Table 2.

List of natural products that target the NADPH oxidase pathway in CVD. The arrow indicate down-regulation and indicate up-regulation of the markers.

Natural Product	Plant	Effective Dosage	Induction of Cardiovascular Condition	Model	Result	NADPH Oxidase Subunit Involved	Reference
Berberine	Rhizoma Coptidis	10 μM	Endothelial microparticles (EMPs)-induced endothelial dysfunction	Human study In vitro using HUVECs	ROS, NOX4, NO, MDA, CD31+/CD42 microparticles	NOX4	[105]
		5.0 μmol/L	Palmitate-induced endothelial dysfunction	In vitro using HUVECs	eNOS, AMPK, NOX4	NOX4	[106]
Paeonol	Paeonia suffruticosa	20 mg/kg/day	Tunicamycin-induced endothelial dysfunction	In vivo	ROS, GRP78, ATF6 and p-eIF2α, NOX2 eNOS, NO	NOX2	[115]
		100 mg/kg/day	Methotrexate (MTX)-induced	In vivo	eNOS, NO, GSH, SOD NOX2, MDA, TLR4	NOX2	[116]
Thymoquinone	Nigella sativa	50 mg/kg/day 20 µmol/L	Angiotensin II-induced cardiac damage	In vivo In vitro (H9c2 cells)	IL-1, IL-6, TNF, collagen I, collagen III NOX4 and p53	NOX4	[125]
		100 mg/kg/day	Sepsis-induced cardiac damage	In vivo	IL-6, TNF, Bax, NOX4, p-PI3K, and p-AKT Bcl-2, Ho-1, and Nrh2 expression	NOX4	[126]
		50 mg/kg/day 5 µM	Transverse aortic constriction	In vivo In vitro (neonatal rat cardiomyocytes)	mRNA levels of NOX4, SOD1, SOD2	NOX4	[127]
Reinioside C	Polygala fallax Hemsl.	30 µM	Arteriosclerosis	In vitro (VSMCs)	ROS, NOX1, NOX4, IB degradation, NF-kB activity, and p-ERK1/2	NOX1 NOX4	[131]
		10 µM	Atherosclerosis	In vitro (HUVECs, THP-1)	NOX2 and p22phox, ICAM-1, P-selectin, NF-κB	NOX2 and p22phox	[132]
Curcumin	Curcuma longa Linn	100 mg/kg/day	Renovascular hypertension	In vivo (2K-1C model) In vitro (VSMCs)	MMP-2 and MMP-9, ROS, MDA and p47phox EDR, eNOS	p47phox	[139]
		30 μmol/L	Atherosclerosis	In vitro (VSMCs)	/> p47phox, MCP-1, TNF	p47phox	[140]
Celastrol	Tripterygium wilfordii Hook F	50 nmol/L	Hypertension	In vitro (HUVECs)	MDA, NOX2 SOD and GPx-SH	NOX2	[147]
		1 mg/kg/day 10 nmol/L	Calcific aortic valve disease	In vivo (rabbit) In vitro (AVICs)	NOX2	NOX2	[148]
Apocynin	Apocynum cannabinum	(30 mg/kg)	Hypertension	In vivo (SHR rats) In vitro (endothelial cells)	ROS, MAP, HR, SBP, DBP, NOX2 and p47phox eNOS, cytosolic calcium, and NO	NOX2 and p47phox	[156]
Oleanolic acid	Oleaceae	100 mg/kg/day 20 µM	Atherosclerosis	In vivo (high-fat diet-induced atherosclerosis in quails) In vitro (HUVECs)	MDA, GSH, gp91phox, p67phox and p47phox, LDL HDL, SOD, CAT GPx-SH, LOX-1, Nrf2 and ho-1	gp91phox, p67phox and p47phox	[163]
Quercetin	Berries, onions, and red wine	10 mg/kg/day	Hypertension	In vivo (SHR)	SBP, HR, NOX1, NOX4, p47phox EDR	NOX1, NOX4, p47phox and p22phox	[170]
		1 mg/kg	Myocardial ischemia-reperfusion injury	In vivo (rabbit)	NOX2, eNOS, iNOS	NOX2	[171]
Delphinidin	Pigmented fruits and vegetables	100 μM	Hypercholesterolemia	In vitro (ox-LDL-induced ROS in PAEC)	NOX2, NOX4, and p22phox, caspase 3	NOX2, NOX4, and p22phox	[179]
		15 mg/kg/day 50 μM	Cardiac hypertrophy	In vivo (TAC-induced pressure overload C57BL/6 mice) In vitro (neonatal rat cardiomyocytes)	p47phox	p47phox	[180]