# _Vaccinium_ Species (Ericaceae): From Chemical Composition to Bio-Functional Activities
## 4 The Chemical Profile of _Vaccinium_ Leaves
In the methanolic extract, the content of flavonoids was higher than that of hydroxycinnamic acids, but in the hydroalcoholic extract, the opposite was observed. In both extracts, the main acid was 2-O-caffeoylarbutin, which is not present in other _Vaccinium_ leaves. Other phenolic acids detected in the methanolic extract were chlorogenic, caffeic, _p_-coumaric and caffeoyl-shikimic acids, together with the coumaroyl quinic acid isomers [41]. Moreover, _V. viitis-idaea_ leaves were characterised by coumaroyl- and caffeoyl-hexose hydroxyphenylols. The most abundant flavonoid was quercetin-3-O-(4\"-3-hydroxy-3-methylglutaroyl)-\(\alpha\)-rhammoside, which represents 5-6% of total phenols in the hydroalcoholic extract and 32% of the methanolic extract. Rutin, hyperoside, and quercitin were also detected in significant amounts in the methanolic extract, while traces of four quercetin glycosides and kaempfer glycosides were also found. Proanthocyanidins and coumaroyl iridoids were also identified [41]. Quercetin-3-O-glucose, quercetin-3-O-rutinoside, kaempfer-3-O-glucose, and kaempfer-3-O-rhammoside were identified in the leaves of _V. arctostayhylos_[45; 81]. The main flavonoids detected in the leaves of _V. corymbosum_ were hyperoside, isoquercetin and rutin. Other flavonoids found were: myricetin [54], quercetin-3-O-glucose, quercetin-3-O-galactoside, quercetin-3-O-arabinoside [82], quercetin-3-O-rhammoside [35; 82; 83], myricetin-3-O-glucose, quercetin-3-O-rutinoside [83], syringetin-3-O-glucose, and kaempfer-3-O-glucose [35; 83]. Several studies have demonstrated the role of collection time of _Vaccinium_ leaves in influencing their phenolic content [79]. In fact, contrary to the fruits, the flavonoid content increases during the development of the leaves, while hydroxycinnamic acid content strongly decreases [84]. Previously, [PERSON] et al. [74] have indicated that the red leaves of _V. corymbosum_ have higher quantities of quercetin and kaempfer, as well as of ferulic, caffeic and _p_-coumaric acid, than green leaves. The main bioactive compounds of _V. myrtillus_ leaves are hydroxycinnamic acids, especially chlorogenic acid [41; 79]; its concentration ranges from 59 to 74% of the total hydroxycinnamic acids [79]. [PERSON] et al. [80] also reported the presence of rosmarinic acid, caffeoylquinic acid, _p_-coumaric and ferulic acid. [PERSON] et al. [41] analysed the methanolic extract of _V. myrtillus_ leaves and identified thirty-five compounds. Other than the abundant chlorogenic acid and its isomers, caffeoyl-shikimic acid, feruloylquinic acid isomer, and traces of caffeic acid were found. In addition, [PERSON] et al. [85] have performed an HPLC-MS analysis of the phenolic profile of _V. axycocos_ leaves; the phenolic acids are mainly chlorogenic and neo-chlorogenic acid, as well as 3-O- and 5-O-coumaroylquinic acids. [PERSON] et al. [86] reported the isolation of caffeic, chlorogenic, neochlorogenic, 3- and 5-_p_-coumaroylquinic acids, and 3,5-dicaffeoylquinic acid from the leaves of _V. arctostayhylos_. Continuing the investigation of the qualitative composition of the leaves, they have isolated six phenolic substances: cryptochlorogenic (4-caffeoyl-quinic) acid, arbutin, rosmarinic acid, caffeoylarbutin, 1-_p_-coumaroylgalactoclose, and _p_-coumaroylarbutin. Twenty different compounds, mainly phenolic acids and flavonoids, were identified in the red dried leaves of _V. corymbosum_ by Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometry (LC/ESI-MS/MS) and High-Performance Liquid Chromatography-Diode-Array Detection (HPLC-DAD) [76; 77]. Interestingly, these two groups were in almost equal concentration in the crude extract (chlorogenic acid and quercetin-3-O-galactoside); as in _V. myrtillus_ leaves, the most abundant compound was chlorogenic acid. LC-MS analysis showed the presence of quinic and caffeic acid. Even though the triprepenes in the leaves comprised only the 4-6% of those in the respective fruits, several compounds were identified in the diethyl ether leaf extract.