|
Compounds | Mechanisms and targets | Ref. |
|
Flavones (15) |
Apigenin | Anti-inflammation: iNOS↓, COX-2↓, p-p38↓, p-JNK↓; histone deacetylases↓; BDNF/CREB/Syn-1↑ | [77, 125] |
APG | Antioxidation: p-STAT3↑ | [126] |
Vitexin | Antiapoptosis: p-Erk↑, p-JNK↓, p-p38↓ | [127] |
Baicalein | Anti-inflammation: NF-κB↓, p-MAPKs↓, arachidonic acid release↓: 12/15-LOX/p38 MAPK/cPLA2↓; antiapoptosis; antiautophagy: PI3K/Akt/mTOR↑ | [82, 109] |
Baicalin | Antiapoptosis: p-CaMKII↓; antioxidation: peroxynitrite scavenging↑; anti-inflammation: TLR2/4/NF-κB↓; mitochondrial function↑: Drp-1↓, Mfn2↓, AMPKα1↑ | [94, 128–131] |
Chrysin | Anti-inflammation: NF-κB↓, COX-2↓, iNOS↓; antioxidation | [78, 132, 133] |
Diosmin | Bcl-2/Bax↑; JAK2/STAT3↑ | [134] |
Ginkgetin | Antioxidation; anti-inflammation: JAK2/STAT3/SIRT1↓ | [135] |
Hispidulin | NLRP3-mediated pyroptosis↓; AMPK/GSK3β↑ | [136] |
Luteolin | Anti-inflammation: TLR4/5/p38/NF-κB↓; antioxidation; antiapoptosis | [95, 137, 138] |
Luteoloside | Anti-inflammation: PPARγ↑/Nrf2↑/NF-κB↓ | [139] |
Orientin | Antioxidation; anti-inflammation: TLR4/NF-κB/TNF-α↓; AQP-4↓ | [140] |
Nobiletin | Anti-inflammation: TLR4/NF-κB↓; antioxidation: Nrf2/HO-1↑; antiapoptosis: Akt/mTOR↑; BDNF-Akt/CREB↑; BBB permeability↓ | [60, 141–143] |
Scutellarin | Anti-inflammation: ACE/Ang II/AT1R↓, microglial activation↓, microglial-mediated astrogliosis↑, Notch-1/Nestin↑; neurotrophin expression↑: BDNF/NGF/GDNF-Akt/CREB↑; antioxidation | [67, 144–147] |
Tricin 7-glucoside | Anti-inflammation: NF-κB activation↓, HMGB1 expression↓ | [148] |
Flavanones (7) |
Eriodictyol | Anti-inflammation | [152] |
Eriodictyol-7-O-glucoside | Antioxidation in astrocytes: Nrf2/ARE↑ | [153] |
Hesperidin | Antioxidation: NO pathway↓ | [154] |
Naringenin | BBB protection: NOD2/RIP2/NF-κB/MMP-9↓; antiapoptosis; anti-inflammation: NF-κB↓; antioxidation: Nrf2 | [61, 85, 155] |
Naringin | ONOO−-mediated excessive mitophagy↓ | [156] |
Neohesperidin | Antiapoptosis; antioxidation: Akt/Nrf2/HO-1↑ | [157] |
Pinocembrin | Antiapoptosis; autophagy↑; anti-inflammation: sEH/EETs↓; neuronal loss↓; astrocyte proliferation↓ | [29, 158–160] |
Flavanols (3) |
(−)-Epicatechin (EC) | Anti-inflammation: microglial activation↓; antioxidation: Nrf2/HO-1↑ | [68, 163] |
(−)-Epigallocatechin-3-Gallate (EGCG) | Calcium modulation and antiexcitotoxicity: TRPC6 degradation↓/MEK/Erk/CREB↑, balance between the excitatory and inhibitory amino acids↑; antiapoptosis: PI3K/Akt/eNOS↑; antioxidation: Nrf2/ARE↑; anti-inflammation: NF-κB↓; BBB protection: MMP-2↓, MMP-9↓; ER stress↓ | [37, 164–170] |
Procyanidin B2 | BBB protection; antioxidation: Nrf2↑ | [171] |
Flavonols (10) |
Fisetin | Anti-inflammation: macrophage infiltration↓, microglial activation↓, JNK/NF-κB↓ | [69] |
Galangin | Microenvironment of the neurovascular unit (NVU)↑: Wnt/β-catenin↑, HIF-1α/VEGF↑; mitochondrial protection and antiapoptosis: Bax/Bcl-2↓ | [101, 175] |
Icariin | HDAC↓/CREB↑; SIRT1/PGC-1α↑; anti-inflammation: PPARα/γ↑, NF-κB↓ | [89, 176, 177] |
Kaempferol-3-O-rutinoside (KRS)/glucoside (KGS) | Anti-inflammation: STAT3↓, NF-κB↓ | [178] |
Kaempferide-7-O-(4-O-acetylrhamnosyl)-3-O-rutinoside | Anti-inflammation; antioxidation; antiapoptosis | [179] |
Quercetin | Energy metabolism↑; antioxidation; PP2A subunit B↑; antiapoptosis | [180–182] |
Rutin | Estrogen receptors↑: BDNF/TrkB/Akt↑ and NGF/TrkA/CREB↑; BBB protection: MMP-9 activity↓ | [119, 183] |
Isoquercetin | Antiapoptosis; anti-inflammation and antioxidation: Nrf2↑, NOX4/ROS/NF-κB↓, MAPK/TLR4/NF-κB↓ | [54, 184] |
Isorhamnetin | Nrf2/HO-1↑; iNOS/NO↓ | [185] |
Myricetin | Anti-inflammation: p38/NF-κB↓; antioxidation; p-Akt↑ | [186] |
Isoflavones (6) |
Calycosin | Anti-inflammation: microglial activation↓; antiapoptosis; antiautophagy; BDNF/TrkB↑; calcium modulation: TRPC6/CREB | [43, 70, 190, 191] |
Calycosin-7-O-β-D-glucoside | BBB protection: NO↓/Cav-1↑/MMPs↓ | [192] |
Formononetin | Bax/Bcl-2↓; PI3K/Akt↑ | [193] |
Genistein | Antioxidation: Nrf2↑; antiapoptosis: PI3K/Akt/mTOR↑; Erk activation↑; ROS/NF-κB↓; antiplatelet aggregation; vascular protection | [194–199] |
Daidzein | ROS production↓ | [200] |
Puerarin | Antiautophagy; anti-inflammation: neutrophil activation↓, HIF-1α↓, α7nAchR↑; antiapoptosis: PI3K/Akt1/GSK-3β/MCL-1↑; BDNF secret↑ | [70, 109, 110] |
Anthocyanidins, chalcones, and flavonolignans (5) |
Cyanidin-3-O-glucoside | Antiapoptosis: oxidative stress-induced AIF release↓ | [211] |
Hydroxysafflor yellow A (HSYA) | Antioxidation↓; anti-inflammation: TLR4/MAPK/NF-κB↓; antiapoptosis: PI3K/Akt/GSK3β↑, mPTP opening↓; neurotrophin release↑: BDNF↑, GFAP↑, NGF↑; autophagy↑: Akt↑; mitochondrial function and biogenesis↑; phenylalanine synthesis↓ | [98, 106, 212–215] |
Xanthohumol | Anti-inflammation; antiapoptosis; platelet activation↓ | [216] |
Silibinin/silybin | Anti-inflammation; antioxidation; antiapoptosis and antiautophagy: PI3K/Akt/mTOR↑ | [104, 217] |
Silymarin | Antioxidation; antiapoptosis | [218] |
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