Evidence-Based Complementary and Alternative Medicine

Review Article

Relationship between Platelet PPARs, cAMP Levels, and P-Selectin Expression: Antiplatelet Activity of Natural Products

Table 1

Antiplatelet effects induced by various agonists of natural products and mechanisms described.
ConstituentsPlatelet aggregationMechanismsReferences
AACollagenU46619ThrombinPAFADPEpinephrineA23187TRAP-6
5-Caffeoylquinic acid/////////Inhibition of COX-1, COX-2, and P-selectin expression.[73]
Adenosine    + +   cAMP and cGMP production. Inhibition of P-selectin expression.[74–77]
Caffedymine
(N-caffeoyldopamine)		/////////Inhibition of TXA2, COX-1, COX-2, and P-selectin expression. cAMP production. [78–80]
Caffeic acid/////////Inhibition of COX-1, COX-2, and P-selectin expression.[73, 81]
Cordycepin/++//////Inhibition of [Ca2+]i and TXA2. cAMP and cGMP production. [82, 83]
Curcumin+///+////PPAR-γ activation, inhibition of [Ca2+]i and TXA2. [84–87]
C-phycocyanin−+++/////Inhibition of TXA2, PDE3, PKC, [Ca2+]i. cGMP production. [88, 89]
Dicentrine++++++///Inhibition of [Ca2+]i and TXA2. cAMP production.[90]
Epigallocatechin-3-gallate/+///−−//Inhibition of [Ca2+]i, TXA2. cAMP production.[91]
Flavonoid alpha-naphthoflavone++/−/+///Inhibition of [Ca2+]i, TXA2, PLC, PKC and phosphoinositide breakdown. cGMP production. [92]
Gallic acid//+//+///Inhibition of [Ca2+]i, P-selectin expression, PKCα/p38 MAPK and Akt/GSK3β.[70]
Girinimbine+++−+////Inhibition of TXA2, PGD2, PGE2, and [Ca2+]i. cAMP production. [93]
Hesperetin++−−/////Inhibition of PLC-γ2, [Ca2+]i and COX-1. [94]
Hydroxychavicol++/−/////Inhibition of [Ca2+]i, TXA2, ROS production, COX-1, and COX-2. [95]
Magnolol++///////PPAR-β/γ activation, upregulation of Akt/NOS/NO/cGMP/PKG and inhibition of PKC-α, COX-1, and Ca2+ mobilization[96]
N-caffeoyl tyramine (N-coumaroyldopamine)/////////Inhibition of TXA2, COX-1, COX-2, and P-selectin expression. cAMP production.[78–80]
Phloroglucinol+/−//////Inhibition of TXA2, ERK/p38, ROS production COX-1, and COX-2 activities.[97]
Quercetin/+/+/+///Inhibition of [Ca2+]i, P-selectin expression, GPIIb/IIIa, PI3K, Akt, ERK2, JNK1, and p38 MAPK. cAMP and VASP production. [98]
Sanguinarine++++/////Inhibition of [Ca2+]i, TXA2, COX-1, and COX-2. cAMP production. [99]
Sesamol++−−/////Inhibition of [Ca2+]i, TXA2, PLC-γ2, PKC, MAPK, and NF-κB signaling events. cAMP, cGMP, and NO production.[100, 101]
Sulforaphane−++−/+///Inhibition of [Ca2+]i, PLC-γ2, PKC, MAPKs, and PI3K/Akt. cAMP production.[102, 103]
α-Lipoic acid++///////PPAR-α/γ activation, inhibition of [Ca2+]i, TXA2, PKCα, and COX-1. cAMP production.[104, 105]
α- and γ-Tocopherol+////+///PPAR-γ activation, inhibition of PKC, and P-selectin expression. [106–109]
“+”: positive antiplatelet effect; “−”: no or little antiplatelet effect; “/”: not reported; AA: arachidonic acid; PAF: platelet-activating factor; COX: cyclooxygenase; PLC: phospholipase C; PKC: protein kinase C; ROS: reactive oxygen species; NO: nitric oxide; TXA2: thromboxane A2; PGD2: prostaglandin D2; MAPKs: mitogen-activated protein kinase.