Extraction, purification, food applications, and recent advances for enhancing the bioavailability of 6-gingerol from ginger – A review

Main Article Content

Ginithillawala Arachchilage Dilukshi Vichakshana
David James Young
Wee Sim Choo https://orcid.org/0000-0003-0495-3303

Keywords

Chromatography, conventional extraction, encapsulation, non-conventional extraction, solubilization, Zingiber officinale

Abstract

6-Gingerol is the major pharmacologically active component of ginger (Zingiber officinale) rhizome widely used in the food, cosmetics, and pharmaceutical industries. Various extraction and purification methods have been developed to obtain highly purified 6-gingerol. 6-Gingerol can be extracted using conventional and nonconventional extraction techniques. Hydroalcoholic solutions and liquid CO2 are the most suitable solvents for the extraction of 6-gingerol, while microwave-assisted extraction is the best extraction method. High-speed counter-current chromatography is the purification technique resulting in the highest purity of 6-gingerol. Despite the various biological properties of 6-gingerol, the low bioavailability of 6-gingerol is the main challenge that limits its application. Novel encapsulation and solubilization techniques, including nano-emulsion, complexation, micelles, and solid dispersion methods, have been introduced to enhance the bioavailability of 6-gingerol, overcoming its limitations. 6-Gingerol showed potential applications as a natural antioxidant, preservative, and flavor enhancer as well as demonstrated a synergistic effect with different ingredients for maintaining the quality and shelf-life of the food products. The current work provides a comprehensive review of the prevailing techniques applied for extraction and purification of 6-gingerol from the rhizome of ginger, current research on the application of 6-gingerol in the food industry, and novel advances for increasing its bioavailability.

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References

Abdel Ghafar, M., Ragab, O., Al-Malt, A., Eissa, R., Samy, S., Abd El-Khalik, S. and Rabahd, H., 2009. Genetic variants of vascular endothelial growth factor gene polymorphism affect the risk and severity of ischemic stroke: a case-control study. Journal of Pharmacy and Bioallied Sciences 1(1): 8–15. 10.4103/ejolm.ejolm_3_20

Agcam, E., Akyıldız, A., Kamat, S. and Balasubramaniam, V.M., 2021. Bioactive compounds extraction from the black carrot pomace with assistance of high-pressure processing: an optimization study. Waste and Biomass Valorization 12(11): 5959–5977. 10.1007/s12649-021-01431-z

Ahmed, S.H.H., Gonda, T. and Hunyadi, A., 2021. Medicinal chemistry inspired by ginger: exploring the chemical space around 6-gingerol. RSC Advances 11: 26687–26699. 10.1039/D1RA04227K

Alvarez-Rivera, G., Bueno, M., Ballesteros-Vivas, D., Mendiola, J.A. and Ibañez, E., 2020. Chapter 13 – pressurized liquid extraction. In: Poole, C.F. (ed.) Liquid-phase extraction, Elsevier, Amsterdam, The Netherlands, pp. 375–398.

Ameer, K., Shahbaz, H.M. and Kwon, J.H., 2017. Green extraction methods for polyphenols from plant matrices and their byproducts: a review. Comprehensive Reviews in Food Science and Food Safety 16(2): 295–315. 10.1111/1541-4337.12253

Anisa, N.I., Azian, N., Sharizan, M. and Iwai, Y., 2014. Temperature effects on diffusion coefficient for 6-gingerol and 6-shogaol in subcritical water extraction. Journal of Physics: Conference Series 495: 12009. 10.1088/1742-6596/495/1/012009

Aris, N.I.A. and Morad, N.A.M., 2014. Effect of extraction time on degradation of bioactive compounds (Zingiber Officinale Roscoe). Jurnal Teknologi 67: 4. 10.11113/jt.v67.2800

Awang, M.A., Azelan, N.A., Mustaffa, N.A.A.W., Aziz, A. and Hasham, R., 2014. Influence of processing parameters on the yield and 6-gingerol content of Zingiber officinale extract. Journal of Chemical and Pharmaceutical Research 6(11): 358–363.

Azian, M.N., Anisa, A.I.N. and Iwai, Y., 2014. Mechanisms of ginger bioactive compounds extract using Soxhlet and accelerated water extraction. International Journal of Chemical, Materials Science and Engineering 8(5): 438–442. 10.5281/zenodo.1092888

Azmir, J., Zaidul, I.S.M., Rahman, M.M., Sharif, K.M., Mohamed, A., Sahena, F., Jahurul, M.H.A., Ghafoor, K., Norulaini, N.A.N. and Omar, A.K.M., 2013. Techniques for extraction of bio-active compounds from plant materials: a review. Journal of Food Engineering 117(4): 426–436. 10.1016/j.jfoodeng.2013.01.014

Azwanida, N., 2015. A review on the extraction methods use in medicinal plants, principle, strength and limitation. Med Aromat Plants 4(196): 1000196.

Bagade, S.B. and Patil, M., 2021. Recent advances in microwave assisted extraction of bioactive compounds from complex herbal samples: a review. Critical Reviews in Analytical Chemistry 51(2): 138–149. 10.1080/10408347.2019.1686966

Boulila, A., Hassen, I., Haouari, L., Mejri, F., Amor, I.B., Casabianca, H. and Hosni, K., 2015. Enzyme-assisted extraction of bioactive compounds from bay leaves (Laurus nobilis L.). Industrial Crops and Products 74: 485–493. 10.1016/j.indcrop.2015.05.050

Cai, L., Wang, Y., Cao, A., Lv, Y. and Li, J., 2015. Effect of alginate coating enriched with 6-gingerol on the shelf life and quality changes of refrigerated red sea bream (Pagrosomus major) fillets. RSC Advances 5(46): 36882–36889. 10.1039/C5RA04551G

Chakraborty, D., Bishayee, K., Ghosh, S., Biswas, R., Kumar Mandal, S. and Rahman Khuda-Bukhsh, A., 2012. [6]-gingerol induces caspase 3 dependent apoptosis and autophagy in cancer cells: drug–DNA interaction and expression of certain signal genes in HeLa cells. European Journal of Pharmacology 694(1): 20–29. 10.1016/j.ejphar.2012.08.001

Chaves, J.O., de Souza, M.C., da Silva, L.C., Lachos-Perez, D., Torres-Mayanga, P. C., Machado, A.P.D.F., Forster-Carneiro, T., Vázquez-Espinosa, M., González-de-Peredo, A.V., Barbero, G.F. and Rostagno, M.A., 2020. Extraction of flavonoids from natural sources using modern techniques. Frontiers in Chemistry 8: 864. 10.3389/fchem.2020.507887

Chemat, F., Abert Vian, M., Fabiano-Tixier, A.S., Nutrizio, M., Režek Jambrak, A., Munekata, P.E.S., Lorenzo, J.M., Barba, F.J., Binello, A. and Cravotto, G., 2020. A review of sustainable and intensified techniques for extraction of food and natural products. Green Chemistry 22(8): 2325–2353. 10.1039/C9GC03878G

Chen, T., Wang, P., Wang, N., Sun, C., Yang, X., Li, H., Zhou, G. and Li, Y., 2018. Separation of three polar compounds from Rheum tanguticum by high-speed countercurrent chromatography with an ethyl acetate/glacial acetic acid/water system. Journal of Separation Science 41(8): 1775–1780. 10.1002/jssc.201701298

Da Silva, R.P.F.F., Rocha-Santos, T.A.P. and Duarte, A.C., 2016. Supercritical fluid extraction of bioactive compounds. TrAC Trends in Analytical Chemistry 76: 40–51. 10.1016/j.trac.2015.11.013

Elsharkasy, O.M., Nordin, J.Z., Hagey, D.W., de Jong, O.G., Schiffelers, R.M., Andaloussi, S.E.L. and Vader, P., 2020. Extracellular vesicles as drug delivery systems: why and how? Advanced Drug Delivery Reviews 159: 332–343. 10.1016/j.addr.2020.04.004

Foudah, A.I., Shakeel, F., Yusufoglu, H.S., Ross, S.A. and Alam, P., 2020. Simultaneous determination of 6-Shogaol and 6-Gingerol in various ginger (Zingiber officinale Roscoe) extracts and commercial formulations using a green RP-HPTLC-densitometry method. Foods 9(8): 1136. 10.3390/foods9081136

Gan, Z., Liang, Z., Chen, X., Wen, X., Wang, Y., Li, M. and Ni, Y., 2016. Separation and preparation of 6-gingerol from molecular distillation residue of Yunnan ginger rhizomes by high-speed counter-current chromatography and the antioxidant activity of ginger oils in vitro. Journal of Chromatography B 1011: 99–107. 10.1016/j.jchromb.2015.12.051

Garavand, F., Rahaee, S., Vahedikia, N. and Jafari, S.M., 2019. Different techniques for extraction and micro/nanoencapsulation of saffron bioactive ingredients. Trends in Food Science and Technology 89: 26–44. 10.1016/j.tifs.2019.05.005

Gawel, K., Kukula-Koch, W., Banono, N.S., Nieoczym, D., Targowska-Duda, K.M., Czernicka, L., Parada-Turska, J. and Esguerra, C.V., 2021. 6-Gingerol, a major constituent of Zingiber officinale rhizoma, exerts anticonvulsant activity in the pentylenetetrazole-induced seizure model in Larval Zebrafish. International Journal of Molecular Sciences 22: 7745. 10.3390/ijms22147745

Gbashi, S., Adebo, O.A., Piater, L., Madala, N.E. and Njobeh, P.B., 2017. Subcritical water extraction of biological materials. Separation and Purification Reviews 46(1): 21–34. 10.1080/15422119.2016.1170035

Ghezzi, M., Pescina, S., Padula, C., Santi, P., Del Favero, E., Cantù, L. and Nicoli, S., 2021. Polymeric micelles in drug delivery: an insight of the techniques for their characterization and assessment in biorelevant conditions. Journal of Controlled Release 332: 312–336. 10.1016/j.jconrel.2021.02.031

Gligor, O., Mocan, A., Moldovan, C., Locatelli, M., Crișan, G. and Ferreira, I.C.F.R., 2019. Enzyme-assisted extractions of polyphenols–a comprehensive review. Trends in Food Science and Technology 88: 302–315. 10.1016/j.tifs.2019.03.029

Guo, J.B., Fan, Y., Zhang, W.J., Wu, H., Du, L.M. and Chang, Y.X., 2017. Extraction of gingerols and shogaols from ginger (Zingiber officinale Roscoe) through microwave technique using ionic liquids. Journal of Food Composition and Analysis 62: 35–42. 10.1016/j.jfca.2017.04.014

Hilphy, A.R., Al-Musafer, A.M. and Gavahian, M., 2020. Pilot-scale ohmic heating-assisted extraction of wheat bran bioactive compounds: effects of the extract on corn oil stability. Food Research International 137: 109649. 10.1016/j.foodres.2020.109649

Hu, J., Guo, Z., Glasius, M., Kristensen, K., Xiao, L. and Xu, X., 2011. Pressurized liquid extraction of ginger (Zingiber officinale Roscoe) with bioethanol: an efficient and sustainable approach. Journal of Chromatography A 1218(34): 5765–5773. 10.1016/j.chroma.2011.06.088

Jeyaraj, E.J., Lim, Y.Y. and Choo, W.S., 2021. Extraction methods of butterfly pea (Clitoria ternatea) flower and biological activities of its phytochemicals. Journal of Food Science and Technology 58(6): 2054–2067. 10.1007/s13197-020-04745-3

Jiang, S.Z., Wang, N.S. and Mi, S.Q., 2008. Plasma pharmacokinetics and tissue distribution of [6]-gingerol in rats. Biopharmaceutics and Drug Disposition 29(9): 529–537. 10.1002/bdd.638

Kawamoto, Y., Ueno, Y., Nakahashi, E., Obayashi, M., Sugihara, K., Qiao, S., Iida, M., Kumasaka, M.Y., Yajima, I., Goto, Y., Ohgami, N., Kato, M. and Takeda, K., 2016. Prevention of allergic rhinitis by ginger and the molecular basis of immunosuppression by 6-gingerol through T cell inactivation. The Journal of Nutritional Biochemistry 27: 112–122. 10.1016/j.jnutbio.2015.08.025

Khan, B.M. and Liu, Y., 2018. High speed counter-current chromatography: overview of solvent-system and elution-mode. Journal of Liquid Chromatography and Related Technologies 41(10): 629–636. 10.1080/10826076.2018.1499528

Khaw, K.Y., Parat, M.O., Shaw, P.N. and Falconer, J.R., 2017. Solvent supercritical fluid technologies to extract bioactive compounds from natural sources: a review. Molecules 22(7): 1186. 10.3390/molecules22071186

Kim, H.S., Lee, S.H., Byun, Y. and Park, H.D., 2015. 6-gingerol reduces Pseudomonas aeruginosa biofilm formation and virulence via quorum sensing inhibition. Scientific Reports 5(1): 8656. 10.1038/srep08656

Kiran, C.R., Chakka, A.K., Amma, K.P.P., Menon, A.N., Kumar, M.M.S. and Venugopalan, V.V., 2013. Influence of cultivar and maturity at harvest on the essential oil composition, oleoresin and [6]-gingerol contents in fresh ginger from Northeast India. Journal of Agricultural and Food Chemistry 61(17): 4145–4154. 10.1021/jf400095y

Kizhakkayil, J. and Sasikumar, B., 2011. Diversity, characterization and utilization of ginger: a review. Plant Genetic Resources 9(3): 464–477. 10.1017/S1479262111000670

Ko, M.J., Nam, H.H. and Chung, M.S., 2019. Conversion of 6-gingerol to 6-shogaol in ginger (Zingiber officinale) pulp and peel during subcritical water extraction. Food Chemistry 270: 149–155. 10.1016/j.foodchem.2018.07.078

Kou, X., Ke, Y., Wang, X., Rahman, M.R.T., Xie, Y., Chen, S. and Wang, H., 2018. Simultaneous extraction of hydrophobic and hydrophilic bioactive compounds from ginger (Zingiber officinale Roscoe). Food Chemistry 257: 223–229. 10.1016/j.foodchem.2018.02.125

Kubra, I.R. and Rao, L.J.M., 2012. An Impression on current developments in the technology, chemistry, and biological activities of ginger (Zingiber officinale Roscoe). Critical Reviews in Food Science and Nutrition 52(8): 651–688. 10.1080/10408398.2010.505689

Latif, Z. and Sarker, S.D., 2012. Isolation of natural products by preparative high performance liquid chromatography (Prep-HPLC). In: Sarker, S.D. and Nahar, L. (eds.) Natural products isolation. Humana Press, Totowa, NJ, pp. 255–274. 10.1007/978-1-61779-624-1_10

Li, J., 2015. Application of tea polyphenols in combination with 6-gingerol on shrimp paste of during storage: biogenic amines formation and quality determination. Frontiers in Microbiology 6: 981. 10.3389/fmicb.2015.00981

Lima, R.M.T., Dos Reis, A.C., De Menezes, A.A.P.M., Santos, J.V.D.O., Filho, J.W.G.D.O., Ferreira, J.R.D.O., De Alencar, M.V.O.B., Da Mata, A.M.O.F., Khan, I.N., Islam, A., Uddin, S.J., Ali, E.S., Islam, M.T., Tripathi, S., Mishra, S.K., Mubarak, M.S. and MeloCavalcante, A.A.D.C., 2018. Protective and therapeutic potential of ginger (Zingiber officinale) extract and 6-gingerol in cancer: a comprehensive review. Phytotherapy Research 32: 1885–1907. 10.1002/ptr.6134

Liu, W., Zhou, C.L., Zhao, J., Chen, D. and Li, Q.H., 2014. Optimized microwave-assisted extraction of 6-gingerol from Zingiber officinale Roscoe and evaluation of antioxidant activity in vitro. Acta Scientiarum Polonorum, Technologia Alimentaria 13(2): 155–168. 10.17306/j.afs.2014.2.5

Luque de Castro, M.D. and Priego-Capote, F., 2010. Soxhlet extraction: past and present panacea. Journal of Chromatography A 1217(16): 2383–2389. 10.1016/j.chroma.2009.11.027

Mahato, N., Sinha, M., Sharma, K., Koteswararao, R. and Cho, M.H., 2019. Modern extraction and purification techniques for obtaining high purity food-grade bioactive compounds and value-added co-products from citrus wastes. Foods 8(11): 523. 10.3390/foods8110523

Man, F., Meng, C., Liu, Y., Wang, Y., Zhou, Y., Ma, J. and Lu, R., 2021. The study of ginger-derived extracellular vesicles as a natural nanoscale drug carrier and their intestinal absorption in rats. AAPS PharmSciTech 22(6): 206. 10.1208/s12249-021-02087-7

Matsumoto, R., Satoh, H. and Ueda, M., 2016. Production of 5-O-α-glucosylgingerol via glucosylation of 6-gingerol by Ensifer sp. M-26. Journal of Molecular Catalysis B: Enzymatic 133: 200–203. 10.1016/j.molcatb.2017.01.005

Md Sarip, M.S., Morad, N.A., Mohamad Ali, N.A., Mohd Yusof, Y.A. and Che Yunus, M.A., 2014. The kinetics of extraction of the medicinal ginger bioactive compounds using hot compressed water. Separation and Purification Technology 124: 141–147. 10.1016/j.seppur.2014.01.008

Md Yusof, K., Makpol, S., Jamal, R., Harun, R., Mokhtar, N. and Wan Ngah, W.Z., 2015. γ-tocotrienol and 6-gingerol in combination synergistically induce cytotoxicity and apoptosis in HT-29 and SW837 human colorectal cancer cells. Molecules 20(6): 10280–10297. 10.3390/molecules200610280

Mena-García, A., Ruiz-Matute, A.I., Soria, A.C. and Sanz, M.L., 2019. Green techniques for extraction of bioactive carbohydrates. TrAC Trends in Analytical Chemistry 119: 115612. 10.1016/j.trac.2019.07.023

Mendes, A.C., Gorzelanny, C., Halter, N., Schneider, S.W. and Chronakis, I.S., 2016. Hybrid electrospun chitosan-phospholipids nanofibers for transdermal drug delivery. International Journal of Pharmaceutics 510(1): 48–56. 10.1016/j.ijpharm.2016.06.016

Mi, H.B., Guo, X. and Li, J.R., 2016. Effect of 6-gingerol as natural antioxidant on the lipid oxidation in red drum fillets during refrigerated storage. LWT–Food Science and Technology 74: 70–76. 10.1016/j.lwt.2016.07.029

Mi, H.B., Zhao, B., Wang, C., Yi, S., Xu, Y. and Li, J., 2017. Effect of 6-gingerol on physicochemical properties of grass carp (Ctenopharyngodon idellus) surimi fortified with perilla oil during refrigerated storage. Journal of the Science of Food and Agriculture 97(14): 4807–4814. 10.1002/jsfa.8350

Mohseni, N.M., Mirzaei, H.O. and Moghimi, M., 2020. Optimization of producing oil and meal from canola seeds using microwave−pulsed electric field pretreatment. OCL 27: 2. 10.1051/ocl/2019050

Murphy, A., Norton, E., Montgomery, F., Jaiswal, A. and Jaiswal, S., 2020. Ultrasound-assisted extraction of polyphenols from ginger (Zingiber officinale) and evaluation of its antioxidant and antimicrobial properties. Journal of Food Chemistry and Nanotechnology 6(2): 88–96. 10.17756/jfcn.2020-08

Mughal, M.H., 2019. 6-gingerol and shogaol; a comprehensive strategy against various maladies. Significances of Bioengineering and Bioscience 3: 1–9. 10.31031/SBB.2019.03.000551

Mustafa, A. and Turner, C., 2011. Pressurized liquid extraction as a green approach in food and herbal plants extraction: a review. Analytica Chimica Acta 703(1): 8–18. 10.1016/j.aca.2011.07.018

Nadar, S.S., Rao, P. and Rathod, V.K., 2018. Enzyme assisted extraction of biomolecules as an approach to novel extraction technology: a review. Food Research International 108: 309–330. 10.1016/j.foodres.2018.03.006

Nagendra Chari, K.L., Manasa, D., Srinivas, P. and Sowbhagya, H.B., 2013. Enzyme-assisted extraction of bioactive compounds from ginger (Zingiber officinale Roscoe). Food Chemistry 139(1): 509–514. 10.1016/j.foodchem.2013.01.099

Nguyen, T.M.C., Gavahian, M. and Tsai, P.J., 2021. Effects of ultra-sound-assisted extraction (UAE), high voltage electric field (HVEF), high pressure processing (HPP), and combined methods (HVEF+UAE and HPP+UAE) on Gac leaves extraction. LWT, 143: 111131. 10.1016/j.lwt.2021.111131

Nooshkam, M. and Varidi, M., 2020. Maillard conjugate-based delivery systems for the encapsulation, protection, and controlled release of nutraceuticals and food bioactive ingredients: a review. Food Hydrocolloids 100: 105389. 10.1016/j.foodhyd.2019.105389

Nourbakhsh Amiri, Z., Najafpour, G., Mohammadi, M. and Moghadamnia, A., 2018. Subcritical water extraction of bio-active compounds from ginger (Zingiber officinale Roscoe). International Journal of Engineering 31(12): 1991–2000. 10.5829/ije.2018.31.12c.01

Ojima, T., Aizawa, K., Saburi, W. and Yamamoto, T., 2012. α-glucosylated 6-gingerol: chemoenzymatic synthesis using α-glucosidase from Halomonas sp. H11, and its physical properties. Carbohydrate Research 354: 59–64. 10.1016/j.carres.2012.03.012

Osorio-Tobón, J.F., 2020. Recent advances and comparisons of conventional and alternative extraction techniques of phenolic compounds. Journal of Food Science and Technology 57(12): 4299–4315. 10.1007/s13197-020-04433-2

Pandotra, P., Sharma, R., Datt, P., Kushwaha, M., Gupta, A.P. and Gupta, S., 2013. Ultrasound-assisted extraction and fast chromolithic method development, validation and system suitability analysis for 6, 8, 10-gingerols and shogaol in rhizome of Zingiber officinale by liquid chromatography-diode array detection. International Journal of Green Pharmacy (IJGP) 7(3): 189–195. 10.4103/0973-8258.120197

Pereira, C.G. and Meireles, M.A.A., 2010. Supercritical fluid extraction of bioactive compounds: fundamentals, applications and economic perspectives. Food and Bioprocess Technology 3(3): 340–372. 10.1007/s11947-009-0263-2

Ren, Q., Xing, H., Bao, Z., Su, B., Yang, Q., Yang, Y. and Zhang, Z., 2013. Recent advances in separation of bioactive natural products. Chinese Journal of Chemical Engineering 21(9): 937–952. 10.1016/S1004-9541(13)60560-1

Said, P.P., Arya, O.P., Pradhan, R.C., Singh, R.S. and Rai, B.N., 2015. Separation of oleoresin from ginger rhizome powder using green processing technologies. Journal of Food Process Engineering 38(2): 107–114. 10.1111/jfpe.12127

Salea, R., Veriansyah, B. and Tjandrawinata, R.R., 2017. Optimization and scale-up process for supercritical fluids extraction of ginger oil from Zingiber officinale var. Amarum. The Journal of Supercritical Fluids 120: 285–294. 10.1016/j.supflu.2016.05.035

Sasikala, P., Chandralekha, A., Chaurasiya, R.S., Chandrasekhar, J. and Raghavarao, K., 2018. Ultrasound-assisted extraction and adsorption of polyphenols from Ginger Rhizome (Zingiber officinale). Separation Science and Technology 53(3): 439–448. 10.1080/01496395.2017.1391290

Schwertner, H.A. and Rios, D.C., 2007. High-performance liquid chromatographic analysis of 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol in ginger-containing dietary supplements, spices, teas, and beverages. Journal of Chromatography B 856(1): 41–47. 10.1016/j.jchromb.2007.05.011

Semwal, R.B., Semwal, D.K., Combrinck, S. and Viljoen, A.M., 2015. Gingerols and shogaols: important nutraceutical principles from ginger. Phytochemistry 117: 554–568. 10.1016/j.phytochem.2015.07.012

Shukla, A., Das, C. and Goud, V.V., 2020. Design of a carrier system for gingerols enriched oleoresin tailored for food applications. Food and Bioproducts Processing 124: 296–306. 10.1016/j.fbp.2020.09.007

Shukla, A., Naik, S.N., Goud, V.V. and Das, C, 2019. Supercritical CO2 extraction and online fractionation of dry ginger for production of high-quality volatile oil and gingerols enriched oleo-resin. Industrial Crops and Products 130: 352-362. 10.1016/j.indcrop.2019.01.005

Si, W., Chen, Y.P., Zhang, J., Chen, Z.Y. and Chung, H.Y., 2018. Antioxidant activities of ginger extract and its constituents toward lipids. Food Chemistry 239: 1117–1125. 10.1016/j.foodchem.2017.07.055

Silva, J.A.D., Becceneri, A.B., Mutti, H.S., Martin, A.C.B.M., Silva, M.F.D.G.F.D., Fernandes, J.B., Vieira, P.C. and Cominetti, M.R., 2012. Purification and differential biological effects of ginger-derived substances on normal and tumor cell lines. Journal of Chromatography B 903: 157–162. 10.1016/j.jchromb.2012.07.013

Sondari, D., Irawadi, T.T., Setyaningsih, D. and Tursiloadi, S., 2017, 23–24 October. Effect temperature of supercritical CO2 fluid extraction on phytochemical analysis and antioxidant activity of Zingiber officinale Roscoe. In: AIP Conference Proceedings, 1904, AIP Publishing LLC, Jakarta, Indonesia.

Supardan, M.D., Fuadi, A., Alam, P.N. and Arpi, N., 2012. Solvent extraction of ginger oleoresin using ultrasound. Makara Journal of Science 15(2): 163–167. 10.7454/mss.v15i2.1066

Swapna Sonale, R. and Kadimi, U.S., 2014. Characterization of gingerol analogues in supercritical carbon dioxide (SC CO2) extract of ginger (Zingiber officinale, R.,). Journal of Food Science and Technology 51(11): 3383–3389. 10.1007/s13197-012-0851-4

Teng, H., Seuseu, K.T., Lee, W.Y. and Chen, L., 2019. Comparing the effects of microwave radiation on 6-gingerol and 6-shogaol from ginger rhizomes (Zingiber officinale Rosc). PLoS One 14(6): e0214893. 10.1371/journal.pone.0214893

Teo, C.C., Tan, S.N., Yong, J.W.H., Hew, C.S. and Ong, E.S., 2010. Pressurized hot water extraction (PHWE). Journal of Chromatography A 1217(16): 2484–2494. 10.1016/j.chroma.2009.12.050

Tintu, I., Dileep, K.V., Remya, C., Augustine, A. and Sadasivan, C., 2012. 6-Gingerol inhibits fungal alpha amylase: enzyme kinetic and molecular modeling studies. Starch–Stärke 64(8): 607–612. 10.1002/star.201200004

Tongnuanchan, P. and Benjakul, S., 2014. Essential oils: extraction, bioactivities, and their uses for food preservation. Journal of Food Science 79(7): 1231–1249. 10.1111/1750-3841.12492

Utama-ang, N., Sida, S., Wanachantararak, P. and Kawee-ai, A., 2021. Development of edible Thai rice film fortified with ginger extract using microwave-assisted extraction for oral antimicrobial properties. Scientific Reports 11(1): 14870. 10.1038/s41598-021-94430-y

Uwineza, P.A. and Waśkiewicz, A., 2020. Recent advances in super-critical fluid extraction of natural bioactive compounds from natural plant materials. Molecules (Basel, Switzerland) 25(17): 3847. 10.3390/molecules25173847

Varakumar, S., Umesh, K.V. and Singhal, R.S., 2017. Enhanced extraction of oleoresin from ginger (Zingiber officinale) rhizome powder using enzyme-assisted three phase partitioning. Food Chemistry 216: 27–36. 10.1016/j.foodchem.2016.07.180

Ventura, S.P.M., e Silva, F.A., Quental, M.V., Mondal, D., Freire, M.G. and Coutinho, J.A.P., 2017. Ionic-liquid-mediated extraction and separation processes for bioactive compounds: past, present, and future trends. Chemical Reviews 117(10): 6984–7052. 10.1021/acs.chemrev.6b00550

Vidana Gamage, G.C., Lim, Y.Y. and Choo, W.S., 2021. Anthocyanins from Clitoria ternatea flower: biosynthesis, extraction, stability, antioxidant activity, and applications. Frontiers in Plant Science 12: 3011. 10.3389/fpls.2021.792303

Wang, C.X., Wang, L.X., Li, C.Y., Hu, C. and Zhao, S.H., 2020. Anti-proliferation activities of three bioactive components purified by high-speed countercurrent chromatography in essential oil from ginger. European Food Research and Technology 246(4): 795–805. 10.1007/s00217-020-03446-7

Wang, Q., Wei, Q., Yang, Q., Cao, X., Li, Q., Shi, F., Tong, S., Feng, C., Yu, Q., Yu, J. and Xu, X., 2017. A novel formulation of [6]-gingerol: proliposomes with enhanced oral bio-availability and antitumor effect. International Journal of Pharmaceutics 535(1–2): 308–315. 10.1016/j.ijpharm.2017.11.006

Wang, S., Zhang, C., Yang, G. and Yang, Y., 2014. Biological properties of 6-gingerol: a brief review. Natural Product Communications 9: 7. 10.1177/1934578x1400900736

Wang, X., Zheng, Z., Guo, X., Yuan, J. and Zheng, C., 2011. Preparative separation of gingerols from Zingiber officinale by high-speed countercurrent chromatography using stepwise elution. Food Chemistry 125(4): 1476–1480. 10.1016/j.foodchem.2010.10.066

Wang, Y., Li, R., Jiang, Z.T., Tan, J., Tang, S.H., Li, T.T., Liang, L.L., He, H.J., Liu, Y.M., Li, J.T. and Zhang, X.C., 2018. Green and solvent-free simultaneous ultrasonic-microwave assisted extraction of essential oil from white and black peppers. Industrial Crops and Products 114: 164–172. 10.1016/j.indcrop.2018.02.002

Wei, Q., Yang, Q., Wang, Q., Sun, C., Zhu, Y., Niu, Y., Yu, J. and Xu, X., 2018. Formulation, characterization, and pharmacokinetic studies of 6-gingerol-loaded nanostructured lipid carriers. AAPS PharmSciTech 19(8): 3661–3669. 10.1208/s12249-018-1165-2

Wen, P., Hu, T.G., Linhardt, R.J., Liao, S.T., Wu, H. and Zou, Y.X., 2019. Mulberry: a review of bioactive compounds and advanced processing technology. Trends in Food Science and Technology 83: 138–158. 10.1016/j.tifs.2018.11.017

Wen, P., Zong, M.-H., Linhardt, R.J., Feng, K. and Wu, H., 2017. Electrospinning: a novel nano-encapsulation approach for bioactive compounds. Trends in Food Science and Technology 70: 56–68. 10.1016/j.tifs.2017.10.009

Xing, J.J., Cheng, Y.L., Chen, P., Shan, L., Ruan, R., Li, D. and Wang, L.J., 2019. Effect of high-pressure homogenization on the extraction of sulforaphane from broccoli (Brassica oleracea) seeds. Powder Technology 358: 103–109. 10.1016/j.powtec.2018.12.010

Xi, J., He, L. and Yan, L., 2017. Continuous extraction of phenolic compounds from pomegranate peel using high voltage electrical discharge. Food Chemistry 230: 354–361. 10.1016/j.foodchem.2017.03.072

Xu, Y., Wang, Q., Feng, Y., Firempong, C.K., Zhu, Y., Omari-Siaw, E., Zheng, Y., Pu, Z., Xu, X. and Yu, J., 2016. Enhanced oral bioavail-ability of [6]-gingerol-SMEDDS: preparation, in vitro and in vivo evaluation. Journal of Functional Foods 27: 703–710. 10.1016/j.jff.2016.10.007

Yang, Q. and Dionysiou, D.D., 2004. Photolytic degradation of chlorinated phenols in room temperature ionic liquids. Journal of Photochemistry and Photobiology A: Chemistry 165(1): 229–240. 10.1016/j.jphotochem.2004.03.022

Young, H.Y., Luo, Y.L., Cheng, H.Y., Hsieh, W.C., Liao, J.C. and Peng, W.H., 2005. Analgesic and anti-inflammatory activities of [6]-gingerol. Journal of Ethnopharmacology 96(1–2): 207–210. 10.1016/j.jep.2004.09.009

Zahoor, A., Yang, C., Yang, Y., Guo, Y., Zhang, T., Jiang, K., Guo, S. and Deng, G., 2020. 6-gingerol exerts anti-inflammatory effects and protective properties on LTA-induced mastitis. Phytomedicine 76(2020): 153248. 10.1016/j.phymed.2020.153248

Zarate, R., Sukrasno and Yeoman, M.M., 1992. Application of two rapid techniques of column chromatography to separate the pungent principles of ginger, Zingiber officinale Roscoe. Journal of Chromatography A 609(1–2): 407–413. 10.1016/0021-9673(92)80189-2

Zhan, K., Xu, K. and Yin, H., 2011. Preparative separation and purification of gingerols from ginger (Zingiber officinale Roscoe) by high-speed countercurrent chromatography. Food Chemistry 126(4): 1959–1963. 10.1016/j.foodchem.2010.12.052

Zhang, H.F., Yang, X.H. and Wang, Y., 2011. Microwave assisted extraction of secondary metabolites from plants: current status and future directions. Trends in Food Science and Technology 22(12): 672–688. 10.1016/j.tifs.2011.07.003

Zhang, J., Wen, C., Zhang, H., Duan, Y. and Ma, H., 2020. Recent advances in the extraction of bioactive compounds with subcritical water: a review. Trends in Food Science and Technology 95: 183–195. 10.1016/j.tifs.2019.11.018

Zhang, Q.W., Lin, L.G. and Ye, W.C., 2018. Techniques for extraction and isolation of natural products: a comprehensive review. Chinese Medicine 13(1): 20. 10.1186/s13020-018-0177-x

Zhen, L., Wei, Q., Wang, Q., Zhang, H., Adu-Frimpong, M., Kesse Firempong, C., Xu, X. and Yu, J., 2020. Preparation and in vitro/ in vivo evaluation of 6-gingerol TPGS/PEG-PCL polymeric micelles. Pharmaceutical Development and Technology 25(1): 1–8. 10.1080/10837450.2018.1558239