Improved antioxidant, antimicrobial and anticancer activity of naringenin on conjugation with pectin
The purpose of the present study was to improve the aqueous solubility of naringenin by conjugating with water-soluble polysaccharide carrier, pectin. The pectin–naringenin conjugate was synthesized employing dicyclohexylcarbodiimide and dimethylaminopyridine. The conjugation was confirmed by various physicochemical characterizations. The results of differential scanning calorimetry, X-ray diffraction and morphological analyses revealed semi-crystalline nature of the conjugate. The chromatographic analysis showed 37.069 µg naringenin/mg of conjugate. The conjugate was determined to have molecular weight of 6.22 × 104 kDa by static light scattering. In silico molecular mechanistic simulations performed for pectin and naringenin revealed the energetic and geometrical stability within the polysaccharide-polyphenol conjugate. The critical aggregation concentration was in the range of 44.67–56.23 μg/mL as determined by dynamic light scattering and fluorescence spectroscopy. On in vitro release, 99.4% (pH 1.2) and 57.62% (pH 7.4) of naringenin were found to be released over a period of 30 h and 48 h, respectively. Further, the release of naringenin followed Higuchi’s square-root kinetics with diffusion as the possible release mechanism. A comparative evaluation for antioxidant activity revealed a significantly higher radical scavenging activity of conjugate over the naringenin. Further, the conjugate exhibited significantly higher antimicrobial action against Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa while a comparable antimicrobial activity was observed against Escherichia coli and Bacillus subtilis. The cytotoxicity studies of the synthesized conjugate showed anti-cancer activity against NIH: OVCAR-5 cells. In conclusion, the pectin-naringenin conjugate presented hydrocolloidal properties with improved therapeutic efficacy and delivery over the native polyphenol.
KeywordsPectin Naringenin Molecular mechanics Dynamic light scattering Critical aggregation concentration Cytotoxicity
The authors express gratitude to Department of Science and Technology, Government of India, for providing financial assistance to Jyoti Mundlia under DST-PURSE programme.
Compliance with ethical standards
Conflict of interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
- Bai F, Diao J, Wang Y, Sun S, Zhang H, Liu Y (2017) A new water-soluble nanomicelle formed through self assembly of pectin-curcumin conjugates: preparation, characterization, and anticancer activity evaluation. J Agric Food Chem 65:6840–6847. https://doi.org/10.1021/acs.jafc.7b002250 CrossRefPubMedGoogle Scholar
- Guo H, Zhang D, Li C, Jia L, Liu G, Hao L, Zheng D, Shen J, Li T, Guo Y, Zhang Q (2013) Self-assembled nanoparticles based on galactosylated O-carboxymethyl chitosan-graft-stearic acid conjugates for delivery of doxorubicin. Int J Pharm 458:31–38. https://doi.org/10.1016/j.ijpharm.2013.10.020. https://www.drugbank.ca/drugs/DB03467. Accessed 8 Aug 2018CrossRefGoogle Scholar
- Khan AW, Kotta S, Ansari SH, Sharma RK, Javed A (2013) Self-nanoemulsifying drug delivery system (SNEDDS) of the poorly water-soluble grapefruit flavonoid Naringenin: design, characterization, in vitro and in vivo evaluation. Drug Deliv. https://doi.org/10.3109/10717544.2013.878003 CrossRefPubMedGoogle Scholar
- Kumar P, Choonara YE, Toit LC, Modi G, Naidoo D, Pillay V (2012) Novel high viscosity polyacrylamidated chitosan for neural tissue engineering: fabrication of anisotropic neurodurable scaffold via molecular disposition of persulfate-mediated polymer slicing and complexation. Int J Mol Sci 13:13966–13984. https://doi.org/10.3390/ijms131113966 CrossRefPubMedPubMedCentralGoogle Scholar
- Kyle JAM, Duthei GG (2006) Flavonoids in foods. In. Andersen OM, Markham KR (Eds) Flavonoids: chemistry, biochemistry and applications. CRC Press Taylor & Francis Group, Boca Raton, pp 219–262Google Scholar
- Pasut G, Veronese FM (2007) Polymer–drug conjugation, recent achievements and general strategies. Progr Polym Sci 32:933–961. https://doi.org/10.1016/j.progpolymsci.2007.05.008 CrossRefGoogle Scholar
- Sayah MY, Chabir R, Benyahia H, Kandri YR, Chahdi FO, Touzani H, Errachidi F (2016) Yield, esterification degree and molecular weight evaluation of pectins isolated from orange and grapefruit peels under different conditions. PLoS One. https://doi.org/10.1371/journal.pone.0161751 CrossRefPubMedPubMedCentralGoogle Scholar
- Semalty A, Tanwar YS, Semalty M (2014) Preparation and characterization of cyclodextrin inclusion of naringenin and critical comparison with phospholipid complexation for improving solubility and dissolution. J Therm Anal Calorim 115:2471–2478. https://doi.org/10.1007/s10973-013-3463-y CrossRefGoogle Scholar
- Wang F, Zhang D, Duan C, Jia L, Feng F, Liu Y, Wang Y, Hao L, Zhang Q (2011) Preparation and characterizations of a novel deoxycholic acid O-carboxymethylated chitosan-folic acid conjugates and self aggregates. Carbohyd Polym 84:1192–1200. https://doi.org/10.1016/j.carbpol.2011.01.017 CrossRefGoogle Scholar
- Wang Y, Wang S, Firempong CK, Zhang H, Wang M, Zhang Y, Zhu Y, Yu J, Xu X (2017) Enhanced solubility and bioavailability of naringenin via liposomal nanoformulation: preparation and in vitro and in vivo evaluations. AAPS Pharm Sci Tech 18:586–594. https://doi.org/10.1208/s12249-016-0537-8 CrossRefGoogle Scholar