A new approach for asymmetric synthesis of alkannin and shikonin is presented. The chiral centers of the targets were introduced via an asymmetric C-arylation of protected chiral glyceraldehyde in high de. The two e...A new approach for asymmetric synthesis of alkannin and shikonin is presented. The chiral centers of the targets were introduced via an asymmetric C-arylation of protected chiral glyceraldehyde in high de. The two enantiomers were prepared with the D-isopropylidenegly- ceraldehyde as the starting material.展开更多
Radiation encephalopathy is the main complication of cranial radiotherapy. It can cause necrosis of brain tissue and cognitive dysfunction. Our previous work had proved that a natural antioxidant shikonin possessed pr...Radiation encephalopathy is the main complication of cranial radiotherapy. It can cause necrosis of brain tissue and cognitive dysfunction. Our previous work had proved that a natural antioxidant shikonin possessed protective effect on cerebral ischemic injury. Here we investigated the effects of shikonin on carbon ion beam induced radiation brain injury in mice. Pretreatment with shikonin significantly increased the SOD and CAT activities and the ratio of GSH/GSSG in mouse brain tissues compared with irradiated group （P〈0.01）, while obviously reduced the MDA and PCO contents and the RO$ levels derived from of the brain mitochondria.展开更多
1 INTRODUCTIONThe production of secondary metabolites using plant cells has been the subject of much inter-est in recent years.Despite that tremendous research efforts had been made in this topic,notmany products have...1 INTRODUCTIONThe production of secondary metabolites using plant cells has been the subject of much inter-est in recent years.Despite that tremendous research efforts had been made in this topic,notmany products have reached the commercial stage.It is generally acknowledged that the mainproblem in this field is the lack of basic knowledge of the biosynthetic routes,and the mechanisms found to bring about the production of such secondary metabolites.There are,however,some techniques that have beneficial effects on the production and ex-展开更多
A novel total synthesis of （±）shikonin 1 was presented. The key intermediate 6 was achieved by the formylation of 1,8：4,5-bis（methylenedioxy）naphthalene 5 with N-methylformanilide in good yield. It was first...A novel total synthesis of （±）shikonin 1 was presented. The key intermediate 6 was achieved by the formylation of 1,8：4,5-bis（methylenedioxy）naphthalene 5 with N-methylformanilide in good yield. It was first reported that the addition of prenyllithium to 2-formyl-1,8：4,5- bismethylenedioxy naphthalene 6 gave 2-（1-hydroxy-4-methylpentyl） 1,8：4,5-bis（methylenedioxy） naphthalene 8 in 45% yield and 2-（1-hydroxy-2,2-dimethyl-3-butenyl）-1,8：4,5-bis（methylenedioxy）naphthalene 9 in 48% yield. After the electrooxide deprotection of 8, （±）shikonin 1 was prepared in high yield.展开更多
Objective:To investigate the potential anti-tumor mechanisms of naphthoquinone compound shikonin(SKN)extracted from the root of Chinese herbal medicine plant lithospermum(Lithospermum erythrorhizon Sieb.&Zucc.).Me...Objective:To investigate the potential anti-tumor mechanisms of naphthoquinone compound shikonin(SKN)extracted from the root of Chinese herbal medicine plant lithospermum(Lithospermum erythrorhizon Sieb.&Zucc.).Methods:We first observed that SKN treatment led to swelling and bubbles in HeLa cells that were similar to the phenotype of cell pyroptosis.Subsequently,the HeLa cells experienced a pyroptotic process with SKN,and this was then assessed using lactate dehydrogenase(LDH)release and propidium iodide(PI)/Hoechst double staining experiments.Pyroptosis is defined as gasdermin-mediated programmed necroptosis.To identify the potential pyroptosis machinery,two strategies were utilized that included a genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)-associated protein 9 screening experiment and a pyroptosis reconstitution assay executed by each of the five known gasdermins(GSDMA-E).Moreover,endogenous cleavage was also detected in a panel of tumor cell lines.Results:Compared with the control,both the LDH release and PI/Hoechst double-staining experiments suggested that SKN induced perforation and enhancement of the permeability of the cell membranes that resulted in pyroptosis in HeLa cells(P=.028 and P=.032,respectively).In addition,the reconstitution assays in human embryonic kidney 293T(HEK-293T)cells and endogenous cleavage assays in HeLa cells indicated that the pyroptosis was controlled by GSDME.In addition,we also found SKN could trigger pyroptosis in a panel of tumor cell lines in which the cellular morphologies were proportional to the GSDME expression levels.Additionally,the cleavage of GSDME was also detected,and this was indicative of a similar GSDME-mediated mechanism.Conclusion:Our study not only explained the molecular mechanism of cytotoxicity of SKN to various tumor cells,but also provided additional information for the potential clinical application of natural naphthoquinone compounds against cancer.展开更多
Controlling fertility of rodent pests has become an effective means of controlling the population of grassland rodents in China. Recently, research has focused on how to select environmentally-friendly sterilants with...Controlling fertility of rodent pests has become an effective means of controlling the population of grassland rodents in China. Recently, research has focused on how to select environmentally-friendly sterilants without pollution effects, and to realize sustainable control of pest rodent populations. Sterilants from plant extracts have been mainly selected. In this study, mice were used as the experimental subjects for research on the anti-fertility effects of plant extracts of shikonin and the anti-fertility mechanism of shikonin extract was determined. The mice were divided into four groups, including one control group and three experimental groups. There were three applications of shikonin extract in different concentrations (5 mg·kg<sup>-1</sup>, 20 mg·kg<sup>-1</sup> and 50 mg·kg<sup>-1</sup>). The mice gavage experiments indicated that a shikonin concentration of 50 mg·kg<sup>-1</sup> had the expected anti-fertility effects. Mice copulation experiments showed that the 50 mg·kg<sup>-1</sup> shikonin treatment had significant anti-fertility effects on both female-treatment and female-male-treatment groups. The results of the PCR analysis on the AgRP and ghrelin mRNA from female ovaries and male testicles indicated that shikonin could control mice reproduction by regulating the pituitary gonadal axis. Shikonin, as plant source sterile agent, would have more ideal effects for functioned both sexes sterility.展开更多
A new facile route for the synthesis of dl-shikonin is presented. Reformatsky reaction assisted cross-coupling of 1, 4, 5, 8-tetramethoxynaphthalene-2-carbaldehyde and ethyl- bromoacetate was employed for introductio...A new facile route for the synthesis of dl-shikonin is presented. Reformatsky reaction assisted cross-coupling of 1, 4, 5, 8-tetramethoxynaphthalene-2-carbaldehyde and ethyl- bromoacetate was employed for introduction of the side chain of dl-shikonin.展开更多
背景:研究表明,紫草素具有促进骨缺损修复、治疗骨质疏松的作用。目的:总结紫草素及其衍生物在口腔软硬组织再生中的应用潜力方法:检索PubMed、Web of Science、万方、中国知网、维普数据库2002-2023年收录的相关文献,中文检索词为“紫...背景:研究表明,紫草素具有促进骨缺损修复、治疗骨质疏松的作用。目的:总结紫草素及其衍生物在口腔软硬组织再生中的应用潜力方法:检索PubMed、Web of Science、万方、中国知网、维普数据库2002-2023年收录的相关文献,中文检索词为“紫草素,口腔,牙周炎,抗菌,成骨分化,破骨细胞,骨质疏松,毒理学”,英文检索词为“shikonin,oral cavity,periodontitis,antibacterial,bone formation,Osteoclast,osteoporosis,toxicology”。结果与结论:紫草素及其衍生物具有抗炎、抑制牙龈卟啉单胞菌等牙周致病菌、促进牙周创面愈合以及牙槽骨组织再生的生物活性。紫草制剂可以治疗口腔阿弗他溃疡、口腔念珠菌病等口腔黏膜疾病。这些证据表明紫草素及其衍生物在治疗牙周病、防治口腔疾病和促进牙周软硬组织再生方面表现出良好的前景。如何将紫草素与组织工程相结合,从而实现更快的口腔软硬组织愈合还有待研究。展开更多
Background：Shikonin is a major active chemical component extracted from Lithospermi Radix,an effective traditional herb in various types of wound healing.Shikonin can accelerate granulomatous tissue formation by the ...Background：Shikonin is a major active chemical component extracted from Lithospermi Radix,an effective traditional herb in various types of wound healing.Shikonin can accelerate granulomatous tissue formation by the rat cotton pellet method and induce neovascularization in granulomatous tissue.The purpose of the study was to investigate its mechanism of action in human skin cells.Methods：MTS assay was used to measure cell growth.The collagen type Ⅰ （COL1） mRNA expression and procollagen type Ⅰ C-peptide （PIP） production were detected by real-time quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay,respectively.Immunofluorescence and western blot analyses were carried out to investigate nuclear factor-κB （NF-κB） signaling pathway.Cell-based proteasome activity assay was used to determine proteasome activity.Results：In this study,we found that 10 μmol/L shikonin stimulated the growth of normal human keratinocytes and 1 μmol/L shikonin promoted growth of human dermal fibroblasts.However,shikonin did not directly induce COLI mRNA expression and PIP production in dermal fibroblasts in vitro.In addition,1 μmol/L shikonin inhibited translocation of NF-κB p65 from cytoplasm to nucleus induced by tumor necrosis factor-α stimulation in dermal fibroblasts.Furthermore,shikonin inhibited chymotrypsin-like activity of proteasome and was associated with accumulation ofphosphorylated inhibitor κB-α in dermal fibroblasts.Conclusions：These results suggested that shikonin may promote wound healing via its cell growth promoting activity and suppress skin inflammation via inhibitory activity on proteasome.Thus,shikonin may be a potential therapeutic reagent both in wound healing and inflammatory skin diseases.展开更多
基金the National Natural Science Foundation of China[32071532]for financial supports
文摘A new approach for asymmetric synthesis of alkannin and shikonin is presented. The chiral centers of the targets were introduced via an asymmetric C-arylation of protected chiral glyceraldehyde in high de. The two enantiomers were prepared with the D-isopropylidenegly- ceraldehyde as the starting material.
基金supported by Key Program of National Natural Science Foundation of China(U1432248)National Natural Science Foundation of China(11175222,11305226)
文摘Radiation encephalopathy is the main complication of cranial radiotherapy. It can cause necrosis of brain tissue and cognitive dysfunction. Our previous work had proved that a natural antioxidant shikonin possessed protective effect on cerebral ischemic injury. Here we investigated the effects of shikonin on carbon ion beam induced radiation brain injury in mice. Pretreatment with shikonin significantly increased the SOD and CAT activities and the ratio of GSH/GSSG in mouse brain tissues compared with irradiated group （P〈0.01）, while obviously reduced the MDA and PCO contents and the RO$ levels derived from of the brain mitochondria.
文摘1 INTRODUCTIONThe production of secondary metabolites using plant cells has been the subject of much inter-est in recent years.Despite that tremendous research efforts had been made in this topic,notmany products have reached the commercial stage.It is generally acknowledged that the mainproblem in this field is the lack of basic knowledge of the biosynthetic routes,and the mechanisms found to bring about the production of such secondary metabolites.There are,however,some techniques that have beneficial effects on the production and ex-
文摘A novel total synthesis of （±）shikonin 1 was presented. The key intermediate 6 was achieved by the formylation of 1,8：4,5-bis（methylenedioxy）naphthalene 5 with N-methylformanilide in good yield. It was first reported that the addition of prenyllithium to 2-formyl-1,8：4,5- bismethylenedioxy naphthalene 6 gave 2-（1-hydroxy-4-methylpentyl） 1,8：4,5-bis（methylenedioxy） naphthalene 8 in 45% yield and 2-（1-hydroxy-2,2-dimethyl-3-butenyl）-1,8：4,5-bis（methylenedioxy）naphthalene 9 in 48% yield. After the electrooxide deprotection of 8, （±）shikonin 1 was prepared in high yield.
基金This research was supported by the Program for the Research Startup Fund Program at the Beijing University of Chinese Medicine(90011451310011)the Key Research Fund for Drug Discovery in Chinese Medicine at the Beijing University of Chinese Medicine(1000061223740)+1 种基金the Experimental Technology Standardization Research Project at the Beijing University of Chinese Medicine(2021-SYJS-009)the Fundamental Research Funds for the Central Universities of the Beijing University of Chinese Medicine(2020-JYB-ZDGG-057).
文摘Objective:To investigate the potential anti-tumor mechanisms of naphthoquinone compound shikonin(SKN)extracted from the root of Chinese herbal medicine plant lithospermum(Lithospermum erythrorhizon Sieb.&Zucc.).Methods:We first observed that SKN treatment led to swelling and bubbles in HeLa cells that were similar to the phenotype of cell pyroptosis.Subsequently,the HeLa cells experienced a pyroptotic process with SKN,and this was then assessed using lactate dehydrogenase(LDH)release and propidium iodide(PI)/Hoechst double staining experiments.Pyroptosis is defined as gasdermin-mediated programmed necroptosis.To identify the potential pyroptosis machinery,two strategies were utilized that included a genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)-associated protein 9 screening experiment and a pyroptosis reconstitution assay executed by each of the five known gasdermins(GSDMA-E).Moreover,endogenous cleavage was also detected in a panel of tumor cell lines.Results:Compared with the control,both the LDH release and PI/Hoechst double-staining experiments suggested that SKN induced perforation and enhancement of the permeability of the cell membranes that resulted in pyroptosis in HeLa cells(P=.028 and P=.032,respectively).In addition,the reconstitution assays in human embryonic kidney 293T(HEK-293T)cells and endogenous cleavage assays in HeLa cells indicated that the pyroptosis was controlled by GSDME.In addition,we also found SKN could trigger pyroptosis in a panel of tumor cell lines in which the cellular morphologies were proportional to the GSDME expression levels.Additionally,the cleavage of GSDME was also detected,and this was indicative of a similar GSDME-mediated mechanism.Conclusion:Our study not only explained the molecular mechanism of cytotoxicity of SKN to various tumor cells,but also provided additional information for the potential clinical application of natural naphthoquinone compounds against cancer.
文摘Controlling fertility of rodent pests has become an effective means of controlling the population of grassland rodents in China. Recently, research has focused on how to select environmentally-friendly sterilants without pollution effects, and to realize sustainable control of pest rodent populations. Sterilants from plant extracts have been mainly selected. In this study, mice were used as the experimental subjects for research on the anti-fertility effects of plant extracts of shikonin and the anti-fertility mechanism of shikonin extract was determined. The mice were divided into four groups, including one control group and three experimental groups. There were three applications of shikonin extract in different concentrations (5 mg·kg<sup>-1</sup>, 20 mg·kg<sup>-1</sup> and 50 mg·kg<sup>-1</sup>). The mice gavage experiments indicated that a shikonin concentration of 50 mg·kg<sup>-1</sup> had the expected anti-fertility effects. Mice copulation experiments showed that the 50 mg·kg<sup>-1</sup> shikonin treatment had significant anti-fertility effects on both female-treatment and female-male-treatment groups. The results of the PCR analysis on the AgRP and ghrelin mRNA from female ovaries and male testicles indicated that shikonin could control mice reproduction by regulating the pituitary gonadal axis. Shikonin, as plant source sterile agent, would have more ideal effects for functioned both sexes sterility.
文摘A new facile route for the synthesis of dl-shikonin is presented. Reformatsky reaction assisted cross-coupling of 1, 4, 5, 8-tetramethoxynaphthalene-2-carbaldehyde and ethyl- bromoacetate was employed for introduction of the side chain of dl-shikonin.
基金Acknowledgments This work was supported by grants from the National High Technology Research and Development Program of China （863 Program） （2006AA02A306）, the National Natural Science Foundation of China （No. 39900082） and the PhD Program Foundation of Ministry of Education of China （No. 204090188）. We thank Dr Courtney M Heney （Massachusetts General Hospital, Harvard University） for critically reading the manuscript.
基金This work was supported National Key R＆D Program of China （No. 2017YFE0102200）, National Natural Science Foundation for Distinguished Young Scholar of China （81625024） and National Natural Science Foundation of China （81773753） to B. Yang.
文摘背景:研究表明,紫草素具有促进骨缺损修复、治疗骨质疏松的作用。目的:总结紫草素及其衍生物在口腔软硬组织再生中的应用潜力方法:检索PubMed、Web of Science、万方、中国知网、维普数据库2002-2023年收录的相关文献,中文检索词为“紫草素,口腔,牙周炎,抗菌,成骨分化,破骨细胞,骨质疏松,毒理学”,英文检索词为“shikonin,oral cavity,periodontitis,antibacterial,bone formation,Osteoclast,osteoporosis,toxicology”。结果与结论:紫草素及其衍生物具有抗炎、抑制牙龈卟啉单胞菌等牙周致病菌、促进牙周创面愈合以及牙槽骨组织再生的生物活性。紫草制剂可以治疗口腔阿弗他溃疡、口腔念珠菌病等口腔黏膜疾病。这些证据表明紫草素及其衍生物在治疗牙周病、防治口腔疾病和促进牙周软硬组织再生方面表现出良好的前景。如何将紫草素与组织工程相结合,从而实现更快的口腔软硬组织愈合还有待研究。
文摘Background：Shikonin is a major active chemical component extracted from Lithospermi Radix,an effective traditional herb in various types of wound healing.Shikonin can accelerate granulomatous tissue formation by the rat cotton pellet method and induce neovascularization in granulomatous tissue.The purpose of the study was to investigate its mechanism of action in human skin cells.Methods：MTS assay was used to measure cell growth.The collagen type Ⅰ （COL1） mRNA expression and procollagen type Ⅰ C-peptide （PIP） production were detected by real-time quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay,respectively.Immunofluorescence and western blot analyses were carried out to investigate nuclear factor-κB （NF-κB） signaling pathway.Cell-based proteasome activity assay was used to determine proteasome activity.Results：In this study,we found that 10 μmol/L shikonin stimulated the growth of normal human keratinocytes and 1 μmol/L shikonin promoted growth of human dermal fibroblasts.However,shikonin did not directly induce COLI mRNA expression and PIP production in dermal fibroblasts in vitro.In addition,1 μmol/L shikonin inhibited translocation of NF-κB p65 from cytoplasm to nucleus induced by tumor necrosis factor-α stimulation in dermal fibroblasts.Furthermore,shikonin inhibited chymotrypsin-like activity of proteasome and was associated with accumulation ofphosphorylated inhibitor κB-α in dermal fibroblasts.Conclusions：These results suggested that shikonin may promote wound healing via its cell growth promoting activity and suppress skin inflammation via inhibitory activity on proteasome.Thus,shikonin may be a potential therapeutic reagent both in wound healing and inflammatory skin diseases.
