• Biomolecules & Therapeutics
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• 제25권3호
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• pp.337-343
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• 2017

Kahweol as a coffee-specific diterpene has been reported to induce apoptosis in human cancer cells. Although some molecular targets for kahweol-mediated apoptosis have been elucidated, the further mechanism for apoptotic effect of kahweol is not known. Activating transcription factor 3 (ATF3) has been reported to be associated with apoptosis in colorectal cancer. The present study was performed to investigate the molecular mechanism by which kahweol stimulates ATF3 expression and apoptosis in human colorectal cancer cells. Kahweol increased apoptosis in human colorectal cancer cells. It also increased ATF3 expression through the transcriptional activity. The responsible cis-element for ATF3 transcriptional activation by kahweol was CREB located between -147 to -85 of ATF3 promoter. ATF3 overexpression increased kahweol-mediated cleaved PARP, while ATF3 knockdown attenuated the cleavage of PARP by kahweol. Inhibition of ERK1/2 and $GSK3{\beta}$ blocked kahweol-mediated ATF3 expression. The results suggest that kahweol induces apoptosis through ATF3-mediated pathway in human colorectal cancer cells.

• BMB Reports
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• 제50권11호
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• pp.566-571
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• 2017

Weight loss ${\geq}5$ percent is sufficient to significantly reduce health risks for obese people; therefore, development of novel weight loss compounds with reduced toxicity is urgently required. After screening of natural compounds with anti-adipogenesis properties in 3T3-L1 cells, we determined that kahweol, a coffee-specific diterpene, inhibited adipogenesis. Kahweol reduced lipid accumulation and expression levels of adipogenesis and lipid accumulation-related factors. Levels of phosphorylated AKT and phosphorylated JAK2, that induce lipid accumulation, decreased in kahweol-treated cells. Particularly, kahweol treatment significantly increased AMP-activated protein kinase (AMPK) activation. We revealed that depletion of AMPK alleviated reduction in lipid accumulation from kahweol treatment, suggesting that inhibition of lipid accumulation by kahweol is dependent on AMPK activation. We detected more rapid reduction in blood glucose levels in mice administrated kahweol than in control mice. We suggest that kahweol has anti-obesity effects and should be studied further for possible therapeutic applications.

• Biomolecules & Therapeutics
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• 제23권2호
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• pp.128-133
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• 2015

Although coffee is known to have antioxidant, anti-inflammatory, and antitumor properties, there have been few reports about the effect and mechanism of coffee compounds in colorectal cancer. Heat shock proteins (HSPs) are molecular chaperones that prevent cell death. Their expression is significantly elevated in many tumors and is accompanied by increased cell proliferation, metastasis and poor response to chemotherapy. In this study, we investigated the cytotoxicity of four bioactive compounds in coffee, namely, caffeine, caffeic acid, chlorogenic acid, and kahweol, in HT-29 human colon adenocarcinoma cells. Only kahweol showed significant cytotoxicity. Specifically, kahweol increased the expression of caspase-3, a pro-apoptotic factor, and decreased the expression of anti-apoptotic factors, such as Bcl-2 and phosphorylated Akt. In addition, kahweol significantly attenuated the expression of HSP70. Inhibition of HSP70 activity with triptolide increased kahweol-induced cytotoxicity. In contrast, overexpression of HSP70 significantly reduced kahweol-induced cell death. Taken together, these results demonstrate that kahweol inhibits colorectal tumor cell growth by promoting apoptosis and suppressing HSP70 expression.

• Bulletin of the Korean Chemical Society
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• 제27권9호
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• pp.1386-1392
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• 2006

Kahweol and cafestol significantly reduced t-BHP-induced oxidative injuries in cultured rat hepatocytes, as determined by cell cytotoxicity, intracellular glutathione (GSH) content and lipid peroxidation in a dose-dependent manner. In addition, kahweol and cafestol provided good protection from the t-BHPinduced production of intracellular reactive oxygen species and DNA damage. The in vivo study showed that pretreatment with kahweol and cafestol prior to the administration of t-BHP significantly prevented the increase in serum levels of hepatic enzyme markers (alanine aminotransferase and aspartate aminotransferase) and reduced oxidative stress, such as GSH content and lipid peroxidation, in the liver in a dose-dependent manner. The histopathological evaluation of the livers also revealed that kahweol and cafestol reduced the incidence of liver lesions induced by t-BHP. Taken together, these results support the anti-oxidative role of kahweol and cafestol and demonstrate that kahweol and cafestol can protect hepatocytes from oxidative stress.

• 생명과학회지
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• 제22권5호
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• pp.697-701
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• 2012

본 연구에서는 항응고제로서의 역할을 가지면서 또한 혈액응고와는 관련 없는 종양세포의 전이 등을 조절하는 것으로 알려진 activated protein C (APC)가 종양세포의 사멸에는 어떠한 영향을 미치는 지에 대한 연구를 수행하였다. Tumor necrosis factor (TNF)-${\alpha}$와 cyclohexamide를 병합 처리하거나 FAS를 처리하게 되면 인간 신장암세포인 Caki에서는 유의적인 세포사멸이 일어난다. 하지만, APC는 이러한 세포사멸에 아무런 영향을 미치지 못하였다. 또한 TRAIL을 인간 뇌 암세포인 T98G와 유방암세포인 MDA231세포에 처리하여 세포사멸을 일으켰을 때에도 APC는 세포사멸을 조절하지 못하였다. 그러나, TRAIL에 대한 민감도를 증가시키기 위한 kahweol과 TRAIL의 병합처리나, kahweol과 malatonin의 병합처리에 의한 신장암세포의 사멸은 APC에 의해 유의적으로 억제되는 것을 확인하였다. 따라서, 이는 APC가 항암치료의 효율성을 조절 할 수 있는 가능성을 가짐을 의미한다.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2005년도 춘계 국제심포지엄 및 학술대회
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• pp.166-166
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• 2005

• Journal of Nutrition and Health
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• 제49권4호
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• pp.213-222
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• 2016

Purpose: Coffee is the most frequently consumed food item in South Korea after rice and cabbage. Coffee contains various substances, including caffeine, cafestol, kahweol, chlorogenic acid, and many other known and unknown ingredients with some health benefits. Especially, cumulative evidence has shown that regular coffee use is associated with lower risk of type 2 diabetes, although limited and inconsistent data are available regarding metabolic syndrome. Methods: This study reviewed all available scientific and epidemiologic evidence on coffee consumption, metabolic syndrome, and the association between them. Most epidemiologic research regarding this association was of a cross-sectional design, and a few case-control and cohort studies were available. We conducted meta-analysis with 11 observational studies investigated in Europe, America, and Asia. Summary odds ratios (OR) were calculated using a random-effects model. Results: The overall OR of metabolic syndrome was 0.90 (95% Confidence Interval (CI), 0.81-0.99) for the highest category of coffee intake compared with the lowest intake category. These associations were stronger in populations of US and Europe (OR 0.84, 95% CI 0.76-0.94), whereas no association was observed in the Asian population (OR 1.00, 95% CI 0.81-1.23). Conclusion: The review results indicate that frequent coffee consumption may be beneficial to metabolic syndrome, but the association between coffee consumption and metabolic syndrome may differ by nations or continents.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제40권
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• pp.44.1-44.17
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• 2018

Background: Coffee extract has been investigated by many authors, and many minor components of coffee are known, such as polyphenols, diterpenes (kahweol and cafestol), melanoidins, and trigonelline, to have anti-inflammatory, anti-oxidant, anti-angiogenic, anticancer, chemoprotective, and hepatoprotective effects. Therefore, it is necessary to know its pharmacological effect on hepatocytes which show the most active cellular regeneration in body. Methods: In order to determine whether coffee extract has a beneficial effect on the liver, 20 C57BL/6J mice were intraperitoneally injected once with dialyzed coffee extract (DCE)-2.5 (equivalent to 2.5 cups of coffee a day in man), DCE-5, or DCE-10, or normal saline (control), and then followed by histological observation and IP-HPLC (immunoprecipitation high performance liquid chromatography) over 24 h. Results: Mice treated with DCE-2.5 or DCE-5 showed markedly hypertrophic hepatocytes with eosinophilic cytoplasms, while those treated with DCE-10 showed slightly hypertrophic hepatocytes, which were well aligned in hepatic cords with increased sinusoidal spaces. DCE induced the upregulations of cellular proliferation, growth factor/RAS signaling, cellular protection, p53-mediated apoptosis, angiogenesis, and antioxidant and protection-related proteins, and the downregulations of NFkB signaling proteins, inflammatory proteins, and oncogenic proteins in mouse livers. These protein expression changes induced by DCE were usually limited to the range ± 10%, suggesting murine hepatocytes were safely reactive to DCE within the threshold of physiological homeostasis. DCE-2.5 and DCE-5 induced relatively mild dose-dependent changes in protein expressions for cellular regeneration and de novo angiogenesis as compared with non-treated controls, whereas DCE-10 induced fluctuations in protein expressions. Conclusion: These observations suggested that DCE-2.5 and DCE-5 were safer and more beneficial to murine hepatocytes than DCE-10. It was also found that murine hepatocytes treated with DCE showed mild p53-mediated apoptosis, followed by cellular proliferation and growth devoid of fibrosis signaling (as determined by IP-HPLC), and subsequently progressed to rapid cellular regeneration and wound healing in the absence of any inflammatory reaction based on histologic observations.

• 산업식품공학
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• 제22권4호
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• pp.337-343
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• 2018

커피는 전 세계적으로 가장 널리 음용되는 음료 중에 하나로, 항산화 및 항염증 활성을 나타내는 카페인, 클로로겐산, 카페스톨, 트리고넬린, 카와웰 등의 물질을 함유하고 있다. Lactobacillus plantarum은 식물성 식품의 발효에 가장 흔하게 사용되는 유산균으로, 식물에 풍부하게 함유되어 있는 페놀 화합물을 분해하여 고부가 가치의 항산화제 및 방향 성분을 생산한다. 본 연구에서는 L. plantarum을 이용한 발효커피를 제조하여 RAW264.7 대식세포에 대한 면역 조절 효과를 조사하였다. 커피 발효에는 에티오피아 예가체프(Ethiopia Yirgacheffe)와 과테말라 안티구아(Guatemala Antigua) 2종의 원두가 사용되었으며, Y2와 A2는 2%의 포도당, Y5와 A5는 5%의 포도당, 그리고 Y10과 A10은 10%의 포도당이 발효를 위해 첨가되었다. lipopolysaccharide에 의해 자극된 RAW264.7 세포에서 유산균 발효 커피 추출물은 nitric oxide 생성 및 inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor ${\alpha}$, interleukin $1{\beta}$, interleukin 6, interferon ${\gamma}$ 등의 면역 관련 유전자의 발현을 유의하게 억제하였으며, Y10과 A10 추출물이 다른 커피 추출물에 비해 상대적으로 높은 항산화 활성을 나타내었다. 반면에 IL-6의 경우에는 Y2와 A2 커피 추출물이 가장 높은 억제효과를 나타내었다. 본 연구 결과는 면역세포에 대한 유산균 발효 커피 추출물의 항염증 기전을 이해하는데 도움이 될 수 있으리라 생각되며, 또한 유산균 발효 커피 추출물은 유용한 항염증성 식품 소재로 이용될 수 있다고 판단된다.