Yellow pigment from gardenia fruit: structural identification and evaluation of cytotoxic activity in HepG2 cells by induction of apoptosis

다국어 초록 (Multilingual Abstract)

The preparation process of yellow pigment (YP) from gardenia (Gardenia jasminoides) fruit was investigated, and the main components of YP were characterized by liquid chromatography-time of flight-mass spectrometer/mass spectrometer (LC-TOF–MS/MS). Furthermore, cytotoxic activity in HepG2 cells by induction of apoptosis was also evaluated. The preparation results indicated that the color value of YP was 498.34, which was 8.6 times higher than crude YP. Fifteen compounds in YP were identified, and crocins were the predominant compounds. The cell experiment results showed that YP inhibited the proliferation of HepG2 cells in a time- and dose-dependent manner. Moreover, YP also inhibited HepG2 cells in G2/M stage, increased the level of intracellular reactive oxygen species (ROS), and enhanced cell apoptosis. Real-time quantitative polymerase chain reaction (RT-PCR) analysis revealed the up-regulation of caspase-3, 8, 9, and bax and down-regulation of bcl-2 in HepG2 cells. Overall, these findings suggested that YP had potential cytotoxic activity in HepG2 cells by induction of apoptosis, which might be beneficial to human health.

참고문헌 (Reference)

1 Xue H, "Ultrasound-assisted deep eutectic solvent extraction of anthocyanins from blueberry wine residues : optimization, identification, and HepG2 antitumor activity" 25 : 5456-, 2020

2 Akbarpoor V, "The saffron effects on expression pattern of critical self-renewal genes in adenocarcinoma tumor cell line(AGS)" 19 : 100629-, 2020

3 Saw CLL, "The berry constituents quercetin, kaempferol, and pterostilbene synergistically attenuate reactive oxygen species : involvement of the Nrf2-ARE signaling pathway" 72 : 303-311, 2014

4 Mollaei H, "The anti-proliferative and apoptotic effects of crocin on chemosensitive and chemoresistant cervical cancer cells" 94 : 307-316, 2017

5 Chaiboonchoe A, "Safranal induces DNA double-strand breakage and ER-stress-mediated cell death in hepatocellular carcinoma cells" 8 (8): 3-16, 2018

6 Amr A, "Saffron-based crocin prevents early lesions of liver cancer : in vivo, in vitro and network analyses" 11 (11): 121-133, 2016

7 Lech K, "Saffron yellow : characterization of carotenoids by high performance liquid chromatography with electrospray mass spectrometric detection" 44 (44): 1661-1667, 2009

8 Fangzhou Y, "Quality control of Gardeniae Fructus by HPLC-PDA fingerprint coupled with chemometric methods" 53 (53): 1685-1694, 2015

9 Moras B, "Quality assessment of saffron ( Crocus sativus L.) extracts via UHPLC-DAD-MS analysis and detection of adulteration using gardenia fruit extract ( Gardenia jasminoides Ellis )" 257 : 325-332, 2018

10 Sun N, "Purification, preliminary structure and antitumor activity of exopolysaccharide produced by Streptococcus thermophilus CH9" 23 (23): 2898-, 2018

11 Rahiman N, "Protective effects of saffron and its active components against oxidative stress and apoptosis in endothelial cells" 118 : 82-89, 2018

12 Feng J, "Preparative separation of crocins and geniposide simultaneously from g ardenia fruits using macroporous resin and reversedᒧphase chromatography" 37 : 314-322, 2014

13 Abedini MR, "Possible role of FLICE-like inhibitory protein(FLIP)in chemoresistant ovarian cancer cells in vitro" 23 : 6997-7004, 2004

14 Bo Z, "Persimmon vinegar polyphenols protect against hydrogen peroxideinduced cellular oxidative stress via Nrf2 signalling pathway" 255 : 23-30, 2018

15 Xiaoshuang C, "Optimization of ultrasound-assisted extraction of gardenia fruit oil with bioactive components and their identifi-cation and quantification by HPLC-DAD/ESI-MS(2)" 6 : 2194-2204, 2015

16 He W, "On-line HPLC-ABTS screening and HPLC-DAD-MS/MS identification of free radical scavengers in Gardenia(Gardenia jasminoides Ellis)fruit extracts" 123 : 521-528, 2010

17 Hou YC, "Metabolism and pharmacokinetics of genipin and geniposide in rats" 46 : 2764-2769, 2008

18 Choi HJ, "Isolation and characterization of the major colorant in Gardenia fruit" 49 (49): 15-20, 2001

19 Monica M, "Investigation on the origin of sperm DNA fragmentation : role of apoptosis, immaturity and oxidative stress" 21 : 109-122, 2015

20 Ko SG, "Induction of apoptosis by Saussurea lappa and Pharbitis nil on AGS gastric cancer cells" 27 (27): 1604-1610, 2004

21 Cui D, "Green synthesis of selenium nanoparticles with extract of hawthorn fruit induced HepG2 cells apoptosis" 56 (56): 528-534, 2018

22 Valavi M, "Effects of combined crocin and epirubicin on apoptosis and cell cycle pathways in a human cervical cancer cell line" 22 : 825-875, 2018

23 Dandan L, "Distinct proapoptotic properties of Zhejiang saffron against human lung cancer via a caspase-8-9-3 cascade" 15 (15): 6075-6080, 2014

24 D’Alessandro AM, "Crocus sativus stigma extract and its major constituent crocin possess significant antiproliferative properties against human prostate cancer" 65 : 930-942, 2013

25 Hoshyar R, "Crocin triggers the apoptosis through increasing the Bax/Bcl-2 ratio and caspase activation in human gastric adenocarcinoma, AGS, cells" 32 : 50-57, 2013

26 Reyhane H, "Crocin triggers the apoptosis through increasing the Bax/Bcl-2 ratio and caspase activation in human gastric adenocarcinoma, AGS, cells" 32 : 50-57, 2013

27 Chong Y, "Crocin induces autophagic apoptosis in hepatocellular carcinoma by inhibiting Akt/mTOR activity" 11 : 2017-2028, 2018

28 Yang C, "Crocin and geniposide profiles and radical scavenging activity of gardenia fruits(Gardenia jasminoides Ellis)from different cultivars and at the various stages of maturation" 81 : 269-273, 2010

29 Min Z, "Chrysotile causes human bronchial epithelial cell apoptosis in response to the Fas-mediated apoptosis pathway" 84 : 229-236, 2017

30 Wenping X, "Chemistry and bioactivity of Gardenia jasminoides" 25 (25): 43-61, 2017

31 Elham MS, "Antiproliferative and proapoptotic effects of crocin combined with hyperthermia on human breast cancer cells" 35 : 340-347, 2016

32 HR R, "Antiproliferative activity of crocin involves targeting of microtubules in breast cancer cells" 7 : 8762-8768, 2017

33 Bathaie SZ, "Anticancer effects of crocetin in both human adenocarcinoma gastric cancer cells and rat model of gastric cancer" 91 : 397-403, 2013

34 Zahra BS, "Anticancer effects of crocetin in both human adenocarcinoma gastric cancer cells and rat model of gastric cancer" 91 : 397-403, 2013

35 Livak JK, "Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T))method" 25 : 402-408, 2001

36 Zhou J, "A systematic metabolic pathway identification of common Gardenia Fruit(Gardeniae Fructus)in mouse bile, plasma, urine and feces by HPLC-Q-TOF-MS/MS" 1145 : 122100-, 2020

37 Wang L, "A strategy for identification and structural characterization of compounds from Gardenia jasminoides by integrating macroporous resin column chromatography and liquid chromatography-tandem mass spectrometry combined with ion-mobility spectrometry" 1452 : 47-57, 2016