Shikonin，TMEM16A 氯通道抑制剂，IC50 为 6.5 μM[1]。此外，紫草激肽特异性抑制 PKM2 [2]。此外，它还可以阻止核因子-κB (NF-κB) 通路的激活并抑制肿瘤坏死因子-α (TNF-α)。与对照相比，当暴露于浓度大于 50 μM 的紫草素时，正常人角质形成细胞 (NHK) 的活力显着降低 (P<0.05)。紫草素预处理两小时可抑制 TNF-α 诱导的 NF-κB p65 核转位 [3]。用 5 和 7.5 μM 紫草素处理 12 小时后，细胞活力显着降低。与 0 小时组相比，两种细胞系的抑制作用也显示出时间依赖性模式。结果发现，在24至48小时的时间段内，5μM紫草素比2.5μM紫草素具有更强的抑制作用。当U87和U251细胞用2.5、5和7.5 μM紫草素处理24和48小时（p<0.01）时，它们的侵袭性远低于对照组[4]。

与骨关节炎组相比，紫草素显着阻止骨关节炎大鼠模型中IL-1β和TNF-α表达水平的升高（P<0.01）。在骨关节炎大鼠模型中，与骨关节炎组相比，紫草素显着降低了 NF-κB 蛋白表达量（P<0.01）。在用紫草素治疗的大鼠骨关节炎模型中，与骨关节炎组相比，诱导的iNOS水平降低(P<0.01)。与骨关节炎组相比，紫草素治疗显着降低了骨关节炎大鼠模型中COX-2蛋白表达的增加（P<0.01）。紫草素治疗的骨关节炎大鼠模型中caspase-3活性的增加明显低于骨关节炎组（P<0.01）。接受紫草素治疗后，骨关节炎组大鼠骨关节炎模型中Akt磷酸化显着恢复（P<0.01）[5]。

Absorption, Distribution and Excretion
Alkannin and shikonin are naturally occurring hydroxynaphthoquinones with a well-established spectrum of wound healing, antimicrobial, anti-inflammatory, and antioxidant activities. Recently, extensive scientific effort has been focused on their effectiveness on several tumors and mechanism(s) of antitumor activity. Liposomes have been proved as adequate drug carriers offering significant advantages over conventional formulations, such as controlled release and targeted drug delivery, leading to the appearance of several liposomal formulations in the market, some of them concerning anticancer drugs. The aim of the present study was to prepare shikonin-loaded liposomes for the first time in order to enhance shikonin therapeutic index. An optimized technique based on the thin film hydration method was developed and liposomes characterization was performed in terms of their physicochemical characteristics, drug entrapment efficiency, and release profile. Results indicated the successful incorporation of shikonin into liposomes, using both 1,2-dipalmitoylphosphatidylcholine and egg phosphatidylcholine lipids. Liposomes presented good physicochemical characteristics, high entrapment efficiency and satisfactory in vitro release profile. In vitro cytotoxicity of liposomes was additionally tested against three human cancer cell lines (breast, glioma, and non-small cell lung cancer) showing a moderate growth inhibitory activity. Practical applications: Shikonin is a naturally occurring hydroxynaphthoquinone and extensive scientific research (in vitro, in vivo, and clinical trials) has been conducted during the last years, focusing on its effectiveness on several tumors and mechanism(s) of antitumor action. The purpose of this work was to prepare and characterize shikonin-loaded liposomes as a new drug delivery system for shikonin. Liposomal formulations provide significant advantages over conventional dosage forms, such as controlled release and targeted drug delivery for anticancer agents. Thus, liposomes could reduce shikonin's side effects, enhance selectivity to cancer cells and protect shikonin from internal biotransformations and instability matters (oxidization and polymerization). Furthermore, liposomal delivery helps overcome the low aqueous solubility of shikonin, which is the major barrier to its oral and internal administration, since it cannot be dissolved and further absorbed from the receptor.

[1]. Shikonin Inhibits Intestinal Calcium-Activated Chloride Channels and Prevents Rotaviral Diarrhea. Front Pharmacol. 2016 Aug 23;7:270.

[2]. Shikonin Suppresses Skin Carcinogenesis via Inhibiting Cell Proliferation. PLoS One. 2015 May 11;10(5):e0126459.

[3]. Shikonin Promotes Skin Cell Proliferation and Inhibits Nuclear Factor-κB Translocation via Proteasome Inhibition In Vitro. Chin Med J (Engl). 2015 Aug 20;128(16):2228-33.

[4]. Shikonin Inhibits the Migration and Invasion of Human Glioblastoma Cells by Targeting Phosphorylated β-Catenin and Phosphorylated PI3K/Akt: A Potential Mechanism for the Anti-Glioma Efficacy of a Traditional Chinese Herbal Medicine. Int J Mol Sci. 2015 Oct 9;16(10):23823-48.

[5]. Shikonin inhibits inflammation and chondrocyte apoptosis by regulation of the PI3K/Akt signaling pathway in a rat model of osteoarthritis. Exp Ther Med. 2016 Oct;12(4):2735-2740.

[6]. Mechanisms associated with biogenesis of exosomes in cancer. Mol Cancer. 2019 Mar 30;18(1):52.

[7]. Shikonin Suppresses NLRP3 and AIM2 Inflammasomes by Direct Inhibition of Caspase-1. PLoS One. 2016 Jul 28;11(7):e0159826.

Shikonin is a hydroxy-1,4-naphthoquinone.
Shikonin has been reported in Arnebia decumbens, Arnebia euchroma, and other organisms with data available.
See also: Arnebia guttata root (part of); Arnebia euchroma root (part of); Lithospermum erythrorhizon root (part of).

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Mechanism of Action
/Investigators/ previously developed a gene-gun-based in vivo screening system and identified shikonin as a potent suppressor of tumor necrosis factor-alpha (TNF-alpha) gene expression. Here... shikonin selectively inhibits the expression of TNF-alpha at the RNA splicing level. Treatment of lipopolysaccharide-stimulated human primary monocytes and THP-1 cells with shikonin resulted in normal transcriptional induction of TNF-alpha, but unspliced pre-mRNA accumulated at the expense of functional mRNA. This effect occurred with noncytotoxic doses of shikonin and was highly specific, because mRNA production of neither a housekeeping gene nor another inflammatory cytokine gene, interleukin-8 (IL-8), was affected. Moreover, cotreatment with lipopolysaccharide (LPS) and shikonin increased the endpoint protein production of IL-8, accompanied by suppressed activation of the double-stranded RNA-activated protein kinase (PKR) pathway. Because PKR inactivation has been shown to down-regulate the splicing process of TNF-alpha RNA and interfere with translation, our findings suggest that shikonin may achieve differential modulation of cytokine protein expression through inactivation of the PKR pathway and reveal that regulation of TNF-alpha pre-mRNA splicing may constitute a promising target for future anti-inflammatory application.
Shikonin isolated from the roots of the Chinese herb Lithospermum erythrorhizon has been associated with anti-inflammatory properties. /Investigators/ evaluated shikonin's chemotherapeutic potential and investigated its possible mechanism of action in a human cutaneous neoplasm in tissue culture. Shikonin preferentially inhibits the growth of human epidermoid carcinoma cells concentration- and time-dependently compared to SV-40 transfected keratinocytes, demonstrating its anti-proliferative effects against this cancer cell line. Additionally, shikonin decreased phosphorylated levels of EGFR, ERK1/2 and protein tyrosine kinases, while increasing phosphorylated JNK1/2 levels. Overall, shikonin treatment was associated with increased intracellular levels of phosphorylated apoptosis-related proteins, and decreased levels of proteins associated with proliferation in human epidermoid carcinoma cells.
... /A previous study showed/ that shikonin, a natural compound isolated from Lithospermun erythrorhizon Sieb. Et Zucc, inhibits adipogenesis and fat accumulation. This study was conducted to investigate the molecular mechanism of the anti-adipogenic effects of shikonin. Gene knockdown experiments using small interfering RNA (siRNA) transfection were conducted to elucidate the crucial role of beta-catenin in the anti-adipogenic effects of shikonin. Shikonin prevented the down-regulation of beta-catenin and increased the level of its transcriptional product, cyclin D1, during adipogenesis of 3T3-L1 cells, preadipocytes originally derived from mouse embryo. beta-catenin was a crucial mediator of the anti-adipogenic effects of shikonin, as determined by siRNA-mediated knockdown. Shikonin-induced reductions of the major transcription factors of adipogenesis including peroxisome proliferator-activated receptor gamma and CCAAT/enhancer binding protein alpha, and lipid metabolizing enzymes including fatty acid binding protein 4 and lipoprotein lipase, as well as intracellular fat accumulation, were all significantly recovered by siRNA-mediated knockdown of beta-catenin. Among the genes located in the WNT/beta-catenin pathway, the levels of WNT10B and DVL2 were significantly up-regulated, whereas the level of AXIN was down-regulated by shikonin treatment. This study ...shows that shikonin inhibits adipogenesis by the modulation of WNT/beta-catenin pathway in vitro, and also suggests that WNT/beta-catenin pathway can be used as a therapeutic target for obesity and related diseases using a natural compound like shikonin...

C16H16O5

288.3

288.099

517-89-5

(-)-Alkannin;517-88-4;Alkannin;23444-65-7;(Rac)-Shikonin;54952-43-1

479503

Brown to reddish brown solid powder

1.4±0.1 g/cm3

567.4±50.0 °C at 760 mmHg

147ºC

311.0±26.6 °C

0.0±1.6 mmHg at 25°C

1.642

4.35

94.83

3

5

3

21

501

1

CC(=CC[C@H](C1=CC(=O)C2=C(C=CC(=C2C1=O)O)O)O)C

NEZONWMXZKDMKF-SNVBAGLBSA-N

InChI=1S/C16H16O5/c1-8(2)3-4-10(17)9-7-13(20)14-11(18)5-6-12(19)15(14)16(9)21/h3,5-7,10,17-19H,4H2,1-2H3/t10-/m1/s1

5,8-dihydroxy-2-[(1R)-1-hydroxy-4-methylpent-3-enyl]naphthalene-1,4-dione

Tokyo Violet Shikonin

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~125 mg/mL (~433.58 mM)

配方 1 中的溶解度: ≥ 2.08 mg/mL (7.21 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 20.8 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.08 mg/mL (7.21 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.08 mg/mL (7.21 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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配方 4 中的溶解度: 30 mg/mL (104.06 mM) in 0.5% CMC-Na/saline water (这些助溶剂从左到右依次添加，逐一添加), 悬浊液; 超声助溶。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。