Table 3.

Natural compounds as anti-prion agents.

Name	Class	Source	Structure	Administration route	Strategy	MOA	Toxicity/BBB	Status	Ref
Baicalein	Flavonoids	Scutellaria lateriflora		Oral	Neuroprotection	Reduce ROS; Inhibit JNK phosphorylation		in vitro in vivo	[217–220]
Cannabidiol	Cannabinoid	Cannabis sativa			not conclusive	Reduce PrPSc levels	Can cross BBB Non-toxic	in vitro	[224]
Carnosic acid/ Carnosol	Catechol	Rosmarinus officinalis			PrPSc	Reduce de novo generation of PrPSc aggregates	Can cross BBB	in vitro	[226–228]
Curcumin	Curcuminoid	Curcuma longa		Oral	PrPC	Prevent PrPC-PrPSc conversion	Can cross BBB Non-toxic	in vitro in vivo (ineffective)	[229–234]
Epigallocatechin gallate	Catechins	Green tea			Autophagy	Cellular trafficking of PrPSC		in vitro	[235–239]
Ginsenosides Rg3	Saponins	Steamed Ginseng			Autophagy	Reduce toxicity of PrPSc		in vitro	[240–242]
Hinokitiol	Tropolone derivative	Cupressus spp.			Autophagy	Reduce toxicity of PrPSc		in vitro	[243–246]
Melatonin	Neuro-endocrine hormone	Pineal gland			Autophagy	Reduce toxicity of PrPSc		in vitro in vivo	[249–254]
Polydatin	Resveratrol glycoside	Polygonum cuspidatum			PrPC	Prevent PrPC-PrPSc conversion		in vitro in silico	[257–259]
Resveratrol	Stilbenoid	Grapes/berries			Autophagy	Reduce PrPSc levels		in vitro	[261,262]
Spermine	Polyamine	Eukaryotic cells			Autophagy	Reduce toxicity of PrPSc Decrease ROS		in vitro	[266]
Tauroursodeoxycholic acid and Ursodeoxycholic acid	Bile acid	Bile			PrPC; Chemical chaperone	Reduce PrPC-PrPSc conversion	Can cross BBB Non-toxic	in vitro in vivo	[221–223]
Trehalose	Disaccharide	Fungi, plants and invertebrates		Oral	Autophagy	Reduce PrPSc accumulation		in vitro in vivo	[268–271]