Sinapic Acid: Is It Safe for Humans?
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FABAD J. Pharm. Sci., 41, 39-49, 2016 REVIEW ARTICLES Sinapic Acid: Is It Safe for Humans? Hasan HAMEED*, Sevtap AYDIN**,o, Nurşen BAŞARAN** Sinapic Acid: Is It Safe for Humans? Sinapik asit: İnsanlarda güvenli mi? SUMMARY ÖZET Phenolic compounds, one of the most commonly occurring groups En yaygın görülen fitokimyasal madde gruplarından biri of phytochemicals, play an important role in the growth and olan fenolik bileşikler, meyve ve sebzeleri asalak ve patojenlere reproduction of plants, providing protection against pathogens karşı korumanın yanı sıra, renk ve duyusal özelliklerine de and predators, also contributing towards the colour and sensory katkıda bulunarak, bitkilerin üreme ve büyümesinde önemli characteristics of fruits and vegetables. In humans, it is also suggested bir rol oynarlar. İnsanlarda da fenolik bileşiklerin antioksidan, to have antioxidant, anti-inflammatory, antimicrobial, anticancer, antiinflamatuvar, antimikrobiyal, kalp koruyucu ve antikanser and cardioprotective effects. Sinapic acid is a small naturally etkileri olduğu iddia edilmektedir. Sinapik asit doğal olarak occurring hydroxycinnamic acid derivative. It is a phenolic compound oluşan ufak bir hidroksisinamik asit türevidir. Sağlığa faydalı ve and a member of the phenylpropanoid family which are assumed as genel olarak toksik olmadığı varsayılan fenilpropanoid ailesinden therapeutically beneficial and generally non-toxic. Sinapic acid is bir fenolik bileşiktir. Sinapik asit bitki dünyasında (meyve, sebze, widespread in the plant kingdom (fruits, vegetables, cereal grains, tahıl taneleri, yağlı tohumlu bitkiler, bazı baharatlar ve şifalı oilseed crops, some spices and medicinal plants) and in human bitkiler) ve insan diyetinde yaygın bulunur. Sinapik asit türevleri diet. Derivatives of sinapic acid are characteristic compounds in the Brassicaceae familyasındaki karakteristik bileşiklerdir. Sinapik asit, Brassicaceae family. Sinapic acid shows antioxidant, antimicrobial, antioksidan, antimikrobiyal, anti-inflamatuvar, antikanser ve anti-inflammatory, anticancer, and anxiolytic activities. Mainly due anksiyolitik aktivite gösterir. Çoğunlukla antioksidan aktiviteleri to their antioxidative activities, these compounds have been suggested nedeniyle, sinapik asit ve türevlerinin gıda işleme, kozmetik ve ilaç for potential use in food processing, cosmetics, and pharmaceutical endüstrisinde potansiyel kullanımı önerilmektedir. Bu derlemede industry. In this review, the pharmacological effect, toxicity and safety sinapik asitin farmakolojik etkileri, toksisitesi ve güvenlik profili profile of sinapic acid were assessed. değerlendirilmiştir. Key Words: Phenolic compounds, sinapic acid, Pharmacokinetic Anahtar kelimeler: Fenolik bileşikler, sinapik asit, effects, pharmacological effects, toxicity, safety. farmakokinetik etkiler, farmakolojik etkiler, toksisite, güvenlilik. Received: 29.01.2017 Revised: 16.02.2017 Accepted: 22.02.2017 * Department of Pharmacology, Faculty of Pharmacy, Basra University, 61004, BAGHDAD ** Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Hacettepe University, Ankara, 06100, TURKEY o Corresponding author/authors: Hacettepe University, Faculty of Pharmacy, Pharmaceutical Toxicology Department, Ankara, 06100, Turkey. Tel: 312 30152167 Fax: 312 311477 E-mail: [email protected] 39 Hameed, Aydın, Başaran INTRODUCTION Sinapic acid Hydroxycinnamic acids (HCAs) are one of the Phenolic compounds are a group of key major classes of phenolic compounds found in nature plant metabolites found abundantly in fruit and (Herrmann and Nagel, 1989). They have been shown vegetables. Because of their antioxidant properties, to have beneficial effects in various human diseases, they play an important role in preventing various particularly atherosclerosis and cancer. They are degenerative disorders or diseases related to oxidative damage. Phenolic compounds exhibit a wide range secondary metabolites derived from phenylalanine of physiological properties, such as antiallergic, and tyrosine, and they all have a C6_C3 carbon antiatherogenic, antiinflammatory, antimicrobial, skeleton with a double bond in the side chain that antioxidant, antithrombotic, cardioprotective and may have a cis or a trans configuration. Among the vasodilatory effects (Tarkoet al., 2013; Aydin et al., most common and well-known HCAs are cinnamic 2015; Tokaç et al., 2014). acid, o-coumaric acid, m-coumaric acid, p-coumaric Phenolic compounds, ubiquitous in plants, are acid, caffeic acid, ferulic acid, and sinapic acid (El- essential parts of human diet, and are of considerable Seedi et al., 2012). HCAs are widely distributed in interest due to their antioxidant properties. These the plant kingdom, including many species that are compounds possess an aromatic ring bearing one or more hydroxyl groups and their structures may consumed as food or made into beverages, such as range from that of a simple phenolic molecule to fruits, vegetables, and grains (Manach et al., 2004). that of a complex high-molecular weight polymer HCAs can occur freely or as components of plant (Bravo, 1998). The antioxidant activity of phenolic polymers (Podsędek, 2007). During the past decade, compounds depends on the structure, in particular HCAs received particular attention because they are the number and the positions of the hydroxyl one of the most abundant antioxidants in our diet groups and the nature of substitutions on the (Kroon et al.,1999; Eryılmaz et al., 2002) aromatic rings (Balasundram et al., 2006). Phenolic compounds are present as conjugates with mono- and Sinapic acid is a small naturally occurring polysaccharides, linked to one or more of the phenolic hydroxycinnamic acid derivative. It is a phenolic groups, and may also occur as functional derivatives compound and a member of the phenylpropanoid such as esters and methyl esters. Phenolic acids family, the member of which are assumed as consist of two subgroups, i.e., the hydroxybenzoic therapeutically beneficial and generally not toxic. and hydroxycinnamic acids. Hydroxybenzoic acids include gallic, p-hydroxybenzoic, vanillic and syringic Sinapic acid is widespread in the plant kingdom (fruits, vegetables, cereal grains, oilseed crops, and acids, which in common have the C6–C1 structure. Hydroxycinnamic acids, on the other hand, are some spices and medicinal plants) and is common aromatic compounds with a three carbon side chain in human diet. Derivatives of sinapic acid are (C6–C3), with caffeic, ferulic, p-coumaric and sinapic characteristic compounds of the Brassicaceae family. acids being the most common (Bravo, 1998). Sinapic acid shows antioxidant, antimicrobial, anti- Plant phenolics are biosynthesized by two basic inflammatory, anticancer, and anxiolytic activity. pathways: The shikimic acid pathway and the malonic Mainly due to their antioxidant activity, these acid pathway. The shikimic acid pathway participates compounds have been suggested for potential use in in the biosynthesis of most plant phenolics. The malonic acid pathway is of more significance in food processing, cosmetics, and the pharmaceutical fungi and bacteria than in higher plants (Özeker, industry (Nićiforovic and Abramovič, 2014; Chen, 1999). The shikimate pathway leads to the synthesis 2016). of aromatic amino acids such as phenylalanine and Chemical and physical properties of sinapic acid tyrosine. Hydroxycinnamic acids are formed by the deamination of phenylalanine or tyrosine to yield The synonyms of sinapic acid(C 11H12O5) (Figure 1) are sinapinic acid; 3,5-dimethoxy-4-hydroxy- the C6_C3 unit that serves as the core structure of the phenylpropanoids; the deamination is catalyzed trans-cinnamic acid; (2E)-3-(4-hydroxy-3,5- by the enzyme phenylalanine ammonia-lyase (Back, dimethoxyphenyl)-2-propenoic acid; 3-(4-Hydroxy- 2001). In plants, tyrosine ammonia-lyase converts 3,5-dimethoxyphenyl) acrylic acid; trans-4-hydroxy- tyrosine into 4-hydroxycinnamic acid. This pathway 3,5-dimethoxy-cinnamic acid; trans-sinapinic acid; is responsible for the biosynthesis of a very large number of diverse secondary metabolites such as 4-hydroxy-3,5-dimethoxy-cinnamic acid. lignins (Fukuda ve Komamine, 1982) 40 FABAD J. Pharm. Sci., 41, 39-49, 2016 (Herrmann and Nagel, 1989). Sinapic acid and its derivatives are especially particularly abundant in various Brassica vegetables: broccoli, tronchuda cabbage, white cabbage, kale, turnip, radish and leaf mustard (Cartea et al., 2010). Sinapic acid has been demonstrated that the esters of sinapic acid were the major constituents of the methanolic extract from the radish sprout (Raphanus sativus L.) and 3 sinapoyl esters were identified as Figure 1. Structure of sinapic acid. methyl sinapate, 1,2-disinapoyl-β-D-glucopyranoside, Sinapic acid may be found in free form, but also and β-D-(3,4-disinapoyl)fructofuranosyl-α-D-(6- in the ester forms. Hydroxycinnamic esters are found sinapoyl)-glucopyranoside (Takaya et al., 2003). It was as sugar esters (glycosides), or as esters of a variety found to be the most abundant phenolic acid in kale of organic compounds (Nićiforovic and Abramovič, seeds (Brassica oleracea convar. acephala) (including 2014). Sinapic acid can also form dimers with itself free, ester, glycoside, and ester-bound forms), which and ferulic acid in cereal cell walls (Shirley and represents 52.4% of all phenolic acids. It was also Chapple, 2003. It is yellow-brown crystalline powder found in the leaves of kale but in a small amounts with the molecular weight of 224.21 g/mol. The (Ayaz