Table 1.

Plant-based CVD therapeutics, their pharmacological activities, mode of actions, and molecular targets.

Compound/class of phytochemical	Natural sources	Pharmacological activities	Mechanism of action (MOA)	Molecular targets	References
Resveratrol/polyphenolic compound	Polygonum cuspidatum, grapes, peanuts, and berries	• Inhibition of lipid peroxidation • Free radical scavenging • Inhibition of platelet aggregation • Anti-inflammatory activity • Vasorelaxation activity • Modulation of lipid metabolism	• Increases the expression of NO synthase • Decreases the expression of vasoconstrictor ET • Inhibits stress-induced ET-1 gene expression • Alteration of eicosanoid synthesis • Attenuation of arachidonic acid and prostaglandin E2 synthesis • Inhibition of phospholipase A2 and COX-2 activities • Antagonizes NF-κB, TNF-α, IL-6, iNOS, MCP-1	AMPK, SIRT-1 pathway, NF-κB, TNF-α, IL-6, iNOS, MCP-1	(Bradamante et al., 2004; Das and Das, 2007; Pagliaro et al., 2015)
Carotenoids	Rosa arvensis, Bibes nigrum, Fagus sylvatica, Malus domestica	Obesity-associated inflammation, atherosclerosis, cardiovascular disease	……………………	IGF-1, IL-1β, IL-6, MCP-1	(Beukes et al., 2014)
Brassica oleracea	Broccoli, cauliflowers, Brussel sprouts, and kale	• Antioxidant • Anti-inflammatory • Antithrombotic effects.	…………………………	Nrf2, MAPK, JNK, Akt, PKB, AMPK, SIRT-1, PPARα, UCP2	(Pagliaro et al., 2015)
Naringenin/flavonoids	Grapefruit and orange	• Antioxidant activity • Protects LDL oxidation	• Increases the activity of antioxidant enzymes and non-enzymatic antioxidants • Inhibits generation of free radicals	LOX and COX pathways	(Vasanthi et al., 2012)
Curcumin/phenolic compound	Turmeric (Curcuma longa)	• Anti-inflammatory, antiplatelet, antioxidant activity	• Inhibition of prostaglandin production and NF-κB activity, an increase of cytokine production • GRP94 induction	JAK2/STAT3, AMPK/UCP2, Akt/Nrf2, ERK, MAPK p38, JNK, ICAM-1, MCP-1, and IL-8	(Kapakos et al., 2012; Zhang et al., 2015)
Isoflavones/polyphenols	Soybeans, fruits, vegetables, legumes, herbs, spices, stems, flowers	• Free radical scavenging and antioxidant activity • Anti-inflammatory activity	• Inhibition of eicosanoid generating enzymes • Modulation of the production of pro-inflammatory cytokines	ERs, Nrf1, iNO, COX-2, TNF-α, ICAM-1, VCAM-1, E-selectin, MCP-1, ERE, CVD ion channels, inhibiting calcium channels or activating potassium channels	(García-Lafuente et al., 2009) (Scholz et al., 2010)
Catechin	Green tea, apples, cocoa, and berries	• Antioxidant, anti-hypertensive, anti-inflammatory, anti-proliferative, anti-thrombogenic, hypocholesterolemia effects	• Upregulation of proinflammatory molecules by suppression of NF-κB activity • Modulation of cholesterol metabolism		(Vasanthi et al., 2012)
Quercetin/flavonoid	Onions, apples, and tea/	• Anti-thrombogenic • Antioxidant • Anti-platelet aggregation • Decreases superoxide production	• Inhibition of phospholipase A2 activity • Inhibition of MAP kinase activation • Decreases platelet aggregation and increases platelet-derived nitric oxide release • Inhibition of phospholipase A2 activity • Blockage of the LOX and COX pathways	LOX and COX pathways, NF-κB gene	(Vasanthi et al., 2012)
Geraniol	Citrus spp.	• Improve insulin resistance, suppresses HMG-CoA) reductase activity, hepatoma, melanoma, and leukemia cells	……………………	PPARγ	(Beukes et al., 2014)
Berberine/alkaloid	Hydrastis canadensis	• Anti-oxidant, anti-inflammatory • Antihyperlipidemic activity • Antihypertensive activity	• Upregulation of SOD and UCP2 • Downregulation of NADPH oxidase expression • Attenuation of ER stress-induced apoptosis • Activation of the Nrf2 pathway	JAK2/STAT3 signaling pathway, UPR signaling pathway, Nrf2 pathway, AK2/STAT3 signaling pathway, C-AMPK and MAPK/ERK pathway, NF-κB signaling pathway	(Vuddanda et al., 2010; Pagliaro et al., 2015)
Abscisic acid	Rosa arvensis, Ribes nigrum, Fagus sylvatica, Malus domestica	• Diabetes, obesity-related inflammation	……………………	PPARγ, NF-κB	(Beukes et al., 2014)
Sulforaphane	Broccoli, cauliflowers, Brussel sprouts, and kale	• Antioxidant activities • Anti-inflammatory activities	• Inhibition of angiogenesis • Inhibition of phase I enzymes and DNA adducts • Induction of phase II antioxidant detoxifying enzyme, • Induction of cell cycle arrest • Expression of Nrf2 • Nrf2-dependent phase 2 enzymes activation • Expression of detoxification enzymes antioxidant response elements (AREs) • Reduction of VCAM-1 synthesis	VCAM-1, Nrf2, ARE	(Pagliaro et al., 2015)

UCP2, uncoupling protein 2.