• 한국미생물·생명공학회지
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• 제18권5호
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• pp.525-529
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• 1990

식물세포인 Lithospermum erythrorhizon을 교반 반응기와 calcium alghinate에 고정화된 상태로 충전층 반응기에서 n-hexadecane으로 동시 추출하면서 shikonin을 생산하여 각각의 생산성을 비교하였다. 교반 반응기에서 shikonin의 비생산과 부피생산성은 각각 1.5mg shikonin/g cell과 400$\mu g$ shikonin/(L.day)였고 충전층 반응기에서는 가각 2.0mg shikonin/g cell과 2857 $\mu g$ shikonin/(L.day)였으며 이는 각각 교반 반응기에 비하여 1.3, 7.1배 높은 것이다. 충전층 반응기에서 shikonin의 생산성이 높은 것은 calcium alginate 입자에 세포가 고농도고 축적되어 단위 반응기 부피당 세로의 부하 능력이 높고 또한 세포가 서로 접촉하기가 쉽고 고정화 입자내의 환경이 세포가 분화하기에 좋은 조건을 형성하기 때문인 것으로 사료된다.

• 한국미생물·생명공학회지
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• 제17권4호
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• pp.343-348
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• 1989

L. erythrorhizon 세포를 polyurethane foam과 함께 증식시킬 경우 shikonin 유도체가 polyurethane에 효과적으로 흡착됨과 동시에 polyurethane을 사용하지 않은 경우와 비교하여 shikonin 생산량이 현저히 증가하였다. 이 같은 증가는 세포를 polyurethane pore에 고정하여 증식시킴으로써 원활한 세포간 접촉을 유지하고 세포 내에 shikonin 농도를 저하시켜shikonin 생성에 좋은 조건을 제공함에 기인한 것으로 생각되었다. 공정의 생산성을 높이기 위하여 여러가지 배양시스템이 검토되었는데, indole-3-acetic acid(1.75mg/ι)와 kinetin(0.1mg/ι)을 함유하는 Schenk-Hildebrandt 배지 (SHIK 배지) 시스템이 가장 효과적이었다. p-Chlorophenoxyacetic acid (2.0 mg/ι)와 kinetin (0.1 mg/ι)를 함유하는 Schenk-Hildebrandt 배지 (SHND 배지) 시스템에 비교하여 SHIK 배지 시스템에서 Shikonin 생성량은 약 4.5배 증가하였다. Polyurethane을 세포를 고정화하는 지지체로 사용할 경우에는 현재 행하여지고 있는 2단계 배양보다 1단계 배양이 더욱 효과적이며 경제적으로도 매우 유리할 것으로 판단되었다.

• 한국약용작물학회지
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• 제10권4호
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• pp.243-248
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• 2002

The effects of basal media, carbon, nitrogen, phosphate and some major macro elements on growth and shikonin production in Lithospermum erythrorhizon hairy root culture were studied. Among examined media, growth of hairy root cultured in B5 liquid medium was rapid, whereas shikonin production was high in MS liquid medium. Under B5 basal medium, sucrose concentration for optimal growth and shikonin production was 9% and 4% respectively. The growth and shikonin production on pH changes in B5 medium resulted little effect in pH 5.8 to pH 8.8 ranges, whereas growth was decreased dramatically in both above 8.8 and under 5.8. Nitrogen source and concentration effected on the growth and shikonin production. The highest growth rate was in B5 medium (50 mM $KNO_3$ and 1 mM $NaH_2PO_4)$, whereas the highest shikonin production was in the condition supplemented with 5 mM $KNO_3$ and 10 mM $NaH_2PO_4$.

• Journal of Microbiology and Biotechnology
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• 제2권1호
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• pp.41-45
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• 1992

Shikonin production was examined in a bubble column bioreactor system with the hairy roots of Lithosphermum erythrorhizon. The volumetric productivity was higher than those obtained from other reactor configurations with free or immobilized cells of the same cell line. The productivities of the bubble column reactor, with and without a product absorption trap, were 7.4 and 4.5 mg of shikonin/l/d, respectively. This indicated the importance of the product removal in the design and operation of the shikonin production system with hairy root culture.

• The Korean Journal of Physiology and Pharmacology
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• 제14권4호
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• pp.199-204
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• 2010

The potential therapeutic action of shikonin in an experimental model of rheumatoid arthritis (RA) was investigated. As a RA animal model, DBA/1J mice were immunized two times with type II collagen. After the second collagen immunization, mice were orally administered shikonin (2 mg/kg) once a day for 35 days, and the incidence, clinical score, bone mineral density (BMD), bone mineral content (BMC) and joint histopathology were evaluated. BMD in the proximal regions of the tibia largely increased in the shikonin treatment group compared with the control group. We also examined the effect of shikonin on inflammatory cytokines and cartilage protection. Shikonin treatment significantly reduced the incidence and severity of collagen-induced arthritis (CIA), markedly abrogating joint swelling and cartilage destruction. Shikonin also significantly inhibited the production of matrix metalloproteinase (MMP)-1 and up-regulated tissue inhibitors of metalloproteinase (TIMP)-1 in mice with CIA. In conclusion, shikonin exerted therapeutic effects through regulation of MMP/TIMP; these results suggest that shikonin is an outstanding candidate as a cartilage protective medicine for RA.

• Advances in Traditional Medicine
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• 제5권4호
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• pp.283-293
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• 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.

• 한국약용작물학회지
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• 제21권6호
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• pp.466-473
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• 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.

• 대한화장품학회지
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• 제13권1호
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• pp.7-14
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• 1987

Production of shikonin derivatives through cell suspension culture of Lithospermum erythrorhizon was investigated. Optimal concentrations of IAA and kinetin on the growth of cell suspension were 0.2 and 0.1 ppm respectively. Pigment content was markedly increased when aluminum oxide was added to the production medium and its optimal concentration was 1.5g/70ml medium. The most effective concentration of IAA was 0.5 ppm and the production of pigment did not depend on the kinetin concentration.

• 한국원자력학회:학술대회논문집
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• 한국원자력학회 2005년도 춘계학술발표회
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• pp.994-995
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• 2005

• 한국식물학회:학술대회논문집
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• 한국식물학회 1995년도 식물학심포지움 식물로부터 유용 2차대사산물의 생산 PRODUCTION OF USEFUL SECONDARY METABOLITES FROM PLANTS
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• pp.40-56
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• 1995

During the past two decades, China has seen her great progress in plant biotechnology. Since the Chinese market of herb medicine is huge, while the plant resources are shrinking, particular emphasis has been placed in plant tissue and cell cultures of medicinal plants, this includes fast propagation, protoplast isolation and regeneration, cell suspension cultures and large scale fermentation. To optimize culture conditions for producing secondary compounds in vitro, various media, additives and elicitors have been tested. Successful examples of large scale culture for the secondary metabolite biosynthesis are quite limited : Lithospermum ery throrhizon and Arnebia euchroma for shikonin derivatives, Panax ginseng, P. notoginseng, P. quinquefolium for saponins, and a few other medicinal plants. Recent development of genetic transformation systems of plant cells offered a new approach to in vitro production of secondary compounds. Hairy root induction and cultures, by using Ri-plasmid, have been reported from a number of medicinal plant species, such as Artemisia annua that produces little artemisinin in normal cultured cells, and from Glycyrrhiza uralensis. In the coming five years, Chinese scientists will continue their work on large scale cell cultures of a few of selected plant species, including Taxus spp. and A. annua, for the production of secondary metabolites with medicinal interests, one or two groups of scientists will be engaged in molecular cloning of the key enzymes in plant secondary metabolism.