Open access peer-reviewed chapter

Modulation of Secondary Metabolites among Mexican Medicinal Plants by Using Elicitors and Biotechnology Techniques

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María Adelina Jiménez-Arellanes and Mariana Z. Pérez-González

Submitted: February 23rd, 2021Reviewed: August 11th, 2021Published: September 10th, 2021

DOI: 10.5772/intechopen.99888

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Abstract

Medicinal plants are being utilized as raw material and the use has increased in recent decades due that these biosynthesize compounds with several pharmacological activities. Some plant species with biological potential are of interest to the industry for preparation of drugs, phytodrugs, or food supplements. This causes overexploitation and deforestation, which endangers plant species-of-interest. In recent years, alternatives have been sought to eradicate this problem. A solution that was give and is maintained is plant biotechnology, which favors the production of active Secondary Metabolites (SMt). Plant biotechnology allows us to increase the yield of a compound-of-interest, reduces its production times and costs, and allows constant and controlled production of the raw material, and while aiding in the protection of medicinal plants that are found in danger of extinction. In the scientific literature, procuring the SMt by means of biotechnological processes is described, highlighting the study of four species from Mexican traditional medicine (Lopezia racemosa, Galphimia glauca, Cnidoscolus chayamansa, Sphaeralceae angustifolia and Buddleja cordata), and the main biological activities are as follows: anti-inflammatory, hepatoprotector, neuroprotector, anxiolytic, antitumoral, antibacterial, and antioxidant, among others.

Keywords

  • Elicitors
  • biotechnology
  • Mexican medicinal plants
  • plant tissue culture
  • secondary metabolites
  • phenolic compounds

1. Introduction

Ever since our ancestors, humanity has been dependent on the consumption of plants as a source of food, health, and for construction/ornamental. In addition, plants have developed a complex defense system against biotic and antibiotic stress: therefore, they can produce diverse secondary metabolites (SMt). The stress to which plants are submitted under natural conditions is caused by different factors, among which stand out: attack by diverse insects and/or microorganisms (viruses, bacteria, and fungi) competition for soil, light, and nutrients, and exposure to sunlight [1].

SMt are compounds that do not play a fundamental role in the vital processes of plants, but they are important as mechanisms of defense. They are responsible for organoleptic and protective properties, such as odor, flavor, color, and consistency. These SMt also act as chemoattractants or chemorepellents. In addition, they are of great interest in industry for the preparation of food additives, agrochemicals, essences, biodiesel, narcotics, insecticides, cosmetics, and aromatics, and one of the most important of these is for the production of substances with pharmaceutical interest. Frequently, the production of SMt wild-collected plant is very low (less than 1% of the plant’s Dry Weight -DW-), and this depends specifically on the plant’s physiological state, the geographic location, the climate, among other factors [2].

Due to the low yield of SMt in wild plants and considering its important biological activity, alternatives or tools are currently being sought to increase its yield. One of these alternatives is the application of several biotechnology processes, a discipline that is oriented toward the development and innovation of technologies that involve the management of biological material for the production of a good or service [3].

One of the advantages in the use of biotechnological processes is to increase the production of bioactive SMt and also reduce the production time, which favors their availability [4]. The purpose of this paper is to summarize all the information that exists on the use of biotechnological processes for the production of bioactive compounds from Mexican medicinal plants.

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2. Products with pharmaceutical importance

Plants constitute a huge reservoir of chemical structures, the most economically important are medicinal plants, due to their diverse biological activities; which over the years have favored human survival thanks to their use in Traditional Medicine (TM) [5, 6, 7]. TM is widely used in some developing countries, where their health system is still growing and is of great economic importance. In Africa, up to 80% of the population employs TM to help satisfy its health needs. In Asia and in Latin America, the populations continue to use TM because of historical circumstances and cultural beliefs. In China, TM is of great importance due to the large percentage of population that utilizes it, being higher than 60%. In some developed countries, the percentage of the population that uses TM is 48% in Australia, 70% in Canada, 42% in the USA, 38% in Belgium and 75% in France [8].

Currently, Medicinal Plants (MP) are employed by 80% of the world population; therefore, these are overexploited not only because are source of active ingredients, also due to the high nutritional, wood, cosmetic, agricultural, and/or medicinal value that many of these have. For example, it is estimate that China exports 120,000 tons of MP and India, some 32,000 tons while Europe imports 400,000 tons of MP. This leads to overexploitation of the species and many of them are in danger of extinction [9, 10].

The World Conservation Union and the World Nature Fund report that there are between 350,000 and 550,000 species of MP in the world, of which only approximately 20% possess documented investigation of their biological potential, and nearly 15,000 species are in danger of extinction due to the overexploitation and destruction of habitats [10, 11].

Nowadays, scientific interest in MP has increased due to the high costs and adverse effects that allopathic drugs cause, in addition to the increasing appearance of strains of microorganisms that are resistant to current treatments [12, 13, 14]. It is noteworthy that almost 25% of the active principles of allopathic drugs currently used were isolated and/or semisynthesized from plants [9]. In modern medicine, digoxin is use as a cardiotonic and was isolated from Digitalis purpurea(purpura, its common name); escin is use as an anti-inflammatory and venotonic and was isolated from Aesculus hippocastanum(its common name, horse chestnut). Another compound utilized is ajmalicin, employed for circulatory disorders, and was isolated from Rauwolfia serpentina; paclitaxel (an anticancer drug) has been semisynthesized by Bristol-Myers Squibb since 2002, and was obtained from the compound 10-deacetylbacatin III, it was obtained from the cell suspension of the Taxus baccata.While diosgenin, a steroidal sapogenin, was obtained from the tubercules of several Dioscoreaspecies, which was the raw material for the semisynthesis of progesterone [15].

Guanidine is a natural product with good hypoglycemic activity that was isolated from Galega officinalis(L); however, this compound has been reported to be toxic for human consumption. Therefore, this compound was semi-synthesized obtaining metformin (dimethylbiguanide), which is less toxic and has a pharmacologic effect similar to the original molecule and is widely used for the treatment of type II diabetes mellitus. It is worth noting, due to the high demand for SMt on the market; several companies have seen the need to discover novel sources of raw material from MP [16].

On the other hand, at present, the use of medicinal plants and/or phytodrugs is very frequent. The phytodrugs are elaborate with plant material and some derivatives of this. The main ingredient is the aerial or subterranean plant’s part; as well as extracts, tinctures, juices, resins, fatty acids, and essential oils presented in pharmaceutical form. The therapeutic effectiveness and safety have been confirmed scientifically [17]. Some examples of these include ginseng, it is obtained from Panax genus (Panax ginsengand P. quinquefolium) native from Asia and America, respectively. The main biological effect of ginseng “tonic” phytodrug is that it possesses the ability to increase the capacity to tolerate tensions, which leads to increased mental and physical yield. Another phytodrug obtained from St. John’s wort (Hypericum perforatum) is Hiperikan, which is standardized based on its content of hypericin; its principal pharmaceutical use is against depression. Ginkgo biloba(Ginkgo) belongs to the Ginkgoaceae family, the active compounds in the leaf’s extracts are gingolides (gingolides A-C, J, and M), along with a mix of sesquiterpene lactones and flavonoids which is used against depression. The majority of commercial preparations from Ginkgo are standardize with approximately 5–7% of terpenic lactones and 22–27% of flavonoids and they are employed mainly for the treatment of the cognitive deterioration associated with alterations in blood circulation in the brain, such as dementia. The phytodrug elaborated with Echinacea purpureais commercially known as EchinaCold (Schwabe Pharma) or Immulone (ATOS Pharma). These are standardized on based of the echinacosides (caffeic acid derivative) content, whose main biological effect is as an immunostimulant [18]. In Oceania region, the extract from Piper methysticum(from root and rhizome) has the commercial name Kava-kava (with 30% of kava lactones), and is utilized for their neurotransmitter activity [19]. Another phytodrug is Vitango, obtained from Rhodiola rosea(with 3.5% rosavins and 1% salidrosides), and it is employed for reducing the stress associated with physical and mental tasks [20]. Plantival has extract mixture from Valeriana officinalis(160 mg) and Melissa officinalis(80 mg) and is use in the treatment of nervousness, restlessness and insomnia as an anxiolytic and antidepressive [21]. Another phytodrug, known as Prostasan, is the extract of Serenoa repens, standardized at 25% of fatty acids; the dose employed is 160 mg, and its principal effect is antiandrogenic and against benign prostatic hyperplasia [22].

Due to the acceptance and growing use of phytodrugs around the world, PM are raw materials of great attention due to high consumption. In addition, MP biosynthesize several bioactive compounds, which are classified as terpenoids, alkaloids, lactones, flavonoids, coumarin, lignans and phenols, among others; many of these have restrictive taxonomical distribution. Although the SMt functions are not directly associated with the plant’s basic function, these compounds carry out some interaction roles in the plant and its environments such as: protection against pathogens, protection against abiotic tensions (ultraviolet radiation radiation), they possess the function of attracting pollinating insects, and they are signaling molecules and active ingredients for drugs [23, 24, 25].

It is estimated that around 50% of the drugs approved by the Federal Drug Administration are products derived from natural sources or analogs deriving from plants or microorganisms [26]. However, raw material can be limited, and its exploitation is one of the main ecological concerns. One of the key objectives of plant biotechnology is the development of large-scale production methods of pharmacologically active products. Additionally, the massive biosynthetic potential of plants has not been completely exploited yet and biotechnology can be employed to generate new chemical compounds that possess unknown biological activities and/or with a different mechanism of action, or a better one, than those in existence [23].

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3. Production of SMt by biotechnology tools

There are distinct strategies to optimize the production and modulation SMt in medicinal plants and food. The main strategies are by uses the elicitors (molecules capable of inducing defense in the plant) [1], which are classified as biotic and abiotic. Biotics are of biological origin, while abiotics can be physical or chemical. Some examples of physical abiotics are the weather, bacteria, and plagues, among others, while chemical abiotics possess an intense variety, with those most utilized being jasmonic acid and salicylic acid [27, 28]. One of the advantages of using elicitors treatment is that they function as signaling compounds for the mechanisms of defense; thus, they increase the production of SMt in an effective and rapid manner [29]. There is great specify in the interaction of plant-elicitor species which implies that the adequate one for each culture, the time of adding it, and the concentration for obtaining best response should be selected [30].

There is other technique very used to obtain SMt in vitro, it focuses on obtaining the roots, which is known as “hairy roots” or transformed roots; for this, the bacterium Agrobacterium rhizogenesis very used. This microorganism transfers the plasmid of the Transfer-DNA (T-DNA) of the T-DNA to the plant cell, to verify whether a root transformation was obtained, this can be confirmed by Southern hybridation analysis (this technique permits the detection of a specific DNA sequence in a complex mixture). A main advantage of these is that they have the capacity of rapid growth without the external administration of Plant Growth Regulators (PGR); the majority of these do not require a light supply, and their yield of metabolites is constant due to their genetic stability [1]. Another internal factor is the culture medium added with macro- and micronutrients, as well the external factors, such as light intensity, temperature, humidity, and stirring speed [31].

In general, formulation of the culture medium begins with the base medium, being the most utilized Muashige & Skoog (MS), B5 of Gamborg and Linsmaier and Skoog (LS), and Nitsch and Nitsch (NN) [32]. These culture mediums contain minerals, vitamins, and a carbon source, normally sucrose and sometimes fructose is used. Although plant cell cultures typically are initiate in solid medium, they require liquid medium for production on a large scale. The mineral content and/or the carbon source in culture medium have a profound impact on biosynthesis of SMt employed in the manufacturing of phytodrugs and/or compound-of-pharmaceutical-interest [33].

Other tools very used to obtain SMt by biotechnological process is through the use of BioCatalyzers; this method has been used to transform polyphenols compounds; for example, Bouvardia ternifoliais utilized for the production of a BioC denominated dehydrodiisoeugenol, which was obtained from the supernatant of cells suspension, demonstrating a yield of around 77%. The dehydrodiisoeugenol obtained from B. ternifoliaallows the production of isoeugenol by biotransformation; it is known that plant peroxides transform phenols substituted for by a methyl group orto position to the corresponding O-radical, which, on establishing itself by resonance, produces a C-radical; the latter is that which leads to dimerization, producing a dimer. This biotransformation represents a clean and green alternative with respect to traditional chemical methods, in which oxidative bonding reactions are affected using catalysts such as FeCl3, K3(FeCN)6, and Cu(OH)Cl [34].

Figure 1.

Chemical structure of some polyphenols and other SMt with biological activity.

Recently, interest in research and development of in vitroplant tissue cultures from MP has grown; however, there are scarce studies, to our knowledge, in which the biological activities of these SMt obtained by this process are described. The majority of works published only mention the conditions of the biotechnological process and the final concentrations of the different metabolites produced, but do not evaluate the pharmacological activity of these SMt, and the authors solely cite that these have been reported in previous works.

In Table 1 and Figure 1, some examples are described. It is important to mention that on some occasions is difficult to establish the biotechnological process conditions to induce the biosynthesis of bioactive SMt from a MP.

SpeciesProductsUseReferences
Alanthus altissimaAlkaloidsAntimicrobial[35]
Ajuga reptansAntocyaninsAntioxidant[36, 37]
Alanthus altissimaCantinones alkaloidsAntimicrobial[38]
Ammi majusCoumarinsAnticoagulant[39]
Anchusa officinalisRosmarinic acidAntioxidant[40, 41]
Anthoceros agrestisRosmarinic acid and GlycosidesAntioxidant[42]
Arachis hypogeaPiceatannolAntioxidant[43]
Artemisia annuaArtemisininAntimalaric[30, 44]
Artemisia judaicaFlavonoidsAntioxidant[45]
Bouvardia ternifoliaDehydrodiisoeugenolBiocatalyst[34]
Beta vulgarisBetalainsAntioxidant[46, 47]
Buddleja cordataVerbascoside (1), linarin (2)Anti-inflammatory, antioxidant[48]
Buddleja cordataPhenylpropanoidsAntioxidant[49]
Caesalpinia pulcherrimaHomo isoflavonesAntimicrobial, antitumoral[50]
Calophyllum inophyllumDipyranocoumarinsAntiHIV[51]
Camelia sinensisThiamine or theanineAntihypertensive[52]
Capsicum frutescensCapsaicin (3)Irritant[53]
Cassia acutifoliaAntraquinonesAntimicrobial[54]
Castilleja tenuifloraVerbascoside (1), Isoverbascoside, aucubinAnti-inflammatory, Antispasmodics[55]
Catharanthus roseusAjmalicinAntihypertensive[56]
Catharanthus roseusVinblastinAnticancer[57]
Cecropia obustifolia
Cecropia peltata
Chlorogenic acid, IsoorientinHypoglycemic[58]
Cephaelis ipecacuanaEmetinAntiparasitic[59]
Cephalo-taxus fortuneiAbietane diterpenoidsAntitumoral[60]
Choisya ternataFuranocoumarinsAntitumoral, Antioxidant[61]
Choisya ternataFuroquinolin alkaloidsAntitumoral, Antimicrobial[62]
Cinchona robustaRobustaquionesAntimalarial[63]
Cistanche deserticolaGlycosidesAntioxidant[64]
Cistanche salsaGlucophenyletanoidsAphrodisiac[65]
Colchium autumnaleColchicine (4)Antitumoral[66]
Coleus forskoliiForskolin (5)Asthma[67]
Comptotheca acuminateCamptotecin (6)Antitumoral[68]
Coptis japonicaBerberin (7)Intestinal infection[69]
Cornus kousaβ-glucogallin, (+)-Catechin, (+)-gallocatechin, procyanidin B-3Hyperglycemic and antimicrobial[70]
Coscinium fenestratumBerberinAntioxidant, Antidiabetic[71]
Crocus sativusCrocinAnticancer[72]
Cynara cardunculusCinarin, Chlorogenic acidAntioxidant[73]
Daucus corataAntocyaninsLipoperoxidation[74]
Digitalis lanataDigoxin (8)Cardiostimulant[75]
Dioscorea deltoideDiosgenin (9)Steroidal stimulant[76]
Drosophyllum lusitanicumPlumbagin (10)Anticancer, Antimicrobial[77]
Eleutherococcus sessiliflorusEleuterosideAnti-inflammatory, diuretic, analgesic,
antipyretic
[78]
Eriobotrya japonicaTriterpenesAnti-inflammatory, antidiabetic, antitumoral[79]
Eucommia ulmoidesChlorogenic acid (11)Antimicrobial, Antioxidant[80]
Fagopyrum esculentumRutin (12)Antioxidant[81]
Fragaria ananassaAntocyaninsAntioxidant[82]
Galphimia glaucaGalphimine B (27)Central nervous system disorders[83]
Glehnia littoralisAntocyaninsAntioxidant[84, 85]
Gymnema sylvestreGymnemicanorAntidiabetic[86]
Helianthus tuberosusInulinAntidiabetic[87]
Hemidesmus indicusRutin (12)Antioxidant[88]
Hypericum perforatumHypericinAntidepressive[89]
Hyssopus officinalisRosmarinic acid (13)Antioxidant[90]
Hyssopus officinalisLithospermic acidAntioxidant[91]
Ipomoea batatasAntocyaninsAntioxidant[92, 93, 94]
Larrea divaricataNordihydroguayaretic acid, QuercetinAntiarthritic, digestive, against venereal diseases[95]
Lavandula veraRosmarinic acid (13)Hepatoprotective[96, 97]
Leucophyllun frutescensCoumarins, lactones, flavonidsAntioxidants[98]
Lithospermum erythrorhizonShikoninAntibacterial[99]
Lopezia racemosa6-O-palmitoyl-3-O-β-D-glucopyra-nosylcampesterol, 6-O-palmi-toyl-3-O-β-D-gluco-pyranosyl-β-sitosterolAnti-inflammatory[100]
Lycium chinenseCerebrosideCellular Growth Regulator[101]
Morinda ellipticaAntraquinonesAntimicrobial[102]
Mucuna pruriensL-dihydroxyphenylalanineAntiParkinson[103]
Ochrosia ellipticaElipticinAntitumoral[104]
Ocimum basiliumRosmarinic acid (13)Antioxidant[105]
Panax ginsengGinkgolides (14)Cognitive deterioration[106]
Panax ginsengGinsenosides (15)Immunomodulator[107]
Papaver somniferumCodeine (16)Sedative[108]
Papaver somniferumMorphine (17)Sedative[109]
Papaver somniferumSanguinarin (18)Platelet stimulator[110]
Passiflora quadrangularisOrientin, Isoorientin, Vitexin, IsovitexinAntioxidant[111]
Petroselinum sativumFlavonolidesAntioxidant[112]
Picrasma quassioidesCuasinAntiphylogistic[113]
Piqueria trinervaMonoterpeneAntifungal[114]
Podophyllum hexandrumPodophylotoxin (19)Antitumoral[115]
Psoralea corylifoliaGenistein and DaidzeinTonic[116]
Rauwolfia serpentinaReserpin (20)Antihypertensive[117]
Rubia tinctorumAntraquin-onesAntimicrobial[118]
Salvia miltiorrhizaCryptotanshinoneAntioxidant, antimicrobial[119]
Salvia miltiorrhizaTanshinoneCardiac problems[120]
Saussurea medusaHispiduline (21), JaceosidineAntitumoral[121]
Silybum marianumSilymarinHepatoprotective[122]
Solanum malacoxylonCholecalcipherolAids calcium absorption[123]
Sphaeralcea angustifoliaSphaeralcic acid (22), Tomentin (23)Antiinflammatory[124]
Swietenia humilisZucc.AlkaloidsCytotoxic[125]
Tanacetum partheniumParthenolide (24)Anticancer[126]
Taxus brevifoliaTaxol (25)Anticancer[127]
Vitis viníferaAntocyaninsAntioxidant[128]
Vitis viníferaResveratrol (26)Antioxidant, Hepatoprotective[129]
Withania somniferaWithanolide AAntioxidant, Antistress[130]

Table 1.

Secondary metabolites obtained for cellular cultures from medicinal plant tissues in vitroand their biological activity.

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4. Anti-inflammatory activity of SMt isolated from vegetal material obtained by biotechnological processes

Some SMt with significant anti-inflammatory activity have been obtain from MP through employment some biotechnological processes. From cell suspension cultures Sphaeralcea angustifolia, two compounds with important anti-inflammatory activity (evaluated in murine models) were isolated. The cell suspension was developed in MS medium with total nitrate 2.74 mM, under this condition was obtained scopoletin, sphaeralcic acid (22) and tomentin (23). From the CH2Cl2:CH3OH extract sphaeralcic acid (22) and tomentin (23) were isolated; these compounds showed 58 and 66% anti-inflammatory activity, in the carrageenin model at 45 mg/kg administered by intraperitoneal (i.p.) route. On the other hand, in the topical anti-inflammatory model (TPA, 12-O-TetradecanoylPhorbol-13-Acetate), tomentin (225 mM/ear) exhibited 57% inhibition in the formation of auricular edema, while sphaeralcic acid (174 mM/ear) revealed 86% inhibition with a dose-dependent effect and one half of the Effective Dose (ED50) = 93 mM. Sphaeralcic acid is the most active compound in both models (topical as well as systemic) [124, 131].

In another study, the anti-inflammatory activity of the cell suspension culture from S. angustifoliais described. In this case, aseptic-leaf explants and Naphthalene Acetic Acid (NAA, such as auxin) in several concentrations (0, 0.5, 1.0, and 2.0 mg/L) in combination with a constant concentration of Kinetin (KIN) were used. For the cell suspension culture, they utilized 4% initial inoculum in MS medium with 2.74 mM of the total nitrates, 1 mg/L of NAA and 0.1 mg/L of KIN and supplemented with 30 g/L of sucrose. The main SMt identified in this suspension cultures were the same compounds (scopoletin, tomentin, and sphaeralcic acid). Scopoletin was excrete in the culture medium, although it also accumulated in the biomass. For evaluation of the anti-inflammatory activity, the authors prepared the CH2Cl2:MeOH extract of the cell’s suspension from S. angustifoliaand this extract was administered i.p. in male ICR mice (35 g) employing the carrageenin model. This extract showed ED50 = 137.63 mg/kg; sphaeralcic aid and tomentin at 45 mg/kg inhibited 67 and 62%, respectively on carrageenan assay and sphaeralcic acid at 1 mg/ear was more active in TPA assay, showed ED50 = 93 mM and tomentin showed 48% of inhibition at 1 mg/ear [132, 133]. In addition, the same extract from biomass of cells in suspension of S. angustifoliaat 100 mg/kg (with 0.10 mg of scopoletin, 0.10 mg of tomentin and 0.19 mg of sphaerelcic acid), as well as tomentin (20 mg/kg) were active as anti-inflammatory agent and reduced the mean body weight lost in Freund adjuvant- and kaolin/carrageenan-induced arthritis, respectively. In this assay, the organic extract and tomentin reduced the levels of pro-inflammatory interleukins such as IL-1β, IL-6 and TNF-α and increased levels of IL-4 and IL-10 (anti-inflammatory cytokines) [133].

In parallel with obtaining cells in vitroof S. angustifolia, the authors performed a preclinical phase study (in rats). The CH2Cl2 extract of the aerial parts of S. angustifolia(wild material) was tested in chronic inflammation model induced with complete Freund’s adjuvant (polyarthritis) The administration of the extract at 100 mg/kg/day during 8 days showed sustained and significant inhibition of edema, being of 62.6% [134]. A double-blind clinical phase study with the extract of S. angustifolia(wild material) standardized at 1% hydroxycoumarin content was conducted; the experiment was performed on 130 patients diagnosed with osteoarthritis. 55 of them were treated with standardized extract of S. angustifolia(gel) and 75 patients were treated with Diclofenac (2%). The therapeutic effectiveness of the gel administered topically for 4 weeks was 89%, while that of the control group (Diclofenac) was 91.3%; it was highlighted in the study that patients who received the treatment (gel of the standardized extract) did not exhibit adverse effects and did show an improvement in their disorder [135].

Another plant utilized in Mexican ethnomedicine is Lopezia racemosaCav. Callus cultures in MS medium were obtain with variable amounts of NAA, 2,4-Dichlorophenoxiacetic acid (2,4-D) and 6-BenzylAminoPurine (BAP). The authors carried out 10 treatments with the previously mentioned PGR. In this case, they employed three types of explants (hypocotyl, stem nodule, and leaf) and several treatments. The combination of 1.0 mg/L of 2,4-D plus 0.5 mg/L of BAP was the best. From these callus material two novel compounds: 6-O-palmitoyl-3-O-β-D-glucopyranosylcampesterol (174.0 μg/g of biomass) and 6-O-palmitoyl-3-O-β-D-glucopyranosyl-β-sitosterol were isolated. When quantifying these compounds, the authors observed that the wild plant contains less quantity than the callus. The topical anti-inflammatory activity of the biomass obtained from the callus was evaluate in the TPA model on CD-1 male mice at 1 mg/ear. Three extracts (hexanic, CH2Cl2, and methanol), was tested and showed 48.74, 57.14, and 16. 81% of inhibition, respectively. The CH2Cl2 extract was the most active, with a half-maximal Inhibitory Concentration (IC50) = 0.93 mg/ear. On the other hand, the pure compound (6-O-palmitoyl-3-O-β-D-glucopyranosyl-campesterol) was tested in the same model at 1 mg/ear showing a 57.14% inhibition, with IC50 = 0.45 mg/ear [100].

The lipophilic extract containing beta-carotene (LMBC) from plant cell cultures of Cleome spinosawas evaluate in two in vivomodels to determine the anti-inflammatory and antinociceptive activities in Swiss Webster (SW) mice of both sexes. The callus culture was obtained of the MS medium supplemented with 1 mg/L of 4- amino-3,5,6-trichloropicolinic acid (picloram) and sub-cultured to culture medium with the same composition at 4-week intervals. The anti-inflammatory activity in carrageenan model at 10 mg/kg by i.p. via was evaluated. LMBC was inactive with respect to extract from whole plant, which showed more than 50% inhibition of edema at the same dose. On the other hand, the LMBC (at 50 mg/kg) showed around 68% decrease in writhes, these data were very similar to that shown in wild plant, and the effect was better than dipyrone (at 100 mg/kg) used as positive control. The authors concluded that the results of LMBC are particularly important; since this active SMt of medicinal interest can be continuously obtain from callus cultures [136].

Buddleja cordatais other medicinal species utilized to treat diseases related with inflammation. This cell suspension was obtained in MS medium supplemented with NAA (9.05 μM) and Kin (2.32 μM). The anti-inflammatory activity of the extracts from wild plant and of the cell suspension cultures were describe. In both extracts, the verbascoside content was quantified by HPLC methods. The extract of the cells suspension has 87.48 mg verbascoside/g Dry Matter (DM), while that the same extract from wild plant only contained 47.34 mg of verbascoside/g DM. In addition, acute toxicity in Balb/C mice of the both extracts were also determined, with half of a Lethal Dose (LD50) of >2 g/kg. On the other hand, the topical anti-inflammatory effect of the wild plant extract and of the cell suspension was assay. The ED50 values was 3.93 and 1.26 mg/ear, respectively, cell suspension extract was the most active due to its greater content of verbascoside. Evaluation of both extracts in the carrageenan model (systemic inflammation), showed ED50 = 251.26 and 204.62 mg/kg for wild plant and cells suspension extracts, respectively; in this case, the latter extract was more active. In the chronic inflammation model (the arthritis model induced with complete Freud’s adjuvant), both extracts showed moderate anti-inflammatory activity (<35%) and favored weight increase in animals with arthritis. The authors concluded that the cell suspension culture of Buddleja cordataobtained through the biotechnological process contained a better anti-inflammatory activity; therefore, it represents a source for obtaining this type of secondary metabolite-of-pharmacological-interest [48].

Cnidoscolus chayamansais medicinal plant whit anti-inflammatory, antiprotozoal, hepatoprotective, hypoglycemic and antimycobacterial activities [137, 138, 139]. Recently, a biotechnology processes was described to obtain callus using BAP (5 mg/L) and 2,4-D (2.5 or 5 mg/L), this callus was used as a biotechnological alternative for in vitropropagation of this plant [140]. After that, this callus was use to establish a cell suspension culture. From the cell suspension, organic extract was prepared and its antioxidant, antibacterial and anti-inflammatory activities were determined, as well as the main SMt was quantified by HPLC analysis. In cell suspension, lupeol acetate (38.1 mg/g DW) was obtained as a main constituent and scopoletin (3.6 mg/g DW) was also quantified; in wild material, both compounds were isolated in low quantity. The organic extract was active against Staphylococcus aureus, S. coagulaseand Listeria monocytogenes,and a moderate antioxidant and anti-inflammatory activities (in TPA and carrageenan models) showed [28, 141].

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5. Antineoplasic activity of the plant material obtained by biotechnological cultures

From the callus culture of Eriobotrya japonica, nine triterpenes (ursolic acid; oleanolic acid; maslinic acid; tormentic acid; 2α,19α-dihydroxy-3-oxo-urs-12-en-28-oic acid; 2α-hydroxyursolic acid; hyptadienic acid, and the mixture of 3-O-cis-p-coumaroyl tormentic acid and 3-O-trans-p-coumaroyl tormentic acid) were isolated. The main triterpenes of the callus tissues were tormentic acid (50 mg/g DW) and 2α,19α-dihydroxy-3-oxo-urs-12-en-28-oic acid (11.8 mg/g DW), the latter compound (2a,19α-dihydroxy-3-oxo-urs-12-en-28-oic acid) is known as a potent protease inhibitor of the human immunodeficiency virus. All these triterpenes were tested in two cell lines (HSC-2 and HSC); seven of the nine triterpenes were active. Showing mean cytotoxic concentration (CC50) between 10 and 48 μg/ml, while the oleanolic acid and 2α,19α-dihydroxy-3-oxo-urs-12-en-28-oic acid exhibited weak cytotoxic activity. Additionally, the authors evaluated the in vivoantitumor activity of the 2α,19α-dihydroxy-3-oxo-urs-12-en-28-oic acid in female ICR mouse skin (n = 15) during two stages of carcinogenesis; in this assay, carcinogenesis was induced topically with (+)-(E)-4-methyl 2[(E)-hydroxyimino]-5-Nitro-6-methoxy-3-hexenamide (NOR1) at a dose of 90 μg/0.1 mL of acetone. One week after NOR1 administration started, TPA (1 μg/0.1 mL of acetone) was administered twice weekly, yielding as a result a weak inhibition of the carcinogenesis. On the other hand, the authors mention that 2α,19α-dihydroxy-3-oxo-urs-12-en-28-oic acid is an antiproliferative agent and that the number of papillomas diminished by 40% in 20 weeks, indicating that this compound possesses potential for the delay of carcinogen in mouse skin [142].

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6. Biological effect of SMt isolated from cell cultures of Galphimia glauca

Galphimia glaucais widely used in Mexican traditional medicine. From this species, some triterpenes such as Galphimine-A, B and E (27) have been isolated. These compounds showed a neuroprotective effect, when these were evaluated in mice convulsions model. To induce the seizure, the authors used strychnine or pentylenetratrazole administered by i.p. or subcutaneous route. In the study’s results, the depressor effects observed on motor activity directed toward an objective or an aim [143]. The pharmacological effect of galphimine B (G-B) was due to selectively inhibiting the discharge of dopaminergic neurons in the central area in in-vivomodels [144]. Due to its therapeutic importance of G-B, the authors proceeded to induce the production of this homogeneous raw material through a biotechnological process.

A first step was to obtain callus from hypocotyl explants in MS medium for 30 days with a combination of NAA and KIN; under these conditions, only great cell growth was obtained, and with 2,4-D at 4 mg/L the G-B production was stimulated with a yield of 0.154 mg/g DW. In addition, under this condition, G-E was also obtained but at less concentration (0.057 mg/g DW). Also, friable callus from suspension culture in MS medium with NAA and KIN (2:2 mg/L) was obtain, denominating this line as ggxl. By means of a growth kinetic, galphimines were shown to be produced in the culture’s stationary stage [83, 145]. The next step was to carry out the scaling of galphimine production in the 5-liter airliftbioreactor and in one with mechanical stirring; the growth indices were 11.66 and 1.7, respectively. However, the authors observed that neither the biomass production, nor the time exerted an influence on the yield of G-B. Because the airliftproduced a greater biomass but with lower yield of G-B (255 mg/L), while the stirring bioreactor at day 10 shown an intracellular as well as an extracellular content of 1381 mg of G-B/L, 5.4-times higher than the airliftat day 25 [146]. Once the biotechnological conditions for the production of G-B were established, this allowed having raw material to carry out the pharmacological evaluation in different models.

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7. Toxicologic effect of Galphimines

Aqueous extract from material obtained by bioreactor was prepared, whose galphamine content was G-A, G-B and G-E = 0.6, 1.034 mg/g, and 1.12 mg/g, respectively. Meanwhile, the content of these galphamine in the ethanolic extract was G-A = 5.35 mg/g, G-B = 18.8 mg/g, and G-E = 17.49 mg/g and the MeOH extract content G-A = 7.29 mg/g, G-B = 17.47 mg/g, and G-E = 11.6 mg/g. Afterward, each extract was administered to Balb/C male and female mice for 28 days (2.5 g/kg). During the study period, there were no deaths, and in the histopathological analysis of the different organs; the latter did not present alterations. Also, analyzed the behavioral parameters, demonstrating a reduction in spontaneous activity. Administration of these extracts for 56 days (2.5 g/kg) in mice did not cause any change in liver-function biochemical parameters. With regard to the cytotoxic evaluation in KB, UISO, and OVCAR-5 cell lines, no cytotoxic effects were found, but all of these extracts specifically inhibited growth of the colon-cancer cell line with ED50 of <2 μg/mL. On the genotoxicity test in vitro, the extracts were evaluated at three concentrations (250, 100, and 50 mg/mL) and none of the three G. glaucaextracts showed a genotoxic effect [147].

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8. Evaluation of the MeOH extract of Galphimia glaucain Behavioral models of anxiety

The anxiolytic and anti-depressive effects were evaluated for the G. glaucaMeOH extract (wild material) standardized with content of G-B (8.3 mg/g), using the elevated light–dark labyrinth and forced swimming in albino (ICR) mice. The extract, administered orally, three times (24, 18, and 1 h prior to the test) at doses of 125, 250, 500, 1,000, and 2,000 mg/kg was capable of significantly increasing (p < 0.05) the number of entries, as well as time spent on the elevated labyrinth’s open arms, which indicates an anti-anxiolytic effect. A similar effect was observed in the light–dark paradigm test: time spent in the light box increased in treated mice. However, this treatment was not able to change any parameter in the forced swimming test [148].

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9. Conclusions

The MP form part of the daily life of the worldwide population. It is currently of scientific interest due to its high consumption, as an alternative treatment and/or co-administered with allopathic treatments for the improvement of chronic-degenerative diseases. On the other hand, the population has been responsible for affording a great boost to the use of MP; therefore, its consumption generates a great demand and consequently overexploitation. This overexploitation is a danger in the extinction of species of pharmaceutical interest. Another problem regarding the consumption of MP is that not all the population has access to species that are endemic and that have great biological potential. All the above led to the search for methods to achieve the production and induction of SMt biosynthesis with important biological activity in less time, with constant, controlled and standardized production. Besides helping to preserve plant species without altering the ecosystem.

In some cases, has been reported that cell suspension cultures increase by up to 300% the production of SMt with biological interest respect to wild plant material. In addition, to the increase in SMt production, these are obtained in less complex mixtures, which facilitates the purification process. In the present work, we describe several SMt obtained for biotechnological processing; however, many of these SMt have not been submitted to in vivostudies that prove their potential biological activity. Therefore, it is necessary to develop projects aimed at obtaining metabolites by biotechnological processes and demonstrate their biological activity in in vivomodels.

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Acknowledgments

Susan Drier for English language corrections.

Funding

This manuscript is a review and we did not have funding.

Competing interest

The author declare no competing interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

SMtSecondary Metabolites
SMBBSociedad Mexicana de Biotecnología y Bioingeniería
TMTradicional Medicine
MPMedicinal Plants
DNADeoxyribonucleic acid
PGRPlany Growth Regulators
BioCBioCatalyzers
TPA12-O-Tetradecanoyl Phorbol 13-Acetate
ED50Half of the Effective Dose
NAANaphthalene Acetic Acid
KINKinetina
2,4-DDichlophenoxiacetic acid
BAP6-BenzylAminoPurine
IC50Hal-maximal Inhibitory concentration
DMDry Metter
LD50Half of a Lethal Dose
DWDry Metter
CC50Mean Cytotoxic Concentration
i.p.Intraperitoneal
S.C.Subcutaneous
G-AGalphimine A
G-BGalphimine B
G-EGalphimine E
C.NKinetine

References

  1. 1.Rao SR, Ravishankar GA (2002) Plant cell cultures: chemical factories of secondary metabolites. Biotechnol Adv 20:101-153. doi: 10.1016/s0734-9750(02)00007-1
  2. 2.Akula R, Ravishankar GA (2011) Influence of abiotic stress signals on secondary metabolites in plants. Plant Signal Behav 6:1720-1731. doi: 10.4161/psb.6.11.17613
  3. 3.SMBB, Sociedad Mexicana de Biotecnología y Bioingeniería. 2016.https://smbb.mx/Access: january 2021
  4. 4.Yue W, Ming QL, Lin B, Rahman K, Zheng CJ, Han T, Qin LP (2016) Medicinal plant cell suspension cultures: pharmaceutical applications and high-yielding strategies for the desired secondary metabolites. Crit Rev Biotechnol 36:215-232. doi: 10.3109/07388551.2014.923986
  5. 5.Vanisree M, Tsay HS (2007) Chapter 12: Plant cell cultures: production of biologically important secondary metabolites from medicinal plants of Taiwan. In: Kayser O, Quax WJ (Eds) Medical Plant Biotechnology: from Basic Research to Industrial Applications. Willey Verlag Gmb H & Co. K GaA, pp 267-285. doi: 10.1002/9783527619771.ch12
  6. 6.Vanisree M, Lee CY, Lo SF, Nalawade SM, Lin CY, Tsay HS (2004) Studies on the production of some important secondary metabolites from medicinal plants by plant tissue cultures. Bot Bull Acad Sin 45:1-22.https://www.researchgate.net/publication/228860673
  7. 7.Newman DJ, Cragg GM (2020) Natural Products as Sources of New Drugs over the Nearly Four Decades from 01/1981 to 09/2019. J Nat Prod 83:770-803.https://doi.org/10.1021/acs.jnatprod.9b01285
  8. 8.WHO. Traditional Medicine Strategy 2002-2005. World Health Organization; Geneva, Switzerland: 2002.https://apps.who.int/iris/handle/10665/67163
  9. 9.Beyene B, Beyene B, Deribe H (2016) Review on application and management of medicinal plants for the livelihood of the local community. J Resour Develop Managem 22:33-39.https://iiste.org/Journals/index.php/JRDM/article/view/31747/32619
  10. 10.Chen SL, Yu H, Luo HM, Wu Q, Li CF, Steinmetz A (2016) Conservation and sustainable use of medicinal plants: problems, progress, and prospects. Chin Med 11:1-37. doi:10.1186/s13020-016-0108-7
  11. 11.Sen T, Samanta SK (2015) Medicinal plants, human health and biodiversity: a broad review. Adv Biochem Eng Biothechnol 147:59-110. doi: 10.1007/10_2014_273
  12. 12.Bahare S, Konovalov DA, Fru P, Kapewangolo P, Peron G, Ksenija M, Pereira OR, Nigam M, Nicola S, Pignata G, Rapposelli S, Sestito S, Anil Kumar NV, Cadiz_Gurrea ML, Segura-Carretero A, Mishra AP, Sharifi-Rad M, Cho WC, Taheri Y, Setzer WN, Sharifi-Rad J (2020) Areca catechu-From farm to food and biomedical applications. Phytother Res 34:2140-2158
  13. 13.Bahare S, Selamoglu Z, Sener B, Kilic M, Kumar Jugran A, de Tommasi N, Sinisgalli C, Milella L, Rajkovic J, Morais-Braga MFB, Bezerra CF, Rocha JE, Coutinho HDM, Oluwaseun AA, Khan SZ, Ahnmad SJ, Erol E, Ali Z, Ostrander EA, Sharifi-Rad J, Cadiz.Gurrea ML, Taheri Y, Martorell M, Segura-Carretero A, Cho WC (2019a) Berberis Plants-Drifting from Farm to Food Applications, Phytotherapy and Phytopharmacology. Foods 8:522
  14. 14.Bahare S, Sener B, Kilic M, Sharifi-Rad J, Naz R, Yousaf Z, Nixwell MF, Tosouh KPV, Ezzat SM, Bishbishy MH, Taheri Y, Lucariello G, Durazzo A, Lucarini M, Rasul Suleira HA, Santini A (2019) Dioscorea Plants: A genus rich in vital nutrapharmaceuticals-A review. Iran J Pharm Res 18:68-69
  15. 15.Farag M, Mohammed MS, Foud I, Ahmed WJ, Malik S, Mohamed MS (2015) The role of natural products in drug discovery and development. World J Pharm Res 4:22-33.https://www.researchgate.net/publication/291830543
  16. 16.Krentz AJ, Bailey CJ (2005) Oral antidiabetic agents: current role in type 2 diabetes mellitus. Drugs 65:385-411. doi: 10.2165/00003495-200565030-00005
  17. 17.Romero-Cerecero O, Reyes-Morales H, Torija-Barrio IT, Herrera-Arellano A, Tortoriello J (2005) Conocimiento sobre fitofármacos en médicos de atención primaria del estado de Morelos. Rev Med Inst Mex Seguro Soc 43:281-286.https://www.medigraphic.com/cgi-bin/new/resumen.cgi?IDARTICULO=4919
  18. 18.Briskin PD (2000) Medicinal plants and Phytomedicines. Linking plant biochemistry and physiology to human health. Plant Physiol 124:507-514. doi: 10.1104/pp.124.2.507
  19. 19.Ulbricht C, Basch E, Boon H, Ernst E, Hammerness P, Sollars D, Tsourounis C, Woods J, Bent S (2005) Safety review of kava(Piper methysticum) by the Natural Standard Research Collaboration. Expert Opin Drug Saf 4:779-794. doi: 10.1517/14740338.4.4.779
  20. 20.Iheozor-Ejiofor P, Dey ES (2009) Extraction of rosavin fromRhodiola rosearoot using supercritical carbon dioxide with water. J Supercrit Fluids 50:29-32.https://doi.org/10.1016/j.supflu.2009.04.011
  21. 21.Müller S F, Klement S (2006) A combination of valerian and lemon balm is effective in the treatment of restlessness and dyssomnia in children. Phytomedicine 13:383-387. doi: 10.1016/j.phymed.2006.01.013
  22. 22.Vela-Navarrete R, Escribano-Burgos M, Farré AL, García-Cardoso J, Manzarbeitia F, Carrasco C (2005)Serenoa repenstreatment modifies bax/bcl-2 index expression and caspase-3 activity in prostatic tissue from patients with benign prostatic hyperplasia. J Urol 173:507-510. doi: 10.1097/01.ju.0000150533.94952.25
  23. 23.Gandhi SG, Mahajan V, Bedi YS (2015) Changing trends in biotechnology of secondary metabolism in medicinal and aromatic plants. Planta 241:303-317. doi: 10.1007/s00425-014-2232-x
  24. 24.Sharifi-Rad J, Taheri Y, Abdulmajid AS, Naderi N, Anil Kumar NK, Koirala N, Khadka S, Karazhan N, Shahinozzaman Md, Sen S, Acharya K, Dey A, Martorell M, Martins N (2020) Biological activities and health-promoting effects of Pyracantha genus: A key approach to the phytochemical´s potential. Cell Mol Biol 66:20-27
  25. 25.Sharifi-Rad J, Rayess YE, Abi Rizk A, Sadaka C, Zgheib R, Zam W, Sestito S, Rapposelli S, Neffe-Skocińska K, Zielińska D, Salehi B, Setzer WN, Dosoky NS, Taheri Y, Beyrouthy ME, Martorell M, Ostrander EA, Rasul Suleira HA, Cho WC, Mroyi A, Martins N (2020). Turmeric and Its Major Compound Curcumin on Health: Bioactive Effects and Safety Profiles for Food, Pharmaceutical, Biotechnological and Medicinal Applications. Front Pharmacol 11:01021
  26. 26.Vuorela P, Leinonen M, Saikku P, Tammela P, Rauha JP, Wennberg T, Vuorela H (2004) Natural products in the process of finding new drug candidates. Curr Med Chem 11:1375-1389. doi: 10.2174/0929867043365116
  27. 27.Patel H, Krishnamurthy R (2013) Elicitors in plant tissue culture. J Pharmacog Phytochem 2:60-65.https://www.phytojournal.com/vol2Issue2/Issue_july_2013/9.1.pdf
  28. 28.Pérez-González MZ, Juárez-Vázquez MdelC Jiménez-Arellanes MA (2020) Establishment of a cell suspension culture with anti-inflammatory activity and the effect of salicylic acid on the production of callus fromCnidoscolus chayamansa. Int J Appl Microb Biotechnol Res 8:40-50.doi.org/10.33500/ijambr.2020.08.005
  29. 29.DiCosmo F, Misawa M (1995) Plant cell and tissue culture: alternatives for metabolite production. Biotechnol Adv 13:425-453. doi: 10.1016/07349750(95)02-005-n
  30. 30.Paniego NB, Giulietti AM (1995) Artemisia annua L.: dedifferentiated and differentiated cultures. Plant Cell Tissue Organ Cul 36 (2), 163-168 doi: 10.1007/BF00037715
  31. 31.Schmitz C, Fritsch L, Fischer R, Schillberg S, Rasche S (2016) Statistical experimental designs for the production of secondary metabolites in plant cell suspension cultures. Biotechnol Lett 38:2007-2014. doi: 10.1007/s10529-016-2206-0
  32. 32.Gaurav N, Singh AP, Kumar A, Som D, Kumar D, Komal HSG (2016)In vitrotissue culture studies from nodal and petiole explants of wild and cultivated traits ofWithania somniferain MS and B5 medium. J Med Plant Stud 4:92-96.https://www.researchgate.net/publication/328699276
  33. 33.McCoy E, O’Connor SE (2008) Natural products from plant cell cultures. Prog Drug Res 65:329-370.https://pubmed.ncbi.nlm.nih.gov/18084920/
  34. 34.Hernández-Vázquez L, Olivera-Flores M, de Jesús T, Luna H, Navarro-Ocaña A (2017) Obtención de dehidrodiisoeugenol por dimerización de isoeugenol con cultivos celulares deBouvardia ternifolia(trompetilla) TIP. Rev Esp Cienc Quim-Biol 20:15-22.http://dx.doi.org/10.1016/j.recqb.2017.04.002
  35. 35.Crespi-Perellino N, Guicciardi A, Malyszko G, Arlandi E, Ballobio E, Ballobio, M, Minghetti A (1986) Occurrence of indole alkaloids in Ailanthus altissima cell cultures. J Nat Prod 49:1010-1014.https://doi.org/10.1021/np50048a007
  36. 36.Callebaut A, Hendrickx G, Voets AM, Motte JC (1990) Anthocyanins in cell cultures ofAjuga reptans. Phytochemistry 29:2153-2158. doi: 10.1016/0031-9422(90)83027
  37. 37.Terahara N, Callebaut A, Ohba R, Nagata T, Ohnishi-Kameyama M, Suzuki M (2001) Acylated anthocyanidin 3-sophoroside-5-glycosides fromAjuga reptansflowers and the corresponding cell cultures. Phytochemistry 58:493-500. doi: 10.1016/s0031-9422(01)00172-8
  38. 38.Anderson LA, Harris A, Phillipson JD (1983) Production of cytotoxic canthin-6-one alkaloids byAilanthus altissimaplant cell cultures. J Nat Prod 46:374-378. doi: 10.1021/np50027a014
  39. 39.Staniszewska I, Królicka A, Maliński E, Łojkowska E, Szafranek J (2003) Elicitation of secondary metabolites inin vitrocultures ofAmmi majusL. Enzyme Microb Technol 33:565-568.https://doi.org/10.1016/S0141-0229(03)00180-7
  40. 40.De-Eknamkul W, Ellis BE (1984) Rosmarinic acid production and growth characteristics ofAnchusa officinaliscell suspension cultures. Planta Med 50:346-350. doi: 10.1055/s-2007-969728
  41. 41.Su WW, Lei F, Su LY (1993) Perfusion strategy for rosmarinic acid production byAnchusa officinalis. Biotechnol Bioeng 42:884-890. doi: 10.1002/bit.260420713
  42. 42.Vogelsang K, Schneide B, Petersen M (2006) Production of rosmarinic acid and a new rosmarinic acid 3′-O-β-D-glycoside in suspension cultures of the hornwortAnthoceros agrestisPaton. Planta 223:369-373. doi: 10.1007/s00425-005-0089-8
  43. 43.Ku KL, Chang PS, Cheng Y C, Lien CY (2005) Production of stilbenoids from the callus ofArachis hypogaea: a novel source of the anticancer compound piceatannol. J Agric Food Chem 53:3877-3881. doi: 10.1021/jf050242o
  44. 44.Baldi A, Dixit VK (2008) Yield enhancement strategies for artemisinin production by suspension cultures ofArtemisia annua. Bioresour Technol 99:4609-4614. doi: 10.1016/j.biortech.2007.06.061
  45. 45.Liu CZ, Murch SJ, El-Demerdash M, Saxena PK. (2004)Artemisia judaica L.: micropropagation and antioxidant activity. J Biotechnol 110:63-71. doi: 10.1016/j.jbiotec.2004.01.011
  46. 46.Hunter CS, Kilby NJ (1999) Betalains. Their accumulation and release in vitro. In: Dall RD (Eds) Plant Cell Culture Protocols. Methods in Molecular Biology, vol 11. Humana Press, pp 403-410. doi: 10.1385/1-59259-583-9:403
  47. 47.Pavlov A, Kovatcheva P, Tuneva D, Ilieva M, Bley T (2005a) Radical scavenging activity and stability of betalains fromBeta vulgarishairy root culture in simulated conditions of human gastrointestinal tract. Plant Foods Hum Nutr 60:43-47.https://doi.org/10.1007/s11130-005-5098-z
  48. 48.Gutiérrez-Rebolledo GA, Estrada-Zúñiga ME, Nieto-Trujillo A, Cruz-Sosa F, Jiménez-Arellanes MA (2018)In vivoanti-inflammatory activity and acute toxicity of methanolic extracts from wild plant leaves and cell suspension cultures ofBuddleja cordataKunth (Buddlejaceae). Rev Mex Ing Quim 17:317-330.http://rmiq.org/ojs311/index.php/rmiq/article/view/42/26
  49. 49.Estrada-Zúñiga ME, Aarland RC, Rivera-Cabrera F, Bernabé-Antonio A, Buendía-González L, Cruz-Sosa F (2016) Micropropagation ofBuddleja cordata and the content of verbascoside and total phenols with antioxidant activity of the regenerated plantlets. Rev Mex Ing Quim 15:333-346.http://rmiq.org/ojs311/index.php/rmiq/article/view/1003
  50. 50.Zhao P, Iwamoto Y, Kouno I, Egami Y, Yamamoto H (2004) Stimulating the production of homoisoflavonoids in cell suspension cultures ofCaesalpinia pulcherrimausing cork tissue. Phytochemistry 65:2455-2461.https://doi.org/10.1016/j.phytochem.2004.08.004
  51. 51.Pawar KD, Thengane SR (2009) Influence of hormones and medium components on expression of dipyranocoumarins in cell suspension cultures ofCalophyllum inophyllumL. Process Biochem 44:916-922.https://doi.org/10.1016/j.procbio.2009.03.005
  52. 52.Orihara Y, Furuya T (1990) Production of theanine and other γ-glutamyl derivatives byCamellia sinensiscultured cells. Plant Cell Rep 9:65-68. doi: 10.1007/BF00231550
  53. 53.Sudha G, Ravishankar GA (2003) Influence of methyl jasmonate and salicylic acid in the enhancement of capsaicin production in cell suspension cultures ofCapsicum frutescensMill. Curr Sci 85:1212-1217.https://www.jstor.org/stable/24108623
  54. 54.Nazif NM, Rady MR, El-Nasr M S (2000) Stimulation of anthraquinone production in suspension cultures ofCassia acutifoliaby salt stress. Fitoterapia 71:34-40.https://doi.org/10.1016/S0367-326X(99)00101-X
  55. 55.Cortes-Morales JA, Lopez-Laredo AR, Zamilpa A, Bermudez-Torres K, Trejo-Espino JL, Trejo-Tapia G (2018) Morphogenesis and secondary metabolites production in the medicinal plantCastilleja tenuiflorabenth. Under nitrogen deficiency and starvation stress in a temporary immersion system. Rev Mex Ing Quim 17:229-242.https://doi.org/10.24275/uam/izt/dcbi/revmexingquim/2018v17n1/Cortes
  56. 56.Ten Hoopen HJG, Vinke JL, Moreno PRH, Verpoorte R, Heijnen JJ (2002) Influence of temperature on growth and ajmalicine production byCatharantus roseussuspension cultures. Enzyme Microb Technol 30:56-65. doi:10.1016/S0141-0229(01)00456-2
  57. 57.Endo T, Goodbody A, Misawa M (1987) Alkaloid production in root and shoot cultures ofCatharanthus roseus. Planta Med 53:479-482. doi:10.1055/s-2006-962777
  58. 58.Nicasio-Torres M, Erazo-Gómez J C, Cruz-Sosa F (2009)In vitropropagation of two antidiabetic species known as guarumbo:Cecropia obtusifoliaandCecropia peltata. Acta Physiol Plant 31:905-914.https://doi.org/10.1007/s11738-009-0304-5
  59. 59.Jha S, Sahu NP, Sen J, Jha TB, Mahato SB (1991) Production of emetine and cephaeline from cell suspension and excised root cultures ofCephaelis ipecacuanha. Phytochemistry 30:3999-4003.https://doi.org/10.1016/0031-9422(91)83452-Q
  60. 60.Xu XH, Zhang W, Cao XP, Xue S (2011) Abietane diterpenoids synthesized by suspension-cultured cells ofCephalotaxus fortunei. Phytochem Lett 4:52-55.https://doi.org/10.1016/j.phytol.2010.12.003
  61. 61.Kitamura Y, Ikenaga T, Ooe Y, Hiraoka N, Mizukami H (1998) Induction of furanocoumarin biosynthesis inGlehnia littoraliscell suspension cultures by elicitor treatment. Phytochemistry 48:113-117.https://doi.org/10.1016/S0031-9422(97)00849-2
  62. 62.Creche J, Trémouillaux-Guiller J, Gröger D, Chénieux J.C, Rideau M (1993)Choisya ternate(Mexican Orange): In Vitro Culture and the Production of Alkaloids. In: Bajaj Y.P.S. (Eds) Medicinal and Aromatic Plants V. Biotechnology in Agriculture and Forestry, vol 24. Springer, Berlin, pp 107-121.https://doi.org/10.1007/978-3-642-58062-8_8
  63. 63.Schripsema J, Ramos-Valdivia A, Verpoorte R (1999) Robustaquinones, novel anthraquinones from an elicitedCinchona robustasuspension culture. Phytochemistry 51:55-60.https://doi.org/10.1016/S0031-9422(98)00470-1
  64. 64.Cheng XY, Wei T, Guo B, Ni W, Liu CZ (2005)Cistanche deserticolacell suspension cultures: phenylethanoid glycosides biosynthesis and antioxidant activity. Process Biochem 40:3119-3124. doi: 10.1016/j.procbio.2005.03.012
  65. 65.Liu JY, Guo ZG, Zeng ZL (2007) Improved accumulation of phenylethanoid glycosides by precursor feeding to suspension culture ofCistanche salsa. Biochem Eng J 33:88-93.https://doi.org/10.1016/j.bej.2006.09.002
  66. 66.Yoshida K, Hayashi T, Sano K (1988) Colchicoside inColchicum autumnalebulbs. Agr Biol Chem 52:593-594.https://doi.org/10.1080/00021369.1988.10868674
  67. 67.Mukherjee S, Ghosh B, Jha S (2000) Establishment of forskolin yielding transformed cell suspension cultures ofColeus forskohliias controlled by different factors. J Biotechnol 76:73-81. doi: 10.1016/s0168-1656(99)00181-9
  68. 68.Pasqua G, Monacelli B, Mulinacci N, Rinaldi S, Giaccherini C, Innocenti M, Vinceri FF (2005) The effect of growth regulators and sucrose on anthocyanin production inCamptotheca acuminatacell cultures. Plant Physiol Biochem 43:293-298.https://doi.org/10.1016/j.plaphy.2005.02.009
  69. 69.Hara Y, Yamagata H, Morimoto T, Hiratsuka J, Yoshioka T, Fujita Y, Yamada Y (1989) Flow cytometric analysis of cellular berberine contents in high-and low-producing cell lines ofCoptis japonicaobtained by repeated selection. Planta Med 55:151-154. doi: 10.1055/s-2006-961910
  70. 70.Ishimaru K, Arakawa H, Neera S (1993) Polyphenol production in cell cultures ofCornus kousa. Phytochemistry 32:1193-1197.https://doi.org/10.1016/S0031-9422(00)95090-8
  71. 71.Kashyap S, Kapoor N, Kale RD. (2016)Coscinium fenestratum: callus and suspension cell culture of the endangered medicinal plant using vermicompost extract and coelomic fluid as plant tissue culture media. Am J Plant Sci 7:899-906. doi: 10.4236/ajps.2016.76085
  72. 72.Chen SA, Wang X, Zhao B, Yuan X, Wang Y (2003) Production of crocin usingCrocus sativuscallus by two-stage culture system. Biotechnol Lett 25:1235-1238.https://link.springer.com/article/10.1023/A:1025036729160
  73. 73.Trajtemberg SP, Apóstolo NM, Fernández G (2006) Calluses ofCynara cardunculusvar.cardunculus cardoon(Asteraceae): determination of cynarine and chlorogenic acid by automated high-performance capillary electrophoresis. In Vitro Cell Dev Biol-Plant 42:534-537.https://doi.org/10.1079/IVP2006803
  74. 74.Ravindra PV, Narayan MS (2003) Antioxidant activity of the anthocyanin from carrot (Daucus carota) callus culture. Int J Food Sci Nut 54:349-355. doi: 10.1080/09637480120092134
  75. 75.Kreis W, Reinhard E (1992) 12β-Hydroxylation of digitoxin by suspension-culturedDigitalis lanatacells: production of digoxin in 20-litre and 300-litre air-lift bioreactors. J Biotechnol 26:257-273.https://doi.org/10.1016/0168-1656(92)90011-W
  76. 76.Tal B, Gressel J, Goldberg I (1982) The effect of medium constituents on growth and diosgenin production byDioscorea deltoideacells grown in batch cultures. Planta Med 44:111-115. doi: 10.1055/s-2007-971414
  77. 77.Komaraiah P, Ramakrishna SV, Reddanna P, Kishor PK (2003) Enhanced production of plumbagin in immobilized cells ofPlumbago roseaby elicitation andin situadsorption. J Biotechnol 101:181-187. doi: 10.1016/s0168-1656(02)00338-3
  78. 78.Shohael AM, Ali MB, Yu KW, Hahn EJ, Islam R, Paek KY (2006) Effect of light on oxidative stress, secondary metabolites and induction of antioxidant enzymes inEleutherococcus senticosus somatic embryos in bioreactor. Process Biochem 41:1179-1185.https://doi.org/10.1016/j.procbio.2005.12.015
  79. 79.Ho HY, Liang KY, Lin WC, Kitanaka S, Wu JB (2010) Regulation and improvement of Triterpene formation in plant cultured cells ofEriobotrya japonicaLindl. J Biosci Bioeng 110:588-592. doi: 10.1016/j.jbiosc.2010.06.009
  80. 80.Wang J, Liao X, Zhang H, Du J, Chen P (2003a) Accumulation of chlorogenic acid in cell suspension cultures ofEucommia ulmoides. Plant Cell Tiss Organ Cult 74:193-195.https://doi.org/10.1023/A:1023957129569
  81. 81.Lee SY, Cho SI, Park MH, Kim YK, Choi JE, Park SU (2007) Growth and rutin production in hairy root cultures of buckwheat (Fagopyrum esculentumM.) Prep Biochem Biotechnol 37:239-246. doi: 10.1080/10826060701386729
  82. 82.Zhang W, Seki M, Furusaki S (1997) Effect of temperature and its shift on growth and anthocyanin production in suspension cultures of strawberry cells. Plant Sci 127:207-214.https://doi.org/10.1016/S0168-9452(97)00124-6
  83. 83.Osuna L, Pereda-Miranda R, Villarreal ML (2002)In vitroproduction of sedative galphimine B by cell suspension cultures ofGalphimia glauca. Biotechnol Lett 24:257-261.https://doi.org/10.1023/A:1014028510775
  84. 84.Miura H, Kitamura Y, Ikenaga T, Mizobe K, Shimizu T, Nakamura M, Kato Y, Yamada T, Maitani T, Goda Y (1998) Anthocyanin production ofGlehnia littoraliscallus cultures. Phytochemistry 48:279-283.https://doi.org/10.1016/S0031-9422(97)01115-1
  85. 85.Kitamura Y, Ohta M, Ikenaga T, Watanabe M (2002) Responses of anthocyanin-producing and non-producing cells ofGlehnia littoralisto radical generators. Phytochemistry 59:63-68. doi: 10.1016/s0031-9422(01)00428-9
  86. 86.Praveen N, Murthy HN, Chung IM (2011) Improvement of growth and gymnemic acid production by altering the macro elements concentration and nitrogen source supply in cell suspension cultures ofGymnema sylvestreR. Br. Ind Crops Prod 33:282-286.https://doi.org/10.1016/j.indcrop.2010.12.015
  87. 87.Taha HS, El-Kawy AA, Fathalla MA (2012) A new approach for achievement of inulin accumulation in suspension cultures of Jerusalem artichoke (Helianthus tuberosus) using biotic elicitors. J Genet Eng Biotechnol 10:33-38.https://doi.org/10.1016/j.jgeb.2012.02.002
  88. 88.Misra N, Misra P, Datta SK, Mehrotra S (2005)In vitrobiosynthesis of antioxidants fromHemidesmus indicusR. Br. Cultures. In Vitro Cell Dev Biol-Plant 41:285-290.https://doi.org/10.1079/IVP2004627
  89. 89.Walker TS, Bais HP, Vivanco JM (2002) Jasmonic acid-induced hypericin production in cell suspension cultures ofHypericum perforatumL. (St. John’s wort). Phytochemistry 60:289-293. doi: 10.1016/s0031-9422(02)00074-2
  90. 90.Murakami Y, Omoto T, Asai I, Shimomura K, Yoshihira K, Ishimaru K (1998) Rosmarinic acid and related phenolics in transformed root cultures ofHyssopus officinalis. Plant Cell Tiss Org 53:75-78.https://doi.org/10.1023/A:1006007707722
  91. 91.Kochan E, Wysokinska H, Chmiel A, Grabias B (1999) Rosmarinic acid and other phenolic acids in hairy roots ofHyssopus officinalis. Z NaturforschC54c:11-16.https://doi.org/10.1515/znc-1999-1-204
  92. 92.Konczak-Islam I, Yoshimoto M, Hou D. X, Terahara N, Yamakawa O (2003) Potential chemopreventive properties of anthocyanin-rich aqueous extracts fromin vitroproduced tissue of sweet potato (Ipomoea batatasL.). J Agric Food Chem 51:5916-5922.https://doi.org/10.1021/jf030066o
  93. 93.Terahara N, Konczak I, Ono H, Yoshimoto M, Yamakawa O (2004) Characterization of acylated anthocyanins in callus induced from storage root of purple-fleshed sweet potato, Ipomoea batatas L. J Biomed Biotechnol 2004:279-286. doi: 10.1155/S1110724304406056
  94. 94.Terahara N, Konczak-Islam I, Nakatani M, Yamakawa O, Goda Y, Honda T (2000) Anthocyanins in callus induced from purple storage root ofIpomoea batatasL. Phytochemistry 54:919-922.https://doi.org/10.1016/S0031-9422(00)00099-6
  95. 95.Palacio L, Cantero JJ, Cusidó RM, Goleniowski ME (2012) Phenolic compound production in relation to differentiation in cell and tissue cultures ofLarrea divaricata(Cav.). Plant Sci 193-194:1-7. doi: 10.1016/j.plantsci.2012.05.007
  96. 96.Georgiev MI, Kuzeva SL, Pavlov AI, Kovacheva EG, Ilieva MP (2007) Elicitation of rosmarinic acid byLavandula veraMM cell suspension culture with abiotic elicitors. World J Microbiol Biotechnol 23:301-304. doi: 10.1007/s11274-006-9214-5
  97. 97.Pavlov AI, Georgiev MI, Panchev IN, Ilieva MP (2005b) Optimization of rosmarinic acid production byLavandula veraMM plant cell suspension in a laboratory bioreactor. Biotechnol Prog 21:394-396. doi: 10.1021/bp049678z
  98. 98.Espinosa-Leal C, Treviño-Neávez JF, Garza-Padrón RA, Verde-Star MJ, Rivas-Morales C, Morales-Rubio ME (2015) Contenido de fenoles totales y actividad anti-radical de extractos metanólicos de la planta silvestre y cultivadain vitrodeLeucophyllum frutescens. Rev Mex Cienc Farm 46:52-56.https://www.redalyc.org/articulo.oa?id=57945705005
  99. 99.Yamamoto H, Inoue K, Yazaki K (2000) Caffeic acid oligomers inLithospermum erythrorhizoncell suspension cultures. Phytochemistry 53:651-657.https://doi.org/10.1016/S0031-9422(99)00623-8
  100. 100.Salinas R, Arellano-García J, Perea-Arango I, Álvarez L, Garduño-Ramírez ML, Marquina S, Zamilpa, A, Castillo-España P (2014) Production of the anti-Inflammatory compound 6-O-Palmitoyl-3-O-β-D-glucopyranosylcampesterol by callus cultures ofLopezia racemosaCav. (Onagraceae) Molecules 19:8679-8690
  101. 101.Jang YP, Lee YJ, Kim YC, Huh H (1998) Production of a hepatoprotective cerebroside from suspension cultures ofLycium chinense. Plant Cell Rep 18:252-254. doi: 10.1007/s002990050566
  102. 102.Chiang L, Abdullah MA (2007) Enhanced anthraquinones production from adsorbent-treatedMorinda ellipticacell suspension cultures in production medium strategy. Process Biochem 42:757-763. doi: 10.1016/j.procbio.2007.01.005
  103. 103.Pras N, Woerdenbag HJ, Batterman S, Visser JF, Van Uden W (1993)Mucuna pruriens: improvement of the biotechnological production of the anti-Parkinson drug L-dopa by plant cell selection. Pharm World Sci 15:263-268. doi: 10.1007/BF01871128
  104. 104.Kouamo K, Creche J, Chénieux JC, Rideau M, Viel C (1985) Alkaloid production byOchrosia ellipticacell suspension cultures. J Plant Physiol 118:277-283. doi: 10.1016/S0176-1617(85)80229-7
  105. 105.Kintzios S, Kollias H, Straitouris E, Makri O (2004) Scale-up micropropagation of sweet basil (Ocimum basilicumL.) in an airlift bioreactor and accumulation of rosmarinic acid. Biotechnol Lett 26:521-523. doi: 10.1023/b:bile.0000019561.89044.30
  106. 106.Kang TH, Park HM, Kim YB, Kim H, Kim N, Do JH, Kang C, Cho Y, Kim SY (2009) Effects of red ginseng extract on UVB irradiation-induced skin aging in hairless mice. J Ethnopharmacol 123:446-451. doi: 10.1016/j.jep.2009.03.022
  107. 107.Zhong JJ, Bai Y, Wang SJ (1996) Effects of plant growth regulators on cell growth and ginsenoside saponin production by suspension cultures ofPanax quinquefolium. J Biotechnol 45:227-234.https://doi.org/10.1016/0168-1656(95)00170-0
  108. 108.Tam WJ, Constabel F, Kurz WG (1980) Codeine from cell suspension cultures ofPapaver somniferum. Phytochemistry 19:486-487. doi: 10.1016/0031-9422(80)83215-8
  109. 109.Huang FC, Kutchan TM (2000) Distribution of morphinan and benzo [c] phenanthridine alkaloid gene transcript accumulation inPapaver somniferum. Phytochemistry 53:555-564.https://doi.org/10.1016/S0031-9422(99)00600-7
  110. 110.Archambault J, Williams RD, Bédard C, Chavarie C (1996) Production of sanguinarine by elicited plant cell culture I. Shake flask suspension cultures. J Biotech 46:95-105. doi: 10.1016/0168-1656(95)00184-0
  111. 111.Antognoni F, Zheng S, Pagnucco C, Baraldi R, Poli F, Biondi S (2007) Induction of flavonoid production by UV-B radiation inPassiflora quadrangularis callus cultures. Fitoterapia 78: 345-352. doi: 10.1016/j.fitote.2007.02.001
  112. 112.Hempel J, Pforte H, Raab B, Engst W, Böhm H, Jacobasch G (1999) Flavonols and flavones of parsley cell suspension culture change the antioxidative capacity of plasma in rats. Mol Nutr Food Res 43:201-204 doi: 10.1002/(SICI)1521-3803(19990601)43:3<201::AID-FOOD201>3.0.CO;2-1
  113. 113.Scragg AH, Allan EJ (1986) Production of the triterpenoid quassin in callus and cell suspension cultures ofPicrasma quassioidesBennett. Plant Cell Rep 5:356-359. doi: 10.1007/BF00268601
  114. 114.Saad I, Dı́az E, Chávez I, Reyes-Chilpa R, Rubluo A, Jiménez-Estrada M (2000) Antifungal monoterpene production in elicited cell suspension cultures ofPiqueria trinervia. Phytochemistry 55:51-57.https://doi.org/10.1016/S0031-9422(00)00211-9doi: 10.3390/molecules19068679
  115. 115.Chattopadhyay S, Srivastava AK, Bhojwani SS, Bisaria VS (2002) Production of podophyllotoxin by plant cell cultures ofPodophyllum hexandrumin bioreactor. J Biosc Bioeng 93:215-220. doi: 10.1016/S1389-1723(02)80017-2
  116. 116.Shinde AN, Malpathak N, Fulzele DP (2009) Studied enhancement strategies for phytoestrogens production in shake flasks by suspension culture ofPsoralea corylifolia. Bioresour Technol 100:1833-1839.https://doi.org/10.1016/j.biortech.2008.09.028
  117. 117.Yamamoto O, Yamada Y (1986) Production of reserpine and its optimization in culturedRauwolfia serpentinaBenth. Cells. Plant Cell Rep 5:50-53. doi: 10.1007/BF00269717
  118. 118.Perassolo M, Quevedo CV, Giulietti AM, Talou JR (2011) Stimulation of the proline cycle and anthraquinone accumulation inRubia tinctorumcell suspension cultures in the presence of glutamate and two proline analogs. Plant Cell Tiss Organ Cult 106:153-159.https://doi.org/10.1007/s11240-010-9903-5
  119. 119.Tsutomu N, Hitoshi M, Masao N, Hideko H, Kaisuke Y (1983) Production of cryptotanshinone and ferruginol in cultured cells ofSalvia miltiorrhiza. Phytochemistry 22:721-722.https://doi.org/10.1016/S0031-9422(00)86969-1
  120. 120.Chen H, Yuan JP, Chen F, Zhang YL, Song JY (1997) Tanshinone production in Ti-transformedSalvia miltiorrhizacell suspension cultures. J Biotechol 58:147-156. doi: 10.1016/s0168-1656(97)00144-2
  121. 121.Zhao DX, Fu CX, Han YS, Lu DP (2005) Effects of elicitation on jaceosidin and hispidulin production in cell suspension cultures ofSaussurea medusa. Process Biochem 40:739-745.https://doi.org/10.1016/j.procbio.2004.01.040
  122. 122.Sánchez-Sampedro MA, Fernández-Tárrago J, Corchete P (2005) Yeast extract and methyl jasmonate-induced silymarin production in cell cultures ofSilybum marianum(L.) Gaertn. J Biotechnol 119:60-69. doi: 10.1016/j.jbiotec.2005.06.012
  123. 123.Aburjai T, Bernasconi S, Manzocchi LA, Pelizzoni F (1997) Effect of calcium and cell immobilization on the production of choleocalciferol and its derivatives bySolanum malacoxyloncell cultures. Phytochemistry 46:1015-1018. doi: 10.1016/S0031-9422(97)00408-1
  124. 124.Pérez-Hernández J, González-Cortázar M, Marquina S, Herrera-Ruiz M, Meckes-Fischer M, Tortoriello J, Cruz-Sosa F, Nicasio-Torres MP (2014) Sphaeralcic acid and Tomentin, Anti-inflammatory compounds produced in cell suspension cultures ofSphaeralcea angustifolia. Planta Med 80:209-214. doi: 10.1055/s-0033-1360302
  125. 125.Rico-Rodríguez L, Ortiz-Butrón R, Silva-Torres R, Díaz-Cedillo F, Franco-Colín M (2015) Diseño bifactorial de reguladores de crecimiento para la obtención de un alcaloide a partir del cultivo celular deSwietenia humilisZucc. Rev Mex Cienc Farm 46:57-61.https://www.redalyc.org/articulo.oa?id=57945705006
  126. 126.Nieto-Trujillo A, Buendía-González L, García-Morales, C, Román-Guerrero, A, Cruz-Sosa F, Estrada-Zúñiga ME (2017) Phenolic compounds and parthenolide production fromin vitrocultures ofTanacetum parthenium. Rev Mex Ing Qum 16:371-387.https://www.redalyc.org/pdf/620/62052087004.pdf
  127. 127.Yukimune Y, Tabata H, Higashi Y, Hara Y (1996) Methyl jasmonate-induced overproduction of Paclitaxel and Baccatin III in Taxus cell suspension cultures. Nat Biotechnol 14:1129-1132.https://doi.org/10.1038/nbt0996-1129
  128. 128.Wang Q, Mawassi M, Li P, Gafny R, Sela I, Tanne E (2003b) Elimination of grapevine virus A (GVA) by cryopreservation ofin vitro-grown shoot tips ofVitis viniferaL. Plant Sci 165:321-327.https://doi.org/10.1016/S0168-9452(03)00091-8
  129. 129.Yue X, Zhang W, Deng M (2011) Hyper-production of 13 C-labeled trans-resveratrol inVitis viniferasuspension cell culture by elicitation andin situadsorption. Biochem Eng J 53:292-296.https://doi.org/10.1016/j.bej.2010.12.002
  130. 130.Nagella P, Murthy HN (2010) Establishment of cell suspension cultures ofWithania somniferafor the production of withanolide A. Bioresour Technol 101:6735-6739.https://doi.org/10.1016/j.biortech.2010.03.078
  131. 131.Pérez-Hernández J, Nicasio-Torres MP, Sarmiento-López LG, Rodríguez-Monroy M (2019) Production of anti-inflammatory compounds in Sphaeralcea angustifolia cell suspension cultivated in stirred tank biorreactor. Eng Life Sci 19:196-205. doi: 10.1002/elsc.201800134
  132. 132.Nicasio-Torres MP, Pérez-Hernández J, González-Cortázar M, Meckes-Fischer M, Tortoriello J, Cruz-Sosa F (2016) Production of potential anti-inflammatory compounds in cell suspension cultures ofSphaeralcea angustifolia(Cav.) G. Don. Acta Physiol Plant 38:209. doi:10.1007/s11738-016-2211-x
  133. 133.Nicasio-Torres MP, Serrano-Román J, Pérez-Hernández J, Jiménez-Ferrer E, Herrera-Ruiz M (2017) Effect of dichloromethane-methanol extract and tomentin obtained from Sphaeralcea angustifolia cell suspensions in a model of kaolin/carrageenan-induced arthritis. Planta Med Int Open 4, e35-e42. doi: 10.1055/s-0043-108760
  134. 134.García-Rodríguez RV, Chamorro-Cevallos G, Siordia G, Jiménez-Arellanes MA, Chávez-Soto MA, Meckes-Fischer M (2012)Sphaeralcea angustifolia(Cav.) G. Don extract, a potential phytomedicine to treat chronic inflammation. BLACPMA 11:454-463.https://www.redalyc.org/articulo.oa?idp=1&id=85624131008&cid=47965
  135. 135.Romero-Cerecero O, Meckes-Fischer M, Zamilpa A, Jiménez-Ferrer JE, Nicasio-Torres P, Pérez-García D, Tortoriello J (2013) Clinical trial for evaluating the effectiveness and tolerability of topicalSphaeralcea angustifoliatreatment in hand osteoarthritis. J Ethnopharmacol 147:467-473. doi: 10.1016/j.jep.2013.03.040
  136. 136.Albarello N, Simotilde C, de Castro TC, Gayer CRM, Coelho MGP, de Moura R.S, Mansur E (2013) Anti-inflammatory and antinociceptive activity of field-growth plants and tissue culture ofCleome spinosa(Jacq.) in mice. J Med Plants Rese 7:1043-1049. doi: 10.5897/JMPR12.153
  137. 137.Pérez-González MZ, Gutiérrez-Rebolledo GA, Yépez-Mulia L, Rojas-Tomé IS, Luna-Herrera J. Jiménez-Arellanes MA (2107) Antiprotozoal, antimycobacterial and anti-inflammatory evaluation ofCnidoscolus chayamansa(Mc Vaugh) extract and the isolated compounds. Biomed Pharmacother 89:89-97. doi: 10.1016/j.biopha.2017.02.021
  138. 138.Pérez-González MZ, Siordia-Reyes AG, Damián-Nava P, Hernández-Ortega S, Macías-Rubalcava ML, Jiménez-Arellanes MA (2018) Hepatoprotective and anti-inflammatory activities of theCnidoscolus chayamansa(Mc Vaugh) leaf extract in chronic models. Evid Based Complement Alternat Med 2018:3896517. doi: 10.1155/2018/3896517
  139. 139.Pérez-González MZ, Macias-Rubalcava ML, Hernández-Ortega S, Siordia-Reyes AG, Jiménez-Arellanes MA (2019) Additional compounds and the therapeutic potential ofCnidoscolus chayamansa(McVaugh) against hepatotoxicity induced by antitubercular drugs. Biomed Pharmacother 117:1091140, 1-10. doi: 10.1016/j.biopha.2019.109140
  140. 140.Pérez-González MZ, Nieto-Trujillo A, García-Martínez I, Estrada-Zuñiga ME, Bernabe-Antonio A, Jiménez-Arellanes MA, Cruz-Sosa F (2018) Establishing a callus culture ofCnidoscolus chayamansaMc Vaugh: A species with ethnopharmacological value. Adv Biochem Biotech 2018:1-5.https://gavinpublishers.com/admin/assets/articles_pdf/1544189353article_pdf1396193972.pdf
  141. 141.Pérez-González MZ, Nieto-Trujillo A, García-Martínez I, Estrada-Zúñiga ME, Bernabé-Antonio A, Jiménez-Arellanes MA Cruz-Sosa F (2019) Lupeol acetate production and antioxidant activity of a cell suspension culture fromCnidoscolus chayamansaleaves. S Afr J Bot 125:30-38.https://doi.org/10.1016/j.sajb.2019.06.030
  142. 142.Taniguchi S, Imayoshi Y, Kobayashi E, Takamatsu Y, Ito H, Hatano T, Harukuni S, Tokudac H, Nishinoc H, Sugitad D, Shimurad S, Yoshida T (2002) Production of bioactive triterpenes byEriobotrya japonicacalli. Phytochemistry 59:315-323.https://doi.org/10.1016/S0031-9422(01)00455-1
  143. 143.Tortoriello J, Ortega A (1993) Sedative effect of galphimine B, a nor-seco-triterpenoid fromGalphimia glauca. Planta Med 59:398-400. doi: 10.1055/s-2006-959717
  144. 144.Tortoriello J, Ortega A, Herrera-Ruíz M, Trujillo J, Reyes-Vázquez C (1998) Galphimine-B modifies electrical activity of ventral tegmental area neurons in rats. Planta Med 64:309-313. doi: 10.1055/s-2006-957440
  145. 145.Osuna L, Pereda-Miranda R, Tortoriello J, Villarreal ML (1999) Production of the sedative triterpene galphimine B inGalphimia glaucatissue culture. Planta Med 65:149-152. doi: 10.1055/s-1999-14057
  146. 146.Osuna L, Moyano E, Mangas S, Bonfill M, Cusidó RM, Piñol MT, Zamilpa A, Tortoriello L, Palazón J (2008) Immobilization ofGalphimia glaucaplant cell suspensions for the production of enhanced amounts of Galphimine-B. Planta Med 74:94-99. doi: 10.1055/s-2007-993763
  147. 147.Aguilar-Santamaría L, Ramírez G, Herrera-Arellano A, Zamilpa A, Jiménez JE, Alonso-Cortés D, Cortés-Gutiérrez EI, Ledesma N, Tortoriello J (2007) Toxicological and cytotoxic evaluation of standardized extracts ofGalphimia glauca. J Ethnopharmacol 109:35-40. doi: 10.1016/j.jep.2006.06.013
  148. 148.Herrera-Ruiz M, Jiménez-Ferrer JE, De Lima TCM, Avilés-Montes D, Pérez-García D, González-Cortázar M, Tortoriello J (2006) Anxiolytic and antidepressant-like activity of a standardized extract fromGalphimia glauca. Phytomedicine 13:23-28. doi: 10.1016/j.phymed.2005.03.003

Written By

María Adelina Jiménez-Arellanes and Mariana Z. Pérez-González

Submitted: February 23rd, 2021Reviewed: August 11th, 2021Published: September 10th, 2021