Top

Published in:

01-06-2019 | Chronic Inflammatory Bowel Disease | Original Paper

Natural CAC chemopreventive agents from Ilex rotunda Thunb.

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

Published in: Journal of Natural Medicines | Issue 3/2019

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.

Available only for authorised users

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90PubMedCrossRef

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

Grivennikov SI (2015) Inflammation and colorectal cancer: colitis-associated neoplasia. Semin Immunopathol 35:229–244CrossRef

Lakatos PLLL (2008) Risk for colorectal cancer in ulcerative colitis: changes, causes and management strategies. World J Gastroenterol 14:3937–3947PubMedPubMedCentralCrossRef

Baumgart DC, Sandborn WJ (2012) Crohn’s disease. Lancet 380:1590–1605PubMedCrossRef

Danese S, Fiocchi C (2011) Medical progress. N Engl J Med 365:1713–1725PubMedCrossRef

Neurath MF (2014) Cytokines in inflammatory bowel disease. Nat Rev Immunol 14:329–342PubMedCrossRef

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

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.

Lu XH (2014) Pharmaceutical king tree. Iron Holly Guangxi Forest 1:28–29

11.

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.

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.

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.

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.

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.

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.

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

18.

colitis-associated cancer. Cancers (Basel) 3:2811–2826CrossRef

19.

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.

Li WK, Xiao PG, Chen ZL (1999) Study on chemical constituents of Huanghua Yuanzhi Chin. J Tradit Chin Med 24:477–479

21.

Zhao AH, Zhao QS, Li RT, Sun HD (2004) Chemical composition of kidney tea. J Plant Diver Resour 26:563–568

22.

Wang W, Yang CR, Zhang YJ (2009) Phenolic ingredients in the fruit of the fruit. Plant Diver Resour 31:284–288

23.

Ming CL, Tang SA, Duan HQ (2010) Chemical consitituents from Onychium japonicum. Chin Tradit Herb Drugs 41:685–688

24.

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.

Liu R, Yu SS, Pei YH (2009) Chemical constituents from leaves of Albizia chinensis. China J Chin Mater Med 34:2063–2066

26.

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.

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.

Mao CM, Li SS, Xu QM, Yang SL (2016) Study on the chemical constituents of the stalk. Chin Herb Med 47:891–896

29.

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.

Wu Z, Ouyang M, Yang C (1999) Polyphenolic constituents of Salvia sonchifolia. Acta Bot Yunnanica 21:393–398

31.

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.

Jakupovic J, Zdero C, Paredes L, Bohlmann F (1988) Sesquiterpene glycosides and other constituents from osteospermum species. Phytochemistry 27:2881–2886CrossRef

33.

Kitagawa I, Wei H, Nagao S, Mahmud T, Kobayashi M, Uji T, Shibuya H (1996) Chem Pharm Bull 44:1162–1167CrossRef

34.

He W, Zhang YM (2012) Study on chemical constituents of stalk. Chin Herb Med 43:1276–1279

35.

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.

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.

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.

Xia WZ, Cui BS, Li S (2016) Study on the chemical constituents of Sijiqing. Chin Herb Med 47:1272–1277

39.

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.

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.

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.

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.

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.

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

Title: Natural CAC chemopreventive agents from Ilex rotunda Thunb.
Authors: Yueqing Han
Lin Zhang
Wei Li
Xinran Liu
Jiao Xiao
Gang Chen
Ning Li
Publication date: 01-06-2019
Publisher: Springer Singapore
Keyword: Chronic Inflammatory Bowel Disease
Published in: Journal of Natural Medicines / Issue 3/2019
Print ISSN: 1340-3443
Electronic ISSN: 1861-0293
DOI: https://doi.org/10.1007/s11418-019-01281-z

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Natural CAC chemopreventive agents from Ilex rotunda Thunb.

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2019

New otonecine-type pyrrolizidine alkaloid from Petasites japonicus

Salacia chinensis stem extract and its thiosugar sulfonium constituent, neokotalanol, improves HbA1c levels in ob/ob mice

B-ring-homo-tonghaosu, isolated from Chrysanthemum morifolium capitulum, acts as a peroxisome proliferator-activated receptor-γ agonist

Two new quassinoids and other constituents from Picrasma javanica wood, and their biological activities

Correction to: Laxative effect of repeated Daiokanzoto is attributable to decrease in aquaporin-3 expression in the colon

Inhibition of melanin production by anthracenone dimer glycosides isolated from Cassia auriculata seeds