TABLE 1.

The role of natural products in the treatment of Chemobrain.

Categories	Monomers	Chemical structures	Chemotherapeutic agents	Effects	Molecular mechanisms	Ref. (PMID)
Phenols	Resveratrol		Doxorubicin	GFAP↓, IBA-1↓	Anti-inflammation	34536813
			Docetaxel, adriamycin, and cyclophosphamide	IL-6↓,TNF-α↓,IL-4↑,IL-10↑ GABAAR↑, NMDAR1↑, p-CaMKII↓, BDNF↑,TrkB↑	Anti-inflammation; Improve neuroplasticity	29534932
	Polydatin		Doxorubicin	MDA↓, GSH↑, TNF-α↓, PGE-2↓, COX-2↓, cleaved caspase-3↓, cleaved caspase-9↓	Anti-inflammation; Anti-apoptosis; Anti-oxidative stress	31992173
	Epigallocatechin-3-gallate		Cisplatin	IL-6↓, TNF-α↓, iNOS↓, MDA↓, NO↓, TAC↑, Cleaved caspase-3↓,Bax↓, Bcl-2↑, BDNF↑, AChE↑, ACh↓	Anti-inflammation; Anti-apoptosis; Anti-oxidative stress; Improve neurotransmitter release	31410684
	Curcumin		Cisplatin	Bax↓, Bcl-2↑, Bim↓, LC3-II/LC3-I↑	Improve neurogenesis and synaptogenesis Increase autophagy	31843707
			Cisplatin	MDA↓,SOD↑, AChE↑	Anti-oxidative stress	25982942
			Doxorubicin	GFAP↓, IBA-1↓	Anti-inflammation	34536813
	nanocurcumin		Doxorubicin	MDA↓,GSH↑, NO↓, AChE↑,MAO↑	Anti-oxidative stress	33882267
			Cisplatin	MDA↓,GSH↑, NO↓, caspase-3↓, TNF-α↓, AChE↓	Anti-inflammation; Anti-apoptosis; Anti-oxidative stress; Improve neurotransmitter release	30257586
	Caffeic acid phenethyl ester		Doxorubicin	MDA↓,GSH↑, GFAP↓, COX-2↓, TNF-α↓,ACh↑, caspase-3↓,	Anti-inflammation; Anti-apoptosis; Anti-oxidative stress	33011199
	Sulforaphane		Cisplatin	AChE↓, LPO↓, GSH↑,NO↑	Anti-oxidative stress; Improve neurotransmitter release	35969308
Flavonoid	Luteolin		Doxorubicin	CAT↑, SOD↑,GST↑,GPX↑,GSH↑,TSH↑,LPO↓,RONS↓,XO↓, AChE↓,NO↓,MPO↓, TNF-α↓,IL-1β, IL-10↑, caspase-3↓	Anti-inflammation; Anti-apoptosis; Anti-oxidative stress	34766659
	Quercetin		Adriamycin	corticosterone↓, GST↑, GSH↑, MDA↓, lymphocytes↑, leukocytes↑	Anti-oxidative stress; Improve immune dysfunction	24947870
			Cyclophosphamide and doxorubicin	SOD↓, CAT↑, GSH↑, MDA↓	Anti-oxidative stress	25260542
	Naringin		Cisplatin	AChE↓, MDA↓, PCO↓, H2O2↓,ROS↓, nitrite formation↓, iNOS↓, GSH↓, Ascorbic acid↓,SOD↑,CAT↑,GPx↑	Anti-oxidative stress; Anti-inflammation; Improve neuroplasticity	25896911
			Doxorubicin	MDA↓, SOD↑, GSH↓, CAT↑, IL-1β↓,TNF-α↓	Anti-oxidative stress; Anti-inflammation	27209303
	Ellagic acid		Doxorubicin	MDA↓, GSH↓, TNF-α↓, iNOS↓, CHE activity↓, 5-HT↑, DA↑, NE↑, caspase-3↓	Anti-oxidative stress; Anti-inflammation; Improve neurotransmitter release	28815802
	Rutin		Doxorubicin	Catalase↑, SOD↑, GSH↑, Total thiols↑, TNF-α↓, ROS↓, Apoptosis↓, neurite length↑, neurite width↓, cell viability↑	Anti-oxidative stress; Anti-inflammation; Anti-apoptosis; Improve neuroplasticity	28408800
			Doxorubicin		Anti-oxidative stress; Anti-inflammation	31679278
			Cisplatin	TBARS↓, glutathione↑, GPX↑	Anti-oxidative stress	28962559
	Morin		Doxorubicin	MDA↓, GSH↑, SOD↑, CAT↑, GPx↑, TNF-α↓, IL-1β↓,Bcl-2↑, Caspase-3↓, AChE↓, GFAP↓	Anti-oxidative stress; Anti-inflammation; Anti-apoptosis	29990832
	Epicatechin		Doxorubicin	CAT↑, SOD↑, GSH↑, MDA↓, Catalase↑, GFAP↓, TNF-α↓, iNOS↓	Anti-oxidative stress; Anti-inflammation	21763406
	Juglanin		Doxorubicin	AchE↑, SOD↑, GSH↑, CAT↑, MDA↓, IL-6↓, IL-1β↓, TNF-α↓, Caspase-3↓	Anti-inflammation; Anti-apoptosis; Anti-oxidative stress; Improve neuroplasticity	35138546
	Galangin		Doxorubicin	MDA↓,NO↓, GSH↑, TNF-α↓, IL-1β↓, IL-6↓, iNOS↓, HMGB1↓, GFAP↓, BDNF↑	Anti-inflammation; Anti-necroptosis; Anti-oxidative stress; Improve neurotransmitter release	35843304
Terpenoids	Ginsenoside		Docetaxel, adriamycin, and cyclophosphamide	TNF-α↓, IL-6↓, IL-10↑, IL-4↑, GFAP↓,IBA-1↓, BDNF↑	Anti-inflammation; Improve neuroplasticity	30659419
			Cisplatin	SOD↑, GSH↑, MDA↓,ROS↓, TNF-α↓, IL-10↑, IL-1β↓, AchE↓, Ach↑,chAt↑	Anti-inflammation; Anti-oxidative stress; Improve neuroplasticity	31695559
	Asiatic acid		5-fluorouracil	Ki-67 positive cells↑, BrdU positive cells	Improve neurogenesis	28700628
			5-Fluorouracil	p21 positive cells↑,MDA↓	Anti-oxidative stress; Improve neurogenesis
	Ganoderic acid		5-fluorouracil	IL-6↓, IL-1β↓, iNOS↓, COX2↓, BDNF↑	Anti-inflammation; Improve neuroplasticity	34821902
	Astaxanthin		Doxorubicin	AChE↓, TNF-α↓,PGE2↓,COX-2↓,GFAP↓, Caspase-3↓,cytochrome c↓	Anti-inflammation; Anti-apoptosis	29039023
Others	CI protein	NA	Doxorubicin	AchE↓,ROS↓,MAO↓,NE↑,DA↑,5-HT↑, MDA↓, SOD↑, GST↑, GR↑, GPx↑, GSH↑, GSSG↓, cleaved caspase-3↓, Cleaved PARP↓, Bad/Bcl-2↓, cytochrome↓, caspase 9↓, Apaf1↓	Anti-inflammation; Anti-necroptosis; Anti-oxidative stress; Improve neuroplasticity	22448708
	C-phycocyanin	NA	Doxorubicin	TNF-α↓, IL-1β↓, IL-6↓, GFAP↓, IBA1↓, MDA↓, Protein carbonyl↓, 8-OHdG↓, GSH↑, SOD↑, Sypnapsin-1↑, PSD95↑	Anti-inflammation; Anti-oxidative stress; Improve neuroplasticity	33237471
	Astragali Radix	NA	Doxorubicin	MDA↓, SOD/MDA↑, Improve amino acid homeostasis	Anti-oxidative stress; Improve amino acid homeostasis	33945017
	Extract of Tiliacora triandra	NA	Cisplatin	MDA↓, GPx↑, SOD↑, GSH↑, CAT↑, AchE↓, TNF-α↓, IL-6↓, IL-1β↓, Caspase-3↓, Bcl-2↑, p53↓	Anti-inflammation; Anti-necroptosis; Anti-oxidative stress; Improve neuroplasticity	34916822
	Ergothioneine		Cisplatin	AchE↓, MDA↓, GSH/GSSG ratio↑	Anti-oxidative stress; Improve neuroplasticity	20932872
	Bixin		Cisplatin	Cell viability↑, micronucleus frequency↓, DNA in tail↓	Anti-DNA damage	22019694