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Erschienen in: Journal of Natural Medicines 3/2019

13.02.2019 | Original Paper

Natural CAC chemopreventive agents from Ilex rotunda Thunb.

verfasst von: Yueqing Han, Lin Zhang, Wei Li, Xinran Liu, Jiao Xiao, Gang Chen, Ning Li

Erschienen in: Journal of Natural Medicines | Ausgabe 3/2019

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Abstract

Colitis-associated cancer (CAC) is one of the most serious complications of inflammatory bowel disease. The pathogenesis of CAC is complicated and so far elusive, and the anti-inflammatory effect does not assure CAC preventive activity, making it difficult to discover CAC preventive drugs. In this study, we report the CAC preventive effect of the ethyl acetate (EIR) of Ilex rotunda Thunb., a traditional Chinese herbal medicine being clinically used to treat intestinal disease. We also report the results of screening for CAC preventive agents from EIR via a nuclear factor-kappa B (NF-κB) translocation model in Caco2 cells, since activated NF-κB can be used by tumor cells at the early stage of tumorigenesis. Twenty-four components were isolated from EIR and identified by multiple chromatography and spectral analysis. MTT experiments in IEC-6 and RAW264.7 cells showed that all 24 compounds were toxic-free to normal cell lines. Furthermore, compound rotundic acid (RA) (19) exhibited an inhibitory effect on LPS-induced NF-κB translocation in Caco2 cells. Moreover, RA did not induce apoptosis in Caco2 tumor cells while possessing an anti-inflammatory effect both in immune and intestinal epithelium cells (RAW264.7 and IEC-6 cells, respectively). Removing RA (19) and its 28-O-glucopyranoside (17) from EIR definitely undermined the in vivo CAC preventive activity of EIR. Therefore, the current study suggested that RA (19) could be a potential therapeutic agent against CAC.
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Literatur
1.
Zurück zum Zitat Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90PubMedCrossRef Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90PubMedCrossRef
2.
Zurück zum Zitat Breynaert C, Vermeire S, Rutgeerts F, Van AG (2008) Dysplasia and colorectal cancer in inflammatory bowel disease: a result of inflammation or an intrinsic risk? Acta Gastroenterol Belg 71:367–372PubMed Breynaert C, Vermeire S, Rutgeerts F, Van AG (2008) Dysplasia and colorectal cancer in inflammatory bowel disease: a result of inflammation or an intrinsic risk? Acta Gastroenterol Belg 71:367–372PubMed
3.
Zurück zum Zitat Grivennikov SI (2015) Inflammation and colorectal cancer: colitis-associated neoplasia. Semin Immunopathol 35:229–244CrossRef Grivennikov SI (2015) Inflammation and colorectal cancer: colitis-associated neoplasia. Semin Immunopathol 35:229–244CrossRef
4.
Zurück zum Zitat Lakatos PLLL (2008) Risk for colorectal cancer in ulcerative colitis: changes, causes and management strategies. World J Gastroenterol 14:3937–3947PubMedPubMedCentralCrossRef Lakatos PLLL (2008) Risk for colorectal cancer in ulcerative colitis: changes, causes and management strategies. World J Gastroenterol 14:3937–3947PubMedPubMedCentralCrossRef
7.
8.
Zurück zum Zitat Zhu Y, Zhou J, Yi Feng, Chen LY, Zhang LH, Yang F, Zha HR, Wang XX, Han X, Shu C, Song Y, Li QJ, Guo B, Zhu B (2018) Control of intestinal inflammation, colitis-associated tumorigenesis, and macrophage polarization by fibrinogen-like protein2. Front Immunol 9:87–117PubMedPubMedCentralCrossRef Zhu Y, Zhou J, Yi Feng, Chen LY, Zhang LH, Yang F, Zha HR, Wang XX, Han X, Shu C, Song Y, Li QJ, Guo B, Zhu B (2018) Control of intestinal inflammation, colitis-associated tumorigenesis, and macrophage polarization by fibrinogen-like protein2. Front Immunol 9:87–117PubMedPubMedCentralCrossRef
9.
Zurück zum Zitat Yang B, Zhu JP, Rong L, Jing Jin, Cao D, Hui Li, Zhou XH, Zhao ZX (2018) Triterpenoids with antiplatelet aggregation activity from Ilex rotunda. Phytochemistry 145:179–186PubMedCrossRef Yang B, Zhu JP, Rong L, Jing Jin, Cao D, Hui Li, Zhou XH, Zhao ZX (2018) Triterpenoids with antiplatelet aggregation activity from Ilex rotunda. Phytochemistry 145:179–186PubMedCrossRef
10.
Zurück zum Zitat Lu XH (2014) Pharmaceutical king tree. Iron Holly Guangxi Forest 1:28–29 Lu XH (2014) Pharmaceutical king tree. Iron Holly Guangxi Forest 1:28–29
11.
Zurück zum Zitat Hu ZY, Tang M, Zhang QH, Zhao LC (2018) Research progress on chemical composition and pharmacological action of Ilex rotunda. J Changchun Norm Univ 37:69–74 Hu ZY, Tang M, Zhang QH, Zhao LC (2018) Research progress on chemical composition and pharmacological action of Ilex rotunda. J Changchun Norm Univ 37:69–74
12.
Zurück zum Zitat Huo X, Liu D, Gao L, Li Y (2016) Flavonoids extracted from licorice prevents colitis-associated carcinogenesis in AOM/DSS mouse model. Int J Mol Sci 17:1343–1370PubMedCentralCrossRef Huo X, Liu D, Gao L, Li Y (2016) Flavonoids extracted from licorice prevents colitis-associated carcinogenesis in AOM/DSS mouse model. Int J Mol Sci 17:1343–1370PubMedCentralCrossRef
13.
Zurück zum Zitat Blennerhassett MG, Bovell FM, Lourenssen S, Mchugh KM (1999) Characteristics of inflammation-induced hypertrophy of rat intestinal smooth muscle cell. Dig Dis Sci 44:1265–1272PubMedCrossRef Blennerhassett MG, Bovell FM, Lourenssen S, Mchugh KM (1999) Characteristics of inflammation-induced hypertrophy of rat intestinal smooth muscle cell. Dig Dis Sci 44:1265–1272PubMedCrossRef
14.
Zurück zum Zitat Kyung-Sook C, Se-Yun C, Seong-Soo R, Minho L, Hyo-Jin A (2018) Chemopreventive effect of Aster glehni on inflammation-induced colorectal carcinogenesis in mice. Nutrients 10:202–213CrossRef Kyung-Sook C, Se-Yun C, Seong-Soo R, Minho L, Hyo-Jin A (2018) Chemopreventive effect of Aster glehni on inflammation-induced colorectal carcinogenesis in mice. Nutrients 10:202–213CrossRef
15.
Zurück zum Zitat Rajan TS, Giacoppo S, Iori R, Rosalind G, Nicola D, Grass G, Pollastro F, Bramanti P, Mazzon E (2016) Anti-inflammatory and antioxidant effects of a combination of cannabidiol and moringin in LPS-stimulated macrophages. Fitoterapia 112:104–105PubMedCrossRef Rajan TS, Giacoppo S, Iori R, Rosalind G, Nicola D, Grass G, Pollastro F, Bramanti P, Mazzon E (2016) Anti-inflammatory and antioxidant effects of a combination of cannabidiol and moringin in LPS-stimulated macrophages. Fitoterapia 112:104–105PubMedCrossRef
16.
Zurück zum Zitat Tao L, Zhang F, Hao L, Wu J, Jia J, Liu JY, Zeng LT, Zhen X (2014) 1-O-Tigloyl-1-O-deacetyl-nimbolinin B inhibits LPS-stimulated inflammatory responses by suppressing NF-κB and JNK activation in microglia cells. Pharmacol Sci 125:364–374CrossRef Tao L, Zhang F, Hao L, Wu J, Jia J, Liu JY, Zeng LT, Zhen X (2014) 1-O-Tigloyl-1-O-deacetyl-nimbolinin B inhibits LPS-stimulated inflammatory responses by suppressing NF-κB and JNK activation in microglia cells. Pharmacol Sci 125:364–374CrossRef
17.
Zurück zum Zitat Chun SC, Jee SY, Sang GL, Park SJ, Lee JR, Sang CK (2007) Anti-inflammatory activity of the methanol extract of moutan cortex in LPS-activated raw264.7 cells. Evid Based Complement Altern Med 4:327–333CrossRef Chun SC, Jee SY, Sang GL, Park SJ, Lee JR, Sang CK (2007) Anti-inflammatory activity of the methanol extract of moutan cortex in LPS-activated raw264.7 cells. Evid Based Complement Altern Med 4:327–333CrossRef
19.
Zurück zum Zitat Zhang D, Mi M, Jiang F, Sun Y, Li Y, Yang L, Fan L, Li Q, Meng J, Yue Z, Liu L, Mei Q (2015) Apple polysaccharide reduces NF-Kb mediated colitis-associated colon carcinogenesis. Nutr Cancer 67:177–190PubMedCrossRef Zhang D, Mi M, Jiang F, Sun Y, Li Y, Yang L, Fan L, Li Q, Meng J, Yue Z, Liu L, Mei Q (2015) Apple polysaccharide reduces NF-Kb mediated colitis-associated colon carcinogenesis. Nutr Cancer 67:177–190PubMedCrossRef
20.
Zurück zum Zitat Li WK, Xiao PG, Chen ZL (1999) Study on chemical constituents of Huanghua Yuanzhi Chin. J Tradit Chin Med 24:477–479 Li WK, Xiao PG, Chen ZL (1999) Study on chemical constituents of Huanghua Yuanzhi Chin. J Tradit Chin Med 24:477–479
21.
Zurück zum Zitat Zhao AH, Zhao QS, Li RT, Sun HD (2004) Chemical composition of kidney tea. J Plant Diver Resour 26:563–568 Zhao AH, Zhao QS, Li RT, Sun HD (2004) Chemical composition of kidney tea. J Plant Diver Resour 26:563–568
22.
Zurück zum Zitat Wang W, Yang CR, Zhang YJ (2009) Phenolic ingredients in the fruit of the fruit. Plant Diver Resour 31:284–288 Wang W, Yang CR, Zhang YJ (2009) Phenolic ingredients in the fruit of the fruit. Plant Diver Resour 31:284–288
23.
Zurück zum Zitat Ming CL, Tang SA, Duan HQ (2010) Chemical consitituents from Onychium japonicum. Chin Tradit Herb Drugs 41:685–688 Ming CL, Tang SA, Duan HQ (2010) Chemical consitituents from Onychium japonicum. Chin Tradit Herb Drugs 41:685–688
24.
Zurück zum Zitat Hu J, Zhang WD, Liu RH, Zhang C, Shen YH, Xu XH, Liang MJ, Li HL (2006) Chemical constituents in root of Zanthoxylum nitidum. China J Chin Mater Med 31:1689–1691 Hu J, Zhang WD, Liu RH, Zhang C, Shen YH, Xu XH, Liang MJ, Li HL (2006) Chemical constituents in root of Zanthoxylum nitidum. China J Chin Mater Med 31:1689–1691
25.
Zurück zum Zitat Liu R, Yu SS, Pei YH (2009) Chemical constituents from leaves of Albizia chinensis. China J Chin Mater Med 34:2063–2066 Liu R, Yu SS, Pei YH (2009) Chemical constituents from leaves of Albizia chinensis. China J Chin Mater Med 34:2063–2066
26.
Zurück zum Zitat Zhao D, Wu TY, Guan YQ, Ma GX, Zhang J, Shi LL (2017) Chemical constituents from roots of Stelleropsis tianschanica. China J Chin Mater Med 9:3379–3384 Zhao D, Wu TY, Guan YQ, Ma GX, Zhang J, Shi LL (2017) Chemical constituents from roots of Stelleropsis tianschanica. China J Chin Mater Med 9:3379–3384
27.
Zurück zum Zitat Wang CH, Wei PL, Yan SK, Jin HZ, Zhang DW (2014) Study on chemical constituents of ethyl acetate fraction of Minnan. Nat Prod Res Dev 26:33–37 Wang CH, Wei PL, Yan SK, Jin HZ, Zhang DW (2014) Study on chemical constituents of ethyl acetate fraction of Minnan. Nat Prod Res Dev 26:33–37
28.
Zurück zum Zitat Mao CM, Li SS, Xu QM, Yang SL (2016) Study on the chemical constituents of the stalk. Chin Herb Med 47:891–896 Mao CM, Li SS, Xu QM, Yang SL (2016) Study on the chemical constituents of the stalk. Chin Herb Med 47:891–896
29.
Zurück zum Zitat Meerungrueang W, Panichayupakaranant P (2014) Antimicrobial activities of some Thai traditional medical longevity formulations from plants and antibacterial compounds from Ficus foveolata. Pharm Microbiol 52:1104–1109 Meerungrueang W, Panichayupakaranant P (2014) Antimicrobial activities of some Thai traditional medical longevity formulations from plants and antibacterial compounds from Ficus foveolata. Pharm Microbiol 52:1104–1109
30.
Zurück zum Zitat Wu Z, Ouyang M, Yang C (1999) Polyphenolic constituents of Salvia sonchifolia. Acta Bot Yunnanica 21:393–398 Wu Z, Ouyang M, Yang C (1999) Polyphenolic constituents of Salvia sonchifolia. Acta Bot Yunnanica 21:393–398
31.
Zurück zum Zitat Li YS, Tian Y, Guo P, Yang JQ, Xu XD (2014) Synthesis and biological activity of caffeate derivatives. Chin Herb Med 45:3538–3542 Li YS, Tian Y, Guo P, Yang JQ, Xu XD (2014) Synthesis and biological activity of caffeate derivatives. Chin Herb Med 45:3538–3542
32.
Zurück zum Zitat Jakupovic J, Zdero C, Paredes L, Bohlmann F (1988) Sesquiterpene glycosides and other constituents from osteospermum species. Phytochemistry 27:2881–2886CrossRef Jakupovic J, Zdero C, Paredes L, Bohlmann F (1988) Sesquiterpene glycosides and other constituents from osteospermum species. Phytochemistry 27:2881–2886CrossRef
33.
Zurück zum Zitat Kitagawa I, Wei H, Nagao S, Mahmud T, Kobayashi M, Uji T, Shibuya H (1996) Chem Pharm Bull 44:1162–1167CrossRef Kitagawa I, Wei H, Nagao S, Mahmud T, Kobayashi M, Uji T, Shibuya H (1996) Chem Pharm Bull 44:1162–1167CrossRef
34.
Zurück zum Zitat He W, Zhang YM (2012) Study on chemical constituents of stalk. Chin Herb Med 43:1276–1279 He W, Zhang YM (2012) Study on chemical constituents of stalk. Chin Herb Med 43:1276–1279
35.
Zurück zum Zitat Yu Y, Gao W, Yi Dai, Li XX, Li JM, Yao XS (2010) Study on lignans in gardenia. Chin Herb Med 41:509–514 Yu Y, Gao W, Yi Dai, Li XX, Li JM, Yao XS (2010) Study on lignans in gardenia. Chin Herb Med 41:509–514
36.
Zurück zum Zitat Sun H, Zhang XQ, Cai Y, Han WL, Wang Y, Ye WC (2009) Study on chemical constituents of Ilex rotunda Thunb. Chem Ind For Prod 29:111–114 Sun H, Zhang XQ, Cai Y, Han WL, Wang Y, Ye WC (2009) Study on chemical constituents of Ilex rotunda Thunb. Chem Ind For Prod 29:111–114
37.
Zurück zum Zitat Nguyen HT, Ho DV, Vo HQ, Le HQ, Nquyen HM, Kodama T, Ito T, Morita H, Raal A (2017) Antibacterial activities of chemical constituents from the aerial parts of Hedyotis pilulifera. Pharm Microbiol 55:787–791 Nguyen HT, Ho DV, Vo HQ, Le HQ, Nquyen HM, Kodama T, Ito T, Morita H, Raal A (2017) Antibacterial activities of chemical constituents from the aerial parts of Hedyotis pilulifera. Pharm Microbiol 55:787–791
38.
Zurück zum Zitat Xia WZ, Cui BS, Li S (2016) Study on the chemical constituents of Sijiqing. Chin Herb Med 47:1272–1277 Xia WZ, Cui BS, Li S (2016) Study on the chemical constituents of Sijiqing. Chin Herb Med 47:1272–1277
39.
Zurück zum Zitat Wang L, Zhang CF, Layba M, Zhang M (2011) Study on the constituents of triterpenoids and sterols from broad-leaved ebony in West Africa. Chin J Tradit Chin Med 18:2511–2514 Wang L, Zhang CF, Layba M, Zhang M (2011) Study on the constituents of triterpenoids and sterols from broad-leaved ebony in West Africa. Chin J Tradit Chin Med 18:2511–2514
40.
Zurück zum Zitat Yao ZR, Li J, Zhou SX, Zhang W, Tu PF (2009) Triterpenoids in the sacral leaves. Chin J Tradit Chin Med 34:999–1001 Yao ZR, Li J, Zhou SX, Zhang W, Tu PF (2009) Triterpenoids in the sacral leaves. Chin J Tradit Chin Med 34:999–1001
41.
Zurück zum Zitat Liu WJ, Peng YY, Chen H, Liu XF, Liang JY, Sun JB (2017) Triterpenoid saponins with potential cytotoxic activities from the root bark of Ilex rotunda Thunb. Chem Biodivers 2017:14 Liu WJ, Peng YY, Chen H, Liu XF, Liang JY, Sun JB (2017) Triterpenoid saponins with potential cytotoxic activities from the root bark of Ilex rotunda Thunb. Chem Biodivers 2017:14
42.
Zurück zum Zitat Li S, Zhao J, Wang W (2015) Seven new triterpenoids from the aerial parts of Ilex cornuta, and protective effects against H2O2-induced myocardial cell injury. Phytochem Lett 14:178–184CrossRef Li S, Zhao J, Wang W (2015) Seven new triterpenoids from the aerial parts of Ilex cornuta, and protective effects against H2O2-induced myocardial cell injury. Phytochem Lett 14:178–184CrossRef
43.
Zurück zum Zitat Ratnam NM, Peterson JM, Talbert EE, Ladner KJ, Rajasekera PV, Schmidt CR, Dillhoff ME, Swanson BJ, Haverick E, Kladney RD, Williams TM, Leone GW, Wang DJ, Guttridge DC (2017) NF-κB regulates GDF-15 to suppress macrophage surveillance during early tumor development. J Clin Invest 127:3796–3809PubMedPubMedCentralCrossRef Ratnam NM, Peterson JM, Talbert EE, Ladner KJ, Rajasekera PV, Schmidt CR, Dillhoff ME, Swanson BJ, Haverick E, Kladney RD, Williams TM, Leone GW, Wang DJ, Guttridge DC (2017) NF-κB regulates GDF-15 to suppress macrophage surveillance during early tumor development. J Clin Invest 127:3796–3809PubMedPubMedCentralCrossRef
44.
Zurück zum Zitat Li F, Zhang J, Arfuso F, Chinnathambi A, Zayed ME, Alharbi SA, Kumar AP, Ahn KS, Sethi G (2015) NF-κB in cancer therapy. Arch Toxicol 89:711–731PubMedCrossRef Li F, Zhang J, Arfuso F, Chinnathambi A, Zayed ME, Alharbi SA, Kumar AP, Ahn KS, Sethi G (2015) NF-κB in cancer therapy. Arch Toxicol 89:711–731PubMedCrossRef
Metadaten
Titel
Natural CAC chemopreventive agents from Ilex rotunda Thunb.
verfasst von
Yueqing Han
Lin Zhang
Wei Li
Xinran Liu
Jiao Xiao
Gang Chen
Ning Li
Publikationsdatum
13.02.2019
Verlag
Springer Singapore
Erschienen in
Journal of Natural Medicines / Ausgabe 3/2019
Print ISSN: 1340-3443
Elektronische ISSN: 1861-0293
DOI
https://doi.org/10.1007/s11418-019-01281-z

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