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.
2.1 Abutilon Species
2.1.1 Ethnopharmacological Properties and Phytochemistry
Abutilon indicum L. (Fam. – Malvaceae) aerial parts and roots have been used for treating inflammations, ulcer, diarrhea, pains, stomach ailments, diabetes, and wounds (Jayaweera 2006; Khare 2010; Ushakumari et al. 2012). Traditional practitioners used the plant to treat diseases like gout, tuberculosis, ulcer, jaundice, leprosy, gonorrhea, bronchitis, lumbago malarial fever, piles, dental problems, and other bleeding disorders (Algesaboopathi 1994; Yoganarsimha 2000; Muthu et al. 2006; Nisha and Rajeshkumar 2010). The grounded leaves of this plant species mixed with wheat flour are used for treating uterus in Indian system of medicine (Mohapatra and Sahoo 2008). There are reports of topical application of leaf paste on the spot of scorpion bite to relieve pain (Dinesh et al. 2013). Flowers of this plant are used by tribal population in Southern India to increase the concentration of semen in men (Ramachandran 2008). Abutilon indicum is found in tropical and subtropical regions of India–China and has therapeutic uses as febrifuge, anthelmintic, antiemetic, and anti-inflammatory and in urinary and uterine discharges, piles, and lumbago (Nadkarni 1954; Chopra et al. 1958; Subramanian and Nair 1972; Badami, et al. 1975; Gaind and Chopra 1976). Seeds are used in a decoction to treat cough (Yasmin et al. 2008). Ethyl acetate fraction of Abutilon grandiflorum showed antimalarial activity (Beha et al. 2004). A. indicum demonstrated hypoglycemic (Seetharam et al. 2002), anxiolytic (Tirumalasetty et al. 2011), antiulcer (Malgi et al. 2009), hepatoprotective (Porchezhian and Ansari 2005), antimicrobial (Poonkothai 2006; Edupuganti et al. 2015), anticonvulsant (Golwala et al. 2010), antidiarrheal (Chandrashekhar et al. 2004), antioxidant (Yasmin et al. 2010), antimicrobial, and anti-inflammatory (Tripathi et al. 2012; Kaladhar et al. 2014) activities (Abat et al. 2017).
Gossyptin-7-glucoside, cyanidin-3-rutinoside, alantolactone and isoalantolactone, gossypetin-8-glucoside (Subramanian and Nair 1972; Sharma and Ahmad 1989), β-sitosterol, fatty acid esters of stearic and palmitic acid and flavonoids (Yasmin et al. 2008), β-amyrin 3-palmitate, squalene, β-sitosterol and stigmasterol (Macabeo and Lee 2014), fumaric acid, caryophyllene, caryophyllene oxide, geraniol, elemene, methyl indole-3-carboxylate, hinesol, cubenol, phytol, γ-sitosterol, lupeol, palmitic acid, 1-lycoperodine, 1-methoxycarbonyl-β-carboline, tetracontane, n-tetracosane, 3-hydroxy-β-damascone, 3-hydroxy-β-ionol, scopoletin, scoparone, methyl coumarate, trans-p-coumaric acid, abutilon A, quercetin, eugenol (4-allyl-2-methoxyphenol), syringic acid, benzoic acid, vanillic acid, gallic acid, N-feruloyl tyrosine, caffeic acid, p-β-D-glucosyloxybenzoic acid, 4-hydroxy-3-methoxy-trans-cinnamic acid methyl ester, methyl caffeate, p-hydroxybenzaldehyde, vanillin, syringaldehyde, 4-hydroxyacetophenone, methylparaben, β-sitosterol, stigmasterol, (R)-N-(10-methoxycarbonyl-20-phenylethyl)-4-hydroxybenzamide, p-β-D-glucosyloxybenzoic acid, p-hydroxybenzoic acid, and caffeic acid were identified