Production Of Phytopharmaceuticals Research Articles

Quality parameters for the medicinal plant Drosera rotundifolia L.: A new approach with established techniques.

Monographs of the European Pharmacopoeia (Ph. Eur.) are the basis for quality control of medicinal plants and therefore important to ensure the consistency, quality, safety, and efficacy of phytopharmaceuticals. The traditional medicinal plant sundew (Drosera sp.) has disappeared from therapy due to nature conservation, but can now be cultivated sustainably on rewetted peatland. However, currently there is no valid Ph. Eur. monograph for the quality control of Droserae herba. In this study, sundew material from different species and sources was investigated with the aim of developing quality control methods based on the Ph. Eur. and defining a uniform quality standard for Droserae herba. It was possible to distinguish between sundew species of different quality, using macroscopic, microscopic, and chromatographic methods. Special emphasis was laid on the content of flavonoids and naphthoquinones as important quality parameters as their content differed between the sundew species. The differences in content and toxicity result in the recommendation that only round-leaved sundew (Drosera rotundifolia L.) should be used as a medicinal plant for the production of phytopharmaceuticals in the future.

Bibliometric review of the economic potential and use of medicinal plants in Brazil

The objective of this study was to conduct a bibliometric review on the economic potential of medicinal plants used as phytotherapeutics. To achieve this, a search was conducted on Google and Google Scholar websites, without a specific time frame, using terms such as medicinal plant, medicinal plants, economic value of medicinal plants, economic potential of medicinal plants, medicinal plants used by the Unified Health System (SUS), and the word “leaflet” followed by the common or scientific name or the phytomedicine. Based on the texts found through this search, this article was elaborated. As a result, the history of medicinal plants and the evolution of their use were introduced, considering them as sources of biologically active molecules that currently hold significant economic potential in the pharmaceutical industry market. Additionally, due to being lower-cost alternatives compared to allopathic medicines, they are widely used by the SUS. The study of new phytotherapeutics is a highly promising field, particularly in Brazil, which possesses an immeasurable quantity of plants with medicinal properties. However, significant research and effective development of new phytomedicines require increased financial investment in the area to boost the production of new Brazilian phytopharmaceuticals and genuine phytotherapeutics. This, in turn, will generate higher profits in this sector.

Season, basal media and plant growth regulators effect in wood plant in vitro propagation: a comprehensive review

Wood plant in-vitro propagation is currently widely used and is not limited to the preparation of superior seeds but has been widely utilized for the production of phytopharmaceuticals and the production of a valuable and specific tree for the benefit of man. Studies focused on the influence of explant collection seasons, selection of basic media, and plant growth hormone. The results of the study showed the magnitude of the variables that must be considered in the propagation of tissue cultures even in the same species and types of cultures. The period of January and March is the best time for explant retrieval because it provides the best explant response in bud breakage, lowest browning, and best bud induction. The basic media of MS (Murashige & Skoog), as well as its various modifications and the basic medium of WPM (Wood Plant Medium), tend to be widely chosen as the basic media at various levels of subcultures in many woody plant species. The application of growth regulators shows a tendency to use BAP (benzyl amino purine) and NAA (naphthalene acetic acid) whose application is separately or in combination with a certain concentration according to the species and subculture phase. Other plant growth regulators (PGRs) that are also quite widely used are the IBA (indole butyric acid), IAA (indole acetic acid), and G3 (gibberellic acid) groups which are used in the multiplication and rooting stages. The information from the study can be used as basic information at the stage of optimizing tissue culture activities in different species, explanatory, and regeneration types. The success of the optimization stage will be used as an improvement to the previous woody plant tissue culture protocol so that optimization of success is achieved. In vitro propagation is always associated with the number of resources used, so efforts to improve in vitro protocols are a very important activity to evaluate that will lead to increased effectiveness to reduce resource inputs, and be able to realize low-cost wood plant tissue culture propagation.

PHARMACEUTICAL WASTE – A NEW THREAT TO LAKE ECOSYSTEMS

According to the Basel Convention (1998), pharmaceutical waste is waste from medical care in hospitals, medical centers and clinics, waste from the production and preparation of pharmaceutical products, waste pharmaceuticals, drugs and medicines, wastes from the production, formulation and use of biocides and phytopharmaceuticals. They belong to the so-called Yellow List, and are all, without exception, regarded hazardous. A review of the results of studies on pharmaceutical wastes in water bodies (rivers and lakes) in Russia and abroad has been produced. Medicines are an integral part of medical practice. They serve the preservation of the health of the population and, as a result, enhance the quality and prolong the duration of life. On the other hand, pharmaceutical industry waste is increasingly affecting wildlife, as unused medicines are often discarded or disposed of improperly. At the beginning of the 21st century, the European Environment Agency (EEA) designated the impact of active pharmaceutical ingredients on the environment as a new environmental problem. The main pathways by which drugs reach the environment have been charted. Meanwhile, Russia has no system to regulate maximum permissible concentrations of drugs in water bodies. The purpose of this study is to work out a methodology for calculating maximum permissible concentrations of drugs in water bodies of fishery importance. An adequate correlation has been established between maximum permissible concentrations of harmful substances in water bodies of fishery importance (MPCf) and their average lethal concentrations for daphnia. Indicative MPCf values have been calculated for 12 pharmaceutical products.

Pea transformation: History, current status and challenges

This review recapitulates the history, important milestones, the current status, and the perspectives of the pea (Pisum sativum L.) transformation as a tool for pea crop breeding. It summarises the developments of the pea transformation from the first methodological experiments to achieving the complete transformation and regeneration of genetically modified (GM) plants, transformation with the first genes of interest (GOI), to recent techniques of targeted genome editing. We show how recent biotechnological methods and genetic engineering may contribute to pea breeding in order to speed up the breeding process and for the creation of new pea cultivars. The focus is laid on genetic engineering which represents an excellent technology to enhance the pea gene pool with genes of interest which are not naturally present in the pea genome. Different methods of pea transformation are mentioned, as well as various GOI that have been used for pea transformation to date, all aimed at improving transgenic pea traits. Tolerance to herbicides or resistance to viruses, fungal pathogens, and insect pests belong, among others, to the pea traits that have already been modulated by methods of genetic engineering. The production of phytopharmaceuticals is also an important chapter in the use of genetically modified peas. We compare different methods of introducing transgenes to peas and also the usage of different selective and reporter genes. The transformation of other major legumes (soybeans, beans) is marginally mentioned. The effect of genetically modified (GM) peas on animal health (feeding tests, allergenicity) is summarised, the potential risks and benefits of pea modification are evaluated and also the prime expectations of GM peas and the real current state of this technology are compared. Unfortunately, this technology or, more precisely, the products created by this technology are under strict (albeit not scientifically-based) legislative control in the European Union.

Биологическая активность экстрактов из корней Vexibia alopecuroides и Salvia deserta

Biologically active compounds (BAC) of plants are represented by various classes of organic compounds and are a prospective raw material for developing therapeutic and preventive remedies. There are more than 6,000 plant species on the territory of the Republic of Kazakhstan that might become a source of raw materials for development and production of new domestic original phyto-pharmaceuticals. Therefore, testing of biologically active compounds extracted from Kazakhstan’s wild-growing plants is a timely and promising task. It was determined that the roots of two wild plants of Kazakhstan flora - Salvia deserta and Vexibia alopecuroides contain biologically active compounds with high a) antibacterial and antifungicidal activities estimated by the IC50 index, b) anti-inflammatory activity estimated by the ability to inhibit production of nitric oxide, c) therapeutically significant antioxidant potential with respect to the ABTS.+ radical cations. Crude extracts of biologically active compounds from the roots of S. deserta and V. alopecuroides plants that have the above mentioned activities were obtained by maceration with methylene chloride, purified into individual compounds using flash and gas chromatography. It was determined that 9 individual compounds that revealed biological activity were isolated from Vexibia alopecuroides roots’ extract, which belongs to flavonoids, and 4 compounds were isolated from Salvia deserta roots’ extract, which belongs to diterpenoids. Individual compounds isolated from Salvia deserta and Vexibia alopecuroides roots’ extract showed antimicrobial activity against S. aureus, Methicillin-resistant S. aureus, P. aeruginosa, C. glabrata, C. krusei, C. albicans with an IC50 index within the range of < 0, 8 to 13.38 μg / ml. It allows to consider them as potential candidates for development of new-galenic phyto-pharmaceuticals. Key words: biologically active compounds, crude extracts, antimicrobial activity, Salvia deserta, Vexibia alopecuroides.

Horizontal natural product transfer: A potential source of alkaloidal contaminants in phytopharmaceuticals

BackgroundIt was recently shown that nicotine and pyrrolizidine alkaloids that leach out from decomposing plant material (donor plants) are subsequently taken up by the roots of acceptor plants and translocated into their leaves. Furthermore, it is well established that plant roots take up xenobiotics, generally by simple diffusion, and that this passive import depends on the physico-chemical properties of the substances. HypothesisBased on the well-known uptake of xenobiotics, we assumed that in analogy, the uptake of alkaloids, which are leached out from plant material (donor plants) represents a quite general feature of plant biology. MethodsUsing barley as a model plant, we analyzed the uptake of alkaloids by applying them to Hordeum vulgare seedlings. Based on HPLC analyses, the presence of the particular alkaloids in the acceptor plants was determined. ResultsWe demonstrated that numerous alkaloids of different structural types are able to diffuse through biomembranes and are taken up by acceptor plants. In contrast, an uptake of quaternary alkaloids, with a permanent positive charge, could not be detected. ConclusionAs most alkaloidal plants generally die back afield, and the corresponding natural products are leached out into the soil. Our findings have substantial relevance for all plant-derived commodities, especially for the production of phytopharmaceuticals and the related safety issues. Moreover, the evidence that plants are inherently able to take up alkaloids from the soil, which are derived from other plants, will alter our appraisal of plant–plant interactions. In this context, the classical definition of xenobiotics, which are considered as “non-natural” substances, might be also extended by including natural products leached out into the soil.

Current Perspective in the International Trade of Medicinal Plants Material: An Update.

The recent years have seen an increased interest in medicinal plants together with the therapeutic use of phytochemicals. Medicinal plants are utilized by the industry for the production of extracts, phytopharmaceuticals, nutraceuticals and cosmeceuticals and their use is expected to grow faster than the conventional drugs. The enormous demand of medicinal plant material has resulted in huge trade both at domestic and international levels. The trade data of medicinal plant material with commodity code HS 1211 (SITC.4, code 292.4) and their derived/related products which are traded under different commodity codes has been acquired from COMTRADE, Trade Map, country reports, technical documents etc for the period 2001 to 2014. The data was analyzed using statistical tools to draw conclusions. The significant features of the global trade; the leading source, consumer, import and export countries; and the striking trends are presented. The trade of the ten key countries and the selected important items is also discussed in detail. The conservative figure of trade of medicinal plants materials and their derived/related products including extracts, essential oils, phytopharmaceuticals, gums, spices used in medicine, tannins for pharmaceutical use, ingredients for cosmetics etc. as calculated from the global export data for the year 2014 is estimated at USD 33 billion. The average global export in medicinal plants under HS 1211 for the fourteen year period was USD 1.92 billion for 601,357 tons per annum and for the year 2014 it stood at 702,813 tons valued at USD 3.60 billion. For the studied period, an annual average growth rate (AAGR) of 2.4% in volumes and 9.2% in values of export was observed. Nearly 30% of the global trade is made up by top two countries of the import and export. China and India from Asia; Egypt and Morocco from Africa; Poland, Bulgaria and Albania from Europe; Chile and Peru from South America are important supply sources. The USA, Japan and Europe are the major consumers of the world.

The relevance of pharmacognosy in pharmacological research on herbal medicinal products.

As all medicines, herbal medicinal products are expected to be safe, effective, and of appropriate quality. However, regulations on herbal medicinal products vary from country to country, and herbal preparations do occur not only in the form of medicinal products but also as less strictly regulated product groups like dietary supplements. Therefore, it is not always easy for the consumers to discriminate high-quality products from low-quality products. On the other hand, herbal medicines have many special features that distinguish them from conventional medicinal products. Plants are complex multicomponent mixtures; in addition, their phytochemical composition is not constant because of inherent variability and a plethora of external influences. Therefore, the production process of an herbal medicinal product needs to be strictly monitored. First of all, the starting materials need to be correctly authenticated and free of adulterants and contaminants. During plant growth, many factors like harvest season and time, developmental stage, temperature, and humidity have a strong impact on plant metabolite production. Also, postharvest processing steps like drying and storage can significantly alter the phytochemical composition of herbal material. As the production of many phytopharmaceuticals includes an extraction step, the extraction solvent and conditions need to be optimized in order to enrich the bioactive constituents in the extract. The quality of finished preparations needs to be determined either on the basis of marker constituents or on the basis of analytical fingerprints. Thus, all production stages should be accompanied by appropriate quality assessment measures. Depending on the particular task, different methods need to be applied, ranging from macroscopic, microscopic, and DNA-based authentication methods to spectroscopic methods like vibrational spectroscopy and chromatographic and hyphenated methods like HPLC, GC-MS and LC-MS. Also, when performing pharmacological and toxicological studies, many features inherent in herbal medicinal products need to be considered in order to guarantee valid results: concerning in vitro studies, difficulties are often related to lacking knowledge of ADME characteristics of the bioactive constituents, nuisance compounds producing false positive and false negative results, and solubility problems. In in vivo animal studies, the route of administration is a very important issue. Clinical trials on herbal medicinal products in humans very often suffer from a poor reporting quality. This often hampers or precludes the pooling of clinical data for systematic reviews. In order to overcome this problem, appropriate documentation standards for clinical trials on herbal medicinal products have been defined in an extension of the CONSORT checklist. This article is part of a Special Issue entitled "Botanicals for Epilepsy".

Flavonoids of willow herb (Chamerion angustifolium (L.) Holub) and their radical scavenging activity during vegetation

PurposeWillow herb has been traditionally used in folk medicine and currently it is a potential raw material for production of phytopharmaceuticals. The aim of this work was to determine the highest amount of flavonoids and the highest radical scavenging activity of willow herb, which was collected in different vegetation phases (intensive growing, bud, massive blooming, ripening of fruits (seeds) and the end of vegetation) and in different parts of the plant (blooms, leaves and stems). Material/methodsRaw material was collected at Kaunas Botanical garden of Vytautas Magnus University. Willow herb was extracted using methanol/water mixture (75/25 v/v, %). Methanolic extracts were purified using solid-phase extraction. For determination of the radical scavenging activity of compounds the HPLC system with the on-line post-column DPPH (1,1-diphenyl-2-picrylhydrazyl) radical reaction detection was used. ResultsFive flavonoids were identified and their quantitative distribution and radical scavenging activity were evaluated. The highest total amount of flavonoids and radical scavenging activity were determined in willow herb collected during the massive blooming phase (11.12±0.34mg/g and 8.71±0.29mg/g, respectively). ConclusionsThe highest amount of flavonoids and radical scavenging activity was determined for raw material collected during the massive blooming phase. Evaluation of different parts of the plant during the massive blooming phase revealed that the highest amount of flavonoids and radical scavenging activity are characteristic for blooms of the plant.

Media optimization in immobilized culture to enhance the content of Kaempferol in Tylophora indica (Asclepeadaceae) and Curcumin in Curcuma longa (Zingiberaceae).

Immobilization of plant cell plays a very important role in exploiting plant cell culture for the production of high value phyto-pharmaceuticals. It is the advanced novel biotechnological approach, through which it is possible to achieve a physiological state conducive for metabolite production .That can overcome many limiting factors of suspension culture with distinct advantage of easier separation from product and also being agreeable for biotransformation of low value compounds to higher value product. In the described study, the immobilized culture of Tylophora indica (Asclepeadaceae) and Curcuma longa (Zingiberaceae) derived from leaves and rhizome respectively were used to enhance the production of their active compounds, Kaempferol and Curcumin. The maximum content of Kaempferol and Curcumin were obtained in cultures fed with 5mg/100ml of Cinnamic acid i.e.3.31%/300beads and 3.36 %/300beads respectively at the age of two weeks in Zenk media .This study also has given a clear image of biosynthetic pathway of these compounds.

Media Optimization in Immobilized Culture to Enhance the Content of Curcumin in Curcuma longa (Zingiberaceae) and Protein Profile of Treated Samples in Static Culture

Plant cell culture system has served as an alternative to enhance the production of high value phyto-pharmaceuticals. In the described study, the immobilized culture and static culture of Curcuma longa (Zingiberaceae) were used to maximize the production of the bioactive compound Curcumin. It was observed that Curcumin content in vitro studies (static as well as immobilize cultures) were enhanced in one week old cultures fed with 5 mg/100 ml of media (Static 8.71%; immobilize 2.03%). Statistically significant (seven fold) enhancement in Curcumin content was obtained in one week old static culture, which was maintained on Zenk production media incorporated with cinnamic acid (Control 1.57% and induced 8.717%). Quantitative estimation was done using HPTLC analysis with standard Curcumin. To evaluate the effect of treatment on total protein in Curcumin biosynthesis, we have examined Curcumin content as well as the protein profile of treated samples of Curcuma longa static culture. All the treated samples were analysed using SDS-PAGE for their proteomic profiles. A 23,420 Da protein was prominently expressed in all samples which may be a glycine rich protein (works on defence mechanism). Treated samples exhibited decreased expression of the protein as compared to control. This may be attributed to the formation of Reactive Oxygen species (ROS) in culture condition due to high concentration of sucrose (5%) in the Curcuma longa culture media that is known to induce oxidative stress and subsequent increase in Curcumin production. Further investigation is required to understand the actual protein involvement in Curcumin synthesis in different cultures treated with different compounds. The study signifies the use of plant explants to develop immobilized and static cultures rather than callus in Zenk media, which reduce the time as well as expenditure. The proteomic profile of C. longa has been discussed earlier, but its effect on proteomic profile of in vitro treated samples is a new study.

Phytochemistry of the Carnivorous Sundew Genus Drosera (Droseraceae) – Future Perspectives and Ethnopharmacological Relevance

Species of the carnivorous genus Drosera L. have long been a source of valuable natural products. The various phytochemicals characteristic of these species, particularly 1,4-naphthoquinones and flavonoids, have contributed to the diverse utilization of sundews in traditional medicine systems worldwide. A growing number of studies have sought to investigate the comparative phytochemistry of Drosera species for improved sources of pharmaceutically important compounds. The outcomes of these studies are here collated, with emergent trends discussed in detail. Important factors which affect production of secondary metabolites in plants are critically examined, such as environmental influences and in vitro culture, and recommendations subsequently presented based on this. Explicitly, the current review aims to i) present an updated, comprehensive listing of the phytochemical constituents of the genus (including quantitative data where available), ii) summarize important factors which may influence the production of phytopharmaceuticals in plants, and iii) recommend guidelines for future research based on the above, including improved standardization and quality control. We have also included a section discussing future perspectives of research on Drosera spp. based on three different research lines i) the potential to produce much needed lead compounds for treatment of tuberculosis, ii) the potential role of anthocyanins in nitrogen transport, and iii) research into 'Natural Deep Eutectic' solvents produced by Drosera spp. in the droplets or 'dew' employed to capture insect prey.

In Vitro Propagation of Medicinally ImportantCassiaSpecies – A Review

Medicinal plants are considered to be an important source of life-saving drugs for majority of the world's population. Recently there has been an increasing interest in the study of medicinal plants and their traditional use in primary healthcare. An ever-increasing demand of uniform medicinal plants and plant based medicines warrants their cloning through plant tissue culture (PTC) strategy. The biotechnological approaches are important to select, multiply and conserve the critical genotypes of medicinal plants. PTC techniques offer an integrated approach for the production of standardized quality phytopharmaceuticals through the mass production of consistent plant material. A variety of medicinal plants have been regenerated through in vitro techniques using various parts. This review is an attempt to highlight the current strategies available for in vitro propagation of medicinally important Cassia species. The genus Cassia is one of the most important genus of subfamily Caesalpinaceae (family Fabaceae), mostly distributed in the tropics and subtropics. It is comprised of about 600 species, most of them having medicinal values and used to cure a broad range of diseases, such as anaemia, bronchitis, cholera, eczema, jaundice, leprosy, liver diseases, scabies, splenic enlargement, typhoid, rheumatism, eye and skin diseases, cough, insomnia, headache, ophthalmia, constipation, hypertension and many more. Cassia spp. also possess anticancer, antidiabetic, antidiuretic, antihelminthic, anti-inflammatory, antigungal and purgative properties. The available literature on in vitro micropropagation of Cassia spp described the differential response to cytokinin and auxin treatment in the media for effective shoot regeneration and plantlet propagation. It was also found that the explants type played a specific role in morphogenesis and multiplication.

Editorial [Hot Topic:Contemporary Approaches Towards Production of Phytopharmaceuticals:Plant Biotechnology Meets Medicinal Chemistry (Guest Editor: Milen I. Georgiev)

Editorial [Hot Topic:Contemporary Approaches Towards Production of Phytopharmaceuticals:Plant Biotechnology Meets Medicinal Chemistry (Guest Editor: Milen I. Georgiev)

Effects of cytokinins on in vitro mineral accumulation and bud development in Annona glabra L.

Annona glabra is a tropical species that has significant agronomic potential in terms of furnishing fruits for in natura consumption and for the production of phyto-pharmaceuticals. In vitro cultivation has been considered the most promising form of propagation for this species, although large scale utilization of this technique is currently limited by high rates of leaf abscission, reduced rates of explant multiplication and slow bud growth. The present work evaluated the effects of different cytokinins on mineral accumulation in shoots of A. glabra cultivated in vitro, and their effects on growth and survival of these plants. Buds of A. glabra were cultivated in Wood Plant Medium (WPM) in the presence of 6-benzilaminopurine (BAP), thidiazuron (TDZ), kinetin (KIN), and zeatin (ZEA). KIN and BAP use resulted in the greatest growth, largest accumulation of dry mass and leaf area development, as well as the greatest survival rate during in vitro cultivation of this species. All cytokinins tested stimulated large accumulations of nitrogen and boron in shoots, but diminished levels of calcium as compared to controls.

Metabolic engineering of plant cell cultures – towards the new resources of alkaloids

Plants produce a wide range of secondary compounds, which have important functions for plants in survival and competing in the ecosystem. One of the major bottlenecks connected with the exploitation of plant cell cultures is that the biosynthetic pathways of secondary compounds are still poorly understood. We have designed a novel technology for unravelling the genes involved in the plant secondary metabolism. This technology called SoluCel® is based on the genome wide identification and functional analysis of genes involved in the production of phytopharmaceuticals in plant cell cultures. The advantage in this technology is that it is applicable to any plant, and no prior knowledge of the gene sequences is required, the fact which very often is encountered when it comes to exotic medicinal plants.

Biotechnological utilization of plant genetic resources for the production of phytopharmaceuticals

Natural products from plants are still important sources for the development of drugs, despite their recent neglect in pharmaceutical discovery programmes. The rapidly dwindling number of species endangers the availability of these natural compounds, which are characterized by the immense chemical and functional diversity ultimately responsible for their pharmaceutical activity. Although many steps in the drug discovery process have been continuously modified during recent years, a common dilemma is still unresolved, i.e. the supply crisis for hits discovered in rare wild plants due to their inaccessibility or lack of reproducibility. New technology, combining tissue culture, functional genomics and metabolomics, shows promise to overcome these problems and even to supply a greater chemical diversity of compounds.

Genomic and ploidy manipulation for enhanced production of phyto-pharmaceuticals

Polyploidization is often accompanied by increased cell size and conspicuous changes in secondary metabolism. Where vegetative plant organs are the source of secondary metabolites, as is the case with most medicinal plants, ploidy manipulations such as direct chromosome doubling or allopolyploidization provide a rapid means to realize enhanced production of phyto-pharmaceuticals. Supported with prospective examples, this article illustrates the potential of genomic and ploidy manipulation to enhance the resourcing of pharmaceuticals of plant origin and suggests some appropriate strategies for optimum utilization.

Necessity and Production of Medicinal Plants under Controlled Environments

The estimated value of the worldwide sales of plant-based medicines exceeds $15 billion in the year 2004. The international trade of plant-based medicines is becoming a major strength in the global economy and the demand is increasing in both developing and industrialized nations. However, the explosive growth of the trade of plant-based medicines has been accompanied by issues of quality, consistency and efficacy and leading to serious health problems associated with traditional field-grown plants or wild-harvest. This article discusses the problems associated with the cultivation, harvesting and process of medicinal plants for the production of phyto-pharmaceuticals. We suggest that it is necessary to ensure the safety and efficacy of plant-based medicines and to protect the genetic diversity of medicinal plants. An alternative is the cultivation of medicinal plants under controlled environments, which allows the precise control of optimized environmental conditions with maximum biomass and medicinal metabolites production and ensures the plants free from biotic and abiotic contaminations with consistent biochemical profiles. The controlled environment technology also ensures application of specific, controlled environment stresses that can optimize the production of medicinal metabolites by inducing natural biochemical changes in plants.