Kahweol, a natural diterpene from coffee, induces peripheral antinociception by endocannabinoid system activation

Kahweol is a compound derived from coffee with reported antinociceptive effects. Based on the few reports that exist in the literature regarding the mechanisms involved in kahweol-induced peripheral antinociceptive action, this study proposed to investigate the contribution of the endocannabinoid system to the peripheral antinociception induced in rats by kahweol. Hyperalgesia was induced by intraplantar injection of prostaglandin E2(PGE2) and was measured with the paw pressure test. Kahweol and the drugs to test the cannabinoid system were administered locally into the right hind paw. The endocannabinoids were purified by open-bed chromatography on silica and measured by LC-MS. Kahweol (80 µg/paw) induced peripheral antinociception against PGE2-induced hyperalgesia. This effect was reversed by the intraplantar injection of the CB1 cannabinoid receptor antagonist AM251 (20, 40, and 80 μg/paw), but not by the CB2 cannabinoid receptor antagonist AM630 (100 μg/paw). Treatment with the endocannabinoid reuptake inhibitor VDM11 (2.5 μg/paw) intensified the peripheral antinociceptive effect induced by low-dose kahweol (40 μg/paw). The monoacylglycerol lipase (MAGL) inhibitor, JZL184 (4 μg/paw), and the dual MAGL/fatty acid amide hydrolase (FAAH) inhibitor, MAFP (0.5 μg/paw), potentiated the peripheral antinociceptive effect of low-dose kahweol. Furthermore, kahweol increased the levels of the endocannabinoid anandamide, but not of the other endocannabinoid 2-arachidonoylglycerol nor of anandamide-related N-acylethanolamines, in the plantar surface of the rat paw. Our results suggested that kahweol induced peripheral antinociception via anandamide release and activation of CB1 cannabinoid receptors and this compound could be used to develop new drugs for pain relief.

Characterization of Roasted Coffea arabica Species by the Relationship Between Caffeine and Diterpenes Contents

Abstract Commercial roasted and ground coffees are usually blends of Coffea arabica and Coffea canephora. Considering the differences in price and sensory characteristics between these two species, the identification of the presence of each species in commercial blends is of great interest. The aim of this study was to describe typical profiles of caffeine and diterpenes (kahweol and cafestol) contents and the ratios among these compounds to support the characterization of Coffea species in roasted coffees. 32 good cup quality Brazilian C. arabica coffees (from coffee quality contests) produced using different postharvest treatments were studied. All analysis were performed by HPLC. Higher ranges were observed in diterpene contents - kahweol varied from 1.75 to 10.68 g/kg (coefficient of variation of 510%) and cafestol from 1.76 to 9.66 g/kg (449%) - than caffeine, that varied from 5.1 to 16.2 g/kg (coefficient of variation of 218%). Wide ranges of the kahweol/cafestol ratio (0.63 to 2.77) and the caffeine/kahweol ratio (0.84 to 5.15) were also observed. Hence it was proposed the additional use of a new parameter, the ratio of caffeine/sum of diterpenes (kahweol + cafestol) that presents values from 0.54 to 2.39. The results indicated that the combined use of these parameters could be a potential tool for discriminating Coffea species in blends of roasted and ground coffee. It was proposed as potentially indicative of C. arabica: values of kahweol/cafestol ratio above 0.50, associated with caffeine/kahweol ratio lower than 5.50 and caffeine/sum of diterpenes ratio lower than 2.50.

Kahweol from Coffee Induces Apoptosis by Upregulating Activating Transcription Factor 3 in Human Colorectal Cancer Cells

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 GSK3β blocked kahweol-mediated ATF3 expression. The results suggest that kahweol induces apoptosis through ATF3-mediated pathway in human colorectal cancer cells.

The Cytotoxicity of Kahweol in HT-29 Human Colorectal Cancer Cells Is Mediated by Apoptosis and Suppression of Heat Shock Protein 70 Expression

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.

Consumo de café segundo métodos de preparo da bebida e associação com perfil lipídico sérico em hipertensos e diabéticos / Intake of different coffee preparations and its association with the serum lipid profile of diabetics and hypertensive individuals

OBJETIVO: Verificar o consumo da bebida café segundo a quantidade ingerida e os métodos de preparo, e sua associação com o perfil lipídico sérico de hipertensos e diabéticos. MÉTODOS: Foram coletados, por meio de entrevista, dados demográficos, de estilo de vida e de consumo alimentar, aferidas medidas antropométricas e colhido sangue para análise de perfil lipídico sérico. Análise descritiva, testes t de Student, qui-quadrado e de correlação linear de Pearson foram utilizados com 5 por cento de probabilidade de erro experimental. RESULTADOS: Foram avaliados 182 indivíduos hipertensos e diabéticos tipo 2, consumidores de café, distribuídos em dois grupos segundo o método de preparo da bebida: à brasileira e fervido. Os grupos foram semelhantes quanto aos dados demográficos, antropométricos, de estilo de vida, de consumo alimentar e de perfil lipídico sérico. A quantidade per capita de pó utilizado no método à brasileira e no fervido foi de M=7,52, DP=4,99g e M=7,91, DP=5,87g, respectivamente. O volume ingerido e a frequência de consumo dos indivíduos do grupo à brasileira foi de M=517,3, DP=402,7mL e M=2,14, DP=1,06 vezes/dia, e para os consumidores de café fervido, M=513,4, DP=409,8mL e M=2,2, DP=0,94 vezes/dia. Não houve associação significativa entre a quantidade ingerida da bebida café e o perfil lipídico sérico. CONCLUSÃO: Não houve associação entre o consumo de café à brasileira ou fervido e o perfil lipídico sérico, possivelmente em função da quantidade consumida e/ou da diluição utilizada. Se, por um lado, os resultados não permitem desestimular o consumo da bebida na quantidade ingerida pela população estudada, como medida de prevenção cardiovascular, por outro lado autorizam concluir que há necessidade de avançar nessa linha de investigação.

OBJECTIVE: This study determined the amount of coffee consumed, the preparation methods and the association between coffee intake and the serum lipid profile of diabetics and hypertensive individuals. METHODS: Interviews were done to collect demographic and lifestyle data and food intake. Blood was collected to determine serum lipid profiles and anthropometric characteristics were measured. Descriptive analysis and the Student's t-test, chi-square test and Pearson's linear correlation were used with p£0.05 to establish statistical significance. RESULTS: A total of 182 hypertensive and type-2 diabetic individuals who consumed coffee were evaluated and categorized according to the preparation method: Brazilian or boiled. The population had similar demographics, anthropometrics, lifestyles, food habits and serum lipid profiles. The per capita amount of powder ingested when the Brazilian preparation method (uses a filter) was used compared with boiling was M=7.52, SD=4.99g and M=7.91, SD=5.87g, respectively. In both groups, those levels were obtained in accordance with the estimated daily intake volume of the drink. The volume ingested by individuals in the "Brazilian" group and intake frequency were: M=517.3, SD=402.7mL and M=2.14, SD=1.06 times/day and in the "boiled" group: M=513.4, SD=409.8mL, and M=2.2 SD=0.94 times/day. There was no significant association between coffee intake and serum lipid profile. CONCLUSION: There was no association between coffee intake and serum lipid profile in the studied population, possibly because of the amount consumed and/or dilution used. If, on the one hand, the results do not allow us to discourage consumption in the amounts consumed by the studied population as a way to prevent cardiovascular disease, on the other hand, it is clear that this line of research requires further investigation.