Table 3.

Synthetic drugs and natural compounds identified as regulators of sirtuin-1 in preclinical studies of diabetic nephropathy in animal models

Substance	Animal model	Mechanism of renoprotection	Pathway	Reference
3,5-Diiodo-L-thyronine	T1DM: STZ-induced diabetic rat	Prevent decrease in sirtuin-1 expression and activity; anti-fibrotic transforming growth factor-β1 expression, fibronectin and type IV collagen	Sirtuin-1/NF-κB	[141]
Allium sativum (garlic)	T1DM: STZ-induced diabetic rat T2DM: STZ + niacinamide–induced diabetic rat	Increase sirtuin-1 and sirtuin-2 gene expression in kidney	Sirtuin-1; sirtuin-2	[21]
Glycyrrhizic acid	T2DM: db/db mouse	Anti-oxidant, anti-fibrotic	AMPK/sirtuin-1/PGC-1α signaling	[22]
Grape seed proanthocyanidin extracts	T2DM: high-carbohydrate/high-fat diet and STZ-induced diabetic rat	Restore mitochondrial function, anti-apoptotic, anti-oxidant, increase nephrin and podocalyxin	AMPK/sirtuin-1/PGC-1α	[59]
Hesperidin and quercetin	T1DM: STZ-induced diabetic rat	Anti-oxidant	NF-κB, sirtuin-1, SOD, CAT	[142]
INT-777 (G protein–coupled bile acid receptor TGR5 agonist)	T2DM: db/db mouse	Increase renal mitochondrial biogenesis, decrease oxidative stress, increase fatty acid beta-oxidation	Sirtuin-1, sirtuin-3, Nrf1, SOD2	[143]
Olmesartan	T2DM: db/db mice	Anti-apoptotic, suppress p38 phosphorylation	Angiotensin II/p38/sirtuin-1	[118]
Probucol	T2DM: high-fat, high-cholesterol Western diet and STZ-induced diabetic mice	Anti-oxidant, anti-fibrotic	p66Shc, AMPK/sirtuin-1/AcH3	[137]
Puerarin (active compound of Radix Puerariae)	STZ-induced diabetes in endothelial nitric oxide synthase–null (eNOS−/−) mouse	Anti-oxidant	NF-κB, NOX4	[81]
	T1DM: STZ-induced diabetic mouse	Anti-oxidant, anti-inflammatory	Sirtuin-1/FOXO1, TNF-α, NF-κB, IL-6	[87]
Panax notoginseng saponins	T1DM: alloxan-induced rat	Anti-inflammatory, anti-oxidant, anti-fibrotic	Sirtuin-1/NF-κB, PAI-1, TGF-β1, MCP-1, SOD	[80]
Resveratrol	T1DM: STZ-induced diabetic rat	Anti-oxidant, prevent dephosphorylation of histone H3, reduce the expression of p38 and p53	Sirtuin, p53, p38	[95]
	T1DM: STZ-induced diabetic rat	Anti-oxidant	Sirtuin-1/FOXO1	[88]
	T1DM: STZ-induced diabetic rat	Modulate angiogenesis	Sirtuin-1, VEGF, Flk-1, Tie-2	[115]
	T1DM: STZ-induced diabetic rat	Anti-oxidant, anti-fibrotic	Sirtuin-1, Nrf2/ARE, TGF-β1, FN	[34]
	T2DM: db/db mouse	Prevent renal lipotoxicity and glucotoxicity, anti-oxidant, anti-apoptotic	AMPK/sirtuin-1/PGC-1α	[56]
	T2DM: STZ-induced diabetic rat	Anti-inflammatory; enhance autophagy	NAD+/sirtuin-1, TNF-α, IL-6, IL-1β, IL-10	[7]
	T1DM: STZ-induced diabetic rat	Anti-oxidant	Sirtuin-1/FoxO3a	[89]
Resveratrol and rosuvastatin	T2DM: STZ + niacinamide–induced diabetic rat	Anti-oxidant, anti-fibrotic	TGF-β1, NF-κB/p65, Nrf2, sirtuin-1, FoxO1	[144]
Roflumilast	T1DM: STZ-induced diabetic rat	Anti-oxidant, anti-fibrotic, anti-apoptotic	AMPK/sirtuin-1, FoxO1, HO-1	[52]
Theobromine	Spontaneously hypertensive rat treated with STZ	Anti-fibrotic	NOX4, AMPK, sirtuin-1/TGF-β	[139]
Tetrahydroxystilbene glucoside (active component extract of Polygonum multiflorum Thunb)	T1DM: STZ-induced diabetic rat	Anti-oxidant	Sirtuin-1/TGF-β1, COX-2	[140]