Abstract
Crude water extracts of 13 traditional Korean medicinal ingredients used for leiomyomal treatment were prepared and used to treat human uterine normal myometrial and leiomyomal cell cultures. All the ingredients inhibited proliferation and altered the morphology of both myometrial and leiomyomal cells. Among the 13 ingredients, n-hexane-, chloroform-, and ethylacetate-soluble fractions were extracted from seven ingredients that potently inhibited cell proliferation in their water extract form. Among these, the ethylacetate-fraction of Phlomis umbrosa and Spatholobus suberectus, and the chloroform-fraction of Curcuma zedoaria and S. suberectus inhibited leiomyomal cell proliferation significantly compared to myometrial cell proliferation. Similarly, immunohistochemical analysis showed the inhibition of transforming growth factor-beta receptor 2 in leiomyomal tissue after treatment with the fractions of the ingredients. Moreover, the chloroform-fraction of C. zedoaria was subfractionated by open column chromatography. Two of the eight subfractions (fractions 6 and 7) potently inhibited cell proliferation in leiomyoma compared to myometrium. Further study will be performed with the goal of isolating specific compounds from two effective subfractions of C. zedoaria, ethylacetate-fraction of P. umbrosa, and the ethylacetate and chloroform-fractions of S. suberectus. The present study may be helpful in developing an alternative remedy to leiomyoma with minimal side-effects compared to the current treatments.
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Baek, S. H., and Kim, D. C., The effect of Leonurus sibiricus on the proliferation inhibition of human uterine leiomyoma cell and expression of gene related cell apoptosis. Korean medical database, 19, 1–12 (2006).
Blobe, G. C., Schiemann, W. P., and Losish, H. F., Role of transforming growth factor β in human disease. N. Engl. J. Med., 342, 1350–1358 (2000).
Chegini, N., Luo, X., Ding, L., and Ripley, D., The expression of Smads and transforming growth factor beta receptors in leiomyoma and myometrium and the effect of gonadotropin releasing hormone analogue therapy. Mol. Cell. Endocrinol., 209, 9–16 (2003).
Dorn, D. C., Alexenizer, M., Hengstler, J. G., and Dorn, A., Tumor cell specific toxicity of Inula helenium extracts. Phytother. Res., 20, 970–980 (2006).
Dou, Q., Zhao, Y., Tarnuzzer, R. W., Rong, H., Williams, R. S., Schultz, G. S., and Chegini N., Suppression of transforming growth factor-beta (TGF beta) and TGF beta receptor messenger ribonucleic acid and protein expression in leiomyomata in women receiving gonadotropin-releasing hormone agonist therapy. J. Clin. Endocrinol. Metab., 81, 3222–3230 (1996).
Flanders, K. C., Smad3 as a mediator of the fibrotic response. Int. J. Exp. Pathol., 85, 47–64 (2004).
Friedman, A. J., Clinical experience in the treatment of fibroids with leuprolide and other GnRH agonists. Obstet. Gynecol. Surv., 44, 311–313 (1989).
Islam, M. A., Ahmed, F., Das, A. K., and Bachar, S. C., Analgesic and anti-inflammatory activity of Leonurus sibiricus. Fitoterapia, 76, 359–362 (2005).
Ka, H., Park, H. J., Jung, H. J., Choi, J. W., Cho, K. S., Ha, J., and Lee, K. T., Cinnamaldehyde induces apoptosis by ROS-mediated mitochondrial permeability transition in human promyelocytic leukemia HL-60 cells. Cancer Lett., 196, 143–152 (2003).
Kim, C. H., Kim, D. I., Kwon, C. N., Kang, S. K., Jin, U. H., Suh, S. J., Lee, T. K., and Lee, I. S., Euonymus alatus (Thunb.) Sieb induces apoptosis via mitochondrial pathway as prooxidant in human uterine leiomyomal smooth muscle cells. Int. J. Gynecol. Cancer, 16, 843–848 (2006).
Kim, D. C., Ramachandran, S., Baek, S. H., Kwon, S. H., Kwon, K. Y., Cha, S. D., Bae, I., and Cho, C. H., Induction of growth inhibition and apoptosis in human uterine leiomyoma cells by isoliquiritigenin. Reprod. Sci., 15, 552–558 (2008a).
Kim, K. W., Jin, U. H., Kim, D. I., Lee, T. K., Kim, M. S., Oh, M. J., Kim, M. S., Kwon, D. Y., Lee, Y. C., and Kim, C.H., Antiproliferative effect of Scutellaria barbata D. Don. on cultured human uterine leiomyoma cells by downregulation of the expression of Bcl-2 protein. Phytother. Res., 22, 583–590 (2008b).
Kwon, B. M., Lee, S. H., Choi, S. U., Park, S. H., Lee, C. O., Cho, Y. K., Sung, N. D., and Bok, S. H., Synthesis and in vitro cytotoxicity of cinnamaldehydes to human solid tumor cells. Arch. Pharm. Res., 21, 147–152 (1998).
Lee, B. S. and Nowak, R. A., Human leiomyoma smooth muscle cells show increased expression of transforming growth factor-beta 3 (TGF beta 3) and altered responses to the antiproliferative effects of TGF beta. J. Clin. Endocrinol. Metab., 86, 913–920 (2001).
Lee, C. W., Lee, S. H., Lee, J. W., Ban, J. O., Lee, S. Y., Yoo, H. S., Jung, J. K., Moon, D. C., Oh, K. W., and Hong J. T., 2-hydroxycinnamaldehyde inhibits SW620 colon cancer cell growth through AP-1 inactivation. J. Pharmacol. Sci., 104, 19–28 (2007).
Lee, S. M., Li, M. L., Tse, Y. C., Leung, S. C., Lee, M. M., Tsui, S. K., Fung, K. P., Lee, C. Y., and Waye, M. M., Paeoniae Radix, a Chinese herbal extract, inhibit hepatoma cells growth by inducing apoptosis in a p53 independent pathway. Life Sci., 71, 2267–2277 (2002).
Lee, S., Lee, Y. S., Jung, S. H., Shin, K. H., Kim, B. K., and Kang, S. S., Anti-tumor activities of decursinol angelate and decursin from Angelica gigas. Arch. Pharm. Res., 26, 727–730 (2003).
Lee, T. K., Lee, J. Y., Kim, D. I., Lee, Y. C., and Kim, C. H., Differential regulation of protein kinase C activity by modulating factors and Euonymus alatus (Thunb.) Sieb in human myometrial and uterine leiomyomal smooth muscle cells. Int. J. Gynecol. Cancer., 15, 349–358 (2005).
Lethaby, A. and Vollenhoven, B., Fibroids (uterine myomatosis, leiomyomas). Clin. Evid., 7, 1666–1678 (2002).
Mehl-Madrona, L., Complementary medicine treatment of uterine fibroids: a pilot study. Altern. Ther. Health Med., 8, 34–46 (2002).
Moon, E. Y., Lee, M. R., Wang, A. G., Lee, J. H., Kim, H. C., Kim, H. M., Kim, J. M., Kwon, B. M., and Yu, D. Y., Delayed occurrence of H-ras12V-induced hepatocellular carcinoma with long-term treatment with cinnamaldehydes. Eur. J. Pharmacol., 530, 270–275 (2006).
Moura, M. D. D., Silva, J. D. S., Oliveira, R. A. G., Diniz, M. F. F. M., and Barbosa-filho, J. M., Natural products reported as potential inhibitors of uterine cervical neoplasia. Acta Farm. Bonaerense, 21, 67–74 (2002).
Nagasawa, H., Onoyama, T., Suzuki, M., Hibino, A., Segawa, T., and Inatomi, H., Effects of motherwort (Leonurus sibiricus L) on preneoplastic and neoplastic mammary gland growth in multiparous GR/A mice. Anticancer Res., 10, 1019–1023 (1990).
Pamplona, C. R., de Souza, M. M., Machado Mda, S., Cechinel Filho, V., Navarro, D., Yunes, R. A., Delle Monache, F., and Niero, R., Seasonal variation and analgesic properties of different parts from Curcuma zedoaria Roscoe (Zingiberaceae) grown in Brazil. Z. Naturforsch. C., 61, 6–10 (2006).
Parker, W. H., Etiology, symptomatology, and diagnosis of uterine myomas. Fertil. Steril., 87, 725–736 (2007).
Sakamoto, S., Yoshino, H., Shirahata, Y., Shimodairo, K., and Okamoto, R., Pharmacotherapeutic effects of Kueichih-fu-ling-wan (Keishi-bukuryo-go) on human uterine myomas. Am. J. Chin. Med., 20, 313–317 (1992).
Sankaran, S., Medical management of fibroids. Best Pract. Res. Clin. Obstet. Gynaecol., 22, 655–676 (2008).
Satoh, M., Satoh, Y., Isobe, K., and Fujimoto, Y., Studies on the constituents of Leonurus sibiricus L. Chem. Pharm. Bull. (Tokyo), 51, 341–342 (2003).
Schnaper, H. W., Hayashida, T., Hubchak, S. C., and Poncelet, A. C., TGF-β signal transduction and mesangial cell fibrogenesis. Am. J. Physiol., 284, F243–F252 (2003).
Tepkeeva, I. I., Moiseeva, E. V., Chaadaeva, A. V., Zhavoronkova, E. V., Kessler, Y. V., Semushina, S. G., and Demushkin, V. P., Evaluation of antitumor activity of peptide extracts from medicinal plants on the model of transplanted breast cancer in CBRB-Rb(8.17)1Iem mice. Bull. Exp. Biol. Med., 145, 464–466 (2008).
Walker, C. L. and Stewart, E. A., Uterine fibroids: the elephant in the room. Science, 308, 1589–1592 (2005).
Yoshioka, T., Fujii, E., Endo, M., Wada, K., Tokunaga, Y., Shiba, N., Hohsho, H., Shibuya, H., and Muraki, T., Anti-inflammatory potency of dehydrocurdione, a zedoary-derived sesquiterpene. Inflamm. Res., 47, 476–481 (1998).
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Bajracharya, P., Lee, E.J., Lee, DM. et al. Effect of different ingredients in traditional Korean medicine for human uterine leiomyoma on normal myometrial and leiomyomal smooth muscle cell proliferation. Arch. Pharm. Res. 32, 1555–1563 (2009). https://doi.org/10.1007/s12272-009-2107-z
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DOI: https://doi.org/10.1007/s12272-009-2107-z