Table 2.

In vivo pharmacological activities of extracts and compounds isolated from Juglans regia.

Compound/Diet	Experimental Model	Treatment Doses	Anticancer Effects	Molecular Targets	References
Juglanin	MCF-7-xenografted male BALB/c-nude mice	0–10 mg/kg/day (7 days)	⬇ Tumour growth	⬆ Caspase 3, 9	[89]
				⬆ LC3B
				⬆ p-JNK
	A549-xenografted athymic nude mice	0–30 mg/kg/day (28 days)	⬇ Tumour volume	⬆ Caspase 3	[90]
			⬇ Tumour weight	⬆ PARP
				⬇ Bcl-2, Bcl-xl, ⬆ Bax, Bad
				⬆ p53
				⬆ TRAIL, DR4, DR5 and FADD
				⬆ PI3K, Akt, and p-ERK1/2
				⬆ p-p38
				⬆ LC3BI/II, ATG7, Beclin1 and PIK3C3
	Hairless mice subjected to UVB radiation	0–20 mg/kg/2 days per week (10 weeks)	Suppression of epidermal hyperplasia and inflammatory cell infiltration	⬇ Ki67	[91]
				⬇ p38/JNK
				⬇ PI3K/AKT
				⬇ IL-1β, TNF-α, IL-6
				⬇ Cyclin D1, CDK1, PCNA
				⬆ p53, p27, p21
				⬆ PARP
				⬆ Caspases 3 and 8
Juglone	Female BALB/c-nu mice implanted with U87 stem-like cells	1 mg/kg/ day per 3 days (5 administrations)	⬇ Tumour growth		[112]
			⬆ Survival
	MDA-MB231-xenografted nude mouse	10–40 mg/kg/day every 3 days (5 administrations)	⬇ Tumour growth		[96]
	Inbred C57BL/6J mice implanted with B16F1	1 mg/kg/day 1, 3 and 5 (3 administrations)	⬇ Tumour growth		[193]
			⬆ Survival
	Weanling male F344 rats treated subcutaneously injections of azoxymethane	200 ppm/once per week (3 weeks)	⬇ Incidence and multiplicity of intestine tumours		[179]
	Ehrlich ascites tumour xenografted swiss/HaICR mice	0–2 mg (single injection)	Mitotic abnormalities		[180]
			⬇ Amount of ascitic fluid
Juglone + Ascorbate	Ehrlich carcinoma- xenografted male BALB/c inbred mice	(1 mg/kg + 100 mg/kg)/day (9 days)	⬇ Tumour growth	⬆ G0/G1 cell-cycle arrest	[115,181]
			⬆ Survival	⬆ p53, p16
				⬇ Cyclin A
				⬆ PARP
				⬆ Bax
				⬇ Bcl-xL
				⬇ HIF-α
				⬇ GLUT1
				⬇ GSH, ⬆ SOD
				⬇ p-Akt
				⬆ Protein carboxylation
				⬆ MDA
				⬆ γ-H2AX
Uro A	C4-2B-xenografted male BALB/c athymic mice (nu/nu)	50 mg/kg/5 days per week (4–5 weeks)	⬇ Tumour growth	⬇ Ki67	[83]
				⬇ Akt
	PC-3-xenografted male BALB/c athymic mice (nu/nu)			⬇ Ki67
Walnut diet	TRAMP mice	100 g whole walnut/kg of diet ad libitum (18 weeks)	⬇ Tumour size	⬇ IGF-1	[188]
				⬇ High density lipoprotein, total cholesterol
				⬆ Insulin sensitivity
				⬇ Glucose-6-phosphate
				⬇ Succinylcarnitine
				⬇ 4-hydroxybutyrate
				⬆ PCK1 and CIDEC
		155 g of whole walnut/kg of diet ad libitum (9, 18, 24 weeks)	⬇ Tumour growth and size.	⬇ Plasma IGF-1	[185]
				⬇ Resistin
				⬇ Low density lipoprotein
	LNCaP xenografted nude mice	113 g of whole walnut/kg of diet ad libitum (126 days)	⬇ Number of tumours		[190]
			⬇ Xenografts growth
	HT-29 xenografted female nude (nu/nu) mice	110 g of whole walnut/kg of diet (25 days)	⬇ Tumour weight	⬇ VEGF	[189]
	Pups born after female SV129 mice bred with transgenic homozygous C(3)1/SV40 T antigen SV129 male mice Female SV129	111 g of walnut/kg of diet ad libitum (optional 2 weeks before breeding + 21 days of weaning + 110, 130 or 145 days)	⬇ Tumour incidence	Altered expression of 84 genes associated with proliferation and differentiation	[191]
			⬇ Tumour Multiplicity
			⬇ Tumour size
	MDA-MB231-xenografted nude mice	113 g of whole walnut/kg of diet (35 days)	⬇ Tumour growth		[194]
	HT-29-xenografted athymic nude (nu/nu) mice	111 g of whole walnut/kg of diet ad libitum (25 days)	⬇ Tumour growth	⬆ ALN, eicosapentaenoic, DHA and total ω-3 fatty acids	[186]
				⬇ Arachidonic acid
				⬇ miRNAs 1903, 467c and 3068, ⬆ miRNA 297a

⬆: Upregulation; ⬇: Downregulation.