Kainic Acid-Induced Excitotoxicity Experimental Model: Protective Merits of Natural Products and Plant Extracts

Table 2

A summary on the protective effect of natural products and plant extracts against KA-induced excitotoxicity in vivo and in vitro experimental models.

Proposed mechanisms	Natural products/extracts/compounds	Sources	Experimental model	Reference(s)
Antioxidant activity	Decursin (purified from ethanol extract of the Angelica gigas Nakai root)	Angelica gigas Nakai	KA-induced in vivo and in vitro primary hippocampal neuronal cells excitotoxicity	[108]
	Asparagus racemosus extract	Asparagus racemosus	KA-induced in vivo excitotoxicity	[119]
	Butanol fraction of methanol extract from Aster scaber Thunb. leaves	Aster scaber Thunb. (Korean chamchwi)	KA-induced in vivo excitotoxicity	[96, 120]
	Acetyl-11-keto-β-boswellic acid (AKBA)	Boswellia serrata	KA-induced in vivo excitotoxicity	[95]
	Green tea leaf extract and gallic acid	Camellia sinensis	KA-induced in vivo excitotoxicity and KA-induced in vitro PC12 cells excitotoxicity	[74]
	Pu-Erh tea leaf extract and gamma-aminobutyric acid (GABA)	Camellia sinensis var. assamica	KA-induced in vivo excitotoxicity and KA-induced in vitro PC12 cells excitotoxicity	[75]
	Capsaicin	Capsicum (hot pepper)	KA-induced in vivo excitotoxicity	[121]
	Apigenin (flavone)	Cirsium japonicum and Carduus crispus	KA-induced in vivo and in vitro primary hippocampal neuronal cells excitotoxicity	[122]
	Curcumin	Curcuma longa Linn (turmeric)	KA-induced in vivo excitotoxicity	[123]
	Ursolic acid	Cynomorium songaricum Rupr. (Souyang)	KA-induced in vitro hippocampal neuronexcitotoxicity	[124]
	Galantamine	Galanthus nivalis	KA-induced in vivo excitotoxicity	[20]
	Gastrodia elata extract	Gastrodia elata	KA-induced in vivo excitotoxicity	[70, 125]
	Anthocyanins	Glycine max (L.) Merr. seed (Korean black bean)	KA-induced in vitro HT22 cells and primary hippocampal neuronal cells excitotoxicity	[111]
	Licorice flavonoids extractedliquiritigenin, isoliquiritigenin, and liquiritin	Glycyrrhiza uralensis	KA-induced in vivo excitotoxicity	[18]
	Naringin (flavonoid)	Grapefruit and citrus fruit	KA-induced in vivo excitotoxicity	[22]
	Vineatrol	Grapes	KA-induced in vivo excitotoxicity	[126]
	Water fraction from methanol extract of Ixeris dentata	Ixeris dentata	KA-induced in vivo excitotoxicity	[127]
	Ginsenosides	Panax ginseng (Asian)	KA-induced in vivo excitotoxicity	[65]
	Red ginseng extract	Panax ginseng (Asian)	KA-induced in vivo and in vitro primary hippocampal neuron cell excitotoxicity	[66]
	Butanol fraction of methanol extract from Petasite japonicus Max. leaves (BMP) and its subfractions (BMP-I or BMP-II)	Petasite japonicus (Sieb. et Zucc.) Maxim. (Compositae) leaves	KA-induced in vivo excitotoxicity	[128]
	Petaslignolide A (lignin glycoside) butanol fraction of methanol extract from Petasite japonicus (Sieb. et Zucc.) Maxim. (Compositae) leaves	Petasite japonicus (Sieb. et Zucc.) Maxim. (Compositae) leaves	KA-induced in vivo excitotoxicity	[129]
	Ethanolic-extracted propolis	Honey bee propolis	KA-induced in vivo excitotoxicity	[84, 85]
	trans-Resveratrol	Red Grapes	KA-induced in vivo excitotoxicity	[130, 131]
	Sesamin	Sesamum indicum (sesame seeds)	KA-induced in vivo excitotoxicity and KA-induced in vitro PC12 cells and BV2 cells excitotoxicity	[132]
	Rhynchophylline and Uncaria rhynchophylla extract	Uncaria rhynchophylla	KA-induced in vivo and in vitro excitotoxicity	[70]
	Branch and leaf ethanol extracts of Vitis thunbergii var. taiwaniana	Vitis thunbergii var. taiwaniana	KA-induced in vivo and in vitro BV2 cells excitotoxicity	[133]
	Withania somnifera extract	Withania somnifera	KA-induced in vivo and in vitro excitotoxicity	[134]
	(−)-Epigallocatechin-3-gallate (EGCG)	Tea	KA-induced in vivo excitotoxicity	[135]
Anti-inflammation	Green tea leaf extract and gallic acid	Camellia sinensis	KA-induced in vivo excitotoxicity and KA-induced in vitro PC12 cells excitotoxicity	[74]
	Pu-Erh tea leaf extract and gamma-aminobutyric acid (GABA)	Camellia sinensis var. assamica	KA-induced in vivo excitotoxicity and KA-induced in vitro PC12 cells excitotoxicity	[75]
	Capsaicin	Capsicum (hot pepper)	KA-induced in vivo excitotoxicity	[121]
	Curcumin	Curcuma longa Linn (turmeric)	KA-induced in vivo excitotoxicity	[110]
	Sesamin	Sesamum indicum (sesame seeds)	KA-induced in vivo excitotoxicity and KA-induced in vitro PC12 cells and BV2 cells excitotoxicity	[132]
	Galantamine	Galanthus nivalis	KA-induced in vivo excitotoxicity	[20]
	Glycyrrhizin (triterpene)	Glycyrrhiza glabra (licorice) root and rhizome	KA-induced in vivo excitotoxicity and primary cortical cultures	[136]
	Naringin (flavonoid)	Grapefruit and citrus fruit	KA-induced in vivo excitotoxicity	[22]
	Baicalin	Scutellaria baicalensis	KA-induced in vivo excitotoxicity	[137]
	Blueberry polyphenols	Blueberry	KA-induced in vivo and in vitro FaO rat hepatoma cells excitotoxicity	[94, 138]
Anticonvulsion and antiepileptic	Chongmyungtang	Acorus gramineus, Polygala tenuifolia, and Poria cocos	KA-induced in vivo excitotoxicity	[113]
	Decursin (purified from ethanol extract of the Angelica gigas Nakai root)	Angelica gigas Nakai	KA-induced in vivo and in vitro primary hippocampal neuronal cells excitotoxicity	[108]
	Acetyl-11-keto-β-boswellic acid (AKBA)	Boswellia serrata	KA-induced in vivo excitotoxicity	[95]
	Green tea leaf extract and gallic acid	Camellia sinensis	KA-induced in vivo excitotoxicity and KA-induced in vitro PC12 cells excitotoxicity	[74]
	Pu-Erh tea leaf extract and gamma-aminobutyric acid (GABA)	Camellia sinensis var. assamica	KA-induced in vivo excitotoxicity and KA-induced in vitro PC12 cells excitotoxicity	[75]
	Capsaicin	Capsicum (hot pepper)	KA-induced in vivo excitotoxicity	[121]
	Sinapic acid	Brassicaceae	KA-induced in vivo excitotoxicity	[139]
	Apigenin (flavone)	Cirsium japonicum and Carduus crispus	KA-induced in vivo and in vitro primary hippocampal neuronal cells excitotoxicity	[122]
	Ethanolic extract of Desmodium adscendens	Desmodium adscendens	KA-induced in vivo excitotoxicity	[140]
	Gastrodia elata extract	Gastrodia elata	KA-induced in vivo excitotoxicity	[70, 125]
	Naringin (flavonoid)	Grapefruit and citrus fruit	KA-induced in vivo excitotoxicity	[22]
	Vineatrol	Grapes	KA-induced in vivo excitotoxicity	[126]
	Ginsenosides	Panax ginseng (Asian)	KA-induced in vivo excitotoxicity	[65]
	Rb ginsenosides (Rb extract)	Panax quinquefolius (America)	KA-induced in vivo excitotoxicity	[26]
	Butanol fraction of methanol extract from Petasite japonicus Max. leaves (BMP) and its subfractions (BMP-I or BMP-II)	Petasite japonicus (Sieb. et Zucc.) Maxim. (Compositae) leaves	KA-induced in vivo excitotoxicity	[128]
	Petaslignolide A (lignin glycoside) butanol fraction of methanol extract from Petasite japonicus (Sieb. et Zucc.) Maxim. (Compositae) leaves	Petasite japonicus (Sieb. et Zucc.) Maxim. (Compositae) leaves	KA-induced in vivo excitotoxicity	[129]
	Rhynchophylline and Uncaria rhynchophylla extract	Uncaria rhynchophylla	KA-induced in vivo and in vitro excitotoxicity	[29, 70]
	Gastrodia elata extract	Gastrodia elata	KA-induced in vivo excitotoxicity	[70, 125]
	trans-Resveratrol	Red Grapes	KA-induced in vivo excitotoxicity	[130, 131]
	Branch and leaf ethanol extracts of Vitis thunbergii var. taiwaniana	Vitis thunbergii var. taiwaniana	KA-induced in vivo and in vitro BV2 cells excitotoxicity	[133]
Modulation of apoptosis-regulatory genes/proteins and signaling pathways	Curcumin	Curcuma longa Linn (turmeric)	KA-induced in vivo excitotoxicity	[110, 123]
	Anthocyanins	Glycine max (L.) Merr. seed (Korean black bean)	KA-induced in vitro HT22 cells and primary hippocampal neuronal cells excitotoxicity	[111]
	Ethanolic-extracted propolis	Honey bee propolis	KA-induced in vivo excitotoxicity	[84]
	Baicalin	Scutellaria baicalensis	KA-induced in vivo excitotoxicity	[137]
	Green tea leaf extract and gallic acid	Camellia sinensis	KA-induced in vivo excitotoxicity and KA-induced in vitro PC12 cells excitotoxicity	[74]
	Pu-Erh tea leaf extract and gamma-aminobutyric acid (GABA)	Camellia sinensis var. assamica	KA-induced in vivo excitotoxicity and KA-induced in vitro PC12 cells excitotoxicity	[75]
	Gastrodia elata extract	Gastrodia elata	KA-induced in vivo excitotoxicity	[70, 125]
	Rhynchophylline and Uncaria rhynchophylla extract	Uncaria rhynchophylla	KA-induced in vivo and in vitro excitotoxicity	[104]
Cognitive enhancer	Blueberry polyphenols	Blueberry	KA-induced in vivo and in vitro FaO rat hepatoma cells excitotoxicity	[94, 138]
	Sinapic acid	Brassicaceae	KA-induced in vivo excitotoxicity	[139]
	Galantamine	Galanthus nivalis	KA-induced in vivo excitotoxicity	[20]
	Gastrodia elata extract	Gastrodia elata	KA-induced in vivo excitotoxicity	[70, 125]
	Licorice flavonoids extractedliquiritigenin, isoliquiritigenin, and liquiritin	Glycyrrhiza uralensis	KA-induced in vivo excitotoxicity	[18]
	Naringin (flavonoid)	Grapefruit and citrus fruit	KA-induced in vivo excitotoxicity	[22]
Manipulation of pro- and anti-inflammatory cytokines	Blueberry polyphenols	Blueberry	KA-induced in vivo and in vitro FaO rat hepatoma cells excitotoxicity	[94, 138]
Manipulation of glial activation and inflammatory cytokines	Chongmyungtang	Acorus gramineus, Polygala tenuifolia, and Poria cocos	KA-induced in vivo excitotoxicity	[113]
	Decursin (purified from ethanol extract of the Angelica gigas Nakai root)	Angelica gigas Nakai	KA-induced in vivo and in vitro primary hippocampal neuronal cells excitotoxicity	[108]
	Sinapic acid	Brassicaceae	KA-induced in vivo excitotoxicity	[139]
	Acacetin (flavone)	Clerodendrum inerme (L.) Gaertn (Ci)	KA-induced in vivo excitotoxicity	[141]
	Curcumin	Curcuma longa Linn (turmeric)	KA-induced in vivo excitotoxicity	[110, 123]
	RVH-1 (stigma-4-en-3-one) and RVH-2 (stigma-4-en-3,6-dione)	Detoxified Rhus verniciflua	KA-induced in vivo excitotoxicity	[142]
	Glycyrrhizin (triterpene)	Glycyrrhiza glabra (licorice) root and rhizome	KA-induced in vivo excitotoxicity and primary cortical cultures	[136]
	trans-Resveratrol	Red Grapes	KA-induced in vivo excitotoxicity	[130, 131]
	Rhynchophylline and Uncaria rhynchophylla extract	Uncaria rhynchophylla	KA-induced in vivo and in vitro excitotoxicity	[29, 72]
Enhancing mitochondrial functions	Ursolic acid	Cynomorium songaricum Rupr. (Souyang)	KA-induced in vitro hippocampal neuronexcitotoxicity	[124]
	Galantamine	Galanthus nivalis	KA-induced in vivo excitotoxicity	[20]
	Ginsenosides	Panax ginseng (Asian)	KA-induced in vivo excitotoxicity	[65]
Inhibition of NO by NOS inhibitors	Branch and leaf ethanol extracts of Vitis thunbergii var. taiwaniana	Vitis thunbergii var. taiwaniana	KA-induced in vivo and in vitro BV2 cells excitotoxicity	[133]
Combating excitotoxicity	Ginkgo biloba leaf extract	Ginkgo biloba	KA-induced in vitro cerebellar neuronal cells excitotoxicity	[116]