Table 2.

Summary of the mechanisms of action of the four discussed plants.

Plant		Mechanism of action	References
Ginseng	Bioactive/active fractions: Rb1, Rg1, Rg3, Re, and Rd Commonly used extracts: Panax ginseng, Panax notoginseng, Panax quinquefolium L., Panax japonicas	Improves lipid profile By acting as an agonist of PPAR Controls hypertension and improve endothelial function By Inhibition of ACE By reducing adrenal catecholamines levels, elevating NO and cGMP levels By activating Ca2+-gated potassium channels Controls inflammation By inhibiting AP‐1 and NF‐κB By reducing COX‐2, IL‐6, IL‐1β, TNF‐α, CD68, MCP-1 and MMP levels Ameliorates oxidative stress By exhibiting free radical scavenging and metal ion chelating abilities By promoting enhanced expression of antioxidant proteins, such as Nrf2 and HO-1 Ameliorates mitochondrial dysfunction Modulates angiogenesis By decreasing VEGF-A and FGF-2 levels	(Kim et al., 1999b; Keum et al., 2003; Park et al., 2005; Persson et al., 2006; Shin Y. et al., 2013; Park J. et al., 2014; Lee H. et al., 2016; Deng et al., 2017; Singh et al., 2017; Lee et al., 2019a)
Gingko Biloba	Bioactive/active fractions: Ginkgolides classified into either A, B, C, J, or M types Commonly used extracts: EGb761	Improves lipid profile By decreasing PPARs levels Controls hypertension and improves endothelial function By decreasing ACE activity, activating cholinergic pathways, limiting LPS-induced proliferation of VSMCs By decreasing ICAM‐1 and VCAM‐1 expression, decreasing phosphorylation of Akt/FoxO3a By restoring eNOS activity, decreasing iNOS expression and consequently elevating NO levels Controls inflammation By suppressing TLR-4 expression By decreasing MMP-1, MCP-1, TNF-α, IL-6, or IL-1β Ameliorates oxidative stress By decreasing NOX activity and level, activating endogenous Akt/Nrf2 antioxidant stress pathway By increasing levels of HO-1, SOD and GSH-Px By reducing the phosphorylation of MAPKs Prevents hypertrophy By activating M2 muscarinic receptors/NO pathway By decreasing calcium overload and inhibiting the Na+/Ca2+ exchanger Prevents apoptosis By decreasing caspase 3 and pro-apoptotic Bax expression and increasing anti-apoptotic Bcl-2 expression	(Akiba et al., 2007; Lin et al., 2007; Mansour et al., 2011; Liu et al., 2013; Liou et al., 2015; Mesquita et al., 2017; Abdel-Zaher et al., 2018; Huang et al., 2018; Chen et al., 2019).
Ganoderma lucidum	Bioactive/active fractions: ganoderic acids A, B, C, D, F, H, K, S, and Y, β-d-Glucan polysaccharides Commonly used extracts: Polysaccharide peptide (PsP) Ganoderma lucidum	Controls hypertension and improves endothelial function By inhibition of ACE, enhancing Angiotensin 1-mediated phosphorylation of eNOS By reducing the levels of vasoconstrictor peptide Endothelin-1 Improves lipid profile By upregulating lipid metabolism (ACOX1 and ACC) Ameliorates oxidative stress and inflammation By enhancing phosphorylation of Nrf2 which upregulates HO-1, GST, NQO-1, SOD, CAT, GSH-Px and GSH By decreasing the levels of MDA and ICAM, and regulation of mTOR/S6K signaling pathways Reduces necrosis By decreasing the levels of creatine phosphokinase	(Hikino et al., 1985; Tomoda et al., 1986; Shi et al., 2002; Shi et al., 2010; Lasukova et al., 2015; Wang et al., 2015; Wihastuti and Heriansyah, 2017; Cuong et al., 2019; Wu et al., 2019)
Gynostemma pentaphyllum	Bioactive/active fractions: dammarane-type triterpene saponins (gypenosides or gynosaponins) Commonly used extracts: Actiponin, Ombuine	Improves lipid profile By activation of PPAR-α and PPAR-δ/β, decreasing the levels of sterol regulatory element binding protein-1c and stearoyl-CoA desaturase-1 By activation of the AMPK pathway Ameliorate oxidative stress and decreases apoptosis By decreasing the levels of MDA, increasing the levels of SOD, GSH, Nrf2, NQO-1 and HO-1 By downregulating Fas/FasL, blocking CHOP pathway By regulating the activation of PI3K/Akt pathway Controls inflammation By decreasing LPS- and TNF-α-induced NF-κB through regulating PPAR-α	(Huang et al., 2006; Megalli et al., 2006; Malek et al., 2013; Yu et al., 2016b; Yang et al., 2017; Wang et al., 2018; Lin et al., 2019)

PPAR, peroxisome proliferator-activated receptor; ACE, acetylcholinesterase; NO, nitric oxide; AP‐1, activator protein 1; NF‐κB, nuclear factor kappa-light-chain-enhancer of activated B cells; COX, cyclooxygenase; IL, interleukin; TNF, tumor necrosis factor; CD, cluster of differentiation; MCP, monocyte chemoattractant; MMP, matrix metalloproteases; Nrf2, nuclear factor erythroid-2-related factor 2; HO-1, hemeoxygenase-1; VEGF, vascular endothelial growth factor; FGF, fibroblast growth factor; VSMCs, vascular smooth muscle cells; ICAM, intercellular adhesion molecule; VCAM, vascular cell adhesion molecule; Akt, protein kinase B; FoxO3a, forkhead box O; eNOS, endothelial nitric oxide synthase; iNOS, inducible nitric oxide synthase; TLR, toll-like receptor; NOC, nicotinamide adenine dinucleotide phosphate oxidase; SOD, superoxide dismutase; GSH-Px, glutathione peroxidase; MAPK, mitogen-activated protein kinase; ACOX1, peroxisomal acyl-coenzyme A oxidase 1; ACC, acetyl-CoA carboxylase; GST, glutathione S-transferase; NQO-1, NAD(P)H dehydrogenase (quinone); GSH, glutathione; MDA, malondialdehyde; mTOR, mammalian target of rapamycin complex; S6K, S6 kinase; AMPK, AMP-activated protein kinase; CHOP, C/EBP homologous protein.