Phenolic compounds are one of the largest and most complex classes of secondary metabolites produced by plants and they arise via the pentose phosphate, shikimate, and phenylpropanoid pathways in plants. They have been the subject of numerous chemical, biological, agricultural, and medical studies (Laganà et al., 2019; Chiocchio et al., 2021). As chemically defined, phenolic compounds have hydroxylated aromatic rings at the centers where the hydroxy group is being attached directly to the phenyl, substituted phenyl, or other aryl groups (Alara et al., 2021). Phenolic compounds as exhibiting anti-inflammatory, anticancer, and antioxidant activities have been studied for their roles in the treatment of diabetes, neurodegenerative diseases, hypertension, and cancer (Chen and Zhang, 2021; Rahman et al., 2021a; Singh et al., 2021a). These roles may also be associated with their protective properties against oxidative stress and some diseases (Rahman et al., 2021b; Seker and Erdogan, 2023). Besides, simple phenolics have bacteriocidal, antiseptic, and anti-helminthic activities (Bekkar et al., 2021; Patil et al., 2021). It is a large group of compounds containing phenolic acids, phlorotannins, bromophenols, and flavonoids (Murray et al., 2018).

Till now, more than 8,000 structures of phenolic materials from plants including simple ones (i.e., phenolic acids) to highly polymerized ones (i.e., tannins) are identified. Their roles in growth, reproduction, and providing a contribution to plants’ colours as well as involvement in the facilitating of resistance against ultraviolet radiation, pathogens, parasites, and predators are reported. Due to being ever-present in all plant organs, flavonoids are ubiquitously found in the human diet. Phenolics are the compounds found to be widespread in plant foods including fruits, vegetables, cereals, olives, legumes, chocolate, and in beverages including tea, coffee, beer, wine (Saha et al., 2019; Dable-Tupas et al., 2023). Furthermore, organoleptic activity is at least partially attributed to plant food properties (Dai and Mumper, 2010; Yasien et al., 2022). Simple phenolic acids and flavonoids are found in plants with insoluble free, soluble esterified, and insoluble-bound configurations (Gulsunoglu et al., 2019).

Regarding the oxidation state of the central C ring, there are six subgroups of flavonoids, which are flavones, flavonols, flavanones, isoflavones, anthocyanins, and polyphenols, and they are most abundantly found in our diets (Reddy et al., 2020; Kumar et al., 2021). They show a very wide distribution of plants. In higher plants, flavonoids are involved in UV (ultraviolet) filtration, symbiotic nitrogen fixation, and floral pigmentation as well as playing roles in many processes as chemical messengers, physiological regulators, and cell cycle inhibitors (Baskar et al., 2018; Gupta et al., 2021; Liu et al., 2022).

Due to having a range of biological activities (antioxidant, anti-mutagenic, anti-inflammatory, and anti-viral properties), these compounds are considered to be a fundamental source of therapeutic applications (Ginwala et al., 2019). As putative inducers, certain flavonoids including naringenin, luteolin, and quercetin exert effects on PPAR-γ activation and escalate insulin sensitivity (Saini, 2010). Among the flavonoids, quercetin has the effects on relieving symptoms of diseases including high fever, eczema, asthma, and sinusitis (Sreeram et al., 2021; Sangeetha et al., 2022). Epidemiological studies have shown that heart diseases are inversely related to flavonoid intake. In addition, it is known that flavonoids have a preventive effect on the occurrence of the oxidation of low-density lipopolysaccharides and reduce the risk of the formation of atherosclerosis (Ginwala et al., 2019; Li et al., 2020).

Flavonoids provide health benefits with their wide spectrum of effects and are essential being as constituents in a variety of nutraceutical, pharmaceutical, medical, and cosmetic applications. This is due to their free radical scavenging properties being as strong anti-oxidants, along with their capacity to modulate basic cellular enzyme functions (Karak, 2019; Carsono et al., 2022). As a result of in vivo and/or in vitro research conducted on flavonoids has shown that flavonoids have anti-oxidant, anti-inflammatory, antipyretic, anti-allergic, anti-ulcer, anti-bacterial, anti-cancer, anti-viral, anti-protozoal, anti-platelets, anti-atherogenic activities (Lesnik and Bren, 2021; Mumtaz et al., 2021; Demir et al., 2022; Puangpraphant et al., 2022; Vo et al., 2022).

Tannin derived from the French “Tanin” is used for defining a range of naturally occurring water-soluble polyphenolic compounds (Khanbabaee and Van Ree, 2001). Tannins, which have two subgroups as hydrolyzable and condensed, form a large group among polyphenols. Hydrolyzable ones have a central core of glucose, or another type of polyol esterified with gallic acid (gallotannins), or with hexahydroxydiphenic acid (ellagitannins) (Dai and Mumper, 2010; Mal and Pal, 2022). As polyphenolic secondary metabolites of higher plants, structurally occurrences of tannins are either as galloyl esters and their derivatives, in which galloyl moieties or their derivatives are attached to a variety of polyol-, catechin- and triterpenoid cores, or as oligomeric and polymeric proanthocyanidins that have possessed of different interflavanyl coupling and substitution patterns (condensed tannins) (Fraga-Corral et al., 2021; Rajasekar et al., 2021).

It is known that tannins, as flavonoids, have antioxidant properties with their free radical scavenging effect and are involved in the complex antioxidant defence system by chelation of transition metals and inhibition of prooxidative enzymes (Koleckar et al., 2008; Pizzi, 2021). Tannins are actively used in the preparation of herbal-based medicines. According to studies, herbal tannins are used as astringents (stopping bleeding, constricting vessels) against diarrhea and as an auretic and anti-inflammatory against stomach and duodenal tumors (Brito-Arias, 2007; Fujiki et al., 2012). In addition, anti-tumor, cardioprotective, anti-inflammatory, and antimicrobial activities are defined for tannins (Hossain et al., 2021; Jing et al., 2022; Maugeri et al., 2022).

The synthesis of terpenoids proceeds via using of isoprenoid units (two five-carbon building blocks). Because of having a large number of building blocks, terpenoids are classified as: monoterpenes such as carvone, geraniol, D-limonene, and peril alcohol; diterpenes such as retinol and retinoic acid; triterpenes such as betulinic acid, lupeol, oleanolic acid, and ursolic acid; and tetraterpenes such as α-carotene, β-carotene, lutein, and lycopene (Thoppil and Bishayee, 2011; Ninkuu et al., 2021; Thomas and Pronin, 2021). The terpene synthases are involved in the biosynthesis of terpenes and related to this; they can easily be modified including new catalytic properties through minor changes in their structures. In the synthesis of monoterpenes, the first step is the formation of geranyl carbocation through dephosphorylation, and ionization of geranyl diphosphate (Bergman and Phillips, 2021). The first step of the sesquiterpene synthesis begins with the ionization of farnesyl diphosphate to farnesyl cation. Also, the formation of nerolidyl cation via isomerization can occur from farnesyl cation (Liang et al., 2021; Kirschning et al., 2022). Two routes are known for the synthesis of diterpenes and the main enzymes for synthesis are diterpene synthases. One route includes a class I type enzyme, which catalyzes the reaction via the ionization of diphosphate and the other route includes a class II type enzyme, which catalyzes the reaction via the substrate protonation at the 14,15-double bond of geranyl diphosphate (Veneziani et al., 2017; Liu et al., 2022). The generation of nonsteroidal triterpenoids is facilitated through the conversion of squalene into oxidosqualene and cyclization following the formation of dammarenyl cation. The enzymes, that catalyze the reaction are oxidosqualene cyclases (Singh and Sharma, 2015; Goyal et al., 2022). Many terpenoid compounds display a wide range of pharmaceutical properties and due to having these properties; nowadays, they are now gaining increased interest for their use in clinical practices. As well-known examples, taxol (diterpene) isolated from Taxus baccata and artemisinin (sesquiterpene lactone) isolated from Artemisia annua can be given for their antineoplastic and antimalarial potential (Croteau et al., 2006; Pollier et al., 2011). The terpenes have activities related to plant interactions, plant defences, and other environmental stresses (Abbas et al., 2017; Ninkuu et al., 2021).

Monoterpenes are a terpene type that consists of two isoprene units and has the molecular formula of C₁₀H₁₆ (Sundriyal, 2022). Studies by various researchers have also reported that monoterpenes have antiseptic, anti-cancer, antibacterial, and antifungal properties (Scariot et al., 2021; Silva et al., 2021). Various monoterpene types are used in foods as a flavoring and fragrant additive (Li et al., 2021; Wackett, 2021; Ignea et al., 2022), and in agriculture and animal husbandry due to their insecticidal and pesticide effects (Alam et al., 2022; Almadiy et al., 2022; Song et al., 2022).

Sesquiterpenes, the largest class of terpenes, consist of three isoprene units and are represented by the molecular formula of C₁₅H₂₄ (dos Santos Franciscato et al., 2022). Some of the important known sesquiterpenes are: bisabolol found in Matricaria recutita (Herrera et al., 2022); chamazulene found in Artemisia absinthium (Mohammed, 2022); farnesol and cumin found in Vachellia farnesiana; guaiazulene found in Cuminum cyminum (Gilbertson and Koenig, 1981); and dicarabrol found in Carpesium abrotanoides L. (Asteraceae) and Lactarius indigo (Jie-Wei et al., 2021).

Diterpenes having four isoprene units are shown by the formula of C₂₀H₃₂ (Somantri et al., 2022). They are widely found in nature and are defined as compounds having various pharmacological activities (Kemboi et al., 2021). For example, it has been reported by various researchers that diterpenes obtained from the plants belonging to the genus Taxus are used in the treatment of prostate, ovarian, lung, and breast cancer (Chen et al., 2021; Acquaviva et al., 2022; Tomiotto-Pellissier et al., 2022).

Triterpenes are terpenes having six isoprene units and being shown by the formula C₃₀H₄₈ (Luo et al., 2021). Triterpenes are produced by all animals, plants, and fungi (Chaudhary, 2022). Examples of this group are squalene (SKU) found in shark liver oil and stigmasterol, oleanan, and ursan found in soybeans, legumes, and nuts. Triterpenes are used in food, cosmetic, and pharmaceutical industry due to their antioxidant, anti-viral, anti-inflammatory, and anti-tumor activities (Sureda et al., 2021; Darshani et al., 2022; Miranda et al., 2022).

Tetraterpenes (Carotenoids) are defined by the formula C₄₀H₅₆ (da Silveira Vasconcelos et al., 2020; Zia-Ul-Haq, 2021). Examples of tetraterpenes consisting of eight isoprene units are the carotenoids found in peaches, carrots, apricots, spinach, and peppers. Carotenes are tetraterpenes with important biological functions including light capture, antioxidant activity and protection against free radicals, synthesis of plant hormones, and structural components of membranes (Săvescu, 2021; Adil et al., 2022; Seker and Erdogan, 2023). In addition, carotenoids are high-value compounds for the food and pharmaceutical industries and can be synthesized via photosynthetic and non-photosynthetic organisms. Xanthophylls are another group of tetraterpene pigments commonly found in nature (Siziya et al., 2022). Carotenoids function as antioxidants, anti-inflammatory, anti-cancer, anti-diabetic, anti-microbial, and autoinflammatory compounds (Sathasivam and Ki, 2018; Karpiński et al., 2021; Zia-Ul-Haq et al., 2021).

Some alkaloids containing basic nitrogen atoms are well recognized as biologically active natural compounds in chemistry and medicine. Target-oriented achievements for the synthesis of alkaloids in laboratory conditions can make possible the study and optimization of their biological properties; however, proceeding in their preparations cannot be that much simpler because of the basicity and nucleophilicity of nitrogen, its susceptibility to oxidation, and its ability to alter reaction outcomes in unexpected ways (Parr et al., 2015; Thawabteh et al., 2021). The main key in alkaloid classification is related to the structure of the molecule containing a basic nitrogen atom at any position that does not bear nitrogen in an amide or peptide bond (Bribi, 2018). Some groups of alkaloids also contain bonding properties related to neutral or weak acidity. In addition to carbon, hydrogen, and nitrogen groups, they also contain groups including oxygen, sulphur, and albeit very little, bromine, chlorine, and phosphorus. Compounds such as amino acids, proteins, peptides, nucleic acids, and amines are generally not called alkaloids (Nicolaou and Chen, 2011; Chen et al., 2021). Alkaloids with complex and diverse structures can be classified most commonly and correctly based on their C-N skeleton profiles. Pyrrolidine, pyridine, quinoline, isoquinoline, indole, quinazoline, steroidal, diterpenoid, and other alkaloids are the groups that alkaloids fall into based on the last signature (Archana and Nagadesi, 2022). They can also be produced by a wide variety of organisms such as bacteria, fungi, animals, and plants (especially). Many are toxic to other organisms and have a wide variety of pharmacological activities (Al-Snafi, 2021; Yan et al., 2021; Cano Ortiz et al., 2022). Alkaloids exhibit various activities including toxicity at organismal and cellular levels in herbivores and vertebrates, and in certain bacteria, fungi, and viruses because of having antibacterial, antifungal, and antiviral properties as well as having effects on molecular targets related to mutagenicity or carcinogenicity. Several alkaloids including nicotine and anabasine are useful in controlling insects as insecticides. Many alkaloids with activity on the nervous system are known in animals (Bribi, 2018; Badri et al., 2019; Hussein and El-Anssary, 2019). The most typical example is morphine, a benzylisoquinoline alkaloid formed as a result of the phenol coupling reaction. Alkaloids such as caulerpin, abisindole alkaloid obtained from algae are isolated due to having anti-inflammatory, anti-tumor, and growth regulatory activities (Bai et al., 2021; Haghighi and Ali, 2021; Zhou et al., 2021).

Being as simple and common, this technique is applied through using of the grounded plant material with a suitable organic solvent (hexane, acetone, methanol, ethanol etc.) together in a reaction vessel (Ashibuogwu et al., 2022). In this method, where the extraction rate can be increased by factors such as heat and mechanical mixing, the extraction process is stopped when the secondary metabolite quantities remaining in the extract and plant material reach equilibrium. The maceration technique, of which works with relatively small volumes and is quite suitable for laboratory-scale extractions, has its own disadvantages and they are: the need for separating of the extract and plant material from each other by a second process (filtration, centrifugation etc.) at the end of the extraction; the need of the time for processing, in which vary from a few hours to several days; the need of a large amount of solvents in the step-applied maceration; and significant losses of secondary metabolites during isolation process after maceration, in which is resulted in low extraction yields (Silva et al., 2021; Pataro et al., 2022; Wela et al., 2022).

Soxhlet extraction is a technique preferred for the secondary metabolite extraction because of its ease of use. The grounded plant material is placed into a cellulose filled thimble and after following is put into the extraction tube. A suitable solvent is introduced into the extraction flask and reflux is initiated by heat application. The solvent applied gone and condensed into the extraction tube reaches to the plant material in the thimble and descends from there to the following collection chamber. The solvent that is reheated in the chamber passes into the gas phase and then returns to the plant material for a new wash (Khongthaw et al., 2022). The process shows a continuous character with requiring shorter time and taking less solvent consumption compared to maceration (Tzanova et al., 2020). However, it is a significant disadvantage that the extract is kept around the boiling point of the solvent throughout the process (Adewale et al., 2022).

This technique is mainly applied for the extraction of volatile plant components such as essential oils, dry or wet plant materials that are dispersed in water (Kshyap et al., 2021). This mixture, being in a container connected to the condenser, is heated, and the resulting steam formed after condenses in the condenser, which is having a two-phase system consisting of extracted essential oil and water in the condensation vessel. Phases are separated using a simple separatory funnel. This technique is suitable for processing large quantities of plant materials, especially for industrial extractions. However, it is not recommended as a suitable technique for the extraction of thermolabile metabolites (Lo et al., 2021).

Microwave-assisted extraction (MAE) is a widely used technique supporting for extracting valuable bioactive molecules (secondary metabolites etc.) from plant materials. MAE is based on the principle that the electromagnetic radiation sent into a polar solvent is absorbed by the substance, and the absorbed energy by the substance increases the intermolecular and intramolecular mobility, resulting in releasing of heat under the “friction force” of the molecules (Delazar et al., 2012). The determinative factors for the efficiency of MAE include the molecular structures of the solvents used (polar or non-polar etc.), the sample/solvent ratio used, the microwave power applied, the time and temperature applied. Although the applied microwave power increases the extraction efficiency, the application of high power may cause overheating of the extraction solution and the subsequent degradation of thermolabile secondary metabolites under the influence of heat. Also, the kind of solvent used in MAE is another important parameter that affects the extraction efficiency. Although the use of water is quite successful due to its ability to absorb microwave energy and provide a homogeneous distribution of the resulting heat, the majority of secondary metabolites derived from plants have very low solubility in aquatic environments. For this reason, various solvent mixtures have been tested by previous studies in order to find a polar and effective solvation environment and their results have been presented (He et al., 2013; Abdelhamid et al., 2019). Besides, numerous studies have also been carried out for the examination of the effectiveness of various reaction parameters in terms of having increased extraction yield using statistical methods (Dang et al., 2018: Poole et al., 2019).

One of the leading advantages of MAE is that the solution system responds very quickly to application, allowing for much greater extraction of total phenolic compounds compared to traditional methods. Microwave energy, being in the frequency range of 300 MHz-1000 GHz, penetrates deeply into the sample, permitting the material to heat up quickly as a whole. Compared to the conditions with long-term and high temperature (110°C) applied in traditional methods, MAE paves the way for shorter-term and higher-efficiency extraction procedures (Magnusson et al., 2017).

This technique works based on the fact that ultrasound waves interact with the material, creating changes in the material at the molecular level as well as in physical properties. The ultrasound wave sent on the sample is dispersed in the solvent medium promoting solvent penetration into the cellular matrices, as well as having a disruptive effect on the cell membrane; thereby, significantly increases the secondary metabolite extraction efficiency (Awad et al., 2012). UAE, using microwave frequencies in the range of 20 kHz-200 kHz, stands out as a technique that operates with short processing times and provides to have high extraction efficiencies with very high qualities (Ho et al., 2016). UAE is also a clean technique, not requiring large quantities of solvents in extraction processes. Compared to traditional techniques such as maceration, steam distillation or Soxhlet, MAE provides benefits including simplification of the working procedure, higher efficiency in a shorter time, high purity level in the final product obtained, and low energy consumption (Mushtaq et al., 2020).

Supercritical fluid refers to any substance, found at certain temperatures over the critical level as well as, being found under certain pressure conditions over the critical level (Maliki et al., 2022). The properties of a substance such as density, viscosity, surface tension and diffusibility under supercritical conditions are distinctly different compared to the properties of the same substance stored under standard atmospheric conditions (Radivojac et al., 2021).

Today, the increasing sensitivity for the environmental pollution pushes both industrial production centers and researchers to take different precautions to eliminate pollution sources and to reduce pollution levels. In SFE technique, the most commonly used supercritical fluid is CO₂ (31.4°C-73.8 bar for CO₂), but water, ammonia, nitrous oxide and low molecular weight organic compounds (ethane, propane, butane etc.) kept under supercritical conditions can also be used as supercritical fluids (Gumerov et al., 2021; Kessler et al., 2022). The main advantages of SFE technique are that the usage of predominantly non-toxic supercritical fluids, being safer in terms of preventing contamination, allowing selective extraction depending on the supercritical fluid used, and minimizing the oxidative and thermal degradation of the targeted secondary metabolites (Thota et al., 2022). There are also some limitations/disadvantages associated with SFE technique. Among these, additional costs incurred during the generation of supercritical pressure conditions and the necessity of taking additional precautions due to working under high pressure conditions are of importance (Geow et al., 2021).

PEFE is an unthermal technique for secondary metabolite extraction with minimal processing using plant material. It is an application of repetitive short high voltage pulse (μs-ms) that the applied electric field strengths is in the range of 0.1-3 kV.cm-1 and the energy applied is in the level of 1 - 20 kJ.kg-1. The logical basis of this technique relies on the creation of pores on the cell membranes and thereby increasing the cell membrane permeability that is gained via leaving the viable cells of the sample under the influence of an electric field. Furthermore, the use of this technique, which causes irreversible damage to the sample’s cells, is sometimes referred to as a “pre-extraction process” (Baiano and Del Nobile, 2016).

As a “high capital cost” technology that provides a medium extraction efficiency, PEFE has very short application time and is suitable for working with thermolabile molecules (Sun et al., 2020). However, in order to increase the yield for the targeted secondary metabolites, the process should be applied carefully. For example, prolonging of the application time or increasing of the number of applied electric field pulses may cause an increase in temperature in the sample (Brahim et al., 2021).

Enzyme-Assisted Extraction (EAE) is a simpler and safer extraction technique than traditional extraction techniques, with advantages such as the use of non-toxic solvents and the ability to work in low temperature conditions. The underlying fact of EAE is being involving of the enzymatic degradation of cell membranes and the release of secondary metabolites from the cells in an enzyme-containing extraction medium (Cheng et al., 2015). Another important advantage of this technique is that it allows the selective extraction of secondary metabolites (Marathe et al., 2017). Extractions performed in moderate solvent environments yield significant yield percentages for the targeted secondary metabolite(s) (Wijesinghe and Jeon, 2012). Although EAE is a good alternative to traditional extraction techniques, particularly for highly valuable products, it does have some limitations in terms of applicability, particularly for large volume extractions. As final remarks, the high cost and easily degradable nature of enzymes, difficulty in the isolation of the target product from the final reaction mixture at the end of the process, and the low reproducibility make the technique as choice of a high-cost alternative (Wang et al., 2015; Wang et al., 2019).

The plant tissue culture applications introduced by Haberlandt (1902) have been used for over 100 years. A media composition widely used in tissue culture protocols with modifications was designed by Murashige and Skoog in, 1962 (Sehgal and Khan, 2020). The model systems established regarding to plant tissue culture applications are often used in research to bring solutions to the various problems related to physiological, biochemical, genetic, and structural conditions of plants (Torres, 2012). Organizations around the world put in use plant tissue culture techniques as well as micropropagation to improve economically important crops widely via transforming different explants and following regenerating them under optimized culture conditions (Chandana et al., 2018; Sehgal and Khan, 2020; Erdem and Uysal, 2021).

Tissue culture approaches mainly include the methods used to obtain and grow plant cells or organs in aseptic conditions using direct and indirect ways, and their usage areas are involved in (1) obtaining molecules having high economic worth such as plant-derived secondary metabolites and recombinant proteins used as biopharmaceuticals, (2) plant reproduction by micropropagation method, (3) conservation of rare or endangered plant species, (4) screening of cells rather than plants for advantageous characters (e.g. herbicide resistance/tolerance), (5) obtaining plants free from pathogens, (6) obtaining hybrid species by interspecies hybridization, (7) obtaining plants having new features when somaclonal variation occurs, (8) production of identical sterile hybrid species, (9) generating haploid plants by anther and microspore culture, (10) cross-pollinating of distantly related species and then application of tissue culturing for creating embryos (embryo rescue), (11) creating chromosome duplication and induction of polyploidy, usually achieved by applications of antimitotic agents such as colchicine or oryzalin (e.g. doubled haploids, tetraploids, and other forms of polyploids), (12) generating new species between cross distantly related species by protoplast fusion and regeneration of the novel hybrids, (13) providing a quick studying way of the molecular basis for physiological, biochemical and reproductive mechanisms in plants (e.g. in vitro selection for stress tolerant plants), (14) storage of gene resources, (15) utilization of cell cultures in in vitro selection studies, (16) large-scale production of artificial seeds by somatic embryogenesis, (17) carrying out germplasm collections and seed conservation, (18) putting into practices for making automated control of cell growth and rational regulation of metabolite processes in order to have contribution to reduce labor costs, and improvements in productivity and (19) using tissue culture serving as a basic tool for transgenic plant production (Ozyigit, 2012; Mukta et al., 2017; Dagustu, 2018; Huyop et al., 2019; Phillips and Garda, 2019; Secgin and Okumus, 2022).

Totipotency special to plants that are highly useful in biotechnological research provides the ability to regenerate a whole plant from a plant part (Finer and Dhillon, 2016). A basic concept in totipotency follows the regeneration of the whole plant from explants, which are the small parts of the plant prepared by dissection of the plant (body, organ, any tissue, etc.) (Bhatia and Dahiya, 2015). Young plants, seedlings, calli, and somatic embryos are preferred to be used in tissue culture systems (Isah et al., 2017; Secgin and Okumus, 2022). Propagating plants in vitro using the tissue culture techniques involve two consecutive steps: the first one is the formation of in vitro cell/callus/cell suspension and protoplast culture and the latter one is direct or indirect organogenesis or somatic embryogenesis via in vitro regeneration (Aasim et al., 2019).

Organogenesis is called the process that involves in vitro formation of plant structures including roots, shoots, and leaves through being derived directly from the meristem or indirectly from the callus ( Figure 1 ). The plant regeneration process via organogenesis is to be enabled through plant growth regulators that are modified by altering their concentrations in nutrient medium to act on is the formation of callus and differentiation of adventitious meristems into organs (Hussain et al., 2012; Pradhan et al., 2022).

Being a non-zygotic embryonic production process, a new plant can be generated through somatic embryogenesis (Secgin and Okumus, 2022). The somatic embryo formation can be carried out either directly from the explant or after the culturing process of the callus ( Figure 2 ), involving the first formation of the embryogenic clumps in an auxin-rich medium and the subsequent transfer of the embryogenic clumps into a medium without auxins. Complete embryonic development requirements include adequate delivery of auxin and nitrogen, which are found in the medium, and at the end, whole plant formation is a result of a process involving asexual reproduction (Hussain et al., 2012; Shahzad et al., 2017; Erdem and Uysal, 2021).

The formation of new plants through in vitro tissue culture can be defined as a model having mainly six fundamental stages, including: (1) setting up a suitable laboratory environment, (2) choosing a donor plant (identification of plant species and plant parts to be used), (3) determining, preparing and sterilizing of suitable nutrient media for the selected plant species, (4) arranging of callus and cell suspensions, promoting plant regeneration from callus or cell suspensions or regenerating of plants directly from somatic or gamete cells via meristem propagation, organogenesis or somatic embryogenesis, (5) proliferating and extending of the formed shoots, and maturating of somatic embryos, and finally (6) rooting of extended shoots and acclimating of rooting plants (Cui et al., 2019; Joo et al., 2019; Cavallaro et al., 2022).

Productions of important compounds including secondary metabolites via plant tissue culture have also been successfully accomplished. These metabolites are released by plants to provide protection against pathogenic attacks or wounding. Secondary metabolites play important roles in adaptation to stressful conditions (Chandana et al., 2018; Erb and Kliebenstein, 2020). Induction of the biosynthesis of secondary metabolites in plants starts via treatment with any elicitor, which is any stress factor causing triggering of defense responses in plants. (Naik and Al-Khayri, 2016; Khanam et al., 2022). Based on their natures, elicitors are broadly classified into two major categories, being as abiotic (AgNO₃, CaCl₂, CdCl₂, ethanol, and methyl jasmonate, etc.) and biotic (chitosan pectin, chitin, elicitin, yeast extract, and fungal homogenate, etc.) (Kaur and Pati, 2018; Piatczak et al., 2018).

Several elicitation and biotransformation techniques have been utilized to provide a high yield in secondary metabolite production in various plant species (Naik and Al-Khayri, 2016; Halder et al., 2019; Bhaskar et al., 2021; Khanam et al., 2022). Besides, as an alternative tool to increase the growth of cultures by bringing down the cost of the requirements of energy, labor, and space, bioreactors have been started to be used (Shahzad et al., 2017; Abahmane, 2020).

Cell line selection was previously proven to be used in the production of cell lines that can provide great increases in secondary metabolite production (Wawrosch & Zotchev, 2021). In vitro production of the berberine in selected cell lines of Coptis japonica was reported by Sato and Yamada (1984) with a production of up to 13.2% (DW). Catharanthus roseus was utilized by Hall and Yeoman (1987) in the production of high amount of anthocyanin using cell line. Camptothecin formation was realized in suspension cultures of Ophiorrhiza mungos through cell line selection, nutrient medium optimization, and jasmonic acid elicitation of 1.12 mg g^-1 DW compared to 0.06 mg g^-1 DW in the original cell line (Deepthi and Satheeshkumar, 2017). Recently, Heydari et al. (2020) improved the production of some phenolic acids (rosmarinic, salvianolic-B, ferulic, and cinnamic) in the cell suspension cultures of Woodland Sage through attaining high-yielding cell lines and carboxyl functionalized multi-walled carbon nanotubes elicitation. To provide the needs required by the pharmaceutical industry, attempts have been done in terms of realization of increase in the secondary metabolite production (Hussain et al., 2012).

As mentioned above, it is possible to produce only the relevant plant part for the production of secondary compounds (Mishra, 2015). These strategies include gene cloning and repeated selection of high-yielding strains from heterogeneous cell populations using plant tissue culture techniques such as clonal micropropagation, callus, hairy root, and protoplast cultures (Solle et al., 2016). Several secondary compounds, being produced by using tissue culture techniques from various explant sources, are identified as follows: phenolics including caffeic acid, rosmarinic acid and rosmarinic acid hexoside, salvianolic acid, salvianolic acid K, salvianolic acid F isomer I, salvianolic acid F isomer II, caffeic acid derivative I, caffeic acid derivative II, and methyl rosmarinate from the leaves and shoots of Salvia bulleyana (Wojciechowska et al., 2020); iridoid glycosides (aucubin, harpagide, harpagoside) and phenylethanoid glycosides (verbascoside and isoverbascoside) from the seeds, leaves and shoots of Rehmannia elata (Piatczak et al., 2019); podophyllotoxin-related compounds (6-methoxy-podophyllotoxin, podophyllotoxin and deoxypodophyllotoxin) from the hypocotyls of Linum flavum (Renouard et al., 2018); psoralen, daidzein and genistein bioactive compounds from the cotyledon callus cultures of Cullen corylifolium (Singh et al., 2020); triterpenoids (madecassoside, asiaticoside, madecassic acid, and asiatic acid) from the petioles and leaves of Centella asiatica (Baek et al., 2020); crocin, pircorcrocin, safronal from the corms of Crocus sativus (Ahamed, 2019); phenolic acids (Caffeic acid, Syringic acid, p-Coumaric acid, ferulic acid, Salicylic acid) and flavonoids (rutin, Myricetin and Kaempferol) from the nodes, internodes and leaves of Sphagneticola calendulacea (Kundu et al., 2018); meroterpene bakuchiol from the cotyledone-derived callus, seeds, leaves, internodes and roots of Psoralea drupacea (Lystvan et al., 2010); tryptophan-derived quinoline alkaloid camptothecin from the shoots and leaves of Ophiorrhiza alata (Ya-ut et al., 2011); monoterpene-derived indole alkaloid camptothecin from the radicle-derived roots of Pyrenacantha volubilis (Hima et al., 2019); and phenolic acids (Rosmarinic acid, Caffeic acid, Lithospermic acid, Chlorogenic acid, Cinnamic acid) from the leaves and shoots of Mentha spicata (Yousefian et al., 2020); flavonoids, phenylpropanoids, alkaloids, fatty acids and aromatic glycosides from callus and suspension cultures of Carthamus tinctorius (Liu et al., 2021); epigallocatechin and chlorogenic acid from callus and suspension cultures of Oryza sativa (El-Beltagi et al., 2022) and phenolics, flavonoids, tannins and essential oils from nodal segments of Artemisia arborescens (Riahi et al., 2022).

As a source of secondary compounds, plants are utilized for the production of pharmaceuticals, flavors, fragrances, coloring agents, food additives, and agrochemicals ( Figure 7 ) (Wang et al., 2017). The productions using plants occur regardless of growth parameters and the productions are not in large quantities as well as their occurrences in different tissues of the same plant are at different rates (Atanasov et al., 2015). The roles of most of these compounds in plants are related to defense and as being the leading alternative, the plant cell/organ culture developed has been given the paving of the way for resulting in advancing of bioreactors for plant cell/organ culture (Srikantan and Srivastava, 2018). However, a number of problems observed as cell productivity below desirable level, slow-growing rate, having genetic instability in high-producing cell lines, poor control in cellular differentiation, and failure in maintaining photoautotrophic growth interfere with performance regarding the practices of plant cell cultures (Sajc et al., 2000; Dörnenburg, 2008).

As an efficient way to produce active biomolecules in vitro, the process used in plant culture depends on factors such as optimization and engineering that affect plant cells what is needed to scale up large bioreactor volumes (Srikantan and Srivastava, 2018). The cultivation strategy involving using bioreactors for plant cell and hairy root cultures is adopted for providing low shear stress, proper mixing, a suitable support system for organ cultures, and ease in scale-up (Honda et al., 2001). To increase biomass and achieve maximum productivity in plant cell suspensions, bioreactors are designed with sterile conditions and approved batch consistency. Regulatory approval systems compatible with bioreactors allow for more successful and faster operations. (Fischer et al., 2012). The bioreactor system offers some key advantages such as allowing cultures to grow rapidly, promoting the bulk transfer of nutrients and gases, promising to scale up the process and save labor costs. Moreover, constant micro-environmental conditions and a high degree of automation of the cultivation process for a liquid medium can be provided by using the bioreactor systems (Yancheva et al., 2019; Sidal, 2022). Similar to microbial and mammalian cell cultures grown in bioreactors that have fulfilled the requirements set by the FDA and EMEA over the past 20 years, plant cell cultures grown in bioreactors show advantages for the production of therapeutics (Huang and McDonald, 2012). Bioreactor configuration for plant cell cultures shows dependence on aerobic conditions with low shear and good mixing. Due to having bigger cell sizes and forming aggregates or organs in comparison with microbial cultures, the operation of bioreactor for cell suspension cultures or hairy root cultures at constant intervals is difficult in terms of the sampling of biomass (Vaghari et al., 2017; Srikantan and Srivastava, 2018).

Different bioreactor configurations have been developed to provide integrative ability with the biological systems to have efficient growth and better product yield (Sharma and Shahzad, 2013). Bioreactors show modifications, including the addition of mist spray, temporary immersion, having mesh or basket according to the cultivation process being performed for the organized plant structures such as hairy roots, somatic embryos, and micropropagation of plantlets (Paek et al., 2005; Srivastava and Srivastava, 2012). Plant cell bioreactors are designed depending on operative capacity which could be mechanically, hydraulically, pneumatically driven, immobilized, or perfusion types (Eibl and Eibl, 2009; Srikantan and Srivastava, 2018). Physical damage (wounding) and shear stress are the factors causing negative effects on the cultivations of hairy roots and callus in bioreactors, of which hairy roots are more sensitive compared to callus; therefore, the usages of low-shear impellers and external support (stainless steel plate or styrofoam mesh) are essential. Due to excessive branching of hairy roots causing self-immobilization by forming an interlocked matrix in the bioreactor, the biochemical mass transfer of nutrients and oxygen becomes limited (Eibl et al., 2018; Srikantan and Srivastava, 2018, Angulo-Bejarano et al., 2019).

Large-scale cultivations of plant cell-based products such as taxol, shikonin, and taliglucerase alfa in bioreactors have been carried out using plant cell suspension cultures (Hidalgo et al., 2018). A modified impeller bioreactor to reduce cell damage from the hydrodynamic stress on cell suspension that cells are found in a homogeneous state is used for cultivation. Bioreactor types with various configurations, including stirred tank, airlift, and bubble column with minor modifications have been commonly employed to grow plant cell suspension cultures. Cell aggregation, foaming, and cell aggregation are issues that cause problems in bioreactors used for plant cell suspension cultures. These difficulties can be overcome by using a suitable low shear impeller and implementing efficient aeration (Huang and McDonald, 2012; Srikantan and Srivastava, 2018).

As discussed above, there are several ways of improving the production yields of secondary compounds via using plant cell cultures or suspensions. They could be by application of biotic or abiotic elicitors; addition of a precursor leading to improvement in the desired compound; modifying the metabolic carbon flux that leads to promoting the expression pathway of the target compound; generating new genotypes by genetic manipulation using genetic engineering or protoplast fusion; treatment with mutagens causing rise the variability already existing in living cells; and using root cultures (Neumann et al., 2009; Bhaskar et al., 2021). For obtaining high productivity, yield, and concentration, a plant cell/tissue-based bioprocess can be designed by taking into consideration of following important parameters. These are the selection of cell lines giving high yields, media optimization, and strategy for optimal bioreactor operation (Srivastava and Srivastava, 2007; Srikantan and Srivastava, 2018).

As examples of recent studies using bioreactors, the followings can be given: phenolic acids, flavonoids and dibenzocyclooctadiene lignans in Schisandra chinensis (Szopa et al., 2018; Szopa et al., 2019); verbascoside, baicalin, wogonoside, luteolin, luteolin-7-glucoside in Scutellaria alpine (Grzegorczyk-Karolak et al., 2017); flavonoids in Gynura procumbens (Pramita et al., 2018); isoflavonoids in Pueraria tuberosa (Kanthaliya et al., 2019); essential oils, p-cymene, geranyl acetate, δ-cadinene, shyobuone, methyl everninate, alloaromadendrene, ledene oxide (II) in Ledum palustre (Jesionek et al., 2018); phenylethanoid glycosides (verbascoside,isoverbascoside) and aucubin in Castilleja tenuiflora (Cortes-Morales et al., 2018); thapsigargin in Thapsia garganica (Lopez et al., 2018); rosmarinic acid and phenolics in Salvia nemorosa (Heydari et al., 2020); flavonoids (Quercetin, Kaempferide, Epicatechin gallate, quercetin-3-o-glucose, Kaempferol-3-rutinoside) in Orostachys cartilaginous (Hao et al., 2020); antifungal saponins SC-2 and SC-3 in Solanum chrysotrichum (Salazar-Magallón and Huerta de la Peña, 2020); six phenolic acids [rosmarinic acid, methyl rosmarinate cafeic acid hexoside, cafeic acid, salvianolic acid F (I) and salvianolic acid F (II)] and four phenylethanoids (verbascoside, leucosceptoside, isoverbascoside and martynoside) in Salvia viridis (Grzegorczyk-Karolak et al., 2022); and some phenolic acids, flavonoids (diosmin, catechin, rutin, and myricetin), a stilbenoid (resver- atrol) and phenylethanoid glycosides (acteoside and echinacoside) in Scrophularia striata (Ahmadi-Sakha et al., 2022).