Journal of Natural Medicines

, Volume 70, Issue 4, pp 731–739 | Cite as

Application of a new method, orthogonal projection to latent structure (OPLS) combined with principal component analysis (PCA), to screening of prostaglandin E2 production inhibitory flavonoids in Scutellaria Root

  • Lian Huang
  • Hiroyuki Fuchino
  • Nobuo Kawahara
  • Yuji Narukawa
  • Noriyasu Hada
  • Fumiyuki Kiuchi
Original Paper

Abstract

A new method consisting of orthogonal projection to latent structure (OPLS) and modified principal component analysis (PCA) was applied to a screening of bioactive compounds from natural products. In this report, extracts of 52 Scutellaria Root (the root of Scutellaria baicalensis Georgi) samples were analyzed by high-performance liquid chromatography (HPLC), and their inhibitory activities towards prostaglandin E2 (PGE2) production in a murine macrophage-like cell line J774.1 were examined. Wogonin and oroxylin A were predicted to be strong inhibitors of PGE2 production by OPLS analysis of the data. However, 6-methoxywogonin, which has been reported to have inhibitory activity, was omitted. Modified PCA was then applied to these data as a filter to exclude compounds less relevant to the activity, and OPLS analysis was applied to the modified data. As a result, this method predicted wogonin, oroxylin A and 6-methoxywogonin to be strong inhibitors of PGE2 production without any prior knowledge. The predictions by the OPLS combined with PCA method of PGE2 production inhibitory activities of 52 samples showed good agreement with the actual data. This method is simple and effective and can be used in screening of bioactive natural compounds without any prior knowledge.

Keywords

Scutellaria baicalensis OPLS PCA PGE2 Flavonoid 

Notes

Acknowledgments

This work was supported in part by MEXT-Supported Program for the Strategic Research Foundation at Private Universities and JSPS Grant-in-Aid for Scientific Research (C).

Supplementary material

11418_2016_1004_MOESM1_ESM.pdf (84 kb)
Supplementary material 1 (PDF 84 kb)

References

  1. 1.
    Wani MC, Taylor HL, Wall ME, Coggon P, Mcphail AT (1971) Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J Am Chem Soc 93:2325–2327CrossRefPubMedGoogle Scholar
  2. 2.
    Hart LG, Call JB, Oliverio VT (1969) A fluorometric method for determination of camptothecin in plasma and urine. Cancer Chemother Rep 53:211–214PubMedGoogle Scholar
  3. 3.
    Frei E 3rd, Franzino A, Shnider BI, Costa G, Golsky J, Brindley CO, Hosley H, Holland JF, Gold GL, Jonsson U (1961) Clinical studies of vinblastine. Cancer Chemother Rep Part 1(12):125–129Google Scholar
  4. 4.
    Oshima N, Narukawa Y, Hada N, Kiuchi F (2013) Quantitative analysis of anti-inflammatory activity of orengedokuto: importance of combination of flavonoids in inhibition of PGE2 production in mouse macrophage-like cell line J774.1. J Nat Med 67:281–288CrossRefPubMedGoogle Scholar
  5. 5.
    Daikonya A, Fuchino H, Arai R, Takahashi Y, Wada H, Goda Y, Kawahara N (2013) Inhibitory effect of Scutellariae Radix (Scutellaria baicalensis Georgi) From the Japanese market on nitric oxide production, and metabolome analysis based on LC/MS. Shoyakugaku Zasshi 67:35–40Google Scholar
  6. 6.
    Ebrahimabadi EH, Ghoreishi SM, Masoum S, Ebrahimabadi AH (2016) Combination of GC/FID/Mass spectrometry fingerprints and multivariate calibration techniques for recognition of antimicrobial constituents of Myrtus communis L. essential oil. J Chromatogr B 1008:50–57CrossRefGoogle Scholar
  7. 7.
    Li HJ, Wang ZH, Li WT, Wang DM, Zheng SH, Huang LF (2015) Analysis of variation of chemical composition of Tussilago farfara by UPLC-Q-TOF/MS before and after fried with honey. Zhongguo Yaofang 26:792–794Google Scholar
  8. 8.
    Harder E, Damm W, Maple J, Chuanjie W, Reboul M, Jinyu X, Lingle W, Lupyan D, Dahlgren MK, Knight JL (2016) OPLS3: a force field providing broad coverage of drug-like small molecules and proteins. J Chem Theory Computation 12:281–296CrossRefGoogle Scholar
  9. 9.
    Daikonya A, Fuchino H (2014) Inhibitory effect of crude drugs on nitric oxide production and metabolome analysis based on LC/MS. Saibou 46:140–145Google Scholar
  10. 10.
    Johan T, Svante W (2002) Orthogonal projection to latent structure. J Chemom 16:119–128CrossRefGoogle Scholar
  11. 11.
    Kim E, Paul G (1987) Principal component analysis. Chemometr Intell Lab 2:37–52CrossRefGoogle Scholar
  12. 12.
    Zhou H J (1993) Ben Cao Jing Ji Zhu; 340Google Scholar
  13. 13.
    Kim H, Kim YS (2001) The plant flavonoid wogonin suppresses death of activated C6 rat glial cells by inhibiting nitric oxide production. Neurosci Lett 309:67–71CrossRefPubMedGoogle Scholar
  14. 14.
    Zhang DY, Wu J (2003) Inhibition of cancer cell proliferation and prostaglandin E2 synthesis by Scutellaria baicalensis. Cancer Res 63:403–407Google Scholar
  15. 15.
    Jung SM, Schumacher H (2007) Reduction of urate crystal-induced inflammation by root extracts from traditional oriental medicinal plants: elevation of prostaglandin D2 levels. Arthritis Res Ther 9:1104CrossRefGoogle Scholar
  16. 16.
    Liweber M (2009) New therapeutic aspects of flavones: the anticancer properties of Scutellaria and its main active constituents wogonin, baicalein and baicalin. Cancer Treat Rev 35:57–68CrossRefGoogle Scholar
  17. 17.
    Krakauer T, Li BQ, Young HA (2001) The flavonoid baicalin inhibits suerantigen-induced inflammatory cytokines and chemokines. FEBS Lett 500:52–55CrossRefPubMedGoogle Scholar
  18. 18.
    Baumann S, Fas SC, Giaisi M, Mueller WW, Merling A, Guelow K, Edler L, Krammer PH, Liweber M (2008) Wogonin preferentially kills malignant lymphocytes and suppresses T-cell tumor growth by inducing PLCy1-and Ca2+-dependent apoptosis. Blood 111:2354–2363CrossRefPubMedGoogle Scholar
  19. 19.
    Na L, Ying G, Yun L, Yan C, Yong Y, Hongyan G, Qi Q, Wei L, Xiaotang W, Qidong Y (2008) Wogonin suppresses tumor growth in vivo and VEGF-induced angiogenesis through inhibiting tyrosine phosphorylation of VEGFR2. Life Sci 82:17–18Google Scholar
  20. 20.
    Hongru S, Jianjun C, Hong M, Yazhen S (2009) Scutellaria flavonoid supplementation reverses ageing-related cognitive impairment and neuronal changes in aged rats. Brain Inj 23:146–153CrossRefGoogle Scholar
  21. 21.
    Takano-Ishikawa Y, Goto M, Yamaki K (2006) Structure-activity relations of inhibitory effects of various flavonoids on lipopolysaccharide-induced prostaglandin E2 production in rat peritoneal macrophages: comparison between subclasses of flavonoids. Phytomedicine 13:310–317CrossRefPubMedGoogle Scholar
  22. 22.
    Michael CA, Dominic AS, Anne M, Miriam LH, Maciej JC, Donald LF, Betty JA, Joseph GM, Robert HS, Michael RB (1988) Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assy. Cancer Res 48:589–601Google Scholar
  23. 23.

Copyright information

© The Japanese Society of Pharmacognosy and Springer Japan 2016

Authors and Affiliations

  • Lian Huang
    • 1
  • Hiroyuki Fuchino
    • 2
  • Nobuo Kawahara
    • 2
  • Yuji Narukawa
    • 1
  • Noriyasu Hada
    • 1
  • Fumiyuki Kiuchi
    • 1
  1. 1.Faculty of PharmacyKeio UniversityTokyoJapan
  2. 2.Research Center for Medicinal Plant ResourcesNational Institute of Biomedical Innovation, Health and NutritionTsukubaJapan

Personalised recommendations