• Archives of Pharmacal Research
• /
• v.21 no.5
• /
• pp.565-569
• /
• 1998

An HPLC method was developed to resolve the enantiomers of shikonin derivatives of the Lithospermi Radix. The optimum mobile phase on a Chiracel AD column was 5% isopropanol in n-hexane with folw rate of 1 ml/min. Establishment of this method made possible to determine the ratios of shikonin/acetylshikonin or alkanin/acetylalkanin in the same root. The correlation of the ratios of these substance pairs appeared characteristic for the country where they were originated from. All of the Korean species showed significantly higher ratios of shikonin/acetylshikonin and alkanin/acetylalkanin than the Chinese ones. this method would be useful to determine the orgin of Lithospermi Radix.

• Journal of Microbiology and Biotechnology
• /
• v.10 no.4
• /
• pp.514-517
• /
• 2000

Abstracts Six shikonin metabolites were obtained from human intestinal bacteria, Bacteriodes fragilis subsp. thetaotus. following biotransformation. The transformation of shikonin (1) was performed anaerobically for 3 day at $37^{\circ}C$ in thc bacterial suspension of B. Fagilis which was cultured overnight in GAM broth. The incubation mixture \vas extracted with EtGAc Lo give a dark-brown residue. The residue was apphed to a silica gel column, which was eluted successively with hexane (Fr. A), $CHCl_3$ (Fr. B), and $CHCl_3$:MeOH (9:I) (Fr. C). Six metabolites. Fr.A (2 and 3), Fr. B (6 and 7), and Fr. C (4 and 5) were isolated by repeated silica gel column chromatography, preparatlVe TLC, followed by Sephadex LH-20. In vitro cytotoxicities were tested against human tumor cell lines; PC-3 (prostate), ACHN (renal), A549 (lung), SW620 (colon), KS62 (leukemia), and Du145 (prostate). The shikonin metabolites 2. 4, 5, and 6 showed weaker cytotoxicity than the parenL shikonin (1). whereas shikonin monomenc metabolite 3 ($ED_{50}{\;}O.44-{\;}1.22{\;}\mu\textrm{g}/ml$) and dimeric metabolite 7 ($ED_{50}{\;}O.48-{\;}2.35{\;}\mu\textrm{g}/ml$) exhibited stronger activities compared with adriamycin, which was used as the positive control.ontrol.

• Journal of Food Hygiene and Safety
• /
• v.15 no.2
• /
• pp.167-172
• /
• 2000

Lithospermum erythrorhyzon has been used as a red fooddye and traditional Chinese medicine to treat wounds, skin diseases and burns. Platelet activation plays an important role in thrombosis and haemostasis. Here, we studied the inhibition of platelet activation and its active compound from the root of Lithospermum erythrorhyzon. Its ethyl acetate extract inhibited the aggregation of washed rabbit platelets induced by collagen or thrombin. Five naphthoquinone pigments , shikonin , acetylshikonin , is obutylshikonin, $\alpha$-methyl-n-butylshikonin and $\beta$,$\beta$-dimethylacrylshikonin were isolated by means of high pressure liquid chromatography. The structures were determined by comparison of their proton nuclear magnetic resonance spectra. The potency of their inhibition was in the following order : $\beta$,$\beta$-dimethylacrylshikonin$\geq$$\alpha$-methyl-n-butylshikonin>isobutylshikonin>acetylshikonin>shikonin. It is suggested that the size of the aliphatic hydroxy group of shikonin is important for the enhancement of potency.

• Advances in Traditional Medicine
• /
• v.5 no.4
• /
• pp.283-293
• /
• 2005

Our previous study showed that a novel synthetic shikonin derivative, 6-(1-hydroxyimino-4-methylpentyl)5,8-dimethyoxy 1,4-naphthoquinone S-52 (DMNQ S-52) induced apoptosis. In the present study, we investigated its anti-metastatic activities as compared with shikonin because DMNQ S-52 was synthesized for overcoming weak points of shikonin such as high toxicity, low solubility and deleterious effects. DMNQ S-52 showed the weaker cytotoxicity $(IC_{50};\;12.3{\pm}1.6\;{\mu}M)$ against Lewis lung carcinoma (LLC) cells than that of shikonin $(IC_{50};\;4.2{\pm}1.1\;{\mu}M)$. DMNQ S-52, at non-toxic concentrations $(less\;than\;10\;{\mu}M)$, significantly inhibited the invasion and migration of LLC cells. DMNQ S-52 also significantly inhibited the production of MMP-9, MTl-MMP and uPAR. Moreover, daily i.p. administration of DMNQ S-52 at dose of 5 mg/kg in mice resulted in a potent inhibition of the primary tumor size of LLC in the lung as well as the metastasis of lymph nodes. These findings suggest that the DMNQ S-52 has therapeutic potential to inhibit metastasis via inhibition of MMP family and uPA/plasminogen system.

• Journal of the Korean Society of Costume
• /
• v.14
• /
• pp.133-144
• /
• 1990

The purpose of this study is to investigate the absorbance of the Shikonin, one of the major purple pigments, and the stability against the effect of light, $O_2$, and temperature. The effect of mordant and mordanting condition to color and color-fastness is compared and analysed through the color-fastness-test, color-difference value-test, and IR-test. The results were as follows; 1. The absorbance of Shikonin was examinated through 6 kinds of solutions and distilled water. Shikonin was absorbed by solutions rather easily than distilled water. 2. The light effect to Shikonin indicated that the solution with the light was more stable than that without it. 3. The effect of $O_2$ to Shikonin showed that the solution with the $O_2$ was more stable that without it $O_2$. 4. Shikonin -methyl alcohol solution was stable in $25^{\circ}C$. It was unstable in $60^{\circ}C$ and $100^{\circ}C$ with lowered absorbance and changed colors. 5. Color-fastness test to silk and cotton indicated washing color-fastness and perspiration color-fastness was more than 3 grade. But the light color-fastness and crocking color-fastness was low. 6. The comparison between non -colored sample and colored-sample showed the latter was better in fastness. 7. Mordant as $Alk(SO_4)_2{\cdot}24H_2O$ and $AlCl_3{\cdot}6H_2O$ was better than anything else in fastness. 8. Color-difference value-test indicated that the mordant which had the jade green color, the original purple pigment color, was the best in use. 9. The best way to extract the original purple pigment color was in $25^{\circ}C$, because extracted dyeing solution by Soxhlet had the bluish color.

• Korean Journal of Medicinal Crop Science
• /
• v.21 no.6
• /
• pp.466-473
• /
• 2013

This study investigates the effect of supercritical fluid extract (CMPB803-C) of Lithospermum erythrorhizon, shikonin and acetylshikonin isolated from Lithospermum erythrorhizon on IL-$1{\beta}$-induced chondrocytes and monosodium iodoacetate (MIA)-induced osteoarthritis in rat. Shikonin ($50{\mu}m$) and acetylshikonin ($3{\mu}M$) treatment reduced significantly the mRNA expression and enzyme activity of matrix metalloproteinase (MMP)-1, -3 and -13 in IL-$1{\beta}$-induced SW1353 chondrosarcoma cells. The chondro-protective effects of CMPB803-C and acetylshikonin were than analyzed in a rat OA model using a single intra-articular injection of MIA (1mg) in the right knee joint. CMPB803-C (200mg/kg) or acetylshikonin (5mg/kg) was orally administered daily for two weeks starting after 1 week of MIA injection. In the histological observation, CMPB803-C and acetylshikonin clearly improved OA lesions being comparable to or better that control group. Our results demonstrated that CMPB803-C and acetylshikonin as active compound of Lithospermum erythrorhizon have a strong chondro-protective effect in OA rats, which likely attributes to its anti-inflammatory activity and inhibition of MMPs production.

• Korean Journal of Medicinal Crop Science
• /
• v.19 no.2
• /
• pp.103-110
• /
• 2011

This study was performed to enhance anticancer activities of Lithospermum erythrorhizon by eluting high amount of shikonin through ultra high pressure process. Extraction yield was increased up to 5~10% by ultra high pressure process, compare to the normal extraction processes such as water solvent extraction, 70% ethyl alcohol solvent extraction. The cytotoxicity of the extracts ($1.0{\mu}g/m{\ell}$) from ultra high pressure process was showed the lowest cytotoxicity 13.4% for human lung cell (HEL299). The anticancer activities showed 80~85% by adding $1.0{\mu}g/m{\ell}$ of the extracts from ultra high pressure process in several cancer cell lines such as AGS, Hep3B, MCF-7 and HeLa cells. Among them, MCF-7 cell of the endocrine system was highest inhibited than other cells. The anticancer activities of the extracts from ultra high pressure extraction process showed 10~15%, which was higher than the extracts from normal extraction processes. From HPLC analysis of the extracts, the contents of shikonin in the extracts from ultra high pressure process was 11.42% (w/w), which was 20% higher than others. This results indicate that ultra high pressure process could increase the extraction yield of shikonin and other contents, which resulted in higher anticancer activities.

• Archives of Pharmacal Research
• /
• v.19 no.5
• /
• pp.416-422
• /
• 1996

Twenty one phenylacetylshikonin analogues were synthesized from various subsitituted phenyl acetic acids and their cytotoxicity values against A549, K562 and L1210 cell lines and antitumor action in mice bearing S-180 cells were measured. All of phenylacetylshikonin analogues expressed a potent cytotoxicity $(ED_{50}, 0.1-1.80{\mu}g/ml)$ against L1210 and K562 cells. L1210 cells were the most sensitive to shikonin analogues among these cells. Except 4-methosyphenylacetylshikonin $(0.098 {\mu}g/ml)$, and a-acetoxyphenylacetylshikonin $(0.10 {\mu}g/ml)$, all other shikonin derivatives sshowed higher $ED_{50}$ values than phenylacetylshikonin $(0.13{\mu}g/ml)$, in L1210. In K562 cell, a-substitution of phenylacetylshikonin $(0.1{\mu}g/ml)$, while other subsitutions increased it slightly; 4-methoxyphenylacetylshikonin $(0.033{\mu}g/ml)$ showed a exceptionally good cytotoxicity against K562 cell. 4-Halogenation tended to decrease the cytotoxic effect on L1210 cells, while it enhanced the effect on K562; 4-bromophenylacetyl $$[ED_{50};(L1210)=1.76{\mu}g/ml, ;ED_{50};(K 562)=0.32 {\mu}g/ml]$$ and 4-chlorophenylacetyl shikonin $$[ED_{50};(L1210)=1.64 {\mu}g/ml, ;ED_{50};(K562)=0.32 {\mu}g/ml]$$. In contrast, A549 cells were much less sensitive to these shikonin analogues which showed $ED_{50}$ values of$1.5-1.35 {\mu}g/ml)$.Most of phenylacetylshikonin derivatives showed good antitumor activity in mice bearing S-180 cells. a-A-cetoxyphenylacetylshikonin and 4-dimethylaminophenylacetylshikonin showed highest T/C value (192-195%), implying that introduction of a-acetyl or of 4-dimethylamino group enhanced the antitumor activity as shown for 4-dimethylaminophenylacetylshikonin (T/C, 192%). It might be due to improvement of water solubility by dimethylamino group in the molecule.

• Journal of the Korean Society of Clothing and Textiles
• /
• v.25 no.8
• /
• pp.1484-1492
• /
• 2001

For the purpose of standardization and practicability of dyeing by natural dye, the mordanting and dyeing properties of Lithodpermum officinale were studied. Appropriate extraction, dveing and mordanting conditions of Lithodpermum officinale were determined, and the effect of mordanting no dye uptake and color fastness of dyed fabric was investigated. The maximum absorbances of Lithopermum officinale solution were at 521 and 561 mn, shikonin solution were 517 and 556 mn. According to the UV-VIS spectroscopy of shikonin solution showed batho chromic shift with the increase of temperature and the absorbance of shikonin solution increased with the increase of temperature. The color of Lithodpermum officinale solution was affected by pH 8∼9, they became dark, reduced reddish and bluish. The optimum conditions for extraction from Lithodpermum officinale were at 80$\^{C}$ and for 1 hour and at 25$\^{C}$ for 24 hours. And effective dyeing conditions with silk fabric were temperature at 80∼100$\^{C}$ and period for 60min. K/S value and color fastness of dyed fabrics were increased by mordanting treatment. In the case of Lithodpermum officinale light fastness was better than Sophora japonica, Gaesalpinia Sappan, Rhusjara,. Cochineal dyeing fabrics. Perspiration fastness of Lithodpermum officinale were good. Fastness of abrasion and dry-cleaning were good these fastness improvement were generatlly effected by post-mordanting treatment.

• Archives of Pharmacal Research
• /
• v.28 no.4
• /
• pp.400-404
• /
• 2005

Activity-guided fractionation of a hexane-soluble extract of the roots of Lithospermum erythrorhizon, using a mouse brain monoamine oxidase (MAO) inhibition assay, led to the isolation of two known naphthoquinones, acetylshikonin and shikonin, and a furylhydroquinone, shikonofuran E. These compounds were shown to inhibit MAO with $IC_{50}$ values of 10.0, 13.3, and $59.1 {\mu}M$, respectively. Although no specificity for MAO-A and MAO-B was shown by acetylshikonin and shikonin, a Lineweaver-Burk plot analysis indicated that the inhibition was competitive for both MAO-A and MAO-B activity.