Secondary metabolites obtained for cellular cultures from medicinal plant tissues
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.
- Mexican medicinal plants
- plant tissue culture
- secondary metabolites
- phenolic compounds
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 .
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 .
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 .
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 . 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.
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 .
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 . In modern medicine, digoxin is use as a cardiotonic and was isolated from
Guanidine is a natural product with good hypoglycemic activity that was isolated from
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 . Some examples of these include ginseng, it is obtained from Panax genus (
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 . 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 .
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) , 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 . 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 .
There is other technique very used to obtain SMt
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) . 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 .
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,
Recently, interest in research and development of
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.
|Rosmarinic acid||Antioxidant||[40, 41]|
|Rosmarinic acid and Glycosides||Antioxidant|||
|Verbascoside (||Anti-inflammatory, antioxidant|||
|Homo isoflavones||Antimicrobial, antitumoral|||
|Thiamine or theanine||Antihypertensive|||
|Verbascoside (||Anti-inflammatory, Antispasmodics|||
|Chlorogenic acid, Isoorientin||Hypoglycemic|||
|Furoquinolin alkaloids||Antitumoral, Antimicrobial|||
|Berberin (||Intestinal infection|||
|β-glucogallin, (+)-Catechin, (+)-gallocatechin, procyanidin B-3||Hyperglycemic and antimicrobial|||
|Cinarin, Chlorogenic acid||Antioxidant|||
|Diosgenin (||Steroidal stimulant|||
|Plumbagin (||Anticancer, Antimicrobial|||
|Eleuteroside||Anti-inflammatory, diuretic, analgesic,|
|Triterpenes||Anti-inflammatory, antidiabetic, antitumoral|||
|Chlorogenic acid (||Antimicrobial, Antioxidant|||
|Galphimine B (||Central nervous system disorders|||
|Rosmarinic acid (||Antioxidant|||
|Antocyanins||Antioxidant||[92, 93, 94]|
|Nordihydroguayaretic acid, Quercetin||Antiarthritic, digestive, against venereal diseases|||
|Rosmarinic acid (||Hepatoprotective||[96, 97]|
|Coumarins, lactones, flavonids||Antioxidants|||
|Cerebroside||Cellular Growth Regulator|||
|Rosmarinic acid (||Antioxidant|||
|Ginkgolides (||Cognitive deterioration|||
|Sanguinarin (||Platelet stimulator|||
|Orientin, Isoorientin, Vitexin, Isovitexin||Antioxidant|||
|Genistein and Daidzein||Tonic|||
|Cholecalcipherol||Aids calcium absorption|||
|Sphaeralcic acid (||Antiinflammatory|||
|Resveratrol (||Antioxidant, Hepatoprotective|||
|Withanolide A||Antioxidant, Antistress|||
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
In another study, the anti-inflammatory activity of the cell suspension culture from
In parallel with obtaining cells
Another plant utilized in Mexican ethnomedicine is
The lipophilic extract containing beta-carotene (LMBC) from plant cell cultures of
5. Antineoplasic activity of the plant material obtained by biotechnological cultures
From the callus culture of
6. Biological effect of SMt isolated from cell cultures of
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
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
8. Evaluation of the MeOH extract of
Galphimia glaucain Behavioral models of anxiety
The anxiolytic and anti-depressive effects were evaluated for the
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
Susan Drier for English language corrections.
This manuscript is a review and we did not have funding.
The author declare no competing interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
Sociedad Mexicana de Biotecnología y Bioingeniería
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