| Description: |
Procyanidin B2 has vascular protective, anti-diabetic nephropathy,anti-cancer, anti-inflammatory, and antioxidant activities. Procyanidin B2 inhibited NLRP3 inflammasome activation via suppression of AP-1 pathway, and up-regulated the expression of GSTP1 via a mechanism that involves ERK and p38 MAPK activation and Nrf2 translocation. It has anti- and pro-oxidant effects on metal-mediated DNA damage by interacting with H2O2 and metal ions. |
| In vitro: |
| Chem Biol Interact. 2015 May 25;233:122-38. | | Mechanisms of DNA methyltransferase-inhibitor interactions: Procyanidin B2 shows new promise for therapeutic intervention of cancer.[Pubmed: 25839702] | DNA methyltransferases (DNMTs) is a key epigenetic enzyme for pharmacological manipulation and is employed in cancer reprogramming. During past few years multiple strategies have been implemented to excavate epigenetic compounds targeting DNMTs.
METHODS AND RESULTS:
In light of the emerging concept of chemoinformatics, molecular docking and simulation studies have been employed to accelerate the development of DNMT inhibitors. Among the DNMT inhibitors known till date, epigallocathechin-3-gallate (EGCG) was identified to be effective in reducing DNMT activity. However, the broad spectrum of EGCG to other diseases and variable target enzymes offers some limitations. In view of this, 32 EGCG analogues were screened at S-Adnosyl-L-homocysteine (SAH) binding pocket of DNMTs and Procyanidin B2-3, 3'-di-O-gallate (Procyanidin B2) was obtained as potent inhibitor having medicinally relevant chemical space. Further, in vitro analysis demonstrates the efficiency of Procyanidin B2 in attenuating DNMT activity at IC50 of 6.88±0.647 μM and subsequently enhancing the expression of DNMT target genes, E-cadherin, Maspin and BRCA1.
CONCLUSIONS:
Moreover, the toxic property of Procyanidin B2 towards triple negative breast cancer cells to normal cells offers platform for pre-clinical trial and an insight to the treatment of cancer. | | Mol Nutr Food Res. 2015 Feb;59(2):262-9. | | Procyanidin B2 inhibits inflammasome-mediated IL-1β production in lipopolysaccharide-stimulated macrophages.[Pubmed: 25379992] | Macrophage stimulation with bacterial LPS triggers inflammasome activation, resulting in pro-inflammatory IL-1β cytokine maturation and secretion. IL-1β underlies the pathologies of many diseases, including type-2 diabetes. Thus, the modulation of the inflammatory response through bioactive food compounds, such as procyanidins, is a powerful tool to promote homeostasis.
METHODS AND RESULTS:
To determine the role of Procyanidin B2 in inflammasome activation, LPS-primed THP-1-macrophages were supplemented with or without Procyanidin B2 . Western blot analysis of COX2 , iNOS, p65, NLRP3 and IL-1β was performed followed by p65 supershift assay, in vivo caspase-1 activation assay and NO, IL-1β and IL-6 determination. Procyanidin B2 mediated inhibition of inflammasome activation includes the inactivation of the NF-κB signalling pathway, the first stage required for the transcription of inflammasome precursors, through the inhibition of p65 nuclear expression and DNA binding, resulting in the transcriptional repression of target genes, such as COX2 , iNOS and production of IL-6 and NO. Furthermore, Procyanidin B2 decreases NLRP3 and pro-IL-1β cytoplasmic pools, limiting components of inflammasome activation and impeding inflammasome assembly and caspase-1 activation, and finally secretion of active IL-1β.
CONCLUSIONS:
This study provides the first evidence that Procyanidin B2 inhibits inflammasome activation and IL-1β secretion during LPS-induced acute inflammation in human macrophages. | | Free Radic Biol Med. 2005 Oct 15;39(8):1041-9. | | Procyanidin B2 has anti- and pro-oxidant effects on metal-mediated DNA damage.[Pubmed: 16198231 ] | Procyanidin B2 (epicatechin-(4beta-8)-epicatechin), which is present in grape seeds, apples, and cacao beans, has antioxidant properties. We investigated the mechanism of preventive action of Procyanidin B2 against oxidative DNA damage in human cultured cells and isolated DNA.
METHODS AND RESULTS:
Procyanidin B2 inhibited the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in the human leukemia cell line HL-60 treated with an H2O2-generating system. In contrast, a high concentration of Procyanidin B2 increased the formation of 8-oxodG in HL-60 cells. Experiments with calf thymus DNA also revealed that Procyanidin B2 decreased 8-oxodG formation by Fe(II)/H2O2, whereas Procyanidin B2 induced DNA damage in the presence of Cu(II), and H2O2 extensively enhanced it. An electron spin resonance spin trapping study utilizing 3,3,5,5-tetramethyl-1-pyrroline-N-oxide (M4PO) demonstrated that Procyanidin B2 decreased the signal of M4PO-OH from H2O2 and Fe(II), whereas Procyanidin B2 enhanced the signal from H2O2 and Cu(II). As an antioxidant mechanism, UV-visible spectroscopy showed that Procyanidin B2 chelated Fe(II) at equivalent concentrations. As a pro-oxidant property, we examined DNA damage induced by Procyanidin B2, using 32P-labeled DNA fragments obtained from genes relevant to human cancer.
CONCLUSIONS:
Our results raise the possibility that Procyanidin B2 exerts both antioxidant and pro-oxidant properties by interacting with H2O2 and metal ions. |
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