Planta Med 2018; 84(18): 1334-1339
DOI: 10.1055/a-0646-4306
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Anti-inflammatory Ingenane Diterpenoids from the Roots of Euphorbia kansui

Jun-Sheng Zhang
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Peopleʼs Republic of China
,
Han-Zhuang Weng
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Peopleʼs Republic of China
,
Jia-Luo Huang
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Peopleʼs Republic of China
,
Gui-Hua Tang
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Peopleʼs Republic of China
,
Sheng Yin
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Peopleʼs Republic of China
› Author Affiliations
Further Information

Publication History

received 21 January 2018
revised 29 May 2018

accepted 14 June 2018

Publication Date:
25 June 2018 (online)

Abstract

Bioassay-guided fractionation of the ethanolic extract of the roots of Euphorbia kansui led to the isolation of two new ingenane diterpenoids, euphorkans A (1) and B (2), together with 16 known analogues (3 – 18). Their structures were determined by combined spectral and chemical methods. All the isolates were evaluated for their inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW264.7 macrophage cells. Compounds 1 – 6 and 10 – 13 exhibited pronounced inhibitory activity with IC50 values in the range of 2.78 – 10.6 µM, and were more potent than the positive control, quercetin (IC50 = 15.8 µM). Compounds 1 and 5 were selected for further assays toward the key inflammation mediators TNF-α and IL-6, and showed a significant inhibition in a dose-dependent manner. The preliminary mechanistic study revealed that 1 and 5 inhibited NF-κB activity, which may exert a role in their anti-inflammatory activity.

Supporting Information

 
  • References

  • 1 Lawrence T, Willoughby DA, Gilroy DW. Anti-inflammatory lipid mediators and insights into the resolution of inflmmation. Nat Rev Immunol 2002; 2: 787-795
  • 2 Weiss U. Inflammation. Nature 2008; 454: 427
  • 3 Ahmed AU. An overview of inflammation: mechanism and consequences. Front Biol 2011; 6: 274-281
  • 4 Tabas I, Glass CK. Anti-inflammatory therapy in chronic disease: challenges and opportunities. Science 2013; 339: 166-172
  • 5 Serhan CN, Chiang N, Van Dyke TE. Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol 2008; 8: 349-361
  • 6 Tak PP, Firestein GS. NF-κB: a key role in inflammatory diseases. J Clin Invest 2001; 107: 7-11
  • 7 Lee JW, Bae CJ, Choi YJ, Kim SI, Kim NH, Lee HJ, Kim SS, Kwon YS, Chun W. 3,4,5-Trihydroxycinnamic acid inhibits LPS-induced iNOS expression by suppressing NF-κB activation in BV2 microglial cells. Korean J Physiol Pharmacol 2012; 16: 107-112
  • 8 China Pharmacopoeia Committee. China Pharmacopoeia. Beijing, China: Medical Pharmaceutical Science and Technology Publishing House; 2010
  • 9 Fei DQ, Dong LL, Qi FM, Fan GX, Li HH, Li ZY, Zhang ZX. Euphorikanin A, a diterpenoid lactone with a fused 5/6/7/3 ring system from Euphorbia kansui . Org Lett 2016; 18: 2844-2847
  • 10 Pan Q, Ip FCF, Ip NY, Zhu HX, Min ZD. Activity of macrocyclic jatrophane diterpenes from Euphorbia kansui in a TrkA fibroblast survival assay. J Nat Prod 2004; 67: 1548-1551
  • 11 Wang LY, Wang NL, Yao XS, Miyata S, Kitanaka S. Euphane and tirucallane triterpenes from the roots of Euphorbia kansui and their in vitro effects on the cell division of xenopus. J Nat Prod 2003; 66: 630-633
  • 12 Wu TS, Lin YM, Haruna M, Pan DJ, Shingu T, Chen YP, Hsu HY. Antitumor agents, 119. Kansuiphorins A and B, two novel antileukemic diterpene esters from Euphorbia kansui . J Nat Prod 1991; 54: 823-829
  • 13 Zhang JS, Tang YQ, Huang JL, Li W, Zou YH, Tang GH, Yin S. Bioactive diterpenoids from Croton laevigatus . Phytochemistry 2017; 144: 151-158
  • 14 Zhu JY, Cheng B, Zheng YJ, Dong Z, Lin SL, Tang GH, Gu Q, Yin S. Enantiomeric neolignans and sesquineolignans from Jatropha integerrima and their absolute configurations. RSC Adv 2015; 5: 12202-12208
  • 15 Shi J, Li Z, Nitoda T, Izumi M, Kanzaki H, Baba N, Kauazu K, Nakajima S. Antinematodal activities of ingenane diterpenes from Euphorbia kansui and their derivatives against the pine wood nematode (Bursaphelenchus xylophilus). Z Naturforsch C 2008; 63: 59-65
  • 16 Matsumoto T, Cyong JC, Yamada H. Stimulatory effects of ingenols from Euphorbia kansui on the expression of macrophage Fc receptor. Planta Med 1992; 58: 255-258
  • 17 Ott HH, Hecker E. Highly irritant ingenane type diterpene esters from Euphorbia cyparissias L. Experientia 1981; 37: 88-91
  • 18 Wang LY, Wang NL, Yao XS, Miyata S, Kitanaka S. Diterpenes from the roots of Euphorbia kansui and their in vitro effects on the cell division of xenopus. J Nat Prod 2002; 65: 1246-1251
  • 19 Wang LY, Wang NL, Yao XS, Miyata S, Kitanaka S. Diterpenes from the roots of Euphorbia kansui and their in vitro effects on the cell division of xenopus (part 2). Chem Pharm Bull 2003; 51: 935-941
  • 20 Shi JX, Li ZX, Nitoda T, Izumi M, Kanzaki H, Baba N, Kauazu K, Nakajima S. Three antinematodal diterpenes from Euphorbia kansui . Biosci Biotechnol Biochem 2007; 71: 1086-1089
  • 21 Pan DJ, Hu CQ, Chang JJ, Lee TTY, Chen YP, Hsu HY, McPhail DR, McPhail AT, Lee KH. Antitumor agents. Part 117. Kansuiphorin-C and -D, cytotoxic diterpenes from Euphorbia kansui . Phytochemistry 1991; 30: 1018-1020
  • 22 Zhang L, Gao L, Li Z, Yan X, Yang Y, Tang YP, Cao YD, Ding AW. Bio-guided isolation of the cytotoxic terpenoids from the roots of Euphorbia kansui against human normal cell lines L-O2 and GES-1. Int J Mol Sci 2012; 13: 11247-11259
  • 23 Uemura D, Ohwaki H, Hirata Y, Chen YP, Hsu HY. Isolation and structures of 20-deoxyingenol, a new diterpene, its derivatives, and an ingenol derivative obtained from “kansui”. Tetrahedron Lett 1974; 29: 2527-2528
  • 24 Teng RW, McManus D, Aylward J, Ogbourne S, Armstrong D, Mau SL, Johns J, Bacic A. Biotransformation of ingenol-3-angelate in four plant cell suspension cultures. Biocatal Biotransform 2009; 27: 186-194
  • 25 Zou YH, Zhao L, Xu YK, Bao JM, Liu X, Zhang JS, Li W, Ahmed A, Yin S, Tang GH. Anti-inflammatory sesquiterpenoids from the Traditional Chinese Medicine Salvia plebeia: Regulates pro-inflammatory mediators through inhibition of NF-κB and Erk1/2 signaling pathways in LPS-induced RAW264.7 cells. J Ethnopharmacol 2018; 210: 95-106
  • 26 Chan PM, Tan YS, Chua KH, Sabaratnam V, Kuppusamy UR. Attenuation of inflammatory mediators (TNF-α and nitric oxide) and up-regulation of IL-10 by wild and domesticated basidiocarps of Amauroderma rugosum (Blume & T. Nees) torrend in LPS-stimulated RAW264.7 cells. PLoS One 2015; 10: e0139593/1-e/21
  • 27 Baldwin jr. AS. The NF-κB and IκB proteins: new discoveries and insights. Annu Rev Immunol 1996; 14: 649-681
  • 28 Lee JW, Jin Q, Jang H, Lee D, Han SB, Kim Y, Hong JT, Lee MK, Hwang BY. Jatrophane and ingenane-type diterpenoids from Euphorbia kansui inhibit the LPS-induced NO production in RAW264.7 cells. Bioorg Med Chem Lett 2016; 26: 3351-3354
  • 29 Nunomura S, Kitanaka S, Ra S. 3-O-(2,3-dimethylbutanoyl)-13-O-decanoylingenol from Euphorbia kansui suppresses IgE-mediated mast cell activation. Biol Pharm Bull 2006; 29: 286-290