Accepted Manuscript

A novel insight on an ancient aromatic plant: the rosemary (Rosmarinus officinalis L.)

Regiane Ribeiro Santos, Denise Carvalho Costa, Carlos Cavaleiro, Helena S. Costa,
Tânia Gonçalves Albuquerque, Maria Conceição Castilho, Fernando Ramos, Nathália
R. Melo, Ana Sanches-Silva

PII: S0924-2244(15)00182-X
DOI: 10.1016/j.tifs.2015.07.015
Reference: TIFS 1694

To appear in: Trends in Food Science & Technology

Received Date: 28 February 2015

Revised Date: 14 July 2015
Accepted Date: 17 July 2015

Please cite this article as: Santos, R.R., Costa, D.C., Cavaleiro, C., Costa, H.S., Albuquerque, T.G.,
Castilho, M.C., Ramos, F., Melo, N.R., Sanches-Silva, A., A novel insight on an ancient aromatic plant:
the rosemary (Rosmarinus officinalis L.), Trends in Food Science & Technology (2015), doi: 10.1016/
j.tifs.2015.07.015.

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1

2 A novel insight on an ancient aromatic plant: the rosemary (Rosmarinus officinalis L.)

a,b,c a,d e,f a,g

3 Regiane Ribeiro Santos ; Denise Carvalho Costa ; Carlos Cavaleiro ; Helena S. Costa ;
a,g e,f e,f
4 Tânia Gonçalves Albuquerque ; Maria Conceição Castilho ; Fernando Ramos ; Nathália R.
b,c a,h,*
5 Melo ; Ana Sanches-Silva

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a
7 Department of Food and Nutrition, National Institute of Health Dr. Ricardo Jorge, I.P., Lisbon,
8 Portugal;

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b
9 Department of Food Technology, Institute of Technology, Federal Rural University of Rio de
10 Janeiro, Seropédica, Brazil

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c
11 Department of Agribusiness Engineering Federal Fluminense University– Volta Redonda, RJ –
12 Brazil

13 d

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ICETA – Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto, Porto,
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14 Portugal;

e
15 Pharmacy Faculty of the University of Coimbra, Coimbra, Portugal;
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f
16 CNC – Center for Neuroscience and Cell Biology, Pharmacy Faculty, University of Coimbra,
17 Coimbra, Portugal;
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g
18 REQUIMTE/LAQV, Faculdade de Farmácia da Universidade do Porto, Porto, Portugal;
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h
19 Centro de Estudos de Ciência Animal (CECA), Universidade do Porto, Porto, Portugal.

20
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21 * Corresponding author
22 Ana Sanches Silva
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23 Department of Food and Nutrition

24 National Institute of Health Dr Ricardo Jorge
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25 Av. Padre Cruz | 1649-016 Lisboa | Portugal

26 Tel.: (+351) 21 752 64 85
27 Fax: (+351) 21 750 81 53
28 e-mail: ana.silva@insa.min-saude.pt
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31 Abstract

32 Background: Rosemary (Rosmarinus officinalis L.) is a widely consumed aromatic plant that
33 belongs to the Lamiaceae family. Fresh and dried leaves are frequently used in traditional
34 Mediterranean cuisine and in folk medicine.
35 Scope and Approach: For this study, an extensive bibliographic review on rosemary was
36 carried out, including its main uses, components (both nutrients and bioactive), biological

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37 activities, interactions with drugs and potential applications.
38 Key Findings and Conclusions: The nutrient composition of rosemary reveals a great amount
39 of vitamins and minerals. The most well studied bioactive compounds are carnosic acid,

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40 carnosol, caffeic acid and its derivative, rosmarinic acid. The levels on bioactive compounds
41 depend on many factors, such as the variety, plant part, edafoclimatic conditions, drying

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42 conditions (if applied) and extraction and analysis methods. Numerous biological activities of
43 rosemary are recognized including antioxidant, antibacterial and antifungal, anti-cancer, anti-
44 inflammatory, among others. Therefore it has a vast range of industrial applications such as

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45 food and food packaging, pharmaceutical, perfumery and cosmetics industries.
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47 Keywords: Antioxidant activity, Bioactive compounds, Biological activities, Interactions with
48 drugs, Medicinal uses, Rosmarinus officinalis L.
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51 Introduction

52 Rosmarinus officinalis L. (rosemary) is an aromatic plant belonging to Lamiaceae family (Ali,

53 Saleem, Ali & Ahmad., 2000; Begum et al., 2013). Rosemary has been used for thousands of
54 years for both culinary and medicinal proposes, due to its aromatic properties and health
55 benefits (Holmes, 1999).

56 The biological activities of this plant are mainly related to the phenolic and the volatile

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57 constituents (Teixeira et al., 2013; Babovic et al., 2010; Arranz et al., 2015) such as carnosol,
58 carnosic acid and rosmarinic acid present in the extract of rosemary and α-pinene, (−)-
59 bornylacetate, camphor and eucalyptol present in the essential oil of this plant (Teixeira et al.,

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60 2013; Babovic et al., 2010; Arranz et al., 2015). Minor components may have a potential
61 influence on the biological activity due to the possibility of synergistic effect among their

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62 components (Hussain et al., 2010).

63 R. officinalis L. can be used fresh, dried or as tea infusion. The essential oil and the extract of
64 rosemary can be obtained for application in food packaging, aromatherapy and medicine
65

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treatment (Holmes, 1999; Peter, 2004; Szumny, Figiel, Gutiérrez-Ortíz & Carbonell-Barrachina,
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66 2010; Amaral et al., 2013; Barreto et al., 2014).

67 Rosemary is used for cooking as flavouring, in the preservation of foods, cosmetics (Peter,
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68 2004; Sasikumar, 2012) or in folk medicine for anti-inflammatory, diuretic and antimicrobial
69 applications (Haloui, Louedec, Michel & Lyoussi, 2000; Rožman & Jeršek, 2009; Teixeira et al.,
70 2013; Arranz et al., 2015) and for the prevention and treatment of diabetes, cancer and
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71 cardiovascular diseases (Bakirel, Bakirel, Keles, Ulgen & Yardibi, 2008; Hussain et al., 2010;
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72 Afonso et al. 2013). Rosemary provides protein, fibre, vitamins and minerals which are known to
73 have disease preventing properties (United States Department of Agriculture [USDA], 2011).

74 Currently, rosemary has been widely investigated as food additive. This aromatic plant can be
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75 added directly to food or incorporated in food packaging, performing as antimicrobial and

76 antioxidant agent. In addition, rosemary essential oil and extract has received recognition as
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77 generally recognized as safe for their intended use, within the meaning of section 409 of the Act
78 Food and Drugs Administration (FDA, 2014a; FDA, 2014b) and according to the Commission
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79 Directive 2010/67/EU and Commission Directive 2010/69/EU, respectively.

80 In view of the potential uses of rosemary as effective antimicrobial and antioxidant for food
81 preservation and their therapeutic properties, this paper overviews the nutritional, medicinal and
82 biological profile of rosemary. The main industrial applications are also reviewed and discussed.

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84 Brief history of Rosemary

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85 The word rosemary is derived from the Latin word ros-roris (dew) and marinus (sea), which
86 means ‘dew of the sea’ (Pintore et al., 2002; Begum et al., 2013). It was also called ‘antos’ by
87 the ancient Greeks, which is ‘the flower’, or ‘libanotis’ because of its incense smell (Pintore et
88 al., 2002; Begum et al., 2013). In the past, nearly two thousand years ago, this aromatic plant
89 was introduced in some European countries, like Britain, Greece and Italy, where rosemary was
90 believed to invigorate the memory and was remembered as the plant of fidelity and
91 remembrance (Begum et al., 2013). It was also associated with love and marriage, once it is still

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92 used in bridal bouquets and in the crib of a new baby to protect him/her against bad influences
93 and forces (Al-Sereitia, Abu-Amerb & Sena, 1999). The plant was also used to recover speech,
94 to enhance menstrual flow and stimulate hair growth, to help digestion and against flatulence

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95 and liver disorders (Heinrich, Kufer, Leonti & Pardo-de-Santayana, 2006). Anthropologists and
96 archaeologists found evidence that this aromatic plant was used as culinary, medicinal and

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97 cosmetic in the ancient Egypt, China, India and Mesopotamia (Stefanovits-Bányai, Tulok,
98 Hegedus, Renner & Varga, 2003). This plant was cultivated worldwide since long ago and over
99 the years rosemary was introduced as a garden plant, since its fragrance is quite pleasant

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100 (Heinrich et al., 2006; Ulbricht et al., 2010; Moreno et al., 2012; Begum et al., 2013).
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102 Botanical description, distribution and cultivation

103 Rosmarinus officinalis L. is generally known as rosemary, common rosemary or garden
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104 rosemary (Ulbricht et al., 2010; Begum et al., 2013). It belongs to Lamiaceae (previous called
105 Labiatae) family (Ali et al., 2000; Begum et al., 2013).
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106 Besides R. officinalis, the genus also includes R. eriocalyx, R. tomentosus, R. lavandulaceus
107 and R. laxiflorus (Arnold, Valentini, Bellomaria & Hocine, 1997; Elamrani, Zrira, Benjilali &
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108 Berrada, 2000; Angioni et al., 2004; Rosselló et al., 2006; Upson, 2006; Zaouali et al., 2010).
109 R. officinalis is the only that grows naturally in the Mediterranean region and the most exploited
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110 species due to its valuable essential oil (EO) but also due to its phenolic content and antioxidant
111 activity (Zaouali, Bouzaine & Boussaid, 2010).

112 More than 20 different types, varieties or cultivars of R. officinalis can be distinguished
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113 according to morphological descriptors (like calyx, corolla, dimension of leaf, inflorescence and
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114 the presence of glandular trichomes) (Zaouali et al., 2010; Begum et al., 2013). However, the
115 infraspecific systematics is confused and uncertain (Pintore et al., 2002; Zaouali et al., 2010;
116 Begum et al., 2013). Table 1 presents the varieties of rosemary and their characteristics.

117 Based on chemical criteria, namely the predominant constituents of the essential oils, several
118 chemotypes (infraspecific chemical varieties) were also distinguished: the 1,8-cineole
119 chemotype, the 1,8-cineole/α-pinene/camphor chemotype, the myrcene chemotype, the α-
120 pinene/verbenone/bornyl acetate chemotype and the 1,8-cineole/borneol/p-cymene chemotype
121 (Lawrence, 1995; Lawrence, 1993; Boutekedjiret, Bentahar, Belabbes, & Bessiere, 1998;

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122 Boutekedjiret, Belabbes, Bentahar & Bessiere, 1999; Rezzoug, Baghdadi, Louka, Boutekedjiret,
123 1998;Tomei, Cioni & Flamini, 1995; Dellacassa et al., 1999; Pintore et al., 2002).

124 R. officinalis is a xeromorphic species that grows spontaneously on sand, cliffs and stony
125 places, near the sea, in different parts of the world, such as Europe, Africa and Asia (Arnold et
126 al., 1997; Bakirel et al., 2008; Miraldi, Giachetti, Mazzoni,& Biagi, 2010). It is an evergreen
127 perennial with fragrant shrub reaching up to 2 m height. Its leaves are strongly curved, leathery,
128 linear and aromatic with prominent midrib, the upper surface of the leaf is dark green and the

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129 lowered surface is grey, with 1.0-2.5 cm long and 4 cm width by 1 to 3 mm thick (Lorenzi &
130 Mattos, 2006; Begum et al., 2013). The corolla is two-lipped and the stamens are curving
131 outwards beyond the corolla (Arnold et al., 1997). Rosemary flowers are small and light blue or

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132 lilac (Arnold et al., 1997; Lorenzi & Mattos, 2006). Leaves and flowers have a strong fragrant
133 characteristic odour due the volatile oil accumulated in typical peltate and capitate glandular

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134 trichomes (Marin et al., 2006; Diaz-Maroto, Pérez-Coello, Sánchez-Palomo & González Viñas,
135 2007).

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136
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137 Culinary and folk medicine uses

138 Many plants are important ingredients of the “folk pharmacopeia” and traditional cuisine,
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139 perfumers and cosmetics. Some of these wild botanicals have been semi domesticated and
140 have been cultivated in home gardens and in every homestead (Peter, 2004). According to the
141 most generally accepted sense, aromatic plants are plants valued for their medicinal and
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142 aromatic properties and are often grown and harvested for these unique properties (Peter,
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143 2004).

144 R. officinalis L. can be used fresh, dried, as extract or as EO (Szumny, Figiel, Gutiérrez-Ortíz &
145 Carbonell-Barrachina, 2010; Amaral et al., 2013; Barreto et al., 2014). It is an ingredient often
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146 used to adjust flavour in cooking and in tea infusion. Since the ancient days, rosemary has been
147 used in folk medicine for manifold conditions (Holmes, 1999; Peter, 2004). EO are natural
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148 products, volatile liquids, aromatic that are extracted from different plant parts such as flowers,
149 buds, seeds, leaves, stems and bark (Burt, 2004; Dvaranauskaite et al., 2009; Wannes et al.,
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150 2010; Lv et al., 2012; Hill, Gomes & Tylor, 2013). EO have been usually extracted by
151 supercritical fluid (SF) extraction, hydro and steam distillation methods (Khajeh, Yamini,
152 Bahramifar, Sefidkon, & Reza Pirmoradei, 2005; Dvaranauskaite et al., 2009; Wannes et al.,
153 2010).

154 The EO contains several components that may produce a synergic effect among them, or when
155 combined with others oils or compounds. This synergistic effect can increase their biological
156 activity (Romano, Abadi, Repetto, Vojnov & Moreno, 2009; Gibriel, Al-Sayed, Rady &
157 Abdelaleem, 2013). The EO as well as plants extracts have been widely used for several

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158 medicinal and culinary applications (Calucci et al. 2003; Shan, Cai, Sun & Corke, 2005; Chan,
159 Kong, Yee, Chua & Loo, 2012; Smeti, Atti, Mahouachi & Munoz, 2013).

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161 Culinary uses

162 The two basic forms of rosemary use in culinary preparations are fresh and dried powdered
163 leaves. It has a bitter astringent taste and it is aromatic. It is frequently used in traditional

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164 Mediterranean cuisine for flavouring foods as condiment (Szumny et al., 2010; Peter, 2012).
165 Rosemary can be added to cooked fish, meat, poultry, pork, soups, stews, sauces, dressings,

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166 preserves and jams (Peter, 2012).
167 In general, drying of fresh rosemary implies decrease of some attributes such as: fresh,
168 vegetable, pine odour, but increases some others as earthy, woody, infusion and hay-like odour

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169 (Díaz-Maroto, Pérez-Coello, Sánchez-Palomo & González Viñas, 2007; Szumny et al., 2010).
170 Fresh plants cannot be supplied in a profitable way to all worldwide locations because of its
171 limited shelf-life. However dried plants lose their quality slowly, making storage and transport
172

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easier compared with fresh plants (Díaz-Maroto et al., 2007).
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174 Folk medicine uses
175 Rosemary is well known as a common aromatic plant used worldwide in folk medicine for its
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176 therapeutic properties. Traditional uses of different parts of rosemary are shown in Table 2.
177 In folk medicine, the aerial parts of rosemary are mainly used in oral administration to anti-
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178 inflammation effects, headache, abdominal pain, antispasmodic, arthritic, gout affections,
179 stomachic, wound healing (poultice), choleretic, diuretic, analgesic, antirheumatic and
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180 antidepressant (Holmes, 1999; González-Trujano et al., 2007; Peng et al. 2007; Martínez,
181 González-Trujano, Chávez, & Pellicer, 2012, Sasikumar, 2012; Karakurum Göksel et al., 2014).
182 Hungary water, the first (European) alcohol-based perfume, was prepared from rosemary and it
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183 was considered to be a revitalizing agent. Distilled water obtained from rosemary’s flowers was
184 used as an eye lotion (Sasikumar, 2012).
185 The whole plant, in the form of decoction, infusion, extract (for external application) and EO,
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186 was administered against digestive disorders (as carminative and gastrointestinal stimulant),
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187 respiratory diseases (as expectorant and antiseptic), heart pain (as heart restorative, arterial
188 stimulant) inflammation and dizziness (Holmes, 1999; Sasikumar, 2012) and to enhance
189 memory (Holmes, 1999; Adsersen et al., 2006; Sasikumar, 2012).
190 Karakurum -Göksel et al. (2014) reported that rosemary therapy is known in 23.6% of patients
191 in Turkey and rosemary has been frequently used in patients with migraine. In Lebanon, 28
192 plants species were considered as being the most important, including the rosemary (Marc et
193 al., 2008).
194 The European Medicines Agency has a monograph on R. officinalis L. (EMA, 2010). Rosemary
195 leaf and oil were described for use as drugs. According to this monograph, R. officinalis L.,
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196 aetheroleum is traditionally used orally for the symptomatic relief of dyspepsia and mild
197 spasmodic disorders of the gastrointestinal tract, while it is traditionally used cutaneously and as
198 bath additive for the relief of minor muscular and articular pain and in minor peripheral
199 circulatory disorders. Well established uses are not indicated for this plant. The monograph also
200 establishes the posology and describes contraindications, according to the method of
201 administration.
202 The European Pharmacopoeia (2005) includes two monographs, one regarding rosemary leaf

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203 (Rosmarini folium) and another regarding rosemary oil (Rosmarini aetheroleum).
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205 Nutritional Composition (macro and micronutrients)

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206 The proximate and minerals content found in rosemary are shown in Tables 3 and 4,
207 respectively. The variation on macro and micronutrients content can be greatly attributed to the

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208 differences in species, varieties, growth conditions, harvesting times, soil properties, climate,
209 origin, and geographic parameters (Arslan & Özcan, 2008; Özcan et al., 2008).
210 Nutrients, as well as compounds responsible for flavour and colour can be degraded due to the

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211 high temperatures and long times applied in some drying methods (Szumny et al., 2010).
212 Aromatic plants provide protein, fibre, volatile components (EO), vitamins (A, C and B), minerals
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213 (Ca, P, Na, K and Fe) and chemical compounds that are known to have disease preventing and
214 promoting health properties (USDA, 2011).
215 Aromatic plants are an excellent substitute of salt due to their composition and nutritional health
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216 functions. Excessive consumption of salt influences the appearance of hypertension, stomach
217 cancer or stroke. The use of plants like rosemary is recommended by Portuguese authorities to
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218 help reduce added salt to food (Direção-Geral da Saúde [DGS], 2014).
219 However, there is limited information about aromatic plants nutritional composition. Some
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220 aromatic plants such as basil, cinnamon, cloves, coriander, cumin, fennel, ginger, nutmeg,
221 oregano, parsley, rosemary, sage and thyme can be found in the American, Australian,
222 Brazilian, Canadian, Danish, Finn, French, Italian, Japanese, Portuguese, Spanish, and
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223 Swedish food composition databases.

224 Dumbravă, Moldovan, Raba and Popa (2012) identified the vitamin C content of raw materials
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225 (18.51 g/100 g), aqueous (0.26 mg/100 mL), alcoholic (0.34 mg/100 mL) and acetonic (0.36
226 mg/100 mL) extract of rosemary leaves. The authors also quantified chlorophyll “a” (14.1 mg/L)
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227 and carotenes plus xanthophylls (30.6 mg/L) in alcohol leaves extract. On the other hand,
228 Loranty, Rembialkowska, Rosa and Bennet (2010) did not detect any pigments in the infusion of
229 rosemary.
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231 Composition on bioactive compounds
232 The main volatiles, phenolics and carotenoids compounds of rosemary are shown in Tables 5
233 and 6, respectively. Aromatic plants are rich in volatile oils, which give pleasurable aromas.
234 Important flavour compounds in rosemary are monoterpenes hydrocarbons, oxygenated

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235 monoterpenes, sesquiterpene hydrocarbons, oxygenated sesquiterpenes, esters, ketones,
236 phenol, alcohol and others (Teixeira et al., 2013; Mathlouthi et al., 2012).
237 Studies have pointed out the variability of the composition profile and yield of the plant materials
238 oil/ extract, due to the influence of factors such as extraction processes, the species, the plant
239 part used, the geographic origin, the time of harvest, the stage of development of plants and
240 age (Flamini et al., 2002.; Khajeh, Yamini, Bahramifar, Sefidkon & Reza Pirmoradei, 2005;
241 Elzaawely, Xuan, Koyama & Tawata, 2007; Hussain, Anwar, Sherazi & Przybylski, 2008;

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242 Mulinacci et al., 2011; Negi, 2012; Riahi et al. 2013). Besides this, the composition of rosemary
243 may be influenced by type of storage (fresh, dried or frozen), drying method and type of solvent
244 used for extraction (Celiktas et al., 2007; Szumny et al., 2010; Dumbravă et al, 2012; Mulinacci

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245 et al., 2011).
246 The influence of the impact of drying method on volatile compounds of rosemary EO was

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247 evaluated by Szumny et al. (2010). Leaves, branches and stems were mixed and subjected to
248 convection (CD), microwave (VMD) and combined (convective pre-drying (CPD) followed by VM
249 finish-drying (VMFD)) drying. The total volatiles concentration of fresh rosemary (135 g/kg)

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250 decreased during CD (87.2 g/kg), VMD (61.9 g/kg) and VMFD (100 g/kg) processes.
251 Flamini et al. (2002) showed that the chemical composition of rosemary EO from different
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252 ecotypes (Lunigian and Cevoli plants), parts (apical, intermediate and lower) and organs
253 (leaves, flowers and stems) clearly differ, and higher EO yield was found in the leaves and
254 flowers than in stems.
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255 The production of rosemary extracts using supercritical fluids extraction and applying different
256 process conditions was carried out by Vicente et al. (2013). Despite the concentration of volatile
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257 compounds obtained in the extracts, the composition of the extract is quite similar, being 1,8-
258 cineole and camphor the most abundant key volatiles present in rosemary.
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259 In in vitro studies, Scollard, Francis and O’Beirne (2014) showed that the method of extraction
260 of rosemary affected antilisterial properties in the following order: hydro-distillate>CO2
261 extract>hexane/acetone extract. The chemical composition of the extracts varied depending on
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262 the extraction method used. However, in all of the rosemary extracts, borneol, bornyl acetate,
263 camphor, caryophyllene and verbenone and camphor were the most abundant compounds.
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264 Higher temperatures can be compensated by higher yields, besides this, SF technique has the
265 advantage of saving time and prevents the conversion of carnosic acid into carnosol which is a
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266 fast reaction in the presence of oxygen molecules (Peng et al., 2007).
267 The traditional extraction method with lipophilic solvents such as n-pentane or n-hexane for 1 to
268 24 hours of contact induced a strong decrease of phenols, with a corresponding increment in its
269 typical oxidized products (carnosol and rosmanol). The enzymatic oxidation of rosmarinic acid in
270 fresh leaves, not observed in the correspondent dried samples, was observed in the presence
271 of the native water which provided a micro environment where the enzyme could act (Bellumori
272 et al., 2014). According to the results of Mulinacci et al. (2011), this fraction is very sensitive to
273 the presence of water during the extraction that favours the conversion of carnosic acid into its
274 oxidized form, carnosol.
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275 Babovic et al. (2010) found, in the antioxidant fraction isolated from rosemary leaves, jasmonic
276 acid (0.25%), cirsimaritin (0.5%), rosmanol, isorosmanol, epirosmanol (2.9%), carnosic acid
277 isomer (0.5%), wogonin, oroxylin A, biochanin A, genkwanin (1.2%), carnosol (21.8%), carnosol
278 isomer (0.8%), rosmadial (2.3%), rosmaridiphenol, cafestol (1.8%), carnosic acid (46.9%),
279 methyl carnosate and 12-methoxycarnosic acid (12.2%).
280 The quantification of both, α-tocopherol (31.62 mg/100 g fresh sample) and γ-tocopherol (0.36
281 mg/100 g fresh sample) was carried out by Gómez-Coronado, Ibañez, Rupérez and Barbas

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282 (2004). The authors also showed the seasonal variability of contents of rosemary leaves,
283 concluding that, in general terms, both tocopherol contents were higher in winter than in
284 summer.

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285 The study of Mulinacci et al. (2011) demonstrated that storing the raw fresh material in the
286 freezer is not appropriate in the case of rosemary, mainly due to the rapid degradation of

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287 rosmarinic acid during the freezing/thawing process. Regarding the flavonolic fraction, a
288 consistent decrease was found in the samples dried at room temperature when compared with
289 the fresh samples. Rosmarinic acid appeared to be very sensitive also to mild drying processes.

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291 Processing effects
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292 Common aromatic plants are marketed in the form of liquid, oils and also as powders resulting
293 from the dryness of a liquid extract. Advantages of the dried extract over conventional liquid
294 forms include lower storage costs and higher concentration and stability of active substances.
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295 Processing can induce partial losses or modification of the components of aromatic plants
296 (Souza, Schiavetto, Thomazini & Oliveira, 2006; Mulinacci et al., 2011). The chemical stability of
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297 the aromatic plants components depends on the storage conditions, drying procedure,
298 extraction solvent and extraction method.
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299 Dehydration of different parts of aromatic plants can be performed using different methods (e.g.
300 sun drying, air-drying at room temperature, convective, oven and microwave drying (Díaz-
301 Maroto, Viñas & Cabezudo, 2003; Arslan & Özcan 2008; Szumny et al., 2010)) which may
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302 affect rosemary composition, biological activity and aroma. Convective (using hot air) and
303 vacuum-microwave drying methods were tested by Szumny et al. (2010) in rosemary plant. The
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304 authors observed that long times of microwave heating and high wattages increased sample
305 temperature (mean temperature of 40 °C). Convection and microwave dried samples contained
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306 64.6% and 54.1% of the fresh rosemary volatiles content, respectively. Authors recommend the
307 use of a combination of both methods due to the higher content of volatile compounds, yield
308 and aroma.
309 Arslan and Özcan (2008) compared the following drying methods: microwave, sun-drying and
310 oven. Microwave oven drying shortened the process, followed by the oven method. However,
311 microwave drying method showed the lowest increase in mineral values while the highest
312 mineral values were determined in oven dried samples when compared to fresh rosemary
313 leaves. Microwave oven drying revealed optimum colour, while oven drying samples were
314 darker when compared to the sun and microwave dried samples.
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315 A consistent decrease of flavonoids fraction of rosemary was higher in the dried samples at
316 room temperature, when compared with the fresh leaves. Rosmarinic acid also appeared very
317 sensitive to mild drying processes (Mulinacci et al., 2011).
318 Regarding the sensorial properties, drying of fresh rosemary implied decreases or changes of
319 the same attributes as fresh, vegetable, pine, herbaceous, balsamic and colour but increased
320 others such as hay-like, earthy, sweet, woody, and infusion (Arslan & Özcan 2008; Szumny et
321 al., 2010).

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322 Several extractive methods are proposed to recover the volatile and non-volatile compounds
323 from rosemary. The technique includes the selection of sample amount, sample state (e.g.
324 fresh, dried or freeze dried), extraction solvent ratio (sample: solvent), number of successive

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325 extractive steps, pressure, time and temperature (Herrero, Plaza, Cifuentes & Ibáñez, 2010;
326 Mulinacci et al., 2011).

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327 Common extraction techniques include extraction with solvents, steam distillation, Soxhlet and
328 hydrodistillation (Roldán-Gutiérrez, Ruiz-Jiménez & Luque de Castro, 2008; Erkan, Ayranci &
329 Ayranci, 2008; Bousbia et al., 2009; Mulinacci et al., 2011). The green processes have low

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330 environmental impact due to being solvent-free or using very low amount of solvents. These
331 have also been applied for the extraction of bioactive compounds from rosemary, such as:
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332 supercritical fluids, pressurized liquid extraction, ultrasound and microwave extraction (Herrero
333 et al., 2010; Borrás Linares et al., 2011; Jacotet-Navarro et al., 2015).
334 Regarding rosemary, total diterpenoids content is sensitive to the presence of water during
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335 extraction because it favours the conversion of carnosic acid towards its oxidized form carnosol.
336 Moreover, extraction yields of rosmarinic and carnosic acids can be improved when mixtures of
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337 alcoholic solvents are used (Mulinacci et al., 2011).

338 Bousbia et al. (2009) reported that higher amounts of oxygenated compounds are present in the
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339 essential oils of rosemary isolated by microwave hydrodiffusion and gravity in comparison with
340 hydrodistillation. Consequently, the essential oil obtained with the microwave method showed a
341 better aroma and an antimicrobial and antioxidant activities slightly higher. Organic compounds
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342 like oxygenated compounds that have a high dipolar moment interact more vigorously with
343 microwaves.
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344 The solvent used in the extraction process has significant effect on the active compounds of
345 rosemary extract. The use of acetone to obtain powdered rosemary extract showed higher
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346 antioxidant potential, total phenolics, carnosic acid, carnosol and essential oils content followed
347 by methanol (Teruel, Garrido, Espinosa & Linares, 2015).
348 Beside the drying and extraction methods, the storage can also change the rosemary
349 constituents. In the study conducted by Mulinacci et al. (2011) it was showed that storing the
350 raw fresh material in the freezer was not appropriate for rosemary, mainly due to the rapid
351 degradation of rosmarinic acid, presumably involving the phenoloxidase activity. The storage
352 time affected the aroma of dried rosemary stored for 6 months, producing an intense spice
353 aroma that was undetectable in the other samples (Díaz-Maroto et al., 2007).
354
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355
356 Biological activities
357 Rosemary is an interesting aromatic plant for its content on bioactive compounds that have
358 putative benefits on human health. Two groups of compounds are mainly responsible for the
359 biological activities of the plant: the volatile fraction and the phenolic constituents (Teixeira et
360 al., 2013; Babovic et al., 2010; Arranz et al., 2015).
361 Modern analysis techniques have enabled the identification and quantification of individual

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362 components and the study of their effects.
363 The influence of dietary polyphenols on human health and volatile compounds on food quality
364 are currently widely accepted. In fact, these compounds have been suggested to positively

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365 influence the prevention of several different chronic diseases and to extend food shelf-life
366 (Babovic et al., 2010).

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367 The biological activities of the EO are often attributed to their major compounds (Burt, 2004;
368 Ojeda-Sana, Van Baren, Elechosa, Juárez, Moreno, 2013). However, the biological activity
369 exhibited by EO can be the result of the contribution of different compounds (Hussain et al.,

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370 2010; Ojeda-Sana et al., 2013). There is some evidence that minor components play a critical
371 role in biological activity, possibly by producing a synergistic effect among other components.
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372 The effectiveness of rosemary EO as antioxidant and antibacterial agents depend on an
373 adequate number and content of key bioactive(s) compound(s) (Ojeda-Sana et al., 2013).
374 Today, rosemary is credited with having many varied biological properties. The medicinal, food
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375 properties and the chemical constituents that are now thought to be involved in these effects are
376 listed in Table 6.
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377
378 Antibacterial and antifungal activity
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379 The volatile compounds 1,8-cineole, camphor, eugenol and α-pinene (Azeredo et al., 2011;
380 Teixeira et al., 2013; Abdollahzadeh, Rezaei & Hosseini et al., 2014; Ojeda-Sana et al., 2013),
381 and the carnosic acid phenolic compound (Rožman & Jeršek, 2009) have been associated with
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382 the antimicrobial activity of rosemary EO.

383 Rosemary EO exhibited better antibacterial activity than 1,8-cineol, the principal component of
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384 this EO according to the study carried out by Hussain et al. (2010). This might be due to the
385 synergistic effect of some minor components present in the oil. The minor components are
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386 critical to the activity and may have a potential influence (Burt, 2004).
387 Rosemary plant was effective against Staphylococcus aureus, Bacillus cereus, Bacillus subtilis,
388 Bacillus pumilis, Pseudomonas aeruginosa, Salmonella poona, Escherichia coli (Hussain et al.,
389 2010), Listeria innoca, Bacillus thermosphacta, Listeria innocua, Listeria monocytogenes,
390 Staphylococcus putrefaciens (Teixeira et al., 2013), Aspergillus flavus and Aspergillus niger
391 fungi (Souza et al., 2013).
392 Antimicrobial activity of rosemary extract was considerably higher than additives commonly
393 used in food such as butylated hydroxytoluene (BHT) and benzoic acid (Romano et al., 2009).

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394 However, the rosemary EO showed to be less effective than the EO of Origanum vulgare and
395 Cinnamomum zeylanicum (Abdollahzadeh, Rezaei & Hosseini, 2014).
396 The rosemary EO showed higher antibacterial activity against Gram-positive bacteria than
397 Gram-negative bacteria (Hussain et al., 2010; Pesavento et al., 2015).
398 Rosemary plant is effective against some pathogens and therefore, it can reduce the risk and
399 incidence of foodborne diseases. However, the same study with EO has showed high minimal
400 inhibitory concentration (MIC, i.e. the lowest concentration of oil that will inhibit the visible

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401 growth of a microorganism) against microorganisms (Azeredo et al.; 2011, Souza et al., 2013;
402 Teixeira et al., 2013). The different MIC obtained are probably due to different microbial
403 susceptibility, microorganisms, characteristics of the EOs used, due to the large variability of the

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404 chemical composition of each EO chemotypes (Flamini et al. 2002; Teixeira et al. 2013;
405 Pesavento et al. 2015).

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406
407 In vitro antioxidant activity

408 The antioxidant activity of rosemary may be attributed to phenolic constituents such as carnosic

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409 acid, carnosol (Babovic et al., 2010; Peng et al., 2007; Peter, 2012), rosmarinic acid (Peter,
410 2012; Kontogianni et al., 2013), rosmanol (Peng et al., 2007; Peter, 2012; Kontogianni et al.,
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411 2013), methyl carnosate (Peng et al., 2007), luteolin (Sasaki et al.,2013), betulinic acid
412 (Kontogianni et al., 2013), myrcene (Ojeda-Sana et al. 2013) and flavonoids as cirsimartin and
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413 genkwain (Peng et al. 2007). Besides this, volatile compounds may also contribute to
414 antioxidant activity (Hussain et al. 2010).

415 Rosemary extract presented better antioxidant activity than the synthetic antioxidant butylated
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416 hydroxyanisole (BHA) (Babovic et al., 2010), trolox and ascorbic acid (Peng et al., 2007).
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417 Moreover, carnosic acid and rosmarinic acid had a considerable higher activity than BHT and α-
418 tocopherol (Romano et al., 2009).

419 The synergistic effect of some minor components present in rosemary was observed when the
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420 rosemary EO showed better radical scavenging activity than their main component (1,8- cineol)
421 (Hussain et al., 2010; Kontaganini et al., 2013). Synergistic effect can maximise the antioxidant
422 activity of EO and minimise the concentrations required to achieve a particular effect (Burt,
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423 2004).
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424 Lamiaceae family presents important compounds for the production of food additives and can
425 be used not only for flavouring food but also to improve the overall quality of the product and to
426 extend the shelf-life of foods (Babovic et al., 2010).

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428 Anti-cancer effect

429 Carnosic acid, carnosol (Bai et al. 2010; Tai, Cheung,Wu & Hasman, 2012; Valdés et al.,
430 2012b; Valdés et al., 2012a; Sánchez-Camargo et al., 2014), and betulinic acid were identified
431 as the main antiproliferative agents of rosemary (Kontogianni et al., 2013). Volatile compounds
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432 such as 1,8-cineol, camphor, and α-pinene of this aromatic plant also showed prominent
433 antiproliferative activity against breast and prostate cancer (Hussain et al., 2010). Phenolic
434 compounds in association with monoterpenes provided a synergistic effect (Sánchez-Camargo
435 et al., 2014).

436 The cytotoxic activity of rosemary could be attributed to carnosic acid, monoterpenes and
437 triterpenoids (betulinic and ursolic acid). The potential synergistic effect among these suggest
438 that the combination of two features (cytotoxic activity and antioxidant activity), could provide

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439 both direct destruction of cancer cells and protection of healthy cells during cancer treatment
440 (Kontogianni et al., 2013; Sánches-Camargo et al., 2014). Kontogianni et al., 2013; Vicente et
441 al., 2013).

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442 Rosemary constituents have demonstrated different cytotoxicity effects depending on the
443 tumour cell type, oil concentration and time of exposition (Valdés et al., 2012a). Valdés et al.

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444 (2012b) carried out a study on antiproliferative effect of dietary polyphenols from rosemary on
445 leukaemia cells, whereas Tai et al. (2012); Valdés et al. (2012a) and Vicente et al. (2013),
446 showed the antiproliferation effect of rosemary extract on human ovarian cancer cells, on

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447 human colon cancer cells and on hepatic tumour progression, respectively.
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448
449 Anti-inflammatory effect
450 Rosemary extracts with carnosic acid, carnosol (Peng et al., 2007; Bai et al., 2010; Arranz et al.,
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451 2015), ursolic acid (Altinier et al., 2007) and flavonoids may play an important role in the anti-
452 inflammatory disorders such as spasmolytic, arthritic and gout affections (González-Trujano et
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453 al., 2007).

454 The volatile aroma compounds of rosemary such as 1,8-cineole, borneol and camphor may be
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455 determinant of the anti-inflammatory activity (Ehrnhöfer-Ressler et al., 2013).

456
457 Anti-diabetic effect
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458 The rosemary extract exerts remarkable anti-diabetogenic effect (Bakirel et al., 2008; Cui et al.,
459 2012), which may be related to the phenolic compound carnosol (Cui et al., 2012).
460 Rosemary extract (200 mg/kg dry sample) showed subacute anti-hyperglycaemic and
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461 insulinotropic effects, due to its potent antioxidant properties, capability to inhibit the lipid
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462 peroxidation and activate the antioxidant enzymes (Bakirel et al., 2008).
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464 Antiulcerogenic effect
465 The rosemary plant inhibited the ulcerative lesion (Dia, Foglio, Possenti & Carvalho 2000;
466 Amaral et al., 2013). Rosemary is able to act as a gastroprotective agent exerting a potent anti-
467 inflammatory effect in the gastric mucosa, reverting swelling and preventing the infiltration of
468 inflammatory cells (Amaral et al., 2013).
469 The antiulcerogenic properties, resulting from different mechanisms, may be attributed to
470 polyphenols as primary source of antioxidants (Dias et al., 2000; Amaral et al., 2013;
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471 Asokkumar, Sen, Umamaheswari, Sivashanmugam & Subhadradevi, 2014) such as carnosic
472 acid and rosmarinic acid. Furthermore, some antiulcerogenic activity of other constituents found
473 in minor quantity might act synergistically (Amaral et al., 2013).
474 The ethanolic extract of rosemary at 500 and 1000 mg/kg was found to induce better
475 gastroprotective effects than omeprazole at 30 mg/kg, a dose clinically used in humans (Dias et
476 al., 2000).
477

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478 Antinociceptive effect
479 The flavonoids like quercetin and kaempherol (González-Trujano et al. 2007), and the
480 triterpenes: micromeric acid, ursolic acid and oleanolic acid are responsible for the analgesic

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481 effect of rosemary (Martínez et al., 2012).
482 Pharmacological activity of rosemary is associated with different routes of administration to

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483 produce antinociceptive effects depending on the kind and intensity of the induced pain
484 (González-Trujano et al., 2007).
485

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486 Antidepressant
487 Extract of R. officinalis causes an antidepressant-like effect (Machado et al. 2009; Machado et
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488 al. 2013; Sasaki et al., 2013). Phytochemical studies have identified active components in this
489 plant, such as of carnosol, betulinic acid, ursolic acid, 1,8-cineole (Machado et al., 2013),
490 luteolin, carnosic acid, rosmarinic acid (Sasaki et al., 2013), components that may be
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491 responsible for the antidepressant effect of rosemary.

492 Rosemary extract (10 mg/kg, per os) was similar to the action produced by the classical
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493 antidepressant fluoxetine, using the same dose (10 mg/kg, per os) (Machado et al., 2009).
494
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495 Antianxiety
496 Ferlemi et al.(2015) revealed that oral administration of rosemary tea by adult male mice
497 reduced anxiety. In humans, the same effect was evidenced by lower scores on test anxiety
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498 measure, personal statements and pulse rates, when using lavender and rosemary essential oil
499 sachets (McCaffrey,Thomas & Kinzelman, 2009).
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500
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501 Antithrombotic effects

502 Rosemary can prevent the arterial thrombotic disease based on inhibition platelet reactivity and
503 inhibition coagulation tests in vivo and in vitro. The antithrombotic effect of rosemary is likely to
504 be based on an inhibitory effect on platelets (Yamamoto et al., 2005; Naemura, Ura, Yamashita,
505 Arai &, Yamamoto, 2008).

506
507 Other effects

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508 The combination of citrus flavonoids and rosemary polyphenols and diterpenes may be
509 considered as an ingredient for oral photoprotection (Pérez -Sánchez et al., 2014). Aruoma et
510 al. (1996) tested the same pure compounds to check for the anti-HIV activity of rosemary. The
511 authors showed that the carnosol exhibited weak but definite anti-HIV activity. The phenolic
512 compound, carnosol, may be useful in the therapeutics of obesity (Cui et al., 2012). Treatment
513 with rosemary leaf extract induced a reduction of weight and fat mass gain due to the inhibition
514 of pancreatic lipase activity induced by rosemary (Harach et al., 2010). While, Afonso et al.

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515 (2013) suggested that rats that received aqueous extract of rosemary improved the antioxidant
516 defense in different tissues and attenuated oxidative stress in diet-induced
517 hypercholesterolemic rats. Different clonal lines of rosemary showed to have α-glucosidase

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518 inhibitory activity (Kwon, Vattem & Shetty, 2006). This activity correlated to the phenolic content,
519 antioxidant activity and phenolic profile of the extracts. Moreover, extracts of rosemary, had high

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520 ACE inhibitory activity (Kwon et al., 2006). Other studies showed that polyphenol-rich diets
521 correlate with a reduced incidence of neurological disorders (Fernández-Fernández et al. 2012).
522 The chlorogenic acid present in the rosemary provides protective effects to Alzheimer’s disease

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523 (Lee et al., 2011), whereas, Fernández, Palomino and Frutos (2013) observed antihypotensive
524 effect of rosemary oil in patients. Ingestion of 500 mg/kg body weight of rosemary reduced
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525 fertility in female and a decline in spermatogenesis in male in in vivo tests (Nusier, Bataineh &
526 Daradkah, 2007). However, in doses between 50 and 100 mg/kg body weight, rosemary did not
527 affect the spermatogenesis as studied by Heidari-Vala, Ebrahimi, Reza & Mehdi (2013).
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528 Rosmarinic acid or carnosic acid, compounds found in rosemary when in combination with
529 lycopene, synergistically inhibit low-density lipoprotein (LDL) oxidation (Fuhrman, Volkova,
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530 Rosenblat & Aviram, 2000). Samman et al., (2001) observed that rosemary extracts inhibited
531 the absorption of iron. The authors suggested that chelation of iron may be one of the
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532 mechanisms of the antioxidant action.

533
534 Possible interactions with drugs
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535 Efficacies of administered drugs can be affected by food. A food-drug interaction can prevent a
536 drug from working the way it should; cause a side effect from a drug to get worse or better, or
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537 cause a new side effect (FDA, 2013). Aromatic plants are often administered in combination
538 with therapeutic drugs, raising the potential interaction between them.
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539 Although there are therapeutic indications for the use of rosemary leaf and oil, as stated earlier,
540 safety data and interactions are not well established. Rosemary can affect how the drugs cines
541 work. It may have an antagonic, additive or synergistic effect with the drug (Vuuren, Suliman &
542 Viljoen, 2009).
543 Possible interactions of rosemary with drugs or foods are presented in Table 2. Ulbricht et al.
544 (2010) carried out an interesting evidence-based systematic review of rosemary including also
545 some interactions with drugs, herbs/supplement and food.
546
547 Potential and current industrial applications
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548 Essential oils of several aromatic plants are approved for direct contact with food because they
549 are considered to be Generally Recognized as Safe (GRAS) according to FDA (FDA, 2014b).
550 In addition, the rosemary extract has received recognition as safe and effective antioxidant for
551 food preservation, according to new European Commission directives 2010/69/EC and
552 2010/67/EC (European Commission, 2010). The level required is dependent on the food and it
553 is expressed as the sum of carnosol and carnosic acid, the main antioxidant components of the
554 rosemary extracts (European Commission, 2010).

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555 When applied in food, rosemary EO as well as rosemary extract can be used as a food additive
556 exerting antioxidant and antimicrobial functions.
557 The effectiveness of rosemary extracts and EO in meat and meat products and animal feed

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558 supplements was studied by Olmedo et al (2013), Ortuño, Serrano & Bañón (2015), Teruel et
559 al. (2015), Pesavento et al. (2015), Tironi, Tomás & Añón (2010), Keokamnerd, Acton, Han &

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560 Dawson (2008) and Mathlouthi et al. (2012).
561 Rosemary EO may be employed in fruit and vegetables products as antimicrobial as reported
562 by Azeredo et al. (2011) and Souza et al. (2013).

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563 Rosemary extract or EO can be incorporated into active films to release flavouring, antimicrobial
564 or antioxidant constituents from the packaging to food (Seydim & Sarikus 2006; Rožman &
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565 Jeršek, 2009; Abdollahi et al., 2012, Fernandez-Pan, Royo, Maté, 2012, Sanches-Silva et al.,
566 2014). Undesirable strong aroma effects can be limited by careful selection of EO according to
567 the type of food (Burt, 2004).
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568 The rosemary extract or EO can be incorporated into polymeric matrices such as polypropylene,
569 polyethylene and low density polyethylene. Currently several studies describe the development
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570 of renewable plastic films from biopolymers matrices such as protein and carbohydrate based
571 (Seydim & Sarikus 2006; Abdollahi et al., 2012; Sanches-Silva et al., 2014).
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572
573 Potential industrial applications
574 Tironi et al. (2010) evaluated the quality loss of sea salmon muscles when applying rosemary
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575 extract during its storage at -11 °C. Results showed that the application of 500 mg/kg of
576 rosemary extract to the fish muscle produced a delay in the development of lipid oxidation
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577 secondary products during the first 7 months in addition to a 50% of reduction of the maximum
578 amount of oxidized compounds. Besides, there was a delay of the loss of the red colour. The
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579 application of 200 mg/kg of rosemary extract showed a less evident effect than 500 mg/kg, due
580 to the lower antioxidant concentration. The results showed the rosemary extract as a promissory
581 natural antioxidant to be used in minced frozen sea salmon products.
582 Olmedo et al. (2013) evaluated the effect of rosemary EO on the oxidative and fermentative
583 stabilities of flavoured cheese prepared with cream cheese base. Regarding sensory attributes,
584 the intensity rating of EO aroma was higher, but significant differences were not detected
585 between samples with and without EO. Rosemary EO prevented lipid oxidation and inhibited the

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586 fermentation. Therefore it is a good natural preserving, that prolongs the shelf-life of this
587 product.
588 Ortuño et al. (2015) studied the use of dietary rosemary to extend the preservation of sulphited-
589 lamb products. Patties were formulated combining meat from different sources (lambs given
590 feed supplemented with 400 mg of dietary rosemary extract/kg were compared with lambs not
591 supplemented), with different levels of added SO2 (between 0-450 mg/kg). Lambs fed with
592 dietary rosemary extract (DRE) and addition of 450 mg/kg of SO2, presented the greater

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593 stabilization and inhibition of lipid oxidation and odour deterioration. The authors suggested a
594 possible synergistic interaction between high SO2 doses and the DRE, improving meat
595 preservation in high-sulphited patties.

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596 The effect of different solvents on the preparation of the rosemary extracts and on the physical-
597 chemical and sensory quality of rosemary frozen chicken nuggets was evaluated by Teruel et al.

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598 (2015). The phenolic content (23.23 g gallic acid equivalents/100 g), concentration of active
599 compounds (28.9 g/kg of carnosol and 179.2 g/kg of carnosic acid) and antioxidant activity were
600 higher in the powder acetone extract than in the two liquid extracts (acetone and methanol). The

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601 extracts were added to chicken nuggets formulations and stored for 9 months. After this period
602 of time, it a slight tendency concerning the effectiveness of the rosemary extracts to inhibit lipid
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603 oxidation was observed. As respect to the mass or crust colour, odour or taste intensity, no
604 alteration was evident during storage. Thus, the addition of these rosemary extracts to chicken
605 nuggets has potential use as an alternative in the production of pre-fried products, and it can be
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606 used as antioxidant.

607 Pesavento et al. (2015) tested antimicrobial activity of rosemary against Listeria monocytogenes
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608 and Staphylococcus aureus. Different concentration of rosemary EO (0.5%, 1%, or 2% (v/w))
609 were added to 25 g of minced meat and inoculated with the suspensions of the pathogens at the
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2 3 4
610 following final concentrations of about 10, 10 , 10 and 10 Colony Forming Units/g and
611 preserved at 4 °C. The presence of the EO began to act immediately after contact. Raw minced
612 meat samples, with added EO, assumed acceptable colour up to the end of the experiment.
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613 Cooked meat containing 0.5% of EO did not exceed the flavour acceptability threshold. Both
614 concentrations of EO (0.5% and 1%) caused bacteriostasis of all pathogen concentrations, even
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615 of the most concentrated pathogens. The minimal bactericidal concentration was only possible
616 for the lowest bacterial concentration, respectively after 11 (2% of EO) and 14 days (1% de EO)
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617 of storage for Listeria monocytogenes and Staphylococcus aureus.

618 Scollard et al. (2014) tested the antilisterial effects of rosemary extract when macerated with
619 contaminated fresh-cut vegetables. Hydro-distillate method of extraction presented higher anti-
620 listeria effect than CO2 and hexane/acetone extract. The rosemary constituents verbenone,
621 followed by camphor, had better antilisterial effectiveness. Besides this, macerated rosemary
622 plant increased levels of their constituents. Thus, it was suggested, in this study, that strong
623 antilisterial effects is obtained in an aqueous medium in which rosemary was crushed during
624 maceration yielding powerful antimicrobial effects in fresh-cut vegetables.

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625 Urbančič, Kolar, Dimitrijević, Demšar, and Vidrih (2014) evaluated the effect of rosemary extract
626 on the stabilization of sunflower oil and reduction of acrylamide formation in potatoes chips
627 during deep-fat frying. The additives, including, rosemary extract was added to sunflower oil
628 (1000 mg/kg), which included 49 mg/kg carnosol and carnosic acid, as the active ingredients.
629 Oil with rosemary extract presented the most stable formulation, showing lower degradation
630 products, lower free fatty acids formation (hydrolysis), and lower acrylamide content than the
631 use of tocopherols (900 mg/kg active ingredient), synthetic antioxidants like tertiary

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632 butylhydroquinone (TBHQ) (200 mg/kg active ingredients) and BHA (200 mg/kg active
633 ingredients) during deep-frying. The unprotected frying oil is more susceptible to degradation
634 during deep-frying than the frying oil with addition of theses antioxidants. The higher thermal

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635 stability of the sunflower oil with the rosemary extract showed exceptional protective effects of
636 deep-fried food.

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637 Doolaege et al. (2012) evaluated the oxidative stability of lever pâté in relation to different
638 concentrations of rosemary extract and sodium nitrite. Smeti et al. (2013) studied the colour
639 stability, lipid oxidation and sensorial properties of fresh Barbarine lamb’s meat with rosemary

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640 EO. Increased shelf life of meat was achieved due to the use of rosemary EO. Hernández,
641 García García, Jordán and Hernández (2014) tested experimental diets supplemented with
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642 different doses of rosemary extract added to feed fish and analyzed the quality of gilthead sea
643 bream in ice storage.
644 The presence of synergistic effect can produce the desired biological effect at a lower
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645 concentration, which does not produce undesirable changes in the flavour or aroma. Synergistic
646 effects could be exploited so as to maximise the biological activity of EOs and to minimise the
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647 concentrations required to achieve a particular effect. Antagonism between EO and food
648 ingredients is undesirable but it can occur (Burt, 2004).
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649
650 Current industrial applications
651 There is a patent related to the use of rosemary extracts as drugs to treat a disorder connected
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652 to reduced neurotransmission, as well as to dietary and pharmaceutical compositions containing

653 such rosemary extracts and their uses (European patent 2081582 A1). Other inventions regard
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654 the use of rosemary extract as coating of food packaging (European patent 1477519-A1) and to
655 control the activity of biogenic amines in food (World Intellectual Property Organization
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656 2013084175 A1).

657 Several trade names are available for rosemary extracts. Guardian® produces Guardian®
658 Rosemary Extract 08 (oil-soluble), Guardian® Rosemary Extract 09 (water-dispersible) and
659 Guardian® Rosemary Extract 11 (powder form) for specific applications directly or in dilution in
660 meat, oil and cereal. These products are used as antioxidants and flavorings. Herbalox®
661 rosemary extract is produced by Kalsec®. It is available in oil dispersible, water dispersible and
662 water soluble forms. The product is used as antioxidant and it can be applied in meat,
663 beverages, oils and snacks.
664
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665 Concluding remarks
666 Nowadays, rosemary attracts great interest of health professionals, researchers, consumers
667 and industry due to be considered a good source of bioactive compounds with putative health
668 benefits. Therefore its consumption is encouraged and promoted. In addition, rosemary can act
669 in the preservation of food, preventing lipid oxidation, extending shelf-life and reducing the risk
670 of foodborne disease. Phenolics and carotenoids are bioactive compounds present in rosemary
671 that can contribute to these properties. The major phenolic compounds present in rosemary are

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672 rosmarinic acid, caffeic acid, carnosic acid and carnosol while β-carotene and lutein are the
673 predominant carotenoids present in this aromatic plant. The levels of these compounds depend
674 on many factors, such as the variety, plant part, edafoclimatic conditions, drying conditions (if

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675 applied) and extraction and analysis methods.

676 Numerous rosemary’s biological activities have been ascribed including antioxidant,

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677 antimicrobial, anti-cancer, anti-inflammatory, anti-diabetic effect, antiulcerogenic effect,
678 antinociceptive effect and antidepressant. Minor constituents may greatly contribute for the
679 biological activities of rosemary due to synergic effect.

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As extract or EO, rosemary has a vast range of applications such as food and food packaging,
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681 pharmaceutical, perfumery and cosmetics industries. In a word, this ancient aromatic plant has
682 easy and wide applicability which can highly benefit consumers, even indirectly. Therefore, it is
683 foreseen that, in the future years, new products and applications will arise based on rosemary
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684 exploitation.
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686 Acknowledgements

687 This work was supported by Project Number PTDC/AGR-TEC/3366/2012 with the acronym
688 Rose4Pack (Biodegradable active packaging with rosemary extract (R. officinalis) to improve
689 food shelf life), and funded by the Foundation for Science and Technology (FCT) and
690 COMPETE Programme [grant number FCOMP-01-0124-FEDER-028015]. Regiane Ribeiro dos
691 Santos (BEX 8754/14-4) is grateful for a research grant funded by Brazilian Federal Agency for
692 Support and Evaluation of Graduate Education (CAPES) and Department of Food Technology,

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693 Institute of Technology, Rural Federal University of Rio de Janeiro, Brazil. Denise Costa is
694 grateful for the research grant under the project Rose4Pack. Tânia G. Albuquerque is grateful
695 for the research grant (BRJ/DAN-2012) funded by the National Institute of Health Dr. Ricardo

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696 Jorge, I.P.
697

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698

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699 References

Abdollahi, M., Rezaei, M., & Farzi, G. (2012). A novel active bionanocomposite film incorporating
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701 rosemary essential oil and nanoclay into chitosan. Journal of Food Engineering, 111(2), 343–
702 350.

Abdollahzadeh, E., Rezaei, M., & Hosseini, H. (2014). Antibacterial activity of plant essential oils and
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704 extracts: The role of thyme essential oil, nisin, and their combination to control Listeria

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705 monocytogenes inoculated in minced fish meat. Food Control, 35(1), 177–183.

Adsersen, A., Gauguin, B., Gudiksen, L., & Jäger, A. K. (2006). Screening of plants used in Danish
706

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707 folk medicine to treat memory dysfunction for acetylcholinesterase inhibitory activity. Journal of
708 Ethnopharmacology, 104(3), 418–22.

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Table 1. Rosemary varieties and their morphological characteristics.

Rosemary varieties Characteristics References

Albus White flowers Ulbricht et al., 2010

Most common; pale blue flowers and Ulbricht et al., 2010; Mattia et al.,
Arp
green-gray foliage 2011; Begum et al., 2013
Aureus leaves speckled yellow Ulbricht et al., 2010
Ulbricht et al., 2010; Begum et al.,
Benenden Blue Blue flowers and dark green foliage

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2013
Blue boy Pale blue flowers and small leaves Ulbricht et al., 2010
Blue Lady blue-violet flowers and very narrow leaves Begum et al., 2013
Blue Spires bright blue flowers on tall upright stems Begum et al., 2013

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Collingwood Ingram Blue flowers and bright green foliage Begum et al., 2013
Foresteri Blue flowers Begum et al., 2013
Girardus Blue flowers and very dense foliage Begum et al., 2013

SC
Ulbricht et al., 2010; Begum et al.,
Golden Rain Blue flowers and yellow leaves in extremity
2013
Gorizia Blue flowers and dark green leaves Begum et al., 2013
Hill Hardy Blue flowers and needle shaped leave Begum et al., 2013
Irene Intense blue flowers Ulbricht et al., 2010

U
Ken Taylor Dark blue flowers Ulbricht et al., 2010
Keneth´s Prostate Blue flowers Begum et al., 2013
AN
lavender blue flowers and dark green Ulbricht et al., 2010; Begum et al.,
Lockwood de Forest
foliage 2013
Logee´s Blue Blue flowers and bluish green foliage Begum et al., 2013
Ulbricht et al., 2010; Begum et al.,
M

Majorica Pink Pink flowers and needle shaped leave

2013
Ulbricht et al., 2010; Begum et al.,
Miss Jessop´s Upright Blue flowers
2013
D

Mrs Howards Small blue flowers Begum et al., 2013

Pinkie Pink flowers Ulbricht et al., 2010
Blue flowers and leaves with pine
TE

Pine-Scented Begum et al., 2013

fragrance
Prostratus Blue flowers Ulbricht et al., 2010
Pyramidalis Pale blue flowers Ulbricht et al., 2010
Rex Blue flowers and dark green foliage Begum et al., 2013
EP

Roseus Pink flowers Ulbricht et al., 2010

Santa Barbara Blue flowers Begum et al., 2013
Ulbricht et al., 2010; Begum et al.,
Severn Sea Violet-blue flowers
2013
C

Suffolk Blue Blue flowers Ulbricht et al., 2010

Ulbricht et al., 2010; Begum et al.,
Tuscan Blue Dense blue flowering
AC

2013
White-Flowered White flowers Begum et al., 2013
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Table 2. Use in folk medicine and health benefits of rosemary plant and possible interactions of rosemary
with drugs, supplements or foods.
Traditional use in
Plant part Extract used References
folk medicine
Ethylic acetate, methanolic, chloroformic,
Leaves Antibacterial agent Erdogrul, 2002
acetonic extracts
Adsersen,
treatment of Gauguin,
Plant Methanolic, aqueous extracts
memory dysfunction Gudiksen &
Jäger, 2006

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Anti-inflammatory
Leaves Ethanolic and acetonic extracts Peng et al., 2007
agent
Antinociceptive and González-
Aerial parts Ethanolic extract anti-inflammatory Trujano et al.,
activity 2007

RI
Marc, Nelly,
Antirheumatic and
Leaves Maceration in alcohol Annick &
antineuralgic
Frederic, 2008

SC
Machado et al.,
Stems and leaves Hydroalcoholic extract Anti-depressant
2009
Antiproliferative,
antioxidant and Hussain et al.,
Leaves Essential oil
antibacterial 2010

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activities
Antinociceptive Martínez et al.,
Aerial parts Hexane, ethyl acetate ethanol extracts
activity 2012
AN
Sasaki, Omri,
Antidepressant
Leaves Ethanolic extracts Kondo, Han &
effect
Isoda, 2013
Antioxidant,
vasodilator and anti- Amaral et al.,
M

Leaves Ethanolic extract

inflammatory 2013
properties
Physiological system Health Benefits*
D

Improves memory; helps with insomnia,

Brain and nervous mental fatigue, nervous anxiety and
TE

tension

Improves circulation and stimulates

Cardiovascular
heart functions
EP

Gastrointestinal Promotes digestion

Female reproductive system Regulates menstrual cycle

C

Promotes liver function and bile

Liver
production
AC

Respiratory Promotes colds recovery

Reference
Drugs/supplements/foods Possible consequences of the interaction with rosemary

Based on in vitro studies, rosemary oil produced an

Wang, Wang & Kuo,
Aminophylline enhancement in the permeability of the epidermis to
2007
(Bronchodilator) aminophylline.

Inhalation of essential oil of rosemary may affect the

Ulbricht et al., 2010
Analgesics perception of pain, without reducing pain sensitivity.

Rosemary essential oil reduced anxiety by inhalation Ulbricht et al., 2010;

Anxiolytics
(synergism). Posadzki et al, 2012
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Rosemary extract exerts a synergistic effect in combination González-Vallinas et

with 5-fluorouracil on colon cancer cells, potentiating the al., 2013
antiproliferative effect of 5-FU.
Antitumors/ Antineoplasics
Carnosic acid-rich rosemary extract, in association with Sharabani et al.,
vitamin D3, enhance the antiproliferative and differentiating 2006
effects in human leukemic cells.
Vuuren, Suliman &
Rosemary oil in combination with ciprofloxacin showed an
Antibiotic Viljoen, 2009;
antagonic effect against Staphylococcus aureus and Candida
(e.g. ciprofloxacin) Posadzki et al, 2012

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albicans (synergism).
Aqueous rosemary extracts enhanced furosemide
Diuretics Laitinen et al., 2004
permeability in in vitro study. Therefore, there is risk of
(e.g. furosemide)
dehydration.

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Ulbricht et al., 2010;
Anticoagulants or Rosemary may affect the blood coagulation and may
Makino et al., 2002;
antiplatelets interfere synergistically with these drugs. Antithrombotic
(e.g. warfarin) Posadzki et al, 2012
activity of rosemary may involve the inhibition of platelets.

SC
Antihypertensives Rosemary may interfere with drugs that inhibit the action of Kwon et al., 2006
(e.g. captpril) Angiotensin Converting Enzyme (ACE).
Beaulieu, 2001;
Immunosupressants
Rosemary may interact with cyclosporine.

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(e.g. cyclosporine) Ulbricht et al., 2010;

Debersac et al.,
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Cytochrome P450-
Rosemary may induce P450 enzymes in the liver. 2001
metabolized agents

Rosemary may interfere with glucose levels in both diabetics Ulbricht et al., 2010
Antidiabetics
and non-diabetics.
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Iron or iron containing Samman et al., 2001

Rosemary may decrease iron absorption
foods
The rosemary components rosmarinic acid and carnosic acid
Lycopene or lycopene- Fuhrman et al., 2000
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may interact synergistically with lycopene inhibiting LDL

containing foods
oxidation.
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*Begum et al., 2013

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Table 3. Nutritional value of Rosemary plant.

Component Units Fresh Rosemary Dried Rosemary
Energy kcal 131 96 331 331 345
Water g/100 g 67.77 73.6 9.31 9.3 9.3
Protein* g/100 g 3.31 1.4 4.88 4.9 5.0
Total lipids (Fat) g/100 g 5.86 4.4 15.22 15.2 15.2
Total carbohydrates g/100 g 20.70 - 64.06 - 46.4

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Total dietary fibre g/100 g 14.10 7.7 42.6 17.7 24.1
Fatty acids
Total saturated g/100 g 2.84 1.14 7.371 3.94 -
Total monounsaturated g/100 g 1.16 0.29 3.014 0.99 -

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Total polyunsaturated g/100 g 0.90 2.25 2.339 7.76 -
Vitamins
Total ascorbic acid mg/100 g 21.8 29 61.2 0.00 50

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Thiamin mg/100 g 0.036 0.10 0.514 0.10 0.5
Riboflavin mg/100 g 0.152 0.21 0.428 0.32 0.00
Niacin mg/100 g 0.912 1.0 1.00 1.0 1.00
Vitamin B6 mg/100 g 0.336 0.09 1.740 0.38 0.00

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Vitamin E mg/100 g - 1.50 - 9.15 0.00
Folate, µg/100 g 109 0.00 307 0.00 0.00
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Vitamin B12 µg/100 g 0.00 - 0.00 - 0.00
Vitamin A, RAE µg/100 g 146 92.0 156 313 313
Vitamin D (D2+D3) µg/100 g 0.00 0.00 0.00
0.00 0.00
References USDA BDA USDA BDA BEDCA
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* Nitrogen Conversion Factor – 6.25

USDA = United States Department of Agriculture; BDA = Banca Dati di Composizione degli Alimenti per Studi
Epidemiologici; BEDCA= Base de Datos Española de Composición de Alimentos.
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Table 4. Minerals content (mg/100 g) of rosemary.

Plant part
Minerals
Dried leaves Fresh Leaves Aerial
(mg/100 g)
- - Oven Sun Microwave oven Fresh Fresh Dried Infusion
Ag - - - - - - - 0.01 0.00
Al 115 - 24.0 23.1 22.5 14.8 - 3.1 0.00

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As - - - - - - - 0.0 0.00
B 2.1 - 3.1 4.6 3.1 2.9 - 0.7 0.01

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Ba - - 3.3 4.1 3.9 2.4 - 0.2 0.00
Bi - - - - - - 0.02 0.00

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Ca 860.5 1280 1358.7 1234.3 1360.0 779.2 317 22.4 2.5
Cd 0.07 - - - - - - 0.005 0.00
Co - - 0.2 0.2 0.1 0.1 - 0.04 0.00

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Cr 1.9 - 1.7 15.3 11.9 9.7 - - 0.00
Cu 0.3 - 0.5 0.5 0.5 0.4 - - 0.00

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Fe 73.4 29.2 76.0 53.5 50.7 33 6.6 - 0.01
K 1111.6 955 2110.4 1961.2 1614.9 1491.6 668 - 9.0

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Li 0.3 - 0.7 0.6 0.5 0.4 - - 0.01
Mg 240.8 220 280.7 261.8 169.8 163.4 91 - 1.0
Mn 2.8 - 3.2 2.9 2.1 1.5 - 0.2 0.01

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Na 489.4 50 444.8 437.7 297.7 271.2 26 4.34 0.01

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Ni 0.8 - 6.0 4.7 4.16 1.9 - 0.04 0.00
P 820.5 70 412.2 210.6 289.5 107.5 66 146.6 0.01
Pb 0.2 - - - - - - 0.034 0.00
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Se - - - - - - - 0.4 0.00
Sr 6.7 - 11.5 10.4 8.8 7.5 - 0.2 0.00
Ti - - - - - - - 0.7 0.00
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V 0.99 - 0.1 0.09 0,07 0.04 - 0.006 0.00

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Zn 3.1 3.2 4.9 4.2 2.8 2.3 0.9 0.7 0.00

Özcan, Ünver,
Özcan & Arslan & Arslan & Arslan & Arslan & Özcan et
Reference USDA USDA Uçar & Arslan,
Akbulut, 2007 Özcan, 2008 Özcan, 2008 Özcan, 2008 Özcan, 2008 al., 2008
2008
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Table 5. Main volatile compounds concentrations(%) found in rosemary

Concentrations of the main volatile compounds of rosemary (%)
Plant
Rosemary
part Borneol α- β- β- 1,8- References
Camphor Eucalyptol Verbenone Myrcene Borneol Camphene
acetate pinene pinene caryophyllene cineole

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Hussain et
Leaves 17.1 12.3 0.2 1.12 1.11 3.25 6.0 38.5 al. 2010.
Olmedo,
Nepote &

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Leaves 35.70 15.80 26.20 Grosso,
2013
Ojeda-

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Sana,Van
Baren,
18.7-
Leaves 0.2-2 7.0-15.4 31.2 1.7 1.7-2.2 2-3 31.1 0.4-4 2-5 Elechosa,
21.6

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Juárez &
Moreno,

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Essential 2013
oils Vicente et
Leaves 1-2 20-32 4-9 6-15 48-67 al., 2013.
Martínez et

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Aerial 6.49 8.75 8.6 14.10 12.02 3.31 4.8 11.5 al., 2012
Machado et
Aerial 21.8 4.62 1.1 4.8 1.37 45.1 al., 2013

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Flower Teixeira et
13,4 35.5 18.2 4.9 1.8 - 2.3 al., 2013
tops

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Flamini et al.,
Flower 7-9.5 10-11.5 15-21 1-3 - 17-19 1-2 15-18 10.6 6-8 2002
Flamini, Cioni,
Stems 1.6 5-8 16-20 2-2.4 - - 0.7-1 12-29 11-12 3-7 Morelli Macchia &
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Ceccarini, 2002
Sánchez-
Extract Leaves - 14-25 - 0.4-14 - 2-4 2.5-5 0.3-2 5-7 0.2-4 40-51 Camargo et
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al., 2014.
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Rao et al.,
Fresh Leaves 3.0 27.9 7.5 5.7 - 4.2 4.4 29.0 1997

Rao et al.,
Dried Leaves 2-4 24-34 - 11.9 - - 6-11 - 3.7 2-6.5 15.5-30 1997
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Table 6. Phenolic and carotenoid compounds of rosemary
Compounds Units Content References
Okamura,Fujimoto, Kuwabara &
Carnosic acid 4205
mg/100 g dried leaves Yagi, 1994
Carnosol 387
Carnosic acid
Carnosol mg/100 g fresh leaves 2279 238 Okamura et al.,1994

Rosmarinic acid
mg/100 g dry weight 700 Zgórka, & Głowniak, 2001

Vanillic acid

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1.73
Caffeic acid
2.95 32.8 Zheng & Wang, 2001
Rosmarinic acid
mg/100 g fresh weight 19.7
Hispidulin
24.4
Cirsimaritin
127

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Carnosic acid
Rosmarinic acid
1000-1100
Caffeic acid mg/ 100 g dried leaves Wang, Provan, & Helliwell, 2004
10-20

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Chlorogenic acid
12
Caffeic acid
mg/100 g dry weight 8 Kivilompolo & Hyotylainen, 2007
Ferulic acid
916

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Caffeic acid
406
Ferulic acid
36.2 Wojdylo, Oszmianski, & Czemerys,
Luteolin mg/100 g dry weight
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616 2007
Apigenin
43.8
Vanillic acid
0.40
Caffeic acid
1.2
Naringin
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57
Rosmarinic acid
208
Hispidulin mg/ 100 g fresh weight Luis, Pérez, & González, 2007.
2.0
Cirsimaritin
8.0
Carnosol
D

58
Carnosic acid
1218
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Clorogenic acid 11.2

caffeic acid 7.63
Rutin 3.07
Rosmarinic acid mg/g ethanolic extract 38.5 Amaral et al., 2013
Quercetin 5.10
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Kaempferol 2.53
Carnosic acid 26.4

Ursolic acid 190.1

Oleanolic acid 89.7
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Betulinic acid 46.9

Methyl carnosate 7.9
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Carnosic acid 177.3

Rosmaridiphenol mg/ g dry weight 18.2 Kontogianni et al.,2013,
Rosmadial 8.7
Carnosol 21.5
Genkwanin 2.0
Rosmarinic acid), 11.6
homoplantaginin 1.5

β-Carotene
1146
Lutein + Zeaxanthin Daly, Jiwan, O’Brien & Aherne,
µg/ 100 g dry weight 944
β-cryptoxanthin 2010.
32
lutein + zeaxanthin µg/ 100 g fresh leaves 14700 Calucci et al.,2003
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Highlights

• Main botanical characteristics of rosemary are described;

• Culinary and folk medicinal uses of rosemary are overviewed;

• Nutritional composition and bioactive compounds of this aromatic plant is compiled;

• Health effects and industrial applications of rosemary are focused in detail.

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