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Lignans from guaiac resin decrease nitric oxide production in interleukin 1β-treated hepatocytes

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Abstract

Guaiac resin, extracted from the heartwood of Guaiacum officinale L. or G. sanctum L., is speculated to have anti-inflammatory effects. Lignans were purified from guaiac resin (also known as gum guaiacum) by monitoring the nitric oxide (NO) production in rat hepatocytes treated with an inflammatory cytokine interleukin-1β (IL-1β). Six lignans were purified from guaiac resin and identified as: dehydroguaiaretic acid (1), (+)-trans-1,2-dihydrodehydroguaiaretic acid (2), furoguaiaoxidin (3), meso-dihydroguaiaretic acid (4), furoguaiacin (i.e., α-guaiaconic acid) (5), and nectandrin B (6). To our knowledge, this is the first time that 1 has been isolated from guaiac resin as a non-derivative. Compounds 2 and 6 were first found in guaiac resin. Compound 3 was first isolated from a natural source as a non-derivative. Furthermore, 1–6 significantly suppressed NO production in IL-1β-treated hepatocytes. Because anti-inflammatory compounds suppress NO production, this system is often used to measure the anti-inflammatory effects of Kampo drugs and herbal constituents. The NO-suppressing activity of the six lignans isolated in this study indicates that guaiac resin has anti-inflammatory effects and that these lignans may be responsible for the anti-inflammatory effects of guaiac resin.

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Abbreviations

EtOAc:

Ethyl acetate

CDCl3 :

Deuterochloroform

CD3OD:

Methanol-d 4

ODS:

Octadecylsilyl

HPLC:

High-performance liquid chromatography

IR:

Infrared

UV:

Ultraviolet

CD:

Circular dichroism

MALDI-TOF MS:

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

EI-MS:

Electron ionization mass spectrometry

NMR:

Nuclear magnetic resonance

HMBC:

Heteronuclear multiple-bond connectivity

COSY:

Correlation spectroscopy

NOE:

Nuclear Overhauser effect

NOESY:

Nuclear Overhauser effect spectroscopy

br:

Broad

d:

Doublet

m:

Multiplet

s:

Singlet

t:

Triplet

TLC:

Thin-layer chromatography

IC50 :

Half-maximal inhibitory concentration

IL-1β:

Interleukin-1β

LDH:

Lactate dehydrogenase

NO:

Nitric oxide

iNOS:

Inducible nitric oxide synthase

CC:

Column chromatography

References

  1. King FE, Wilson JG (1964) The chemistry of extractives from hardwoods. Part XXXVI. The lignans of Guaiacum officinale L. J Chem Soc, pp 4011–4024

  2. Majumder P, Bhattacharyya M (1975) Furoguaiaoxidin—a new enedione lignan of Guaiacum officinale L.: a novel method of sequential introduction of alkoxy functions in the 3- and 4-methyl groups of 2,5-diaryl-3,4-dimethylfurans. J Chem Soc Comm 17:702–703

    Article  Google Scholar 

  3. Kratochvil JF, Burris RH, Seikel MK, Harkin JM (1971) Isolation and characterization of α-guaiaconic acid and the nature of guaiacum blue. Phytochemistry 10:2529–2531

    Article  CAS  Google Scholar 

  4. Chavez KJ, Feng X, Flanders JA, Rodriguez E, Schroeder FC (2011) Spirocyclic lignans from Guaiacum (Zygophyllaceae) induce apoptosis in human breast cancer cell lines. J Nat Prod 74:1293–1297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ahmad VU, Saba N, Ali Z, Zahid M, Alam L (2000) A new triterpenoidal saponin from the bark of Guaiacum officinale L. Z Naturforsh 55b:227–230

    Google Scholar 

  6. Moeller DD (1984) The odyssey of guaiac. Am J Gastroenterol 79:236–237

    CAS  PubMed  Google Scholar 

  7. Bartram T (1998) Bartram’s Encyclopedia of herbal medicine: the definitive guide to the herbal treatments of diseases. Marlowe & Company, New York, p 208

    Google Scholar 

  8. Young GP, Symonds EL, Allison JE, Cole SR, Fraser CG, Halloran SP, Kuipers EJ, Seaman HE (2015) Advances in fecal occult blood tests: the FIT revolution. Dig Dis Sci 60:609–622

    Article  PubMed  Google Scholar 

  9. Duwiejua M, Zeitlin IJ, Waterman PG, Gray AI (1994) Anti-inflammatory activity of Polygonum bistorta, Guaiacum officinale and Hamamelis virginiana in rats. J Pharm Pharmacol 46:286–290

    Article  CAS  PubMed  Google Scholar 

  10. Sarkar A, Datta P, Das AK, Gomes A (2014) Anti-rheumatoid and anti-oxidant activity of homeopathic Guaiacum officinale in an animal model. Homeopathy 103:133–138

    Article  PubMed  Google Scholar 

  11. Zhao J, Zhao Y, Chen W, Li YM, Bian XW (2008) The differentiation-inducing effect of Nordy on HPV-16 subgenes-immortalized human endocervical cells H8. Anticancer Drugs 19:713–719

    Article  PubMed  Google Scholar 

  12. Colasanti M, Suzuki H (2000) The dual personality of NO. Trends Pharmacol Sci 21:249–252

    Article  CAS  PubMed  Google Scholar 

  13. Kitade H, Sakitani K, Inoue K, Masu Y, Kawada N, Hiramatsu Y, Kamiyama Y, Okumura T, Ito S (1996) Interleukin 1 β markedly stimulates nitric oxide formation in the absence of other cytokines or lipopolysaccharide in primary cultured rat hepatocytes but not in Kupffer cells. Hepatology 23:797–802

    CAS  PubMed  Google Scholar 

  14. Ohno N, Yoshigai E, Okuyama T, Yamamoto Y, Okumura T, Sato K, Ikeya Y, Nishizawa M (2012) Chlorogenic acid from the Japanese herbal medicine Kinginka (Flos Lonicerae japonicae) suppresses the expression of inducible nitric oxide synthase in rat hepatocytes. HOAJ Biol 1:2. doi:10.7243/2050-0874-1-2

    Article  Google Scholar 

  15. Takimoto Y, Qian HY, Yoshigai E, Okumura T, Ikeya Y, Nishizawa M (2013) Gomisin N in the herbal drug gomishi (Schisandra chinensis) suppresses inducible nitric oxide synthase gene via C/EBPβ and NF-κB. Nitric Oxide 28:47–56

    Article  CAS  PubMed  Google Scholar 

  16. Tanemoto R, Okuyama T, Matsuo H, Okumura T, Ikeya Y, Nishizawa M (2015) The constituents of licorice (Glycyrrhiza uralensis) differentially suppress nitric oxide production in interleukin-1β-treated hepatocytes. Biochem Biophys Rep 2:153–159. doi:10.1016/j.bbrep.2015.06.004

    PubMed  PubMed Central  Google Scholar 

  17. Nakajima A, Yamamoto Y, Yoshinaka N, Namba M, Matsuo H, Okuyama T, Yoshigai E, Okumura T, Nishizawa M, Ikeya Y (2015) A new flavanone and other flavonoids from green perilla leaf extract inhibit nitric oxide production in interleukin 1β-treated hepatocytes. Biosci Biotechnol Biochem 79:138–146

    Article  CAS  PubMed  Google Scholar 

  18. Wang Q, Yang Y, Li Y, Yu W, Hou ZJ (2006) An efficient method for the synthesis of lignans. Tetrahedron 62:6107–6112

    Article  CAS  Google Scholar 

  19. Koga Y, Kusama H, Narasaka K (1998) Preparations of furans from α-bromo ketones and enol ethers catalyzed by a rhenium (I) nitrogen complex. Bull Chem Soc Jpn 71:475–482

    Article  CAS  Google Scholar 

  20. Hattori M, Hada S, Kawata Y, Tezuka Y, Kikuchi T, Namba T (1987) New 2,5-bis-aryl-3,4-dimethyltetrahydrofuran lignans from the aril of Myristica fragrans. Chem Pharm Bull (Tokyo) 35:3315–3322

    Article  CAS  Google Scholar 

  21. Innocenti G, Puricelli L, Piacente S, Caniato R, Filippini R, Cappelletti EM (2002) Patavine, a new arylnaphthalene lignan glycoside from shoot cultures of Haplophyllum patavinum. Chem Pharm Bull (Tokyo) 50:844–846

    Article  CAS  Google Scholar 

  22. Pinto MMM, Kijjoa A, Mondranondra I, Gutiérrez AB, Herz W (1990) Lignans and other constituents of Knema furfuracea. Phytochemistry 29:1985–1988

    Article  CAS  Google Scholar 

  23. Fonseca SF, Nielsen LT, Rúveda EA (1979) Lignans of Araucaria angustifolia and 13C NMR analysis of some phenyltetralin lignans. Phytochemistry 18:1703–1708

    Article  CAS  Google Scholar 

  24. Kamino T, Shimokura T, Morita Y, Tezuka Y, Nishizawa M, Tanaka K (2016) Comparative analysis of the constituents in Saposhnikoviae Radix and Glehniae Radix cum Rhizoma by monitoring inhibitory activity of nitric oxide production. J Nat Med 70:253–259

    Article  CAS  PubMed  Google Scholar 

  25. Kanemaki T, Kitade H, Hiramatsu Y, Kamiyama Y, Okumura T (1993) Stimulation of glycogen degradation by prostaglandin E2 in primary cultured rat hepatocytes. Prostaglandins 45:459–474

    Article  CAS  PubMed  Google Scholar 

  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 126:131–138

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank Drs. Hiromitsu Maeda (College of Life Sciences, Ritsumeikan University) and Yuji Hasegawa (Central Equipment Room, Daiichi University of Pharmacy) for the MS measurements.

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    Authors and Affiliations

    1. Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga, 525-8577, Japan

      Yuki Nakano, Mana Kano, Hiroshi Kameoka, Tetsuya Okuyama & Mikio Nishizawa

    2. Department of Pharmacy, College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga, 525-8577, Japan

      Masaaki Nasu & Yukinobu Ikeya

    3. Department of Pharmacy Educational Assist Center, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka, 815-8511, Japan

      Yukinobu Ikeya

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    1. Yuki Nakano
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    Correspondence to Yukinobu Ikeya.

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    No potential conflict of interest was reported by the authors.

    Authors’ contributions

    M. Nishizawa and Y. Ikeya designed the experiments and wrote the manuscript. Y. Nakano, M. Nasu, M. Kano, and H. Kameoka performed the experiments as students. T. Okuyama performed the experiments and analyzed the data.

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    Y. Nakano and M. Nasu contributed equally to this study.

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    Nakano, Y., Nasu, M., Kano, M. et al. Lignans from guaiac resin decrease nitric oxide production in interleukin 1β-treated hepatocytes. J Nat Med 71, 190–197 (2017). https://doi.org/10.1007/s11418-016-1048-3

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    • DOI: https://doi.org/10.1007/s11418-016-1048-3

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