인간진피섬유아세포에서 코코아 주요성분인 Procyanidin B1이 JNK-AP1-TRE Axis를 통한 Matrix-Metalloprotease 1 발현조절에 미치는 영향

차화준,김영주 대한피부미용학회 2015 대한피부미용학회지 Vol.13 No.6

Cocoa extracts contain various anti-oxidant which play as anti-skin aging agents. Procyanidin B1 is one of major ingredients in cocoa. However, in dermis, effects of Procyanidin B1 are not understood currently. Therefore, we investigated whether procyanidin B1 regulated extra-cellular matrix (ECM) and exerts its therapeutic action and its effect on the anti-wrinkle. We show firstly cytotoxicity of procyanidin B1. Under 100 μg/ml procyanidin B1 show no cytotoxicity in normal human dermal fibroblasts (nHDFs). In addition, we measured matrix metalloprotease 1 (MMP1) mRNA expression in procyanidin B1 exposed nHDFs. As shown results, procyanidin B1 repressed oxidative stress induced increase of MMP1 mRNA expression. And procyanidin B1 repressed activity of TPA responsive element (TRE) which is DNA binding site of AP-1 complex which consist c-Jun and c-Fos. JNK-c-Jun axis is implicated oxidative stress-mediated MMP1 mRNA regulation. In addition, JNK is activated using phosphorylation of JNK. Therefore, we shown phosphorylation in procyanidin B1-exposed nHDFs. As shown results, procyanidin B1 decreased oxidativemediated JNK phosphorylation of JNK. Overall, our results suggest procyanidin B1 is a potential cosmetic ingredient repressed antiaging and anti-wrinkle in skin using repression of oxidative-induced MMP1 expression.

Cocoa Flavanols and Procyanidins Can Modulate the Lipopolysaccharide Activation of Polymorphonuclear Cells In Vitro

Thomas P. Kenny,Shang-an Shu,Yuki Moritoki,Carl L. Keen,M. Eric Gershwin 한국식품영양과학회 2009 Journal of medicinal food Vol.12 No.1

Flavanols and procyanidins isolated from cocoa have been reported to possess multiple activities potentially relevant to oxidant defenses, vascular function, and immune function. In a combination of in vivo and in vitro studies, we and others have observed that cocoa can be an anti-inflammatory modulator and that compounds in cocoa are capable of modulating eicosanoid production, platelet aggregation, and the pool size of nitric oxide. The present study extends these findings by examining the in vitro effects of cocoa procyanidins on polymorphonuclear cells (PMNs). PMNs, part of the innate arm of the immune system, represent 50–60% of the total peripheral white blood cells and are the first cells to be recruited to the sites of inflammation or injury secondary to bacterial infections. Herein, we demonstrate that certain flavanols and procyanidins isolated from cocoa can moderate a subset of signaling pathways derived from lipopolysaccharide (LPS) stimulation of PMNs, mainly, PMN oxidative bursts and activation markers, and they can influence select apoptosis mechanisms. We hypothesize that flavanols and procyanidins can decrease the impact of LPS on the N-formyl-Met-Leu-Phe-primed PMN ability to generate reactive oxygen species by partially interfering in activation of the mitogen-activated protein kinase pathway.

Cocoa Flavanols and Procyanidins Can Modulate the Lipopolysaccharide Activation of Polymorphonuclear Cells In Vitro

Kenny, Thomas P.,Shu, Shang-An,Moritoki, Yuki,Keen, Carl L.,Gershwin, M. Eric The Korean Society of Food Science and Nutrition 2009 Journal of medicinal food Vol.12 No.1

Flavanols and procyanidins isolated from cocoa have been reported to possess multiple activities potentially relevant to oxidant defenses, vascular function, and immune function. In a combination of in vivo and in vitro studies, we and others have observed that cocoa can be an anti-inflammatory modulator and that compounds in cocoa are capable of modulating eicosanoid production, platelet aggregation, and the pool size of nitric oxide. The present study extends these findings by examining the in vitro effects of cocoa procyanidins on polymorphonuclear cells (PMNs). PMNs, part of the innate arm of the immune system, represent 50-60% of the total peripheral white blood cells and are the first cells to be recruited to the sites of inflammation or injury secondary to bacterial infections. Herein, we demonstrate that certain flavanols and procyanidins isolated from cocoa can moderate a subset of signaling pathways derived from lipopolysaccharide (LPS) stimulation of PMNs, mainly, PMN oxidative bursts and activation markers, and they can influence select apoptosis mechanisms. We hypothesize that flavanols and procyanidins can decrease the impact of LPS on the N-formyl-Met-Leu-Phe-primed PMN ability to generate reactive oxygen species by partially interfering in activation of the mitogen-activated protein kinase pathway.

Antioxidant and apoptotic activity of cocoa bean husk extract on prostate cancer cells

Choi Jinhee,Yang Changwon,Lim Whasun,Song Gwonhwa,최해연 대한독성 유전단백체 학회 2022 Molecular & cellular toxicology Vol.18 No.2

Background Although prostate cancer is the most commonly diagnosed cancer in men, its incidence among Asians, who consume foods rich in phenols, is relatively low compared with that in other populations. Cocoa bean husk (CBH) is an important by-product of the cocoa industry; its polyphenol content (catechin, epicatechin, and procyanidin B) is as high as that of cocoa beans. However, there are no studies on the anticancer effect of CBH. Herein, we assessed the antioxidant and anticancer effects of CBH on prostate cancer cells. Objectives We fractionated CBH ethanol crude extract and compared the total polyphenol content, total flavonoid content, and DPPH and ABTS + radical scavenging activities of the fractions. Catechin, epicatechin, and procyanidin B were analysed by HPLC in the ethyl acetate (EAF) and butanol (BF) fractions, which had the highest physiological content and antioxidant activity. PC3 and DU145 cells were treated with the two fractions, and annexin V/propidium iodide, and TUNEL assays were performed to assess apoptosis and DNA fragmentation, respectively. Results The highest phytochemical content and antioxidant activity were observed in EAF, followed by those in BF. HPLC analysis revealed high content of phenolic compounds in both these fractions. Notably, catechin (5.64 mg/g), epicatechin (20.47 mg/g), and procyanidin B (20.29 mg/g) were abundant in EAF. Both fractions induced apoptosis in a concentrationdependent manner in PC3 and DU145 cells, and DNA fragmentation at a concentration of 200 μg/mL. Conclusion CBH, a by-product of cocoa processing, contains large amounts of phenolic compounds and exhibits high antioxidant activity and anticancer effects on prostate cancer cells. CBH has potential applications as a functional food material.

Cocoa procyanidins protect PC12 cells from hydrogen-peroxide-induced apoptosis by inhibiting activation of p38 MAPK and JNK

Cho, Eun Sun,Lee, Ki Won,Lee, Hyong Joo Elsevier 2008 Mutation research Vol.640 No.1

<P><B>Abstract</B></P><P>Oxidative stress induced by reactive oxygen species has been strongly associated with the pathogenesis of neurodegenerative disorders, including Alzheimer's disease. In this study, we investigated the possible protective effects of a cocoa procyanidin fraction (CPF) and procyanidin B2 (epicatechin-(4β-8)-epicatechin) – a major polyphenol in cocoa – against apoptosis of PC12 rat pheochromocytoma (PC12) cells induced by hydrogen peroxide (H<SUB>2</SUB>O<SUB>2</SUB>). CPF (1 and 5μg/ml) and procyanidin B2 (1 and 5μM) reduced PC12 cell death caused by H<SUB>2</SUB>O<SUB>2</SUB>, as determined by MTT and trypan blue exclusion assays. CPF and procyanidin B2 attenuated the H<SUB>2</SUB>O<SUB>2</SUB>-induced fragmentation of nucleus and DNA in PC12 cells. Western blot data demonstrated that H<SUB>2</SUB>O<SUB>2</SUB> induced cleavage of poly(ADP-ribose)polymerase (PARP), downregulated Bcl-X<SUB>L</SUB> and Bcl-2 in PC12 cells. Pretreatment with CPF or procyanidin B2 before H<SUB>2</SUB>O<SUB>2</SUB> treatment diminished PARP cleavage and increased Bcl-X<SUB>L</SUB> and Bcl-2 expression compared with those only treated with H<SUB>2</SUB>O<SUB>2</SUB>. Activation of caspase-3 by H<SUB>2</SUB>O<SUB>2</SUB> was inhibited by pretreatment with CPF or procyanidin B2. Furthermore, H<SUB>2</SUB>O<SUB>2</SUB>-induced rapid and significant phosphorylation of c-Jun N-terminal protein kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), and both of these effects were attenuated by CPF or procyanidin B2 treatment. These results suggest that the protective effects of CPF and procyanidin B2 against H<SUB>2</SUB>O<SUB>2</SUB>-induced apoptosis involve inhibiting the downregulation of Bcl-X<SUB>L</SUB> and Bcl-2 expression through blocking the activation of JNK and p38 MAPK.</P>