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Planta Med 2012; 78(10): 1002-1009
DOI: 10.1055/s-0031-1298621
Natural Product Chemistry
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Sesquiterpene Lactones from Inula hupehensis Inhibit Nitric Oxide Production in RAW264.7 Macrophages

Jiang-Jiang Qin
1   School of Pharmacy, Shanghai Jiao Tong University, Shanghai, PR China
4   Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, USA
,
Jia-Xian Zhu
1   School of Pharmacy, Shanghai Jiao Tong University, Shanghai, PR China
,
Qi Zeng
1   School of Pharmacy, Shanghai Jiao Tong University, Shanghai, PR China
,
Xiang-Rong Cheng
1   School of Pharmacy, Shanghai Jiao Tong University, Shanghai, PR China
,
Shou-De Zhang
1   School of Pharmacy, Shanghai Jiao Tong University, Shanghai, PR China
,
Hui-Zi Jin
1   School of Pharmacy, Shanghai Jiao Tong University, Shanghai, PR China
,
Wei-Dong Zhang
1   School of Pharmacy, Shanghai Jiao Tong University, Shanghai, PR China
2   School of Pharmacy, King Saud University, Riyadh, Saudi Arabia
3   Department of Phytochemistry, Second Military Medical University, Shanghai, PR China
› Author Affiliations
Further Information

Publication History

received 15 December 2011
revised 12 March 2012

accepted 26 April 2012

Publication Date:
30 May 2012 (online)

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Abstract

Phytochemical investigation of the aerial parts of Inula hupehensis Ling. led to the isolation and identification of 27 sesquiterpene lactones (1–27), including three new eudesmanolides (3–5), three new germacranolides (9–11), one new xanthanolide (16), two new carabrone derivatives (25–26), and 18 known sesquiterpene lactones. The structures were elucidated by extensive spectroscopic methods and comparison to previously reported spectroscopic data. All compounds were evaluated for their inhibitory effects against LPS-induced nitric oxide production in RAW264.7 macrophages, and compound 5 showed the strongest activity with the IC50 value of 3.2 ± 0.4 µM.

Key words

Inula hupehensis Ling. - Asteraceae - sesquiterpene lactones - nitric oxide production - structure-activity relationships

Supporting Information

 

  • References

  • 1 Zhang SD, Qin JJ, Jin HZ, Yin YH, Li HL, Yang XW, Li X, Shan L, Zhang WD. Sesquiterpenoids from Inula racemosa Hook. f. inhibit nitric oxide production. Planta Med advance online publication 14.10.2011; DOI: 10.1055/s-0031-1280294.
    PubMedGoogle Scholar
  • 2 Qin JJ, Zhu JX, Zeng Q, Cheng XR, Zhu Y, Zhang SD, Shan L, Jin HZ, Zhang WD. Pseudoguaianolides and guaianolides from Inula hupehensis as potential anti-inflammatory agents. J Nat Prod 2011; 74: 1881-1887
    CrossrefPubMedGoogle Scholar
  • 3 Cheng XR, Zeng Q, Ren J, Qin JJ, Zhang SD, Shen YH, Zhu JX, Zhang F, Chang RJ, Zhu Y, Zhang WD, Jin HZ. Sesquiterpene lactones from Inula falconeri, a plant endemic to the Himalayas, as potential anti-inflammatory agents. Eur J Med Chem 2011; 46: 5408-5415
    CrossrefPubMedGoogle Scholar
  • 4 Qin JJ, Jin HZ, Zhu JX, Fu JJ, Zeng Q, Cheng XR, Zhu Y, Shan L, Zhang SD, Pan YX, Zhang WD. New sesquiterpenes from Inula japonica Thunb. with their inhibitory activities against LPS-induced NO production in RAW264.7 macrophages. Tetrahedron 2010; 66: 9379-9388
    CrossrefPubMedGoogle Scholar
  • 5 Nie LY, Qin JJ, Huang Y, Yan L, Liu YB, Pan YX, Jin HZ, Zhang WD. Sesquiterpenoids from Inula lineariifolia inhibit nitric oxide production. J Nat Prod 2010; 73: 1117-1120
    CrossrefPubMedGoogle Scholar
  • 6 Qin JJ, Huang Y, Wang D, Cheng XR, Zeng Q, Zhang SD, Hu ZL, Jin HZ, Zhang WD. Lineariifolianoids A−D, rare unsymmetrical sesquiterpenoid dimers comprised by xanthane and guaiane framework units from Inula lineariifolia . RSC Adv 2012; 2: 1307-1309
    CrossrefPubMedGoogle Scholar
  • 7 Qin JJ, Wang LY, Zhu JX, Jin HZ, Fu JJ, Liu XF, Li HL, Zhang WD. Neojaponicone A, a bioactive sesquiterpene lactone dimer with an unprecedented carbon skeleton from Inula japonica . Chem Commun 2011; 47: 1222-1224
    CrossrefPubMedGoogle Scholar
  • 8 Qin JJ, Jin HZ, Zhu JX, Fu JJ, Hu XJ, Liu XH, Zhu Y, Yan SK, Zhang WD. Japonicones E–L, dimeric sesquiterpene lactones from Inula japonica Thunb. Planta Med 2010; 76: 278-283
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Qin JJ, Jin HZ, Fu JJ, Hu XJ, Wang Y, Yan SK, Zhang WD. Japonicones A−D, bioactive dimeric sesquiterpenes from Inula japonica Thunb. Bioorg Med Chem Lett 2009; 19: 710-713
    CrossrefPubMedGoogle Scholar
  • 10 Ling Y. Inula L. In: Ling Y, editor Flora of China. Beijing: Science Press; 1979: 248-281
    Google Scholar
  • 11 Schmidt HHHW, Kelm M. Methods in nitrix oxide research, chapter 33. London: John Wiley & Sons, Ltd.; 1996: 491-497
    Google Scholar
  • 12 Denizot F, Lang R. Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J Immunol Methods 1986; 89: 271-277
    CrossrefPubMedGoogle Scholar
  • 13 Bohlmann F, Jakupovic J, Ates N, Schuster A, Pickard J, King RM, Robinson H. Steiractinolides, a new group of sesquiterpene lactones. Liebigs Ann Chem 1983; 6: 962-973
    PubMedGoogle Scholar
  • 14 Doskotch RW, Hufford CD, El-Feraly FS. Further studies on the sesquiterpene lactones tulipinolide and epitulipinolide from Liriodendron tulipifera L. J Org Chem 1972; 37: 2740-2744
    CrossrefPubMedGoogle Scholar
  • 15 Matsueda S, Geissman TA. Sesquiterpene lactones of Artemisia species. III. Arglanine from Artemisia douglasiana . Tetrahedron Lett 1967; 8: 2013-2015
    CrossrefPubMedGoogle Scholar
  • 16 Geissman TA, Ellestad GA. Vulgarin, a sesquiterpene lactone from Artemisia vulgaris L. J Org Chem 1962; 27: 1855-1859
    CrossrefPubMedGoogle Scholar
  • 17 Maruyama M, Karube A, Sato K. Sesquiterpene lactones from Carpesium abrotanolides . Phytochemistry 1983; 22: 2773-2774
    CrossrefPubMedGoogle Scholar
  • 18 Bohlmann F, Mahanta PK, Jakupovic J, Rastogi RC, Natu AA. New sesquiterpene lactones from Inula species. Phytochemistry 1978; 17: 1165-1172
    CrossrefPubMedGoogle Scholar
  • 19 Jakupovic J, Zdero C, Grenz M, Tsichritzis F, Lehmann L, Hashemi-Nejad SM, Bohlman F. Twenty-one acylphloroglucinol derivatives and further constituents from South African Helichrysum species. Phytochemistry 1989; 28: 1119-1131
    CrossrefPubMedGoogle Scholar
  • 20 Ito K, Iida T. Seven sesquiterpene lactones from Inula britannica var. chinensis . Phytochemistry 1981; 20: 271-273
    CrossrefPubMedGoogle Scholar
  • 21 Yang JL, Wang R, Liu LL, Shi YP. Sesquiterpenoids from Inula britannica . Planta Med 2011; 77: 362-367
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 Spring O, Vargas D, Fischer NH. Sesquiterpene lactones and benzofurans in glandular trichomes of three Pappobolus species. Phytochemistry 1991; 30: 1861-1867
    CrossrefPubMedGoogle Scholar
  • 23 Kuo YH, Lin BY. A new dinorxanthane and chromone from the root of Tithonia diversifolia . Chem Pharm Bull 1999; 47: 428-429
    CrossrefPubMedGoogle Scholar
  • 24 Matsuo K, Yokoe H, Shishido K, Shindo M. Synthesis of diversifolide and structure revision. Tetrahedron Lett 2008; 49: 4279-4281
    CrossrefPubMedGoogle Scholar
  • 25 Ohno S, Tomita-Yokotani K, Kosemura S, Node M, Suzuki T, Amano M, Yasui K, Goto T, Yamamura S, Hasegawa K. A species-selective allelopathic substance from germinating sunflower (Helianthus annuus L.) seeds. Phytochemistry 2001; 56: 577-581
    CrossrefPubMedGoogle Scholar
  • 26 Lanzetta R, Lama G, Mauriello G, Parrilli M, Racioppi R, Sodano G. Ichthyotoxic sesquiterpenes and xanthanolides from Dittrichia graveolens . Phytochemistry 1991; 30: 1121-1124
    CrossrefPubMedGoogle Scholar
  • 27 Maruyama M, Omura S. Carpesiolin from Carpesium abrotanoides . Phytochemistry 1977; 16: 782-783
    CrossrefPubMedGoogle Scholar
  • 28 Bartel S, Bohlmann F. Total synthesis of the elemanolides (±) zempoalin A and B. Tetrahedron Lett 1989; 30: 685-688
    CrossrefPubMedGoogle Scholar
  • 29 Gonzalez A, Barrera JB, Mendez JT, Sanchez ML, Eiroa Martinez JL. Sesquiterpene lactones and other constituents of Tanacetum species. Phytochemisty 1992; 31: 1821-1825
    CrossrefPubMedGoogle Scholar
  • 30 Uchiyama T, Miyase T, Ueno A, Usmanghani K. Terpenic glycosides from Pluchea indica . Phytochemistry 1989; 28: 3369-3372
    CrossrefPubMedGoogle Scholar
  • 31 Chandra A, Misra LN, Thakur RS. Germacranolides and an alkyl glucoside from Tanacetum vulgare . Phytochemistry 1987; 26: 1463-1465
    CrossrefPubMedGoogle Scholar