Neuroprotective role of baicalein and baicalin in Alzheimer’s disease.
| Mechanism/Effect | Major outcomes | Model/Method | Reference(s) |
|---|---|---|---|
| Baicalein | |||
| ER stress inhibition | Inhibited ROS, CHOP induction, mitochondrial depolarization | HT22 cells, thapsigargin & brefeldin A-induced stress | [128] |
| H2O2-induced oxidative stress | Blocked JNK/ERK pathways, restored GSH, reduced ROS | PC12 cells | [127] |
| Aβ toxicity & antioxidant action | Antioxidant activity > vitamin C, protected PC12 cells | PC12, Aβ-induced | [126] |
| Gut-brain axis modulation | Improved cognition via microbiota modulation | AD mouse model | [103] |
| Tau aggregation inhibition | Dissolved preformed tau fibrils | In vitro, MALDI-TOF | [123] |
| Paired helical filament inhibition | Promoted non-toxic tau oligomers | In vitro | [105] |
| Reversed Aβ-induced memory loss | Regulated cAMP/cGMP-pCREB-BDNF pathway | Aβ-injected mice | [133] |
| Synaptic protection & memory rescue | Restored spine density, inhibited Aβ & tau pathology | AD mouse model | [125] |
| Anxiety & memory deficits | Reduced AChE activity, improved anxiety in zebrafish | Scopolamine-induced model | [104] |
| Memory improvement | Enhanced ChAT neurons, reduced microglia | Ibotenic acid rat model | [105] |
| Aβ25–35-induced amnesia | Prevented & reversed memory loss | Passive avoidance test | [106] |
| Neuroplasticity regulation | Restored CaM-CamkIV-CREB signaling | Composite AD rat model | [107] |
| Tau hyperphosphorylation reduction | Reduced tau pathology in the hippocampus/cortex | AD rat model | [108] |
| Myelin sheath degeneration reversal | Upregulated myelin proteins, modulated sphingomyelin metabolism | AD rat model | [137] |
| Inhibits astrocytic GABA synthesis | Inhibited MAO-B, reversed tonic inhibition | LPS mouse model | [129] |
| Microglial M2 polarization | Reduced neuroinflammation, improved cognition | 3Tg-AD mice | [130–132] |
| Dual inhibition of Aβ & AChE | Aryl-coumarin derivative is more potent than donepezil | Zebrafish AD model | [109] |
| α-syn & Aβ aggregation inhibition | Prevented/Disaggregated α-syn & AβOs | In vitro, cell lines | [51, 116, 122] |
| Inhibits Aβ42 membrane permeabilization | The flavone scaffold is effective in membrane protection | Liposome assay | [114, 115] |
| IDO-1 inhibition | Inhibited IDO-1, promoted neurite outgrowth in hNSCs | In vitro | [138] |
| Aβ/AMPA/NMDA depolarization reversal | Inhibited receptor-induced depolarization | DiBAC4(3) dye, cortical neurons | [110] |
| BACE1 & AChE inhibition | Strong dual inhibition with good docking affinity | In vitro, in silico | [111] |
| Lipoxygenase & GSK3β inhibition | Lowered BACE1 & Aβ levels | Hippocampal slices | [125] |
| Proteomic alterations | Altered proteins linked to metabolism & signaling | AD rat model, proteomics | [112] |
| With trans-chalcone | Reduced ROS & Aβ42 more effectively | Yeast model | [56] |
| With daidzein | Synergistic estrogenic & neuroprotective activity | PC12 cells | [139] |
| With wogonin | Reduced TNF-α, NO, and apoptosis | PC12 cells, Aβ25–35 | [140] |
| With memantine | Decreased plaques, increased BDNF | Wistar rats, AD model | [141] |
| Baicalin | |||
| Aβ Aggregation Inhibition | Inhibits Aβ aggregation (± Cu2+), reduces oxidative stress, and H2O2-induced toxicity. | SH-SY5Y cell line | [51] |
| Anti-apoptotic effect | Inhibits NO, TNF-α, and PGE2 in PC12 cells | In vitro | [143] |
| Anti-apoptotic and antioxidant effect | Improves cognition, reduces oxidative stress markers, restores antioxidant enzymes, and prevents mitochondrial damage via the Nrf2 pathway. | Aβ1–42-induced rat model | [86] |
| Anti-neuroinflammatory | Reduces TNF-α, IL-6, and glial activation; improves memory | Aβ1–42 mouse model | [144] |
| Microglial modulation | Suppresses TLR4/NF-κB and NLRP3 inflammasome, reduces microglia-mediated inflammation, and improves cognition. | APP/PS1 mice, BV2 microglial cells | [143] |
| Mitochondrial plasticity | Improves synaptic proteins, inhibits PDE4 & mitochondrial fission | AβO-induced model | [83] |
| Neural regeneration | Enhances spatial learning, hippocampal neurogenesis, and regulates NPTX-1/2 and CRP levels. | AD rat model | [145] |
| Synaptic & mitochondrial protection | Increases synaptic proteins (PSD95, MAP-2), reduces mitochondrial fragmentation and dysfunction via PDE4 inhibition. | AβO-induced model | [83] |
ER: endoplasmic reticulum; ROS: reactive oxygen species; CHOP: C/EBP homologous protein; GSH: glutathione; Aβ: amyloid-beta; AD: Alzheimer’s disease; MALDI-TOF: matrix-assisted laser desorption/ionization-time of flight; AChE: acetylcholinesterase; ChAT: choline acetyltransferase; GABA: gamma-aminobutyric acid; MAO-B: monoamine oxidase B; LPS: lipopolysaccharide; α-syn: alpha-synuclein; IDO-1: indoleamine dioxygenase 1; hNSCs: human neural stem cells; TNF-α: tumor necrosis factor-alpha; IL-6: interleukin-6; AβO: Aβ oligomer; CRP: C-reactive protein.
The supplementary table for this article is available at: https://www.explorationpub.com/uploads/Article/file/1004121_sup_1.pdf.
PS: Validation, Writing—review & editing. JM: Validation, Supervision. SP: Conceptualization, Writing—original draft, Writing—review & editing. All authors have read and approved the submitted version.
The authors declare that they have no conflicts of interest.
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