Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
권호 표지
DOI QR코드

DOI QR Code

New hydroperoxylated and 20,24-epoxylated dammarane triterpenes from the rot roots of Panax notoginseng

  • Shang, Jia-Huan (State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences) ;
  • Sun, Wen-Jie (State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences) ;
  • Zhu, Hong-Tao (State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences) ;
  • Wang, Dong (State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences) ;
  • Yang, Chong-Ren (State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences) ;
  • Zhang, Ying-Jun (State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences)
  • Received : 2018.10.30
  • Accepted : 2019.01.31
  • Published : 2020.05.15
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Root rot is a serious destructive disease of Panax notoginseng, a famous cultivated araliaceous herb called Sanqi or Tianqi in Southwest China. Methods: The chemical substances of Sanqi rot roots were explored by chromatographic techniques. MS, 1D/2D-NMR, and single crystal X-ray diffraction were applied to determine the structures. Murine macrophage RAW264.7 and five human cancer cell lines were used separately for evaluating the antiinflammatory and cytotoxic activities. Results and Conclusion: Thirty dammarane-type triterpenes and saponins were isolated from the rot roots of P. notoginseng. Among them, seven triterpenes, namely, 20(S)-dammar-25-ene-24(S)-hydroperoxyl-3β,6α,12β,20-tetrol (1), 20(S)-dammar-3-oxo-23-ene-25-hydroperoxyl-6α,12β,20-triol (2), 20(S)-dammar-12-oxo-23-ene-25-hydroperoxyl-3β,6α,20-triol (3), 20(S)-dammar-3-oxo-23-ene-25-hydroperoxyl-12β,20-diol (4), 20(S),24(R)-epoxy-3,4-seco-dammar-25-hydroxy-12-one-3-oic acid (5), 20(S),24(R)-epoxy-3,4-seco-dammar-25-hydroxy-12-one-3-oic acid methyl ester (6), and 6α-hydroxy-22,23,24,25,26,27-hexanordammar-3,12,20-trione (7), are new compounds. In addition, 12 known ones (12-16 and 19-25) were reported in Sanqi for the first time. The new Compound 1 showed comparable antiinflammatory activity on inhibition of NO production to the positive control, whereas the known compounds 9, 12, 13, and 16 displayed moderate cytotoxicities against five human cancer cell lines. The results will provide scientific basis for understanding the chemical constituents of Sanqi rot roots and new candidates for searching antiinflammatory and antitumor agents.

Keywords

References

  1. Guo YX, Zhao LB, Wang L, Jiang JL, Yuan YJ. New progress in basic research of compound danshen dropping pills. Chin Tradit Herbal Drugs 2003;34:U4-5.
  2. Liu D, Cui XM. Preliminary study on the photosynthetic characteristics of Panax notoginseng. South Chin J Agric Sci 1992;5:41-3.
  3. Mao ZS, Long YJ, Zhu SS, Chen ZJ, Wei FG, Zhu YX, He XH. Research progress of root rot of Panax notoginseng. Chin Med Mat 2013;36:2051-4.
  4. Luo WF, Yu SF, He CF, Li ZY, Wang CL, Cui XM. On the combined infection root rot pathogens on Panax notoginseng. Acta Phytopathol Sin 1997;27:85-91.
  5. Xia PG, Zhang SC, Liang ZS, Qi ZH. Study on chemical constituents of Panax notoginseng. Chin Tradit Herbal Drugs 2014;45:2564-70.
  6. Gu CZ, Lv JJ, Zhang XX, Qiao YJ, Yan H, Li Y, Wang D, Zhu HT, Luo HR, Yang CR, et al. Triterpenoids with promoting effects on the differentiation of PC12 cells from the steamed roots of Panax notoginseng. J Nat Prod 2015;78:1829-40. https://doi.org/10.1021/acs.jnatprod.5b00027
  7. Gu CZ, Lv JJ, Zhang XX, Yan H, Zhu HT, Luo HR, Wang D, Yang CR, Xu M, Zhang YJ. Minor dehydrogenated and cleavaged dammarane-type saponins from the steamed roots of Panax notoginseng. Fitoterapia 2015;103:97-105. https://doi.org/10.1016/j.fitote.2015.03.014
  8. Tai RQ, TanWZ, Yang E, Feng Y, Li HZ. Variation of saponins in Panax notoginseng root rot diseases by LC-MS. J Kunming Univ Sci Technol (Nat. Sci) 2015;40:85-8.
  9. Popovich DG, Kitts DD. Structure-function relationship exists for ginsenosides in reducing cell proliferation and inducing apoptosis in the human leukemia (THP-1) cell line. Arch Biochem Biophys 2002;406:1-8. https://doi.org/10.1016/S0003-9861(02)00398-3
  10. Saklani A, Kutty SK. Plant-derived compounds in clinical trials. Drug Discov Today 2008;13:161-71. https://doi.org/10.1016/j.drudis.2007.10.010
  11. Ahn S, Siddiqi MH, Noh HY, Kim YJ, Kim YJ, Jin CG, Yang DC. Anti-inflammatory activity of ginsenosides in LPS-stimulated RAW264.7 cells. Sci Bull 2015;60:773-84. https://doi.org/10.1007/s11434-015-0773-4
  12. Xie J. Anti-inflammatory and analgesic effects and the mechanism of actions of ginsenoside Rg1. Chin J Hosp Pharm 2013;33:1592-7.
  13. Sun WJ, Zhu HT, Zhang TY, Zhang MY, Wang D, Yang CR, Zhang YX, Zhang YJ. Two new alkaloids from Fusarium tricinctum SYPF 7082, an endophyte from the root of Panax notoginseng. Nat Prod Bioprosp 2018;8:391-6. https://doi.org/10.1007/s13659-018-0171-0
  14. Gu CZ, Lv JJ, ZhangXX,YangHui,Wang D, ZhuHT, LuoHR, Yang CR,XuM, Zhang YJ. Triterpenoid saponins with promoting effects on differentiation of PC12 cells from the steamed roots of Panax notoginseng. J Nat Prod 2015;78:1829-40. https://doi.org/10.1021/acs.jnatprod.5b00027
  15. Guang TC, Yang X, Lin Y, Qu XG, Inventors; Nantong University, assignee. Protopanaxadiol peroxidation derivatives and their preparation and application. Chinese patent CN 102766184 B. 2014 Aug 13. Chinese.
  16. Lars P. Christensen. Ginsenosides: chemistry, biosynthesis, analysis, and potential health effects. In: Steve T, editor. Advances in food and nutrition research. Cambridge: Elsevier; 2008. p. 1-99.
  17. Asakawa J, Kasai R, Yamasaki K, Tanaka O. $^{13}C$NMR study of ginseng sapogenins and their related dammarane type triterpenes. Tetrahedron 1977;33:1935-9. https://doi.org/10.1016/0040-4020(77)85008-4
  18. Fujita S, Kasai R, Ohtani K, Yamasaki K, Chiu MH, Nie RL, Tanaka O. Dammarane glycosides from aerial parts of Neoalsomitra integrifoliola. Phytochemistry 1995;39:591-602. https://doi.org/10.1016/0031-9422(95)00020-8
  19. Ma SG, Jiang YT, Song SJ, Wang ZH, Bai J, Xu SX, Liu K. A lkaline-degradation products of ginsenosides from leaves and stems of Panax quinquefolium. Acta Pharm Sin 2005;40:924-30. https://doi.org/10.3321/j.issn:0513-4870.2005.10.013
  20. Zhang J, Guo H, Tian Y, Liu P, Li N, Zhou J, Guo D. Biotransformation of 20(S)- protopanaxatriol by Mucor spinosus and the cytotoxic structure activity relationships of the transformed products. Phytochemistry 2007;68:2523-30. https://doi.org/10.1016/j.phytochem.2007.05.028
  21. Shen RZ, Cao X, Laval S, Sun JS, Yu B. Synthesis of ocotillol-type ginsenosides. J Org Chem 2016;81:10279-94. https://doi.org/10.1021/acs.joc.6b01265
  22. Ismail IS, Santhanaraju C, Morita H, Malek EA, Mahmod II . Terpenes of Walsura chrysogyne (Meliaceae). Lett Org Chem 2013;10:584-9. https://doi.org/10.2174/1570178611310080009
  23. Roux D, Martin MT, Adeline MT, Sevenet T, Hadi AH, Pais M. Foveolins A and B, dammarane triterpenes from Aglaia foveolata. Phytochemistry 1998;49:1745-8. https://doi.org/10.1016/S0031-9422(98)00305-7
  24. Sugimoto S, Nakamura S, Matsuda H, Kitagawa N, Yoshikawa M. Chemical constituents from seeds of Panax ginseng: structure of new dammarane-type triterpene ketone, panaxadione, and hplc comparisons of seeds and flesh. Chem Pharm Bull 2009;57:283-7. https://doi.org/10.1248/cpb.57.283
  25. Atopkina LN, Denisenko VA. Synthesis of $3{\beta}$,20S-dihydroxydammar-24-en-12-one 3,20-di-O-${\beta}$-D-glucopyranoside (chikusetsusaponin-LT8), a glycoside from Panax japonicus. Chem Nat Compd 2006;42:55-60. https://doi.org/10.1007/s10600-006-0035-4
  26. Ko SR, Choi KJ, Suzuki K, Suzuki Y. Enzymatic preparation of ginsenosides Rg2, Rh1, and F1. Chem Pharm Bull 2003;51:404-8. https://doi.org/10.1248/cpb.51.404
  27. Liu X, Qiao LR, Xie D, Zhang Y, Zou JH, Chen XG, Dai JG. Microbial transformation of ginsenoside-Rg1 by Absidia coerulea and the reversal activity of the metabolites towards multi-drug resistant tumor cells. Fitoterapia 2011;82:1313-7. https://doi.org/10.1016/j.fitote.2011.09.001
  28. Yang JL, Ha TKQ, Dhodary B, Kim KH, Park JS, Lee CH, Kim YC, Oh WK. Dammarane triterpenes as potential SIRT1 activators from the leaves of Panax ginseng. J Nat Prod 2014;77:1615-23. https://doi.org/10.1021/np5002303
  29. Tung NH, Song GY, Minh CV, Kiem PV, Jin LG, Boo HJ, Kang HK, Kim YH. Steamed ginseng-leaf components enhance cytotoxic effects on human leukemia HL-60 cells. Chem Pharm Bull 2010;58:1111-5. https://doi.org/10.1248/cpb.58.1111
  30. Nakamura S, Sugimoto S, Matsuda H, Yoshikawa M. Medicinal flowers. XVII. new dammarane-type triterpene glycosides from flower buds of American ginseng, Panax quinquefolium L. Chem Pharm Bull 2007;55:1342-8. https://doi.org/10.1248/cpb.55.1342
  31. Chen GT, Yang X, Li JL, Ge HJ, Song Y, Ren J. Biotransformation of 20(S)-protopanaxadiol by Aspergillus niger AS 3.1858. Fitoterapia 2013;91. 256-30. https://doi.org/10.1016/j.fitote.2013.09.019
  32. Liu GY, Li XW, Wang NB, Zhou HY, Wei W, Gui MY, Yang B, Jin YR. Three new dammarane-type triterpene saponins from the leaves of Panax ginseng C. A. Meyer. J Asian Nat Pro Res 2010;12:865-73. https://doi.org/10.1080/10286020.2010.508035
  33. Yu P, He WN, Sun BH, Huang J, Gao HY, Wu LJ. A new dammarane-type triterpene from the root of Panax notoginseng. Asian J Tradit Med 2008;3:160-2.
  34. Huang W, inventor; Panagin Pharmaceuticals Inc, assignee. [Novel dammarane sapogenins and their use as anti-cancer agents]. World patent WO 2005/040189 A1. 2005 May 6.
  35. Liu JP, Tian X, Liu HY, Zhang QH, Lu D, Li PY, Zhao CF. Two novel dammaranetype compounds from the leaves and stems of Panax quinquefolium L. J Asian Nat Prod Res 2013;15:974-8. https://doi.org/10.1080/10286020.2013.794416

Cited by

  1. New 12,23-Epoxydammarane Type Saponins Obtained from Panax notoginseng Leaves and Their Anti-Inflammatory Activity vol.25, pp.17, 2020, https://doi.org/10.3390/molecules25173784
  2. Comprehensive Quality Evaluation of American Ginseng for Different Parts and Abnormal Trait Based on the Major Ginsenoside Contents and Morphological Characteristics vol.2021, 2020, https://doi.org/10.1155/2021/8831080
  3. Notoginsenoids, a new class of hexa-nortriterpenoids from biotransformation of Panax notoginseng saponins vol.1252, 2020, https://doi.org/10.1016/j.molstruc.2021.132096