The amount of total phenolic contents (mg GAE/g d.w.) and content of total flavonoids (mg QE/g d.w.) in L. nobilis extracts.
\r\n\tHowever, despite the positive outlook and trends in routing protocol design, there are still several open or unresolved challenges that researchers are still grappling with. Providing adequate responses to those challenges is essential for next-generation networks in order to maintain its reputation and sustain its preponderance in cyber and physical security. Some of the challenges include, but are not limited to, the following:
\r\n\t• Robustness and reliability of routing protocol
\r\n\t• Reduced dependencies on heterogeneous networks
\r\n\t• Security of routing protocols
\r\n\t• Dynamic Adhoc routing Protocols
\r\n\t• Routing in 5G Networks
\r\n\t• Routing IoT enabled networks
\r\n\t• Scalable and dependable routing system architectures
\r\n\t• QoS and QoE Models and Routing Architectures
\r\n\t• Context-Aware Services and Models
\r\n\t• Routing Mobile Edge Computing
\r\n\tThe goal of the book is to present the state of the art in routing protocol and report on new approaches, methods, findings, and technologies developed or being developed by the research community and the industry to address the aforementioned challenges.
\r\n\tThe book will focus on introducing fundamental principles and concepts of key enabling technologies for routing protocol applied for next-generation networks, disseminate recent research and development efforts in this fascinating area, investigate related trends and challenges, and present case studies and examples.
\r\n\tThe book also investigates the advances and future in research and development in Routing Protocols in the context of new generation communication networks.
The history of medicinal herb usage dates back to the distant past, many centuries and civilizations ago. Plants have played an important role in many cultures in the treatment of various diseases, and floral fragrances have been used to refine the spirit and body, to attract partners, and to establish a psychophysical balance. The first written testimonials on the use of herbs for treatment are found in China. Emperor Kin-Nong knew about 100 medicinal plants in 3000 years BC. One of the oldest classical medical texts of ancient China is “Pent-Sao,” which was written 2500 years BC and is composed of 52 books; of which, two books are dedicated to herbal remedies. In the nineteenth century, medicinal and exotic plants have become lucrative, as more and more people began growing plants in their homes. China, Japan, and South America were overwhelmed by collectors from plant companies who looked for tropical plants to meet the needs of society. This instigated scientific pharmacy and the start of chemical and physiological research on medicinal herbs. It can be said that the nineteenth century was the century of alkaloids, because hundreds were isolated from plants from all over the world. The beginning of the twentieth century threatened medicinal herbs to be completely thrown out of use. Thus, “medicines” that have been successfully used for thousands of years have become subject to mockery and disdain. The expulsion of medicinal herbs from therapy can be compared to the darkness of the Middle Ages that had ruled Europe.
In the last four decades, especially in the developed countries of Europe and America, scientists have shown increasing interest in plant research. It is estimated that today about 60% of the total world population in treatment relies on herbs and natural products that are thus recognized as an important source of drugs [1]. Phytochemistry studies a huge variety of organic substances that have been discovered and which accumulate in plants. Furthermore, phytochemistry is also defining the structure of these compounds, their biosynthesis, metabolism, natural distribution, and biological activities [2]. An important place among them is occupied by aromatic plants, whose aroma is associated with the presence of essential oils and complex mixtures of volatile compounds, dominated by mono- and sesquiterpenes. In addition to essential oils, aromatic plants are characterized by the presence of plant phenolic compounds, primarily coumarins and phenylpropanoids, that have been shown to possess multiple pharmacological activities. Investigations of these secondary biomolecules intensified when some commercial synthetic antioxidants were found to exhibit toxic, mutagenic, and carcinogenic effects [3]. It was also found that excessive production of oxygen radicals in the body initiates the oxidation and degradation of polyunsaturated fatty acids. It is known that free radicals attack the highly unsaturated fatty acid membrane systems and induce lipid peroxidation, which is a key process in many pathological conditions and one of the reactions that cause oxidative stress. Particularly, the biological membrane lipids in the spinal cord and brain are vulnerable, because they contain high levels of polyunsaturated fatty acids. Moreover, the brain contains significant amounts of transitional prooxidant metals and consumes a lot of oxygen. These features facilitate the formation of oxygen radicals involved in the processes of aging, Alzheimer’s and Parkinson’s disease, ischemic heart damage, arthritis, myocardial infarction, arteriosclerosis, and cancer. Phenolic antioxidants “stop” free oxygen radicals and free radicals formed from the substrate by donating hydrogen atoms or electrons. Many plant species and aromatic plants have been tested because of their antioxidant and antiradical activities [4].
The aim of this chapter was to show the antioxidant role of phenolic acids and flavonoids presented in aromatic plants and to assess their potential capacity as scavengers of different free radicals.
Atmospheric oxygen (O2) is present as a biradical with two unpaired electrons, which have the same spin quantum number and are located opposite the orbited orbits. This electronic structure of molecular oxygen determines its chemical reactivity and allows the absorption of individual electrons, with the formation of numerous intermediate, partially reduced oxygen species that are commonly referred to as reactive oxygen species (ROS) [5, 6]. These reactive oxygen species are able to react with basic cellular structures and biomolecules [7] and are responsible for the emergence of many diseases and degenerative damage [8].
The normal concentration of free radicals in the body is very low. However, the effects are very disruptive, as the chain reaction allows one free radical to cause changes in thousands of molecules and damage DNA, RNA, and enzymes in cell membranes and leads to the formation of lipoxygenation products before being inactivated. Which part of the cell (proteins, nucleic acids, membrane lipids, cytosolic molecules) or the extracellular component (hyaluronic acid, collagen) will react with free radicals depends on the nature of the radical and the site of its formation (e.g., cytosolic membranes, mitochondria, endoplasmic reticulum, peroxisome, cell membranes). Due to the presence of molecular oxygen in aerobic organisms and its ability to easily receive electrons, free radicals of oxygen origin start more reactions in the cell. The reactions responsible for their formation are respiration, processes of autoxidation of hydroquinone and catecholamine, reduced transition metals, some herbicides and drugs, as well as irradiation that causes water decomposition.
Any disorder of oxygen species’ regulation resulting from a disturbance in the balance between the formation of reactive oxygen metabolites and their elimination by the antioxidant protection system is the state of oxidative stress. In oxidative stress, the formation and accumulation of reactive metabolites are increased, resulting in oxidative processes of destruction of cellular components and genetic material.
ROS, RNOS, and LP are considered to be the major contributors to the etiology of atherosclerosis and various chronic disorders such as coronary disease, stroke, and ischemic dementia [9]. Antioxidants introduced through food can reduce the occurrence of cardiovascular diseases by inhibiting the production of free radicals and oxidative stress, protecting LDL from oxidation and aggregation, and inhibiting the synthesis of proinflammatory cytokines [10].
Oxidative stress often occurs in the brain, because although it represents only 2% of the body weight, the brain uses up to 20% of oxygen added. Also, the brain contains large amounts of polyunsaturated fatty acids subject to lipid peroxidation under conditions of high oxygen concentration [11, 12].
Although there are insufficient facts to confirm that the presence of free radicals is necessary in the process of carcinogenesis, it is clear that they can lead to mutations, transformations, and cancers [13]. Regarding the development of cancer, the most important target for ROS is DNA. Carcinogenesis is the result of successive mutations in DNA molecules leading to uncontrolled growth and cell phenotypic modification. One of the first steps in this process is the direct interaction of electrophiles or free radicals with cellular DNA in which promutagen lesions develop. If no repair is performed, these lesions result in mutations in the next generation of cells [14]. An increased intake of antioxidants through diet or dietary supplements is associated with a reduction in the onset of cancer.
A reduced amount of free radicals or a reduction in the speed of their production postpones the aging process and a whole series of diseases related to the aging process [15]. A certain maximum life potential characterizes each animal species. There is a reciprocal correlation between the speed of oxygen consumption (and therefore the production of free radicals) and the maximum life potential. Some studies have shown that the aging process can be slowed by increased food intake that increases antioxidant capacity (e.g., fruit and vegetables) or by supplemental intake of vitamins E, C, and β-carotene [16].
The process of oxidative modification of proteins, carbohydrates, DNA, and lipids is a universal mechanism of damage to the cell, especially at the membrane level. On the other hand, the numerous roles of free radicals in physiological processes make their creation a mandatory precondition of life, which is why a protective system has been established during evolutionary development. The basic role of this protection system is to reduce the amount and uncontrolled creation of free radicals and their precursors in the cell.
From a functional point of view, the antioxidant protection of the organism includes three levels of action:
Antioxidant protection systems that prevent the endogenous formation of free radicals. This level of protection is ensured by the spatial separation of processes in which free radicals are formed.
Engagement of the system in conditions of normal and enhanced formation of free radicals. According to the nature and method of action, antioxidants are divided into two types:
Enzymatic (superoxide-dismutase, catalase, xanthine oxidase, peroxidase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase). These enzymes make the so-called primary line of antioxidant protection.
Nonenzymatic or the so-called secondary line of defense.
Enzymatic antioxidants involved in the reparation of oxidative damage of lipids, proteins, carbohydrates, and nucleic acids.
During the evolution, the plants developed effective defense mechanisms against the harmful effects of visible, ultraviolet light and radiation and are a natural source of various antioxidants. Several thousands of biologically active secondary biomolecules of higher plants for phenolic compounds (vitamin E, flavonoids, biflavonols, benzophenones, xanthones, stilbene, quinones, betacities, phenolic acids, acetophenones, phenylpropanoids, coumarins, isocoumarins, chromones, phenols, and diterpenic alcohols) and different nitrogen compounds (alkaloids, amines, amino acids, and chlorophyll derivatives) have been shown to exhibit strong antioxidant activity, but antioxidant activity of essential oils of many spice plants is intense. Their significance is higher because it has been found that many synthetic antioxidants exhibit undesired effects after a prolonged use (e.g., some of them are withdrawn from the market as a possible carcinogen). These biomolecules exhibit their activity through various mechanisms: removing free radicals, binding metal ions, inhibiting enzymatic systems that produce free radical forms, increasing the concentration of biologically important endogenous antioxidants, and inducing the expression of a variety of genes responsible for the synthesis of enzymes that inhibit oxidative stress [14]. The term “herbal phenols” encompasses a wide range of plant substances that form one of the most numerous classes of secondary biomolecules that have a common characteristic of an aromatic ring carrying one or more hydroxyl groups as substituents, including functional derivatives (esters, glycosides, etc.). However, this broad definition also includes some non-phenolic substances. For this reason, it is recommended to combine a definition that includes a chemical description and a biogenetic origin. In nature, there are two general biosynthetic pathways for the synthesis of plant phenols: (1) a polyacetate route and (2) a phenylpropanoid route with scrub acid as an intermediate. Some phenols are formed by a combination of these two times [17].
The efficiency of phenolic compounds in protection against oxidative stress depends on their reactivity in relation to toxic oxygen species and the reactivity of phenoxy radicals relative to critical biomolecules. Chemical or enzymatic oxidation of phenolic components of plant tissue results in a dark color which is of particular importance in food technology. Their susceptibility to oxidation allows their use in the protection of fats and oils.
Phenolic compounds also increase the activity of antioxidant enzymes, thus indirectly affecting the concentration of harmful oxygen radicals in the living cell. In high concentrations, radical reactions such as DNA damage, superoxide anion production, etc. can also be act as a prooxidant [18].
The term “phenolic acid” includes hydroxy and other functional derivatives of benzoic acid (C6▬C1) and cinnamic acid (C6▬C3) [19, 20]. Figures 1 and 2 give the structures of the basic representatives of these acids.
Chemical compounds of basic benzoic acid derivatives.
Chemical formulas of basic derivatives of cinnamic acid.
Cinnamic acids, especially hydroxy-cinnamic acids, have the role of basic precursors in the biosynthesis of various plant phenols. The cinnamic acid and its derivatives are produced by condensation of the acidic acids with phosphoenolpyruvate to give the horizmic acid. Additional reactions of interconversion, decarboxylation, transamination, and disinfection lead to the formation of cinnamon (3-phenylpropenoic acid) and hydroxy-cinnamic acid. Subsequent reactions of hydroxylation, methoxylation, etc. produce cimetic acid derivatives such as p-coumaric acid (p-hydroxy cinnamic acid), β-acid (2,3-dihydroxy cinnamic acid), ferulic acid (2-methoxy-3-hydroxy cinnamic acid), and synapartoic acid (2,4-dimethoxy-3-hydroxy cinnamic acid).
The derivatives of cinnamic acid, in particular hydroxy-cinnamic acids, are the basis of the overall phenylpropanoid metabolism consisting of complex biochemical reactions which as a result supply the plant with important phenolic components [21].
The term “flavonoids” was proposed by Geisman and Heinseiner [21] to describe all plant pigments having a C6▬C3▬C6 skeleton, in which two benzene rings are linked via the C3 unit. These natural products, varying in color from white to yellow, except anthocyanidins responsible for almost all pink and violet shades [20], are widely distributed in the plant kingdom with the exception of algae and fungi. So far, more than 4000 flavonoids have been found in plants, fruits, and vegetables [22]. The most common are seeds, citrus fruits, olive oil, tea, and red wine [23]. They are found in vacuoles, chloroplasts, and chromoplasts, in the form of glycosides, and in the extinct cells free of glycosides. The presence of OH groups directly linked to the carbon atoms of the benzene ring determines the antioxidant role of flavonoids, phenolic acids, and their esters. The expressed activity is shown by compounds with two hydroxyl groups, arranged as for catechol, and three hydroxyl groups arranged as in pyrogallol.
The structure of all flavonoids is based on the C15 skeleton of the chromatic structure for which the secondary ring (B) is attached (Figure 3) [24, 25].
Basic structure of flavonoids.
Flavonoids are divided according to the substitution profile of the heterocyclic ring. In the classification of flavonoids, the oxidation state of the heterocyclic ring as well as the position of the secondary aromatic ring is taken into account. A total of about 12 subgroups of flavonoids are distinguished. The secondary (B) ring may be in position 2 (flavones, flavonols, dihydroflavonols, catechins, flavans, and anthocyanidins), position 3 (isoflavonoids), or position 4 (4-phenyl-coumarins, neoflavonoids). In a few cases, the six-membered heterocyclic ring occurs in an open isomeric form (chalcones and dihydrochalcones) or is replaced by a five-membered ring.
The most widespread of all flavonoids are flavonols (3-hydroxyflavones) and flavones. The most commonly used flavonoids are quercetin, kaempferol, and myricetin. Quercetin is considered the most widespread component of all plant phenols. More than 100 glycosides of quercetin are known. Among flavonols there are about 200–300 known aglycons of these compounds [26].
Phenolic acids are important not only for ensuring the construction of lignin but also for regulating plant growth and disease resistance. Hydroxy-cinnamic acids are associated with the role of growth regulators and proteins in the development of certain diseases. In addition, it is possible that they are important for chloroplasts and the process of photosynthesis itself. Benzoic acid has been shown to inhibit photosynthesis in chloroplasts of spinach [17]. p-Coumaric acid is the most widespread compound among plant phenols. Furthermore, rosmarinic acid has antioxidant, anti-inflammatory, and antimicrobial effects. Its antioxidant effect is stronger than vitamin E. Rosemary acid prevents damage to cells caused by free radicals and reduces the risk of cancer and atherosclerosis. Unlike antihistamines, rosemary acid prevents the activation of immune system cells that cause swelling and fluid collection. It is used in the treatment of stomach ulcers, arthritis, cataracts, cancer, and bronchial asthma [27, 28]. Caffeic acid far exceeds other antioxidants because it reduces the production of α-toxin by more than 95%. It has been proven that high doses of coffee acids have a detrimental effect on the rats because they cause gastric papillomas. However, the combination of different antioxidants, including baconic acid, had a pronounced effect on the reduction of colon tumors in the same rats. The harmful effects of bicarbonate on human health are not known [29]. Calcium acid and its derivative caffeic acid phenethyl ester (CAPE) show a reduction in tumors and show anti-inflammatory and anticancer effects on ultraviolet-exposed skin, especially UVC and UVB rays [30]. Anticancer activity was observed in mice whose skin was treated with bee propolis and a papilloma-causing agent (TPA). CAPE significantly reduced the number of papillomas [31].
Flavonoids have a high ecological significance. They function as pigments that attract insect pollinators, not only as signal molecules for microorganisms that are useful for the plant but also as antimicrobial agents [32]. In this sense, yellow flavones and flavonols are particularly important. Because of the intense absorption of UV radiation, flavonoids protect the plant tissue from UV radiation, thereby influencing vital processes in chloroplasts.
In a pharmacological view, flavonoids show antiviral, antiallergic, antitumor, antibacterial, antifungal, and antithrombotic activity [33]. They act on blood vessels, namely, flavanones and catechins, that increase the resistance of the capillaries. They show an anti-inflammatory activity that depends on the structure of flavonoids [34]. The flavonoid anti-inflammatory activity was also confirmed by in vitro testing of the ability to inhibit lipoxygenase and cyclooxygenase [35]. Flavonoids eliminate pathological changes on capillaries and are used against diabetes, hypertension, and atherosclerosis. Flavonoids have been found to stimulate the secretion of bile and inhibit enzymes and enzymatic systems. Many flavonoids have antimicrobial and antiviral activity. A certain number of flavonoids show some cytotoxic activity. The common structural feature of cytotoxic flavonoids is trisubstituted ring A, methylation at position C4 [21].
For many flavonoids, high antioxidant activity has been demonstrated in various in vitro systems [36, 37, 38]. It has been shown that quercetin, rhamnetin, and isorhamnetin can reduce the amount of serum and liver cholesterol in addition to the in vivo antioxidant activity they show [39]. Flavonoids have been found to inhibit the activity of XOD and have the ability to capture superoxide radicals. Based on this, it is assumed that flavonoids can help in the treatment of gout and ischemia by reducing the amount of uric acid and superoxide anion of radicals in tissues [40]. Two flavonol glycoside-gallate esters showed inhibitory activity on human immunodeficiency virus-1 (HIV-1) integrase [41]. The HIV-1 integrase manages the process of incorporating viral DNA into the DNA of the host cell molecule, which is necessary for the virus to reproduce and produce virions. In this way, the inhibition of the given enzyme can be effective in anti-AIDS therapy. For example, quercetin has a beneficial effect on human health: it improves heart rate and reduces the risk of cancer. It has an anti-inflammatory and antiallergic effect. All of these effects are caused by a strong antioxidant effect of quercetin. Like many other flavonoids, quercetin inhibits the oxidation of LDL cholesterol, and its anti-inflammatory activity derives from inhibition of lipoxygenase enzyme and inhibition of inflammatory mediators. Quercetin also inhibits the release of histamine. Studies have shown that quercetin lowers the risk of prostate, uterine, breast, tissue, and colon cancer. It is presumed to reduce the production of uric acid by inhibiting XOD. It also shows NO inhibitory activity. Rutin has a strong antioxidant effect, as well as the ability to build chelates with metal ions (e.g., iron) and reduces Fenton’s reaction in which harmful oxygen radicals are produced. It is supposed to stabilize vitamin C. If rutin is taken along with vitamin C, the activity of ascorbic acid increases. Rutin strengthens the capillaries, which helps people who easily bleed or get bruises. It prevents the formation of various edemas, which is an early symptom of a chronic vein disease. It has an anti-inflammatory effect. There are indications that rutin can inhibit some carcinogenic and precancerous conditions, prevent atherogenesis, and reduce the cytotoxicity of oxidized LDL cholesterol [22]. Furthermore, kaempferol prevents arteriosclerosis by inhibiting the oxidation of low-density lipoproteins and the formation of blood platelets. It has a role of a chemopreventive agent, which means it prevents the formation of cancer cells. Quercetin has a synergistic effect in reducing the proliferation of malignant cells, so treatment with quercetin and kaempferol combinations is more effective than their individual use [42]. In addition, tangeretin acts as an anticancer agent, and in in vitro studies, it has been shown to act against some forms of malignant cells. It strengthens the cell wall and protects it from attack. It also causes apoptosis of cells suffering from leukemia, while normal cells remain undamaged [43]. Tangeretin prevents tumor suppression of intercellular bonds when transmitting the signal [44]. In the G1 phase of the cell cycle, it “freezes” the cancer cells and prevents their replication. In short, in vitro studies have shown that tangerine exhibits antimutagenic, noniinvasive, and antiproliferative activity [45]. Animal studies have shown that tangeretin reduces cholesterol levels [46] and has a potentially protective effect from Parkinson’s disease [47].
The Lauraceae family comprises over 2500 species, which occur within the subtropics and tropics of Eastern Asia and South and North America. Most species possess aromatic roots, stems, and fruits. One of the most well-known and most frequently used plants from this family is Laurus nobilis L., also called bay laurel. L. nobilis is a species held in high esteem since ancient times. It was dedicated to Apollo, the ancient Greek god of light, and a symbol of peace and victory used to make wreaths for emperors, generals, and poets (Figure 4) [48].
Laurus nobilis L [21].
Laurel is a tree or a large bush of pyramidal shape with aromatic, constantly green leaves and shiny gray corn. It reaches a height of up to 5.5 m, but the cultivated form is usually lower (1–3 m). The leaves are elliptical, fairly thick, leathery, and shiny green. Clusters of tiny, yellow, single-polar flowers appear in the spring. Berries (fruit) (Lauri Fructus), when dry, are black and wrinkled and contain two oval fat seeds. Laurel is cultivated in several cultivated forms: spp. aurea with yellowish young leaves, spp. angustifolia with narrow leaves (often called Vrbolik laurel), and spp. undulata with corrugated leaf edges. Laurel is commercially grown for aromatic leaves in Turkey, Algeria, Morocco, Portugal, Spain, Italy, France, and Mexico [49, 50].
The distillation of laurel leaves produces green-yellow volatile oil that contains a high percentage of oxidized components. Essential oil leaf (0.8–3%) contains mainly 1,8-cineol (50%) and then eugenol, acetyleugenol, methyl eugenol, α- and β-pinene, felsenren, linalool, geraniol, and terpineol. Dried berries can extract green mass (melting point about 30°C) containing several percent essential oils (0.6–10%), depending on the conditions of breeding and storage. Berries contain both volatile and fixed oils. The others are known under the common name “laurel oil” (Oleum Lauri expressum, Oleum laurinum, and Oleum Lauri unguinosum). As essential ingredients, the oil contains laurosterin, glycerol ester with lauric acid, and sesquiterpenoid (the costume and dehydrocostus lactone), while the rest is made up of fats: triglycerides with lauric, myristic, and elastic acids. As with leaves, the aroma is mainly due to terpenes (cineol, terpineol, α- and β-pinene, citral) but also cinnamic acid and its methyl ester [51].
The main flavonoids in bay leaf are quercetin, kaempferol, rutin, and their derivatives (Figure 5).
Structures of the main flavonoids present in L. nobilis [21].
Kaempferol appears in the form of four nonpolar glycosides (Figure 6) [52, 53].
Structures of kaempferol and its glucosides present in L. Nobilis [21].
Laurus nobilis is characterized by the presence of the other important plant phenolic substances such as phenolic acids (rosmarinic and caffeic acids) (Figure 7).
Structures of two phenolic acids in L. nobilis.
As a medicinal plant, bay leaves and fruits have been employed against rheumatism, skin rashes, and earaches. In addition, it has been used as a stomachic, astringent, carminative, diaphoretic, stimulant, emetic, emmenagogue, abortifacient, and insect repellent. The essential oil is used by the cosmetic industry in creams, perfumes, and soaps.
Numerous investigations of qualitative composition of plant extracts have revealed the presence of high concentration of phenols in the extracts obtained using polar solvents [54]. The extracts that display the highest antioxidant activity have the highest concentration of phenols. Because of that, our research on laurel was recently extended to the comprehensive in vitro and in vivo studies of antioxidant activity of different extracts of leaves, to assess their potential capacity as scavengers of free radicals. Results of determination of total phenolic contents and total flavonoid contents in laurel leaf extracts are given in Table 1.
Extracts | Et2O | CHCl3 | EtOAc | n-BuOH | H2O |
---|---|---|---|---|---|
Total phenolic content | 2.41 | 2.85 | 4.53 | 3.96 | 3.20 |
Total flavonoid content | 0.76 | 1.02 | 1.56 | 1.07 | 0.68 |
The amount of total phenolic contents (mg GAE/g d.w.) and content of total flavonoids (mg QE/g d.w.) in L. nobilis extracts.
The amount of total phenolics in L. nobilis extracts ranged from 2.41 mg GAE/g d.w. (Et2O extract) to 4.53 mg GAE/g d.w. (EtOAc extract). A significant amount of these compounds has also been observed in the n-BuOH extract (3.96 mg GAE/g d.e.). Furthermore, a considerable total flavonoid content was determined in the EtOAc and n-BuOH extracts. A little less amount of total flavonoids was determined in the CHCl3 extract, while the smallest quantity of these compounds was found in the Et2O and H2O extracts. HPLC-DAD analysis indicates a significant presence of flavonoids and phenolic in the EtOAc and n-BuOH extracts. Quercetin glycosides and flavonoids (e.g., kaempferol-3-O-Glc) were detected in EtOAc extract. In addition, the presence of phenolic acids (such as caffeic acid) and flavonoids (rutin and kaempferol) was proven in the H2O extract. The amount of flavonoids in extracts plays a significant role in their antioxidant capacity. Differences in flavonoid content between extracts and between plant organs can be explained by different numbers of secretory structures in various plant tissues [42, 55, 56].
It should be considered that the number of identified and quantified compounds in MeOH extract of L. nobilis L. has been expanded in the present work (Table 2).
Compounds | Extract | |
---|---|---|
Phenolic acid | p-Hydroxybenzoic acid | 38.46 |
Protocatechuic acid | n.d. | |
p-Coumaric acid | n.d. | |
Vanillic acid | n.d. | |
Gallic acid | n.d. | |
Caffeic acid | 16.18 | |
Quinic acid | n.d. | |
Ferulic acid | n.d. | |
Syringic acid | n.d. | |
Chlorogenic acid | 13.11 | |
Cinnamic acid | n.d. | |
Flavonoids | Apigenin | n.d. |
Naringenin | n.d. | |
Luteolin | 5.19 | |
Kaempferol | 11.97 | |
Apigenin-7-O-β-glucoside | n.d. | |
Luteolin-7-O-β-glucoside | n.d. | |
Kaempferol-3-O-glucoside | 56.15 | |
Quercetin-3-O-glucoside | 31.18 | |
Rutin | 17.44 | |
Quercetin | 21.62 | |
Quercitrin | 7.14 |
LC-MS-MS quantification of bioactive compounds presented in L. nobilis L. crude MeOH extract (μg/g d.w.).
The results indicate that the major bioactive compounds in L. nobilis extracts were kaempferol-3-O-glucoside, quercetin, and rutin. Phenolic acids were also observed in the high level, where the antioxidant, caffeic, and chlorogenic acids were found in the highest amount. Furthermore, p-hydroxybenzoic acid was also found in very high amount. The rest of the phenolic acids were not detected [57, 58, 59].
Furthermore, antioxidant activity was observed in the study of laurel leaf extracts in different solvents on the content of DPPH•, O2•−, NO•, and OH• radicals (Table 3).
Extract | Et2O | CHCl3 | EtOAc | n-BuOH | H2O |
---|---|---|---|---|---|
DPPH radical | 127.38 | 139.42 | 83.24 | 181.35 | 161.83 |
O2•− radical | 327.60 | 429.43 | 163.57 | 288.64 | 486.32 |
NO radical | 168.77 | 322.84 | 158.63 | 386.80 | 618.42 |
OH radical | 442.84 | 241.18 | 121.84 | 213.36 | 187.65 |
IC50 values (μg/mL) of L. nobilis for different antioxidant assays.
The obtained results could point to strong quenching activities of flavonoids present in the leaves of laurel against DPPH radicals, and a high degree of correlation is observed between total phenol content and the ability of EtOAc extract to neutralize DPPH radicals. This is indicated by the fact that phenolic compounds play a key role in neutralizing free radical species which occurs by the mechanism of electron transfer. But, it can be supposed that such antiradical activity is also caused, besides flavonoids, by terpenoids, since nonpolar solvents also exhibited high antiradical potential. When investigating neutralization of O2•− and NO radicals, ethyl acetate extract has also exhibited the greatest ability of their scavenging. These results can be attributed to the presence of sesquiterpene lactones isolated from the plant that possess certain biological and pharmacological activity [60, 61]. Matsuda et al. [62] have also established that the methanolic extract from the leaves of L. nobilis was found to inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-activated mouse peritoneal macrophages. It was concluded that seven sesquiterpene lactones (costunolide, dehydrocostus lactone, eremanthine, zaluzanin C, magnolialide, santamarine, and spirafolide) potently inhibited LPS-induced NO production. Inhibition of NO radicals with laurel extracts is very significant, having in mind the ability to neutralize the superoxide anion radicals as well. The common reaction between superoxide anion radical and nitrogen oxide radical yields a very reactive peroxynitrite anion (ONOO−) which is very active in reaction of nitrification of phenols—e.g., nitrification of thyroxine causes enzyme dysfunctions, and increased amounts of 3-nitrothyrozine were found in various pathological states [63]. If formation of nitroderivatives of thyroxine is prevented, the occurrence of these diseases due to oxidative stress is reduced. Ethyl acetate extract of laurel leaves is especially suited in this process since it neutralizes both superoxide anion radical and NO radical. Obtained results can be related to the experiments in which the total amount of phenols and flavonoids were determined (Table 1), which show that ethyl acetate extract of laurel leaf contains the largest amounts of total phenolic content and total flavonoid content. The cellular damage resulting from hydroxyl radical is strongest among free radicals. Hydroxyl radical can be generated by biochemical reaction. Superoxide radical is converted by superoxide dismutase (SOD) to H2O2, which can subsequently produce extremely reactive OH• radicals in the presence of transition metal ions such as iron and cooper [64, 65]. A good antioxidant potential of neutralization OH radical was shown by the EtOAc (IC50 = 121.84 μg/mL) and H2O (IC50 = 187.65 μg/mL) extracts. Such a good antioxidant activity of H2O and EtOAc extracts is expected, because it is known that the antioxidant activity of phenols is primarily a result of the ability of these compounds to act as donors of hydrogen atoms removing free radicals with the formation of less reactive phenoxyl radicals [66]. The increased stability of the formed phenoxyl radicals primarily attributed to electron delocalization and the existence of multiple resonant forms. Researching dependence of activity on the structure was found to have three structural features as important factors of radical removal potential and/or antioxidant potential of flavonoids: (1) o-dihydroxy function of ring B, which serves as the target of radicals; (2) 2,3-double bond in conjugation with 4-oxo function, which is responsible for electron delocalization of the ring B; and (3) the additional presence of 3- and 5-hydroxyl groups for the maximum radical scavenging potential [67]. The positive relationship between increased hydroxylation and increased antioxidant activity of flavonoids was found in different lipid systems, such as oil and liposome systems. Also, for phenolic acids and coumarins, it has been shown that vicinal diol groups are important for radical scavenging capacity and that methoxylation or glycosylation of o-hydroxy group in the coumarins and esterification of phenolic acids reduce the antioxidant activity of these compounds [68]. For example, it was determined that rosmarinic acid has stronger antioxidant effect than vitamin E. Rosmarinic acid prevents cell damage caused by free radicals and reduces the risk of cancer and atherosclerosis. In contrast to the histamines, rosmarinic acid prevents activation of the immune system cells that cause swelling and fluid collection [27, 69]. Furthermore, the action of some flavonoids is based on their ability to chelate transition metal ions, thereby preventing the formation of radicals (initiators of LP), catching radical initiators of LP (ROS), scavenging lipid alkoxyl and lipid peroxyl radicals, and regenerating α-tocopherol by reduction of α-tocopherol radicals. Different metals have different binding affinities of the flavonoids. Thus, for example, iron has the highest binding affinity for 3-OH group of ring C, then catechol group ring B, and at the end of 5-OH group of ring A, while the copper ions bind to the first ring catechol group B [70]. Also, in the previous investigation, on L. nobilis, different groups of chemicals were isolated (luteolin, apigenin, alkaloids, monoterpene, and germacrane alcohols) [71].
One of the paradoxes of life on Earth is that, on the one hand, oxygen is necessary for the life of aerobic organisms. On the other hand, increased concentrations of oxygen and especially its reactive metabolites (reactive oxygen species) may lead to the development of numerous diseases. A major source of free radicals in biological systems is molecular oxygen (O2). The results of our in vitro assays of examined five different extracts of Laurus nobilis leaves expressed significant protective effects on ROS (DPPH, O2•−, NO, and OH radicals), which was found to be correlated to different compounds. HPLC-DAD analysis indicates a significant presence of flavonoids and phenolic in the EtOAc and n-BuOH extracts. Quercetin glycosides and flavonoids (e.g., kaempferol-3-O-Glc) were detected in EtOAc extract. In addition, the presence of phenolic acids (such as caffeic acid) and flavonoids (rutin and kaempferol) was proven in the H2O extract. The amount of flavonoids in extracts plays a significant role in their antioxidant capacity, and it can be concluded that ethyl acetate proved to be the best solvent for extraction of plant material. Furthermore, it can be concluded that these extracts can be used in the preparation of various herbal medicines.
This work was supported by the Ministry of Science and Environmental Protection of the Republic of Serbia (Project No. 172058).
The authors declare that there is no conflict of interest.
An incubator is a way for the community to help entrepreneurs who have good ideas but do not have the resources to start their activities independently.
\nSmall business incubators are a way of boosting economic development, whose practice began in the United Kingdom since the 1970s as artists’ cooperatives, often being located in historic buildings. In the USA, incubators have been used, for example, to (i) assist the recovery of ruined and impoverished neighborhoods, (ii) promote scientific innovation by linking partnerships between universities and business, and (iii) help entrepreneurs who want to expand their specialist knowledge through interaction with other small business owners [1, 2, 3].
\nInterest in incubators lies partly in the role that small businesses play in most local economies, for example, in the jobs created and the innovation generated. Furthermore, small businesses can be developed in greater numbers faster than the larger companies often not local.
\nIncubators are a vehicle of aid to local entrepreneurs as they constitute the local economy and are more likely to maintain their activity locally than multinational enterprises. In addition, supporting the creation of small local businesses can help locally engage young entrepreneurs by avoiding the loss of specialized skills in some geographical regions of the interior. However, there is a risk that 50% of small businesses will fail in the first 4 years of operation. This reality has diverse implications for local economic development, in the following aspects [4, 5, 6]:
Small businesses are important because they can generate employment for residents.
Small businesses often carry out activities in areas of technological innovation or artistic or creative areas that do not require many resources to operate the business.
The development of small businesses contributes to the creation of local and regional economic capital (specialized knowledge and brands).
Significant efforts must be made to ensure that the companies created will not fail.
Because of the risk of small business failure, incubators should not be seen as the cornerstone of an economic development strategy but rather as a contribution of efforts to promote the development of SMEs in a given community.
A brief note to mention is that start-ups usually fit into the reality of a small business.
\nStart-up incubators support the creation and growth of business through organizational and technical assistance, which at the same time contributes to the reduction of entrepreneurial failure. The three most common objectives of incubation programs are the following [5, 7]:
The creation of employment in the community
The creation—or acceleration of growth—of a local industry
Diversification of the local economy
The incubation can be physical or virtual. Virtual incubation does not consist of a work space, but it is included in a credible address destined to the market for professional contacts, including the holding of work meetings. We can affirm that an incubator is constituted by a common space of which a space (like office) is made available that is used for the beginning of activity of a new business. The price of rents may be lower than the market price due to public subsidies to promote entrepreneurship.
\nIn addition to lower incomes, location sharing, or coworking among start-ups with similar activities, the incubator includes a set of support services to serve the technical and operational needs of start-ups, often owned by inexperienced entrepreneurs. In turn, coworking constitutes a physical space that fits a transversal work model for entrepreneurs with similar activities at the level of operational resources. It is a functional structure that allows entrepreneurs to have an office as reference location and professional contacts, enjoying a series of services shared with other entrepreneurs.
\nThe physical facilities provided by the incubators may take different forms depending on the sector of activity of the start-ups to be incubated. For example, the service start-up incubator may consist of individual offices with shared common areas (reusing a residential or commercial space), while incubators for high-tech manufacturing start-ups require larger spaces (industrial buildings).
\nBusiness incubators offer tangible and intangible benefits to start-ups [7, 8]. Tangible benefits often include the following operational aspects:
Shared use of equipment such as photocopying machines, telephones, computers, and Internet access
Shared conference spaces and meeting rooms and informal interactions with other incubators
Shared services for start-ups, such as secretarial, accounting, marketing, and legal support
Technical assistance in marketing plan, business plan, financial system, and accounting
Joint acquisition to suppliers and links between incubated start-ups relative to operating factors upstream and downstream in the value chain
Assistance in obtaining funding in the start-up phase
The intangible benefits derive from the ability of entrepreneurs to act as a support system among incubated start-ups. Intangible benefits are more likely to occur among start-ups with similar activities. For example, incubated high-tech start-ups can share the development of ideas and innovation. Biotech start-ups can support each other in the development and commercialization of innovative products.
\nEven in incubators with start-ups operating in distinct sectors of activity, entrepreneurs can share their experience, ideas, and knowledge on certain subjects such as marketing, product development, recruitment, and accounting.
\nFollowing the above, we can briefly state that the main objective of incubators is to support the development of start-ups, which leave the incubator when they increase in size or become sufficiently stable to operate without specific benefits offered by the incubator. This makes room for other start-ups to start their incubator operations.
\nThere are several economic development tools that can be used in conjunction with the incubation of start-ups, which will be addressed in the following subsections.
\nFor entrepreneurs, money is a resource but not an end in itself. It is true that an innovative idea needs capital to subsist. It is also true that a large number of businesses fail due to lack of adequate funding. However, other resources are equally vital to entrepreneurial success, such as specialized work teams and sales and distribution capabilities. Having financial capacity is not (always) a guarantee that the appropriate resources are put together in the right way and at the right time.
\nInitial or seed financing programs can take a variety of forms and are often used in combination with the most effective incubators. Small loans from investment funds (made up of grants from the government and/or local government), with below-market interest rates, are provided to support the creation of new businesses [9]. As the loans are paid, the money of the fund is reinvested in subsequent deals. The incubators can also help start-ups incubated to obtain financing, first linking up with business angels and venture capital investors and on the other hand giving technical support in the preparation of documents and presentations.
\nBusiness angels invest in small start-ups or entrepreneurs, can have multiple origins (including family or friends of the entrepreneur), and invest in one go to boost the business or make a continuous injection of money to support the company in the early stages more difficult. Venture capital consists of investor financing for start-ups and small businesses that are believed to have long-term growth potential. For companies that do not have access to the capital market, venture capital is an essential source of money. The risk is typically high for investors, but they have intervention in company decisions, which is a disadvantage for the company funded.
\nBusiness angels offer advantages compared to venture capital: business angels invest in the early stage of the business, that is, they help start-ups take their first steps in the market, while venture capital investors bet on the viability of the business and can profit from the business by the investment. In this sense, business angels are the opposite of venture capital investors.
\nAnother way for entrepreneurs to get the resources they need or use is through crowdfunding, which is a process directed at individuals to raise funds to finance a specific cause or project in return for a variety of rewards. Thus, we can say that crowdfunding bases its dynamics on raising funds to finance a business or a project: (i) in exchange for share capital; (ii) in exchange for tangible, non-monetary rewards, such as a product finished; or (iii) in exchange for a financial return at a future date.
\nAlthough not essential to the effective operation of a small business incubator, there are benefits to locating it within municipal industrial parks. The incubator can provide a space with the necessary infrastructure at the lowest cost and close to similar start-ups. The industrial park also wins with the installation of the incubator, as it enhances the local demonstration effect for the creation of other start-ups. Incubators can also be installed in old abandoned facilities (state, military, and industrial) to stimulate local development [10].
\nEmployment and skill development programs enhance local qualifications, increasing individuals’ willingness to develop innovative start-ups or collaborate on incubated start-ups. The existence of qualified human resources at the level of high technology facilitates the development of start-ups.
\nPrograms aimed at the emergence of local entrepreneurs are directly complementary to the start-up incubators. These programs provide the necessary skills and competencies—for example, marketing, financial planning, hiring and human resource management, information systems and strategy—to successfully build and manage start-ups.
\nIn addition to entrepreneurship training, investing in local education infrastructure is a boon to the development of start-ups. Educational institutions provide the human resource base crucial to economic development. Thus, higher education institutions can create a series of synergies with the community—for example, service delivery and the development of strategic partnerships—increasing the effectiveness of start-up incubators. Universities are sources of new ideas to create start-ups of high technology and with differentiated value for society. The faculty can, on the one hand, provide students with the necessary skills to encourage the creation of start-ups and, on the other hand, provide services to the community, thereby contributing to economic growth.
\nEducation plays a vital role in the development of entrepreneurship in society. Being the curricular structure of higher education courses—first and second cycles—is a good indicator of the relationship between the training provided (knowledge transmitted) in educational institutions and the technical skills and competences needs verified in society and in business fabric.
\nCurrently, there is a great difficulty in obtaining a job where the knowledge acquired in a higher education course can be applied, through the conclusion of a stable employment contract, and with a remuneration proportional to the education effort carried out as a personal investment. Therefore, it is imperative to adapt the education system to the challenges in the labor market. Therefore, rather than teaching someone to work for entrepreneurs, it will be necessary to pass on knowledge in order to encourage the emergence of new entrepreneurs in the community.
\nThe university as a reference in entrepreneurship education contributes to the preparation of future economic actors through the execution of programs in entrepreneurship. This allows you to impart knowledge and techniques that facilitate the creation of a business and simultaneously encourage students to create new business. In this way it is possible to increase the entrepreneurial potential of the students, but few start new business during and after the conclusion of the studies [1, 11].
\nIn this sense, the entrepreneurial education constitutes a challenge, on the one hand, to the institutions of higher education in what concerns the design and implantation of incubation in articulated network with diverse economic actors and, on the other hand, to the traditional pedagogical methodology of transmission of knowledge and learning in the classroom.
\nTherefore, entrepreneurship education aims at increasing students’ awareness of the various aspects of business creation, emphasizing a philosophy of learning oriented to practice and action in a turbulent environment.
\nEntrepreneurs are challenging existing competitive assumptions by creating value for consumers through new forms of business. This created value may lead to consumer willingness to (i) pay for a new benefit, (ii) pay more for something perceived as better, or (iii) receive a previously available benefit at a lower cost. Consequently, value translates the willingness of the consumer to purchase a product or a service, at a certain price, for recognizing attributes that contribute to their satisfaction of needs, fulfillment of wishes, or resolution of a problem [12].
\nThe constant value creation imposed by increased competition is changing management practice by redefining operational activity in the fields of production, sales, and distribution of products and services. This competitive reality stems from an unstoppable, complex change in which advances in technology combine with the development of suppliers and customers. We can identify eight major areas of change in the competitive environment:
Technological environment: accelerated development of new technologies, rapid product obsolescence, and greater difficulty in protecting intellectual property
Economic environment: unpredictability of prices, operating costs, exchange rates, interest rates, tax incentives, and shorter business life cycle
Competitive environment: highly innovative competitors, competition from nontraditional strategies, and threat of new competitors who may also be customers or business partners—which sets up a competition between economic actors
Work environment: shortage of skilled employees, greater mobility and less employee loyalty, increased employee costs, and contractual obligations in labor relations
Resource environment: increasing scarcity of resources, increasingly specialized resources, limited alternative sources, and rapid obsolescence of resources
Customer environment: greater demand through varied channels, more complex customers in markets that are more fragmented or atomized (more competitors), more segmented (greater variety of customers) and focused on creating value for the consumer—which stems from an innovation process that establishes or enhances the consumer’s assessment of the consumer benefits (value in use) of a product or service
Legal and regulatory environment: more aggressive regulation, virtually unlimited product liability, increasing regulatory compliance costs, increased emphasis on free and fair trade, and increased environmental regulation and associated compliance costs
Global environment: real-time communication and production, distribution to anywhere in the world, suppliers as business partners, customers and competitors more sophisticated and located anywhere in the world, and obtaining a competitive advantage, for example, by means of outsourcing and strategic alliances
This change has important implications for business, as many entrepreneurs struggle more to survive than to achieve sustained growth. Stakeholders are constantly changing (customers, suppliers, distributors, alliance partners, and regulators). As the required resources (physical, organizational, technological, and human) have become increasingly specialized and less predictable in terms of the duration of their competitive relevance, entrepreneurs tend to contract in the short term the use of resources subject to greater competitive obsolescence, instead of opting for their acquisition.
\nThus, entrepreneurs have, in general, a lack of control over their competitive environment. And the size of business is not an unequivocal condition of success. However, the exploitation of valuable, rare, and inimitable resources generates a sustainable competitive advantage and, consequently, a superior performance in the market [13].
\nTurbulence in the competitive environment has caused and forced a transformation in management operations. Traditional bureaucratic models, hierarchical management systems, and a philosophy of controlling the company’s operations are not feasible in the contemporary competitive environment. However, it is not clear what gives us assurances of working well, but management must consider that the organizational structure, leadership style, and ways of rewarding and motivating employees can contribute to increases in competitiveness.
\nThere is also a positive side to the competitive environment as it becomes more complex and dynamic, as there are opportunities to serve customers who are dissatisfied. Traditionally, competitive advantage was achieved through a number of strands, namely:
Lower costs than competitors
Offer superior product quality
Addition of new product features
Providing better customer services
At present, the continuous improvement of these aspects is a minimum criterion for maintaining market competitiveness.
\nThe pursuit of competitive advantage requires entrepreneurs to continually reinvent business and can come from five key capabilities:
Adaptability: timely adjustment to new technologies, customer needs, regulatory rules, and other changes in competitive conditions without losing the focus of their core business.
Flexibility: design strategies, processes, and operational approaches that can simultaneously meet the diverse demands of stakeholders (customers, distributors, suppliers, financiers, and regulators).
Speed: act quickly on emerging opportunities, develop new products and services more swiftly, and make critical operational decisions without lengthy deliberations.
Aggressiveness: a focused and proactive market approach in order to differentiate itself from competitors, retaining customers and motivating employees.
Innovation: continuous priority of development and launch of new products, services, and technologies, aiming at market leadership.
The most adaptable, flexible, fast, aggressive, and innovative entrepreneurs are best positioned not only to adjust to a complex, threatening, and dynamic competitive environment but also to create the change in that environment. Entrepreneurs must affirm themselves as agents of change by leading clients instead of following them, creating new markets and defining new competitive rules [14].
\nEntrepreneurship is the main source of sustainable competitive advantage through the production and/or marketing of products and services that are more advanced than the competition, i.e., unique in the market compared to the value supplied to consumers.
\nAlthough competitive instability is most felt in some sectors, none is immune to its challenges. Increasingly, competitive conditions in markets become unpredictable beyond the short term. This economic landscape has implications for entrepreneurs, which can turn in their favor.
\nA measure generally adopted in the face of aggressive price pressure from competitors is to reduce costs to the lowest possible levels. The goal of this cost reduction effort is often the workforce (the employees), but the need to produce the product or provide the service remains. Hence, suppliers are used to perform the operational tasks eliminated via downsizing, engaging in outsourcing, which has become a business opportunity for small businesses, which include small and microenterprises.
\nThe threats that large companies experience offer small business opportunities. In addition to receiving outsourcing requests, a small business can also compete in another market based on subcontracting services to other companies.
\nIn reality, a small business can establish partnerships (strategic alliances or joint ventures) with a variety of suppliers covering value chain activities and thus can enter into markets it might not otherwise be able to achieve. In practice, we are talking about a virtual company, that is, a company that does not have the (own) resources needed to compete in a particular market segment but has the possibility of forming partnerships with other companies in order to perform the key management functions to the pursuit of the own business [15, 16].
\nAnother change that is happening in the markets is their continued fragmentation (increase in the number of competitors) or the development of niches. Within the markets there are small groups of consumers who value a set of unique attributes in a product, which is a niche market. Many niches do not interest large corporations because they are small in terms of turnover, providing small businesses with business opportunities. To benefit from these opportunities, entrepreneurs must focus on a clearly identified market niche so that they understand and meet the expectations of these consumers.
\nSmall businesses have important advantages that enable them to be successful, namely, their sensitivity to market conditions and trends, which derives from their close relationship with customers, enabling them to understand their needs.
\nThe existence of a personal relationship with customers ensures that the entrepreneur is the first to perceive the changes in consumer preferences that will affect the market as well as gives him the possibility to convey the message that interests the customer. This small business communication process encourages market learning by expressing interest in the business of customers.
\nAnother factor that distinguishes successful small business from typical large enterprises is their ability to innovate. The entrepreneurial company has a quick reaction when changes or opportunities arise in the market. While large corporations recognize the need to change quickly, the burdens of bureaucratic procedures slow them down. The ability of small businesses to innovate encompasses product innovation (new relevant features), process innovation (improvement of the production process), and service innovation (offering something new in the service). It should be noted that innovation is related to organizational flexibility, which comes from personal attitude and organizational practices based on the creation of knowledge as the main competitive resource [17, 18].
\nIn addition, small businesses tend to invest less than large companies in rigid production equipment. This enables greater agility in changing.
\nTogether, responsiveness, organizational flexibility, and innovation practices make small businesses more competitive in a rapidly changing environment.
\nSmall businesses can be developed within the family universe, translating into family businesses, or constitute a situation of self-employment.
\nA small business is not necessarily a family business. In the family business, ownership and management are concentrated in the family members, predominantly a family-based intraorganizational relationship. Family nature issues are prioritized against other objectives. For example, the company’s property control by the family will not be sacrificed to fund the development and growth of the business. Indeed, family property is not diluted to include non-family investors. Therefore, the available financial resources are those generated by the company and those of the family itself. However, credit may be used with banking institutions to finance the growth of the business.
\nThe uniqueness of the family business lies in the integration of family and business in the same context. The collaboration of the family members in the company may be an indication that the admission criteria are not governed by the higher academic and professional qualifications, which are more suitable for the performance of duties [19]. However, instead of prevailing the replacement of generations in the management of the company, the owners can choose to hire professional managers to create wealth but preserving the intra-family relationship in the company. On the other hand, family firms often find it difficult to attract and retain highly skilled managers, partly because of the limitations of career advancement and the absence of personal reward policies, as well as the lack of goal-oriented professional management and continuous improvement.
\nThere are immense advantages and disadvantages of self-employment (being your own boss), and the entrepreneur must be aware of both before starting a business. We start by highlighting the three main advantages:
Autonomy: the need for independence and freedom to make decisions are the main advantages. The feeling of being your own boss is very satisfying to most entrepreneurs.
Challenge of a new company/sense of accomplishment: for a large number of entrepreneurs, the challenge of a new company is fun. The opportunity to develop a concept and make it a profitable business provides a meaningful sense of accomplishment where the entrepreneur knows that he or she is solely responsible for the success of the idea.
Independence/financial control: while frequent mention is made of the financial independence of entrepreneurs, it does not necessarily mean that they want to be wealthy but want more control over their financial situation. They do not want to be subject to unexpected announcement dismissal of employees after years of dedicated work to the company.
If self-employment were easy to achieve, there could be a much larger number of self-employed people. In fact, it is one of the most difficult professional careers anyone can choose. Some of the disadvantages of this life option are described below:
Personal sacrifices: especially in the early years of the business, the entrepreneur often has to work many hours during the 6 or 7 days of the week. This leads almost to lack of time for fun, family life, or personal reflection. Business takes up a lot of time in the lives of entrepreneurs, resulting in stress in family life and a high level of stress. The entrepreneur must wonder about how much he is willing to sacrifice himself in order to make the business successful.
Overload of responsibility: the entrepreneur has a burden of responsibility distinct from that of the employees of a company. In companies, employees are usually surrounded by other people—of a similar professional or technical level—with the same interests. It is possible to share information while having lunch or after working hours, assuming a sense of cooperation. In turn, the entrepreneur knows that he is alone in the organizational top. While employees in companies specialize in specific areas such as marketing, financial, or commercial, entrepreneurs have to manage all these operational functions until the business is sufficiently profitable to hire employees with the necessary technical knowledge. The need to master several technical areas is a considerable burden on the entrepreneur.
Small margin for error: large companies often make decisions that prove to be unprofitable, for example, the launch of products that are not well accepted by the market and the opening of points of sale in disadvantageous places. On the other hand, small businesses operate with a narrow financial cushion because the only financial resources available are those of the entrepreneur. Even after years of successful activity, a wrong decision or a weakness in management can result in the end of the business.
In short, small businesses’ ability to innovate stems from their learning of the market, recognition of the need for rapid change, and organizational flexibility [20]. These valences are a support to the decision-making in the self-employment before the obtained feedback of the market.
\nIncubation of new businesses contributes to the creation of new businesses and, consequently, to economic and social development.
\nThe installation of incubators is a way of encouraging the creation of small businesses and recognition of their role in local economic dynamism in terms of job creation, the establishment of qualified young people, and the development of areas of sectorial and technological specialization [6].
\nIn this context, complementary instruments can be used to promote economic development (local, regional, and national), such as:
Professional training to meet the technical needs of the labor market
Entrepreneurial training leading to the emergence of new start-ups
Academic training in line with Government’s sectoral and regional bets
Creation of specialized university citadels, by technical-scientific areas, with the provision of all sociocultural, economic, and financial services inherent in business development
Creation of sectoral industrial parks
Launching public funding programs in conjunction with (i) technological parks, (ii) sectoral industrial parks, (iii) incubators, and (iv) universities (units/centers/research centers), in order to place academic research at the service of development and economic growth, in particular through its practical application to business and economic realities
In this respect, the following question may be raised:
\nWhat is the current added value for the economics emanating from academic papers published in specialty journals—for example, in terms of setting up start-ups, creating business and new products and services in incumbent companies, and penetrating new international markets or expansion in regional markets, increased efficiency, and business productivity?
\nTherefore, an integrated national structure (incubators, technological parks, sectoral industrial parks, and specialized university centers) will have to be implemented in order to propagate a climate conducive to the emergence of new, tangible ideas, on the one hand, in improving the competitiveness of established companies and, on the other hand, in creating new businesses.
\nThis work was partially supported by the Polytechnic Institute of Lisbon through the Projects for Research, Development, Innovation and Artistic Creation (IDI&CA), within the framework of the project IEOMAB—internationalization of companies operating in the Angolan and Brazilian markets, IPL/2019/IEOMAB_ISCAL.
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\\n\\nThe Author and Co-Authors also confirm and warrant that: (i) he/she has the power to enter into this Publication Agreement on his or her own behalf and on behalf of each Co-Author; and (ii) has the necessary rights and/or title in and to the Work to grant IntechOpen, on behalf of themselves and any Co-Author, the rights and licenses granted in this Publication Agreement. If the Work was prepared jointly by the Author and Co-Authors, the Author and Co-Authors confirm and warrant that: (i) all Co-Authors agree to the submission, license and publication of the Work on the terms of this Publication Agreement; and (ii) they have the authority to enter into this binding Publication Agreement on behalf of each Co-Author. The Author shall: (i) ensure each Co-Author complies with all relevant provisions of this Publication Agreement, including those relating to confidentiality, performance and standards, as if a party to this Publication Agreement; and (ii) remain primarily liable for all acts and/or omissions of each Co-Author.
\\n\\nThe Author agrees to indemnify IntechOpen for all liabilities, costs, expenses, damages and losses, as well as all reasonable legal costs and expenses suffered or incurred by IntechOpen arising out of, or in connection with, any breach of the agreed confirmations and warranties. This indemnity shall not apply in a situation in which a claim results from IntechOpen's negligence or willful misconduct.
\\n\\nNothing in this Publication Agreement shall have the effect of excluding or limiting any liability for death or personal injury caused by negligence or any other liability that cannot be excluded or limited by applicable law.
\\n\\nTERMINATION
\\n\\nIntechOpen has the right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including, without limitation: (i) if the Author and/or any Co-Author materially breaches this Publication Agreement; (ii) if the Author and/or any individual Co-Author is the subject of a bankruptcy petition, application or order; or (iii) if the Author and/or any corporate Co-Author commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for, or enters into, any compromise or arrangement with any of its creditors.
\\n\\nIn the event of termination, IntechOpen will notify the Author of the decision in writing.
\\n\\nINTECHOPEN’S DUTIES AND RIGHTS
\\n\\nUnless prevented from doing so by events beyond its reasonable control, IntechOpen, at its discretion, agrees to publish the Work attributing it to the Author and Co-Authors.
\\n\\nIntechOpen has the right to include/use the Author and Co-Authors´ names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion, and marketing of the Work and has the right to contact the Author and Co-Authors until, and while, the Work is publicly available on any platform owned and/or operated by IntechOpen.
\\n\\nIntechOpen is granted the authority to enforce the rights from this Publication Agreement on behalf of the Author and Co-Authors against third parties, for example in cases of plagiarism or copyright infringements. In respect of any such infringement or suspected infringement of the copyright in the Work, IntechOpen shall have absolute discretion in addressing any such infringement that is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the alleged infringer.
\\n\\nMISCELLANEOUS
\\n\\nFurther Assurance: The Author shall ensure that any relevant third party, including any Co-Author, shall execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of providing IntechOpen the full benefit of the provisions of this Publication Agreement.
\\n\\nThird Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
\\n\\nEntire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by or on behalf of the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (known as the "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of any fraudulent pre-contract misrepresentation or concealment.
\\n\\nWaiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement, or by law, shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
\\n\\nVariation: No variation of this Publication Agreement shall have effect unless it is in writing and signed by the parties, or by their duly authorized representatives.
\\n\\nSeverance: If any provision, or part-provision, of this Publication Agreement is, or becomes, invalid, illegal or unenforceable, it shall be deemed modified to the minimum extent necessary to make it valid, legal and enforceable. If such modification is not possible, the relevant provision or part-provision shall be deemed deleted.
\\n\\nAny modification to, or deletion of, a provision or part-provision under this clause shall not affect the validity and enforceability of the remainder of this Publication Agreement.
\\n\\nNo partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Author or any Co-Author, nor authorize any party to make or enter into any commitments for, or on behalf of, any other party.
\\n\\nGoverning law: This Publication Agreement and any dispute or claim, including non-contractual disputes or claims arising out of, or in connection with it, or its subject matter or formation, shall be governed by, and construed in accordance with, the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of, or in connection with, this Publication Agreement, including any non-contractual disputes or claims.
\\n\\nPolicy last updated: 2018-09-11
\\n"}]'},components:[{type:"htmlEditorComponent",content:'When submitting a manuscript, the Author is required to accept the Terms and Conditions set out in our Publication Agreement – Chapters below:
\n\nAUTHOR'S GRANT OF RIGHTS
\n\nSubject to the following Article, the Author grants, and shall ensure that each Co-Author grants, to IntechOpen during the full term of copyright, and any extensions or renewals of that term, the following rights:
\n\nThe foregoing licenses shall survive the expiry or termination of this Publication Agreement for any reason.
\n\nThe Author, on his or her own behalf and on behalf of any Co-Authors, reserves the following rights in the Work but agrees not to exercise them in such a way as to adversely affect IntechOpen's ability to utilize the full benefit of this Publication Agreement: (i) reprographic rights worldwide, other than those which subsist in the typographical arrangement of the Work as published by IntechOpen; and (ii) public lending rights arising under the Public Lending Right Act 1979, as amended from time to time, and any similar rights arising in any part of the world.
\n\nThe Author, and any Co-Author, confirms that they are, and will remain, a member of any applicable licensing and collecting society and any successor to that body responsible for administering royalties for the reprographic reproduction of copyright works.
\n\nSubject to the license granted above, copyright in the Work and all versions of it created during IntechOpen's editing process, including the published version is retained by the Author and any Co-Authors.
\n\nSubject to the license granted above, the Author and Co-Authors retain patent, trademark and other intellectual property rights to the Work.
\n\nAll rights granted to IntechOpen in this Article are assignable, sublicensable or otherwise transferrable to third parties without the specific approval of the Author or Co-Authors.
\n\nThe Author, on his or her own behalf and on behalf of any Co-Authors, will not assert any rights under the Copyright, Designs and Patents Act 1988 to object to derogatory treatment of the Work as a consequence of IntechOpen's changes to the Work arising from translation of it, corrections and edits for house style, removal of problematic material and other reasonable edits as determined by IntechOpen.
\n\nAUTHOR'S DUTIES
\n\nWhen distributing or re-publishing the Work, the Author agrees to credit the Publication in which the Work has been published as the source of first publication, as well as IntechOpen. The Author guarantees that Co-Authors will also credit the Publication in which the Work has been published as the source of first publication, as well as IntechOpen, when they are distributing or re-publishing the Work.
\n\nThe Author agrees to:
\n\nThe Author is responsible for the payment of the Open Access Publishing Fees.
\n\nAll payments shall be due 30 days from the date of issue of the invoice. The Author or whoever is paying on behalf of the Author and Co-Authors will bear all banking and similar charges incurred.
\n\nThe Author shall obtain in writing all consents necessary for the reproduction of any material in which a third-party right exists, including quotations, photographs and illustrations, in all editions of the Work worldwide for the full term of the above licenses, and shall provide to IntechOpen, at its request, the original copies of such consents for inspection or photocopies of such consents.
\n\nThe Author shall obtain written informed consent for publication from those who might recognize themselves or be identified by others, for example, from case reports or photographs.
\n\nThe Author shall respect confidentiality during and after the termination of this Agreement. The information contained in all correspondence and documents as part of the publishing activity between IntechOpen and the Authors and Co-Authors are confidential and are intended only for the recipients. The contents of any communication may not be disclosed publicly and are not intended for unauthorized use or distribution. Any use, disclosure, copying, or distribution is prohibited and may be unlawful.
\n\nAUTHOR'S WARRANTY
\n\nThe Author and Co-Authors confirm and warrant that the Work does not and will not breach any applicable law or the rights of any third party and, specifically, that the Work contains no matter that is defamatory or that infringes any literary or proprietary rights, intellectual property rights, or any rights of privacy.
\n\nThe Author and Co-Authors confirm and warrant that: (i) the Work is their original work and is not copied wholly or substantially from any other work or material or any other source; (ii) the Work has not been formally published in any other peer-reviewed journal or in a book or edited collection, and is not under consideration for any such publication; (iii) Authors and any applicable Co-Authors are qualifying persons under section 154 of the Copyright, Designs and Patents Act 1988; (iv) Authors and any applicable Co-Authors have not assigned, and will not during the term of this Publication Agreement, or purport to assign any of the rights granted to IntechOpen under this Publication Agreement; and (v) the rights granted by this Publication Agreement are free from any security interest, option, mortgage, charge or lien.
\n\nThe Author and Co-Authors also confirm and warrant that: (i) he/she has the power to enter into this Publication Agreement on his or her own behalf and on behalf of each Co-Author; and (ii) has the necessary rights and/or title in and to the Work to grant IntechOpen, on behalf of themselves and any Co-Author, the rights and licenses granted in this Publication Agreement. If the Work was prepared jointly by the Author and Co-Authors, the Author and Co-Authors confirm and warrant that: (i) all Co-Authors agree to the submission, license and publication of the Work on the terms of this Publication Agreement; and (ii) they have the authority to enter into this binding Publication Agreement on behalf of each Co-Author. The Author shall: (i) ensure each Co-Author complies with all relevant provisions of this Publication Agreement, including those relating to confidentiality, performance and standards, as if a party to this Publication Agreement; and (ii) remain primarily liable for all acts and/or omissions of each Co-Author.
\n\nThe Author agrees to indemnify IntechOpen for all liabilities, costs, expenses, damages and losses, as well as all reasonable legal costs and expenses suffered or incurred by IntechOpen arising out of, or in connection with, any breach of the agreed confirmations and warranties. This indemnity shall not apply in a situation in which a claim results from IntechOpen's negligence or willful misconduct.
\n\nNothing in this Publication Agreement shall have the effect of excluding or limiting any liability for death or personal injury caused by negligence or any other liability that cannot be excluded or limited by applicable law.
\n\nTERMINATION
\n\nIntechOpen has the right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including, without limitation: (i) if the Author and/or any Co-Author materially breaches this Publication Agreement; (ii) if the Author and/or any individual Co-Author is the subject of a bankruptcy petition, application or order; or (iii) if the Author and/or any corporate Co-Author commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for, or enters into, any compromise or arrangement with any of its creditors.
\n\nIn the event of termination, IntechOpen will notify the Author of the decision in writing.
\n\nINTECHOPEN’S DUTIES AND RIGHTS
\n\nUnless prevented from doing so by events beyond its reasonable control, IntechOpen, at its discretion, agrees to publish the Work attributing it to the Author and Co-Authors.
\n\nIntechOpen has the right to include/use the Author and Co-Authors´ names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion, and marketing of the Work and has the right to contact the Author and Co-Authors until, and while, the Work is publicly available on any platform owned and/or operated by IntechOpen.
\n\nIntechOpen is granted the authority to enforce the rights from this Publication Agreement on behalf of the Author and Co-Authors against third parties, for example in cases of plagiarism or copyright infringements. In respect of any such infringement or suspected infringement of the copyright in the Work, IntechOpen shall have absolute discretion in addressing any such infringement that is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the alleged infringer.
\n\nMISCELLANEOUS
\n\nFurther Assurance: The Author shall ensure that any relevant third party, including any Co-Author, shall execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of providing IntechOpen the full benefit of the provisions of this Publication Agreement.
\n\nThird Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
\n\nEntire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by or on behalf of the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (known as the "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of any fraudulent pre-contract misrepresentation or concealment.
\n\nWaiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement, or by law, shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
\n\nVariation: No variation of this Publication Agreement shall have effect unless it is in writing and signed by the parties, or by their duly authorized representatives.
\n\nSeverance: If any provision, or part-provision, of this Publication Agreement is, or becomes, invalid, illegal or unenforceable, it shall be deemed modified to the minimum extent necessary to make it valid, legal and enforceable. If such modification is not possible, the relevant provision or part-provision shall be deemed deleted.
\n\nAny modification to, or deletion of, a provision or part-provision under this clause shall not affect the validity and enforceability of the remainder of this Publication Agreement.
\n\nNo partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Author or any Co-Author, nor authorize any party to make or enter into any commitments for, or on behalf of, any other party.
\n\nGoverning law: This Publication Agreement and any dispute or claim, including non-contractual disputes or claims arising out of, or in connection with it, or its subject matter or formation, shall be governed by, and construed in accordance with, the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of, or in connection with, this Publication Agreement, including any non-contractual disputes or claims.
\n\nPolicy last updated: 2018-09-11
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