Browse > Article
http://dx.doi.org/10.3839/jabc.2009.038

Inhibitory Effect of Acetylshikonin from Roots of Lithospermum erythrorhizon on LDL Oxidation and FPTase Activity  

Kim, Geum-Soog (Department of Herbal Crop Research, National Institute of Horticultural & Herbal Science, RDA)
Jeong, Tae-Sook (Korea Research Institute of Bioscience & Biotechnology)
Kwon, Byoung-Mok (Korea Research Institute of Bioscience & Biotechnology)
Kim, Young-Ok (Department of Herbal Crop Research, National Institute of Horticultural & Herbal Science, RDA)
Cha, Seon-Woo (Department of Herbal Crop Research, National Institute of Horticultural & Herbal Science, RDA)
Song, Kyung-Sik (College of Agriculture and Life Sciences, Kyungpook National University)
Bek, Nam-In (Graduate School of Biotechnology, Kyung Hee University)
Publication Information
Journal of Applied Biological Chemistry / v.52, no.4, 2009 , pp. 221-225 More about this Journal
Abstract
Lithospermum erythrorhizon has been known well as one of traditional medicine for fever reduction, detoxication, and blood circulation improvement. This study was carried out to isolate biological active compounds from roots of Lithospermum erythrorhizon and to investigate their low density lipoprotein (LDL) antioxidant and anticancer activities. The hexane extract of Lithospermi Radix has been separated on silica gel chromatography and a naphthoquinone pigment compound 1 has been isolated. The structure of the compound 1 has been identified by spectroscopic technique, including MS and NMR, as acetylshikonin (1). Acetylshikonin showed significantly inhibitory activity on $Cu^{2+}$-induced human LDL oxidation with $IC_{50}$ value of $8.8\;{\mu}M$ and obvious anticancer effect by inhibiting farnesyl:protein transferase (FPTase) activity with $IC_{50}$ value of $23\;{\mu}M$, which suggested that acetylshikonin might be useful for the treatment of atherosclerosis and cancer.
Keywords
acetylshikonin; FPTase; LDL oxidation; Lithospermum erythrorhizon;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
Times Cited By SCOPUS : 0
연도 인용수 순위
1 Ahn BT, Lee SG, Lee SB, Lee ES, Kim JG, Bok SH, and Jeong TS (2001) Low-density lipoprotein-antioxidant constituents of Saururus chinensis. J Nat Prod 64, 1562-1564   DOI   ScienceOn
2 Bjorkhem I, Henriksson-Freyschuss A, Breuer O, Diczfalusy U, Berglund L, and Henriksson P (1991) The antioxidant butylated hydroxytoluene protects against atherosclerosis. Arterioscler Thromb 11, 15-22   PUBMED   ScienceOn
3 Chang YS, Kuo SC, Weng SH, Jan SC, Ko FN, and Teng CM (1993) Inhibition of platelet aggregation by shikonin derivatives isolated from Arnebia euchromoma. Planta Med 59, 401-404   DOI   ScienceOn
4 Hwang SY, Hwang BY, Kang SS, Kim CM, Park JH, Bae KH, Son KH, Lee SH, Chang SY, Kan SJ, Ro JS, and Lee KS (2000) Isolation and quantitative analysis of acetylshikonin from Lithospermi Radix. Kor J Pharmacogn 31, 295-299   과학기술학회마을   ScienceOn
5 Jeong TS, Kim JR, Kim KS, Cho KH, Bae KH, and Lee WS (2004) Inhibiatory effects of multi-substituted benzylidenethiazolidine-2,4-diones on LDL oxidation. Bioorg Med Chem 12, 4017-4023   DOI   ScienceOn
6 Mashima R, Witting PK, and Stecker R (2001) Oxidants and antioxidants in atherosclerosis. Curr Opin Lipidol 12, 411-418   DOI   ScienceOn
7 Nagnao Y, Nakamura T, Matsuzawa Y, Cho M, Ueda Y, and Kita T (1992) Probucol and atherosclerosis in the Watanabe heritable hyperlipidemic rabbit:long-term antiatherogenic effect and effects on established plaques. Atherosclerosis 92, 131-140   DOI   PUBMED
8 Omer CA, Chen Z, Diehl RE, Conner MW, Chen HY, Trumbauer ME, Gopal-Truter S, Seeburger G, Bhimnathwala H, Abrams MT, Davide JP, Ellis MS, Gibbs JB, Greenberg I, Hamilton K, Koblan KS, Kral AM, Liu D, Lobell RB, Miller PJ, Mosser SD, O'Neill TJ, Rands E, Schaber MD, Senderak ET, Oliff A, and Kohl NE (2000) Mouse mammary tumor virus-Ki-rasB transgenic mice develop mammary carcinomas that can be growth-inhibited by a farnesyl:protein transferase inhibitor. Cancer Res 60, 2680-2688   PUBMED   ScienceOn
9 Steinberg D, Parthasarathy S, Carew TE, Khoo JC, and Witztum JL (1989) Beyond cholesterol: modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 320, 915-924   DOI   PUBMED   ScienceOn
10 Sankawa U, Ebizuka Y, Miyazaki T, Isomura Y, and Otsuka H (1977) Antitumor activity of shikonin and its derivatives. Chem Pharm Bull 25, 1392-1395   PUBMED
11 Sankawa U, Otsuka H, Kataoka Y, Iitaka Y, Hoshi A, and Kuretani K (1981) Antitumor activity of shikonin and its derivatives. II. X-ray analysis of cyclo-alkannin leucoacetate, tautomerism of alkannin and cyclo-alkannin and antitumor activity of alkannin derivatives. Chem Pharm Bull 29, 116-122   PUBMED   ScienceOn
12 Reiss Y, Seabra MC, Goldstein JL, and Brown MS (1990b) Purification of ras farnesyl:protein transferase. Methods: Companion Methods Enzymol 1, 241-245   DOI
13 Tabata M, Tsukada M, and Fukui H (1982) Antimicrobial activity of quinone derivatives from Echium lycopsis callus cultures. Planta Med 44, 234-236   DOI   ScienceOn
14 Reiss Y, Goldstein JL, Seabra MC, Casey PJ, and Brown MS (1990a) Inhibition of purified $p21^{ras}$ farnesyl:protein transferase by Cys-AAX tetrapeptides. Cell 62, 81-88   DOI   ScienceOn
15 Havel RJ, Eder HA, and Bragdon JH (1955) The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest 34, 1345-1353   DOI   PUBMED   ScienceOn
16 Tanaka S, Tajima M, Tsukada M, and Tabata M (1986) A comparative study on anti-inflammatory activities of the enantiomers, shikonin and alkannin J Nat Prod 49, 466-469   DOI   PUBMED
17 Staniforth V, Wang SY, Shyur LF, and Yang NS (2004) Shikonins, phytocompounds from Lithospermum erythrorhizon, inhibit the transcriptional activation of human tumor necrosis factor $\acute{a}$ promoter in vivo. J Biol Chem 279, 5877-5885   DOI   ScienceOn
18 Leonard DM (1997) Ras farnesyltransferase: A new therapeutic target. J Med Chem 40, 2971-2990   DOI   PUBMED   ScienceOn
19 Lee SH, Kim HK, Seo JM, Kang HM, Kim JH, Son KH, Lee HS, and Kwon BM (2002) Arteminolides B, C, and D, new inhibitors of farnesyl protein transferase from Artemisia argyi. J Org Chem 67, 7670-7675   DOI   ScienceOn
20 Lee HJ, Lee HJ, Magesh V, Nam DW, Lee EO, Ahn KS, Jung MH, Ahn KS, Kim DK, Kim JY, and Kim SH (2008) Shikonin, acetylshikonin, and isobutyroylshikonin inhibit VEGF-induced angiogenesis and suppress tumor growth in Lewis lung carcinoma-bearing mice Yakugaku Zasshi 128, 1681-1688   DOI   ScienceOn
21 Kwon BM, Kim SH, Baek NI, Lee SI, Kim EJ, Yang JH, Chae BS, Lee JH, Park HW, Park JS, and Kim DK (2009) Farnesyl protein transferase inhibitory components of Polygonum multiflorum. Arch Pharm Res 32, 495-499   DOI   ScienceOn
22 Weng XC, Xiang GQ, Jiang AL, Liu YP, Wu LL, Dong XW, and Duan S (2000) Antioxidant properties of components extracted from puccoon (Lithospermum erythrorhizon Sieb. et Zucc.). Food Chem 69, 143-146   DOI   ScienceOn
23 Hsu MF, Chang LC, Huang LJ, Kuo SC, Lee HY, Lu MC, and Wang JP (2009) The influence of acetylshikonin, a natural naphthoquinone, on the production of leukotriene B-4 and thromboxane A(2) in rat neutrophils. Eur J Pharmacol 607, 234-243   DOI   PUBMED   ScienceOn
24 Diaz MN, Frei B, Vita JA, and Jr. Keaney JF (1997) Antioxidants and atherosclerotic heart disease. N Engl J Med 337, 408-416   DOI   ScienceOn
25 Jeong TS, Ryu YB, Kim HY, Curtis-Long MJ, An SJ, Lee JH, Lee WS, and Park KH (2008) Low density lipoprotein (LDL)-antioxidant flavonoids from roots of Sophora flavescens. Biol Pharm Bull 31, 2097-2102   DOI   ScienceOn
26 Pompliano DL, Rands E, Schaber MD, Mosser SD, Anthony NJ, and Gibs JB (1992) Steady-state kinetic mechanism of ras farnesy1:protein transferase. Biochemistry 31, 3800-3807   DOI   ScienceOn
27 Sekine T, Masumizu T, Maitani Y, and Nagai T (1998) Evaluation of superoxide anion radical scavenging activity of shikonin by electron spin resonance. Int J Pharm 174, 133-139   DOI   ScienceOn
28 Buege JA and Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52, 302-310   DOI   PUBMED
29 Sharma N, Sharma UK, Gupta AP, Devla, Sinha AK, Lal B, and Ahuja PS (2009) Simultaneous densitometric determination of shikonin, acetylshikonin, and beta-acetoxyisovaleryl-shikonin in ultrasonic-assisted extracts of four Arnebia species using reversed-phase thin layer chromatography. J Sep Sci 32, 3239-3245   DOI   ScienceOn
30 Lee KS, Ahn DK, Shin MK, Kim CM et al. (1998) In The Encyclopedia of Oriental Herbal Medicine, pp. 4657-4663, Jungdam Pubishing Co., Seoul, Korea