disease in Rats 3 Biotech Xuan W.‐T. 359 10 2020 10.1007/s13205-020-02354-7 Berberine Ameliorates Rats Model of Combined Alzheimer's Disease and Type 2 Diabetes Mellitus via the Suppression of Endoplasmic Reticulum Stress Neurotoxicology Oliveira J. S. 241 57 2016 10.1016/j.neuro.2016.10.008 Berberine Protects Against Memory Impairment and Anxiogenic‐Like Behavior in Rats Submitted to Sporadic Alzheimer's‐Like Dementia: Involvement of Acetylcholinesterase and Cell Death BMC Complementary and Alternative Medicine Abd El‐Wahab A. E. 218 13 2013 10.1186/1472-6882-13-218 In Vitro Biological Assessment of Berberis vulgaris and Its Active Constituent, Berberine: Antioxidants, Anti‐Acetylcholinesterase, Anti‐Diabetic and Anticancer Effects ScientificWorldJournal Ji H.‐F. 823201 2012 2012 Molecular Basis of Inhibitory Activities of Berberine Against Pathogenic Enzymes in Alzheimer's Disease PLoS One Ismail H. e0286349 18 2023 10.1371/journal.pone.0286349 Bioassays Guided Isolation of Berberine From Berberis lycium and Its Neuroprotective Role in Aluminium Chloride Induced Rat Model of Alzheimer's Disease Combined With In Silico Molecular Docking Frontiers in Pharmacology Huang S. 618787 11 2021 10.3389/fphar.2020.618787 Berberine Protects Against NLRP3 Inflammasome via Ameliorating Autophagic Impairment in MPTP‐Induced Parkinson's Disease Model Neuroscience Letters Kwon I. H. 29 486 2010 10.1016/j.neulet.2010.09.038 Effects of Berberine on 6‐Hydroxydopamine‐Induced Neurotoxicity in PC12 Cells and a Rat Model of Parkinson's Disease Archives of Pharmacal Research Shin K. S. 759 36 2013 10.1007/s12272-013-0051-4 Neurotoxic Effects of Berberine on Long‐Term l‐DOPA Administration in 6‐Hydroxydopamine‐Lesioned Rat Model of Parkinson's Disease Immunity, Inflammation and Disease Tavaf M. J. e766 11 2023 10.1002/iid3.766 Berberine Promotes Immunological Outcomes and Decreases Neuroinflammation in the Experimental Model of Multiple Sclerosis Through the Expansion of Treg and Th2 Cells Journal of Immunology Qin X. 1855 185 2010 10.4049/jimmunol.0903853 Regulation of Th1 and Th17 Cell Differentiation and Amelioration of Experimental Autoimmune Encephalomyelitis by Natural Product Compound Berberine Neurological Research Jiang Y. 360 35 2013 10.1179/1743132812Y.0000000156 The Protective Effect of Berberine Against Neuronal Damage by Inhibiting Matrix Metalloproteinase‐9 and Laminin Degradation in Experimental Autoimmune Encephalomyelitis PLoS One Jiang W. e0134142 10 2015 10.1371/journal.pone.0134142 Therapeutic Effect of Berberine on Huntington's Disease Transgenic Mouse Model Neuroscience Letters Ravandi S. G. 151 706 2019 10.1016/j.neulet.2019.05.029 Ameliorating Effects of Berberine on MK‐801‐Induced Cognitive and Motor Impairments in a Neonatal Rat Model of Schizophrenia BMC Complementary Medicine and Therapies Gholizadeh N. 303 23 2023 10.1186/s12906-023-04107-4 Berberine Improves Inhibitory Avoidance Memory Impairment of Toxoplasma gondii ‐Infected Rat Model of Ketamine‐Induced Schizophrenia Psychiatry Research Li M. 113899 300 2021 10.1016/j.psychres.2021.113899 The Effect of Berberine Adjunctive Treatment on Glycolipid Metabolism in Patients With Schizophrenia: A Randomized, Double‐Blind, Placebo‐Controlled Clinical Trial European Archives of Psychiatry and Clinical Neuroscience Li M. 633 272 2022 10.1007/s00406-021-01359-4 Improvement of Adjunctive Berberine Treatment on Negative Symptoms in Patients With Schizophrenia Traditional and Integrative Medicine Sarani E. M. 287 7 2022 Evaluation of the Effect of Alkaloid Berberine on the Positive and Negative Symptoms of the Patients with Schizophrenia: A Double‐Blind Randomized Placebo‐Controlled Clinical Trial Psychiatry and Clinical Neurosciences Chan M. 77 76 2022 10.1111/pcn.13323 Adjunctive Berberine Reduces Antipsychotic‐Associated Weight Gain and Metabolic Syndrome in Patients With Schizophrenia: A Randomized Controlled Trial International Journal of Molecular Sciences Li Y. 1865 17 2016 10.3390/ijms17111865 Berberine Alleviates Olanzapine‐Induced Adipogenesis via the AMPKα–SREBP Pathway in 3T3‐L1 Cells Iranian Journal of Basic Medical Sciences Aski M. L. 53 21 2018 Neuroprotective Effect of Berberine Chloride on Cognitive Impairment and Hippocampal Damage in Experimental Model of Vascular Dementia Clinical and Experimental Hypertension Yin S. 708 41 2019 10.1080/10641963.2018.1545846 Berberine Suppresses the Ectopic Expression of miR‐133a in Endothelial Cells to Improve Vascular Dementia in Diabetic Rats European Journal of Pharmacology Singh D. P. 98 720 2013 10.1016/j.ejphar.2013.10.043 Verapamil Augments the Neuroprotectant Action of Berberine in Rat Model of Transient Global Cerebral Ischemia Chinese Journal of Applied Physiology Sun K. 656 36 2020 [Protective Effect and Immune Mechanism of Berberine on Cerebral Ischemia/Reperfusion Injury in Rats] Journal of Chemical Neuroanatomy Maleki S. N. 54 87 2018 10.1016/j.jchemneu.2017.04.008 Berberine Confers Neuroprotection in Coping With Focal Cerebral Ischemia by Targeting Inflammatory Cytokines Traditional & Kampo Medicine Mehboodi D. 222 11 3 2024 10.1002/tkm2.1431 Berberine Alleviates Cerebellar Damage in Global Cerebral Ischemia: A Comprehensive Study With Stereological Analysis, Evaluation of the Antioxidant Response, and Locomotor Function in rat Models PLoS One Chen C.‐C. e115694 9 2014 10.1371/journal.pone.0115694 Berberine Protects Against Neuronal Damage via Suppression of Glia‐Mediated Inflammation in Traumatic Brain Injury Neurochemical Research Huang S.‐X. 1814 43 2018 10.1007/s11064-018-2597-5 Berberine Protects Secondary Injury in Mice With Traumatic Brain Injury through Anti‐Oxidative and Anti‐Inflammatory Modulation Molecular Medicine Reports Wang J. 6881 17 2018 Neuroprotective Effect of Berberine Agonist Against Impairment of Learning and Memory Skills in Severe Traumatic Brain Injury via Sirt1/p38 MAPK Expression International Journal of Neuroscience Tentu P. M. 80 135 2023 10.1080/00207454.2023.2286209 Oxyberberine an Oxoderivative of Berberine Confers Neuroprotective Effects in Controlled‐Cortical Impact Mouse Model of Traumatic Brain Injury Neuroimmunomodulation Wu X. 317 29 2022 10.1159/000520747 Berberine Protects Against Neurological Impairments and Blood‐Brain Barrier Injury in Mouse Model of Intracerebral Hemorrhage Journal of Mazandaran University of Medical Sciences Anbai S. 1 31 2022 Neuroprotective Effects of Berberine After Severe Traumatic Brain Injury in Male Rats: The Role of IL‐1β and IL 10 International Journal of Clinical and Experimental Pathology Wang J. 4900 10 2017 Berberine Improves Motor Function Recovery by Inhibiting Endoplasmic Reticulum Stress‐Induced Neuronal Apoptosis via AMPK Activation in Rats With Spinal Cord Injury Neurotherapeutics Suzuki Y. 1976 19 2022 10.1007/s13311-022-01310-y High‐Throughput Screening Assay Identifies Berberine and Mubritinib as Neuroprotection Drugs for Spinal Cord Injury via Blood‐Spinal Cord Barrier Protection FASEB Journal Duan H. 36 2022 10.1096/fasebj.2022.36.S1.00R62 Effects of Berberine on Neurological Recovery After Spinal Cord Injury in Rats Oncotarget Wang H. 98312 8 2017 10.18632/oncotarget.21203 Berberine Attenuated Pro‐Inflammatory Factors and Protect Against Neuronal Damage via Triggering Oligodendrocyte Autophagy in Spinal Cord Injury Current Molecular Medicine Cai Z.‐Y. 342 19 2019 10.2174/1566524019666190315164120 Berberine Alleviates Amyloid‐Beta Pathogenesis via Activating LKB1/AMPK Signaling in the Brain of APP/PS1 Transgenic Mice Journal of Medicinal Food Kim H. J. 909 18 2015 10.1089/jmf.2014.3346 Berberine Ameliorates Allodynia Induced by Chronic Constriction Injury of the Sciatic Nerve in Rats Journal of Medicinal Food Kim S. O. 511 16 2013 10.1089/jmf.2012.2648 Berberine Ameliorates Cold and Mechanical Allodynia in a Rat Model of Diabetic Neuropathy Frontiers in Pharmacology Zhang X.‐H. 1073 11 2020 10.3389/fphar.2020.01073 Berberine Ameliorates Subarachnoid Hemorrhage Injury via Induction of Sirtuin 1 and Inhibiting HMGB1/NF‐κB Pathway Journal of Neurochemistry Novak J. E. 2322 74 2000 10.1046/j.1471-4159.2000.0742322.x Increased Expression of Gα Q/11 and of Phospholipase‐Cβ1/4 in Differentiated Human NT2‐N Neurons Toxicology and Applied Pharmacology Hsu Y.‐Y. 787 272 2013 10.1016/j.taap.2013.08.008 Berberine, a Natural Antidiabetes Drug, Attenuates Glucose Neurotoxicity and Promotes Nrf2‐related Neurite Outgrowth Planta Medica Halbsguth C. 305 69 2003 10.1055/s-2003-38869 Positive Cooperation of Protoberberine Type 2 Alkaloids From Corydalis Cava on the GABA A Binding Site Experimental Neurobiology Lee T. 140 19 2010 10.5607/en.2010.19.3.140 Effect of Berberine on Cell Survival in the Developing Rat Brain Damaged by MK‐801 Brain Research Wu J. 214 775 1997 10.1016/S0006-8993(97)00960-8 Tetrahydroberberine Blocks Membrane K + Channels Underlying Its Inhibition of Intracellular Message‐Mediated Outward Currents in Acutely Dissociated CA1 Neurons From Rat Hippocampus Behavior Genetics Lacaille F. 554 39 2009 10.1007/s10519-009-9286-8 Feminization and Alteration of Drosophila Taste Neurons Induce Reciprocal Effects on Male Avoidance Behavior Science Goedert M. 777 314 2006 10.1126/science.1132814 A Century of Alzheimer's Disease Pharmacological Research Ribeiro F. M. 179 115 2017 10.1016/j.phrs.2016.11.013 Metabotropic Glutamate Receptors and Neurodegenerative Diseases Frontiers in Cellular Neuroscience Shinjyo N. 765217 15 2021 10.3389/fncel.2021.765217 Infection and Immunometabolism in the Central Nervous System: A Possible Mechanistic Link Between Metabolic Imbalance and Dementia International Journal of Pharmaceutics Ameen D. 465 529 2017 10.1016/j.ijpharm.2017.07.031 Transdermal Delivery of Dimethyl Fumarate for Alzheimer's Disease: Effect of Penetration Enhancers Journal of Molecular Neuroscience Bandiwadekar A. 653 72 2022 10.1007/s12031-021-01922-7 Emerging Novel Approaches for the Enhanced Delivery of Natural Products for the Management of Neurodegenerative Diseases Scientific Reports Fan J. 1310 7 2017 10.1038/s41598-017-01035-5 Berberine Produces Antidepressant‐Like Effects in Ovariectomized Mice Life Sciences Zhang N. 117637 252 2020 10.1016/j.lfs.2020.117637 Berberine Attenuates Aβ42‐Induced Neuronal Damage Through Regulating circHDAC9/miR‐142‐5p Axis in Human Neuronal Cells Biochemical and Biophysical Research Communications Asai M. 498 352 2007 10.1016/j.bbrc.2006.11.043 Berberine Alters the Processing of Alzheimer's Amyloid Precursor Protein to Decrease Aβ Secretion Life Sciences Raju M. 119990 285 2021 10.1016/j.lfs.2021.119990 Berberine Loaded Nanostructured Lipid Carrier for Alzheimer's Disease: Design, Statistical Optimization and Enhanced In Vivo Performance Lancet Bloem B. R. 2284 397 2021 10.1016/S0140-6736(21)00218-X Parkinson's Disease Lancet Kalia L. V. 896 386 2015 10.1016/S0140-6736(14)61393-3 Parkinson's Disease Aging Aguado J. 1592 14 2022 10.18632/aging.203925 Exploring Aging Interventions in Human Brain Organoids PLoS One Xiao C.‐W. e0124265 10 2015 10.1371/journal.pone.0124265 Digital Gene Expression Analysis of Microsporum canis Exposed to Berberine Chloride Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology Wang L. 109151 249 2021 Treatment of Parkinson's Disease in Zebrafish Model With a Berberine Derivative Capable of Crossing Blood Brain Barrier, Targeting Mitochondria, and Convenient for Bioimaging Experiments Signal Transduction and Targeted Therapy Wang Y. 77 6 2021 10.1038/s41392-020-00456-5 Oral Berberine Improves Brain Dopa/Dopamine Levels to Ameliorate Parkinson's Disease by Regulating Gut Microbiota Contrast Media & Molecular Imaging Li J. 8381870 2022 2022 10.1155/2022/8381870 Effect of Berberine Hydrochloride on the Diversity of Intestinal Flora in Parkinson's Disease Patients Pharma Innovation Kahale V. 101 3 2014 To Determine the Effect of Berberine on 6‐OHDA Induced Memory Impairment in Parkinson's Disease in Rodents Chinese Journal of Natural Medicines Jing W. 111 20 2022 10.1016/S1875-5364(22)60145-6 Demethylenetetrahydroberberine Protects Dopaminergic Neurons in a Mouse Model of Parkinson's Disease European Journal of Neurology Dobson R. 27 26 2019 10.1111/ene.13819 Multiple Sclerosis—A Review Phytotherapy Research Kulkarni S. 317 24 2010 10.1002/ptr.2968 Berberine: A Plant Alkaloid With Therapeutic Potential for central Nervous System Disorders Immunity, Inflammation and Disease Yazdanpanah E. e1213 12 2024 10.1002/iid3.1213 Berberine: A Natural Modulator of Immune Cells in Multiple Sclerosis PLoS One Ma X. e13489 5 2010 10.1371/journal.pone.0013489 Berberine Attenuates Experimental Autoimmune Encephalomyelitis in C57 BL/6 Mice Neuroscience & Biobehavioral Reviews Patel S. 589 83 2017 10.1016/j.neubiorev.2017.08.025 Crosstalk Between Endoplasmic Reticulum Stress and Oxidative Stress in Schizophrenia: The Dawn of New Therapeutic Approaches ChemMedChem Tarrago T. 354 2 2007 10.1002/cmdc.200600303 The Natural Product Berberine Is a Human Prolyl Oligopeptidase Inhibitor Chinese Medicine Pu Z. 41 18 2023 10.1186/s13020-023-00746-4 Berberine Improves Negative Symptoms and Cognitive Function in Patients With Chronic Schizophrenia via Anti‐Inflammatory Effect: A Randomized Clinical Trial Asian Journal of Psychiatry Qiu Y. 102896 67 2022 10.1016/j.ajp.2021.102896 Berberine Treatment for Weight Gain in Patients With Schizophrenia by Regulating Leptin Rather Than Adiponectin Hong Kong Medical Journal Chan M. Y. 1 29 3 2023 Berberine for Antipsychotic‐Induced Metabolic Syndrome in Patients With Schizophrenia Spectrum Disorders: Abridged Secondary Publication Journal of Hainan Medical University Dong W. 151 23 2017 Effect of Berberine Combined With Risperidone Therapy on Endocrine Hormones and Oxidative Stress in Patients With Schizophrenia Journal of Ethnopharmacology Zou H. 115 178 2016 10.1016/j.jep.2015.12.001 Induced Cortical Neurogenesis After Focal Cerebral Ischemia—Three Active Components From Huang‐Lian‐Jie‐Du Decoction Neuroscience Letters Zhou X.‐Q. 31 447 2008 10.1016/j.neulet.2008.09.064 Neuroprotective Effects of Berberine on Stroke Models In Vitro and In Vivo Biological and Pharmaceutical Bulletin Yoo K.‐Y. 623 29 2006 10.1248/bpb.29.623 Berberry Extract Reduces Neuronal Damage and N‐Methyl‐D‐Aspartate Receptor 1 Immunoreactivity in the Gerbil Hippocampus After Transient Forebrain Ischemia Brain Research Wang F. 91 999 2004 10.1016/j.brainres.2003.11.036 Effects of Berberine on Potassium Currents in Acutely Isolated CA1 Pyramidal Neurons of Rat Hippocampus Journal of Neuroscience Research Hong J. S. 489 90 2012 10.1002/jnr.22756 Effects of Berberine on Hippocampal Neuronal Damage and Matrix Metalloproteinase‐9 Activity Following Transient Global Cerebral Ischemia Frontiers in Pharmacology Zhao L. 609693 12 2021 10.3389/fphar.2021.609693 Berberine Attenuates Cerebral Ischemia‐Reperfusion Injury Induced Neuronal Apoptosis by Down‐Regulating the CNPY2 Signaling Pathway Neurochemical Research Yang J. 702 43 2018 10.1007/s11064-018-2472-4 Berberine Ameliorates MCAO Induced Cerebral Ischemia/Reperfusion Injury via Activation of the BDNF–TrkB–PI3K/Akt Signaling Pathway Pharmacological Research Liu D.‐Q. 104385 148 2019 10.1016/j.phrs.2019.104385 Berberine Protects Against Ischemia‐Reperfusion Injury: A Review of Evidence From Animal Models and Clinical Studies Brain Research Zhang X. 61 1459 2012 10.1016/j.brainres.2012.03.065 Neuroprotection of Early and Short‐Time Applying Berberine in the Acute Phase of Cerebral Ischemia: Up‐Regulated pAkt, pGSK and pCREB, Down‐Regulated NF‐κB Expression, Ameliorated BBB Permeability European Journal of Pharmacology Chai Y.‐S. 44 708 2013 10.1016/j.ejphar.2013.02.041 Effect of Berberine on Cell Cycle Arrest and Cell Survival During Cerebral Ischemia and Reperfusion and Correlations With p53/Cyclin D1 and PI3K/Akt BMC Pharmacology and Toxicology Azadi R. 54 22 2021 10.1186/s40360-021-00525-7 Anti‐Inflammatory Efficacy of Berberine Nanomicelle for Improvement of Cerebral Ischemia: Formulation, Characterization and Evaluation in Bilateral Common Carotid Artery Occlusion Rat Model Journal of Chemical Neuroanatomy Wang N. 102119 123 2022 10.1016/j.jchemneu.2022.102119 Berberine Protects Against Chronic Cerebral Hypoperfusion‐Induced Cognitive Impairment and Hippocampal Damage via Regulation of the ERK/Nrf2 Pathway European Journal of Pharmacology Wang X. 175782 953 2023 10.1016/j.ejphar.2023.175782 Berberine Modulates Gut Microbiota to Attenuate Cerebral Ferroptosis Induced by Ischemia‐Reperfusion in Mice Lancet Neurology Jensen T. S. 924 13 2014 10.1016/S1474-4422(14)70102-4 Allodynia and Hyperalgesia in Neuropathic Pain: Clinical Manifestations and Mechanisms Journal of Traditional Chinese Medicine Shuai H. 915 43 2023 Inhibitory Effect of Berberine on Morphine Tolerance and Hyperalgesia in Mice Biomedicine & Pharmacotherapy Sandeep M. 605 94 2017 10.1016/j.biopha.2017.07.142 Influence of Quercetin, Naringenin and Berberine on Glucose Transporters and Insulin Signalling Molecules in Brain of Streptozotocin‐Induced Diabetic Rats Journal of Basic and Clinical Physiology and Pharmacology Adefegha S. A. 389 33 2022 10.1515/jbcpp-2020-0173 Effects of Berberine on Cholinesterases and Monoamine Oxidase Activities, and Antioxidant Status in the Brain of Streptozotocin (STZ)‐induced Diabetic Rats Journal of Integrative Medicine Shinjyo N. 125 18 2020 10.1016/j.joim.2020.01.004 Berberine for Prevention of Dementia Associated With Diabetes and Its Comorbidities: A Systematic Review Frontiers in Pharmacology Hao Y. 917375 13 2022 10.3389/fphar.2022.917375 Neuroprotective Effect and Possible Mechanisms of Berberine in Diabetes‐Related Cognitive Impairment: A Systematic Review and Meta‐Analysis of Animal Studies European Journal of Pharmacology Dewanjee S. 472 833 2018 10.1016/j.ejphar.2018.06.034 Molecular Mechanism of Diabetic Neuropathy and Its Pharmacotherapeutic Targets Neuropharmacology Yerra V. G. 256 131 2018 10.1016/j.neuropharm.2017.12.029 Adenosine Monophosphate‐Activated Protein Kinase Modulation by Berberine Attenuates Mitochondrial Deficits and Redox Imbalance in Experimental Diabetic Neuropathy European Journal of Pharmacology Zhou J. 87 774 2016 10.1016/j.ejphar.2016.02.007 Neuroprotective Effect of Berberine Is Mediated by MAPK Signaling Pathway in Experimental Diabetic Neuropathy in Rats Neuropsychiatric Disease and Treatment Gao F. 2139 10 2014 10.2147/NDT.S73210 Berberine Exerts an Anticonvulsant Effect and Ameliorates Memory Impairment and Oxidative Stress in a Pilocarpine‐Induced Epilepsy Model in the Rat Basic and Clinical Neuroscience Mojarad T. B. 124 5 2014 The Anticonvulsant and Antioxidant Effects of Berberine in Kainate‐Induced Temporal Lobe Epilepsy in Rats Iranian Journal of Basic Medical Sciences Sadeghnia H. R. 588 20 2017 Berberine Attenuates Convulsing Behavior and Extracellular Glutamate and Aspartate Changes in 4‐Aminopyridine Treated Rats Reports of Biochemistry & Molecular Biology Ghanem H. B. 362 10 2021 10.52547/rbmb.10.3.362 Impact of Berberine on Some Epigenetic, Transcription Regulation and Inflammatory Biomarkers in a Mice Model of Epilepsy European Journal of Pharmaceutics and Biopharmaceutics El‐Nahas A. E. 182 188 2023 10.1016/j.ejpb.2023.04.008 Berberine‐Loaded Zein/Hyaluronic Acid Composite Nanoparticles for Efficient Brain Uptake to Alleviate Neuro‐degeneration in the Pilocarpine Model of Epilepsy Life Sciences Zhu H. 122347 336 2024 10.1016/j.lfs.2023.122347 Integrated Non‐Targeted Metabolomics and Network Pharmacology to Reveal the Mechanisms of Berberine in the Long‐Term Treatment of PTZ‐Induced Epilepsy European Journal of Pharmaceutical Sciences Hsu Y.‐Y. 415 46 2012 10.1016/j.ejps.2012.03.004 Berberine Activates Nrf2 Nuclear Translocation and Protects Against Oxidative Damage via a Phosphatidylinositol 3‐Kinase/Akt‐Dependent Mechanism in NSC34 Motor Neuron‐Like Cells European Journal of Pharmacology Hu J. 132 674 2012 10.1016/j.ejphar.2011.11.014 PI3K p55γ Promoter Activity Enhancement Is Involved in the Anti‐Apoptotic Effect of Berberine Against Cerebral Ischemia–Reperfusion Biological and Pharmaceutical Bulletin Cui H.‐S. 79 32 2009 10.1248/bpb.32.79 Berberine Exerts Neuroprotective Actions Against In Vitro Ischemia‐Induced Neuronal Cell Damage in Organotypic Hippocampal Slice Cultures: Involvement of B‐Cell Lymphoma 2 Phosphorylation Suppression Acta Physiologica Hungarica Benaissa F. 213 96 2009 10.1556/APhysiol.96.2009.2.6 Berberine Reduces the Hypoxic‐Ischemic Insult in Rat Pup Brain Behavioural Brain Research Bhutada P. 30 220 2011 10.1016/j.bbr.2011.01.022 Protection of Cholinergic and Antioxidant System Contributes to the Effect of Berberine Ameliorating Memory Dysfunction in Rat Model of Streptozotocin‐Induced Diabetes Food Research International Siow Y. L. 2409 44 2011 10.1016/j.foodres.2010.12.038 Redox Regulation in Health and Disease—Therapeutic Potential of Berberine Journal of Medicinal Plants Research Luo A. 3702 5 2011 Antioxidant Activities of Berberine Hydrochloride Advances in Pharmacological and Pharmaceutical Sciences Tilaoui M. 3018498 2018 2018 Studies on the Dual Cytotoxicity and Antioxidant Properties of Berberis vulgaris Extracts and Its Main Constituent Berberine Aging and Disease Xu Z. 760 8 2017 10.14336/AD.2016.0620 Rhizoma Coptidis and Berberine as a Natural Drug to Combat Aging and Aging‐Related Diseases via Anti‐Oxidation and AMPK Activation Phytotherapy Research Lin X. 1501 32 2018 10.1002/ptr.6107 Berberine: Pathways to Protect Neurons Biomedicine & Pharmacotherapy Fusi J. 805 101 2018 10.1016/j.biopha.2018.03.006 An In Vitro Comparative Study of the Antioxidant Activity and SIRT1 Modulation of Natural Compounds European Journal of Pharmacology Kumar A. 288 761 2015 10.1016/j.ejphar.2015.05.068 Current Knowledge and Pharmacological Profile of Berberine: An Update Iranian Journal of Basic Medical Sciences Mohammadzadeh N. 538 20 2017 Berberis vulgaris and Its Constituent Berberine as Antidotes and Protective Agents Against Natural or Chemical Toxicities Neural Regeneration Research Nam K. N. 1384 5 2010 Berberine Inhibits Inflammatory Activation of Rat Brain Microglia Annals of Neurology Kurth J. H. 368 33 1993 10.1002/ana.410330406 Association of a Monoamine Oxidase B Allele With Parkinson's Disease Neurochemical Research Rego A. C. 1563 28 2003 10.1023/A:1025682611389 Mitochondrial Dysfunction and Reactive Oxygen Species in Excitotoxicity and Apoptosis: Implications for the Pathogenesis of Neurodegenerative Diseases Cell St‐Pierre J. 397 127 2006 10.1016/j.cell.2006.09.024 Suppression of Reactive Oxygen Species and Neurodegeneration by the PGC‐1 Transcriptional Coactivators Neuroscience Research Yang L. 261 42 2002 10.1016/S0168-0102(02)00005-6 Increased Expression of Intranuclear AChE Involved in Apoptosis of SK‐N‐SH Cells Expert Opinion on Therapeutic Targets Holzgrabe U. 161 11 2007 10.1517/14728222.11.2.161 Targeting Acetylcholinesterase to Treat Neurodegeneration Journal of Neuroscience Vargas M. R. 13574 28 2008 10.1523/JNEUROSCI.4099-08.2008 Nrf2 Activation in Astrocytes Protects Against Neurodegeneration in Mouse Models of Familial Amyotrophic Lateral Sclerosis Free Radical Biology and Medicine Vries H. E. 1375 45 2008 10.1016/j.freeradbiomed.2008.09.001 Nrf2‐Induced Antioxidant Protection: A Promising Target to Counteract ROS‐Mediated Damage in Neurodegenerative Disease? Experimental Neurology Perry T. 293 203 2007 10.1016/j.expneurol.2006.09.028 Evidence of GLP‐1‐Mediated Neuroprotection in an Animal Model of Pyridoxine‐Induced Peripheral Sensory Neuropathy Vitamins & Hormones Hölscher C. 331 84 2010 10.1016/B978-0-12-381517-0.00013-8 The Role of GLP‐1 in Neuronal Activity and Neurodegeneration Proceedings of the National Academy of Sciences of the United States of America Li Y. 1285 106 2009 10.1073/pnas.0806720106 GLP‐1 Receptor Stimulation Preserves Primary Cortical and Dopaminergic Neurons in Cellular and Rodent Models of Stroke and Parkinsonism Molecular and Cellular Biology Kennedy S. G. 5800 19 1999 10.1128/MCB.19.8.5800 Akt/Protein Kinase B Inhibits Cell Death by Preventing the Release of Cytochrome c From Mitochondria Current Opinion in Neurobiology Brunet A. 297 11 2001 10.1016/S0959-4388(00)00211-7 Transcription‐Dependent and ‐Independent Control of Neuronal Survival by the PI3K–Akt Signaling Pathway Neuroscience Letters Nakaso K. 146 432 2008 10.1016/j.neulet.2007.12.034 Caffeine Activates the PI3K/Akt Pathway and Prevents Apoptotic Cell Death in a Parkinson's Disease Model of SH‐SY5Y Cells Nature Genetics Mantamadiotis T. 47 31 2002 10.1038/ng882 Disruption of CREB Function in Brain Leads to Neurodegeneration Frontiers in Bioscience Dragunow M. 100 9 2004 10.2741/1197 CREB and Neurodegeneration Journal of Pharmacology and Pharmacotherapeutics Schulz K. F. 100 1 2010 10.4103/0976-500X.72352 CONSORT 2010 Statement: Updated Guidelines for Reporting Parallel Group Randomised Trials The Organic Chemistry of Drug Design and Drug Action Silverman R. B. 2014 Phytotherapy Research Imenshahidi M. 504 33 2019 10.1002/ptr.6252 Berberine and Barberry ( Berberis vulgaris ): A Clinical Review Chinese Journal of Contemporary Neurology & Neurosurgery Zhu F.‐Q. 43 15 2015 Influence of Berberine Combining With Atorvastatin on Serum High‐Sensitivity C‐Reactive Protein and Adipocyte Fatty Acid‐Binding Protein in Patients With Acute Ischemic Stroke Genome Medicine Ming J. 125 13 2021 10.1186/s13073-021-00942-7 Effectiveness and Safety of Bifidobacterium and Berberine in Human Hyperglycemia and Their Regulatory Effect on the Gut Microbiota: A Multi‐Center, Double‐Blind, Randomized, Parallel‐Controlled Study China Journal of Chinese Materia Medica Li Y. 4066 41 2016 Effects of Berberine on Serum Inflammatory Factors and Carotid Atherosclerotic Plaques in Patients With Acute Cerebral Ischemic Stroke Drug Delivery and Translational Research Soudi S. A. 906 9 2019 10.1007/s13346-019-00626-1 Protective Effect of Surface‐Modified Berberine Nanoparticles Against LPS‐Induced Neurodegenerative Changes: A Preclinical Study BMC Neuroscience Zhu F. 78 7 2006 10.1186/1471-2202-7-78 Berberine Chloride Can Ameliorate the Spatial Memory Impairment and Increase the Expression of Interleukin‐1beta and Inducible Nitric Oxide Synthase in the Rat Model of Alzheimer's Disease Bioorganic & Medicinal Chemistry Letters Huang L. 6649 20 2010 10.1016/j.bmcl.2010.09.013 Berberine Derivatives, With Substituted Amino Groups Linked at the 9‐Position, as Inhibitors of Acetylcholinesterase/Butyrylcholinesterase Neurotoxicology Riederer P. 271 25 2004 10.1016/S0161-813X(03)00106-2 Monoamine Oxidase‐B Inhibition in Alzheimer's Disease Planta Medica Kong L. D. 74 67 2001 10.1055/s-2001-10874 Monoamine Oxidase Inhibitors From Rhizoma of Coptis chinensis World journal of gastroenterology Xu X. Y. 5403 25 36 2019 10.3748/wjg.v25.i36.5403 Chinese Guidelines on Management of Hepatic Encephalopathy in Cirrhosis Tianjin Medical Journal Li J. 1143 44 2016 The Impact of Berberine on Insulin Resistance and Cytokines in Patients With Schizophrenia Frontiers in Pharmacology Dan L. 1287750 14 2024 10.3389/fphar.2023.1287750 Neuroprotective Effects and Possible Mechanisms of Berberine in Animal Models of Alzheimer's Disease: A Systematic Review and Meta‐Analysis Frontiers in Pharmacology Liu J.‐Y. 1301102 14 2024 10.3389/fphar.2023.1301102 Effect of Berberine on Cognitive Function and β‐Amyloid Precursor Protein in Alzheimer's Disease Models: A Systematic Review and Meta‐Analysis Phytotherapy Research Luo D. 3820 37 2023 10.1002/ptr.7920 Effects of Adjuvant Berberine Therapy on Acute Ischemic Stroke: A Meta‐Analysis Phytotherapy Research Imenshahidi M. 1745 30 2016 10.1002/ptr.5693 Berberis vulgaris and Berberine: An Update Review Chinese Pharmaceutical Journal‐Beijing Baaxin L. 33 35 2000 Study on the Pharmacokinetics of Berberine in Single Dosage and Coadministration With Oryzanol in Rabbits and Healthy Volunteers Frontiers in Pharmacology Xiong H. 942955 13 2022 10.3389/fphar.2022.942955 Integrated Serum Pharmacochemistry, Metabolomics, and Network Pharmacology to Reveal the Material Basis and Mechanism of Danggui Shaoyao San in the Treatment of Primary Dysmenorrhea Biological and Pharmaceutical Bulletin Xiong Q. 1580 19 12 1996 10.1248/bpb.19.1580 Antioxidative Effects of Phenylethanoids From Cistanche Deserticola Acta Pharmacologica Sinica Pan J.‐F. 77 23 2002 Identification of Three Sulfate‐Conjugated Metabolites of Berberine Chloride in Healthy Volunteers' Urine After Oral Administration Aaps Pharmscitech Chen W. 705 12 2011 10.1208/s12249-011-9632-z Bioavailability Study of Berberine and the Enhancing Effects of TPGS on Intestinal Absorption in Rats Fitoterapia Liu C.‐S. 274 109 2016 10.1016/j.fitote.2016.02.001 Research Progress on Berberine With a Special Focus on Its Oral Bioavailability Food and Chemical Toxicology Kheir M. M. 1105 48 2010 10.1016/j.fct.2010.01.033 Acute Toxicity of Berberine and Its Correlation With the Blood Concentration in Mice Journal of Nutrition Terpstra A. 2067 131 2001 10.1093/jn/131.7.2067 Differences Between Humans and Mice in Efficacy of the Body Fat Lowering Effect of Conjugated Linoleic Acid: Role of Metabolic Rate Metabolism Yin J. 712 57 2008 10.1016/j.metabol.2008.01.013 Efficacy of Berberine in Patients With Type 2 Diabetes Mellitus Journal of Pharmaceutical and Biomedical Analysis Hua W. 931 44 2007 10.1016/j.jpba.2007.03.022 Determination of Berberine in Human Plasma by Liquid Chromatography–Electrospray Ionization–Mass Spectrometry Journal of Natural Products Spinozzi S. 766 77 2014 10.1021/np400607k Berberine and Its Metabolites: Relationship Between Physicochemical Properties and Plasma Levels After Administration to Human Subjects Drug Metabolism and Disposition Liu Y.‐T. 1779 38 2010 10.1124/dmd.110.033936 Extensive Intestinal First‐Pass Elimination and Predominant Hepatic Distribution of Berberine Explain Its Low Plasma Levels in Rats Xenobiotica Zhang X. 290 41 2011 10.3109/00498254.2010.529180 Intestinal Absorption Mechanisms of Berberine, Palmatine, Jateorhizine, and Coptisine: Involvement of P‐Glycoprotein Pharmacology & Toxicology Pan G. Y. 193 91 2002 10.1034/j.1600-0773.2002.t01-1-910403.x The Involvement of P‐Glycoprotein in Berberine Absorption Drug Metabolism Reviews Wang K. 139 49 2017 10.1080/03602532.2017.1306544 The Metabolism of Berberine and Its Contribution to the Pharmacological Effects PLoS One Tan X.‐S. e77969 8 2013 10.1371/journal.pone.0077969 Tissue Distribution of Berberine and Its Metabolites After Oral Administration in Rats Journal of Ethnopharmacology Guo Y. 111 138 2011 10.1016/j.jep.2011.08.058 Dose–Response of Berberine on Hepatic Cytochromes P450 mRNA Expression and Activities in Mice Journal of Ethnopharmacology Yi J. 303 145 2013 10.1016/j.jep.2012.10.062 Safety Evaluation of Main Alkaloids From Rhizoma Coptidis Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy Di Pierro F. 213 5 2012 10.2147/DMSO.S33718 Pilot Study on the Additive Effects of Berberine and Oral Type 2 Diabetes Agents for Patients With Suboptimal Glycemic Control Frontiers in Molecular Biosciences Singh N. 21 5 2018 10.3389/fmolb.2018.00021 Toxicological Effects of Berberine and Sanguinarine Journal of Biochemical and Molecular Toxicology Phogat A. e23434 37 2023 10.1002/jbt.23434 Neuroprotective Potential of Berberine Against Acetamiprid Induced Toxicity in Rats: Implication of Oxidative Stress, Mitochondrial Alterations, and Structural Changes in Brain Regions