Kahweol

Food Chem Toxicol. 2007 Nov;45(11):2118-25.

Hepatoprotective and antioxidant effects of the coffee diterpenes kahweol and cafestol on carbon tetrachloride-induced liver damage in mice.[Pubmed: 17590492 ]

The hepatoprotective effects of Kahweol and cafestol, coffee-specific diterpenes, on the carbon tetrachloride (CCl(4))-induced liver damage as well as the possible mechanisms involved in these protections were investigated.
METHODS AND RESULTS:
Pretreatment with Kahweol and cafestol prior to the administration of CCl(4) significantly prevented the increase in the serum levels of hepatic enzyme markers (alanine aminotransferase and aspartate aminotransferase) and reduced oxidative stress, such as reduced glutathione 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 CCl(4). Treatment of the mice with Kahweol and cafestol also resulted in a significant decrease in the cytochrome P450 2E1 (CYP2E1), the major isozyme involved in CCl(4) bioactivation, specific enzyme activities, such as p-nitrophenol and aniline hydroxylation. Kahweol and cafestol exhibited antioxidant effects on FeCl(2)-ascorbate induced lipid peroxidation in a mouse liver homogenate, and on superoxide radical scavenging activity.
CONCLUSIONS:
These results suggest that the protective effects of Kahweol and cafestol against the CCl(4)-induced hepatotoxicity possibly involve mechanisms related to their ability to block the CYP2E1-mediated CCl(4) bioactivation and free radical scavenging effects.

PLoS One. 2011;6(8):e23407.

Anti-angiogenic and anti-inflammatory properties of kahweol, a coffee diterpene.[Pubmed: 21858104]

Epidemiological studies have shown that unfiltered coffee consumption is associated with a low incidence of cancer. This study aims to identify the effects of Kahweol, an antioxidant diterpene contained in unfiltered coffee, on angiogenesis and key inflammatory molecules.
METHODS AND RESULTS:
The experimental procedures included in vivo angiogenesis assays (both the chicken and quail choriallantoic membrane assay and the angiogenesis assay with fluorescent zebrafish), the ex vivo mouse aortic ring assay and the in vitro analysis of the effects of treatment of human endothelial cells with Kahweol in cell growth, cell viability, cell migration and zymographic assays, as well as the tube formation assay on Matrigel. Additionally, two inflammation markers were determined, namely, the expression levels of cyclooxygenase 2 and the levels of secreted monocyte chemoattractant protein-1. We show for the first time that Kahweol is an anti-angiogenic compound with inhibitory effects in two in vivo and one ex vivo angiogenesis models, with effects on specific steps of the angiogenic process: endothelial cell proliferation, migration, invasion and tube formation on Matrigel. We also demonstrate the inhibitory effect of Kahweol on the endothelial cell potential to remodel extracellular matrix by targeting two key molecules involved in the process, MMP-2 and uPA. Finally, the anti-inflammatory potential of this compound is demonstrated by its inhibition of both COX-2 expression and MCP-1 secretion in endothelial cells.
CONCLUSIONS:
Taken together, our data indicate that, indeed, Kahweol behaves as an anti-inflammatory and anti-angiogenic compound with potential use in antitumoral therapies. These data may contribute to the explanation of the reported antitumoral effects of Kahweol, including the recent epidemiological meta-analysis showing that drinking coffee could decrease the risk of certain cancers.

Food Chem Toxicol. 2002 Aug;40(8):1155-63.

Cafestol and kahweol, two coffee specific diterpenes with anticarcinogenic activity.[Pubmed: 12067578]

Epidemiological studies have found an inverse association between coffee consumption and the risk of certain types of cancers such as colorectal cancers. Animal data support such a chemopreventive effect of coffee. Substantial research has been devoted to the identification of coffee components that may be responsible for these beneficial effects.
METHODS AND RESULTS:
In animal models and cell culture systems, the coffee diterpenes cafestol and Kahweol (C+K) were shown to produce a broad range of biochemical effects resulting in a reduction of the genotoxicity of several carcinogens including 7,12-dimethylbenz[a]anthracene (DMBA), aflatoxin B(1) (AFB(1)), benzo[a]pyrene (B[a]P) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Different mechanisms appear to be involved in these chemoprotective effects: an induction of conjugating enzymes (e.g. glutathione S-transferases, glucuronosyl S-transferases), an increased expression of proteins involved in cellular antioxidant defense (e.g. gamma-glutamyl cysteine synthetase and heme oxygenase-1) and an inhibition of the expression and/or activity of cytochromes P450 involved in carcinogen activation (e.g. CYP2C11, CYP3A2). In animal models, the C+K-mediated induction of conjugating and antioxidant enzymes has been observed in hepatic, intestinal and kidney tissues. In the small intestine, these inductions were shown to be mediated by Nrf2-dependent transcriptional activation. In vitro investigations obtained in cell cultures of human origin indicate that the effects and mechanisms observed in animal test systems with C+K are likely to be of relevance for humans. In human liver epithelial cell lines transfected to express AFB(1)-activating P450s, C+K treatment resulted in a reduction of AFB(1)-DNA binding. This protection was correlated with an induction of GST-mu, an enzyme known to be involved in AFB(1) detoxification. In addition, C+K was found to inhibit P450 2B6, one of the human enzymes responsible for AFB(1) activation.
CONCLUSIONS:
Altogether, the data on the biological effects of C+K provide a plausible hypothesis to explain some of the anticarcinogenic effects of coffee observed in human epidemiological studies and in animal experiments.

FEBS Lett. 2004 Jul 2;569(1-3):321-6.

Suppressive effects of the kahweol and cafestol on cyclooxygenase-2 expression in macrophages.[Pubmed: 15225655 ]

Inducible cyclooxygenase-2 (COX-2) has been suggested to play a role in the processes of inflammation and carcinogenesis. Recent studies have shown the chemoprotective effects of Kahweol and cafestol, which are coffee-specific diterpenes.
METHODS AND RESULTS:
This study investigated the effects of Kahweol and cafestol on the expression of COX-2 in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. Kahweol and cafestol significantly suppressed the LPS-induced production of prostaglandin E(2), COX-2 protein and mRNA expression, and COX-2 promoter activity in a dose-dependent manner. Furthermore, Kahweol blocked the LPS-induced activation of NF-kappaB by preventing IkappaB degradation and inhibiting IkappaB kinase activity.
CONCLUSIONS:
These results will provide new insights into the anti-inflammatory and anti-carcinogenic properties of Kahweol and cafestol.