Table 1.

Mechanism of action of Paeonol in cardiovascular diseases.

Effects	Models	Mechanism	Reference
Anti-oxidative effect	Oxidized low-density lipoprotein induced HUVEC apoptosis	↓ LOX-1, ↓ P38 MAPK, ↓ NF-κB, and ↓ Caspase-3	[48]
	Paeonol protects against premature senescence in HUVEC cells	↓ P53, ↓ Ac-H3 K14, ↓ Ac-H4 K16 and ↓ SA-beta-galactosidase ↑ Sirt1, ↑ BrdU and ↑ Cell growth profile	[50]
	Paeonol attenuated intracellular lipid accumulation in RAW264.7 macrophages and ApoE−/− mice	↓ HO-1, ↓ CD36, ↓ c-Jun-AP-1, and ↓ Calpain ↑ ABCA1 and ↑ Wogonin	[51]
Anti-inflammatory	Rat aortic endothelial cells (RAECs).	↓ TNF-α-induced ↓ monocytic cell adhesion to rat aortic endothelial cells by of VCAM-1 expression ↓ VCAM1 viaregulation of ERK ½ and p38	[58]
	Rat model of carrageenan-evoked thermal hyperalgesia, bFGF stimulated HUVECs	↓ TNFα, ↓ IL-1ß, ↓ iNOS, ↓ COX-2 and ↓ PGE2 ↓ essential angiogenesis pathways such as proliferation and migration in FGF	[59]
	Ox-LDL stimulated VECs isolated from rat thoracic aorta	↑ miR 126 expression to monocyte adhesion ↓ PI3K/Akt/NF-κB signalling pathway	[60]
	Ox-LDL stimulated VECs isolated from rat thoracic aorta	↑ survival rate of ox-LDL treated VECs ↓ Release of ox-LDL induced TNF-α reverse the PTEN expression	[61]
	High fat diet ApoE−/− mice & HUVECs	↑ miR 223 expression ↓ STAT3 pathway ↓ IL-1ß and IL6 ↓ VCAM 1 and ICAM 1	[62]
	Wistar rats with ischemic reperfusion (IR) injury	↓ No-reflow area ↓ myocardial ischemic damage ↓ CK, CRP, LDH, TnT levels	[63]
	ApoE−/− mice	↑ LXRα-ABCA1–dependent cholesterol efflux	[64]
Regulation of vascular tone	Spontaneously Hypertensive rats	↓ elevated blood pressure and increased the cerebral blood flow velocity ↓ vascular endothelium injury	[83]
	Isolated SD rat aorta preparation	NO dependent vasodilator effects (-) voltage-dependent and receptor-operated Ca2+ channel, as well as intracellular Ca2+ release	[13,76]
	Tunicamycin-induced endothelial dysfunction in mice and HUVECs	↑ AMPK, ↑ PPARγ, ↑ peNOS and ↑NO ↓ AT6, ↓ GRP78, ↓ peIF2α and ↓ ROS,	[78,79]
	LPS-induced endothelial dysfunction in mice and HUVECs	↓ TLR4, ↓ BMP4, ↓ ROS, ↓ p38 and ↓ iNOS, ↑ peNOS and ↑ NO	[82]
Anti-apoptosis effect	Epirubicin-induced Cardiotoxicity in rat cardiac myocytes H9C2 and mice cardiomyocytes LH-1 cell death	↓ Caspase 3, ↓ Bax and ↓ PI3K/AKT/mTOR ↑ Bcl-2	[104]
	I/R-induced apoptosis in H9c2 embryonic rat myocardium-derived cells	↓ Caspase 3, Bax ↑ Bcl-2, Notch1	[110]
	(ISO)-induced myocardial infarction in rats	↓ Fas, ↓ TNF-α, ↓ Bax, ↓ caspase-3, ↓ caspase-8, ↓ caspase-9, ↓ cytochrome c, ↓ CK-MB, ↓ cTnI and ↓ cTnT ↑ Bcl-2/Nrf2/PI3K/Akt	[112]
	Streptozotocin-induced diabetic cardiomyopathy model in rat	↓ caspase-3, ↓ TNF-α, ↓ IL-6, ↓ NF-κB, ↓ p65 and ↓ p-Iκ-Bα ↑ PI3K/Akt-GSK-3β	[115]