ReviewSynthesis, characterization, bioactivity and potential application of phenolic acid grafted chitosan: A review
Introduction
Chitin is the second most abundant polysaccharide mainly extracted from the exoskeleton of sea creatures, such as crayfish, lobster, prawns, crab and shrimp. Chitosan is the deacetylated product of chitin obtained by alkaline treatment (Kumar, Muzzarelli, Muzzarelli, Sashiwa, & Domb, 2004). Chitosan is also a unique cationic polysaccharide with many special features including viscosity, polyelectrolyte behavior, mucoadhesivity, film forming and metal chelating ability (Pillai, Paul, & Sharma, 2009; Shukla, Mishra, Arotiba, & Mamba, 2013). Besides, due to its non-toxic, non-antigenic, biocompatible and biodegradable properties, chitosan has wide applications in food, tissue engineering, pharmaceutical, textile, agriculture, water treatment and cosmetics industries (Aider, 2010; Ngo et al., 2015; Rinaudo, 2006; Suh & Matthew, 2000; Vakili et al., 2014). However, the use of chitosan is greatly limited by its poor solubility in water, because chitosan is only soluble in acidic media. Chemical modification is an efficient approach to improve the water solubility as well as endow some new characteristics for chitosan (Alves & Mano, 2008; Prashanth & Tharanathan, 2007). Among various chemical modification methods, graft copolymerization reaction has been most widely used (Jayakumar, Prabaharan, Reis, & Mano, 2005; Thakur & Thakur, 2014). Graft copolymerization can introduce desired physicochemical and biological properties into chitosan, making molecular design possible.
In order to improve the physicochemical and biological properties of chitosan, increasing efforts have been made to graft phenolics, especially phenolic acids onto chitosan through graft copolymerization since 2008 (Božič, Gorgieva, & Kokol, 2012; Curcio et al., 2009; Pasanphan & Chirachanchai, 2008). Phenolics are the most abundant secondary metabolites widespread throughout the plant kingdom, such as fruit, vegetables, cereals, olives, dry legumes, cocoa, tea, coffee, and wine (Oroian & Escriche, 2015). Phenolics are an essential part of human diet with various valuable biological activities, including antioxidant, antimicrobial, anti-diabetic, anti-inflammatory, anticancer and metabolic regulation properties (Ali Asgar, 2013; Roleira et al., 2015; Shahidi & Ambigaipalan, 2015). More than 8000 naturally occurring chemical compounds belong to the category of “phenolics”, which share a common structural feature, i.e. an aromatic ring bearing at least one hydroxyl substituent (Costa et al., 2015). Based on the number of phenol rings and the way they bond, phenolics can be divided into five different categories including phenolic acids, flavonoids, tannins, stilbenes and lignans (Stalikas, 2007). As an important category of phenolics, naturally occurring phenolic acids usually possess one carboxylic acid group with two distinctive carbon frameworks, i.e. the hydroxybenzoic and hydroxycinnamic structures (Khadem & Marles, 2010; Lochab, Shukla, & Varma, 2014). Accordingly, phenolic acids can be further divided into two subcategories: hydroxybenzoic acids and hydroxycinnamic acids (Table 1). In the past decade, phenolic acids have been demonstrated to possess potent antioxidant, antimicrobial, anticancer, antiviral, anti-inflammatory, antimutagenic, antirheumatic, antipyretic, antiseptic, anthelmintic, neuroprotective and hepatoprotective activities (Heleno, Martins, Queiroz, & Ferreira, 2015).
Nowadays, four kinds of grafting techniques including carbodiimide based coupling, enzyme catalyzed grafting, free radical mediated grafting and electrochemical methods are frequently used for the synthesis of phenolic acid grafted chitosan (phenolic acid-g-chitosan) (Božič, Štrancar, & Kokol, 2013; Kim et al., 2010; Liu, Lu, Kan, & Jin, 2013b; Pasanphan & Chirachanchai, 2008). The introduction of phenolic groups onto chitosan backbone not only greatly alters the structural and physicochemical properties (solubility, thermal stability, crystallinity and rheological properties) of chitosan, but also remarkably increases biological activities (antioxidant, antimicrobial, antitumor, anti-allergic, anti-inflammatory, anti-diabetic and acetylcholinesterase inhibitory activity) of chitosan (Cirillo et al., 2016; Liu, Lu, Kan, Wen, & Jin, 2014a; Oliver, Vittorio, Cirillo, & Boyer, 2016). Notably, phenolic acid-g-chitosan shows potential applications in many fields of food technology, which can be used as functional foods, food coating agents, food packing materials, encapsulation agents for functional dietary ingredients, and bioadsorbents for the treatment of iron overload diseases (Aljawish, Chevalot, Jasniewski, Scher, & Muniglia, 2015; Hu et al., 2015, Liu et al., 2015b, Liu et al., 2016a). Therefore, the functional phenolic acid-g-chitosan needs to be extensively researched and utilized in the future. This review systematically focuses on the recent advances of phenolic acid-g-chitosan in many aspects, including the synthetic method, structural characterization, physicochemical property, biological activity with detailed functional mechanism, potential applications in food technology and future perspectives.
Section snippets
Carbodiimide based chemical coupling method
Carbodiimide based chemical coupling reagents, such as 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and dicyclohexylcarbodiimide (DCC) have been widely used for the synthesis of phenolic acid-g-chitosan (Eom, Senevirathne, & Kim, 2012; Pasanphan & Chirachanchai, 2008; Schreiber, Bozell, Hayes, & Zivanovic, 2013; Xie, Hu, Wang, & Zeng, 2014). Carbodiimide mediated grafting method is highly efficient and requires only mild reaction conditions. The grafting reactions usually proceed in
Thin-layer chromatography (TLC)
To confirm the successful grafting of phenolic acid onto chitosan backbone, it is essential to characterize the conjugate by different analytic methods. Although less used, TLC has been adopted for phenolic analysis since 1960s. TLC is often used to simultaneously analyze several phenolic samples (Stalikas, 2007). In addition, TLC can be also used to distinguish phenolic acid-g-chitosan from free phenolic acid. Hu et al. (2015) separated gallic acid and gallic acid-g-chitosan on silica gel
Solubility
One of the main goals for the synthesis of phenolic acid-g-chitosan is to increase the water solubility of chitosan. Therefore, the solubility of phenolic acid-g-chitosan is often an important concern of most researchers. In general, chitosan usually shows improved water solubility after grafting with phenolic acid (Aljawish et al., 2014b; Chatterjee et al., 2015; Kumar et al., 1999; Liu et al., 2013b; Pasanphan & Chirachanchai, 2008; Schreiber et al., 2013; Woranuch & Yoksan, 2013). Some
Non-cytotoxicity
In order to confirm the safety of phenolic acid-g-chitosan, several conjugates have been tested by the cell viability assay. Results showed phenolic acid-g-chitosan did not exert any obvious toxic effect on normal cells, such as PC12 cells (Cho et al., 2011a), human umbilical vein endothelial cells (HUVEC) (Aljawish et al., 2014c; Kim, Kim, Ryu, & Lee, 2015; Soliman, Zhang, Merle, Cerruti, & Barralet, 2014), RAW264.7 macrophage cells (Ahn et al., 2016, Cho et al., 2011b, Lee et al., 2014b, Ngo
Coating solutions for food preservation
Chitosan based edible coatings have received increasing attention in recent years. They can not only delay respiration rate, decrease weight loss, and prolong shelf life of food; but also prevent the decrease in contents of natural antioxidants during food storage. Recently, some phenolic acid-g-chitosan coating solutions have been developed (Wu et al., 2016a, Yang et al., 2016a; Zhang, Zhang, & Yang, 2015b).
Zhang et al. (2015b) synthesized salicylic acid-g-chitosan and evaluated its effect on
Conclusions and future perspectives
Till now, four kinds of grafting methods including carbodiimide based coupling, enzyme catalyzed grafting, free radical mediated grafting and electrochemical methods have been used for the synthesis of phenolic acid-g-chitosan. Among these methods, free radical mediated grafting reaction is the most promising approach. In future, more in-depth experiments are needed to reveal the mechanism of free radical mediated grafting reaction.
Several instrumental methods including TLC, HPLC, UV–vis,
Acknowledgements
This work was supported by Grants-in-Aid for scientific research from the National Natural Science Foundation of China (No. 31571788 and 31101216), Natural Science Foundation of Jiangsu Province (No. BK20151310), Qing Lan Project of Jiangsu Province, Jiangsu Provincial Government Scholarship for Overseas Studies, and High Level Talent Support Program of Yangzhou University.
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