Coompo Research Chemicals

The capacity of different procyanidins to modulate lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) production in THP1 human monocytes and their effects on the redox regulated protein kinases activity: IkB kinase beta (IKKb) and the extracellular signal-regulated kinase (ERK). LPS-triggered increase of ROS was prevented by cell pre-incubation with procyanidins. LPS induced ERK1/2 activation through phosphorylation, which was inhibited by all the compounds tested, the most active being epigallocatechin (EG), followed by epigallocatechin gallate (EGCG) and C1. Procyanidins inhibited IKKb activity in vitro. C1 and procyanidin extract (PE) exerted the maximal IKKb inhibition, followed by EGCG and dimer B1. Catechin exerted a slight but significant IKKb inhibition, in contrast to epicatechin, which was ineffective. In conclusion, procyanidins reduce the LPS-induced production of ROS and they exert their anti-inflammatory effects by inhibiting ERK1/2 and IKKb activity.

Treatment of RAECs with 50μM procyanidin C1 (4β→8 trimer) resulted in a time- and dose-dependent hyperpolarization using the membrane potential-sensitive probe bis-(1,3-dibutylbarbituric acid) trimethine oxonol, while no effect was observed for (-)-epicatechin (a monomer) and procyanidin B2 (4β→8 dimer). The C1-induced hyperpolarization was inhibited by iberiotoxin, a specific inhibitor of large-conductance Ca(2+)-activated K(+) (BK(Ca)) channel, as well as 2-aminoethyl diphenylborinate (2-APB), a store-operated Ca(2+) entry inhibitor. Procyanidin C1 caused a significant increase in NO production from RAECs via phosphorylation of both eNOS and Akt, and the effect was completely inhibited by N(G)-monomethyl-l-arginine or combined treatment with iberiotoxin and the phosphatidylinositol 3-kinase (PI3K) specific inhibitor, wortmannin, as well as combined treatment with 2-APB and wortmannin. Taken together, these findings provide critical evidence that procyanidin C1, but not B2, has potential to induce NO production in RAECs via both Ca(2+)-dependent BK(Ca) channel-mediated hyperpolarization and Ca(2+)-independent PI3K/Akt pathways.

Procyanidin C1 plays a potent role in promoting Ca(2+)-mediated signals such as the hyperpolarization via multiple K(+) channel activations and the NO release in RAECs, suggesting that procyanidin C1 may represent novel and effective therapy for the treatment of cardiovascular diseases.