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 (1–7) and ten known (8–17) 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 1–3; 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 15–17 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.
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Flora of China Editorial Committee (1995) Flora of China (Gentianaceae), vol 16. Science, Beijing, pp 1–139
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
The Ministry of Health, Labour and Welfare (2011) The Japanese Pharmacopoeia (English version), 16th edn. p 1669
Ikeshiro Y, Tomita Y (1983) A new bitter secoiridoid glucoside from Gentiana scabra var. buergeri. Planta Med 48:169–173
Tang HQ, Tan RX (1997) Glycosides from Gentiana scabra. Planta Med 63:388
Kakuda R, Iijima T, Yaoita Y, Machida K, Kikuchi M (2001) Secoiridoid glycosides from Gentiana scabra. J Nat Prod 64:1574–1575
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
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
Kakuda R, Iijima T, Yaoita Y, Machida K, Kikuchi M (2002) Triterpenoids from Gentiana scabra. Phytochemistry 59:791–794
Xu M, Wang D, Zhang YJ, Yang CR (2007) Dammarane triterpenoids from the roots of Gentiana rigescens. J Nat Prod 70:880–883
Xu M, Yang CR, Zhang YJ (2009) Minor antifungal aromatic glycosides from the roots of Gentiana rigescens (Gentianaceae). Chin Chem Lett 20:1215–1217
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
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
Kondo Y, Takano F, Hojo H (1994) Suppression of chemically and immunologically induced hepatic injuries by gentiopicroside in mice. Planta Med 60:414–416
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
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
Nathan CF, Hibbs JB Jr (1991) Role of nitric oxide synthesis in macrophage antimicrobial activity. Curr Opin Immunol 3:65–70
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
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
Bauqh JA, Bucala R (2001) Mechanisms for modulating TNF alpha in immune and inflammatory disease. Curr Opin Drug Discov Dev 4:635–650
Garcia J, Mpondo EM, Kaouadji M (1990) Kingiside and derivative from Gentiana pyrenaica. Phytochemistry 29:3353–3355
Garcia J, Lavaitte S, Gey C (1989) 8-epikingiside and its vanillate ester, isolated from Gentiana pyrenaica. Phytochemistry 28:2199–2201
Xu M, Wang D, Zhang YJ, Yang CR (2008) Iridoid glucosides from Gentiana rhodantha. J Asian Nat Prod Res 10:491–498
Inouye H, Yoshida T, Tobita S, Tanaka K, Nishioka T (1970) Absolute struktur des oleuropeins und einiger verwandter glucoside. Tetrahedron Lett 28:2459–2464
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
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
Kikuchi M, Kakuda R, Kikuchi M, Yaoita Y (2005) Secoiridoid glycosides from Gentiana scabra. J Nat Prod 68:751–753
Liu YH, Li XC, Liu YQ, Yang CR (1994) Iridoid glycosides from Gentiana macrophylla. Acta Botanica Yunnanica 16:85–89
Mpondo EM, Chulia AJ (1988) 6′-O-β-d-Glucosyl aentiopicroside: a new secoiridoid from Gentiana asclepiadea. Planta Med 54:185–186
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
Caliş I, Rüegger H, Chun Z, Sticher O (1990) Secoiridoid glucosides isolated from Gentiana gelida. Planta Med 56:406–409
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
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
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
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
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
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.
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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). https://doi.org/10.1007/s11418-015-0894-8
- Secoiridoid glycosides
- Gentiana scabra
- Anti-inflammatory activity
- 8-epi-kingiside derivative
- Kingiside derivative