Phytopharmaceuticals. Группа авторов

melanoidins, generated by chemical browning during roasting. Due to the high organic matter in coffee grounds, (annual production in Spain in 2014 was estimated at 270,000 tons) there is a high biological oxygen demand with the genesis of up to 51,000 tons of CO₂/year. Therefore, this increases the content of greenhouse gases, aggravating the problem of global warming of the atmosphere by preventing adequate reflection of the sun rays. Coffee grounds may also be very polluting when added directly to the lithosphere, since they contain toxic compounds such as caffeine, and polyphenols, especially tannins. Thus, coffee processing by-products may induce toxicity in the ecosystem of the cultivation soils and air, causing a great negative environmental impact [94]. Recently, different investigations have been carried out looking for possible uses of coffee by-products [95]: as composting fertilizers; for adsorption-removal of heavy metals; for the production of enzymes and non-fossil fuels such as bioethanol, biodiesel and hydrogen; as a source of polysaccharides with immunostimulant activity; as biosurfactants for the removal of pesticides from cultivation soils; as substrates in fermentation technology; as potential functional ingredients with antioxidant, prebiotic, antimicrobial or anti-hypertensive capacities [96].

      Coffee by-products can be potentially used as prebiotics, since they provide components that match prebiotics definition: “nondigestible food components beneficial to the consumer (soluble fiber) that cross the gastrointestinal tract without being digested until reaching the colon, where they are fermented by selective components of the microbiota (lactic acid bacteria, mainly bifidobacteria and lactobacilli), selectively increasing their growth and/or activity with the strengthening of consumer health”. In addition to these requirements, prebiotics must be stable during food processing [97]. The beneficial effects on health include the generation of acetic, propionic and butyric acids in the colon, which lower the pH that inhibits the development of pathogenic and putrefactive bacteria in the colon microbiota. Low molecular weight fatty acids stimulate the development and differentiation of the colonocytes, improving the intestinal barrier function and decreasing the bacterial translocation associated to inflammatory bowel disease problems [97]. While butyrate facilitates the energy supply in the colonocytes, acetate and propionate do so in the liver, where propionyl-CoA also facilitates the inhibition of the enzyme that directs the endogenous synthesis of cholesterol, hydroxy-methyl-glutaryl-CoA-reductase, causing blood cholesterol levels decrease and lipid profile improvement [97].

       2.2.6.3 Healthy Compounds From Olive Oil Wastes

      For thousands of years, olive trees (Olea europaea L.) have been cultivated mainly for the production of olive oil, with high economic value. Leaves, mills—alpechin—and pomace oil—orujo-, which are wastes from this industry, have a high content of valuable phenolic compounds, being leaves around 10% of the total collected matter [98].

      Oleuropein (OE) is an ester of hydroxytyrosol and elenolic acid, and it is the most abundant polyphenol in olive leaves. It has several health-promoting benefits, against oxidative damage, as cardioprotective, anti-inflammatory, hypoglycemic and hypo-cholesterolemic agent [98]. Especially OE, but also other phenolic compounds that have also been identified in olive leaves [99], could be incorporated as food ingredients in functional and/or healthy food design. However, when the polyphenols are extracted from leaves, they are susceptible of degradation from environmental (light, oxygen, humidity and temperature, etc.), food (pH, enzymes) and gastrointestinal conditions (pH and digestives enzymes) [100], and the encapsulation of olive leaves extracts (OLE) represents an alternative to protect and control release the phenolic compounds in a site and/or at a specific rate (Section 2.3.3).

OE degrades during in vitro digestion [101], animal models [102] and human models [103]. Although OE metabolism has not been elucidated yet, it seems that only a small amount of it reaches the blood circulation [103]. OE that is not hydrolyzed in the stomach, could be metabolized, and its metabolites absorbed and distributed through the bloodstream. On the other hand, the OE absorption mechanism in the small intestine could be through the intercellular junctions of the small intestine by passive diffusion, involving a glucose transporter, or as OE aglycone by the action of the enzyme lactase florocin hydrolase (LPH) [104]. However, the simple diffusion of OE through the cellular lipid bilayer or the intestine intercellular junctions is unlikely, due to the high molecular weight and polarity [104]. It has been reported that after intestinal digestion the unaltered OE could reach the colon, where a fermentation process generated by bacterial strains, could lead into HT [103]. Unaltered OE molecules that reach the colon are the most suitable precursors of HT [104], but its degradation products may provide a beneficial effect [105] in gastrointestinal illnesses, for example, in colon cancer and ulcerative colitis [101]. An increase of OE bioaccessibility and bioavailability during intestinal or colonic digestion is a challenge for OE encapsulation, as will be discussed in Section 2.3.3.

2.3 Technologies for Obtaining Stable Natural Bioactive Extracts

      The valuation of natural sources is primordially dependent on technologies developed in the extraction stage, in which viable yields and levels of desired selectivity to biodiversitysourced processes are established.

      2.3.1 Extraction Techniques

      Bioactive compounds are present in low concentrations and are often associated with complex chemical structures, complicating the extraction process. Traditional extraction methodologies include maceration with different solvents, heat reflux and Soxhlet extraction [106]. However, these processes are associated with the consumption of large volumes of solvents, energy, long extraction times, and degradation of bioactive compounds. Recently, new technologies have been developed to solve these disadvantages. Among them, extraction assisted by ultrasound (UAE), enzymes (EAE) or microwaves (MAE) are recognized as simple, ecological and efficient processes [107, 108].

      Ultrasound waves propagate through a fluid with a frequency between 20 kHz and 10 MHz. This movement generates cavitation bubbles that cause cell disruption, allowing a better penetration of the solvent, thus, increasing the mass transfer of bioactive compounds to it. Extraction efficiency improves by decreasing extraction time and energy consumption in comparison with traditional processes [109].

      UAE equipment is simpler than other extraction techniques and more economical. In the extraction of bioactive phenolic compounds from olives UAE showed a higher yield than the obtained by maceration, in lesser time (30 min vs. 4.7 h, respectively) [110]. Hydroxytyrosol, oleuropein and rutin, with excellent antioxidant activity.

      The implementation of these techniques requires the optimization of the experimental variables (UAE frequency, solvent type, temperature, time), which affect the extraction efficiency [111].

      EAE is based on the enzymatic hydrolysis of cell wall components, which improves the extraction of compounds that are associated to the fiber. Phenolic compounds, functional oils and proteins present in by products of vegetable origin have been extracted by EAE. At industrial level, the main advantage is the reduction in the use of organic solvents, with a direct effect on the environment, and a reduction in the loss of bioactivity [112]. The most used enzymes as extraction agents are pectinases, cellulases and hemicellulases, mainly from bacteria and fungi, but they can also be from animal or vegetable origin [113].

By means of EAE a significant increase in polyphenols, flavonoids, and tannins contents from white grape marc (Vitis vinifera L.) was observed [114], with greater antioxidant and anti-tyrosinase activities than the extracts without enzyme treatment. The same enzymatic complex increased up to 3 times the content of protocatechuic and vanillic acids in extracts from rice bran [115].

      Commercial combination of cellulolytic and xylanolytic enzymes (Viscozyme L and CeluStar XL) improved the extraction of bioactives from chokeberry pomace [76], increasing the free radicals scavenging capacity. Xylanase-assisted extraction alone did not change the yield of soluble phenols from guava leaves (PGL), whereas cellulase and β-glucosidase did improve PGL extraction. The use of glucoamylase, protease and cellulose in rice bran increased the release of free