Search Results (24)

Background/Objectives: Mitophagy, the selective removal of damaged mitochondria, plays a pivotal role in regulating cardiac hypertrophy and fibrosis under pressure overload. Targeting mitophagy may help mitigate adverse cardiac remodeling. This preclinical study examined the effects of cafestol, a coffee-derived diterpene, on pressure overload-induced cardiac hypertrophy and fibrosis in mice, with emphasis on mitophagy modulation and mitochondrial ultrastructure. Methods: Male normotensive mice underwent transverse aortic constriction (TAC) and received cafestol at 2, 10, or 50 mg/kg/day via oral gavage for 28 days. Cardiac function was assessed by echocardiography. Histological and molecular analyses quantified fibrosis, inflammation, and apoptosis. Protein expression of CD68, CTGF, DDR2, α-SMA, CD44, galectin-3 (Gal3), collagen I, GAPDH, Bcl-2, Bax, cleaved caspase-3, GRP78, p-ERK/ERK, ATF4, p-mTOR/mTOR, and p62 was evaluated. Transmission electron microscopy (TEM) was used to assess autophagosome formation and mitochondrial morphology. Results: TAC induced significant cardiac hypertrophy and fibrosis, accompanied by elevated expression of fibrotic (CTGF, DDR2, α-SMA, collagen I), inflammatory (CD68, CD44, Gal3), apoptotic (Bax, cleaved caspase-3), and endoplasmic reticulum stress markers (GRP78, ATF4). TEM revealed increased autophagosome accumulation and disrupted mitochondrial architecture. Cafestol treatment reduced collagen deposition, immune cell infiltration, and apoptotic signaling; enhanced Bcl-2 expression; and restored p62 levels. TEM findings demonstrated decreased autophagosome burden and preserved mitochondrial structure, consistent with improved mitophagic flux and mitochondrial homeostasis. Conclusions: Cafestol mitigated pressure overload-induced cardiac remodeling in mice by modulating mitophagy, suppressing fibrotic and inflammatory responses, and preserving mitochondrial integrity. These findings support further investigation of cafestol’s mechanisms and safety profile in preclinical models of cardiovascular disease. Full article

The main diterpenes found in coffee, kahweol and cafestol, possess anti-inflammatory, anti-diabetic, and anticancer properties but are also reported to cause hypercholesterolemic effects. Their concentrations are known to be variable in coffee. This review aimed to discuss the concentrations of kahweol and cafestol from green coffee beans to brewed coffee. The results showed that the average concentrations of kahweol and cafestol in Arabica green beans were higher than in roasted and brewed coffee. The decrease in kahweol from green beans to roasted beans was 14.83%. In brewed coffee, kahweol was reduced by 90.26% and cafestol by 88.28%, compared to green beans. The changes in kahweol and cafestol levels were found to be influenced by various factors, including roasting methods and brewing techniques. The ratio of kahweol to cafestol in Arabica green beans was 1.7; in green coffee oil and roasted coffee oil, 1.2; in roasted beans, 1.3; and in brewed coffee, 1.1. In addition to their health-related functional properties, kahweol and cafestol concentrations and their ratio are suggested to be relevant markers in distinguishing between coffee species at various processing stages. Full article

Coffee oil derived from spent coffee grounds of Coffea arabica is considered a novel food in the European Union (EU), requiring pre-market approval supported by comprehensive toxicological data. The effects of coffee oil on human health, particularly on blood parameters and liver enzymes, have been investigated in several studies. This review article summarizes the available toxicological literature on coffee oil, including its bioactive diterpenes cafestol and kahweol, which are known for their potential health effects. Considering the different modes of action of these two diterpenes, moderate consumption of coffee oil may be considered safe for healthy adults. Based on the changes in serum values in humans, this review provides initial estimations of LOAEL, NOAEL, and ADI for these diterpenes. The findings suggest that an intake of 225 mg of coffee oil per day might be considered safe assuming that coffee oil contains about 0.4% diterpenes. In summary, the assessment based on the published data indicates that (i) the consumption of coffee oil contained in any type of prepared coffee appears to be safe because the homeostasis of lipid levels in the blood is not significantly affected, and (ii) a low consumption of coffee oil as such might be acceptable but would require a refined risk assessment considering the exposure levels of the intended food product, which must be provided for novel food approval procedures. Full article

This study focuses on the extraction, characterization, and biological evaluation of diterpenes from green coffee beans, specifically, cafestol and kahweol. These compounds, known for their potential health benefits, were isolated via optimized extraction and saponification processes. Separation was achieved using silver nitrate-impregnated silica gel, and structural elucidation was performed through advanced 1D and 2D NMR techniques, including HSQC, HMBC, and (IN)ADEQUATE. Due to kahweol’s instability, the research prioritized cafestol for the synthesis of rhodamine B conjugates. Initial ester-linked conjugates proved unstable, prompting the development of more robust derivatives through amide linkage strategies and further functionalization via acetylation and oxidation reactions. Some oxidation methods led to furan ring cleavage, impacting structural integrity. Selected compounds were tested for cytotoxicity using SRB assays on human tumor cell lines (MCF7, A2780) and non-malignant fibroblasts (NIH 3T3). While the parent diterpenes and many derivatives showed minimal activity, several cafestol–rhodamine B conjugates demonstrated notable cytotoxic effects. Compound 6, in particular, exhibited selective activity against cancer cells with reduced toxicity toward non-malignant cells. Full article

This research paper investigates the phytochemical profile, antioxidant activity, antidiabetic potential, and antibacterial activity of Myrtus communis berries. Two extraction methods were employed to obtain the extracts: solid–liquid ultrasound-assisted extraction (UAE) and supercritical fluid extraction (SFE). The extracts were characterized using spectrophotometric methods and Reversed-Phase High-Performance Liquid Chromatography (RP-HPLC). The UAE extract exhibited higher total flavonoid and anthocyanin content, while the SFE extract prevailed in total phenolic content and antioxidant activity in the DPPH radical screening assay. RP-HPLC characterization identified and quantified several polyphenolic compounds. In the UAE extract, epigallocatechin was found in a concentration of 2656.24 ± 28.15 µg/g dry weight (DW). In the SFE extract, cafestol was the identified compound with the highest content at a level of 29.65 ± 0.03 µg/g DW. Both extracts contained several anthocyanin compounds, including cyanidin 3-O-glucoside chloride, cyanidin-3-O-rutinoside chloride, malvidin-3-O-glucoside chloride, pelargonidin 3-O-glucoside chloride, peonidin 3-O-glucoside chloride, and peonidin-3-O-rutinoside chloride. The antidiabetic potential was evaluated in vitro by measuring the inhibition of α-amylase from porcine pancreas (type I-A). The results highlighted the ability of myrtle berry extracts to inhibit α-amylase enzymatic activity, suggesting its potential as an alternative for controlling postprandial hyperglycemia. The UAE extract showed the lowest IC50 value among the two extracts, with an average of 8.37 ± 0.52 µg/mL DW. The antibacterial activity of the extracts was assessed in vitro against Bacillus spp., Escherichia coli, and Staphylococcus aureus using the disk diffusion method. Both myrtle berry extracts exhibited similar antibacterial activity against the tested bacterial strains. The results support further investigation of myrtle berries extracts as a potential ingredient in functional food formulation, particularly due to its antioxidant, antidiabetic, and antibacterial properties. Full article

Coffee is one of the most important beverages in the world and is produced from Coffea spp. beans. Diterpenes with ent-kaurane backbones have been described in this genus, and substances such as cafestol and kahweol have been widely investigated, along with their derivatives and biological properties. Other coffee ent-kaurane diterpenoids have been reported with new perspectives on their biological activities. The aim of this review is to update the chemical diversity of ent-kaurane diterpenoids in green and roasted coffee, detailing each new compound and reporting its biological potential. A systematic review was performed using the bibliographic databases (SciFinder, Web of Science, ScienceDirect) and specific keywords such as “coffea diterpenes”, “coffee diterpenes”, “coffee ent-kaurane diterpenes” and “coffee diterpenoids”. Only articles related to the isolation of coffee ent-kaurane compounds were considered. A total of 146 compounds were related to Coffea spp. since the first report in 1932. Different chemical skeletons were observed, and these compounds were grouped as furan-type, oxidation-type, rearrangement-type, lacton-type, and lactam-type, among others. In general, the new coffee diterpenoids showed potential as antidiabetic, antidiapogenic, α-glucosidade inhibition, antiplatelet activity, and Cav.3 inhibitors agents, revealing the possibilities for the design, discovery, and development of new drugs. Full article

Liver inflammation is frequently linked to oxidative stress and dysregulation of bile acid and fatty acid metabolism. This review focuses on the farnesoid X receptor (FXR), a critical regulator of bile acid homeostasis, and its interaction with the nuclear factor erythroid 2-related factor 2 (Nrf2), a key modulator of cellular defense against oxidative stress. The review explores the interplay between FXR and Nrf2 in liver inflammatory diseases, highlighting the potential therapeutic effects of natural FXR agonists. Specifically, compounds such as auraptene, cafestol, curcumin, fargesone A, hesperidin, lycopene, oleanolic acid, resveratrol, rutin, ursolic acid, and withaferin A are reviewed for their ability to modulate both the FXR and Nrf2 pathways. This article discusses their potential to alleviate liver inflammation, oxidative stress, and damage in diseases such as metabolic-associated fatty liver disease (MAFLD), cholestatic liver injury, and viral hepatitis. In addition, we address the molecular mechanisms driving liver inflammation, including oxidative stress, immune responses, and bile acid accumulation, while also summarizing relevant experimental models. This review emphasizes the promising therapeutic potential of targeting both the Nrf2 and FXR pathways using natural compounds, paving the way for future treatments for liver diseases. Finally, the limitations of the clinical application were indicated, and further research directions were proposed. Full article

Background: Coffee consumption is inversely associated with type 2 diabetes. Cafestol, a bioactive compound in coffee, has demonstrated glucose-lowering and insulin-secretory properties in cell and animal studies. The acute effects of cafestol on glucose metabolism in humans have only been briefly investigated, and longer-term effects have not been explored. This study aimed to assess the effects of purified cafestol on insulin sensitivity and other metabolic parameters in healthy individuals with increased waist circumference at risk of developing type 2 diabetes. Methods: A 12-week randomized, placebo-controlled, parallel trial was conducted with 40 participants. Insulin suppression tests, mixed meal tests, and MRI scans were performed before and after the intervention. Results: Administering 6 mg of cafestol twice daily did not alter insulin sensitivity or glucose tolerance but led to significant reductions in body weight (2%), visceral fat volume (5%), and gamma-glutamyl transferase levels (15%) compared to the placebo. Conclusions: Cafestol may hold promise for weight and visceral fat reduction. Cafestol did not improve insulin sensitivity or glucose tolerance in this study but might still contribute to the observed inverse association between coffee consumption and type 2 diabetes. Future research should explore higher dosages and longer treatment durations, particularly in individuals with impaired glucose metabolism and type 2 diabetes. Full article

Green and roasted coffee oils are products rich in bioactive compounds, such as linoleic acid and the diterpenes cafestol and kahweol, being a potential ingredient for food and cosmetic industries. An overview of oil extraction techniques most applied for coffee beans and their influence on the oil composition is presented. Both green and roasted coffee oil extractions are highlighted. Pressing, Soxhlet, microwave, and supercritical fluid extraction were the most used techniques used for coffee oil extraction. Conventional Soxhlet is most used on a lab scale, while pressing is most used in industry. Supercritical fluid extraction has also been evaluated mainly due to the environmental approach. One of the highlighted activities in Brazilian agribusiness is the industrialization of oils due to their increasing use in the formulation of cosmetics, pharmaceuticals, and foods. Green coffee oil (raw bean) has desirable bioactive compounds, increasing the interest of private companies and research institutions in its extraction process to preserve the properties contained in the oils. Full article

Hyperpigmentation skin disorders are marked by an abnormal accumulation or export of melanin pigment synthesized within melanocytes and pose a significant aesthetic concern. The search for novel natural compounds that exhibit pharmacological potential for treating pigmentation disorders is growing. In this study, kahweol (KW) and cafestol (CFS), two structural analogs of coffee diterpenes, were evaluated and compared for their effects on melanogenesis using B16F10 mouse melanoma cells and primary human melanocytes derived from Asian and African American skin. To the best of our knowledge, there are no reports of the effects of KW and CFS on melanogenesis yet. We first screened nontoxic concentrations of both compounds using an MTS assay after 72 h incubations and subsequently tested their effects on melanin synthesis and export. Cellular tyrosinase activity and cell-free mushroom tyrosinase activity were assayed to study the mechanisms of melanogenesis suppression. Human melanocytes from a moderately pigmented donor (HEMn-MP cells) and from a darkly pigmented donor (HEMn-DP cells) were next examined, and effects on cellular viability, melanin content, cellular tyrosinase activity, and melanin export (quantitated via dendricity) were similarly examined for both compounds. Our results show that KW and CFS did not significantly affect intracellular melanin content but suppressed extracellular melanin in B16F10 cells and dendritic parameters in human melanocytes, indicating their unique capacity to target extracellular melanogenesis and melanin export. Although KW showed a greater extracellular melanogenesis inhibitory capacity in B16F10 cells, in both primary melanocyte cells, CFS emerged as a potent inhibitor of melanin export compared to KW. Together, these results reveal novel modes of action of both compounds and indicate a promise to use CFS as a novel candidate for treating hyperpigmentation disorders of the human skin for clinical and cosmetic use. Additional research is necessary to shed light on the molecular pathways and the efficacy of melanogenesis inhibition by CFS in 3D human skin equivalents and in vivo studies. Full article

The diterpene cafestol represents the most potent cholesterol-elevating compound known in the human diet, being responsible for more than 80% of the effect of coffee on serum lipids, with a mechanism still not fully clarified. In the present study, the interaction of cafestol and 16-O-methylcafestol with the stabilized ligand-binding domain (LBD) of the Farnesoid X Receptor was evaluated by fluorescence and circular dichroism. Fluorescence quenching was observed with both cafestol and 16-O-methylcafestol due to an interaction occurring in the close environment of the tryptophan W454 residue of the protein, as confirmed by docking and molecular dynamics. A conformational change of the protein was also observed by circular dichroism, particularly for cafestol. These results provide evidence at the molecular level of the interactions of FXR with the coffee diterpenes, confirming that cafestol can act as an agonist of FXR, causing an enhancement of the cholesterol level in blood serum. Full article

Cafestol, a bioactive compound found in coffee, has attracted considerable attention due to its potential impact on cardiovascular health. This review aims to comprehensively explore the association between cafestol and cardiovascular diseases. We delve into the mechanisms through which cafestol influences lipid metabolism, inflammation, and endothelial function, all of which are pivotal in cardiovascular pathophysiology. Moreover, we meticulously analyze epidemiological studies and clinical trials to elucidate the relationship between cafestol and cardiovascular outcomes. Through a critical examination of existing literature, we aim to provide insights into the potential benefits and risks associated with cafestol concerning cardiovascular health. Full article

Alzheimer’s disease (AD) is characterized by excessive formation of beta-amyloid peptides (Aβ), mitochondrial dysfunction, enhanced production of reactive oxygen species (ROS), and altered glycolysis. Since the disease is currently not curable, preventive and supportive approaches are in the focus of science. Based on studies of promising single substances, the present study used a mixture (cocktail, SC) of compounds consisting of hesperetin (HstP), magnesium-orotate (MgOr), and folic acid (Fol), as well as the combination (KCC) of caffeine (Cof), kahweol (KW) and cafestol (CF). For all compounds, we showed positive results in SH-SY5Y-APP₆₉₅ cells—a model of early AD. Thus, SH-SY5Y-APP₆₉₅ cells were incubated with SC and the activity of the mitochondrial respiration chain complexes were measured, as well as levels of ATP, Aβ, ROS, lactate and pyruvate. Incubation of SH-SY5Y-APP₆₉₅ cells with SC significantly increased the endogenous respiration of mitochondria and ATP levels, while Aβ_1–40 levels were significantly decreased. Incubation with SC showed no significant effects on oxidative stress and glycolysis. In summary, this combination of compounds with proven effects on mitochondrial parameters has the potential to improve mitochondrial dysfunction in a cellular model of AD. Full article

Coffee silverskin (CS) is the thin epidermis covering and protecting the coffee bean and it represents the main by-product of the coffee roasting process. CS has recently gained attention due to its high content in bioactive molecules and the growing interest in valuable reutilization of waste products. Drawing inspiration from its biological function, here its potential in cosmetic applications was investigated. CS was recovered from one of the largest coffee roasters located in Switzerland and processed through supercritical CO₂ extraction, thereby generating coffee silverskin extract. Chemical profiling of this extract revealed the presence of potent molecules, among which cafestol and kahweol fatty acid esters, as well as acylglycerols, β-sitosterol and caffeine. The CS extract was then dissolved in organic shea butter, yielding the cosmetic active ingredient SLVR’Coffee™. In vitro gene expression studies performed on keratinocytes showed an upregulation of genes involved in oxidative stress responses and skin-barrier functionality upon treatment with the coffee silverskin extract. In vivo, our active protected the skin against Sodium Lauryl Sulfate (SLS)-induced irritation and accelerated its recovery. Furthermore, this active extract improved measured as well as perceived skin hydration in female volunteers, making it an innovative, bioinspired ingredient that comforts the skin and benefits the environment. Full article

One of the objectives of this study consists of the assessment of the antitumor activity of several extracts from three selected plant species: Xanthium spinosum L., Trifolium pratense L., and Coffea arabica L. and also a comparative study of this biological activity, with the aim of establishing a superior herbal extract for antitumor benefits. The phytochemical profile of the extracts was established by HPLC-MS analysis. Further, the selected extracts were screened in vitro for their antitumor activity and antioxidant potential on two cancer cell lines: A549—human lung adenocarcinoma and T47D-KBluc—human breast carcinoma and on normal cells. One extract per plant was selected for in vivo assessment of antitumor activity in an Ehrlich ascites mouse model. The extracts presented high content of antitumor compounds such as caffeoylquinic acids in the case of X. spinosum L. (7.22 µg/mL—xanthatin, 4.611 µg/mL—4-O-caffeoylquinic acid) and green coffee beans (10.008 µg/mL—cafestol, 265.507 µg/mL—4-O-caffeoylquinic acid), as well as isoflavones in the case of T. pratense L. (6806.60 ng/mL—ononin, 102.78 µg/mL—biochanin A). Concerning the in vitro results, the X. spinosum L. extracts presented the strongest anticancerous and antioxidant effects. In vivo, ascites cell viability decreased after T. pratense L. and green coffee bean extracts administration, whereas the oxidative stress reduction potential was important in tumor samples after T. pratense L. Cell viability was also decreased after administration of cyclophosphamide associated with X. spinosum L. and T. pratense L. extracts, respectively. These results suggested that T. pratense L. or X. spinosum L. extracts in combination with chemotherapy can induce lipid peroxidation in tumor cells and decrease the tumor viability especially, T. pratense L. extract. Full article