The anti-inflammatory secoiridoid glycosides from Gentianae Scabrae Radix: the root and rhizome of Gentiana scabra


Gentianae Scabrae Radix is a well-known traditional medicine that is used for the treatment of hepatitis, cholecystitis and inflammatory diseases. It consists mainly of secoiridoid glycosides, with representatives of gentiopicroside, sweroside and swertiamarin. In the present study, a chemical investigation of the CHCl3 extract of Gentianae Scabrae Radix derived from Gentiana scabra Bunge yielded seven new (17) and ten known (817) secoiridoid glycosides. Their structures were elucidated by extensive spectroscopic analyses and comparison with literature data. All 17 compounds were evaluated for their inhibitory effects against NO, IL-6 and TNF-α productions induced by lipopolysaccharide (LPS) in RAW264 cells. Among them, 8-epi-kingiside derivatives 13; kingiside derivatives 4, 5 and 10; and a sweroside derivative 6 showed inhibition activity against IL-6 production with IC50 values of 51.70–61.10 μM, whereas sweroside derivatives 12 and 1517 and a swertiamarin derivative 13 showed inhibition effects on both NO and IL-6 productions with IC50 values of 64.74–94.95 and 48.91–75.45 μM, respectively. All the compounds exhibited weak inhibitory activity (IC50 > 100 μM) in a TNF-α bioassay. Finally, a primary structure–activity relationship of these secoiridoid glycosides is discussed.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3


  1. 1.

    Flora of China Editorial Committee (1995) Flora of China (Gentianaceae), vol 16. Science, Beijing, pp 1–139

  2. 2.

    The State Pharmacopoeia Commission of P. R. China (2010) Pharmacopoeia of the People’s Republic of China (English version), vol 1. China Medical Science, Beijing, pp 205–206

  3. 3.

    The Ministry of Health, Labour and Welfare (2011) The Japanese Pharmacopoeia (English version), 16th edn. p 1669

  4. 4.

    Ikeshiro Y, Tomita Y (1983) A new bitter secoiridoid glucoside from Gentiana scabra var. buergeri. Planta Med 48:169–173

    CAS  PubMed  Article  Google Scholar 

  5. 5.

    Tang HQ, Tan RX (1997) Glycosides from Gentiana scabra. Planta Med 63:388

    CAS  PubMed  Article  Google Scholar 

  6. 6.

    Kakuda R, Iijima T, Yaoita Y, Machida K, Kikuchi M (2001) Secoiridoid glycosides from Gentiana scabra. J Nat Prod 64:1574–1575

    CAS  PubMed  Article  Google Scholar 

  7. 7.

    Jiang RW, Wong KL, Chan YM, Xu HX, Pui-Hay But P, Shaw PC (2005) Isolation of iridoid and secoiridoid glycosides and comparative study on Radix Gentianae and related adulterants by HPLC analysis. Phytochemistry 66:2674–2680

    CAS  PubMed  Article  Google Scholar 

  8. 8.

    Wang SF, Xu YM, Jiang W, Zhang YF (2013) Isolation and identification of constituents with activity of inhibiting nitric oxide production in RAW 264.7 macrophages from Gentiana triflora. Planta Med 79:680–686

    CAS  PubMed  Article  Google Scholar 

  9. 9.

    Kakuda R, Iijima T, Yaoita Y, Machida K, Kikuchi M (2002) Triterpenoids from Gentiana scabra. Phytochemistry 59:791–794

    CAS  PubMed  Article  Google Scholar 

  10. 10.

    Xu M, Wang D, Zhang YJ, Yang CR (2007) Dammarane triterpenoids from the roots of Gentiana rigescens. J Nat Prod 70:880–883

    CAS  PubMed  Article  Google Scholar 

  11. 11.

    Xu M, Yang CR, Zhang YJ (2009) Minor antifungal aromatic glycosides from the roots of Gentiana rigescens (Gentianaceae). Chin Chem Lett 20:1215–1217

    CAS  Article  Google Scholar 

  12. 12.

    Park KS, Kim BH, Chang IM (2010) Inhibitory potencies of several iridoids on cyclooxygenase-1, cyclooxygnase-2 enzymes activities, tumor necrosis factor-α and nitric oxide production in vitro. Evid Based Complement Altern Med 7:41–45

    Article  Google Scholar 

  13. 13.

    Saravanan S, Hairul Islam VI, Prakash Babu N, Pandikumar P, Thirugnanasambantham K, Chellappandian M, Simon Durai Raj C, Gabriel Paulraj M, Ignacimuthu S (2014) Swertiamarin attenuates inflammation mediators via modulating NF-κB/I κB and JAK2/STAT3 transcription factors in adjuvant induced arthritis. Eur J Pharm Sci 56:70–86

    CAS  PubMed  Article  Google Scholar 

  14. 14.

    Kondo Y, Takano F, Hojo H (1994) Suppression of chemically and immunologically induced hepatic injuries by gentiopicroside in mice. Planta Med 60:414–416

    CAS  PubMed  Article  Google Scholar 

  15. 15.

    Mihailović V, Katanić J, Mišić D, Stanković V, Mihailović M, Uskoković A, Arambašić J, Solujić S, Mladenović M, Stanković N (2014) Hepatoprotective effects of secoiridoid-rich extracts from Gentiana cruciata L. against carbon tetrachloride induced liver damage in rats. Food Funct 5:1795–1803

    PubMed  Article  Google Scholar 

  16. 16.

    Chiba K, Yamazaki M, Kikuchi M, Kakuda R, Kikuchi M (2011) New physiological function of secoiridoids: neuritogenic activity in PC12h cells. J Nat Med 65:186–190

    CAS  PubMed  Article  Google Scholar 

  17. 17.

    Nathan CF, Hibbs JB Jr (1991) Role of nitric oxide synthesis in macrophage antimicrobial activity. Curr Opin Immunol 3:65–70

    CAS  PubMed  Article  Google Scholar 

  18. 18.

    Kobayashi Y (2010) The regulatory role of nitric oxide in proinflammatory cytokine expression during the induction and resolution of inflammation. J Leukoc Biol 88:1157–1162

    CAS  PubMed  Article  Google Scholar 

  19. 19.

    Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S (2011) The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta 1813:878–888

    CAS  PubMed  Article  Google Scholar 

  20. 20.

    Bauqh JA, Bucala R (2001) Mechanisms for modulating TNF alpha in immune and inflammatory disease. Curr Opin Drug Discov Dev 4:635–650

    Google Scholar 

  21. 21.

    Garcia J, Mpondo EM, Kaouadji M (1990) Kingiside and derivative from Gentiana pyrenaica. Phytochemistry 29:3353–3355

    CAS  Article  Google Scholar 

  22. 22.

    Garcia J, Lavaitte S, Gey C (1989) 8-epikingiside and its vanillate ester, isolated from Gentiana pyrenaica. Phytochemistry 28:2199–2201

    CAS  Article  Google Scholar 

  23. 23.

    Xu M, Wang D, Zhang YJ, Yang CR (2008) Iridoid glucosides from Gentiana rhodantha. J Asian Nat Prod Res 10:491–498

    CAS  PubMed  Article  Google Scholar 

  24. 24.

    Inouye H, Yoshida T, Tobita S, Tanaka K, Nishioka T (1970) Absolute struktur des oleuropeins und einiger verwandter glucoside. Tetrahedron Lett 28:2459–2464

    Article  Google Scholar 

  25. 25.

    Inouye H, Yoshida T, Tobita S, Kanaka K, Nishioka T (1974) Uber die monoterpenglucoside und verwandte naturstoffe. XXII. Absolutstrukturen des oleuropeins, Kingisids und Morronisids. Tetrahedron 30:201–209

    CAS  Article  Google Scholar 

  26. 26.

    Inouye H, Yoshida T, Nakamura Y, Tobita S (1970) Uber die monoterpenglucoside. XI. chemische korrelation des asperulosids mit swerosid. Chem Pharm Bull 18:1889–1899

    CAS  Article  Google Scholar 

  27. 27.

    Kikuchi M, Kakuda R, Kikuchi M, Yaoita Y (2005) Secoiridoid glycosides from Gentiana scabra. J Nat Prod 68:751–753

    CAS  PubMed  Article  Google Scholar 

  28. 28.

    Liu YH, Li XC, Liu YQ, Yang CR (1994) Iridoid glycosides from Gentiana macrophylla. Acta Botanica Yunnanica 16:85–89

    Google Scholar 

  29. 29.

    Mpondo EM, Chulia AJ (1988) 6′-O-β-d-Glucosyl aentiopicroside: a new secoiridoid from Gentiana asclepiadea. Planta Med 54:185–186

    Article  Google Scholar 

  30. 30.

    Kim JA, Son NS, Son JK, Jahng Y, Chang HW, Jang TS, Na MK, Lee SH (2009) Two new secoiridoid glycosides from the rhizomes of Gentian scabra Bunge. Arch Pharm Res 32:863–867

    CAS  PubMed  Article  Google Scholar 

  31. 31.

    Caliş I, Rüegger H, Chun Z, Sticher O (1990) Secoiridoid glucosides isolated from Gentiana gelida. Planta Med 56:406–409

    PubMed  Article  Google Scholar 

  32. 32.

    Tan RX, Wolfender JL, Zhang LX, Ma WG, Fuzzati N, Marston A, Hostettmann K (1996) Acyl secoiridoids and antifungal constituents from Gentiana macrophylla. Phytochemistry 42:1305–1313

    CAS  PubMed  Article  Google Scholar 

  33. 33.

    Inouye H, Ueda S, Nakamura Y, Inoue K, Hayano T, Matsumura H (1974) Über die monoterpenglucoside und verwandte naturstoffe-XXIV: Triflorosid, ein neues secoiridoidglucosid aus Gentiana triflora var. japonica. Tetrahedron 30:571–577

    CAS  Article  Google Scholar 

  34. 34.

    Wang ZG, Wang SS, Sun YJ, Wang HY, Chen G, Wang XJ, Hattori M, Zhang HL (2014) New analytical method for the study of the metabolism of gentiopicroside in rats after oral administration by LC–TOF-MS following picolinoyl derivatization. J Sep Sci 37:237–243

    CAS  PubMed  Article  Google Scholar 

  35. 35.

    Lv T, Xu M, Wang D, Zhu HT, Yang CR, Zhang TT, Zhang YJ (2012) The chemical constituents from the roots of Gentiana crassicaulis and their inhibitory effects on inflammatory mediators NO and TNF-α. Nat Prod Bioprospect 2:217–221

    CAS  PubMed Central  Article  Google Scholar 

  36. 36.

    Tanaka T, Nakashima T, Ueda T, Tomii K, Kouno I (2007) Facile discrimination of aldose enantiomers by reversed-phase HPLC. Chem Pharm Bull 55:899–901

    CAS  PubMed  Article  Google Scholar 

Download references


The authors would like to thank Dr. Shengli Wei from the School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, China, for helping with sample collection. They are also grateful to Dr. Feng Li from Joint Usage/Research Center for Science-Based Natural Medicine Research Promotion Office, Institute of Natural Medicine, University of Toyama, Toyama, Japan, for assistance with 2D-NMR experimental acquisition and troubleshooting. This work was supported by JSPS KAKENHI Grant Number 24406005.

Author information



Corresponding author

Correspondence to Katsuko Komatsu.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (XLSX 11 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

He, YM., Zhu, S., Ge, YW. et al. The anti-inflammatory secoiridoid glycosides from Gentianae Scabrae Radix: the root and rhizome of Gentiana scabra . J Nat Med 69, 303–312 (2015).

Download citation


  • Secoiridoid glycosides
  • Gentiana scabra
  • Gentianaceae
  • Anti-inflammatory activity
  • 8-epi-kingiside derivative
  • Kingiside derivative