*2.3. Perilla*

Perilla (*Perilla frutescens* L. Briit) belongs to the Lamiaceae family (formely Labiateae) which consists of 235 genera and more than 700 species [76]. Perilla is an edible herb widely consumed in Asian countries such as China, Korea, Japan, and India. Similar to spinach, perilla leaves are also characterized by a high concentration of carotenoids. In fact, according to Müller-Waldeck et al. [77], perilla may contain high contents of carotenoids, especially up to five-fold higher lutein than other carotenoid-rich leafy vegetables. The leaves of perilla contain a range of bioactive phenolic molecules such as caffeic acid, catechin, chrysoeriol, ferrulic acid, luteolin, quercetin, and rosmarinic acid [78,79]. In particular, secondary metabolites such as rosmarinic acid and perillaldehyde (an essential oil constituent) have demonstrated potential to prevent a wide range of diseases particularly owing to their anti-diabetic, anti-depressant, anti-bacterial, anti-cancer, and antimicrobial properties [76]. Thus the concentrations of these two phytochemicals are crucial for their clinical and culinary applications. It is worth noting that these two secondary metabolites are produced in perilla by two different biosynthetic pathways, namely the monoterpene and phenylpropanoid pathways, and may increase independently in relation to the perilla chemotype and abiotic environmental stress conditions [80]. Perilla is present in nature in two main chemical-varietal phenotypes: (i) The red-pigmented cultivar *P. frutescens* var. *crispa*, known as "Zi-So" and widely grown in China where it is used as a spicy herb, leafy vegetable, and medicinal plant, and (ii) the non-pigmented green cultivar *P. frutescens* var. *frutescens* known in Japan as "Shisoyo" or "Shiso" and mainly

used as an oil crop but also as ingredient of skin creams and food products [81,82]. According to Meng et al. [78,83], three cinnamic derivates (caffeic acid, coumaroyl tartaric acid, and rosmarinic acid) ranged from 0.1 to 11 mg/g; six flavonoids (apigenin 7-*O*-caffeoylglucoside, apigenin 7-*O*-diglucuronide, luteolin 7-*O*-diglucuronide, luteolin 7-*O*-glucuronide, scutellarein 7-O-diglucuronide, and scutellarein 7-*O*-glucuronide) ranged from 3.5 to 18.5 mg/g; and six anthocyanins (0.7–2 mg/g) including cis-shisonin, cyanidin 3-*O*-(*E*)-caffeoylglucoside-5-*O*-malonylglucoside malonylshisonin and shisonin were detected on eight tested cultivars of perilla. Concerning the health effects of perilla extract, Narisawa et al. [84] reported that perilla leaves carry anti-tumor properties. In their work, the authors showed that treatment of female rats with a 12% fat diet based on perilla extract and safflower oil in 1:3 or 1:1 ratio effected better protection against colon cancers as compared to safflower oil alone [84].

Comparing green (Korean cultivar) and red-pigmented (Japanese cultivar) perilla, Rouphael et al. [82] observed that green perilla produced exclusively perilla ketone (PK), whereas the red perilla contained perillaldehyde (PA). Similar results were reported by Martinetti et al. [81] in a study profiling two red-leaf ("Aka Shiso" and "Purple Zi Su") and three green-leaf cultivars ("Ao Shiso", "Qing Su", and "Korean perilla") with the later containing PK instead of PA. The terpenoid component present in green-pigmented perilla has been demonstrated to be toxic for cattle and horses, since PK is considered a potent lung toxin [77,85], but the health-effect as well as the toxic dose/concentration to humans is still controversial, therefore Müller-Waldeck and co-workers [77] concluded that some Korean genotypes (green-pigmented cultivars) are not suitable/recommended for fresh consumption. Interestingly, several authors showed that PA and PK present in red and green perilla can stimulate the TRPA1 (Transient Receptor Potential) cation channels which are actively involved in multiple biological mechanisms such as pain perception and their functional role in the prevention of certain types of tumor has been proved [86,87].
