The chemical composition of the aerial parts essential oil of Achillea cretica L. (Asteraceae) growing wild in Crete (Greece)

Abstract Achillea cretica (L.) (Asteraceae) is a suffruticosa camefite plant, mainly distributed in Crete, Aegean Islands, and eastern Mediterranean area. In the present study, the chemical composition of the essential oil from aerial parts of a not previously investigated accession of Achillea cretica, collected in Crete, was analysed by GC-MS. The results showed the presence of large quantity of α-bisabolol (53.88%) followed by the related compound α-bisabolol-oxide (2.76%), and spathulenol (5.94%). Based on the composition of the essential oils of all the other Achillea taxa, several consideration have been carried out. Graphical Abstract


Introduction
The genus Achillea L. (Asteraceae) comprises more than 100 species of herbaceous, plants which are mainly distributed in Europe, Northern and Western Asia (Plants of the World Online 2022).Several species of this genus have been reported to have a large use in traditional medicine of different countries.In Colorado and New Mexico, A. millefolium L. was used by ancestral Americans and early colonists as an astringent treatment in wound healing and against bleeding (Dodson and Dummire 2007).In Europe, the same species was utilised to treat gastrointestinal, urinary, respiratory, and dermatological disorders (Mohammadhosseini et al. 2017) and in Russia as hemostatic and anti-inflammatory agent (Shikov et al. 2014).In Turkey, A. aleppica and A. bibersteinii have been used as diuretic and wound healing agent and useful for treatment of gastrointestinal disorders including abdominal pains and hemorrhoids (Sezik et al. 2001) whereas A. wilhelmsii for treatment of gastrointestinal and pulmonary problems in Italy and Turkey (Maffei et al. 1994;Cakilcioglu et al. 2011).A. atrata has been reported to be effective in respiratory tract disorders in Serbia (Ristic et al. 2004).In traditional Persian literature, some species of Achillea are reported to have restorative, anti-inflammatory, spasmolytic, emmenagogue, and wound healing properties, as well as being used to treat rheumatic sores and pneumonia (Zagari 1996) and, in particular, A. cretica has been utilised for treatment of gynecological disorders and pathological symptoms similar to endometriosis (Bina et al. 2020).In Chinese medicine, Achillea ssp.are regarded for their tonic, diaphoretic and anti-hypertensive effects (Ross 2003).Some Italian taxa have been recently investigated: A. ligustica All.(Venditti et al. 2016) and A. tenorii (Grande) (Venditti et al. 2014), and two reviews on the phytochemistry and medicinal properties of the genus Achillea have been published (Saeidnia et al. 2011;Mohammadhosseini et al. 2017).
Achillea cretica L. [syn. A. sphaciotica Rikli; A. erioclada DC.; A. santolina Lindl.; A. santolina Sm.; Santolina alpina Sieber ex Steud; Santolina anthemoides L.] (World Flora Online 2022), is a suffruticosa camefite (Ch suffr) plants with ascending stems up to 40 (60) cm branched at the top and normally covered by a thick felt of short white hairs.The sessile and alternating leaves are pinnatifid with suborbicular lobes.The white flowers are organised in flower heads, gathered in a composed corymb, carried by peduncles of (5) 10-10 (25) mm, with external ligulate flowers of 3-4 mm, female and ovate-oblong, the internal ones tubular hermaphrodites (Tutin et al. 1976).The species, well differentiated from Achillea santolinoides Lag., has a limited distribution in Crete, Aegean Islands, SE Cyclades and Rhodes, while, further east, it is sporadically reported along the coasts of Cyprus and southwestern Anatolia (Valant-Vetskera 1955).
Previous phytochemical investigations on the non-volatile constituents of A. cretica, collected in Crete, Greece, showed that it was characterised by the predominance of 6-C-glucosylflavones: isoorientin, isoorientin 7-O-methyl ether (swertiajaponin), isovitexin 7-O-methyl ether (swertisin), besides some di-C-glycosylflavones (Valant 1978;Valant et al. 1980), whereas from plants collected in Cyprus, seven new 4-oxobisabol-2-enes and two lignans were isolated and characterised (Bruno et al. 1996).Several flavonoids and two hydroxycinnamic acid derivatives were identified in the extract of plant material bought in local market in Iran (Bina et al. 2020), whereas from a population growing in Tunisia, of dubious botanical identification, due to the fact that this species is not reported for this country (WFO 2022), several sesquiterpene lactone and flavonoids were isolated (Hichri et al. 2015(Hichri et al. , 2018a(Hichri et al. , 2018b)).
At the best of our knowledge only two previous studies have been published on essential oils of A. cretica, collected in Turkey (K€ uc¸€ ukbay et al. 2012) and Tunisia (Hichri et al. 2018c), respectively, and their results will be discussed later.
In the frame of our ongoing research on the volatiles from Mediterranen species (Rigano et al. 2020;Badalamenti et al. 2022), we describe here the essential oil composition of a not previously studied accession of A. cretica, growing wild in Crete (Greece).

Results and discussion
Hydrodistillation of A. cretica aerial parts gave a pale-yellow oil (AC).Overall, sixteen compounds were identified, representing 97.52% of total components, listed in Table S1 according to their retention indices on a DB-Wax column and classified only into two classes based on their chemical structures.Oxygenated sesquiterpenes formed the main class, representing 64.54% of the oil, with a-bisabolol (53.88%), by far, as the most abundant component of the class followed by the related compound a-bisabolol-oxide (2.76%), and spathulenol (5.94%).Sesquiterpene hydrocarbons occurred in good amount (32.98%) being isoledene (11.07%) the principal constituents of the class, followed by alloaromadendrene (4.74%).
The chemical profile of this accession of A. cretica is quite peculiar as it is rich of bisabolene derivatives (56.64%), rarely present in the other oils of Achillea species, studied so far.In fact, a-bisabolol has been detected only in A. millefolium L. (Suleimenov et al. 2001;Turkmenoglu et al. 2015) and A. aleppica D.C. (Is¸can et al. 2006) and a-bisabolol-oxide in A. setacea Walldst & Kit.(Turkmenoglu et al. 2015), A. tenuifolia Lam.(Maffei et al. 1994) and A. lingulata Waldst & Kit.(Boskovic et al. 2005).On the other hand the presence of non-volatile bisabolene derivatives has been reported in the population of A. cretica growing in Cyprus (Bruno et al. 1996).Furthermore, the two previous reports on the essential oils of A. cretica showed a very different composition with respect to AC.In fact, the main constituents of the oil from