Abstract
This study examnined the effects of tanshinone derivatives (tanshinone I, cryptotanshinone, 15,16-dihydrotanshinone I) on prostaglandin (PG) and nitric oxide (NO) metabolism in an attempt to establish their anti-inflammatory mechanisms and to present a scientific rationale for the use of Salvia miltiorrhiza (danshen) in inflammatory conditions. From lipopolysaccharidetreated RAW 264.7 cells, cyclooxygenase-2 (COX-2)-mediated PGE2 production was inhibited by tanshinone I, cryptotanshinone and 15,16-dihydrotanshinone I, while only cryptotanshinone and 15,16-dihydrotanshinone I inhibited inducible NO synthase (iNOS)-mediated NO synthesis at 1-50 μM. Particularly, cryptotanshinone was found to be a down-regulator of proinflammatory molecule expression, including COX-2 and iNOS. The electrophoretic mobility shift assay showed that cryptotanshinone and 15,16-dihydrotanshinone I also inhibited the activation of the transcription factors, such as nuclear transcription factor-κB and activator protein-1. Moreover, cryptotanshinone exhibited in vivo anti-inflammatory activity against carrageenaninduced paw edema in rats. Overall, these results provide additional scientific rationale for the anti-inflammatory use of danshen in Chinese medicine. Especially, cryptotanshinone and 15,16-dihydrotanshinone I are important constituents.
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Bae, K., In Bae, K. (Ed.). The medicinal plants of Korea, Kyo-Hak Pub. Co., Seoul, pp. 444, (2000).
Chi, Y. S., Cheon, B. S., and Kim, H. P., Effect of wogonin, a plant flavone from Scutellaria radix, on the suppression of cyclooxygenase-2 and the induction of inducible nitric oxide synthase in lipopolysaccharide-treated RAW 264.7 cells. Biochem. Pharmacol., 61, 1195–1203 (2001).
Choi, H.-S., Cho, D.-I., Choi, H.-K., Im, S. Y., Ryu, S.-Y., and Kim, K.-M., Molecular mechanisms of inhibitory activity of tanshinones on lipopolysaccharide-induced nitric oxide generation in RAW 264.7 cells. Arch. Pharm. Res., 27, 1233–1237 (2004).
Choi, H. S. and Kim, K. M., Tanshinones inhibit mast cell degranulation by interfering with IgE receptor-mediated tyrosine phosphorylation of PLCγ 2 and MAPK. Planta Med., 70, 178–180 (2004).
Duke, J. A. and Ayensu, E. S., In Duke, J. A. and Ayensu, E. S. (Eds.). Medicinal plants of China. Reference Publications, Inc., Algonquin, Michigan, Vol. 2, pp. 381, (1985).
Gallin, J. I. and Snyderman, R., Overview, In Gallin, J. I. and Snyderman, R. (Eds.). Inflammation: Basic principles and clinical correlates 3rd ed. Lippincott Williams & Wilkins, Philadelphia, pp. 1–4, (1999).
Hsu, Y.-W., Chi, K.-H., Huang, W.-C., and Lin, W.-W., Ceramide inhibits lipopolysaccharide-mediated nitric oxide synthase and cyclooxygenase-2 induction in macrophages: Effects on protein kinases and transcription factors. J. Immunol., 166, 5388–5397 (2001).
Jang, S. I., Jeong, S. I., Kim, K. J., Kim, H. J., Yu, H. H., Park, R., Kim, H. M., and You, Y. O., Tanshinone IIA from Salvia miltiorrhiza inhibits inducible nitric oxide synthase expression and production of TNF-α, IL-1β and IL-6 in activated RAW 264.7 cells. Planta Med., 69, 1057–1059 (2003).
Jin, D. Z., Yin, L. L., Ji, X. Q., and Zhu, X. Z., Cryptotanshinone inhibits cyclooxygenase-2 enzyme activity but not its expression. Eur. J. Pharmacol., 549, 166–172 (2006).
Kang, B. Y., Chung, S. W., Kim, S. H., Ryu, S. Y., and Kim, T. S., Inhibition of interleukin-12 and interferone-γ production in immune cells by tanshinones from Salvia miltiorrhiza. Immunopharmacol., 49, 355–361 (2000).
Kang, H. S., Chung, H. Y., Jung, J. H., Kang, S. S., and Choi, J. S., Antioxidant effect of Salvia miltiorrhiza. Arch. Pharm. Res., 20, 496–500 (1997).
Kim, H., Lee, H. S., Chang, K. T., Ko, T. H., Baek, K. J., and Kwon, N. S., Chloromethyl ketones block induction of nitric oxide synthase in murine macrophages by preventing activation of nuclear factor-κB. J. Immunol., 154, 4741–4748 (1995).
Kim, S. Y., Moon, T. C., Chang, H. W., Son, K. H., Kang, S. S., and Kim, H. P., Effects of tanshinone I isolated from Salvia miltiorrhiza on arachidonic acid metabolism and in vivo inflammatory responses. Phytotherapy Res., 16, 616–620(2002).
Dweck, A. C., The folklore and cosmetic use of various Salvia species, In Kintzios, S. E. (Ed.). SAGE The genus Salvia, Overseas Publishers Association, New York, pp. 9–18, (2000).
Lee, P., Hur, J., Lee, J., Kim, J., Jeong, J., Kang, I., Kim, S. Y., and Kim, H., 15,16-Dihydrotanshinone I suppresses the activation of BV-2 cell, a murine microglia cell line, by lipopolysaccharide. Neurochem. Int., 48, 60–66 (2006).
Mosmann, T., Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxic assays. J. Immunol. Methods, 65, 55–63 (1983).
Ryu, S. Y., No, Z., Kim, S. H., and Ahn, J. W., Two novel abietane diterpenes from Salvia miltiorrhiza. Planta Med., 63, 44–46 (1997).
Ryu, S. Y., Oak, M. H., and Kim, K. M., Inhibition of mast cell degranulation by tanshinones from the roots of Salvia miltiorrhiza. Planta Med., 65, 654–655 (1999).
Suh, N., Honda, T., Finlay, H. J., Barchowsky, A., Williams, C., Benoit, N. E., Xie, Q., Nathan, C., Gribble, G. W., and Sporn, M. B., Novel triterpenoids suppress inducible nitric oxide synthase (iNOS) and inducible cyclooxygenase (COX-2) in mouse macrophages. Cancer Res., 58, 712–723 (1998).
Suh, S. J., Jin, U. H., Choi, H. J., Chang, H. W., Son, J. K., Lee, S. H., Jeon, S. J., Son, K. H., Chang, Y. C., Lee, Y. C., and Kim, C. H., Cryptotanshinone from Salvia miltiorrhiza Bunge has an inhibitory effect on TNF-α-induced matrix metalloproteinase-9 production and HASMC migration via downregulated NF-κB and AP-1. Biochem. Pharmacol., 72, 1680–1689 (2006).
Winter, C. A., Risley, E. A., and Nuss, G. W., Carrageenaninduced edema in the hindpaw of the rat as an assay for antiinflammatory drugs. Proc. Soc. Exp. Biol. Med., 111, 544–547(1962).
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Jeon, S.J., Son, K.H., Kim, Y.S. et al. Inhibition of prostaglandin and nitric oxide production in lipopolysaccharide-treated RAW 264.7 cells by tanshinones from the roots of Salvia miltiorrhiza bunge. Arch. Pharm. Res. 31, 758–763 (2008). https://doi.org/10.1007/s12272-001-1223-4
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DOI: https://doi.org/10.1007/s12272-001-1223-4