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Planta Med 2013; 79(18): 1685-1697
DOI: 10.1055/s-0033-1350934
Reviews
Georg Thieme Verlag KG Stuttgart · New York

Pharmacological Properties of Shikonin – A Review of Literature since 2002

Isabel Andújar
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Valencia, Spain
,
José Luis Ríos
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Valencia, Spain
,
Rosa María Giner
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Valencia, Spain
,
María Carmen Recio
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Valencia, Spain
› Author Affiliations
Further Information

Publication History

received 23 May 2013
revised 29 July 2013

accepted 16 September 2013

Publication Date:
23 October 2013 (online)

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Abstract

The naphthoquinone shikonin is the main active principle of Zicao, a traditional Chinese herbal medicine made from the dried root of Lithospermum erythrorhizon. Studies carried out over the past 30 years have provided a scientific basis for the use of Zicao which has been long employed in folk medicine to treat a variety of inflammatory and infectious diseases. In particular, shikonin has been shown to possess many diverse properties, including antioxidant, anti-inflammatory, antithrombotic, antimicrobial, and wound healing effects. The fact that shikonin shows so many beneficial properties has increased the interest in this molecule dramatically, especially in the past few years. The aim of this review is to provide an update of the new data published on shikonin, whose wide spectrum of pharmacological effects as well as pharmacokinetic properties and toxicity make it a highly interesting target molecule.

Key words

anti-infectious - anti-inflammatory - antioxidant - glucose metabolism - wound healing - shikonin - Lithospermum erythrorhizon - Boraginaceae
 

  • References

  • 1 Chen X, Yang L, Oppenheim JJ, Howard OMZ. Cellular pharmacology studies of shikonin derivatives. Phytother Res 2002; 16: 199-209
    CrossrefPubMedGoogle Scholar
  • 2 Papageorgiou VP, Assimopoulou AN, Couladouros EA, Hepworth D, Nicolaou KC. The chemistry and biology of alkannin, shikonin, and related naphthazarin natural products. Angew Chem Int Ed Engl 1999; 38: 270-301
    CrossrefPubMedGoogle Scholar
  • 3 Albreht A, Vovk I, Simonovska B. Addition of β-lactoglobulin produces water-soluble shikonin. J Agric Food Chem 2012; 60: 10834-10843
    CrossrefPubMedGoogle Scholar
  • 4 Papageorgiou VP, Assimopoulou AN, Ballis AC. Alkannins and shikonins: a new class of wound healing agents. Curr Med Chem 2008; 15: 3248-3267
    CrossrefPubMedGoogle Scholar
  • 5 Assimopoulou AN, Papageorgiou VP. Encapsulation of isohexenylnaphthazarins in cyclodextrins. Biomed Chromatogr 2004; 18: 240-247
    CrossrefPubMedGoogle Scholar
  • 6 Chen CY, Chen FA, Wu AB, Hsu HC, Kang JJ, Cheng HW. Effect of hydroxypropyl-β-cyclodextrin on the solubility, photostability and in vitro permeability of alkannin/shikonin enantiomers. Int J Pharm 1996; 141: 171-178
    CrossrefPubMedGoogle Scholar
  • 7 Xia H, Tang C, Gui H, Wang X, Qi J, Wang X, Yang Y. Preparation, cellular uptake and angiogenic suppression of shikonin-containing liposomes in vitro and in vivo . Biosci Rep 2013; 33: e00020
    PubMedGoogle Scholar
  • 8 Assimopoulou AN, Papageorgiou VP, Kiparissides C. Synthesis and release studies of shikonin-containing microcapsules prepared by the solvent evaporation method. J Microencapsul 2003; 20: 581-596
    CrossrefPubMedGoogle Scholar
  • 9 Huang YI, Cheng YH, Yu CC, Tsai TR, Cham TM. Microencapsulation of extract containing shikonin using gelatin–acacia coacervation method: a formaldehyde-free approach. Colloids Surf B Biointerfaces 2007; 58: 290-297
    CrossrefPubMedGoogle Scholar
  • 10 Han J, Chen TX, Branford-White CJ, Zhu LM. Electrospun shikonin-loaded PCL/PTMC composite fiber mats with potential biomedical applications. Int J Pharm 2009; 382: 215-221
    CrossrefPubMedGoogle Scholar
  • 11 Kontogiannopoulos KN, Assimopoulou AN, Tsivintzelis I, Panayiotou C, Papageorgiou VP. Electrospun fiber mats containing shikonin and derivatives with potential biomedical applications. Int J Pharm 2011; 409: 216-228
    CrossrefPubMedGoogle Scholar
  • 12 Kontogiannopoulos KN, Assimopoulou AN, Hatziantoniou S, Karatasos K, Demetzos C, Papageorgiou VP. Chimeric advanced drug delivery nano systems (chi-aDDnSs) for shikonin combining dendritic and liposomal technology. Int J Pharm 2012; 422: 381-389
    CrossrefPubMedGoogle Scholar
  • 13 Kourounakis AP, Assimopoulou AN, Papageorgiou VP, Gavalas A, Kourounakis PN. Alkannin and shikonin: effect on free radical processes and on inflammation – a preliminary pharmacochemical investigation. Arch Pharm (Weinheim) 2002; 335: 262-266
    CrossrefPubMedGoogle Scholar
  • 14 Landa P, Kutil Z, Temml V, Vuorinen A, Malik J, Dvorkova M, Marsik P, Konoska L, Pribylova M, Schuster D, Vanek T. Redox and non-redox mechanism of in vitro cyclooxygenase inhibition by natural quinones. Planta Med 2012; 78: 326-333
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Zeng YQ. Identificación y actividad farmacológica de principios de especies antiinflamatorias [PhD Thesis]. Valencia: University of Valencia; 2006
    PubMedGoogle Scholar
  • 16 Kundakovic T, Fokialakis N, Dobric S, Pratsinis H, Kletsas D, Kovacevic N, Chinou I. Evaluation of the anti-inflammatory and cytotoxic activities of naphthazarine derivatives from Onosma leptantha . Phytomedicine 2006; 13: 290-294
    CrossrefPubMedGoogle Scholar
  • 17 Staniforth V, Wang SY, Shyur LF, Yang NS. Shikonins, phytocompounds from Lithospermum erythrorhizon, inhibit the transcriptional activation of human tumor necrosis factor α promoter in vivo . J Biol Chem 2004; 279: 5877-5885
    CrossrefPubMedGoogle Scholar
  • 18 Andújar I, Recio MC, Bacelli T, Giner RM, Ríos JL. Shikonin reduces oedema induced by phorbol ester by interfering with IκBα degradation thus inhibiting translocation of NF-κB to the nucleus. Br J Pharm 2010; 160: 376-388
    CrossrefPubMedGoogle Scholar
  • 19 Cheng YW, Chang CY, Lin KL, Hu CM, Lin CH, Kang JJ. Shikonin derivatives inhibited LPS-induced NOS in RAW 264.7 cells via downregulation of MAPK/NF-κB signaling. J Ethnopharmacol 2008; 120: 264-271
    CrossrefPubMedGoogle Scholar
  • 20 Lu L, Qin A, Huang H, Zhou P, Zhang C, Liu N, Li S, Wen G, Zhang C, Dong W, Wang X, Dou QP, Liu J. Shikonin extracted from medicinal Chinese herbs exerts anti-inflammatory effect via proteasome inhibition. Eur J Pharmacol 2011; 658: 242-247
    CrossrefPubMedGoogle Scholar
  • 21 Dai Q, Fang J, Zhang FS. Dual role of shikonin in early and late stages of collagen type II arthritis. Mol Biol Rep 2009; 36: 1597-1604
    CrossrefPubMedGoogle Scholar
  • 22 Kim YO, Hong SJ, Yim SV. The efficacy of shikonin on cartilage protection in a mouse model of rheumatoid arthritis. Korean J Physiol Pharmacol 2010; 14: 199-204
    CrossrefPubMedGoogle Scholar
  • 23 Chakir H, Wang H, Lefebvre DE, Webb J, Scott FW. T-bet/GATA-3 ratio as a measure of the Th1/Th2 cytokine profile in mixed cell populations: predominant role of GATA-3. J Immunol Methods 2003; 278: 157-169
    CrossrefPubMedGoogle Scholar
  • 24 Lesuis N, Befrits R, Nyberg F, van Vollenhoven RF. Gender and the treatment of immune-mediated chronic inflammatory diseases: rheumatoid arthritis, inflammatory bowel disease and psoriasis: an observational study. BMC Med 2012; 10: 82
    CrossrefPubMedGoogle Scholar
  • 25 Andújar I, Ríos JL, Giner RM, Cerdá-Nicolás M, Recio MC. Beneficial effect of shikonin on experimental colitis induced by dextran sulfate sodium in BALB/c mice. Evid Based Complement Alternat Med 2012; DOI: 10.1155/2012/271606.
    PubMedGoogle Scholar
  • 26 Takano-Ohmuro H, Yoshida LS, Yuda Y, Morioka K, Kitani S. Shikonin inhibits IgE-mediated histamine release by human basophils and Sky kinase activity. Inflamm Res 2008; 57: 484-488
    CrossrefPubMedGoogle Scholar
  • 27 Lee CC, Wang CN, Lai YT, Kang JJ, Liao JW, Chiang BL, Chen HC, Cheng YW. Shikonin inhibits maturation of bone marrow-derived dendritic cells and suppresses allergic airway inflammation in a murine model of asthma. Br J Pharmacol 2010; 161: 1496-1511
    CrossrefPubMedGoogle Scholar
  • 28 Lee CC, Kang JJ, Chiang BL, Wang CN, Cheng YW. Shikonin inhibited mitogen-activated IL-4 and IL-5 production on EL-4 cells through downregulation of GATA-3 and c-Maf induction. Life Sci 2011; 89: 364-370
    CrossrefPubMedGoogle Scholar
  • 29 Wang XC, Feng J, Huang F, Fan YS, Wang YY, Cao LY, Wen CP. Effects of shikonin isolated from zicao on lupus nephritis in NZB/W F1 mice. Biol Pharm Bull 2009; 32: 1565-1570
    CrossrefPubMedGoogle Scholar
  • 30 Xiong J, Ni J, Hu G, Shen J, Zhao Y, Yang L, Shen J, Yin G, Chen C, Yu G, Hu Y, Xing M, Wan R, Wang X. Shikonin ameliorates cerulein-induced acute pancreatitis in mice. J Ethnopharmacol 2013; 145: 573-580
    CrossrefPubMedGoogle Scholar
  • 31 Bai GZ, Yu HT, Ni YF, Li XF, Zhang ZP, Su K, Lei J, Liu BY, Ke CK, Zhong DX, Wang YJ, Zhao JB. Shikonin attenuates lipopolysaccharide-induced acute lung injury in mice. J Surg Res 2013; 182: 303-311
    CrossrefPubMedGoogle Scholar
  • 32 Chiu SC, Tsao SW, Hwang PI, Vanisree S, Chen YA, Yang NS. Differential functional genomic effects of anti-inflammatory phytocompounds on immune signaling. BMC Genomics 2010; 11: 513
    CrossrefPubMedGoogle Scholar
  • 33 Li T, Yan F, Wang R, Zhou H, Liu L. Shikonin suppresses human T lymphocyte activation through inhibition of IKKβ activity and JNK phosphorylation. Evid Based Complement Alternat Med 2013; 2013: 379536
    PubMedGoogle Scholar
  • 34 Assimopoulou AN, Papageorgiou VP. Radical scavenging activity of Alkanna tinctoria root extracts and their main constituents, hydroxynaphthoquinones. Phytother Res 2005; 19: 141-147
    CrossrefPubMedGoogle Scholar
  • 35 Jin R, Bai Y. Theoretical investigation of the radical scavenging activity of shikonin and acylshikonin derivatives. J Mol Model 2012; 18: 1401-1408
    CrossrefPubMedGoogle Scholar
  • 36 Nishizawa M, Kohno M, Nishimura M, Kitagawa A, Niwano Y. Presence of peroxyradicals in cigarette smoke and the scavenging effect of shikonin, a naphthoquinone pigment. Chem Pharm Bull 2005; 53: 796-799
    CrossrefPubMedGoogle Scholar
  • 37 Wang Z, Liu T, Gan L, Wang T, Yuan X, Zhang B, Chen H, Zheng Q. Shikonin protects mouse brain against cerebral ischemia/reperfusion injury through its antioxidant activity. Eur J Pharmacol 2010; 643: 211-217
    CrossrefPubMedGoogle Scholar
  • 38 Nam KN, Son MS, Park JH, Lee EH. Shikonins attenuate microglial inflammatory responses by inhibition of ERK, Akt, and NF-κB: neuroprotective implications. Neuropharmacology 2008; 55: 819-825
    CrossrefPubMedGoogle Scholar
  • 39 Esmaeilzadeh E, Gardaneh M, Gharib E, Sabouni F. Shikonin protects dopaminergic cell line PC12 against 6-hydroxydopamine-mediated neurotoxicity via both glutathione-dependent and independent pathways and by inhibiting apoptosis. Neurochem Res 2013; 38: 1590-1604
    CrossrefPubMedGoogle Scholar
  • 40 Andrikopoulos NK, Kaliora AC, Assimopoulou AN, Papapeorgiou VP. Biological activity of some naturally occurring resins, gums and pigments against in vitro LDL oxidation. Phytother Res 2003; 17: 501-507
    CrossrefPubMedGoogle Scholar
  • 41 Yoshida LS, Kawada T, Irie K, Yuda Y, Himi T, Ikemoto F, Takano-Ohmuro H. Shikonin directly inhibits nitric oxide synthases: possible targets that affect thoracic aorta relaxation response and nitric oxide release from RAW 264.7 macrophages. J Pharmacol Sci 2010; 112: 343-351
    CrossrefPubMedGoogle Scholar
  • 42 Rajasekar S, Park da J, Park C, Park S, Park YH, Kim ST, Choi YH, Choi YW. In vitro and in vivo anticancer effects of Lithospermum erythrorhizon extract on B16F10 murine melanoma. J Ethnopharmacol 2012; 144: 335-345
    CrossrefPubMedGoogle Scholar
  • 43 Kretschmer N, Rinner B, Deutsch AJ, Lohberger B, Knausz H, Kunert O, Blunder M, Boechzelt H, Schaider H, Bauer R. Naphthoquinones from Onosma paniculata induce cell-cycle arrest and apoptosis in melanoma cells. J Nat Prod 2012; 75: 865-869
    CrossrefPubMedGoogle Scholar
  • 44 Min R, Zun Z, Min Y, Wenhu D, Wenjun Y, Chenping Z. Shikonin inhibits tumor invasion via down-regulation of NF-κB-mediated MMP-9 expression in human ACC-M cells. Oral Dis 2011; 17: 362-369
    CrossrefPubMedGoogle Scholar
  • 45 Yang H, Zhou P, Huang H, Chen D, Ma N, Cui QC, Shen S, Dong W, Zhang X, Lian W, Wang X, Dou QP, Liu J. Shikonin exerts antitumor activity via proteasome inhibition and cell death induction in vitro and in vivo . Int J Cancer 2009; 124: 2450-2459
    CrossrefPubMedGoogle Scholar
  • 46 Chang IC, Huang YJ, Chiang TI, Yeh CW, Hsu LS. Shikonin induces apoptosis through reactive oxygen species/extracellular signal-regulated kinase pathway in osteosarcoma cells. Biol Pharm Bull 2010; 33: 816-824
    CrossrefPubMedGoogle Scholar
  • 47 Chen J, Xie J, Jiang Z, Wang B, Wang Y, Hu X. Shikonin and its analogs inhibit cancer cell glycolysis by targeting tumor pyruvate kinase-M2. Oncogene 2011; 30: 4297-4306
    CrossrefPubMedGoogle Scholar
  • 48 Li W, Liu J, Zhao Y. PKM2 inhibitor Shikonin suppresses TPA-induced mitochondrial malfunction and proliferation of skin epidermal JB6 cells. Mol Carcinogen 2012; DOI: 10.1002/mc.21988.
    PubMedGoogle Scholar
  • 49 Yingkun N, Lvsong Z, Huimin Y. Shikonin inhibits the proliferation and induces the apoptosis of human HepG2 cells. Can J Physiol Pharmacol 2010; 88: 1138-1146
    CrossrefPubMedGoogle Scholar
  • 50 Han W, Li L, Qiu S, Lu Q, Pan Q, Gu Y, Luo J, Hu X. Shikonin circumvents cancer drug resistance by induction of a necroptotic death. Mol Cancer Ther 2007; 6: 1641-1649
    CrossrefPubMedGoogle Scholar
  • 51 Andújar I, Recio MD, Giner RM, Ríos JL. Traditional Chinese medicine remedy to jury: the pharmacological basis for the use of shikonin as an anticancer therapy. Curr Med Chem 2013; 20: 2892-2898
    CrossrefPubMedGoogle Scholar
  • 52 Huang C, Luo Y, Zhao J, Yang F, Zhao H, Fan W, Ge P. Shikonin kills glioma cells through necroptosis mediated by RIP-1. PLoS ONE 2013; 8: e66326
    CrossrefPubMedGoogle Scholar
  • 53 Piao JL, Cui ZG, Furusawa Y, Ahmed K, Rehman MU, Tambuchi Y, Kadowaki M, Kondo T. The molecular mechanisms and gene expression profiling for shikonin-induced apoptotic and necroptotic cell death in U937 cells. Chembiol Interact 2013; DOI: 10.1016/j.cbi.2013.06.011.
    PubMedGoogle Scholar
  • 54 Ahn J, Won M, Choi JH, Kim YS, Jung CR, Im DS, Kyun ML, Lee K, Song KB, Chung KS. Reactive oxygen species-mediated activation of the Akt/ASK1/p 38 signaling cascade and p 21(Cip1) downregulation are required for shikonin-induced apoptosis. Apoptosis 2013; 18: 870-881
    CrossrefPubMedGoogle Scholar
  • 55 Zhang B, Chen N, Chen H, Wang Z, Zheng Q. The critical role of redox homeostasis in shikonin-induced HL-60 cell differentiation via unique modulation of the Nrf2/ARE pathway. Oxid Med Cell Longev 2012; 2012: 781516
    PubMedGoogle Scholar
  • 56 Wang H, Wu C, Wan S, Zhang H, Zhou S, Liu G. Shikonin attenuates lung cancer cell adhesion to extracellular matrix and metastasis by inhibiting integrin β1 expression and the ERK1/2 signaling pathway. Toxicology 2013; 308: 104-112
    CrossrefPubMedGoogle Scholar
  • 57 Haghbeen K, Pourmolaei S, Mareftjo MJ, Mousavi A, Akbari Noghabi K, Hosseini Shirazi F, Meshkat A. Detailed investigations on the solid cell culture and antimicrobial activities of the Iranian Arnebia euchroma . J Biomed Biotechnol 2011; 2011: 165852
    PubMedGoogle Scholar
  • 58 Ding X, Yin B, Qian L, Zeng Z, Yang Z, Li H, Lu Y, Zhou S. Screening for novel quorum-sensing inhibitors to interfere with the formation of Pseudomonas aeruginosa biofilm. J Med Microbiol 2011; 60: 1827-1834
    CrossrefPubMedGoogle Scholar
  • 59 Shen CC, Syu WJ, Li SY, Lin CH, Lee GH, Sun CM. Antimicrobial activities of naphthazarins from Arnebia euchroma . J Nat Prod 2002; 65: 1857-1862
    CrossrefPubMedGoogle Scholar
  • 60 Li HM, Tang YL, Zhang ZH, Liu CJ, Li HZ, Li RT, Xia XS. Compounds from Arnebia euchroma and their related anti-HCV and antibacterial activities. Planta Med 2012; 78: 39-45
    Article in Thieme ConnectPubMedGoogle Scholar
  • 61 Kuo HM, Hsia TC, Chuang YC, Lu HF, Lin SY, Chung JG. Shikonin inhibits the growth and N-acetylation of 2-aminofluorene in Helicobacter pylori from ulcer patients. Anticancer Res 2004; 24: 1587-1592
    PubMedGoogle Scholar
  • 62 Sasaki K, Abe H, Yoshizaki F. In vitro antifungal activity of naphthoquinone derivatives. Biol Pharm Bull 2002; 25: 669-670
    CrossrefPubMedGoogle Scholar
  • 63 Miao H, Zhao L, Li C, Shang Q, Lu H, Fu Z, Wang L, Jiang Y, Cao Y. Inhibitory effect of shikonin on Candida albicans growth. Biol Pharm Bull 2012; 35: 1956-1963
    CrossrefPubMedGoogle Scholar
  • 64 Michaelakis A, Strongilos AT, Bouzas EA, Koliopoulos G, Couladouros EA. Larvicidal activity of naturally occurring naphthoquinones and derivatives against the West Nile virus vector Culex pipiens . Parasitol Res 2009; 104: 657-662
    CrossrefPubMedGoogle Scholar
  • 65 Ali A, Assimopoulou AN, Papageorgiou VP, Kolodziej H. Structure/antileishmanial activity relationship study of naphthoquinones and dependency of the mode of action on the substitution patterns. Planta Med 2011; 77: 2003-2012
    Article in Thieme ConnectPubMedGoogle Scholar
  • 66 Chen X, Yang L, Zhang N, Turpin JA, Buckheit RW, Osterling C, Oppenheim JJ, Howard OM. Shikonin, a component of Chinese herbal medicine, inhibits chemokine receptor function and suppresses human immunodeficiency virus type 1. Antimicrob Agents Chemother 2003; 47: 2810-2816
    CrossrefPubMedGoogle Scholar
  • 67 Min BS, Miyashiro H, Hattori M. Inhibitory effects of quinones on RNase H activity associated with HIV-1 reverse transcriptase. Phytother Res 2002; 16: S57-S62
    CrossrefPubMedGoogle Scholar
  • 68 Gao H, Liu L, Qu ZY, Wei FX, Wang SQ, Chen G, Qin L, Jiang FY, Wang YC, Shang L, Gao CY. Anti-adenovirus activities of shikonin, a component of Chinese herbal medicine in vitro . Biol Pharm Bull 2011; 34: 197-202
    CrossrefPubMedGoogle Scholar
  • 69 Karayannopoulou M, Tsioli V, Loukopoulos P, Anagnostou TL, Giannakas N, Savvas I, Papazoglou LG, Kaldrymidou E. Evaluation of the effectiveness of an ointment based on Alkannins/Shikonins on second intention wound healing in the dog. Can J Vet Res 2011; 75: 42-48
    PubMedGoogle Scholar
  • 70 Hsiao CY, Tsai TH, Chak KF. The molecular basis of wound healing processes induced by Lithospermi Radix: a proteomics and biochemical analysis. Evid Based Complement Alternat Med 2012; DOI: 10.1155/2012/508972.
    PubMedGoogle Scholar
  • 71 Andújar I, Ríos JL, Giner RM, Recio MC. Shikonin promotes intestinal wound healing in vitro via induction of TGF-β release in IEC-18 cells. Eur J Pharm Sci 2013; 49: 637-641
    CrossrefPubMedGoogle Scholar
  • 72 Gwon SY, Ahn JY, Chung CH, Moon BK, Ha TY. Lithospermum erythrorhizon suppresses high-fat diet-induced obesity, and acetylshikonin, a main compound of Lithospermum erythrorhizon, inhibits adipocyte differentiation. J Agric Food Chem 2012; 60: 9089-9096
    CrossrefPubMedGoogle Scholar
  • 73 Lee H, Kang R, Yoon Y. Shikonin inhibits fat accumulation in 3 T3-L1 adipocytes. Phytother Res 2010; 24: 344-351
    CrossrefPubMedGoogle Scholar
  • 74 Lee H, Bae S, Kim K, Kim W, Chung SI, Yang Y, Yoon Y. Shikonin inhibits adipogenesis by modulation of the WNT/β-catenin pathway. Life Sci 2011; 88: 294-301
    CrossrefPubMedGoogle Scholar
  • 75 Kamei R, Kitagawa Y, Kadokura M, Hattori F, Hazeki O, Ebina Y, Nishihara T, Oikawa S. Shikonin stimulates glucose uptake in 3 T3-L1 adipocytes via an insulin-independent tyrosine kinase pathway. Biochem Biophys Res Commun 2002; 292: 642-651
    CrossrefPubMedGoogle Scholar
  • 76 Nigorikawa K, Yoshikawa K, Sasaki T, Iida E, Tsukamoto M, Murakami H, Maehama T, Hazeki K, Hazeki O. A naphthoquinone derivative, shikonin, has insulin-like actions by inhibiting both phosphatase and tensin homolog deleted on chromosome 10 and tyrosine phosphatases. Mol Pharmacol 2006; 70: 1143-1149
    CrossrefPubMedGoogle Scholar
  • 77 Öberg AI, Yassin K, Csikasz RI, Dehvari N, Shabalina IG, Hutchinson DS, Wilcke M, Östenson CG, Bengtsson T. Shikonin increases glucose uptake in skeletal muscle cells and improves plasma glucose levels in diabetic Goto-Kakizaki rats. PLoS One 2011; 6: e22510
    CrossrefPubMedGoogle Scholar