Table 1.

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

Sr No	Mol. Mech	Drug	Model	Effect	Ref.
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 Nrf2a	[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 pathwayb • 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 Aktc signaling pathways	[69]
8	Modulation of Signalling Pathways	EGCG	• 6-OHDA induced neurotoxicity in human neuroblastoma (NB) SH-SY5Y cell	• Modulates Erk1/2d 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 MAPKe signaling pathway	[180]
11	Modulation of Signalling Pathways	EGCG	• Long-term serum deprivation of human SH-SY5Y neuroblastoma cells	• Modulates HIF-1αf pathway	[181]
12	Modulation of Signalling Pathways	EGCG	• β-amyloid (Aβ) induced toxicity in human SH-SY5Y neuroblastoma cells	• Modulates PKCg 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]

^aTranscription factor Nrf2 is a master regulator of the antioxidant response

^bNFkB signalling pathway is the pathway which is activated in response to cell stress

^cAkt signalling pathway promotes survival and growth in response to extracellular signals

^dERK1/2 cascade plays an important role in cellular proliferation, differentiation and survival

^eMAPK signalling pathway plays an important role in cellular proliferation, differentiation and survival

^fHIF – 1α plays an integral role in the body's response to low oxygen concentrations

^gPKC signalling pathway regulates many cellular responses such as gene expression, cell proliferation, and inflammatory responses