Reviews A Review of the Traditional Uses, Phytochemistry and Biological Activities of the Genus Santolina Authors Rosa Tundis, Monica Rosa Loizzo Affiliation Correspondence Department of Pharmacy, Health and Nutritional Sciences, Prof. Rosa Tundis University of Calabria, Rende (CS), Italy Department of Pharmacy, Health and Nutritional Sciences, University of Calabria Key words Via P. Bucci – Edificio polifunzionale, 87036 Rende (CS), Italy Santolina, Asteraceae, ethnobotany, phytochemicals, Phone:+39984493246,Fax:+3998449310774 biological activities [email protected] received November 15, 2017 ABSTRACT revised February 5, 2018 The genus Santolina is a taxonomically complex group of plant accepted February 16, 2018 species widely distributed in the Mediterranean flora and used Bibliography in traditional medicine since ancient times for their biological DOI https://doi.org/10.1055/a-0585-6153 properties, including antimicrobial, anti-inflammatory, anti- Published online March 8, 2018 | Planta Med 2018; 84: 627– spasmodic, digestive, and analgesic activities. Phytochemical 637 © Georg Thieme Verlag KG Stuttgart · New York | investigations of Santolina species have revealed the presence ISSN 0032‑0943 of terpenoids as the main bioactive constituents of the genus. Coumarins and flavonoids were also identified. This review deals, for the first time, with information on the traditional uses, chemical profile, and biological properties of plants of the genus Santolina in order to provide input for future re- search prospects. tolina africana Jord. & Fourr., Santolina benthamiana Jord. & Fourr., ABBREVIATIONS Santolina canescens Lag., Santolina chamaecyparissus L., Santolina GPT glutamate pyruvate transaminase corsica Jord. & Fourr., Santolina decumbens Mill., Santolina elegans HD hydrodistillation Boiss. ex DC., Santolina etrusca (Lacaita) Marchi & DʼAmato, Santo- HSV-1 herpes simplex type 1 lina insularis (Gennari ex Fiori) Arrigoni, Santolina magonica Romo, HSV-2 herpes simplex type 2 Santolina melidensis Rodr.Oubiña & S.Ortiz, Santolina neapolitana MIC minimum inhibitory concentration Jord. & Fourr., Santolina oblongifolia Boiss., Santolina pectinata This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. MPLC medium-pressure liquid chromatography Lag., Santolina pinnata Viv., Santolina rosmarinifolia L., Santolina NF-κB nuclear factor-kappa B semidentata Hoffmanns. & Link, Santolina tincloria “Molina”, San- PLA1 phospholipase A1 tolina villosa Mill., and Santolina virens Mill.). It is a taxonomically PLA2 phospholipase A2 complex genus consisting of plant species whose classification SFE supercritical fluid extraction has been revised several times. S. chamaecyparissus L., S. pectinata Lag., and Santolina viridis W. are the most widespread [1]. With increasing interest in bioactive secondary metabolites from Santolina spp., several studies related Introduction to the investigation of the phytochemical composition and bio- logical properties of species from this genus have been carried The Santolina genus (family Asteraceae, tribe Anthemideae) com- out. In recent decades, phytochemical studies have discovered prises species widely distributed in the Mediterranean area. The the presence of terpenoids, particularly eudesmane and germa- Plant List includes 103 scientific plant names of species of this ge- crane sesquiterpenoids, chrysanthemane monoterpenoids [2,3], nus. However, of these, only 20 are accepted species names (San- dammarane-type triterpenes [4], flavonoids [5,6], and coumarins Tundis R, Loizzo MR. A Review of … Planta Med 2018; 84: 627–637 627 Reviews ▶ Table 1 Ethnomedicinal uses of Santolina species. Santolina species Local name Traditional uses Part used Country Ref. S. chamaecyparissus lavender cotton, gray san- antispasmodic, digestive, analgesic, inflorescence Mediterranean [11–14] tolina anti-inflammatory, antiseptic, stimulant, area, India and antimicrobial; to treat dermatitis S. chamaecyparissus manzanilla, manzanilla de to treat ophthalmological problems, inflorescence Spain [15,16] subsp. squarrosa monte, manzanilla basta, headache, belly pain, stomach problems, manzanilla de burro and as digestive and depurative S. corsica crespolina di Corsica intestinal vermifuge, parasite repellent inflorescence Italy [19, 20] S. etrusca canfora antiparasitic aerial parts Italy [21] S. insularis crespolina maggiore, san- vermifuge and to repel insects inflorescence Italy [19] tolina, crespolina sarda S. insularis crespolina insulare sedative, febrifuge, and antitussive leaves Italy [18] S. neapolitana green santolina, crespolina cough suppressant aerial parts Italy [17] napoletana S. oblongifolia manzanilla de Gredos anti-inflammatory and digestive inflorescence Spain [7] S. rosmarinifolia green lavender cotton antipyretic, antihypertensive, hepato- flower heads Spain [22,26] protective, and anti-inflammatory [6, 7] in plant species of this genus. The literature data revealed Traditional Uses that Santolina species show various biological activities, including antibacterial, antifungal, antiviral, anti-inflammatory, cytotoxic, For a long time, several plant species have been used for medicinal and hepatoprotective effects [2, 5, 8–11]. purposes. Among Santolina species, S. chamaecyparissus, S. etrus- The aim of this review is to provide a complete overview of ex- ca, S. insularis, S. neapolitana,andS. oblongifolia have been re- isting knowledge on the traditional uses, chemical constituents, ported in traditional medicine. A summary of their traditional and biological properties of plant species from the Santolina ge- use is presented in ▶ Table 1. S. chamaecyparissus has been in- nus. serted in the Ayurvedic system of medicine in India for the treat- The available information on this genus was collected from sci- ment of liver diseases. Moreover, the yellow inflorescences of entific databases up until November 2017. The following elec- S. chamaecyparissus are widely used in Mediterranean traditional tronic databases were used: PubMed, SciFinder, Science Direct, medicine for their analgesic, anti-inflammatory, antispasmodic, Scopus, Web of Science, Wiley, ACS, Springer, and Google Scholar. antiseptic, and antimicrobial properties [11, 12]. Moreover, this The search terms used for this review included Santolina, Santolina plant, commonly called “lavender cotton” or “gray santolina”,is chamaecyparissus, Santolina insularis, Santolina corsica, Santolina employed for the treatment of numerous kinds of dermatitis, as oblongifolia, Santolina canescens, Santolina neapolitana, Santolina a stimulant, and as a stomachic [13,14]. In the traditional medi- pinnata, Santolina pectinata, Santolina rosmarinifolia, Santolina cine of Spain, S. chamaecyparissus subsp. squarrosa wasusedasa etrusca, Santolina semidentata, Santolina tincloria, Santolina villosa, substitute for Artemisia granatensis, “manzanilla real”, for the Santolina virens, phytochemical composition, essential oils, ses- treatment of ophthalmological problems, headache, belly pain, quiterpenes, phenols, flavonoids, coumarins, traditional uses, ac- stomach problems, and as a digestive and depurative [15, 16]. tivity, pharmacology, and toxicity. No limitations were set for lan- This species is locally named “manzanilla de monte”, “manzanilla guages. “The Plant List” (www.theplantlist.org) was used to val- basta”,and“manzanilla de burro” [16]. This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. idate the scientific names of the Santolina species. Seventy-five Savo et al. [17] reported the use of S. neapolitana (= S. pinnata potentially relevant records were found, from which seven were subsp. neapolitana) against cough in the Amalfi Coast (Campania, excluded after screening the titles or abstracts. Southern Italy). A decoction of the leaves of S. insularis, known in From the available literature, two species, namely, S. chamae- Italy as “crespolina maggiore”, has been used as a sedative, febri- cyparissus and S. insularis, have been the most investigated. S. cor- fuge, and antitussive [18]. The whole plant was used as an intesti- sica, S. oblongifolia, S. canescens, S. rosmarinifolia,andS. etrusca nal vermifuge against horse strongyloidiasis and as a parasite re- have also been phytochemically and biologically studied. S. pecti- pellent [19, 20]. Another Santolina species used in Italy as an intes- nata and S. semidentata were investigated for the chemical com- tinal vermifuge and parasite repellent is S. corsica [19,20]. S. etrus- position of their essential oil, but no biological studies were de- ca (“canfora”) is known in Italy for its traditional uses. This is an scribed. endemic species growing in the gravel beds of rivers, clayey, and Critical evaluation of biological studies in terms of their rela- arid hills, and is found exclusively in Central Italy, particularly in tion to the chemical profile is highlighted. Available information Northern Latium, Tuscany, and Umbria. Its antiparasitic activity on these species allows us to provide the scientific basis for future has been reported [21]. In the traditional medicine of Spain, S. ob- research studies and to explore their potential therapeutic use. longifolia, known as “manzanilla de Gredos”, is used as a digestive 628 Tundis R, Loizzo MR. A Review of … Planta Med 2018; 84: 627–637 ▶ Table 2 ThemainvolatilesoftheessentialoilsfromSantolina species. Plant species Country Main compounds Reference S. africana Algeria