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Table 2 Impact of resveratrol on the expression of genes in the context of CNS disorders

From: Disease-associated regulation of gene expression by resveratrol: Special focus on the PI3K/AKT signaling pathway

Type of disease

Dose range

Cell line

Target

Pathway

Function

Refs.

In vivo studies

Subarachnoid Hemorrhage (SAH)

60 mg/kg

–

Beclin-1, LC3-II, Bcl-2, p62, Caspase-3/9

AKT /mTOR

RVT via downregulating AKT/mTOR pathway could promote the autophagy process in SAH model rats

[19]

Cerebral Ischemia Injury (CII)

30 mg/kg

–

BcL-2, Bax, Caspase-3

JAK2/STAT3, PI3K/AKT/mTOR

RVT via activating JAK2/STAT3/PI3K/AKT/mTOR pathway could provide neuroprotection against cerebral I/R injury

[20]

CII

100 mg/kg

–

IL-1β, TNFα, COX2

PI3K/AKT

RVT via activating PI3K/AKT pathway could attenuate brain damage in permanent focal cerebral ischemia

[21]

CII

30 mg/kg

–

–

AKT/GSK-3β

RVT via regulating the AKT/GSK-3β pathway could improve neuronal damage against MCAO-induced CII

[24]

CII

20 mg/kg

–

GSK-3β, DJ-1, PTEN, Nrf-2, Bax, Caspase-3, Bcl-2

PI3K/AKT,

RVT via reducing of DJ-1 expression and activating of PI3K/AKT/GSK-3β pathway could contribute to post I/R cerebral damage

[25]

Chronic cerebral hypoperfusion (CCH)

50 mg/kg

–

Caspase-3, Bcl-2, Bax, LC3B, 4E-BP1, Beclin-1, S6K1

PI3K/AKT/mTOR

RVT via the AKT/mTOR pathway could Improve cognitive dysfunction in rats with CCH

[26]

Alzheimer’s Disease (AD)

0–40 μM

PC12

HO1

PI3K/AKT/Nrf2

RVT by upregulating heme oxygenase-1 (HO-1) via the PI3K/AKT/Nrf2 axis could attenuate the cytotoxicity induced by amyloid-β1–42 in PC12 cells

[22]

AD

300 mg/kg

–

PP2A, GSK-3β, Tau, Caspase-3, Bcl2, Bax

PI3K/AKT, AMPK

RVT via activating PP2A and PI3K/AKT induced-inhibition of GSK-3β could inhibit Tau phosphorylation in rat brain

[23]

Parkinson's Disease (PD)

15–30 mg/kg

–

Bax, Bcl-2, Caspase-3, PDK1

PI3K/AKT

RVT via activating the PI3K/AKT pathway could protect dopaminergic neurons from 6-hydroxy dopamine (6-OHDA)-induced apoptosis

[27]

Spinal Cord Injury (SCI)

100 mg/kg, 40 μM

Primary microglia, neurons

Beclin-1, Caspase-3, LC3B

PI3K

RVT-primed exosomes via the PI3K pathway could promote the recovery of motor function in SCI rats

[28]

In vitro studies

Intervertebral Disc Degeneration (IVDD)

200 mM

NPCs

Caspase-3, NF-κB, GSK-3β

PI3K/AKT/mTOR

RVT and 17β-estradiol via The PI3K/AKT/GSK-3β and PI3K/AKT/mTOR pathways could prevent IL-1β induced apoptosis in the human nucleus pulposus

[29]

IVDD

10–200 μM

NPCs

Caspase-3, MMP-3, MMP-13, COL2a-1, Aggrecan

PI3K/AKT

RVT and 17β-estradiol via the PI3K/AKT/caspase-3 pathway could play a role in apoptosis induced by interleukin-1β in rat nucleus pulposus cells

[30]

IVDD

50–100 μM

NP

GAPDH, SOX9, Aggrecan, Collagen II

PI3K/AKT

RVT via activating the PI3K/AKT pathway could increase nucleus pulposus matrix synthesis

[31]

IVDD

50 μM

NP

Aggrecan, Collagen II, Beclin-1, LC3

PI3K/AKT

RVT via the PI3K/AKT pathway by activating autophagy could enhance matrix biosynthesis of nucleus pulposus cells

[32]