Plant Metabolites in Plant Defense Against Pathogens

3.1 The bioactive potential of secondary metabolites derived from the medicinal plant

Plants are formed by a primary metabolism that is responsible for the physiological processes and development of the plant, such as lipids, carbohydrates, and proteins [23]. The secondary metabolism is not essential in the basic processes of plants. However, these bioactive compounds play an important role in the defense of plants, and these secondary metabolites can be classified as phenolic compounds, carotenoids, terpenes, alkaloids, and sulfur compounds, among others, as shown in Table 1 [24].

Table 1.

Types of plant secondary metabolites.

Phenolic compounds are aromatic substances formed during the passage of the shikimic acid pathway or mainly the mevalonic pathway. These can be divided into insoluble compounds such as condensed tannins, lignins, and hydroxamic acids bound to the cell walls, and soluble compounds are phenolic acids, flavonoids, and kinases [25]. Carotenoids are lipophilic molecules and are found in plants giving orange tones. The importance of these compounds is the intervention they have in photosynthesis, and they also protect the photosynthetic apparatus from excess energy [25]. The carotenoid contents in plants are affected by various factors, such as plant development, stress conditions, postharvest conditions, or cooking treatments, but the interest of these compounds has been increasing due to their potential antioxidant activity [26]. Terpenes are lipid-soluble compounds that include one- or more five-carbon isoprene units, which are synthesized by all organisms through two pathways, mevalonate and deoxy-D-xylulose [27]. Terpenoids are classified according to the number of isoprene units they contain; terpenes and terpenoids are basic constituents of many types of plant essential oils [28]. Alkaloids are bioactive compounds that generally contain nitrogen derived from an amino acid of great importance because it has physiological and medicinal properties, for example, caffeine, nicotine, morphine, atropine, and quinine [29].

Now well, all these compounds mentioned above help the plants to develop complex defense systems against different types of stress for the survival or the systematic forces in their metabolism for resistance against pests and diseases. Stress provoked in the plant involves several signaling response pathways for pathogens and insects, and some of these response pathways are induced by the microorganisms themselves. Also, the plants have specific recognition and signaling systems allowing them to detect the pathogens and initiate an effective defense response [30, 31]. The defence system broadest have the plants against pathogens are the phenolic compounds (phenylpropanoids and flavonoids). These substances have different mechanisms of action they can dissociate the ions of the phenolic hydroxyl and forming phenolates, ionic and hydrogen bonds with peptides and proteins causing a high astringency and protein denaturation. In the other hand, they interfere with the pathogen's cell signalling compounds and affect their physiological activities through enzymatic inhibition, DNA alkylation and altering their reproductive system [31]. The compounds with allelopathic effects affect positively or negatively on the ecosystem’s structure to remove or eliminate microorganisms from the plants. Some phenolic compounds are allelochemicals that have been shown to have an activity as antibiotics, antifungals, and antipredator [31]. Phenolic acids, such as benzoic, hydroxybenzoic, vanillic, and caffeic, have antimicrobial and antifungal properties produced by the inhibition of enzymes. Caffeic, chlorogenic, sinapic, ferulic, and p-coumaric acids have antioxidant activity by the inhibition of oxidation of lipids and the elimination of reactive oxygen species. These effects are important to the plant defense [32].

3.2 Improving production of plant secondary metabolites through biotic and abiotic stresses

Classification of secondary metabolites related to the defense of plants is commonly used in the form of synthesis and accumulation of phytochemicals with interaction effect of the pathogenic plant against plant insect, virus, fungi, and antibacterial compounds. For example, phytoalexins are produced very quickly after infection of a pathogen producing toxicity to an ambiguous environment of fungi or bacteria [33, 34].

Phenylpropanoids and flavonoids have hydroxyl groups that contain phenolic compounds, which dissociate into phenolate ions, and the phenolic hydroxyl groups form ionic bonds and hydrogen bonds with peptides and protons, producing a high astringency and denaturation that thus show an antifungal effect acting together with cellular signaling compounds and physiological activities or acting on the parts of the pathogen, reproductive system, enzymatic inhibition, etc. [35]. The properties of the proteins change with any change in protein conformation, for example, by changing the three-dimensional structure forming covalent bonds with SH, OH or free amino groups there is inactivation or protein function loss. When polyphenols of the plants bind to some proteins of phytopathogens are less toxic for them but can protect the plant of abiotic elicitors [36]. On the other hand, phytoalexins are induced against the attack of microbes and insects activated by β-glucosidase by the release of biocidal aglycones [37]. In the same way act the benzoxazinoids (BX), these phytochemical compounds are produced and released by tissue damage and hydrolysis by β-glucosidase and act as insect repellents too [38].

At present, several biotechnological strategies have been used to increase the productivity of secondary metabolites, using different inducers of secondary metabolites such as at the cellular, organic, and plant levels, as well as the most effective methods to improve the synthesis of these secondary metabolites in endemic and medicinal plants [39]. These secondary metabolites accumulate in plants when they are prone to various stress types, inducers, or signal molecules. Thus, there are different modulating factors of secondary metabolites, as well as microbial, physical, or chemical effects such as abiotic or biotic elicitors, inducing the biosynthesis of specific compound that plays an important role in the adaptations of plants to stress conditions, and these phenomena cause a greater synthesis and accumulation of secondary metabolites [40]. In Table 2 the authors focus on the abiotic elicitors that are substances of biological origin such as proteins and carbohydrates that are initiator compounds or coupling responses at the cellular level activating several enzymes or signaling canals. There are also microorganisms and chemical compounds with elicitor effect that stress the plant and produce the expression of a greater amount of metabolites or new metabolites which cause physiological changes in the plant against pathogens. As shown in Table 2, glycoprotein-type proteins produce phytoalexins that have been used to identify ion channels in cell membranes and thus transfer signals by external stimuli, as demonstrated by Alami [41] where the Plantanus x acerifolia cultures were applied to an inducer of Ceratocystis fimbriata f. sp. These, in turn, induced the synthesis of phytoalexins (hydroxycoumarin, scopoletin, and umbelliferone), and upon isolating the glycoprotein produced the synthesis of coumarin by 80%. On the other hand, oligogalacturonic acids are found in the cell wall of the plant inducing the biosynthesis of phytoalexins, whereas chitin is found in the cell wall of fungi, generating signaling factors in plants such as Hypericum perforatum production stress in the plant and increasing the production of phenolic compounds for their defense against pathogens [39, 42]. Rhizobacteria function as modelers of secondary metabolites with pharmacological activity. Rhizobacteria colonize the rhizospheres of the plants and improve the growth of the plant, being localized in the bark or root nodules acting as inducers of the enzymes that participate in the metabolic pathways of bioactive compounds and jasmonic acid biosynthesis; these act as signal transducers [43, 44]. Other signal inducers are the mycorrhizal fungi that help the plant to absorb more water and show defense against other pathogens such as fungi, bacteria, or parasites that affect the roots of the plant. These mycorrhizal fungi produce secondary metabolites such as phenolic compounds and alkaloids, among others [45, 46, 47, 48]. Elicitors such as salicylic acid, jasmonic acid, hydrogen peroxide, chitosan, etc. act as plant hormones in the expression of genes interacting as target signaling causing a physiological response in the plant which increases the production of phenolic compounds, vitamin C, carotenoids, or defense stimuli against pathogens; there are also synergistic effects between salicylic acid and jasmonic acid providing resistance against pathogens by the induction of the octadecanoic acid pathway [49, 50, 51, 52, 53].

Table 2.

Effect of biotic elicitor on the production of various secondary metabolites in plants [54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64].

On the other hand, Table 3 shows some research that has the influence of different abiotic elicitors that are considered substance and that are not of biological origin such as salt, drought, light or heavy metals, and temperature, among others. Table 3 shows different perspectives of research on medicinal or aromatic plants in hydroponic crops, outdoors, and the application of elicitors in different stages of growth or postharvest. For example, heavy metals such as Al³⁺, Cr³⁺, Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺, and Cd²⁺, among others, are considered high toxicity compounds depending on the concentrations applied in the sprinkler system or because they are used as biocontrol since they alter the production of metabolites in plants. Similarly, Zobayed [65] demonstrated that the temperature in high concentrations in Panax quinqufolius improves the senescence of the leaves and produces a greater quantity of bioactive compounds in the root of the plant. So the investigations using high or low temperatures demonstrate the production of secondary metabolites, but the temperatures that have been investigated the most are the low producing physiological changes in the plant, increasing the lignification by the production of suberin in the cell wall and the metabolites such as sorbitol, raffinose, proline, melatonin, anthocyanins, etc. However, light by means of ultraviolet radiations generates the production of essential oils and phenolic compounds and decreases the production of toxic compounds in some plants [66]. On the other hand, salinity and drought produce death leading to cellular dehydration or osmotic stress and in certain concentrations can reduce the growth or development of plants but alter many physiological and metabolic processes that stimulate the production of polyphenolic compounds, anthocyanins, terpenes, and alkaloids, among others. Salinity can be produced in plants by ionic or osmotic means and drought by environmental or intentional changes due to water deficit which are always accompanied by temperature or solar radiation [67, 68, 69]. Then we can say that the biotic and abiotic factors are modular secondary metabolites influencing the metabolic level and the production of secondary metabolites. Therefore, the current research focuses on the use of elicitors, for the regulation of metabolic pathways, and target signaling in genes that influence the overproduction of secondary metabolites using various applications but taking care of the production performance of fruits, vegetables, or different plants.

Table 3.

Effect of abiotic elicitor on the production of various secondary metabolites in plants [70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81].

Recent studies focused on evaluating the secondary metabolites of medicinal plants that are active against phytopathogens show that the potential use that these compounds can have in the future is for the control of phytopathogenic fungi, mainly against different species of Fusarium [14, 15, 16]. In this regard, the most active compounds have been found mainly in the essential oil obtained from the aerial parts of various medicinal plants, which suggests that the bioactive compounds are liposoluble; this may explain why they are active mainly against fungi, because the cell wall of these specimens are composed mainly of ergosterol, the active liposoluble compounds present in the essential oil to easily cross the cell wall of the fungus and in the interior act on their cell target, or they can alter the permeability of the wall of the fungus [82]. It can cause rupture and lysis of the fungal cell; however, it is necessary to study the toxicodynamics of these substances in order for them to know how to act in the fungi cell. On the other hand, the antifungal activity has been evaluated in vitro, by the agar diffusion and microdilution method; in general terms the range of the evaluated IC50 varies in a range that goes from 0.0035 to 8 mg/ml of the extract. It is important to mention that one of the main limitations of these studies is that this activity has only been evaluated at the laboratory level [83, 84, 85]. Table 4 shows different types of extracts made with medicinal plants, and their biological activity reported in vitro tests at the laboratory level.

Table 4.

Secondary metabolites of medicinal plants with biological activity against phytopathogens [86, 87, 88, 89, 90, 91, 92, 93, 94].

Finally, in the realization of a retrospective of the secondary metabolite modulating factors in our workgroup, Garcia-Mier [95] demonstrated that the use of mixtures of elicitors such as jasmonic acid, hydrogen peroxide, and chitosan in different concentrations applied in various stages of plant development of the sweet bell red pepper and in different stages of ripening of the fruit has a positive effect on the increase of polyphenolic and carotenoid compounds, where the results showed that the maturation stage of 95% produces a greater quantity of bioactive compounds. On the other hand, Vargas-Hernández [96] demonstrated that the foliar application of hydrogen peroxide in Capsicum chinense Jacq. has an effect on the antimicrobial activity, where the different concentrations of hydrogen peroxide potentiated the production of secondary metabolites such as flavonoids, capsaicin, and dihydrocapsaicin, where these metabolites had an effect on microorganisms such as Staphylococcus aureus, Escherichia coli, Streptococcus mutant, Salmonella thompson, Listeria monocytogenes, Streptococcus faecalis, and Candida albicans, and the results showed that the application of hydrogen peroxide increases the inhibitory effect against pathogenic microorganisms, showing greater activity against S. aureus, S. Thompson, and C. albicans in the jaguar variety, while the variety Chichen-Itza was more potent against E. faecalis and E. coli. Also, Zunun-Pérez [97] evaluated the effect of modulating factors of secondary metabolites by spray application that is performed in Capsicum annuum L. in weekly applications and 1 day before collection with elicitors such as hydrogen peroxide, salicylic acid, and oligosaccharide of xyloglucan on capsiate concentration and the expression of genes such as phenylalanine ammonia-lyase, aminotransferase, capsaicin synthase, and β-keto acyl synthase where the results showed that hydrogen peroxide in weekly applications significantly increases capsiate concentrations and gene expression and the yields of the production of the plant are not affected by the application of these elicitors.