Journal of Natural Medicines

, Volume 70, Issue 2, pp 276–281 | Cite as

Anti-inflammatory terpenylated coumarins from the leaves of Zanthoxylum schinifolium with α-glucosidase inhibitory activity

  • Phi-Hung Nguyen
  • Bing Tian Zhao
  • Okhwa Kim
  • Jeong Hyung Lee
  • Jae Sue Choi
  • Byung Sun Min
  • Mi Hee Woo


Nine terpenylated coumarins, namely 7-[(E)-3′,7′-dimethyl-6′-oxo-2′,7′-octadienyl]oxy-coumarin (1), schinilenol (2), schinindiol (3), collinin (4), 7-[(E)-7′-hydroxy-3′,7′-dimethy-locta-2′,5′-dienyloxy]-coumarin (5), 8-methoxyanisocoumarin (6), 7-(6′R-hydroxy-3′,7′-dimethyl-2′E,7′-octadienyloxy)coumarin (7), (E)-4-methyl-6-(coumarin-7′-yloxy)hex-4-enal (8), and aurapten (9), along with a 4-quinolone alkaloid (10) and integrifoliodiol (11), were isolated from the leaves of Zanthoxylum schinifolium. Of the isolates, compounds 4 and 7 potentially inhibited NO production in lipopolysaccharide (LPS)-stimulated macrophage RAW264.7 cells, with IC50 values of 5.9 ± 0.8 and 18.2 ± 1.8 μM, respectively. Furthermore, compounds 4 and 7 dose-dependently reduced the LPS-induced iNOS expression. Moreover, pre-incubation of cells with 4 and 7 significantly suppressed LPS-induced COX-2 protein expression. In addition, compounds 4, 7, 8, and 10 showed strong α-glucosidase inhibitory effects, with IC50 values of 92.1 ± 0.7, 90.6 ± 0.9, 78.2 ± 0.2, and 82.4 ± 0.8 μM, respectively. Compounds 1, 5, and 11 displayed moderate effects with IC50 values of 161.6 ± 0.3, 164.4 ± 1.1, and 155.4 ± 0.9 μM, while acarbose, a positive control, possessed an IC50 value of 121.5 ± 1.0 μM. This is the first investigation on the α-glucosidase inhibitory effect of components from Zanthoxylum schinifolium. Further studies should be made on active compounds.


Zanthoxylum schinifolium Terpenylated coumarins Anti-inflammation α-Glucosidase 



This research was supported by the research grants funded by the Catholic University of Daegu in 2013. The authors are grateful to S.H. Kim and collaborators at the Korea Basic Science Institute (Daegu) for measuring the mass spectra.


  1. 1.
    Schottenfeld D, Beebe-Dimmer J (2006) Chronic inflammation: a common and important factor in the pathogenesis of neoplasia. CA Cancer J Clin 56:69–83CrossRefPubMedGoogle Scholar
  2. 2.
    Yoon T, Cheon MS, Lee AY, Lee DY, Moon BC, Chun JM (2010) Anti-inflammatory activity of methylene chloride fraction from Glehnia littoralis extract via suppression of NF-kappa B and mitogen-activated protein kinase activity. J Pharmacol Sci 112:46–55CrossRefPubMedGoogle Scholar
  3. 3.
    Kanwar JR, Kanwar RK, Burrow H, Baratchi S (2009) Recent advances on the roles of NO in cancer and chronic inflammatory disorders. Curr Med Chem 16:2373–2394CrossRefPubMedGoogle Scholar
  4. 4.
    Vuolteenaho K, Moilanen T, Knowles RG, Moilanen E (2007) The role of nitric oxide in osteoarthritis. Scand J Rheumatol 36:247–258CrossRefPubMedGoogle Scholar
  5. 5.
    Groves JT, Wang CC (2000) Nitric oxide synthase: models and mechanisms. Curr Opin Chem Biol 4:687–695CrossRefPubMedGoogle Scholar
  6. 6.
    Farrell AJ, Blake DR, Palmer RM, Moncada S (1992) Increased concentrations of nitrite in synovial fluid and serum samples suggest increased nitric oxide synthesis in rheumatic diseases. Ann Rheum Dis 51:1219–1222PubMedCentralCrossRefPubMedGoogle Scholar
  7. 7.
    Paik SY, Koh KH, Baek SM, Paek SH, Kim JA (2005) The essential oils from Zanthoxylum schinifolium pericarp induce apoptosis of HepG2 human hepatoma cells through increased production of reactive oxygen species. Biol Pharm Bull 28:802–807CrossRefPubMedGoogle Scholar
  8. 8.
    Kim DS, Bang W, Yeum DM (1987) Degradation of carcinogenic nitrosamine formation factor by natural food components. Nitrite-scavenging of vegetable extracts. Bull Korean Fish Soc 20:463–468Google Scholar
  9. 9.
    Liu ZL, Chu SS, Jiang GH (2009) Feeding deterrents from Zanthoxylum schinifolium against two stored product insects. J Agric Food Chem 57:10130–10133CrossRefPubMedGoogle Scholar
  10. 10.
    Han MK, Kim SI, Ahn YJ (2006) Insecticidal and antifeedant activities of medicinal plant extracts against Attagenus unicolor japonicas (Coleoptera: Dermestidae). J Stored Prod Res 42:15–22CrossRefGoogle Scholar
  11. 11.
    Liu SL, Wei LX, Wang D, Gao CY (1991) Studies on the chemical constituents from the peel of Zanthoxylum schinifolium Sieb et Zucc. Yao Xue Xue Bao 26:836–840PubMedGoogle Scholar
  12. 12.
    Mun SI, Ryu HS, Lee HJ, Choi JS (1994) Further screening for antioxidant activity of vegetable plants and its active principles from Zanthoxylum schinifolium. J Korean Soc Food Nutr 23:466–471Google Scholar
  13. 13.
    Jo YS, Huong DTL, Bae KW, Lee MK, Kim YH (2002) Monoamine oxidase inhibitory coumarin from Zanthoxylum schinifolium. Planta Med 68:84–85CrossRefPubMedGoogle Scholar
  14. 14.
    Kim JS, Jun DY, Woo MH, Rhee IK, Kim YH (2006) Chemical composition and antitumor apoptogenic activity of methylene chloride extracts from the leaves of Zanthoxylum schinifolium. J Life Sci 16:546–554CrossRefGoogle Scholar
  15. 15.
    Min BK, Hyun DG, Jeong SY, Kim YH, Ma ES, Woo MH (2011) A new cytotoxic coumarin, 7-[(E)-3′,7′-dimethyl-6′-oxo-2′,7′-octadienyl] oxy coumarin, from the leaves of Zanthoxylum schinifolium. Arch Pharm Res 34:723–726CrossRefPubMedGoogle Scholar
  16. 16.
    Chen IS, Lin YC, Tsai IL, Teng CM, Ko FN, Ishikawa T, Ishii H (1995) Coumarins and anti-platelet aggregation constituents from Zanthoxylum schinifolium. Phytochemistry 39:1091–1097CrossRefPubMedGoogle Scholar
  17. 17.
    Fang Z, Jun DY, Kim YH, Min BS, Kim AK, Woo MH (2010) Cytotoxic constituents from the leaves of Zanthoxylum schinifolium. Bull Korean Chem Soc 31(4):1081–1084CrossRefGoogle Scholar
  18. 18.
    Liu ZL, Chu SS, Jiang GH (2009) Feeding deterrents from Zanthoxylum schinifolium against two stored-product insects. J Agric Chem 57:10130–10133CrossRefGoogle Scholar
  19. 19.
    Kim DH, Shin EK, Kim YH, Lee BW, Jun J-G, Park JHY, Kim J-K (2009) Suppression of inflammatory responses by celastrol, a quinone methide triterpenoid isolated from Celastrus regelii. Eur J Clin Invest 39:819–827CrossRefPubMedGoogle Scholar
  20. 20.
    Frandsen T, Svensson B (1998) Plant α-glucosidases of the glycoside hydrolase family 31. Molecular properties, substrate specificity, reaction mechanism, and comparison with family members of different origin. Plant Mol Biol 37:1–13CrossRefPubMedGoogle Scholar
  21. 21.
    Bertozzi CR, Kiessling LL (2001) Chemical glycobiology. Science 291:2357–2364CrossRefPubMedGoogle Scholar
  22. 22.
    Taha M, Ismail NH, Imran S, Rokei MQ, Saad SM, Khan KM (2015) Synthesis of new oxadiazole derivatives as α-glucosidase inhibitors. Bioorg Med Chem 23(15):4155–4162CrossRefPubMedGoogle Scholar
  23. 23.
    Chang CT, Doong SL, Tsai IL, Chen IS (1997) Coumarins and anti-HBV constituents from Zanthoxylum schinifolium. Phytochemistry 45:1419–1422CrossRefGoogle Scholar
  24. 24.
    Kohno H, Suzuki R, Curini M, Epifano F, Maltese F, Gonzales SP, Tanaka T (2006) Dietary administration with prenyloxycoumarins, auraptene and collinin, inhibits colitis-related colon carcinogenesis in mice. Int J Cancer 118:2936–2942CrossRefPubMedGoogle Scholar
  25. 25.
    Min BK, Hyun DG, Jeong SY, Kim YH, Ma ES, Woo MH (2011) A new cytotoxic coumarin, 7-[(E)-3′,7′-dimethyl-6′-oxo-2′,7′-octadienyl] oxy coumarin, from the leaves of Zanthoxylum schinifolium. Arch Pharm Res 34:723–726CrossRefPubMedGoogle Scholar
  26. 26.
    Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem 126:131–138CrossRefPubMedGoogle Scholar
  27. 27.
    Shin CY, Kundel M, Wells DG (2004) Rapid, activity-induced increase in tissue plasminogen activator is mediated by metabotropic glutamate receptor-dependent mRNA translation. J Neurosci 24:9425–9433CrossRefPubMedGoogle Scholar
  28. 28.
    Lee SC, Kim SY, Jeong SM, Park JH (2006) Effect of far-infrared irradiation on catechins and nitrite scavenging activity of green tea. J Agric Food Chem 54:399–403CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Pharmacognosy and Springer Japan 2016

Authors and Affiliations

  • Phi-Hung Nguyen
    • 1
  • Bing Tian Zhao
    • 1
  • Okhwa Kim
    • 2
  • Jeong Hyung Lee
    • 2
  • Jae Sue Choi
    • 3
  • Byung Sun Min
    • 1
  • Mi Hee Woo
    • 1
  1. 1.College of PharmacyCatholic University of DaeguHayangRepublic of Korea
  2. 2.College of Natural ScienceKangwon National UniversityKangwonRepublic of Korea
  3. 3.Faculty of Food Science and BiotechnologyPukyong National UniversityBusanRepublic of Korea

Personalised recommendations