Читать книгу Secondary Metabolites of Medicinal Plants - Bharat Singh - Страница 7

Traditional system of medicine is also known as indigenous medicine system used to maintain our health and to diagnose and treat several complaints based on theories, beliefs, and family experiences. The indigenous system of medicine has been in practice since the last thousands of years; contributions from community practitioners have maintained their popularity at a global level (Sofowora 1982). The traditional knowledge of plants could be attributed to acceptability, affordability, pleasant feeling, and affectivity against any type of disease as compared with modern medicine (Giday et al. 2003; Tolossa et al. 2013). In the case of traditional medicine, the knowledge is transferred from the elders to the younger generation verbally or by just showing the growing plants in the open fields. Several studies have revealed that transfer of medicinal knowledge of plants to the coming generations is adversely affected by development of modern medicine. The interest of younger generation to traditional knowledge is diminishing day by day (Yineger and Yewhalaw 2007). The wide acceptance of indigenous medicine and limited approach to modern healthcare facilities could be considered as main reasons for the continuation of the traditional practices. The documentation of traditional knowledge can be used to support human healthcare system to maintain healthy lives. The documented information will be used in future course of studies to validate biological and pharmacological activities as exhibited by medicinal plants; therefore it is an urgent need of modern time to enhance the affordability and acceptability of plants in rural and modern healthcare systems (Demie et al. 2018).

The secondary metabolites are not considered as energy sources at the cellular level but play important roles in the interaction of plants with surrounding environment. They protect the plants from abiotic (high temperature, drought) and biotic (bacteria, fungi, insects, nematodes) stresses. On the other hand, the secondary metabolites contribute in systematic determination, used as markers in the classification of plants. The biosynthesis of secondary metabolites is organ and individual specific and in low molecular weight compounds. Similarly, the primary metabolites are useful in performing various metabolic activities for growth and development in plants (Piel 2010; Pagare et al. 2015). The secondary metabolites are used as bioactive compounds for the treatment of various diseases. These secondary metabolites can be grouped into three classes based on their biosynthetic pathways, viz. terpenoids, polyketides, and phenylpropanoid (Verpoorte and Alfermann 2000). The alkaloids are nitrogenous molecules, synthesized by amino acids, viz. tyrosine, phenylalanine, and lysine, by using various enzymes (Croteau et al. 2000). Some secondary metabolites (anthocyanins, anthocyanidins, carotenoids, and flavonoids) have specific roles in pollination and seed dispersal; hence, they are involved in reproduction cycles of plants (Winkel-Shirley 2001). Plant-derived secondary metabolites have made an important contribution in the treatment of various diseases including cancer, infections, and inflammations. The immunomodulatory vaccines (edible vaccines) have been obtained from plant sources and are exploring clinically for treatment of viral infections (Woods et al. 2017). Secondary metabolites in plants can be divided into the following chemically defined groups: terpenes, phenolics, nitrogen, and sulfur compounds.

The terpenoids constitute the largest class of natural products, and many interesting products are extensively applied in the industrial sector as flavors, fragrances, and spices and are also used in perfumery and cosmetics. Many terpenoids have biological activities and are also used for medical purposes. In higher plants, the conventional acetate–mevalonic acid pathway operates mainly in the cytosol and mitochondria and synthesizes sterols, sesquiterpenes, and ubiquinones mainly. In the plastid, the non-mevalonic acid pathway takes place and synthesizes hemi-, mono-, sesqui-, and diterpenes along with carotenoids and phytol tail of chlorophyll. The monoterpenes are widely distributed natural products found in herbs, spices, citrus, conifers, and most flowers and fruits. These are C10, short chain compounds, normally found in combination with sesquiterpenes, that play many significant roles, viz. antimicrobial, insect repellant, and pollinator attractants (Davis 2010). Iridoids are characterized by skeletons – in which a six-membered ring, containing an oxygen atom, is combined to an iridane skeleton – and are found in plants combined with sugar as glycosides. The iridoids are classified as iridoid glycosides (aucubin, harpagoside), nonglycosylated iridoids (loganin), secoiridoids (gentiopicroside), and bisiridoids, developed by dimerization of iridoids and secoiridoids (Ludwiczuk et al. 2017). Sesquiterpenes (C15) are less volatile than monoterpenes but have more potential for stereochemical diversities and odors and possess anti-inflammatory and antimicrobial properties (Buckle, 2015). The seed maintenance and bud dormancy are regulated by abscisic acid (sesquiterpene), and it also responded positively to water stress by modifying the properties of cell membrane (Berli et al. 2010). Triterpenoids are widely distributed in plants often accumulated in their glycosylated form. Saponins comprise hydrophobic triterpenoid aglycones called sapogenin and one or more hydrophilic sugar moieties. The triterpenoids possess antimicrobial and anti-inflammatory activities (Vincken et al. 2007).

The phenolic compounds are aromatic benzene ring molecules synthesized by plants mainly as protection against biotic and abiotic stresses (Robles-Sanchez et al. 2009; Velderrain-Rodríguez et al. 2014). These compounds provide structural integrity and scaffolding support to plants. The plant phytoalexins released from wounded sites help in repelling or killing many microbes (Bhattacharya et al. 2010). The phenolic compounds are widely occurred in the plant kingdom, especially contributing color, flavor, and astringency to flowers and fruits. The accumulation of phenolic compounds may vary from 0.3 to 5.0 g/100 g dry weight of a plant material. These compounds are considered to be by-products of the metabolism of the aromatic amino acid phenylalanine (Swanson 2003). The phenolic compounds are synthesized in plants by two biosynthetic pathways, viz. shikimic acid and pentose phosphate, through phenylpropanoid (Randhir et al. 2004). The glucose moves to pentose phosphate pathway by converting glucose-6-phosphate irreversibly to ribulose-5-phosphate. The reaction catalyzed by glucose-6-phosphate dehydrogenase. In the second pathway, erythrose-4-phosphate along with phosphoenolpyruvate is used for the phenylpropanoid pathway to synthesize phenolic molecules after being channeled to the shikimic acid pathway to produce phenylalanine (Vattem et al. 2005; Lin et al. 2010, 2016). Some coumarins and their derivatives have significant antifungal activity against several soilborne fungi and demonstrate higher stability than original coumarin compounds. Furanocoumarins are found in Umbelliferae members known for their use in the treatment of fungal diseases in plants (Brooker et al. 2008; Ali et al. 2008). The flavonoids are chemically polyphenolic in nature and occur in fruits, flowers, and vegetables (Burak and Imen 1999) and have miscellaneous favorable antioxidative effects associated with various diseases such as cancer, Alzheimer's disease, atherosclerosis, etc. (Castañeda-Ovando et al. 2009). They are also associated with a broad spectrum of health-promoting effects and are indispensable constituents in various nutraceutical, pharmaceutical, medicinal, and cosmetic products (Lee et al. 2009).

The quinones are a group of compounds occur in several plant species and are synthesized via the shikimate or polyketide pathways (Scott Obach and Kalgutkar 2010). The benzoquinones, naphthoquinones, and anthraquinones are found in higher plant species. Till today, nearly 600 quinones have been identified from various plant families, viz. Rubiaceae (Harborne 1982). These compounds are cyclic α,β-diketones, which can be converted by reduction into hydroquinones (Morrison and Boyd 1973). The oxidized form of conjugated quinones are colorful (yellow color) like p-benzoquinone, while reduced forms are colorless. By fusing the second aromatic ring with benzoquinone, the naphthaquinones are formed. Similarly, if both sides of benzoquinone fused with aromatic ring, then the formed molecule is called as anthraquinone. The many quinones are biosynthesized by acetate–malonate pathways, some from shikimic acid pathways, while few are generated by oxidative modification of secondary metabolites from a variety of other pathways (Seigler 1998).

The nitrogen-containing natural products include alkaloids, cyanogenic glucosides, and amino acids. The alkaloids are generally bicyclic, tricyclic, or tetracyclic derivatives of the molecule quinolizidine. The alkaloids are biosynthesized by amino acids (lysine, tyrosine, and tryptophan) and approximately found in 20% plant species of the plant kingdom (Glencross 2016). More than 12 000 alkaloids have been identified from 150 families of plants; alkaloids generally exist as salts of organic acids like acetic acid, malic acid, lactic acid, citric acid, oxalic acid, tartaric acid, tannic acid, and other acids. Some alkaloids are weak and basic in nature while few occur in glycosidic forms as solanine, piperine, and atropine. The alkaloids are used as pharmaceuticals, narcotics, and stimulants (morphine, quinine, codeine, etc.), and their lower doses are pharmacologically significant, while their higher doses may be toxic such as strychnine, nicotine, etc. (Richard et al. 2013). The alkaloids are very complex in their structure; they can be classified on the basis of set of parameters including features of their structure and pathways of biogenesis. They can be grouped as follows (Hussain et al. 2018): pyridine group (piperine, coniine, trigonelline, arecoline, arecaidine, guvacine, cytisine, lobeline, nicotine, anabasine, sparteine, pelletierine), pyrrolidine group (hygrine, cuscohygrine, nicotine), tropane group (atropine, cocaine, ecgonine, scopolamine, catuabine), indolizidine group (senecionine, swainsonine), quinoline group (quinine, quinidine, dihydroquinine, dihydroquinidine, strychnine, brucine, veratrine, cevadine), isoquinoline group (papaverine, narcotine, narceine, pancratistatin, sanguinarine, hydrastine, berberine, emetine, berbamine, oxyacanthine), phenanthrene alkaloids (morphine, codeine, thebaine, oripavine), phenethylamine group (mescaline, ephedrine, dopamine), indole group (serotonin, bufotenine, psilocybin, ergine, ergotamine, lysergic acid), β-carbolines (harmine, harmaline, tetrahydroharmine), yohimbans (reserpine, yohimbine), vinca alkaloids (vinblastine, vincristine), kratom alkaloids (mitragynine, 7-hydroxymitragynine), tabernanthe iboga (ibogaine, voacangine, coronaridine), strychnos nux-vomica (strychnine, brucine), purine group (xanthines, caffeine, theobromine, theophylline), terpenoid group (aconitine, solanidine, solanine, chaconine), and veratrum alkaloids (veratramine, cyclopamine, cycloposine, jervine, muldamine). The secondary metabolites are biosynthesized by three main pathways in plants – the shikimate pathway, the isoprenoid pathway, and the polyketide pathway. The shikimic acid pathway is the major pathway for synthesis of aromatic compounds. This pathway occurs in plants, normally manipulated for targeting the affectivity of antibiotics and herbicides, because this pathway does not occur in animals. The biological reaction of conversion of chorismate into the aromatic amino acids in plants catalyzed by chorismate mutase and anthranilate synthase enzymes. The phenylpropanoid pathway is followed by 20% of plants; the chorismate mutase is a key enzyme that regulates the whole reactions. The important compounds as lignans, alkaloids, flavonoids, and anthocyanins are synthesized by this pathway. The phenylalanine converts to trans-cinnamic acid by a non-oxidative deamination and the biochemical reaction catalyzed by phenylalanine ammonia lyase. The isoprenoid pathway is known for synthesis of terpenoids (Behenna et al. 2008; Brooker et al. 2008; da Rocha 2013).

Normally the secondary metabolites of medicinal importance are obtained from their respective plants by growing in the open fields or in green houses. The secondary metabolites extracted from the plant tissues but day by day, so many plant species are getting extinct. Similarly, the relative yield of secondary metabolites from plants is also low. In this context, the cell culture techniques may be explored as an alternative source for increasing the productivity of secondary metabolites (Kirakosyan and Kaufman 2002). The plant cell culture technology is more economically feasible in production of high-value secondary metabolites (paclitaxel, shikonin, atropine, etc.) from rare and/or threatened plants. The formation of valuable products in callus cultures can be optimized by developing suitable bioreactor configurations (e.g. disposable reactors) and the optimization of bioreactor culture environments for improvement yields and bioreactor operational modes (Georgiev et al. 2009). The hairy roots are developed by infection of wounded plants with Agrobacterium rhizogenes, which causes neoplastic growth by culturing transformed roots in hormone-free culture medium. The hairy roots produce higher amounts of valuable product than control roots (Pistelli et al. 2010). The accumulation of polysaccharides and phenolic compounds was threefold higher in hairy transformed roots of Echinacea purpurea than non-transformed roots (Wang et al. 2006). By application of genetic engineering, the Atropa belladonna plants were transformed to encode the enzymes converting L-hyoscyamine into L-scopolamine, and new plants were generated, which produced scopolamine as the major product (Liu et al. 2010; Zhang et al. 2004). Several research papers have already been published on genetic engineering of pharmaceutically important tropane alkaloids (Oksman-Caldentey and Arroo 2000). Therefore, plant cell manipulations can be used efficiently used in increasing the productivity of valuable secondary metabolites.