The Experts below are selected from a list of 3747 Experts worldwide ranked by ideXlab platform
Yoosik Yoon - One of the best experts on this subject based on the ideXlab platform.
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Shikonin inhibits adipogenesis by modulation of the WNT/β-catenin pathway.
Life sciences, 2010Co-Authors: Haeyong Lee, Sungmin Bae, Kijeong Kim, Wonyong Kim, Sang-in Chung, Young Yang, Yoosik YoonAbstract:Our previous study showed for the first time 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 β-catenin in the anti-adipogenic effects of Shikonin. Shikonin prevented the down-regulation of β-catenin and increased the level of its transcriptional product, cyclin D1, during adipogenesis of 3T3-L1 cells, preadipocytes originally derived from mouse embryo. β-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 γ and CCAAT/enhancer binding protein α, 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 β-catenin. Among the genes located in the WNT/β-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 clearly shows that Shikonin inhibits adipogenesis by the modulation of WNT/β-catenin pathway in vitro, and also suggests that WNT/β-catenin pathway can be used as a therapeutic target for obesity and related diseases using a natural compound like Shikonin, even though the in vivo effects of Shikonin and its clinical significance remain to be elucidated. Copyright © 2010 Elsevier Inc. All rights reserved.
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Shikonin inhibits adipogenesis by modulation of the WNT/β-catenin pathway.
Life Sciences, 2010Co-Authors: Haeyong Lee, Sungmin Bae, Kijeong Kim, Wonyong Kim, Sang-in Chung, Young Yang, Yoosik YoonAbstract:Abstract Aim Our previous study showed for the first time 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. Main methods Gene knockdown experiments using small interfering RNA (siRNA) transfection were conducted to elucidate the crucial role of β-catenin in the anti-adipogenic effects of Shikonin. Key findings Shikonin prevented the down-regulation of β-catenin and increased the level of its transcriptional product, cyclin D1, during adipogenesis of 3T3-L1 cells, preadipocytes originally derived from mouse embryo. β-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 γ and CCAAT/enhancer binding protein α, 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 β-catenin. Among the genes located in the WNT/β-catenin pathway, the levels of WNT10B and DVL2 were significantly up-regulated, whereas the level of AXIN was down-regulated by Shikonin treatment. Significance This study clearly shows that Shikonin inhibits adipogenesis by the modulation of WNT/β-catenin pathway in vitro , and also suggests that WNT/β-catenin pathway can be used as a therapeutic target for obesity and related diseases using a natural compound like Shikonin, even though the in vivo effects of Shikonin and its clinical significance remain to be elucidated.
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Shikonin inhibits fat accumulation in 3T3-L1 adipocytes.
Phytotherapy research : PTR, 2010Co-Authors: Haeyong Lee, Ryunhwa Kang, Yoosik YoonAbstract:Shikonin, 5,6-dihydroxyflavone-7-glucuronic acid, is the main ingredient of Lithospermum erythrorhizon Sieb. et Zucc, and was reported to have various biological activities including antiinflammatory, anticancer, antimicrobial and others. This study aimed to elucidate, for the first time, the antiobesity activity of Shikonin and its mechanism of action. Shikonin was found to inhibit fat droplet formation and triglyceride accumulation in 3T3-L1 adipocytes. The half inhibitory concentration, IC(50), for the inhibition of triglyceride accumulation was found to be 1.1 microM. The expression of genes involved in lipid metabolism, such as FABP4 and LPL, were significantly inhibited following Shikonin treatment. Shikonin also inhibited the ability of PPAR gamma and C/EBP alpha, the major transcription factors of adipogenesis, to bind to their target DNA sequences. The expressions of mRNA and protein of PPAR gamma and C/EBPa were significantly down-regulated following Shikonin treatment. Among the upstream regulators of adipogenesis, only SREBP1C was found to be down-regulated by Shikonin. The results of this study suggest that Shikonin down-regulates the expression of SREBP1C and subsequently the expression of PPAR gamma and C/EBP alpha. Together, these changes result in the down-regulation of lipid metabolizing enzymes and reduced fat accumulation.
Kojiro Takanashi - One of the best experts on this subject based on the ideXlab platform.
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two bahd acyltransferases catalyze the last step in the Shikonin alkannin biosynthetic pathway
Plant Physiology, 2020Co-Authors: Haruka Oshikiri, Kazufumi Yazaki, Bunta Watanabe, Hirobumi Yamamoto, Kojiro TakanashiAbstract:Several Boraginaceae plants produce biologically active red naphthoquinone pigments, derivatives of the enantiomers Shikonin and alkannin, which vary in acyl groups on their side chains. Compositions of Shikonin/alkannin derivatives vary in plant species, but the mechanisms generating the diversity of Shikonin/alkannin derivatives are largely unknown. This study describes the identification and characterization of two BAHD acyltransferases, Shikonin O-acyltransferase (LeSAT1) and alkannin O-acyltransferase (LeAAT1), from Lithospermum erythrorhizon, a medicinal plant in the family Boraginaceae that primarily produces the Shikonin/alkannin derivatives acetylShikonin and β-hydroxyisovalerylShikonin. Enzyme assays using Escherichia coli showed that the acylation activity of LeSAT1 was specific to Shikonin, whereas the acylation activity of LeAAT1 was specific to alkannin. Both enzymes recognized acetyl-CoA, isobutyryl-CoA, and isovaleryl-CoA as acyl donors to produce their corresponding Shikonin/alkannin derivatives, with both enzymes showing the highest activity for acetyl-CoA. These findings were consistent with the composition of Shikonin/alkannin derivatives in intact L. erythrorhizon plants and cell cultures. Genes encoding both enzymes were preferentially expressed in the roots and cell cultures in the dark in pigment production medium M9, conditions associated with Shikonin/alkannin production. These results indicated that LeSAT1 and LeAAT1 are enantiomer-specific acyltransferases that generate various Shikonin/alkannin derivatives.
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Two BAHD Acyltransferases Catalyze the Last Step in the Shikonin/Alkannin Biosynthetic Pathway.
Plant physiology, 2020Co-Authors: Haruka Oshikiri, Kazufumi Yazaki, Bunta Watanabe, Hirobumi Yamamoto, Kojiro TakanashiAbstract:Several Boraginaceae plants produce biologically active red naphthoquinone pigments, derivatives of the enantiomers Shikonin and alkannin, which vary in acyl groups on their side chains. Compositions of Shikonin/alkannin derivatives vary in plant species, but the mechanisms generating the diversity of Shikonin/alkannin derivatives are largely unknown. This study describes the identification and characterization of two BAHD acyltransferases, Shikonin O-acyltransferase (LeSAT1) and alkannin O-acyltransferase (LeAAT1), from Lithospermum erythrorhizon, a medicinal plant in the family Boraginaceae that primarily produces the Shikonin/alkannin derivatives acetylShikonin and β-hydroxyisovalerylShikonin. Enzyme assays using Escherichia coli showed that the acylation activity of LeSAT1 was specific to Shikonin, whereas the acylation activity of LeAAT1 was specific to alkannin. Both enzymes recognized acetyl-CoA, isobutyryl-CoA, and isovaleryl-CoA as acyl donors to produce their corresponding Shikonin/alkannin derivatives, with both enzymes showing the highest activity for acetyl-CoA. These findings were consistent with the composition of Shikonin/alkannin derivatives in intact L. erythrorhizon plants and cell cultures. Genes encoding both enzymes were preferentially expressed in the roots and cell cultures in the dark in pigment production medium M9, conditions associated with Shikonin/alkannin production. These results indicated that LeSAT1 and LeAAT1 are enantiomer-specific acyltransferases that generate various Shikonin/alkannin derivatives.
Haeyong Lee - One of the best experts on this subject based on the ideXlab platform.
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Shikonin inhibits adipogenesis by modulation of the WNT/β-catenin pathway.
Life sciences, 2010Co-Authors: Haeyong Lee, Sungmin Bae, Kijeong Kim, Wonyong Kim, Sang-in Chung, Young Yang, Yoosik YoonAbstract:Our previous study showed for the first time 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 β-catenin in the anti-adipogenic effects of Shikonin. Shikonin prevented the down-regulation of β-catenin and increased the level of its transcriptional product, cyclin D1, during adipogenesis of 3T3-L1 cells, preadipocytes originally derived from mouse embryo. β-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 γ and CCAAT/enhancer binding protein α, 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 β-catenin. Among the genes located in the WNT/β-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 clearly shows that Shikonin inhibits adipogenesis by the modulation of WNT/β-catenin pathway in vitro, and also suggests that WNT/β-catenin pathway can be used as a therapeutic target for obesity and related diseases using a natural compound like Shikonin, even though the in vivo effects of Shikonin and its clinical significance remain to be elucidated. Copyright © 2010 Elsevier Inc. All rights reserved.
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Shikonin inhibits adipogenesis by modulation of the WNT/β-catenin pathway.
Life Sciences, 2010Co-Authors: Haeyong Lee, Sungmin Bae, Kijeong Kim, Wonyong Kim, Sang-in Chung, Young Yang, Yoosik YoonAbstract:Abstract Aim Our previous study showed for the first time 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. Main methods Gene knockdown experiments using small interfering RNA (siRNA) transfection were conducted to elucidate the crucial role of β-catenin in the anti-adipogenic effects of Shikonin. Key findings Shikonin prevented the down-regulation of β-catenin and increased the level of its transcriptional product, cyclin D1, during adipogenesis of 3T3-L1 cells, preadipocytes originally derived from mouse embryo. β-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 γ and CCAAT/enhancer binding protein α, 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 β-catenin. Among the genes located in the WNT/β-catenin pathway, the levels of WNT10B and DVL2 were significantly up-regulated, whereas the level of AXIN was down-regulated by Shikonin treatment. Significance This study clearly shows that Shikonin inhibits adipogenesis by the modulation of WNT/β-catenin pathway in vitro , and also suggests that WNT/β-catenin pathway can be used as a therapeutic target for obesity and related diseases using a natural compound like Shikonin, even though the in vivo effects of Shikonin and its clinical significance remain to be elucidated.
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Shikonin inhibits fat accumulation in 3T3-L1 adipocytes.
Phytotherapy research : PTR, 2010Co-Authors: Haeyong Lee, Ryunhwa Kang, Yoosik YoonAbstract:Shikonin, 5,6-dihydroxyflavone-7-glucuronic acid, is the main ingredient of Lithospermum erythrorhizon Sieb. et Zucc, and was reported to have various biological activities including antiinflammatory, anticancer, antimicrobial and others. This study aimed to elucidate, for the first time, the antiobesity activity of Shikonin and its mechanism of action. Shikonin was found to inhibit fat droplet formation and triglyceride accumulation in 3T3-L1 adipocytes. The half inhibitory concentration, IC(50), for the inhibition of triglyceride accumulation was found to be 1.1 microM. The expression of genes involved in lipid metabolism, such as FABP4 and LPL, were significantly inhibited following Shikonin treatment. Shikonin also inhibited the ability of PPAR gamma and C/EBP alpha, the major transcription factors of adipogenesis, to bind to their target DNA sequences. The expressions of mRNA and protein of PPAR gamma and C/EBPa were significantly down-regulated following Shikonin treatment. Among the upstream regulators of adipogenesis, only SREBP1C was found to be down-regulated by Shikonin. The results of this study suggest that Shikonin down-regulates the expression of SREBP1C and subsequently the expression of PPAR gamma and C/EBP alpha. Together, these changes result in the down-regulation of lipid metabolizing enzymes and reduced fat accumulation.
Haruka Oshikiri - One of the best experts on this subject based on the ideXlab platform.
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two bahd acyltransferases catalyze the last step in the Shikonin alkannin biosynthetic pathway
Plant Physiology, 2020Co-Authors: Haruka Oshikiri, Kazufumi Yazaki, Bunta Watanabe, Hirobumi Yamamoto, Kojiro TakanashiAbstract:Several Boraginaceae plants produce biologically active red naphthoquinone pigments, derivatives of the enantiomers Shikonin and alkannin, which vary in acyl groups on their side chains. Compositions of Shikonin/alkannin derivatives vary in plant species, but the mechanisms generating the diversity of Shikonin/alkannin derivatives are largely unknown. This study describes the identification and characterization of two BAHD acyltransferases, Shikonin O-acyltransferase (LeSAT1) and alkannin O-acyltransferase (LeAAT1), from Lithospermum erythrorhizon, a medicinal plant in the family Boraginaceae that primarily produces the Shikonin/alkannin derivatives acetylShikonin and β-hydroxyisovalerylShikonin. Enzyme assays using Escherichia coli showed that the acylation activity of LeSAT1 was specific to Shikonin, whereas the acylation activity of LeAAT1 was specific to alkannin. Both enzymes recognized acetyl-CoA, isobutyryl-CoA, and isovaleryl-CoA as acyl donors to produce their corresponding Shikonin/alkannin derivatives, with both enzymes showing the highest activity for acetyl-CoA. These findings were consistent with the composition of Shikonin/alkannin derivatives in intact L. erythrorhizon plants and cell cultures. Genes encoding both enzymes were preferentially expressed in the roots and cell cultures in the dark in pigment production medium M9, conditions associated with Shikonin/alkannin production. These results indicated that LeSAT1 and LeAAT1 are enantiomer-specific acyltransferases that generate various Shikonin/alkannin derivatives.
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Two BAHD Acyltransferases Catalyze the Last Step in the Shikonin/Alkannin Biosynthetic Pathway.
Plant physiology, 2020Co-Authors: Haruka Oshikiri, Kazufumi Yazaki, Bunta Watanabe, Hirobumi Yamamoto, Kojiro TakanashiAbstract:Several Boraginaceae plants produce biologically active red naphthoquinone pigments, derivatives of the enantiomers Shikonin and alkannin, which vary in acyl groups on their side chains. Compositions of Shikonin/alkannin derivatives vary in plant species, but the mechanisms generating the diversity of Shikonin/alkannin derivatives are largely unknown. This study describes the identification and characterization of two BAHD acyltransferases, Shikonin O-acyltransferase (LeSAT1) and alkannin O-acyltransferase (LeAAT1), from Lithospermum erythrorhizon, a medicinal plant in the family Boraginaceae that primarily produces the Shikonin/alkannin derivatives acetylShikonin and β-hydroxyisovalerylShikonin. Enzyme assays using Escherichia coli showed that the acylation activity of LeSAT1 was specific to Shikonin, whereas the acylation activity of LeAAT1 was specific to alkannin. Both enzymes recognized acetyl-CoA, isobutyryl-CoA, and isovaleryl-CoA as acyl donors to produce their corresponding Shikonin/alkannin derivatives, with both enzymes showing the highest activity for acetyl-CoA. These findings were consistent with the composition of Shikonin/alkannin derivatives in intact L. erythrorhizon plants and cell cultures. Genes encoding both enzymes were preferentially expressed in the roots and cell cultures in the dark in pigment production medium M9, conditions associated with Shikonin/alkannin production. These results indicated that LeSAT1 and LeAAT1 are enantiomer-specific acyltransferases that generate various Shikonin/alkannin derivatives.
Kazufumi Yazaki - One of the best experts on this subject based on the ideXlab platform.
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two bahd acyltransferases catalyze the last step in the Shikonin alkannin biosynthetic pathway
Plant Physiology, 2020Co-Authors: Haruka Oshikiri, Kazufumi Yazaki, Bunta Watanabe, Hirobumi Yamamoto, Kojiro TakanashiAbstract:Several Boraginaceae plants produce biologically active red naphthoquinone pigments, derivatives of the enantiomers Shikonin and alkannin, which vary in acyl groups on their side chains. Compositions of Shikonin/alkannin derivatives vary in plant species, but the mechanisms generating the diversity of Shikonin/alkannin derivatives are largely unknown. This study describes the identification and characterization of two BAHD acyltransferases, Shikonin O-acyltransferase (LeSAT1) and alkannin O-acyltransferase (LeAAT1), from Lithospermum erythrorhizon, a medicinal plant in the family Boraginaceae that primarily produces the Shikonin/alkannin derivatives acetylShikonin and β-hydroxyisovalerylShikonin. Enzyme assays using Escherichia coli showed that the acylation activity of LeSAT1 was specific to Shikonin, whereas the acylation activity of LeAAT1 was specific to alkannin. Both enzymes recognized acetyl-CoA, isobutyryl-CoA, and isovaleryl-CoA as acyl donors to produce their corresponding Shikonin/alkannin derivatives, with both enzymes showing the highest activity for acetyl-CoA. These findings were consistent with the composition of Shikonin/alkannin derivatives in intact L. erythrorhizon plants and cell cultures. Genes encoding both enzymes were preferentially expressed in the roots and cell cultures in the dark in pigment production medium M9, conditions associated with Shikonin/alkannin production. These results indicated that LeSAT1 and LeAAT1 are enantiomer-specific acyltransferases that generate various Shikonin/alkannin derivatives.
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Two BAHD Acyltransferases Catalyze the Last Step in the Shikonin/Alkannin Biosynthetic Pathway.
Plant physiology, 2020Co-Authors: Haruka Oshikiri, Kazufumi Yazaki, Bunta Watanabe, Hirobumi Yamamoto, Kojiro TakanashiAbstract:Several Boraginaceae plants produce biologically active red naphthoquinone pigments, derivatives of the enantiomers Shikonin and alkannin, which vary in acyl groups on their side chains. Compositions of Shikonin/alkannin derivatives vary in plant species, but the mechanisms generating the diversity of Shikonin/alkannin derivatives are largely unknown. This study describes the identification and characterization of two BAHD acyltransferases, Shikonin O-acyltransferase (LeSAT1) and alkannin O-acyltransferase (LeAAT1), from Lithospermum erythrorhizon, a medicinal plant in the family Boraginaceae that primarily produces the Shikonin/alkannin derivatives acetylShikonin and β-hydroxyisovalerylShikonin. Enzyme assays using Escherichia coli showed that the acylation activity of LeSAT1 was specific to Shikonin, whereas the acylation activity of LeAAT1 was specific to alkannin. Both enzymes recognized acetyl-CoA, isobutyryl-CoA, and isovaleryl-CoA as acyl donors to produce their corresponding Shikonin/alkannin derivatives, with both enzymes showing the highest activity for acetyl-CoA. These findings were consistent with the composition of Shikonin/alkannin derivatives in intact L. erythrorhizon plants and cell cultures. Genes encoding both enzymes were preferentially expressed in the roots and cell cultures in the dark in pigment production medium M9, conditions associated with Shikonin/alkannin production. These results indicated that LeSAT1 and LeAAT1 are enantiomer-specific acyltransferases that generate various Shikonin/alkannin derivatives.
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Effects of Methyl Jasmonate on Shikonin and Dihydroechinofuran Production in Lithospermum Cell Cultures
Plant and Cell Physiology, 1997Co-Authors: Kazufumi Yazaki, Kenta Takeda, Mamoru TabataAbstract:Methyl jasmonate, when administered to Lithospermum erythrorhizon cell suspension cultures, was found to induce the production of Shikonin derivatives (the red naphthoquinone pigments of the root) and dihydroechinofuran (an abnormal metabolite of geranylhydroquinone). Culture experiments showed that methyl jasmonate caused a rapid increase in the activities of enzymes involved in the biosynthesis of Shikonin such asp-hydroxybenzoate geranyltransferase, which was followed by the rapid accumulation of dihydroechinofuran and the delayed production of Shikonin. The induction patterns observed were similar to those elicited by oligogalacturonides in Lithospermum cells, suggesting that jasmonic acid or its derivative may act as a signaling molecule in the elicitation of Shikonin biosynthesis. Interestingly, however, the copper ion, which is essential for inducing Shikonin biosynthesis by oligogalacturonides, was not required for Shikonin induction by methyl jasmonate.
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Measurement of Phenolic Compounds and Their Effect on Shikonin Production in Lithospermum Cultured Cells.
Bioscience biotechnology and biochemistry, 1997Co-Authors: Kazufumi Yazaki, Hiroshi Fukui, Yumiko Nishikawa, Mamoru TabataAbstract:Shikonin production by Lithospevmum cell cultures is induced by transferring the cells into production medium. Six phenolic compounds, p-hydroxybenzoic acid, caffeic acid, sinapic acid, ferulic acid, syringaldehyde, and salicyclic acid, were detected in both Shikonin-producing and non-producing cells. Their contents in the former were much lower than those in the latter except for salicylic acid, the content of which strongly increased when cells were producing Shikonin. The cell wall fraction, after alkaline hydrolysis, gave two phenolic compounds, p-hydroxybenzoic acid and caffeic acid. Their contents were much higher in Shikonin-producing cells than in Shikonin-free cells. Of these compounds, exogenous addition of p-hydroxybenzoic acid increased Shikonin production in the production medium. Although it is a precursor of Shikonin, the increment of Shikonin produced was much larger than the administered p-hydroxybenzoic acid, suggesting this compound has a stimulatory effect on Shikonin biosynthesis at a low concentration.
