Table 1 Neuroprotective effects of EGCG in in vitro and in vivo models of neurotoxicity

1

Antioxidant Effects

EGCG

• SOD1-G93A transgenic mice

• Regulates the expression of PI3-K, pAkt, and pGSK-3 signals

• Reduces activation of NF-KB and caspase-3

• Prolongs the life span

• Delays the onset of symptoms

[75, 175]

2

Antioxidant Effects

EGCG

• Age-associated oxidative damage in rat brain

• Increases activity levels of enzymic antioxidants like SOD and catalase

• Increases activity of non-enzymic antioxidants like tocopherol and ascorbic acid

[90]

3

Antioxidant Effects

EGCG

• Glucose oxidase-induced neurotoxicity in H 19-7 cells

• Increases cellular resistance to glucose oxidase-mediated oxidative damage

• Activates transcription factor Nrf2^a

[176]

4

Antioxidant Effects

EGCG

• Glutamate-induced toxicity in HT22 mouse hippocampus neuronal cells

• Kainic acid-induced neurotoxicity in rats

• Decreases glutamate-induced oxidative cytotoxicity

• Inactivates NF-kB signaling pathway^b

• Reduces ROS accumulation

[177]

5

Antioxidant Effects

Tea poly-phenol

• NMDA-induced neurotoxicity in mice

• Decreases ROS production

[178]

6

Antioxidant Effects

Tea poly-phenol

• Mice NMDA toxicity model

• Enhances behavioral and neurotoxic effects of NMDA

• Decreases ROS production

[179]

7

Modulation of Signalling Pathways

EGCG

• 6-OHDA induced neurotoxicity in human neuroblastoma (NB) SH-SY5Y cell

• Modulates Akt^c signaling pathways

[69]

8

Modulation of Signalling Pathways

EGCG

• 6-OHDA induced neurotoxicity in human neuroblastoma (NB) SH-SY5Y cell

• Modulates Erk1/2^d pathway

[15]

9

Modulation of Signalling Pathways

EGCG

• Inflammatory response induced by IL -1β and Aβ [25–35] in human astrocytoma, U373MG cells

• Modulates NF-kB signaling pathway

[180]

10

Modulation of Signalling Pathways

EGCG

• Inflammatory response induced by IL -1β and Aβ [25–35] in human astrocytoma, U373MG cells

• Modulates MAPK^e signaling pathway

[180]

11

Modulation of Signalling Pathways

EGCG

• Long-term serum deprivation of human SH-SY5Y neuroblastoma cells

• Modulates HIF-1α^f pathway

[181]

12

Modulation of Signalling Pathways

EGCG

• β-amyloid (Aβ) induced toxicity in human SH-SY5Y neuroblastoma cells

• Modulates PKC^g pathway

[182]

13

Protective effect against protein aggregation

EGCG

• Long-term serum deprivation of human SH-SY5Y neuroblastoma cells

• Regulates APP

• Reduced levels of toxic β-amyloid peptides in CHO cells over-expressing the APP “Swedish” mutation.

[102]

14

Protective effect against protein aggregation

EGCG

• MPTP- and DA-induced neurodegeneration in mice and rats

• Prevents the accumulation of iron and α-synuclein in the substantia nigra

[54]

15

Protective effect against protein aggregation

EGCG

• β-amyloid (Aβ) induced toxicity in human SH-SY5Y neuroblastoma cells.

• C57/BL mice

• Increases PKCα and PKC levels

• Enhances release of non-amyloidogenic sAPPα

[15]

16

Protective effect against protein aggregation

EGCG

• Biochemical assay

• Binds to β-sheet-rich aggregates

• Converts mature α-synuclein and Aβ fibrils into smaller nontoxic aggregates

[183]

17

Protective effect against protein aggregation

EGCG

• Biochemical assay

• Inhibits amyloid-fibril formation

[184]

18

Protective effect against protein aggregation

EGCG

• Biochemical assay

• Inhibits the fibrillogenesis of both α-synuclein and Aβ

• Promotes formation of nontoxic α-synuclein and Aβ oligomers. Prevents their conversion into toxic aggregates

[185]

19

Protective effect against protein aggregation

EGCG

• N2a cells stably transfected with “Swedish” mutant human APP

• Elevates active ADAM10 protein

• Increases APP α cleavage and α-secretase activity

• Produces no alteration in β-or γ-secretase activities

[186]

20

Protective effect against protein aggregation

EGCG

• PS2 transgenic mice model of AD

• Enhances memory function

• Induces α -secretase activity

• Reduces β- and γ-secretase activities

[187]

21

Modulation of cell death and survival genes

EGCG

• 6-OHDA induced neurotoxicity in neuroblastoma SH-SY5Y cells

• Decreases expression of pro-apoptotic genes like bax, bad, mdm1, caspase 1, caspase 6, TRAIL, p21, gadd45 and fas ligand.

• No effect on the expression of anti-apoptotic genes like bcl-w, bcl-2 and bcl-xL

[162, 163]

22

Modulation of cell death and survival genes

EGCG

• 6-OHDA induced neurotoxicity in neuroblastoma SH-SY5Y cells

• Decreases expression levels of bcl-2, bcl-xL and bcl-w.

[162]

23

Modulation of cell death and survival genes

EGCG

• 6-OHDA induced neurotoxicity in neuroblastoma SH-SY5Y cells

• Increases expression levels of bax, bad, gadd45, fas, fas ligand, caspase 3, caspase 6 and caspase 10

[163]

24

Modulation of cell death and survival genes

EGCG

• MPTP and 6-OHDA induced toxicity in Male C57-BL mice

• Decreases bax, caspase-6, gadd45 and TRAIL expression levels

[54]

25

Modulation of cell death and survival genes

EGCG

• Head and neck squamous cell carcinoma (HNSCC) cells

• Decreases levels of Bcl-2 and Bcl-XL proteins

• Increases Bax protein levels

• Activates caspase 9

[166]

26

Modulation of cell death and survival genes

EGCG

• Human prostate carcinoma LNCaP cells

• Decreases expression of the proapoptotic protein Bcl-2

• Activates p21/WAF1, Bax and caspase 3.

[167]