Biorefinery and Stepwise Strategies for Valorizing Coffee By-Products as Bioactive Food Ingredients and Nutraceuticals

Featured Application: This study presents a comprehensive and stepwise strategy for utilizing coffee by-products as a sustainable source to develop bioactive food ingredients and nutraceuticals. Coffee by-products can be transformed into versatile functional food ingredients and nutraceuticals by implementing green extraction techniques and employing a biorefinery approach. These products offer a wide range of benefits, including antioxidant, anti-inflammatory, and anti-obesity effects, as well as the potential to regulate energy metabolism and blood sugar levels and serve as adjunct therapies for conditions such as cardiovascular disease, diabetes, and neurodegenerative disorders. This research not only contributes to the creation of functional food products and supplements but also promotes sustainability and addresses the prevention and management of chronic diseases. Coffee production generates significant amounts of by-products, posing challenges for waste management in the industry. Recent research has revealed that coffee by-products are rich in bioactive compounds suitable to produce functional food ingredients and nutraceuticals. In this review, we explore biorefinery strategies for extracting and utilizing bioactive compounds from coffee by-products, including the production of bio-based chemicals and materials, as well as the extraction of phenolic compounds, antioxidants, and dietary fiber for food applications. We propose a stepwise approach for the development of functional food ingredients and nutraceuticals from coffee by-products, covering the identification of needs, comprehensive characterization, in vitro and in vivo research, unraveling the mechanism of action, food and nutraceutical formulation, sensory analysis, shelf-life stability, scale-up, randomized control trials, and biostatistics and bioinformatic integration. Additionally, we discuss the market potential, regulatory issues, and technological innovation surrounding the commercialization of coffee by-product-based products. Emphasizing the importance of regulatory compliance and sustainability in the coffee industry, this review highlights the potential of coffee by-products to be transformed from waste into valuable functional food ingredients and nutraceuticals, offering a promising avenue for waste reduction and promoting sustainability in the coffee industryThis research was funded by the COCARDIOLAC (RTI 2018-097504-B-I00) and ECOPULP (TED2021-129262A-I00) projects from the Spanish Ministry of Science and Innovation and the Excellence Line for University Teaching Staff within the Multiannual Agreement between the Community of Madrid and the UAM (2019–2023). M. Rebollo-Hernanz received funding from the FPU program of the Ministry of Universities for his predoctoral fellowship (FPU15/04238) and a grant for the requalification of the Spanish university system (CA1/RSUE/2021-00656)

Caffeine, but not other phytochemicals, in mate tea (Ilex paraguariensis St. Hilaire) attenuates high-fat-high-sucrose-diet-driven lipogenesis and body fat accumulation

Authors followed the guidelines of the National Institutes of Health guide for the care and use of Laboratory animals (NIH Publications No.8023, revised 1978)The objective was to examine the effectiveness of mate tea (MT, Ilex paraguariensis St. Hilaire) and caffeine from mate tea (MC) on in vitro lipid accumulation and in vivo diet-driven-obesity. MC and decaffeinated mate (DM) were obtained using supercritical CO2 extraction and mainly composed of caffeine and caffeoylquinic acids, respectively. MC reduced lipid accumulation (41%) via downregulation of fatty acid synthase (Fasn) (39%) in 3T3-L1 adipocytes. Rats fed a high-fat-high-sucrose-diet and 0.1% of caffeine from MC, MT, or DM. MC attenuated weight gain (16%) and body fat accumulation (22%). MC reduced Fasn expression in both adipose tissue (66%) and liver (37%). MC diminished pyruvate kinase (PK, 59%) and microsomal triglyceride transfer protein (MTP, 50%) hepatic expression. In silico, neochlorogenic acid interacted with PK and MTP allosteric sites. FAS β‐ketoacyl reductase domain showed the highest affinity to 3,5-dicaffeoylquinic acid. Caffeine suppressed lipid accumulation and body weight gain, through the modulation of lipogenic gene expressio

Revalorization of coffee husk: Modeling and optimizing the green sustainable extraction of phenolic compounds

This study aimed to model and optimize a green sustainable extraction method of phenolic compounds from the coffee husk. Response surface methodology (RSM) and artificial neural networks (ANNs) were used to model the impact of extraction variables (temperature, time, acidity, and solid-to-liquid ratio) on the recovery of phenolic compounds. All responses were fitted to the RSM and ANN model, which revealed high estimation capabilities. The main factors affecting phenolic extraction were temperature, followed by solid-to-liquid ratio, and acidity. The optimal extraction conditions were 100◦C, 90 min, 0% citric acid, and 0.02 g coffee husk mL−1 . Under these conditions, experimental values for total phenolic compounds, flavonoids, flavanols, proanthocyanidins, phenolic acids, o-diphenols, and in vitro antioxidant capacity matched with predicted ones, therefore, validating the model. The presence of chlorogenic, protocatechuic, caffeic, and gallic acids and kaemferol-3-O-galactoside was confirmed by UPLC-ESI-MS/MS. The phenolic aqueous extracts from the coffee husk could be used as sustainable food ingredients and nutraceutical productsThis research was funded by the Spanish Ministry of Science and Innovation, SUSCOFFEE (grant number AGL2014–57239-R), COCARDIOLAC (grant number RTI 2018-097504-B-I00) projects, and the Community of Madrid and UAM Agreement (2019–2023). M. Rebollo-Hernanz thanks to the FPU program of the Ministry of Universities for his predoctoral fellowship (grant number FPU15/04238

Extraction of phenolic compounds from cocoa shell: modeling using response surface methodology and artificial neural networks

This work's objective was to model and optimize a green extraction method of phenolic compounds from the cocoa shell as a strategy to revalorize this by-product, obtaining novel high-value products. According to a Box-Behnken design, 27 extractions were carried out at different conditions of temperature, time, acidity, and solid-to-liquid ratio. Total phenolic compounds, flavonoids, flavanols, proanthocyanidins, phenolic acids, o-diphenols, and in vitro antioxidant capacity were assessed in each extract. Response surface methodology (RSM) and artificial neural networks (ANN) were used to model the effect of the different parameters on the green aqueous extraction of phenolic compounds from the cocoa shell. The obtained mathematical models fitted well for all the responses. RSM and ANN exhibited high estimation capabilities. The main factors affecting phenolic extraction were temperature, followed by solid-to-liquid ratio, and acidity. The optimal extraction conditions were 100 °C, 90 min, 0% citric acid, and 0.02 g cocoa shell mL−1 water. Under these conditions, experimental values for the response variables matched those predicted, therefore, validating the model. UPLC-ESI-MS/MS revealed the presence of 15 phenolic compounds, being protocatechuic acid, procyanidin B2, (−)-epicatechin, and (+)-catechin, the major ones. Spectrophotometric results showed a significant correlation with the UPLC results, confirming their potential use for screening and optimization purposes. Aqueous phenolic extracts from the cocoa shell would have potential use as sustainable food-grade ingredients and nutraceutical productsThis work was supported by UAM-Santander (grant number 2017/ EEUU/01) and COCARDIOLAC (grant number RTI2018-097504-B-I00) projects, and Community of Madrid and UAM Agreement (2019–2023). M. Rebollo-Hernanz thanks to the FPU program of the Ministry of Universities for his predoctoral fellowship (grant number FPU15/04238

Inhibition of the Maillard reaction by phytochemicals composing an aqueous coffee silverskin extract via a mixed mechanism of action

This work aimed to evaluate the contribution of isoflavones and melatonin to the aqueous extract obtained from the coffee silverskin (CSE) antiglycative properties, which has not been previously studied. To achieve this goal, two model systems constituted by bovine serum albumin (BSA) and reactive carbonyls (glucose or methylglyoxal) in the presence or absence of pure phytochemicals (chlorogenic acid (CGA), genistein, and melatonin) and CSE were employed. Glucose was used to evaluate the effect on the formation of glycation products formed mainly in the early stage of the reaction, while methylglyoxal was employed for looking at the formation of advanced products of the reaction, also called methylglyoxal-derivative advanced glycation end products (AGE) or glycoxidation products. CGA inhibited the formation of fructosamine, while genistein and melatonin inhibited the formation of advanced glycation end products and protein glycoxidation. It was also observed that phenolic compounds from CSE inhibited protein glycation and glycoxidation by forming BSA-phytochemical complexes. CSE showed a significant antiglycative effect (p < 0.05). Variations in the UV-Vis spectrum and the antioxidant capacity of protein fractions suggested the formation of protein-phytochemical complexes. Fluorescence quenching and in silico analysis supported the formation of antioxidant-protein complexes. For the first time, we illustrate that isoflavones and melatonin may contribute to the antiglycative/antiglycoxidative properties associated with CSE. CGA, isoflavones, and melatonin composing CSE seem to act simultaneously by different mechanisms of actionM.R.H thanks the JAE Intro fellowship (JAEINT_15_00086) and the FPU predoctoral program of the Ministry of Science, Innovation, and Universities (FPU15/04238

Bioaccessibility of phenolic compounds from cocoa shell subjected to in vitro digestion and its antioxidant activity in intestinal and hepatic cells

The cocoa shell is a by-product generated by the cocoa processing industry that could be used as a nutraceutical owing to the significant amounts of bioactive compounds it contains. This work aimed to study the bioaccessibility of phenolic compounds present in the flour (CSF) and an aqueous extract (CSE) from cocoa shells through an in vitro simulated digestion and to assess their antioxidant capacity in vitro by using intestinal and hepatic cell culture models (IEC-6 and HepG2 cells). The bioaccessibility of phenolic compounds was determined using a simulated in vitro digestion model (INFOGEST). Total phenolic compounds (TPC) and antioxidant activity were measured using in vitro techniques. Reactive oxygen species (ROS) were evaluated in IEC-6 and HepG2 cells after t-BOOH stimulation. TPC present in CSE were more bioaccessible than phenolic compounds present in CSF. During digestion, the bioaccessibility of phenolic compounds from CSF fluctuated in the gastric (2.8 mg/g), intestinal (7.6 mg/g), and colonic (5.7 mg/g) phases. Similarly, for the phenolics of CSE, the bioaccessibility increased from 50.6 mg/g in the gastric phase to 53.4 mg/g in the intestinal phase and decreased in the colonic phase to 37.2 mg/g. The in vitro antioxidant capacity followed a similar behavior, increasing throughout the digestion in CSF (8.8- to 10.6-fold) and CSE (6.0- to 7.4-fold). Digested CSF and CSE were not cytotoxic for IEC-6 and HepG2 cells and protected their viability under oxidative stress conditions (93–100%). t-BOOH-induced ROS were prevented by CSF (72–88%) and CSE (81–94%) bioaccessible fractions in both intestinal and hepatic cells. In conclusion, cocoa shells are a source of potentially bioavailable antioxidant phenolic compounds that may protect cells from oxidative stress

Understanding the gastrointestinal behavior of the coffee pulp phenolic compounds under simulated conditions

Numerous residues, such as the coffee pulp, are generated throughout coffee processing. This by-product is a source of antioxidant phytochemicals, including phenolic compounds and caffeine. However, the antioxidant properties of the phenolic compounds from the coffee pulp are physiologically limited to their bioaccessibility, bioavailability, and biotransformation occurring during gastrointestinal digestion. Hence, this study explored the phenolic and caffeine profile in the coffee pulp flour (CPF) and extract (CPE), their intestinal bioaccessibility through in vitro digestion, and their potential bioavailability and colonic metabolism using in silico models. The CPE exhibited a higher concentration of phenolic compounds than the CPF, mainly phenolic acids (protocatechuic, chlorogenic, and gallic acids), followed by flavonoids, particularly quercetin derivatives. Caffeine was found in higher concentrations than phenolic compounds. The antioxidant capacity was increased throughout the digestive process. The coffee pulp matrix influenced phytochemicals’ behavior during gastrointestinal digestion. Whereas individual phenolic compounds generally decreased during digestion, caffeine remained stable. Then, phenolic acids and caffeine were highly bioaccessible, while flavonoids were mainly degraded. As a result, caffeine and protocatechuic acid were the main compounds absorbed in the intestine after digestion. Non-absorbed phenolic compounds might undergo colonic biotransformation yielding small and potentially more adsorbable phenolic metabolites. These results contribute to establishing the coffee pulp as an antioxidant food ingredient since it contains bioaccessible and potentially bioavailable phytochemicals with potential health-promoting propertie

Exploring the potential of phenolic compounds from the coffee pulp in preventing cellular oxidative stress after in vitro digestion

The coffee pulp, a by-product of the coffee industry, contains a high concentration of phenolic compounds and caffeine. Simulated gastrointestinal digestion may influence these active compounds’ bioaccessibility, bioavailability, and bioactivity. Understanding the impact of the digestive metabolism on the coffee pulp's phenolic composition and its effect on cellular oxidative stress biomarkers is essential. In this study, we evaluated the influence of in vitro gastrointestinal digestion of the coffee pulp flour (CPF) and extract (CPE) on their phenolic profile, radical scavenging capacity, cellular antioxidant activity, and cytoprotective properties in intestinal epithelial (IEC-6) and hepatic (HepG2) cells. The CPF and the CPE contained a high amount of caffeine and phenolic compounds, predominantly phenolic acids (3′,4′-dihydroxycinnamoylquinic and 3,4-dihydroxybenzoic acids) and flavonoids (3,3′,4′,5,7-pentahydroxyflavone derivatives). Simulated digestion resulted in increased antioxidant capacity, and both the CPF and the CPE demonstrated free radical scavenging abilities even after in vitro digestion. The CPF and the CPE did not induce cytotoxicity in intestinal and hepatic cells, and both matrices exhibited the ability to scavenge intracellular reactive oxygen species. The coffee pulp treatments prevented the decrease of glutathione, thiol groups, and superoxide dismutase and catalase enzymatic activities evoked by tert-butyl hydroperoxide elicitation in IEC-6 and HepG2 cells. Our findings suggest that the coffee pulp could be used as a potent food ingredient for preventing cellular oxidative stress due to its high content of antioxidant compoundsThis research was funded by the COCARDIOLAC project from the Spanish Ministry of Science and Innovation (RTI 2018-097504-B-I00) and the Excellence Line for University Teaching Staff within the Multiannual Agreement between the Community of Madrid and the UAM (2019-2023). M. Rebollo-Hernanz received funding from the FPU program of the Ministry of Universities for his predoctoral fellowship (FPU15/04238) and his grant for the requalification of the Spanish university system (CA1/RSUE/2021-00656