Enzymatic hydrolysis of geniposide from gardenia jaminoides to produce genipin as a pigment precursor and crosslinking agent

MINISTRY OF EDUCATION AND TRAINING HO CHI MINH CITY UNIVERSITY OF TECHNOLOGY AND EDUCATION FACULTY FOR HIGH QUALITY TRAINING GRADUATION THESIS FOOD TECHNOLOGY ENZYMATIC HYDROLYSIS OF GENIPOSIDE FROM GARDENIA JAMINOIDE TO PRODUCE GENIPIN AS A PIGMENT PRECURSOR AND CROSSLINKING AGENT SUPERVISOR: VO THI NHA NGUYEN VINH TIEN STUDENT: DANG HOANG DUC HO DAC LOC SKL009152 Ho Chi Minh City, August, 2022 HO CHI MINH CITY UNIVERSITY OF TECHNOLOGY AND EDUCATION FACULTY FOR HIGH QUALITY TRAINING GRADUATION PROJECT Thesis code 2022-18116009 ENZYMATIC HYDROLYSIS OF GENIPOSIDE FROM GARDENIA JAMINOIDE TO PRODUCE GENIPIN AS A PIGMENT PRECURSOR AND CROSSLINKING AGENT DANG HOANG DUC Student ID: 18116009 HO DAC LOC 18116022 Major: FOOD TECHNOLOGY Supervisor: VO THI NGA, PhD NGUYEN VINH TIEN, ASSOC PROF Ho Chi Minh City, August 2022 HO CHI MINH CITY UNIVERSITY OF TECHNOLOGY AND EDUCATION FACULTY FOR HIGH QUALITY TRAINING GRADUATION PROJECT Thesis code 2022-18116009 ENZYMATIC HYDROLYSIS OF GENIPOSIDE FROM GARDENIA JAMINOIDES TO PRODUCE GENIPIN AS A PIGMENT PRECURSOR AND CROSSLINKING AGENT DANG HOANG DUC Student ID: 18116009 HO DAC LOC 18116022 Major: FOOD TECHNOLOGY Supervisor: VO THI NGA, PhD NGUYEN VINH TIEN, ASSOC PROF Ho Chi Minh City, August 2022 DECLARATION Except where there is clear acknowledgment and reference to the work of others, we thus declare that all content and materials included in and presented in this thesis are our original creations Additionally, we guarantee that the materials acknowledged in the thesis have been cited appropriately and properly in line with requirements , August 2022 Signature I ACKNOWLEDGEMENT "No research without action, no action without research" is a well-known quote attributed to Kurt Lewin (2012) Indeed, in order to finish and attain the current outcome, we have addressed and conquered all the difficulties and obstacles inherent in and throughout the project In addition, our beloved professors, classmates, and families have made a substantial contribution that stimulates and supports us Therefore, we would like to sincerely thank all the lecturers in charge of the Department of Food Technology, Faculty of Chemical and Food Technology, and Ho Chi Minh City University of Technology and Education for providing us with valuable knowledge and the best equipment and facilities to complete our thesis We would also want to express our gratitude to our cherished supervisors, PhD Vo Thi Nga and Assoc Prof Nguyen Vinh Tien, who have passionately guided and shared their teaching expertise and experience in order for us to complete this thesis Sincerely, we would like to thank Ms Ho Thi Thu Trang of the Department of Food Technology for allowing and assisting us in using the available measuring instruments and equipment at the Faculty of Chemical and Food Technology laboratory Nonetheless, we would want to express our gratitude to our classmates for supporting and organizing the thesis's complex experiment II III IV V VI 1155 cm-1 [72] Following other FTIR studies on genipin treated biopolymers , the samples showed additional peaks after genipin cross-linking at 1281, 1423, and 1639 cm -1 in 0.0025 genipin/NH2 These peaks were attributed to the C-O-C asymmetric stretching, the CH bending of the methyl ester, and the C=C ring stretching, respectively According to the literature [73], these characteristics imply that the carboxymethyl group of genipin reacted with the amino group of chitosan to generate a secondary amide From the results of Figure 3.22, we can see that when increasing the concentration of genipin in the chitosan solution, the peak will change with an increasing trend from 1638 to 1653 cm -1 , which means that the FTIR spectrum tends to be -1 -1 wider At the peak of 1281 cm , there is also an increasing trend But at the peak of 1423cm , there is a decreasing trend The C-N stretch of the tertiary aromatic amine of the cross-linked genipin nitrogen iridoid, which is covalently attached to the chitosan, was identified as the source of the band at 1112 cm -1 [73] Additionally, the cross-linked spectrum's band at 1070 cm -1 is noticeably stronger than the comparable band in the spectrum of pure genipin, indicating that this absorption band is primarily connected to modes created by the cross-linking process From the results, the peak 1070 tends to decrease when increasing genipin concentration, this can be understood that when increasing genipin concentration, the ability to cross-link is higher 3.3.3 Moisture content of genipin – chitosan films (%) Table Moisture content of genipin – chitosan films genipin/ NH2 content Note: different lowercase letters in a column illustrate significant differences (p < 0.05) The purpose of measuring the moisture content of the film is to see the change in moisture content when genipin cross-links with chitosan From the results of Table 3.6, we can see that the moisture content of the samples compared with the control samples gradually decreased 49 Includes four samples according to increasing genipin concentration in chitosan solution from 0.0025 to 0.01 genipin/NH2 Perhaps it was the reaction between genipin and chitosan that changed the structure of genipin Specifically, genipin will have membranes that block water molecules that can easily penetrate 3.3.4 Mechanical properties of genipin – chitosan films (Thickness, TS and EL) Table Mechanical properties of genipin-chitosan films Genipin/ NH2 content 0.0025 0.005 0.0075 0.01 Note: different lowercase letters in a column illustrate significant differences (p < 0.05) The goal of this experiment is to measure the tensile strength and elongation of the films, as well as their flexibility and mechanical resistance, which determine the film's integrity and sustainability criteria when change genipin concentrations To obtain a film that is stable and insoluble in water, we must find the concentration of genipin to put in chitosan Here we have investigated concentrations of genipin and a control sample without genipin The largest sample was 0.01 genipin/NH2 and the smallest sample was 0.0025 genipin/NH The amount of crosslinking reagent required to complete the crosslinking reaction is less than that needed for gel formation in a 2% chitosan solution, and the concentration of the solution rises as a result of film formation during solvent evaporation The film created at this genipin/NH ratio was colorless for 24 hours following solvent evaporation before becoming blue and water-repellent [57] However, reducing the genipin content in the chitosan solution not only did not reduce the strength but even increased the strength of the film As a result of Table 3.7, we can see that the films with a concentration of 0.0075 genipin/NH2 has higher durability than the film with a concentration of 0.01 genipin/NH2 because the crosslinking of the chitosan solution was not fully 50 completed before the solvent evaporated the macromolecular chains of chitosan and may also result from the chains' immobilization in the equilibrium state, where more intermolecular interactions take place [57] 3.3.5 Swelling content of genipin – chitosan films Table Swelling content of genipin – chitosan films Genipin/ NH2 content Note: different lowercase letters in a column illustrate significant differences (p < 0.05) In this experiment, we can see that the water repellency of the film is based on different genipin concentrations In table 3.8, we can see that the swelling ratio of 0.0025 genipin/chitosan film is the highest and tends to decrease with low genipin concentration The swelling ratios of the crosslinked chitosan films were reduced as the concentration of genipin utilized was increased [74] Perhaps because the crosslinking between genipin and chitosan prevented water from entering and deepening the internal structure, when the genipin content was increased, the crosslinking became denser Therefore, it is harder for water molecules to penetrate 51 CHAPTER 4: CONCLUSION From the experimental results, some conclusions are drawn as follows: - A method for preparing gardenia blue pigment that includes the following steps: a) Geniposide is subjected to cellulase to produce a hydrolysate b) The hydrolysate produced in step a) is extracted with EtOAc and the solvent is removed after extraction to provide a genipin-containing product c) The genipin-containing product from step b) is dissolved in ethanol and then reacted with an aqueous solution of an amino acid or its salt to form the gardenia blue pigment In roughly 0.2 g of cellulase per g of geniposide, cellulase is introduced to the reaction in step a) - The optimal conditions of the study: The pH of the treatment performed in step a) is 4.5 The duration of the treatment performed in step a) is completed in hours Monosodium glutamate is the amino acid that is chosen to react with genipin in step c) to produce the gardenia blue pigment The pH of the treatment performed in step a) is The duration of the treatment performed in step a) is completed in 10 hours - For the process of reacting between genipin and protein extracted from Lima bean: the most preferable pH for the reaction between genipin and protein extracted from Lima bean is 10 - When genipin reacts with amino acids, amino acids give the best results specifically, the solution is blue pigment And when genipin with primary and secondary amines, there is still a pigment forming reaction but it is not blue - When changing the concentration of genipin/NH2 from small to large, the cross- linked genipin-chitosan film and the blue pigment increased In terms of mechanical properties, with a concentration of 0.0075, the film has the highest tensile strength As for moisture and swelling, it gradually decreases with the concentration of genipin/NH2 52 REFERENCES [1] E F Gilman, Gardenia jasminoides, no 1432 2012 doi: 10.2165/00128415201214320-00091 [2] M L He, X W Cheng, J K Chen, and T S Zhou, “Simultaneous determination of five major biologically active ingredients in different parts of Gardenia jasminoides fruits by HPLC with diode-array detection,” Chromatographia, vol 64, no 11–12, pp 713–717, Dec 2006, doi: 10.1365/s10337-006-0099-0 [3] W Xiao, S Li, S Wang, and C T Ho, “Chemistry and bioactivity of Gardenia jasminoides,” Journal of Food and Drug Analysis, vol 25, no Elsevier Taiwan LLC, pp 43–61, Jan 01, 2017 doi: 10.1016/j.jfda.2016.11.005 [4] H Liu, Y F Chen, F Li, and H Y Zhang, “Fructus Gardenia (Gardenia jasminoides J Ellis) phytochemistry, pharmacology of cardiovascular, and safety with the perspective of new drugs development,” Journal of Asian Natural Products Research, vol 15, no pp 94–110, Jan 01, 2013 doi: 10.1080/10286020.2012.723203 [5] W Tao et al., “Optimization of supercritical fluid extraction of oil from the fruit of Gardenia jasminoides and its antidepressant activity,” Molecules, vol 19, no 12, pp 19350–19360, Dec 2014, doi: 10.3390/molecules191219350 [6] S Yamada, H Oshima, I Saito, and J Hayakawa, “Adoption of crocetin as an indicator compound for detection of gardenia yellow in food products (analysis of natural coloring matters in food V),” J Food Hyg Soc Japan, vol 37, no 6, pp 372–377, 1996, doi: 10.3358/shokueishi.37.6_372 [7] H Liu et al., “Analysis of volatile ingredients in Gardeniae Fructus and its processed products by GC-MS,” Zhongguo Zhong Yao Za Zhi, vol 40, pp 1732–1737, May 2015, doi: 10.4268/cjcmm20150919 [8] J Chaichana, W Niwatananun, S Vejabhikul, S Somna, and S Chansakaow, “VOLATILE CONSTITUENTS AND BIOLOGICAL ACTIVITIES OF GARDENIA JASMINOIDES,” 2009 [9] S Zhao, Y Yang, D Liang, D Liang, and C Zhang, “Quantitative analysis of geniposide in fructus Gardeniae and its different processed products,” Zhongguo Zhong Yao Za Zhi, vol 19, pp 601-602,638, Nov 1994 [10] E J Lee, J K Hong, and W K Whang, “Simultaneous determination of bioactive marker compounds from Gardeniae fructus by high performance liquid chromatography,” Arch Pharm Res., vol 37, no 8, pp 992–1000, 2014, doi: 10.1007/s12272-013-0293-1 [11] B Yang, X Liu, and Y Gao, “Extraction optimization of bioactive compounds (crocin, geniposide and total phenolic compounds) from Gardenia (Gardenia jasminoides Ellis) fruits with response surface methodology,” Innov Food Sci Emerg Technol., vol 10, no 53 4, pp 610–615, Oct 2009, doi: 10.1016/j.ifset.2009.03.003 [12] X S Wang, Y F Wu, S L Dai, R Chen, and Y Shao, “Ultrasound-assisted extraction of geniposide from Gardenia jasminoides,” Ultrason Sonochem., vol 19, no 6, pp 1155– 1159, 2012, doi: 10.1016/j.ultsonch.2012.03.012 [13] I K Hong, H Jeon, and S B Lee, “Extraction of natural dye from Gardenia and chromaticity analysis according to chi parameter,” J Ind Eng Chem., vol 24, pp 326– 332, Apr 2015, doi: 10.1016/j.jiec.2014.10.004 [14] X Zhu, Y Mang, F Shen, J Xie, and W Su, “Homogenate extraction of gardenia yellow pigment from Gardenia Jasminoides Ellis fruit using response surface methodology,” J Food Sci Technol., vol 51, no 8, pp 1575–1581, 2014, doi: 10.1007/s13197-012-0683-2 [15] S J Jun and J K Chun, “Design of U-column microwave-assisted extraction system and its application to pigment extraction from food,” Food Bioprod Process Trans Inst Chem Eng Part C, vol 76, no 4, pp 231–236, 1998, doi: 10.1205/096030898532133 [16] Y Yu et al., “Chemical constituents from the fruits of Gardenia jasminoides Ellis,” Fitoterapia, vol 83, no 3, pp 563–567, Apr 2012, doi: 10.1016/j.fitote.2011.12.027 [17] T Debnath, P J Park, N C Deb Nath, N B Samad, H W Park, and B O Lim, “Antioxidant activity of Gardenia jasminoides Ellis fruit extracts,” Food Chem., vol 128, no 3, pp 697–703, Oct 2011, doi: 10.1016/j.foodchem.2011.03.090 [18] T Q Pham, F Cormier, E Farnworth, H Van Tong, and M R Van Calsteren, “Antioxidant properties of crocin from Gardenia jasminoides Ellis and study of the reactions of crocin with linoleic acid and crocin with oxygen,” J Agric Food Chem., vol 48, no 5, pp 1455–1461, May 2000, doi: 10.1021/jf991263j [19] Y I Chen et al., “Peroxisome proliferator-activated receptor activating hypoglycemic effect of Gardenia jasminoides Ellis aqueous extract and improvement of insulin sensitivity in steroid induced insulin resistant rats,” BMC Complement Altern Med., vol 14, no January, 2014, doi: 10.1186/1472-6882-14-30 [20] L Guan et al., “Genipin ameliorates age-related insulin resistance through inhibiting hepatic oxidative stress and mitochondrial dysfunction,” Exp Gerontol., vol 48, no 12, pp 1387–1394, Dec 2013, doi: 10.1016/j.exger.2013.09.001 [21] K Kojima et al., “Preventive Effect of Geniposide on Metabolic Disease Status in Spontaneously Obese Type Diabetic Mice and Free Fatty Acid-Treated HepG2 Cells,” 2011 [22] S Y Wu et al., “Effect of geniposide, a hypoglycemic glucoside, on hepatic regulating enzymes in diabetic mice induced by a high-fat diet and streptozotoci,” Acta Pharmacol Sin., vol 30, no 2, pp 202–208, Feb 2009, doi: 10.1038/aps.2008.17 [23] G F Wang et al., “Geniposide inhibits high glucose-induced cell adhesion through the NF-B signaling pathway in human umbilical vein endothelial cells,” Acta Pharmacol Sin., 54 vol 31, no 8, pp 953–962, Aug 2010, doi: 10.1038/aps.2010.83 [24] J li Chen et al., “1H NMR-based metabolic profiling of liver in chronic unpredictable mild stress rats with genipin treatment,” J Pharm Biomed Anal., vol 115, pp 150–158, Nov 2015, doi: 10.1016/j.jpba.2015.07.002 [25] S L Liu, Y C Lin, T H Huang, S W Huang, and W H Peng, “Anti-depressive activity of Gardeniae fructus and geniposide in mouse models of depression,” African J Pharm Pharmacol., vol 5, no 13, pp 1580–1588, 2011, doi: 10.5897/ajpp11.335 [26] J H Kim, G H Kim, and K H Hwang, “Monoamine oxidase and dopamine βhydroxylase inhibitors from the fruits of Gardenia jasminoides,” Biomol Ther., vol 20, no 2, pp 214–219, May 2012, doi: 10.4062/biomolther.2012.20.2.214 [27] K K Toshiyuki Kaji, Tomohiro HAYASHI, Marie Nsimba Miezi, “Gardenia Fruit Extract Does Not Stimulate the Proliferation of Cultured Vascular Smooth Muscle Cells, A10,” Gard Fruit Extr Does Not Stimul Prolif Cult Vasc Smooth Muscle Cells, A10, vol 39, no 5, pp 1312–1314, 1991 [28] Y X Zhou, R Q Zhang, K Rahman, Z X Cao, H Zhang, and C Peng, “Diverse Pharmacological Activities and Potential Medicinal Benefits of Geniposide,” Evidencebased Complementary and Alternative Medicine, vol 2019 Hindawi Limited, 2019 doi: 10.1155/2019/4925682 [29] T N Weerapath Winotapun, Praneet Opanasopit and T Rojanarata, “One-enzyme catalyzed simultaneous plant cell disruption and conversion of released glycoside to aglycone combined with in situ product separation as green one-pot production of genipin from gardenia fruit,” Enzyme Microb Technol., vol 53, pp 92–96, 2013 [30] M Manickam, Balamurugan; Sreedharan, Rajesh; Elumalai, “‘Genipin’ – The Natural Water Soluble Cross-linking Agent and Its Importance in the Modified Drug Delivery Systems: An Overview,” Bentham Sci Publ., vol 11, no 1, pp 139–145, 2014 [31] M F Butler, Y F Ng, and P D A Pudney, “Mechanism and kinetics of the crosslinking reaction between biopolymers containing primary amine groups and genipin,” J Polym Sci Part A Polym Chem., vol 41, no 24, pp 3941–3953, 2003, doi: 10.1002/pola.10960 [32] Y Zhu and M B Chan-Park, “Density quantification of collagen grafted on biodegradable polyester: Its application to esophageal smooth muscle cell,” Anal Biochem., vol 363, no 1, pp 119–127, 2007, doi: 10.1016/j.ab.2007.01.007 [33] C Nishi, N Nakajima, and Y Ikada, “In vitro evaluation of cytotoxicity of diepoxy compounds used for biomaterial modification,” J Biomed Mater Res., vol 29, no 7, pp 829–834, 1995, doi: 10.1002/jbm.820290707 [34] H W Sung, Y Chang, I L Liang, W H Chang, and Y C Chen, “Fixation of biological tissues with a naturally occurring crosslinking agent: Fixation rate and effects of pH, temperature, and initial fixative concentration,” J Biomed Mater Res., vol 52, no 1, pp 55 77–87, 2000, doi: 10.1002/1097-4636(200010)52:13.0.CO;2-6 [35] M Xu et al., “Microbial transformation of geniposide in Gardenia jasminoides Ellis into genipin by Penicillium nigricans,” Enzyme Microb Technol., vol 42, no 5, pp 440– 444, 2008, doi: 10.1016/j.enzmictec.2008.01.003 [36] Y Suzuki, K Kondo, Y Ikeda, and K Umemura, “Antithrombotic effect of geniposide and genipin in the mouse thrombosis model,” Planta Med., vol 67, no 9, pp 807–810, 2001, doi: 10.1055/s-2001-18842 [37] H J Koo, K H Lim, H J Jung, and E H Park, “Anti-inflammatory evaluation of gardenia extract, geniposide and genipin,” J Ethnopharmacol., vol 103, no 3, pp 496– 500, 2006, doi: 10.1016/j.jep.2005.08.011 [38] H W Sung, R N Huang, L L H Huang, C C Tsai, and C T Chiu, “Feasibility study of a natural crosslinking reagent for biological tissue fixation,” J Biomed Mater Res., vol 42, no 4, pp 560–567, 1998, doi: 10.1002/(SICI)10974636(19981215)42:43.0.CO;2-I [39] Y Chang, C C Tsai, H C Liang, and H W Sung, “In vivo evaluation of cellular and acellular bovine pericardia fixed with a naturally occurring crosslinking agent (genipin),” Biomaterials, vol 23, no 12, pp 2447–2457, 2002, doi: 10.1016/S0142-9612(01)00379-9 [40] Y Q Chen and G Zhao, “The puzzling abundance pattern of HD 134439 and HD 134440,” Mon Not R Astron Soc., vol 370, no 4, pp 2091–2096, 2006, doi: 10.1111/j.1365-2966.2006.10640.x [41] S W Lee, J M Lim, S H Bhoo, Y S Paik, and T R Hahn, “Colorimetric determination of amino acids using genipin from Gardenia jasminoides,” Anal Chim Acta, vol 480, no 2, pp 267–274, 2003, doi: 10.1016/S0003-2670(03)00023-0 [42] H Y S R Iwahori A., “NII-Electronic Library Service,” Chem Pharm Bull., no 43, p 2091, 1970 [43] M Tanaka, M Yamazaki, and K Chiba, “Neuroprotective action of genipin on tunicamycin-induced cytotoxicity in neuro2a cells,” Biol Pharm Bull., vol 32, no 7, pp 1220–1223, 2009, doi: 10.1248/bpb.32.1220 [44] M Yamamoto et al., “Genipin, a metabolite derived from the herbal medicine Inchin-ko-to, and suppression of Fas-induced lethal liver apoptosis in mice,” Gastroenterology, vol 118, no 2, pp 380–389, 2000, doi: 10.1016/S00165085(00)70220-4 [45] J S Yoo, Y J Kim, S H Kim, and S H Choi, “Study on genipin: A new alternative natural crosslinking agent for fixing heterograft tissue,” Korean J Thorac Cardiovasc Surg., vol 44, no 3, pp 197–207, 2011, doi: 10.5090/kjtcs.2011.44.3.197 [46] S Sundararaj, P Slusarewicz, M Brown, and T Hedman, “Genipin crosslinker releasing sutures for improving the mechanical/repair strength of damaged connective tissue,” J Biomed Mater Res - Part B Appl Biomater., vol 105, no 8, pp 2199–2205, 2017, doi: 56 10.1002/jbm.b.33753 [47] A Ozaki, M Kitano, N Furusawa, H Yamaguchi, K Kuroda, and G Endo, “Genotoxicity of gardenia yellow and its components,” Food Chem Toxicol., vol 40, no 11, pp 1603–1610, 2002, doi: 10.1016/S0278-6915(02)00118-7 [48] C A Hobbs et al., “Genotoxicity evaluation of the naturally-derived food colorant, gardenia blue, and its precursor, genipin,” Food Chem Toxicol., vol 118, no July, pp 695–708, 2018, doi: 10.1016/j.fct.2018.06.001 [49] Z Z Qing HE, Xiaoping HUANG, Xiaojia HU, Kun PENG, “A PROCESS FOR PRODUCING GARDENIA BLUE PIGMENT FROM GENIPOSIDE,” 2018 [50] 张张张, 张张张张张, “Method for hydrolyzing and preparing gardenia cyanine by using supercritical CO2 to catalyze geniposide,” 2013 [51] C Feng, “Method for preparing high-color-value gardenia blue pigment,” 2013 [52] S Lijun, X Xiaohui, S Chang, and S Aiguang, “Producing natural gardenia blue pigment with two-stage method,” J Nanjing Agric Univ., vol 17, no 4, p 98—101, 1994, [Online] Available: http://europepmc.org/abstract/CBA/267822 [53] L Li, Y Guo, L Zhao, Y Zu, H Gu, and L Yang, “Enzymatic hydrolysis and simultaneous extraction for preparation of genipin from bark of eucommia ulmoides after ultrasound, microwave pretreatment,” Molecules, vol 20, no 10, pp 18717–18731, Oct 2015, doi: 10.3390/molecules201018717 [54] F L Mi, S S Shyu, and C K Peng, “Characterization of ring-opening polymerization of genipin and pH-dependent cross-linking reactions between chitosan and genipin,” J Polym Sci Part A Polym Chem., vol 43, no 10, pp 1985–2000, May 2005, doi: 10.1002/pola.20669 [55] R A A Muzzarelli, “Genipin-crosslinked chitosan hydrogels as biomedical and pharmaceutical aids,” Carbohydr Polym., vol 77, no 1, pp 1–9, 2009, doi: 10.1016/j.carbpol.2009.01.016 [56] A Bigi, G Cojazzi, S Panzavolta, N Roveri, and K Rubini, “Stabilization of gelatin films by crosslinking with genipin,” Biomaterials, vol 23, no 24, pp 4827–4832, 2002, doi: 10.1016/S0142-9612(02)00235-1 [57] N Kildeeva et al., “Influence of genipin crosslinking on the properties of Chitosanbased films,” Polymers (Basel)., vol 12, no 5, 2020, doi: 10.3390/POLYM12051086 [58] N T H NHUNG, “NGHIÊN CỨU QUÁ TRÌNH TRÍCH LY HỢP CHẤT CROCIN, VÀ GENIPOSIDE TRONG QUẢ DÀNH DÀNH GARDENIA JASMINOIDES ELLIS BẰNG PHƯƠNG PHÁP VI SÓNG,” 2014 [59] O Moreno, C Pastor, J Muller, L Atarés, C Gonzalez-Martinez, and A Chiralt, “Physical and bioactive properties of corn starch – Buttermilk edible films,” J Food Eng., vol 141, pp 27–36, Nov 2014, doi: 10.1016/j.jfoodeng.2014.05.015 57 [60] Y.-J Fu et al., “Enzyme assisted extraction of luteolin and apigenin from pigeonpea [Cajanuscajan (L.) Millsp.] leaves.,” Food Chem., vol 111, no 2, pp 508–512, Nov 2008, doi: 10.1016/j.foodchem.2008.04.003 [61] X S Yao et al., “Natural medicine chemistry,” People’s Med Publ House, Beijing, 2004 [62] J E Brauch, Underutilized Fruits and Vegetables as Potential Novel Pigment Sources, no July 2010 Elsevier Ltd, 2016 doi: 10.1016/B978-0-08-100371-8.00015-4 [63] W Chi, Y.-L Cui, and J Tian, Biotransformation of geniposide in Gardenia jasminoides Ellis into genipin 2009 [64] D Yang, M Zhou, W Wei, H Zhu, and X Fan, “Preparation of a genipin blue from egg protein and genipin,” Nat Prod Res., vol 26, pp 765–769, Sep 2011, doi: 10.1080/14786419.2010.547859 [65] K F Junya YAMASHITA, Masahiro NISHIKAWA, Kaori MIURA, “* EP003957690A1 *,” 2022 [66] K Delmar and H Bianco-peled, “The dramatic effect of small pH changes on the properties of chitosan hydrogels crosslinked with genipin,” Carbohydr Polym., vol 127, pp 28–37, 2015, doi: 10.1016/j.carbpol.2015.03.039 [67] N Moritome, Y Kishi, and S Fujii, “Properties of red pigments prepared from geniposidic acid and amino acids,” J Sci Food Agric., vol 79, pp 810–814, May 1999, doi: 10.1002/(SICI)1097-0010(19990501)79:63.0.CO;2-7 [68] M Moghadam, M Salami, M Mohammadian, and Z Emam-Djomeh, “Development and characterization of pH-sensitive and antioxidant edible films based on mung bean protein enriched with Echium amoenum anthocyanins,” J Food Meas Charact., vol 15, no 4, pp 2984–2994, 2021, doi: 10.1007/s11694-021-00872-3 [69] J.Kan, J Liu, H Yong, Y Liu, Y Qin, and J Liu, “Int J Biol Macr,” Int J Biol Macromol., vol 140, pp 384–392, 2019, doi: 10.1016/j.ijbiomac.2019.05.029 [70] M O Okekunle, K O Adebowale, B I Olu-Owolabi, and A Lamprecht, “Physicochemical, morphological and thermal properties of oxidized starches from Lima bean (Phaseolus lunatus),” Sci African, vol 8, no June, 2020, doi: 10.1016/j.sciaf.2020.e00432 [71] M F Butler, Y.-F Ng, and P D A Pudney, “Mechanism and Kinetics of the Crosslinking Reaction between Biopolymers Containing Primary Amine Groups and Genipin,” 2003 [72] J Y Lai, Y T Li, and T P Wang, “In vitro response of retinal pigment epithelial cells exposed to chitosan materials prepared with different cross-linkers,” Int J Mol Sci., vol 11, no 12, pp 5256–5272, 2010, doi: 10.3390/ijms11125256 [73] S Dimida, A Barca, N Cancelli, V De Benedictis, M G Raucci, and C Demitri, “Effects of genipin concentration on cross-linked chitosan scaffolds for bone tissue 58 engineering: Structural characterization and evidence of biocompatibility features,” Int J Polym Sci., vol 2017, 2017, doi: 10.1155/2017/8410750 [74] F.-L Mi, Y.-C Tan, H.-C Liang, R.-N Huang, and H.-W Sung, “In vitro evaluation of a chitosan membrane cross-linked with genipin,” 2001 59