Procyanidin A2

Int J Mol Sci. 2016 Nov 12;17(11). pii: E1888.

Procyanidin A2 Modulates IL-4-Induced CCL26 Production in Human Alveolar Epithelial Cells.[Pubmed: 27845745 ]

Allergic asthma is an inflammatory lung disease that is partly sustained by the chemokine eotaxin-3 (CCL26), which extends eosinophil migration into tissues long after allergen exposure. Modulation of CCL26 could represent a means to mitigate airway inflammation.
METHODS AND RESULTS:
Here we evaluated Procyanidin A2 as a means of modulating CCL26 production and investigated interactions with the known inflammation modulator, Interferon γ (IFNγ). We used the human lung epithelial cell line A549 and optimized the conditions for inducing CCL26. Cells were exposed to a range of Procyanidin A2 or IFNγ concentrations for varied lengths of time prior to an inflammatory insult of interleukin-4 (IL-4) for 24 h. An enzyme-linked immunosorbent assay was used to measure CCL26 production. Exposing cells to 5 μM Procyanidin A2 (prior to IL-4) reduced CCL26 production by 35% compared with control. Greatest inhibition by Procyanidin A2 was seen with a 2 h exposure prior to IL-4, whereas IFNγ inhibition was greatest at 24 h. Concomitant incubation of Procyanidin A2 and IFNγ did not extend the inhibitory efficacy of Procyanidin A2.
CONCLUSIONS:
These data provide evidence that Procyanidin A2 can modulate IL-4-induced CCL26 production by A549 lung epithelial cells and that it does so in a manner that is different from IFNγ.

Food Chemistry, 2010, 119(2):753-7.

Antioxidant activities and contents of polyphenol oxidase substrates from pericarp tissues of litchi fruit[Reference: WebLink]

The experiments were performed to extract and purify substrates for polyphenol oxidase (PPO) from pericarp tissue of postharvest litchi fruit. Two purified PPO substrates were identified as (−)-epicatechin and Procyanidin A2. The antioxidant properties of two PPO substrates were further evaluated in the present study.
METHODS AND RESULTS:
Variation in the content of the major substrate (−)-epicatechin of litchi fruit during storage at 25 °C was analysed using the HPLC-UV method. The results showed that (−)-epicatechin exhibited stronger antioxidant capability than Procyanidin A2, in terms of reducing power and scavenging activities of DPPH radical, hydroxyl radical and superoxide radical. Furthermore, (−)-epicatechin content in pericarp tissue tended to decrease with increasing skin browning index of litchi fruit during storage at 25 °C.
CONCLUSIONS:
Thus, these two compounds can be used as potential antioxidants in litchi waste and the fresh pericarp tissue of litchi fruit exhibited a better utilisation value.

J Physiol Pharmacol. 2016 Apr;67(2):243-52.

Preventive effects of procyanidin A2 on glucose homeostasis, pancreatic and duodenal homebox 1, and glucose transporter 2 gene expression disturbance induced by bisphenol A in male mice.[Pubmed: 27226184]

Procyanidins (PCs) as oligomeric compounds with antidiabetic properties formed from catechin and epicatechin molecules. Bisphenol A(BPA) is a common chemical material use in food and beverage packaging.
METHODS AND RESULTS:
The aim of this study was to explore the protective effects of Procyanidin A2 (PCA2) against glucose homeostasis disturbance and gene expression of pancreatic and duodenal homebox 1 (Pdx1) as well as glucose transporter 2 (Glut2) induced by BPA in male mice. First tested these five concentrations of PCA2 (3 - 300 μM) alone and in combination with BPA(100 μg/L), on insulin secretion from isolated islets at in vitro condition. Next, examined the influence of BPA and PCA2 on islet apoptosis using flowcytometry. At in vivo condition, the BPA (100 μg/kg) and PCA2 (10 μmol/kg) administered for 20 days then, blood glucose and insulin, Pdx1 and, Glut2 genes expression, and oxidative stress markers examined.
CONCLUSIONS:
The results indicated that PCA2 strongly prevents islet cells apoptosis induced by BPA and, co-administration of PCA2 and BPA modified hyperglycemia. BPA reduced Pdx1 and Glut2 mRNA expression and antioxidant level in pancreas tissue, whereas PCA2 prevented from these effects. The findings from these studies suggest that use of PCA2 rich plants have preventive effects on hyperglycemia, and type 2 diabetes.

Int J Mol Sci. 2017 Jun 26;18(7).

5-(3',4'-Dihydroxyphenyl-γ-valerolactone), a Major Microbial Metabolite of Proanthocyanidin, Attenuates THP-1 Monocyte-Endothelial Adhesion.[Pubmed: 28672844 ]

Several metabolomics of polymeric flavan-3-ols have reported that proanthocyanidins are extensively metabolized by gut microbiota. 5-(3',4'-dihydroxyphenyl)-γ-valerolactone (DHPV) has been reported to be the major microbial metabolite of proanthocyanidins.
METHODS AND RESULTS:
We demonstrated that DHPV has stronger prevention effect on tumor necrosis factor (TNF)-α-stimulated adhesion of THP-1 human monocytic cells to human umbilical vein endothelial cells compared to its potential precursors such as procyanidin A1, Procyanidin A2, procyanidin B1 and procyanidin B2, (+)catechin, (-)epicatechin and its microbial metabolites such as 3-(3,4-dihydroxyphenyl)propionic acid and 2-(3,4-dihydroxyphenyl)acetic acid. Mechanism study showed that DHPV prevents THP-1 monocyte-endothelial cell adhesion by downregulating TNF-α-stimulated expressions of the two biomarkers of atherosclerosis such as vascular cell adhesion molecule-1 and monocyte chemotactic protein-1, activation of nuclear factor kappa B transcription and phosphorylation of I kappa-B kinase and IκBα.
CONCLUSIONS:
We suggested that DHPV has higher potentiality in prevention of atherosclerosis among the proanthocyanidin metabolites.

Exp Ther Med. 2017 Jun; 13(6): 2839–2847.

Hepatoprotective effects of litchi (Litchi chinensis) procyanidin A2 on carbon tetrachloride-induced liver injury in ICR mice[Pubmed: 28587348 ]

Drug tolerance, lacking liver regenerative activity and inconclusive inhibition of steatosis and cirrhosis by silymarin treatment during chronic liver injury have increased the demand for novel alternative or synergistic treatments for liver damage. Litchi fruit is abundant in polyphenolic compounds and is used in traditional Chinese medicine for treatments that include the strengthening of hepatic and pancreatic functions.
METHODS AND RESULTS:
Unique polyphenolic compounds obtained from litchi pericarp extract (LPE) were studied in vitro and in vivo for hepatoprotection. Epicatechin (EC) and Procyanidin A2 (PA2) of LPE were obtained by fractionated-extraction from pulverized litchi pericarps. All fractions, including LPE, were screened against silymarin in carbon tetrachloride (CCl4)-treated murine embryonic liver cell line (BNL). The effects of daily gavage-feeding of LPE, silymarin (200 mg/kg body weight) or H2O in CCl4-intoxicated male ICR mice were evaluated by studying serum chemicals, liver pathology and glutathione antioxidative enzymes. The effects of EC and PA2 on liver cell regenerative activity were investigated using a scratch wound healing assay and flow cytometric cell cycle analysis; the results of which demonstrated that LPE protected BNL from CCl4-intoxication. Gavage-feeding of LPE decreased serum glutamic oxaloacetate transaminase and glutamic pyruvic transaminase levels, and exhibited superior retention of the hexagonal structure of hepatocytes and reduced necrotic cells following liver histopathological examinations in CCl4-intoxicated ICR mice. Glutathione peroxidise and glutathione reductase activities were preserved as the normal control level in LPE groups. EC and PA2 were principle components of LPE. PA2 demonstrated liver cell regenerative activity in scratch wound healing assays and alcohol-induced liver cell injury in vitro.
CONCLUSIONS:
The present findings suggest that litchi pericarp polyphenolic extracts, including EC and PA2, may be a synergistic alternative to silymarin in hepatoprotection and liver cell regeneration.