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Triterpenoids and diarylheptanoids from alnus hirsuta inhibit HIF-1 in ags cells

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Abstract

Bioassay-guided fractionation and purification of the EtOAc soluble fraction from the MeOH extract of the stem bark of Alnus hirsuta (Betulaceae), using an in vitro HIF-1 assay, led to the isolation of four triterpenoids (1–4) and six diarylheptanoids (5–10). Their structures were determined by comparison with the physicochemical and spectroscopic data in the literature. These compounds were investigated for their effects on the hypoxia-induced HIF-1 activation using an HIF-1 a mediated reporter gene assay in AGS cells. Among them, two diarylheptanoids, 2-oxatrycyclo[13.2.2.13,7]eicosa-3,5,7(20),15,17,18-hexaen-10-16-diol (6) and 2-oxatrycyclo [13.2.2.13,7]eicosa-3,5,7-(20), 15, 17, 18-hexaen-10-one (7), inhibited HIF-1 activation dose-dependently with IC50 values of 11.2 μM and 12.3 μM, respectively. These two compounds had no significant cytotoxicity to the AGS cells at the effective concentration for the inhibition of HIF-1 activation.

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References

  • Bae, C. I., Gong, J. M., Oh, J. W., Kim, H. J., Oh, G. J., Park, S. K., Chung, S. G., and Cho, E. H., Studies on the cytotoxic constituent ofAlnus hirsuta.Yakhak Hoechi, 41, 559–564 (1997).

    CAS  Google Scholar 

  • Chang, J. H., Cho, J. H., Kim, H. H., Lee, K. P., Lee, M. W., Han, S. S., and Lee, D. I., Antitumor activity of pedunculagin, one of the ellagitannin.Arch. Pharm. Res., 18, 396–401 (1995).

    Article  CAS  Google Scholar 

  • Giaccia, A., Siim, B. G., and Johnson, R. S., HIF-1 as a target for drug development.Nat. Rev. Drug Discovery, 2, 803–811 (2003).

    Article  CAS  Google Scholar 

  • Harris, A. L., Hypoxia-α key regulatory factor in tumour growth.Nat. Rev. Cancer, 2, 38–47 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Jeong, D. W., Kim, J. S., Cho, S. M., Lee, Y. A., Kim, K. H., Kim, S. W., and Lee, M. W., Diarylheptanoids from the stem bark ofAlnus hirsuta var.sibirica. Kor. J. Pharmacogn., 31, 28–33 (2000).

    CAS  Google Scholar 

  • Jiang, G. L., Tanaka, T., Inutsuka C., Kouno, I. and I., Alkaloids, Diarylheptanoid, and Naphthalene Carboxylic Acid Ester fromRhoiptelea chiliantha.Chem. Pharm. Bull., 49, 737–740 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Jiang, Z. H., Tanaka, T., Kirata, H., Fukuoka, R., and Kuono, I., Three Diarylheptanoids fromRhoiptelea chiliantha.Phytochemistry, 43, 1049–1054 (1996).

    Article  CAS  Google Scholar 

  • Joo, S. S., Kim, H. J., Kwon, H. S., and Lee, D. I., Augmentation of macrophage antitumor activities and nitric oxide production by oregonin.Arch. Pharm. Res., 25, 457–462 (2002-a).

    Article  PubMed  CAS  Google Scholar 

  • Joo, S. S., Kim, M. S., Oh, W. S., and Lee, D. I., Enhancement of NK cytotoxicity, antimetastasis and elongation effect of survival time in B16-F10 melanoma cells by oregonin.Arch. Pharm. Res., 25, 493–499 (2002-b).

    Article  PubMed  CAS  Google Scholar 

  • Kazuhito, O., Mmatsutake, H., Kozo, H., and Takayuki, S., Triterpenes from the leaves ofParsonsia Iaevigata, Phytochemistry, 26, 783–785 (1987).

    Article  Google Scholar 

  • Kim, D. K., Nam, Y. I., Kim, J. W., Shin, T. Y., and Lim, J. P., Pentacyclic triterpenoids fromIlex macropoda.Arch. Pharm. Res., 25, 617–620 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Lee, D. I., Cho, J. H., and Lee, M. W., Antitumor effect of natural products, purified tannin from plants and screening of BRM function.Yakhak Hoechi, 42, 345–352 (1998).

    CAS  Google Scholar 

  • Lee, K. S., Li, G., Lee, C. S., Woo, M. H., Lee, S. H., Jhang, Y. D., and Son, J. K., Cytotoxic Diarylheptanoids from the Roots ofJuglans mandshurica.J. Nat. Prod., 65, 1707–1708 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Lee, M. W., Jeong, D. W., Lee, Y. A., Park, M. S., and Toh, S. H., Flavonoids from the leaves ofAlnus hirsuta.Yakhak Hoechi, 43, 547–552 (1999).

    CAS  Google Scholar 

  • Lee, M. W., Kim, J. H., Jeong, D. W., Ahn, K. H., Toh, S. H., and Surh, Y. J., Inhibition of cyclooxygenase-2 expression by diarylheptanoids from the bark ofAlnus hirsuta var.sibirica. Biol. Pharm. Bull., 23, 517–518 (2000-a).

    CAS  Google Scholar 

  • Lee, M. W., Kim, N. Y., Park, M. S., Ahn, K. H., Toh, S. H., Hahn, D. R., Kim, Y. C., and Chung, H. T., Diarylheptanoids within vitro inducible nitric oxide synthesis inhibitory activity fromAlnus hirsuta.Planta Med., 66, 551–553 (2000-b).

    Article  PubMed  CAS  Google Scholar 

  • Lee, M. W., Park, M. S., Jeong, D. W., Kim, K. H., Kim, H. H., and Toh, S. H., Diarylheptanoids from the leaves ofAlnus hirsuta Turcz.Arch. Pharm. Res., 23, 50–53 (2000-c).

    Article  PubMed  CAS  Google Scholar 

  • Lee, M. W., Tanaka, T., Nonaka, G., and Nishioka, I., Tannins and related compounds. Part 110. Hirsunin, an ellagitannin with a diarylheptanoid moiety, fromAlnus hirsuta var.microphylla. Phytochemistry, 31, 967–970 (1992).

    CAS  Google Scholar 

  • Lee, S. J., Korea Folk Medicine. Seoul: Seoul National University Publishing Center Press, p.40 (1996).

    Google Scholar 

  • Lee, Y. A., Kim, K. H., Kim, J. S., Cho, S. M., Kim, S. W., and Lee, M. W., Antioxidative effects of diarylheptanoids fromAlnus hirsuta, Yakhak Hoechi, 44, 193–196 (2000-d).

    CAS  Google Scholar 

  • Matsunaga, S., Tanaka, R., and Akagi, M., Triterpenoids fromEuphorbia maculata.Phytochemistry, 27, 535–537 (1988).

    Article  CAS  Google Scholar 

  • Mohammed, K. A., Hossain, C. F., Zhang, L., Bruick, R. K., Zhou, Y. D., and Nagle, D. G., Laurenditerpenol, a new diterpene from the tropical marine algaLaurencia intricata that potently inhibits HIF-1 mediated hypoxic signaling in Brest Tumor cells.J. Nat. Prod., 67, 2002–2007 (2004).

    Article  PubMed  CAS  Google Scholar 

  • Morihara, M., Sakurai, N., Inoue, T., Kawai, K., and Nagai, M., Two Novel Diarylheptanoid Glucosides fromMyrica gale var. tomentosa and Absolute structure of plane — Chiral Galeon.Chem. Pharm. Bull., 45, 820–823 (1997).

    CAS  Google Scholar 

  • Rischin, D., Peters, L., Hicks, R., Hughes, P., Fisher, R., Hart, R., Sexton, M., D’Costa, I., and Von Roemeling, R., Phase I trial of concurrent tirapazamine, cisplatin, and radiotherapy in patients with advanced head and neck cancer.J. Clin. Oncol., 19, 535–542 (2001).

    PubMed  CAS  Google Scholar 

  • Sakkurai, N., Yaguci, Y., and Inoue, T., Triterpenoids fromMyrica rubra.Phytochemistry, 26, 217–219 (1987).

    Article  Google Scholar 

  • Semenza, G. L., Targeting HIF-1 for cancer therapy.Nat. Rev. Cancer, 3, 721–732 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Terazawa, M., Miyake, M., and Okuyama, H., Phenolic compounds in living tissue of woods. V. Reddish orange staining in keyamahannoki (Alnus hirsuta) and hannoki (A. japonica) [Betulaceae] caused by the interaction of hirsutoside and catechol oxidase after cutting the woods.Mokuzai Gakkaishi, 30, 601–607 (1984a).

    CAS  Google Scholar 

  • Terazawa, M., Okuyama, H., and Miyake, M., Isolation of hirsutanonol and hirsutenone, two new diarylheptanoids from the green bark of Keyamahannoki,Alnus hirsuta.Mokuzai Gakkaishi, 19, 45–46 (1973).

    CAS  Google Scholar 

  • Terazawa, M., Okuyama, H., Miyake, M., and Sasaki, M., Phenolic compounds in living tissue of woods. IV. Hirsutoside from the green bark of keyamahannoki (Alnus hirsuta) [Betulaceae] and its seasonal variations in the living tissues of hannoki (A. japonica).Mokuzai Gakkaishi, 30, 587–600 (1984-b).

    CAS  Google Scholar 

  • Uvarova, N. I., Oshitok, G I., Suprunov, N. I., and Elyakov, G. B., Triterpenoids and other constituents from the Far Eastern species ofAlnus.Phytochemistry, 11, 741–743 (1972).

    Article  CAS  Google Scholar 

  • Von Pawel, J., Von Roemeling, R., Gatzemeier, U., Boyer, M., Elisson, L. O., Clark, P., Talbot, D., Rey, A., Butler, T. W., Hirsh, V., Olver, I., Bergman, B., Ayoub, J., Richardson, G., Dunlop, D., Arcenas, A., Vescio, R., Viallet, J., and Treat, J., Tirapazamine plus cisplatin versus cisplatin in advanced non- small-cell lung cancer: A report of the international CATAPULT I study group. Cisplatin and Tirapazamine in Subjects with Advanced Previously Untreated Non-Small- Cell Lung Tumors.J. Clin. Oncol., 18, 1351–1359 (2000).

    Google Scholar 

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Correspondence to KiHwan Bae.

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Jin, W., Cai, X.F., Na, M. et al. Triterpenoids and diarylheptanoids from alnus hirsuta inhibit HIF-1 in ags cells. Arch Pharm Res 30, 412–418 (2007). https://doi.org/10.1007/BF02980213

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