Spices, Condiments, Extra Virgin Olive Oil and Aromas as Not Only Flavorings, but Precious Allies for Our Wellbeing

Spices, condiments and extra virgin olive oil (EVOO) are crucial components of human history and nutrition. They are substances added to foods to improve flavor and taste. Many of them are used not only to flavor foods, but also in traditional medicine and cosmetics. They have antioxidant, antiviral, antibiotic, anticoagulant and antiinflammatory properties and exciting potential for preventing chronic degenerative diseases such as cardiomyopathy and cancer when used in the daily diet. Research and development in this particular field are deeply rooted as the consumer inclination towards natural products is significant. It is essential to let consumers know the beneficial effects of the daily consumption of spices, condiments and extra virgin olive oil so that they can choose them based on effects proven by scientific works and not by the mere illusion that plant products are suitable only because they are natural and not chemicals. The study begins with the definition of spices, condiments and extra virgin olive oil. It continues by describing the pathologies that can be prevented with a spicy diet and it concludes by considering the molecules responsible for the beneficial effects on human health (phytochemical) and their eventual transformation when cooked.


Introduction
Spices and condiments have played an essential role in human nutrition and participated in developing most cultures worldwide. The use of curry was known in 2000 B.C.E. in India. In Egypt and Babylon, spices such as garlic, cumin and coriander were considered magical. The Greeks and Romans used anise, savory, basil, garlic, hyssop, fennel, mustard, capers, cumin, coriander, oregano, myrtle, parsley, verbena in the kitchen, medicine and cosmetics. Marco Polo in the 13th and the European colonization of Africa, America and Asia during the 15th to 17th centuries improved and spread condiments and spices worldwide [1]. Spices and cooking processes contribute to the ethnic identity of food [2]. Ethnic foods have increased their popularity among consumers worldwide since tourism, international trade and immigration raised the possibility of tasting them. Social media and the opportunity to share culinary experiences also contributed [3][4][5][6]. Partly driven by the improved popularity of ethnic food consumption, the global seasoning and spices market was USD 136.24 billion in 2019 and its growth rate is probable to grow by 4.8% from 2015 to 2025 steadily. The global seasoning and spices market size was valued at USD 13.77 billion in 2019 and is expected to grow at a compound annual growth rate (CAGR) of 6.3% from 2020 to 2027 [7]. The nutrients and phytochemicals in spices, extra virgin olive oil and flavorings are widely used in traditional medicine, pharmaceuticals, dental preparation, aromatherapy and nutraceuticals [8]. The Dietary Supplement and the Education Act have defined "nutraceuticals" as supplements containing herbs, plant products, metabolites, or extracts singly or combined [9]. Currently, the cosmetics industry uses spices and extra virgin olive oil to prepare food supplements and topical skincare cosmetics to combat blemishes from the inside and outside simultaneously [10][11][12][13]. In this The EVOO quality is linked to olive fruits free of damage and the absence of pesticide residues (e.g., fungicides, insecticides and herbicides). Biological control using Trichoderma species or their metabolites are new options to select the EVOO phenolic profile [40] and terpenoid profiles [42]. The nutraceutical importance of phenolics forced researchers to develop reliable analytical methods for their oil dosage [43]. Moreover, EVOO contains tocopherols [31]. They act as free radical scavengers in membranes and lipoproteins and transform fatty acid peroxyl radicals into tocopheroxyl radicals. α-tocopherol regulates signal transduction, apoptosis pathways and transcriptional regulation of the cell cycle [44].

Fish Sauce
Fish sauce is a fermented condiment with a mild fishy flavor, traditionally used in East and Southeast Asian countries [58]. It is obtained by transforming lipids and proteins with enzymes and halophilic microorganisms [59]. Endogenous proteases and proteases produced by microorganisms hydrolyze the proteins in fish into peptides and amino acids [60,61]. The amino acids in fish sauces contribute to the umami taste and have some biological activity among these anti-oxidative, antithrombotic, hypocholesterolemic, antidiabetic and antihypertensive effects are reported [62,63]. Moreover, they inhibit the ACE enzyme (angiotensin I-converting enzyme) [64], able to stabilize blood pressure by transforming angiotensin I to the potent vasoconstrictor angiotensin II and inactivating the vasodilator peptide bradykinin [65]. The fish sauce contains vitamins (A, B1, B2, B3 and B9), fat, protein, minerals (iron, calcium and phosphorus), carbohydrates [66,67] and high levels of docosahexaenoic acid [68] are able to regulate the symptoms of atopic dermatitis [69].

Tabasco
Tabasco is red pepper hot-sauce sauce obtained by lactic acid fermentation due to autochthonous bacteria [70]. Sodium chloride is added to the peppers to make the pulp microbiologically safe. It selects homofermentative lactic acid bacteria and destroys enter-obacteria [71]. After four weeks, vinegar and salt are added to pepper extract to obtain tabasco sauce. Tabasco contains vitamins (C, B1, B2, B3, B5, B6, B9, A and E), fat, protein, minerals (iron, calcium, magnesium, potassium, sodium and phosphorus), carbohydrates [72]. Enzymatic hydrolysis disrupts the cell walls cutting the polysaccharide chains, improve the extract yield and make available bioactive molecules, such as capsaicinoids (capsaicin, dihydrocapsaicin and nordihydrocapsaicin), carotenoids, flavor compounds and polyphenols [73].

Oxidative Stress
Oxidative stress is produced by an excess of the reactive oxygen species (ROS, e.g., superoxide, hydroxyl radical, hydrogen peroxide and singlet oxygen) and reactive nitrogen species (RNS, e.g., nitric oxide, peroxynitrite, nitrogen dioxide) [116]. ROS production in living organisms is due to phagocytosis, respiratory chain (endogenous reactions), exposure to UV radiation, air pollutants and other physical and chemical agents. The electrons made in the mitochondrial respiratory chain are transferred to molecular oxygen forming superoxide anion. The nitric oxide improves the generation of superoxide anion-producing peroxynitrite enzyme, leading to the increased oxidation of proteins, carbohydrates and lipids. ROS make membrane lipid peroxidation and determines the loss of membrane fluidity, altering cell homeostasis. Humans have endogenous defense mechanisms, such as superoxide dismutase, glutathione peroxidase and catalase, to protect against ROS-induced damage. Improved ROS production alters the balance between oxidant and antioxidant levels, determining a pro-oxidative condition [117]. Oxidative stress is involved in some diseases, including inflammation, atherosclerosis, type 2 diabetes mellitus and cancer [118]. Biomarkers of oxidative stress are lipoproteins oxidation, lipid hydroperoxides, conjugated dienes, malondialdehyde (MDA), F2-isoprostanes (F2-IsoPs), glutathione, protein carbonyls and activities of antioxidant enzymes [119]. A universal index does not identify oxidative stress since the biomarkers used to define the stress status have different kinetics of production and elimination [120]. The assay methods used to control lipid peroxidation determine the levels of lipid peroxides or the end products of lipid peroxidation. [121]. The standard assays to determine protein modifications measure the nitration of protein tyrosine residues and the carbonyl groups of the oxidized proteins [122,123].

The Immune Response
The immune system is a biological system that evolved host protection against viruses, bacteria, fungi, parasites and cancer cells [124]. Four functions of the immune system determine host defense. These include barrier production to stop pathogens, identifying and removing the pathogens that pass the barrier by immune cells and immunological memory creation [125]. Physical barriers are skin, respiratory, gastrointestinal tract (including microbiota), nasopharynx, hair and cilia. Immune cells are granulocytes (neutrophils, basophils and eosinophilic), lymphocytes (T-, B-and natural killer-cells) and phagocytes (monocytes, macrophages, dendritic cells and mast cells) [126]. Cellular and humoral responses can be innate and adaptive in the identification and eradication of pathogens. The innate responses are non-specific responses to pathogens that occur when there is no previous exposure or immunization. This action's actors are physical barriers, biochemical mechanisms, inflammatory response, complement system and phagocytes [127]. The speed and effectiveness of these responses are independent of the number of exposures to the pathogen. The adaptive responses are linked to the immunological "memory" and can generate an antigen-specific response. They involve antigen-specific T lymphocytes, which determine the adaptive response or destroy virally infected cells and B lymphocytes can secrete immunoglobulins (antibodies specific against the infecting pathogen) [127]. When the adaptive immune responses occur, the T helper cells (Th1 and Th17) migrate into circulation from lymphoid tissue, penetrate infected sites and make cytokines. The innate and adaptive immune responses control inflammation and the progress of the self and non-self-discrimination. Immature T cell populations express antigen-specific receptors that distinguish self or non-self-macromolecules [128]. In the thymus, T lymphocytes with T cell receptors (TCRs) recognize the self-peptides and major histocompatibility complex (MHC) proteins destroy nonself-macromolecules [129]. Autoimmune diseases happen when central and or induced peripheral tolerance do not work. Old age, obesity and diet determine the most severe symptoms of the disease. Aging can cause the thymus involution that decreases the output of naive T lymphocytes (T CD8+ kill cells directly and T CD4+, T helper cells that secrete cytokines) [130][131][132][133], the answer to new antigens and an increase of the inflammatory mediators in the blood (inflammageing) [134]. An excessive inflammatory response determines a loss in acquired immunity [134]. Obesity reduces T lymphocytes, B lymphocytes, natural killer cell activity, the antibody and IFN-γ (Interferongamma) production [135][136][137]. Food bioactive molecules and micronutrients can increase immune functions [138]. Fatty acids, amino acids, vitamins and mineral ions produce leukotrienes, prostaglandins, chemokines, immunoglobulins, cytokines and acute-phase proteins [135,139], valid for the immunity response. Carbazoles and tryptophan-enriched proteins determine antiinflammatory action, activating aryl hydrocarbon receptors. Moreover, diet regulates the microbiota to produce short-chain fatty acids that affect immune responses activating the G-protein-coupled receptors and epigenetic mechanisms [140].

Lipids
Lipids are essential energy sources for the human body. Fatty acids are constituents of fats and oils. They are classified into: saturated (without double bond), monounsaturated (with one double bond) and polyunsaturated fatty acids (with some double bond). Polyunsaturated fatty acids (PUFAs) are considered essential acids because humans cannot synthesize them. They are divided into two groups: the omega-3 and omega-6 fatty acids [141]. The free fatty acids (FFAs) serve as energy sources and natural ligands free fatty acid receptors, regulating the secretion of peptide hormones and inflammation. The viruses use the fats to fuse the viral membrane and host cell during replication, endocytosis and exocytosis [142].

Unsaturated Fatty Acids Monounsaturated Fatty Acids' Health Properties
Monounsaturated fatty acids (MUFAs) are carboxylic acids with hydrocarbon chains having only one double bond. MUFAs inhibit coagulation, improve blood pressure and glucose homeostasis, reduce oxidative states and inflammation and modify plasma lipids, lipoprotein patterns, membrane composition and fluidity of blood cells [29]. In EVOO, the main MUFA by content is the oleic acid (18:1 ω-9), representing 49% to 83% of the total fatty acid. It promotes bile secretion and enhances gastric mucosa protection by decreasing hydrochloric acid secretion [143]. The American Heart Association sets a limit of MUFA consumption at 20% of total energy. The American Diabetes Association and Dietitians of Canada approve almost 25% of energy [144].

Vitamin A
Vitamin A is a fat-soluble retinoid group (retinol, retinyl esters and retinal) [154][155][156]. Retinol is obtained from animal sources as retinyl palmitate, or it can be synthesized in the intestine starting from beta carotene, a precursor/pro vitamin of vegetable origin. Vitamin A controls the differentiation of epithelial tissue, the imprinting of the B and T cells with gut-homing specificity, the arranging T cells and IgA+ cells into intestinal tissues [157], supports the gut barrier [158][159][160], reduces the toxic effects of ROS and regulate the membrane fluidity and gap-junctional communication [161,162]. Vitamin A improves epithelial construction (keratinization, stratification, differentiation) and functional maturation of epithelial cells [163]. It is part of the respiratory and intestine apparatus's mucus layer, promoting the antigen non-specific immunity function enhancing mucin secretion [163][164][165]. Vitamin A promotes the proliferation and regulation of the thymocytes apoptosis [166,167]. It plays a crucial role in controlling the differentiation, maturation and function of macrophages and neutrophils, which respond to pathogen invasion through phagocytosis and activation of natural killer T cells [168,169]. Vitamin A supervises the early differentiation of the natural killer T (CD4+) and dendritic cells (antigen-presenting cells) [170] and synthesizes immunoglobulins [171]. The balance between T helper 1 and T helper 2 lymphocytes is altered when vitamin A is deficient. Retinoic acid is essential for CD8+ T lymphocyte proliferation and antibody generation by B lymphocytes [172].

B-Group Vitamins
B vitamins are a family of water-soluble vitamins able to act as cofactors and coenzymes in metabolic pathways and play roles in maintaining immune homeostasis [173,174]. B vitamins are obtained from the intestinal microbiota and diet [175]. They contribute to gut barrier function controlling the intestinal immune regulation and are involved in intestinal immune regulation. Vitamin B6 regulates T lymphocyte migration, the folic acid and the T cells in the small intestine [176,177]. Vitamin B12 influences the phagocytic and bacterial killing capacity of the neutrophils [125]. Human gut microbes use vitamin B12 as a cofactor for metabolic pathways [126]. Both vitamins maintain or enhance NK cell cytotoxic activity [177][178][179]. Villarruz-Sulit and Cabaluna (2020) hypothesized that vitamin B supplementation affects the treatment of COVID-19 [179].

Flavonoids
The flavonoids consist of two aromatic rings bound together (A and B) and one heterocycle (ring C). They are divided into six subclasses depending on the degree of unsaturation and oxidation of the C ring and the carbon of the C ring on which the B ring is attached: flavones, flavonols, isoflavones, chalcones, anthocyanins, flavanones, flavanols, catechins and proanthocyanidins [255] (Table 1). Flavonoids have antioxidant, anti-mutagenic antiangiogenic, antibacterial, anti-allergic, antiinflammatory, anticancer, enzyme modulation properties [256][257][258]. They can directly scavenge ROS, stabilize the free radicals, chelate metal ions with phenolic hydroxyl groups, activate phase II detoxification enzymes and block pro-oxidant enzymes. [259]. The flavonoids' anticancer mechanisms employ the control of the ROS-scavenging enzyme's activities, autophagy, apoptosis and inhibition of the cancer cell proliferation and invasiveness [259]. The flavonoid's antiinflammatory actions involve immune cell regulation, suppressing the chemokines, COX-2, cytokines, proinflammatory transcription factors and kappa kinase/c-Jun amino-terminal kinases [260,261]. FDA (Food and Drug Administration) approved a clinical trial of quercetin against Covid-19 [262]. In silico modeling works have shown that quercetin is one of the top five most potent compounds in a database of 8000 small molecules) able to bind the interface site of the ACE2 receptors and theoretically disrupt the initiating infection process of the SARS-CoV-2 Viral Spike Protein [263]. Apigenin, a 5,7-trihydroxyflavon, employs immune-regulatory activity in an organ-specific manner modulating NF-κB activity in the lungs [264], decreasing the secretion of the mast cell [265], T cells [266], COX-2, IL, TNF and NO [267]. In silico modeling, works have shown that apigenin binds the interface site of the ACE2 receptors and has great potential to act as COVID-19 main proteases inhibitors [268]. Isoflavones are phytoestrogens belonging to the non-steroidal estrogens. They improve the adaptive immune system, inhibiting lymphocyte proliferation, antigen-specific immune activities (T-and B-cells) and allergic responses [269][270][271][272]. The isoflavone genistein enhances CD8 T-cells and cytokines' production by T-cells [269,[273][274][275][276]. Phytoestrogens interact with the T-cell and contribute to cytokine responses compartment enhancing or inhibiting the NF-kB pathway. Kojima et al. have shown that they improve gene expression mediated by ROR γ and α (retinoic-acid-receptor-related orphan receptor) in T-lymphoma cells and enhancing the expression of IL-17 [275]. The phytoestrogens interact with the B-cell compartment. The isoflavones inhibit IgG2a (immunoglobulin G2a) antibodies [270][271][272], the antigen-specific IgG1 and IgG3 in thyroiditis [272], the expression of IgE [270], the inflammatory immune response by inhibiting the antigen-presentation and functions of dendritic cells (DCs) [270,271]. They modulate the innate immune system inhibiting the production of IFN-γ, TNF-α, IL-9 and IL-13 from CD4+ T-cells [270,271], suppress allergic inflammation-reducing mast cell degranulation [270,272] and control NK cell activity reducing expression of IL-18Rα (IL-18 receptor α) and IFN-γ production in response to IL-12 and IL-18 [277]. Finally, they induce antiinflammatory responses in macrophages. Dia et al. showed that some phytoestrogens (daidzein and genistein) reduce the production of NO (nitric oxide), the expression of iNOS (inducible nitric oxide synthase) and enhance the superoxide dismutase and catalase activities [278]. Table 1. Class of flavonoids and their seasoning sources.
The isoflavone genistein enhances CD8 T-cells and cytokines' production by T-cells [269,[273][274][275][276]. Phytoestrogens interact with the T-cell and contribute to cytokine responses compartment enhancing or inhibiting the NF-kB pathway. Kojima et al. have shown that they improve gene expression mediated by ROR γ and α (retinoic-acid-receptor-related orphan receptor) in T-lymphoma cells and enhancing the expression of IL-17 [275]. The phytoestrogens interact with the B-cell compartment. The isoflavones inhibit IgG2a (immunoglobulin G2a) antibodies [270][271][272], the antigen-specific IgG1 and IgG3 in thyroiditis [272], the expression of IgE [270], the inflammatory immune response by inhibiting the antigen-presentation and functions of dendritic cells (DCs) [270,271]. They modulate the innate immune system inhibiting the production of IFN-γ, TNF-α, IL-9 and IL-13 from CD4+ T-cells [270,271], suppress allergic inflammation-reducing mast cell degranulation [270,272] and control NK cell activity reducing expression of IL-18Rα (IL-18 receptor α) and IFN-γ production in response to IL-12 and IL-18 [277]. Finally, they induce antiinflammatory responses in macrophages. Dia et al. showed that some phytoestrogens (daidzein and genistein) reduce the production of NO (nitric oxide), the expression of iNOS (inducible nitric oxide synthase) and enhance the superoxide dismutase and catalase activities [278].
The isoflavone genistein enhances CD8 T-cells and cytokines' production by T-cells [269,[273][274][275][276]. Phytoestrogens interact with the T-cell and contribute to cytokine responses compartment enhancing or inhibiting the NF-kB pathway. Kojima et al. have shown that they improve gene expression mediated by ROR γ and α (retinoic-acid-receptor-related orphan receptor) in T-lymphoma cells and enhancing the expression of IL-17 [275]. The phytoestrogens interact with the B-cell compartment. The isoflavones inhibit IgG2a (immunoglobulin G2a) antibodies [270][271][272], the antigen-specific IgG1 and IgG3 in thyroiditis [272], the expression of IgE [270], the inflammatory immune response by inhibiting the antigen-presentation and functions of dendritic cells (DCs) [270,271]. They modulate the innate immune system inhibiting the production of IFN-γ, TNF-α, IL-9 and IL-13 from CD4+ T-cells [270,271], suppress allergic inflammation-reducing mast cell degranulation [270,272] and control NK cell activity reducing expression of IL-18Rα (IL-18 receptor α) and IFN-γ production in response to IL-12 and IL-18 [277]. Finally, they induce antiinflammatory responses in macrophages. Dia et al. showed that some phytoestrogens (daidzein and genistein) reduce the production of NO (nitric oxide), the expression of iNOS (inducible nitric oxide synthase) and enhance the superoxide dismutase and catalase activities [278].
The isoflavone genistein enhances CD8 T-cells and cytokines' production by T-cells [269,[273][274][275][276]. Phytoestrogens interact with the T-cell and contribute to cytokine responses compartment enhancing or inhibiting the NF-kB pathway. Kojima et al. have shown that they improve gene expression mediated by ROR γ and α (retinoic-acid-receptor-related orphan receptor) in T-lymphoma cells and enhancing the expression of IL-17 [275]. The phytoestrogens interact with the B-cell compartment. The isoflavones inhibit IgG2a (immunoglobulin G2a) antibodies [270][271][272], the antigen-specific IgG1 and IgG3 in thyroiditis [272], the expression of IgE [270], the inflammatory immune response by inhibiting the antigen-presentation and functions of dendritic cells (DCs) [270,271]. They modulate the innate immune system inhibiting the production of IFN-γ, TNF-α, IL-9 and IL-13 from CD4+ T-cells [270,271], suppress allergic inflammation-reducing mast cell degranulation [270,272] and control NK cell activity reducing expression of IL-18Rα (IL-18 receptor α) and IFN-γ production in response to IL-12 and IL-18 [277]. Finally, they induce antiinflammatory responses in macrophages. Dia et al. showed that some phytoestrogens (daidzein and genistein) reduce the production of NO (nitric oxide), the expression of iNOS (inducible nitric oxide synthase) and enhance the superoxide dismutase and catalase activities [278].
The isoflavone genistein enhances CD8 T-cells and cytokines' production by T-cells [269,[273][274][275][276]. Phytoestrogens interact with the T-cell and contribute to cytokine responses compartment enhancing or inhibiting the NF-kB pathway. Kojima et al. have shown that they improve gene expression mediated by ROR γ and α (retinoic-acid-receptor-related orphan receptor) in T-lymphoma cells and enhancing the expression of IL-17 [275]. The phytoestrogens interact with the B-cell compartment. The isoflavones inhibit IgG2a (immunoglobulin G2a) antibodies [270][271][272], the antigen-specific IgG1 and IgG3 in thyroiditis [272], the expression of IgE [270], the inflammatory immune response by inhibiting the antigen-presentation and functions of dendritic cells (DCs) [270,271]. They modulate the innate immune system inhibiting the production of IFN-γ, TNF-α, IL-9 and IL-13 from CD4+ T-cells [270,271], suppress allergic inflammation-reducing mast cell degranulation [270,272] and control NK cell activity reducing expression of IL-18Rα (IL-18 receptor α) and IFN-γ production in response to IL-12 and IL-18 [277]. Finally, they induce antiinflammatory responses in macrophages. Dia et al. showed that some phytoestrogens (daidzein and genistein) reduce the production of NO (nitric oxide), the expression of iNOS (inducible nitric oxide synthase) and enhance the superoxide dismutase and catalase activities [278].

Curcuminoids
Curcuminoids are phenolic compounds with neuroprotective, antioxidant, antitumor, anti-acidogenic, antiinflammatory and radioprotective activities [279]. They have a diarylheptanoic nucleus with varying degrees of oxidation and unsaturation ( Figure 2). Curcumin, the principal polyphenol of Curcuma longa helps the antiinflammatory system to decrease the metabolism of arachidonic acid, lipoxygenase and cyclooxygenase activities, tumor necrosis factor, interleukins cytokines, nuclear factor-κB and steroids production [280]. It supports antioxidant defense mechanisms, such as scavenge hydroxyl radicals and superoxide anions, protection of cells from DNA damage, lipid peroxidation, protein carbonylation, protein oxidation, improvement of the glutathione's levels, stabilization of the superoxide-dismutase, glutathione S-transferase and glutathione peroxidase [281] and chelation of the heavy metals (aluminum, cadmium, copper, manganese, zinc and iron) responsible of the ROS production [282]. Curcumin carries out chemopreventive activities improving the glutathione transferase and NADPH quinone reductase (phase 2 detoxification enzymes), reducing cytochrome formation P450 1A1, a pro-carcinogen activating phase 1 enzyme and arachidonic acid production [283]. It has potential as a therapeutic agent for neurological diseases (e.g., Alzheimer's) since it inhibits amyloid-beta protein aggregation (e.g., α-synuclein, huntingtin, phosphorylated tau, prion proteins, Fenugreek, soy sauce, Miso.

Curcuminoids
Curcuminoids are phenolic compounds with neuroprotective, antioxidant, antitumor, anti-acidogenic, antiinflammatory and radioprotective activities [279]. They have a diarylheptanoic nucleus with varying degrees of oxidation and unsaturation ( Figure 2). Curcumin, the principal polyphenol of Curcuma longa helps the antiinflammatory system to decrease the metabolism of arachidonic acid, lipoxygenase and cyclooxygenase activities, tumor necrosis factor, interleukins cytokines, nuclear factor-κB and steroids production [280]. It supports antioxidant defense mechanisms, such as scavenge hydroxyl radicals and superoxide anions, protection of cells from DNA damage, lipid peroxidation, protein carbonylation, protein oxidation, improvement of the glutathione's levels, stabilization of the superoxide-dismutase, glutathione S-transferase and glutathione peroxidase [281] and chelation of the heavy metals (aluminum, cadmium, copper, manganese, zinc and iron) responsible of the ROS production [282]. Curcumin carries out chemopreventive activities improving the glutathione transferase and NADPH quinone reductase (phase 2 detoxification enzymes), reducing cytochrome formation P450 1A1, a pro-carcinogen activating phase 1 enzyme and arachidonic acid production [283]. It has potential as a therapeutic agent for neurological diseases (e.g., Alzheimer's) since it inhibits amyloid-beta protein aggregation (e.g., α-synuclein, huntingtin, phosphorylated tau, prion proteins, Tumeric Curcuminoids Curcuminoids are phenolic compounds with neuroprotective, antioxidant, antitumor, anti-acidogenic, antiinflammatory and radioprotective activities [279]. They have a diarylheptanoic nucleus with varying degrees of oxidation and unsaturation ( Figure 2). Curcumin, the principal polyphenol of Curcuma longa helps the antiinflammatory system to decrease the metabolism of arachidonic acid, lipoxygenase and cyclooxygenase activities, tumor necrosis factor, interleukins cytokines, nuclear factor-κB and steroids production [280]. It supports antioxidant defense mechanisms, such as scavenge hydroxyl radicals and superoxide anions, protection of cells from DNA damage, lipid peroxidation, protein carbonylation, protein oxidation, improvement of the glutathione's levels, stabilization of the superoxide-dismutase, glutathione S-transferase and glutathione peroxidase [281] and chelation of the heavy metals (aluminum, cadmium, copper, manganese, zinc and iron) responsible of the ROS production [282]. Curcumin carries out chemopreventive activities improving the glutathione transferase and NADPH quinone reductase (phase 2 detoxification enzymes), reducing cytochrome formation P450 1A1, a pro-carcinogen activating phase 1 enzyme and arachidonic acid production [283]. It has potential as a therapeutic agent for neurological diseases (e.g., Alzheimer's) since it inhibits amyloid-beta protein aggregation (e.g., α-synuclein, huntingtin, phosphorylated tau, prion proteins, Aβ-oligomers and fibrils) and enhances motor coordination and cognition peroxidase [281]. Finally, curcumin has cardioprotective actions (e.g., antiplatelet and anticoagulant) and improves the activities of detoxifying enzymes (e.g., glutathione-S-transferase) [284].

Capsaicinoids
Capsaicinoids (CAPs) (Figure 3) are compounds responsible for the burning sensation. Thirteen different CAPs are identified. They are characterized by one vanillyl group, a carboxamide group and a variable aliphatic chain (Figure 3). Capsaicinoids have hypocholesterolemic, antioxidant, antiinflammatory, antitumoral, antidiabetic and antiobesity properties [285]. Capsaicin and dihydrocapsaicin have shown hypocholesterolemic action obtained by reducing cholesterol absorption, improving its hepatic conversion to bile acids, the excretion in the feces and inducing expression of hepatic LDL receptors [286]. Antioxidant activity of CAPs is due to inhibition of lipid peroxidation; radical scavenge formation, depletion of total hepatic thiols and hepatic antioxidant enzyme activities (glutathionereductase, glutathione-transferase, superoxide dismutase and catalase) [286]. CAPs block the arachidonate metabolites' production (PgE2, leukotrienes) and the release of the lysosomal enzymes (elastase, hyaluronidase and collagenase) by macrophages [287]. Antitumoral properties are related to the interaction with microsomal xenobiotic-metabolizing enzymes, inactivation of cytochrome P-450 HE1 (and other isoforms of the P-450 family) block of microsomal monooxygenases interested in carcinogen activation [288]. Capsaicinoids have potential application in diabetes prevention since they improve insulin secretion by activating, in islet β-cells, the transient receptor potential vanilloid subfamily member 1 (TRPV1) [289] decrease the concentration of postprandial blood glucose, enhance insulin secretion and glucose tolerance [290]. Finally, capsaicinoids have an antiobesity effect due to their ability to stimulate human brown adipose tissue growth. The human brown adipose tissue is the primary site of non-shivering thermogenesis (NST). It increases whole-body energy expenditure and regulates energy balance and body fatness [291].

Organosulfur Compounds
Organosulfur compounds are biosynthesized for defensive purposes against abiotic stressors by the Allium family's plants (e.g., garlic and onion). Thiosulfates are transformed by pH, temperature and solvent, into alk(en)yl cysteine sulfoxides, mono-di-and tri-sulfides, S-allyl cysteine, (E)-and (Z)-ajoene and vinyl dithiins [292]. Organosulfur compounds act as anticancer molecules improving the immune system and inducing proliferative signals by converting allyl sulfides into sulfane sulfur [293,294]. They stimulate apoptosis, induce xenobiotic-metabolizing enzymes, enhance the detoxification of carcinogens, have a role in cell cycle arrest and prevent nitrosamines and hydrocarbons' metabolism, scavenging free radicals and modulate the enzymes responsible for DNA repair [295,296]. Organosulfur compounds have antiinflammatory activities. The allicin inhibits the proinflammatory cytokines from epithelial digestive cells, blocking TNF-α secretion. Diallyl sulfide (DAS), diallyl tri-(DATS), tetra-sulfides and S-allylcysteine (SAC) decreased inflammatory lipopolysaccharide. The allyl methyl disulfide reduces the formation of the IL-8/IP-10 by the TNF-α in intestinal cells [297].

Effect of Spices and Herbs on the Shelf Life of Foods
In past few years, the protective effects of essential oils (Eos) as antimicrobial and antifungal agents in dairy products (e.g., chicken and meat) have been studied. Essential oils are mixtures of organic chemical compounds from the terpenoid family (mainly monoand sesquiterpenes), phenols, aldehydes and ketones [298]. Eos have different modes of fungal inactivation: chalcones reduce the synthesis of the cell wall polysaccharide 1,3beta-D-glucan causing fungal cell wall disruption [299] and decrease the conversion of tubulin into microtubules, causing the interruption of the cell division [300]; aldehydes inhibit fungal cell division by reacting with sulfhydryl involved in fungal cell division and interfere with fungal metabolism forming a charge-transfer complex with electron donors in fungal cells [301]; enones and enals stop fungal growth reacting with nucleophiles in fungi [302]; ascaridole decrease hemin making toxic radicals in the presence of Fe 2+ [303]; carvacrol causes a breakdown of ion gradients distributing into membranes and interferes with the intracellular calcium homeostasis, improving the passive permeability of the cell membrane, modulating the Ca 2+ permeable transient receptor channels, preventing sarcoplasmic reticulum Ca 2+ ATPase and activating ryanodine receptors [303].

Spice Essential Oils in Postharvest Disease Mitigation
The composite solutions of aqueous extract of ginger, garlic and onion improve the shelf life (for about 5-6 days), anti-bacteria, antioxidation and sensory quality of stewed pork [304]. The addition in active packaging of ginger Eos extend the shelf life of poultry meat and meat products since they reduce lipid oxidation and microbiological growth [305,306]. Nanoemulsions of Thymus daenensis L. Eos are antibacterial, which can prolong stability and meliorate sensorial attributes in mayonnaise [307]. Garlic and ginger extracts improve the antioxidant activity, antimicrobial ability against some foodborne pathogens (e.g., Bacillus subtilis DB 100 host, Escherichia coli BA 12296, Clostridium botulinum ATCC 3584, Staphylococcus aureus NCTC10788 and Salmonella senftenberg ATCC 8400) and reduce thiobarbituric acid reactive substances levels, in herring fish fillet [305]. The nanoencapsulated form of the Garlic Eos is more effective than free form when incorporating into an active packaging (chitosan and whey protein films) to extend the shelf life of refrigerated vacuum-packed sausage [308].

Herb Essential Pils in Postharvest Disease Mitigation
The cumin and clove essential oils reduced Escherichia coli, Listeria monocytogenes, Salmonella, Campylobacter jejuni, Yersinia enterocolitica, Clostridium perfringens, Toxoplasma Gondi and Staphylococcus aureus bacterial cells in processed meat products [309].
Extracts of oregano and clove inhibit the lipid oxidation and reduce the Listeria monocytogenes, Salmonella enterica and Staphylococcus aureus numbers in cheese at room temperature [311].
The Ocimum basilicum L. Eos. have antifungal activity against Candida albicans, Aspergillus niger [312], Aspergillus flavus [313] and Penicillium nalgiovense [314]. The basil (Ocimum basilicum) leaves extract added to active film extends the shelf life of eggplant up to 16 days. It reserved eggplants' moisture loss, retarded the improvement in total soluble solids, firmness and color changes [315]. Recently, Gundewadi et al. (2018) have shown a desirable inhibitory activity of basil Eos against fungi, P. chrysogenum and A. flavus when the nanoemulsions of the lipophilic active ingredients are dispersed in an aqueous media and sapindus extract serves as a surfactant for nano emulsification purposes [316].
Chitosan packages infused with Origanum vulgare essential oil maintain the grapes' quality, physical and sensory attributes in post-harvest storage [317].
Eugenol and thymol extend strawberry shelf life by improving resistance to spoilage, deterioration and enhances their free radical scavenging capacity [318]. Eugenol and thymol reduce weight loss, skin color variation, ripening and decay of grape berries when used in a modified atmosphere package [319].
The fennel Eos addition to biodegradable film (based on polyhydroxybutyrate and polylactic acids) preserves oysters' shelf-life improving the oxygen barrier performance, antioxidant activity and antimicrobial activity against aerobic and anaerobic bacteria [320]. Carvacrol, perillaldehyde and anethole improve total anthocyanins, phenolics and antioxidant activity, in blueberry fruit [321].

Sauce Contribution in Postharvest Disease Mitigation
The soy sauce added to the Tambaqui fillet (processed by the sous vide) improves its shelflife [323].

Condiment Contribution in Postharvest Disease Mitigation
Vinegar prolongs the shelf life and palatability of common mackerel [324]. The powdered-buffered vinegar and liquid-buffered vinegar decrease the psychrotrophic growth of Salmonella typhimurium in ground beef patties [325]. During chilled storage, vinegar added to silver carp inhibit acid phosphatase (related to the freshness and flavor of fish) and alkaline phosphatase and enhances the accumulation of inosine monophosphate and free amino acids [326].

Food-to-Food Fortification
Food fortification aims to enhance people's health. The main problem of classic food fortification depends on the economic problems related to food processing, especially in developing countries where the risk of malnutrition is very worrying. Food to food fortification is a new approach to food fortification. It uses the accessible local resource (animal or plant) to fortify another food [327]. Herbs, spices (essential oils, extract powder, fresh, etc.) and sauces are added to dairy products to improve their functional properties [323].

Spice's Contribution to the Functional Properties of Foods
The addition of Allium sativum water extract during fermentation increases lactic acid bacteria in yogurt [328].
The supplement of cinnamon powder into yogurt enhances the antioxidant activity, the total phenolic content and phenolics bioaccessibility into the gastrointestinal tract [329]. The addition of ginger extracts into yogurt improves its antigenotoxic and antioxidant effects [330].

Herb's Contribution to the Functional Properties of Foods
The supplement of basil into yogurt enhances the content of bioactive peptides and antioxidant properties [331]. The addition of dry basil leaves preserves and functionalizes cheeses.
The basil leaves improve the cheese's antioxidant activity, prevent the degradation of the protein (due to basil's antimicrobial activity), fatty acids peroxidation and accelerating moisture loss [332]. The treatment of shredded iceberg lettuce with basil leaves' extract positively affects its total phenolic content, antioxidant potential and no effect on consumer acceptability [333].
The fortify of cheese with dry rosemary and parsley improves cheese's antioxidant properties [334].
The supplement of sage, or thyme and cumin essential oils to butter enhances its oxidative stability during storage time [335,336].
The addition of ginger into ice cream improves its total phenols and antioxidant activity [337].

Sauces Contribution to the Functional Properties of Foods
Soy sauce reduces lipid oxidation in meat products through the chelating activity of Fe 2+ [338]. Soy sauce, Miso and fish sauces improve the Z-isomerization of lycopene in processed tomato products, enhancing the functionality of dishes since Z isomer is the most bioavailable [339].

Condiments Contribution to the Functional Properties of Foods
Extra virgin olive oil improves polyunsaturated fatty acids oxidative stability in algae oil. The EVOO's MUFA decreased the n-3 algae' PUFA and the EVOO's secoiridoid reduced the algae's triglyceride hydrolysis, simplifying their industry's application [340].

Effect of Cooking on Spices
The radical scavenging potential of ginger, garlic, cinnamon and turmeric depends on the cooking method. Microwaves decrease antioxidant activity. Instead, boiling and steaming increase it. Heat treatment also regulates their antimicrobial activity. Microwave, bake, grill and frying determine to lose their antimicrobial activity. Instead, boiled and steam methods decreased it [341]. The use of pepper onion, garlic, chili pepper, fennel and cumin, before grilling, frying, or roasting the meat prevents the formation of heterocyclic aromatic amines (Has) and polycyclic aromatic hydrocarbons (PAHs), compounds known to be associated with cancer development [342,343]. HAs are made during the cooking of protein-rich foods by the interaction between creatine/creatinine and free amino acids or with hexoses from the Maillard reaction [344]. The incomplete pyrolysis or combustion makes PAHs of organic matter. They are obtained by thermal degradation of fatty acids, triglycerides, steroids and amino acids [345]. The phenolics and organosulfur compounds in spices suppress the reactive species and/or interact on reactions, stopping byproducts' formation [342]. Cooking methods and the fermentation process affect garlic antioxidant capacities. Raw garlic has more antioxidant activity than cooked garlic and black garlic (fermented garlic) has more significant antioxidant activity than crude garlic [346].

Effects of Cooking on Soy Sauce
Soy sauce preserves lipids from oxidation during cooking [347]. Phenolic compounds (by soybean) and antioxidative Maillard reaction products (by a non-enzymatic browning reaction) chelate ferrous ion a catalyst of lipid oxidation reaction [348].

Effects of Cooking on EVOO Degradation
EVOO has good thermal resistance in comparison with other vegetable oils. It is due to the high MUFA profile, phenolic composition and vitamin E. The initial olive oil composition, the period of the olive harvest and heating conditions (temperature, cooking process time and food presence) regulate the degradation rate and time required to degrade the antioxidant pool [338]. The absence of refining gave a high acidity to the EVOO and decreased its upper thermal limits in response to the released free fatty acids' lower boiling point. Under frying and roasting conditions (180)(181)(182)(183)(184)(185)(186)(187)(188)(189)(190) • C), EVOO performance is better than other vegetable oils. It is quickly degraded under microwave processing, but food decreases the thermo-oxidative effects of microwave heating [338]. EVOO degradation and underwater boiling conditions, mainly depend on heating time, food and loss of phenolic compounds into the water phase. As a result, wherever possible, olive oil must be added more closely to the final cooking process [349].

Spices Side Effects
The consumption of some spices can cause side effects. For example, ginger can determine gastrointestinal (e.g., heartburn, diarrhea, bloating, gas, abdominal pain and epigastric distress), cardiovascular and respiratory symptoms [350]. High doses are not recommended in pregnancy, lactation and patient with bleeding disorders since it has antiplatelet property [351]. The most common garlic's side effect is halitosis (bad breath) and body odor, especially when the raw form of the herbs is taken due to allyl methyl sulfide. A rare allergy to garlic was ascribed to protein allinase, which made hypersensitivity responses via immunoglobulin E [352]. Fenugreek ingestion can determine hypoglycemia in diabetics persons, diarrhea, abdominal distention, dyspepsia and flatulence [353]. Tumeric and curcumin can determine dermatitis and urticaria (immunoglobulin E mediated) especially following direct curcumin exposure to the skin or scalp [354]. Higher curcumin doses increase carcinogenesis, enhancing ROS cell levels [355].

Conclusions
The spices and condiments play an essential role in our diet that goes far beyond flavoring our dishes. They can be considered supplements of molecules functional to prevent oxidative stress injury, inflammation damage and chronic degenerative diseases that afflict our society, such as cardiovascular diseases and cancer. When multiple spices are used to prepare a dish, there is the possibility that they can have synergistic effects, increasing their health potential. However, more in-depth information on the effects of exposure to their bio components is needed to define intervention strategies to maximize beneficial effects and minimize unwanted side effects.

Conflicts of Interest:
The authors declare no conflict of interest.