Study on Structure-Function Relationship of the Anti-inflammatory and Anti-cancer Effects of Catechins Using Cell Models andNetwork Pharmacology

YING Sihui; LU Sen; CHEN Zhongzheng; ZHANG Yuanyuan; LI Bin; LIN Xiaorong

doi:10.13386/j.issn1002-0306.2023050014

Volume 45 Issue 5

Feb. 2024

Turn off MathJax

Article Contents

Abstract

References

Supplements

Science and Technology of Food Industry > 2024 > 45(5): 18-29. > DOI: 10.13386/j.issn1002-0306.2023050014

YING Sihui, LU Sen, CHEN Zhongzheng, et al. Study on Structure-Function Relationship of the Anti-inflammatory and Anti-cancer Effects of Catechins Using Cell Models andNetwork Pharmacology[J]. Science and Technology of Food Industry, 2024, 45(5): 18−29. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2023050014.

Citation:

PDF (8268 KB)

Study on Structure-Function Relationship of the Anti-inflammatory and Anti-cancer Effects of Catechins Using Cell Models andNetwork Pharmacology

College of Food Science, South China Agricultural University, Guangzhou 510642, China

More Information

Received Date: May 04, 2023
Available Online: January 03, 2024

Graphical Abstract

Abstract

Abstract

Objective: To explore the relationship between the structure of tea catechins and their anti-inflammatory and anti-cancer activities and to preliminarily elucidate the underlining mechanism behind the structure-function relationship. Methods: The lipopolysaccharide-induced murine macrophage cells RAW 264.7 and human colorectal cancer cells HCT116 were used as in vitro models for inflammation and cancer. The in vitro anti-inflammatory and anti-cancer activities of catechins were analyzed by Griess reagent colorimetric method and tetramethyl azothiazole blue colorimetric method. The key targets and pathways of the anti-inflammatory and anti-cancer of each catechin monomer were predicted by network pharmacology. The interactions between catechins and key target proteins were simulated by molecular docking technique, and the binding ability of each component to key targets was compared. Results: The significant in vitro anti-inflammatory and anti-cancer potentials of eight catechins were confirmed. Additionally, the galloyl group in gallated catechins, the pyrogallol moiety of B-ring in pyrogallol-type catechins, and the trans-type structure of C₂-C₃ in trans catechins were found to be beneficial for their anti-inflammatory and anti-cancer activities, however, an antagonistic effect was also observed between the pyrogallol moiety in B-ring and the galloyl group of pyrogallol-type gallated catechins. Furthermore, multiple targets and pathways were predicted to be involved in the anti-inflammatory and anti-cancer effects of eight catechin monomers. The galloyl group in catechins was found to be beneficial for their regulatory effects on multiple targets and their interaction with key target proteins including IL6, TNF, and AKT1 through hydrogen bonding. The present study preliminarily reveals the structure-function relationship behind the anti-inflammatory and anti-cancer functions of catechins. It provides theoretical and technical instruction for further elucidation of the relationship between the functional effects and the molecular structures of catechins.
- catechins,
- anti-inflammatory,
- anti-cancer,
- structure-function relationship,
- network pharmacology,
- molecular docking

FullText(HTML)

References (46)

References

[1]	MOLDOGAZIEVA N T, LUTSENKO S V, TERENTIEV A A. Reactive oxygen and nitrogen species-induced protein modifications:Implication in carcinogenesis and anticancer therapy[J]. Cancer Research,2018,78(21):6040−6047. doi: 10.1158/0008-5472.CAN-18-0980
[2]	李晓飞, 高雄, 林晓蓉, 等. 基于RAW264.7细胞模型的不同茶类抗炎功能特性[J]. 食品工业科技,2017,38(19):67−73. [LI X F, GAO X, LIN X R, et al. Anti-inflammatory activities of six types of tea in LPS-induced RAW264.7 cells[J]. Science and Technology of Food Industry,2017,38(19):67−73.] LI X F, GAO X, LIN X R, et al. Anti-inflammatory activities of six types of tea in LPS-induced RAW264.7 cells[J]. Science and Technology of Food Industry, 2017, 38（19）: 67−73.
[3]	PANJI M, BEHMARD V, ZARE Z, et al. Synergistic effects of green tea extract and paclitaxel in the induction of mitochondrial apoptosis in ovarian cancer cell lines[J]. Gene,2021,787:145638. doi: 10.1016/j.gene.2021.145638
[4]	陈美艳, 刘芬, 林勇, 等. L-茶氨酸对CUMS抑郁大鼠海马和肠道损伤的干预作用研究[J]. 茶叶科学,2021,41(4):511−524. [CHEN M Y, LIU F, LIN Y, et al. Intervention effects of L-theanine on the damage of Hippocampus and gut in CUMS depressed rats[J]. Journal of Tea Science,2021,41(4):511−524.] CHEN M Y, LIU F, LIN Y, et al. Intervention effects of L-theanine on the damage of Hippocampus and gut in CUMS depressed rats[J]. Journal of Tea Science, 2021, 41（4）: 511−524.
[5]	YANG C S, WANG H, SHERIDAN Z P. Studies on prevention of obesity, metabolic syndrome, diabetes, cardiovascular diseases and cancer by tea[J]. Journal of Food and Drug Analysis,2018,26(1):1−13. doi: 10.1016/j.jfda.2017.10.010
[6]	YANG C S, ZHANG J, ZHANG L, et al. Mechanisms of body weight reduction and metabolic syndrome alleviation by tea[J]. Molecular Nutrition & Food Research,2016,60(1):160−174.
[7]	宛晓春. 茶叶生物化学[M]. 北京:中国农业出版社, 2003. [WAN X C. Tea biochemistry[M]. Beijing:China Agriculture Press, 2003.] WAN X C. Tea biochemistry[M]. Beijing: China Agriculture Press, 2003.
[8]	HIGDON J V, FREI B. Tea catechins and polyphenols:Health effects, metabolism, and antioxidant functions[J]. Critical Reviews in Food Science and Nutrition,2003,43(1):89−143. doi: 10.1080/10408690390826464
[9]	NAKAGAWA T, YOKOZAWA T. Direct scavenging of nitric oxide and superoxide by green tea[J]. Food and Chemical Toxicology, 2002, 40(PII S0278-6915(02)00169-212):1745−1750.
[10]	KINJO J, NAGAO T, TANAKA T, et al. Activity-guided fractionation of green tea extract with antiproliferative activity against human stomach cancer cells[J]. Biological and Pharmaceutical Bulletin,2002,25(9):1238−1240. doi: 10.1248/bpb.25.1238
[11]	DU G, ZHANG Z, WEN X, et al. Epigallocatechin gallate (EGCG) is the most effective cancer chemopreventive polyphenol in green tea[J]. Nutrients,2012,4(11):1679−1691. doi: 10.3390/nu4111679
[12]	BRAICU C, PILECKI V, BALACESCU O, et al. The relationships between biological activities and structure of flavan-3-ols[J]. International Journal of Molecular Sciences,2011,12(12):9342−9353. doi: 10.3390/ijms12129342
[13]	ICHIMATSU D, NOMURA M, NAKAMURA S, et al. Structure-activity relationship of flavonoids for inhibition of epidermal growth factor-induced transformation of JB6 Cl 41 cells[J]. Molecular Carcinogenesis,2007,46(6):436−445. doi: 10.1002/mc.20292
[14]	WANG R, PENG J, SHI X, et al. Change in membrane fluidity induced by polyphenols is highly dependent on the position and number of galloyl groups[J]. Biochim Biophys Acta, Biomembr,2022,1864(11):184015. doi: 10.1016/j.bbamem.2022.184015
[15]	WANG X, SONG K S, GUO Q X, et al. The galloyl moiety of green tea catechins is the critical structural feature to inhibit fatty-acid synthase[J]. Biochemical Pharmacology,2003,66(10):2039−2047. doi: 10.1016/S0006-2952(03)00585-9
[16]	FUJIMURA Y, UMEDA D, YAMADA K, et al. The impact of the 67 kDa laminin receptor on both cell-surface binding and anti-allergic action of tea catechins[J]. Archives of Biochemistry and Biophysics,2008,476(2):133−138. doi: 10.1016/j.abb.2008.03.002
[17]	MITANI S, OUCHI A, WATANABE E, et al. Stopped-flow kinetic study of the aroxyl radical-scavenging action of catechins and vitamin C in ethanol and micellar solutions[J]. Journal of Agricultural and Food Chemistry,2008,56(12):4406−4417. doi: 10.1021/jf703770m
[18]	MUKAI K, MITANI S, OHARA K, et al. Structure-activity relationship of the tocopherol-regeneration reaction by catechins[J]. Free Radical Biology and Medicine,2005,38(9):1243−1256. doi: 10.1016/j.freeradbiomed.2005.01.011
[19]	SUGIHARA N, TSUTSUI Y, TAGASHIRA T, et al. The ability of gallate and pyrogallol moieties of catechins to inhibit P-glycoprotein function[J]. Journal of Functional Foods,2011,3(4):298−304. doi: 10.1016/j.jff.2011.05.005
[20]	BABICH H, KRUPKA M E, NISSIM H A, et al. Differential in vitro cytotoxicity of (-)-epicatechin gallate (ECG) to cancer and normal cells from the human oral cavity[J]. Toxicology in Vitro,2005,19(2):231−242. doi: 10.1016/j.tiv.2004.09.001
[21]	CAI Y J, MA L P, HOU L F, et al. Antioxidant effects of green tea polyphenols on free radical initiated peroxidation of rat liver microsomes[J]. Chemistry and Physics of Lipids, 2002, 120(PII S0009-3084(02)00110-X1-2):109−117.
[22]	MÍKA M, KOSTOGRYS R B, FRANCZYK-ZARÓW M, et al. Anti-atherosclerotic activity of catechins depends on their stereoisomerism[J]. Atherosclerosis,2015,240(1):125−130. doi: 10.1016/j.atherosclerosis.2015.02.026
[23]	XIE L, GUO Y, CAI B, et al. Epimerization of epigallocatechin gallate to gallocatechin gallate and its anti-diabetic activity[J]. Medicinal Chemistry Research,2013,22(7):3372−3378. doi: 10.1007/s00044-012-0352-z
[24]	LEE S M, KIM C W, KIM J K, et al. GCG-rich tea catechins are effective in lowering cholesterol and triglyceride concentrations in hyperlipidemic rats[J]. Lipids,2008,43(5):419−429. doi: 10.1007/s11745-008-3167-4
[25]	TIMMEL M A, BYL J A W, OSHEROFF N. Epimerization of green tea catechins during brewing does not affect the ability to poison human type II topoisomerases[J]. Chemical Research in Toxicology,2013,26(4):622−628. doi: 10.1021/tx4000667
[26]	YOSHINO K, MIYASE T, SANO M. Preventive effects of C-2 epimeric isomers of tea catechins on mouse type I allergy[J]. Journal of Nutritional Science and Vitaminology,2010,56(3):211−215. doi: 10.3177/jnsv.56.211
[27]	刘志华, 孙晓波. 网络药理学:中医药现代化的新机遇[J]. 药学学报,2012,47(6):696−703. [LIU Z H, SUN X B. Network pharmacology:New opportunity for the modernization of traditional Chinese medicine[J]. Acta Pharmaceutica Sinica,2012,47(6):696−703.] LIU Z H, SUN X B. Network pharmacology: New opportunity for the modernization of traditional Chinese medicine[J]. Acta Pharmaceutica Sinica, 2012, 47（6）: 696−703.
[28]	LI S. Network pharmacology evaluation method guidance-draft[J]. World Journal of Traditional Chinese Medicine,2021,7(1):146.
[29]	ZHANG G, LI B, LEE C H, et al. Cysteine and glutathione mixed-disulfide conjugates of thiosulfinates:Chemical synthesis and biological activities[J]. Journal of Agricultural and Food Chemistry,2010,58(3):1564−1571. doi: 10.1021/jf9029354
[30]	MOSMANN T. Rapid colorimetric assay for cellular growth and survival:Application to proliferation and cytotoxicity assays[J]. Journal of Immunological Methods,1983,65(1−2):55−63. doi: 10.1016/0022-1759(83)90303-4
[31]	王腾飞, 段瑞斌, 杨佳丽, 等. 基于网络药理学和分子对接探讨毛建茶干预高脂血症的作用机制[J]. 食品科学,2023,44(9):7−14. [WANG T F, DUAN R B, YANG J L, et al. Exploring the mechanism of Dracocephalum rupestre hance tea interfering with hyperlipidemia based on network pharmacology and molecular docking[J]. Food Science,2023,44(9):7−14.] WANG T F, DUAN R B, YANG J L, et al. Exploring the mechanism of Dracocephalum rupestre hance tea interfering with hyperlipidemia based on network pharmacology and molecular docking[J]. Food Science, 2023, 44（9）: 7−14.
[32]	CHOI S J, HONG Y D, LEE B, et al. Separation of polyphenols and caffeine from the acetone extract of fermented tea leaves ( Camellia sinensis) using high-performance countercurrent chromatography[J]. Molecules,2015,20(7):13216−13225. doi: 10.3390/molecules200713216
[33]	GRIVENNIKOV S, KARIN M. Autocrine IL-6 signaling:A key event in tumorigenesis?[J]. Cancer Cell,2008,13(1):7−9. doi: 10.1016/j.ccr.2007.12.020
[34]	LANGOWSKI J L, ZHANG X, WU L, et al. IL-23 promotes tumour incidence and growth[J]. Nature,2006,442(7101):461−465. doi: 10.1038/nature04808
[35]	COURTOIS G, GILMORE T D. Mutations in the NF-kappaB signaling pathway:Implications for human disease[J]. Oncogene,2006,25(51):6831−6843. doi: 10.1038/sj.onc.1209939
[36]	VORONOV E, SHOUVAL D S, KRELIN Y, et al. IL-1 is required for tumor invasiveness and angiogenesis[J]. Proceedings of the National Academy of Sciences of the United States of America,2003,100(5):2645−2650.
[37]	SZLOSAREK P W, BALKWILL F R. Tumour necrosis factor alpha:A potential target for the therapy of solid tumors[J]. Lancet Oncol,2003,4(9):565−573. doi: 10.1016/S1470-2045(03)01196-3
[38]	FECHTNER S, SINGH A, CHOURASIA M, et al. Molecular insights into the differences in anti-inflammatory activities of green tea catechins on IL-1 β signaling in rheumatoid arthritis synovial fibroblasts[J]. Toxicology and Applied Pharmacology,2017,329:112−120. doi: 10.1016/j.taap.2017.05.016
[39]	KIM I, KIM D, LEE S, et al. Inhibition of IL-8 production by green tea polyphenols in human nasal fibroblasts and A549 epithelial cells[J]. Biological and Pharmaceutical Bulletin,2006,29(6):1120−1125. doi: 10.1248/bpb.29.1120
[40]	陈榆. 基于肝-肾-肠轴代谢及分子对接研究高氨基酸绿茶提取物对小鼠高尿酸血症的缓解作用[D]. 重庆:西南大学, 2022. [CHEN Y. Alleviating effect of green tea extract with high amino acid on hyperuricemia through the hepato-kidney-intestinal axis and molecular docking study[D]. Chongqing:Southwest University, 2022.] CHEN Y. Alleviating effect of green tea extract with high amino acid on hyperuricemia through the hepato-kidney-intestinal axis and molecular docking study[D]. Chongqing: Southwest University, 2022.
[41]	雷志伟, 林艺璐, 李露露, 等. 儿茶素及其类似物体外抗H1N1流感病毒活性及其构效关系的研究[J]. 贵州茶叶,2020,48(1):20−23. [LEI Z W, LIN Y L, LI L L, et al. In vitro antiviral activity of catechins and their analogs against H1N1 and their structure-activity relationship[J]. Journal of Guizhou Tea,2020,48(1):20−23.] LEI Z W, LIN Y L, LI L L, et al. In vitro antiviral activity of catechins and their analogs against H1N1 and their structure-activity relationship[J]. Journal of Guizhou Tea, 2020, 48（1）: 20−23.
[42]	UEKUSA Y, KAMIHIRA M, NAKAYAMA T. Dynamic behavior of tea catechins interacting with lipid membranes as determined by NMR spectroscopy[J]. Journal of Agricultural and Food Chemistry,2007,55(24):9986−9992. doi: 10.1021/jf0712402
[43]	CATURLA N, VERA-SAMPER E, VILLALAIN J, et al. The relationship between the antioxidant and the antibacterial properties of galloylated catechins and the structure of phospholipid model membranes[J]. Free Radical Biology and Medicine,2003,34(6):648−662. doi: 10.1016/S0891-5849(02)01366-7
[44]	HASHIMOTO T, KUMAZAWA S, NANJO F, et al. Interaction of tea catechins with lipid bilayers investigated with liposome systems[J]. Bioscience, Biotechnology, and Biochemistry,1999,63(12):2252−2255. doi: 10.1271/bbb.63.2252
[45]	GAO X, LIN X R, LI X F, et al. Cellular antioxidant, methylglyoxal trapping, and anti-inflammatory activities of cocoa tea ( Camellia ptilophylla Chang)[J]. Food & Function,2017,8(8):2836−2846.
[46]	LI K K, PENG J M, ZHU W, et al. Gallocatechin gallate (GCG) inhibits 3T3-L1 differentiation and lipopolysaccharide induced inflammation through MAPK and NF- κB signaling[J]. Journal of Functional Foods,2017,30:159−167. doi: 10.1016/j.jff.2017.01.016