**7. Conclusions and prospects**

**6.2.** *Lamiaceae* **spp. metabolites**

90 Secondary Metabolites - Sources and Applications

in Trivellini et al. [64].

The mint family (*Lamiaceae*) contains about 236 genera and more than 7000 species with cosmopolitan distribution [64]. Some of the most important genera are *Hyptis*, *Lavandula*, *Nepeta*, *Salvia*, *Scutellaria*, *Thymus*, and *Teucrium.* Species from the family inhabit different natural ecosystems, and many are already cultivated. Most of the species belonging to this family are aromatic (possess essential oils) and are widely used in traditional medicine to cure various disorders. They also have great economic value due to their use in culinary or as ornamentals, and for cosmetic, flavoring, fragrance, perfumery, pesticide, and pharmaceutical applications [65]. Many *Lamiaceae* contain high levels of phenolics, which are probably the most relevant group of secondary metabolites synthesized by plants due to their health promotion effects [64]. Among phenolic compounds, rosmarinic acid is present in the tissues of many of these species being used as a chemical marker of the family [64, 66, 67]. In some species, this compound is accumulated as the main phenolic compound at a concentration above 0.5% dry weight [64]. Several species in the *Lamiaceae* family can also accumulate high levels of other phenolic acids, flavonoids, or phenolic terpenes [64]. There are some phenolic compounds as carnosic and clerodendranoic acids that are exclusive from this family [68, 69]. The interested reader can find an excellent overview on the phytochemical characterization and biological effects of *Lamiaceae* species

Phenolic compounds are generally produced as a defense mechanism or as a response to stressful environment conditions [9]. The activation of these protective mechanisms by applying stress stimulus can be used as a strategy to increase the production of phenolic compounds in plant cell and organ cultures [70]. Recently, several attempts were made regarding the production of secondary metabolites by several *Lamiaceae* species (mainly phenolics) using plant tissue cultures particularly applying elicitation as a strategy to achieve higher production yields [64]. These studies involve mainly the use of chemical elicitors like jasmonic

duction of many compounds as essential oil constituents, phenylpropanoids, flavonoids, and phenolic acids. Overall, the results demonstrated that these elicitors had an immediate effect

The revised study showed that a high number of studies reported an increase in the production of rosmarinic acid after elicitation of cultures of several *Lamiaceae*, such as *Coleus*, *Lavandula,* and *Salvia* genera [64, 66, 71]. Several studies reported the increase in rosmarinic acid production through the application of elicitors (**Table 2**). Elicitation with jasmonic acid induces a 4.6-fold increase of rosmarinic acid production in *L. officinalis* L. cell suspension cultures [72], and elicitation with methyl jasmonate induces a 3.4-fold increase in *C. forskohlii* (Willd.) Briq. hairy root cultures [73]. The production of this compound also increased (2.3 fold) in leaves of *Rosmarinus officinalis* L. after 14 days of UV-B exposure [74]. Recently, rosmarinic acid attracted the attention of the scientists due to its broad range of biological activities, such as anti-inflammatory, antioxidant, cognitive-enhancing, cancer chemoprotection effects, among others [71]. In the last years, there are many progresses in the

), to increase the pro-

acid (or methyl jasmonate), or physical elicitors as UV-B and ozone (O3

on enhancing the production of phenolics [64].

Plant cell and tissue culture techniques are an attractive system for the cultivation of a broad range of secondary metabolites, including important alkaloids with anticancer properties and bioactive phenolics. This alternative provides a continuous, sustainable, economical, and viable production of secondary metabolites, independent of geographic and climatic conditions, which is particularly useful for the production of species at risk. Despite the great progresses in this area in the last decades, in some cases, production occurs at very low yields, and there are many difficulties in scaling up the production, and limited commercial success is achieved. Incomplete knowledge about the biosynthetic pathways of bioactive molecules limited the improvement of the production yields. Exploiting modern molecular biology techniques emerged as an alternative that needs to be harnessed to improve production efficiency by engineering biosynthetic pathway(s) of the molecules in plant cells. Also promising are new elicitors and permeabilizing agents such as coronatin or cyclodextrins. The production of bioactive molecules in endophytes also appears as an attractive alternative, although till date, there is no reported commercial exploitation.
