The study aimed to explore the efficacy and potential mechanisms of a naturally aromatic cyanogenic compound amygdalin(AMY)in treating glucocorticoid(GC)-associated necrosis of the femoral head(GANFH).We demonstrated ...The study aimed to explore the efficacy and potential mechanisms of a naturally aromatic cyanogenic compound amygdalin(AMY)in treating glucocorticoid(GC)-associated necrosis of the femoral head(GANFH).We demonstrated that GC exacerbates the oxidative stress(OS)microenvironment via promoting nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4)expression in human,rat,and mesenchymal stem cells(MSCs)samples,thus generating excessive reactive oxygen species(ROS),leading to increased apoptosis and unbalanced osteolipogenic differentiation.Furthermore,computational docking results revealed that AMY could bind specifically to the predicted binding sites of NOX4.Additionally,AMY ameliorated the OS microenvironment of MSCs via decreasing NOX4 expression and inhibiting NOX4/ROS/p38MAPK signaling,thereby reversing the GC-induced apoptosis and imbalanced osteolipogenic differentiation,and ultimately alleviating GANFH.In summary,we demonstrated for the first time that AMY attenuated apoptosis and maintained osteolipogenic differentiation balance in MSCs via specifically targeting NOX4,inhibiting NOX4/ROS/p38MAPK signaling,thereby treating GANFH.展开更多
AIM： The genes were divided into seven categories according to biological function; apoptosis-related, immune response-related, signal transduction-related, cell cyclerelated, cell growth-related, stress response-rel...AIM： The genes were divided into seven categories according to biological function; apoptosis-related, immune response-related, signal transduction-related, cell cyclerelated, cell growth-related, stress response-related and transcription-related genes. METHODS： We compared the gene expression profiles of SNU-C4 cells between amygdalin-treated （5 mg/mL, 24 h） and non-treated groups using cDNA microarray analysis. We selected genes downregulated in cDNA microarray and investigated mRNA levels of the genes by RT- PC R. RESULTS： Microarray showed that amygdalin downregulated especially genes belonging to cell cycle category： exonuclease 1 （EXO1）, ATP-binding cassette, sub-family F, member 2 （ABCF2）, MRE11 meiotic recombination 11 homolog A （MRE11A）, topoisomerase （DNA） Ⅰ （TOP1）, and FK506 binding protein 12-rapamycin-associated protein 1 （FRAP1）. RT-PCR analysis revealed that mRNA levels of these genes were also decreased by amygdalin treatment in SNU-C4 human colon cancer cells. CONCLUSION： These results suggest that amygdalin have an anticancer effect via downregulation of cell cycle-related genes in SNU-C4 human colon cancer cells, and might be used for therapeutic anticancer drug.展开更多
Summary: The pathogenesis of hyperoxia lung injury and the mechanism of amygdalin on type 2 alveolar epithelial cells (AEC2) isolated from premature rat lungs in vitro were investigated. AEC2 were obtained by primary ...Summary: The pathogenesis of hyperoxia lung injury and the mechanism of amygdalin on type 2 alveolar epithelial cells (AEC2) isolated from premature rat lungs in vitro were investigated. AEC2 were obtained by primary culture from 20-days fetal rat lung and hyperoxia-exposed cell model was established. Cell proliferating viability was examined by MTT assay after treatment of amygdalin at various concentrations. DNA content and the proliferating cell nuclear antigen (PCNA) protein expression of AEC2 were measured by using flow cytometry and immunocytochemistry respectively after 24 h of hyperoxia exposure or amygdalin treatment. The results showed that hyperoxia inhibited the proliferation and decreased PCNA protein expression in AEC2 of premature rat in vitro. Amygdalin at the concentration range of 50-200 μmol/L stimulated the proliferation of AEC2 in a dose-dependent manner, however, 400 μmol/L amygdalin inhibited the proliferation of AEC2. Amygdalin at the concentration of 200 μmol/L played its best role in facilitating proliferation of AEC2s in vitro and could partially ameliorated the changes of proliferation in hyperoxia exposed AEC2 of premature rat. It has been suggested that hyperoxia inhibited the proliferation of AEC2s of premature rat, which may contribute to hyperoxia lung injury. Amygdalin may play partial protective role in hyperoxia-induced lung injury.展开更多
OBJECTIVE:To analyze the transdermal profile of pseudoephedrine and amygdalin in the Traditional Chinese Medicine majiepingchuan in rat skin and to reveal their interaction.METHODS:A Franz diffusion cell was used in v...OBJECTIVE:To analyze the transdermal profile of pseudoephedrine and amygdalin in the Traditional Chinese Medicine majiepingchuan in rat skin and to reveal their interaction.METHODS:A Franz diffusion cell was used in vitro to evaluate the transdermal parameters of cumulative transdermal flux(Q_(tot)),cumulative transmission(T_(tot)),and mean penetration rate(Kp)of pseudoephedrine and amygdalin in majiepingchuan.Linear regression analyses of Q_(tot)over time of pseudoephedrine vs amygdalin and their ratios was adopted for correlation evaluation.RESULTS:At 1,2,4,6,and 8 h,the Q_(tot),T_(tot)and Kp of pseudoephedrine showed a good correlation with that of amygdalin.CONCLUSION:There was a small difference in theratios of Q_(tot),T_(tot)and Kp between pseudoephedrine and amygdalin,and a correlation between them.展开更多
Objective:To observe the effect of amygdalin on liver fibrosis in a liver fibrosis mouse model,and the underlying mechanisms were partly dissected in vivo and in vitro.Methods:Thirty-two male mice were randomly divide...Objective:To observe the effect of amygdalin on liver fibrosis in a liver fibrosis mouse model,and the underlying mechanisms were partly dissected in vivo and in vitro.Methods:Thirty-two male mice were randomly divided into 4 groups,including control,model,low-and high-dose amygdalin-treated groups,8 mice in each group.Except the control group,mice in the other groups were injected intraperitoneally with 10%carbon tetrachloride(CCl4)-olive oil solution 3 times a week for 6 weeks to induce liver fibrosis.At the first 3 weeks,amygdalin(1.35 and 2.7 mg/kg body weight)were administered by gavage once a day.Mice in the control group received equal quantities of subcutaneous olive oil and intragastric water from the fourth week.At the end of 6 weeks,liver tissue samples were harvested to detect the content of hydroxyproline(Hyp).Hematoxylin and eosin and Sirius red staining were used to observe the inflammation and fibrosis of liver tissue.The expressions of collagenⅠ(Col-Ⅰ),alpha-smooth muscle actin(α-SMA),CD31 and transforming growth factorβ(TGF-β)/Smad signaling pathway were detected by immunohistochemistry,quantitative real-time polymerase chain reaction and Western blot,respectively.The activation models of hepatic stellate cells,JS-1and LX-2 cells induced by TGF-β1 were used in vitro with or without different concentrations of amygdalin(0.1,1,10μmol/L).The effect of different concentrations of amygdalin on the expressions of liver sinusoidal endothelial cells(LSECs)dedifferentiation markers CD31 and CD44 were observed.Results:High-dose of amygdalin significantly reduced the Hyp content and percentage of collagen positive area,and decreased the mRNA and protein expressions of Col-Ι,α-SMA,CD31 and p-Smad2/3 in liver tissues of mice compared to the model group(P<0.01).Amygdalin down-regulated the expressions of Col-Ⅰandα-SMA in JS-1 and LX-2 cells,and TGFβR1,TGFβR2 and p-Smad2/3 in LX-2 cells compared to the model group(P<0.05 or P<0.01).Moreover,1 and 10μmol/L amygdalin inhibited the mRNA and protein expressions of CD31 in LSECs and increased CD44 expression compared to the model group(P<0.05 or P<0.01).Conclusions:Amygdalin can dramatically alleviate liver fibrosis induced by CCl4 in mice and inhibit TGF-β/Smad signaling pathway,consequently suppressing HSCs activation and LSECs dedifferentiation to improve angiogenesis.展开更多
苦杏仁苷是存在于苦杏仁等蔷薇科植物中的一种含氰基糖苷化合物。近年研究显示苦杏仁苷具有较好的抗纤维化作用,主要与调控相关细胞凋亡、控制有关胶原蛋白表达等密切相关。此外,苦杏仁苷抗肿瘤、抗炎等药理作用也取得明显进展,其通过...苦杏仁苷是存在于苦杏仁等蔷薇科植物中的一种含氰基糖苷化合物。近年研究显示苦杏仁苷具有较好的抗纤维化作用,主要与调控相关细胞凋亡、控制有关胶原蛋白表达等密切相关。此外,苦杏仁苷抗肿瘤、抗炎等药理作用也取得明显进展,其通过抑制细胞周期、诱导肿瘤细胞凋亡、调节免疫反应等抑制肿瘤生长,通过抑制炎症介质[白细胞介素-17(IL-17)、肿瘤坏死因子-α(TNF-α)]表达,调节MAPK/NF-κB等信号通路,减轻炎症反应。但苦杏仁苷被β-葡萄糖苷代谢分解后形成有害物质氢氰酸,导致其临床应用受到限制。为解决苦杏仁苷生物利用度低、稳定性差限制其应用的问题,有研究将其开发成新型制剂,如自微乳化药物递送系统、纳米制剂、凝胶等,实现靶向递送并调控代谢路径,有效提高其稳定性和安全性,对提升苦杏仁苷的临床用药疗效具有重要的应用价值。该文基于国内外对苦杏仁苷的研究现状,通过检索中国知网、维普、PUBMED、Web of Science等国内外数据库,综述苦杏仁苷的药理作用及其制剂的研发进展,为苦杏仁苷的研究开发和临床应用提供科学依据。展开更多
基金supported by the Natural Science Foundation of China(81873325)the State Administration of Traditional Chinese Medicine of Zhejiang Province(2021ZZ014).
文摘The study aimed to explore the efficacy and potential mechanisms of a naturally aromatic cyanogenic compound amygdalin(AMY)in treating glucocorticoid(GC)-associated necrosis of the femoral head(GANFH).We demonstrated that GC exacerbates the oxidative stress(OS)microenvironment via promoting nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4)expression in human,rat,and mesenchymal stem cells(MSCs)samples,thus generating excessive reactive oxygen species(ROS),leading to increased apoptosis and unbalanced osteolipogenic differentiation.Furthermore,computational docking results revealed that AMY could bind specifically to the predicted binding sites of NOX4.Additionally,AMY ameliorated the OS microenvironment of MSCs via decreasing NOX4 expression and inhibiting NOX4/ROS/p38MAPK signaling,thereby reversing the GC-induced apoptosis and imbalanced osteolipogenic differentiation,and ultimately alleviating GANFH.In summary,we demonstrated for the first time that AMY attenuated apoptosis and maintained osteolipogenic differentiation balance in MSCs via specifically targeting NOX4,inhibiting NOX4/ROS/p38MAPK signaling,thereby treating GANFH.
基金Supported by a grant of the Oriental Medicine R&D Project, Ministry of Health Welfare, Republic of Korea, No. 03-PJ9-PG3-21600-0014 and No. 0405-OMOO-0815-0001 Korea Institute of Oriental Medicine
文摘AIM： The genes were divided into seven categories according to biological function; apoptosis-related, immune response-related, signal transduction-related, cell cyclerelated, cell growth-related, stress response-related and transcription-related genes. METHODS： We compared the gene expression profiles of SNU-C4 cells between amygdalin-treated （5 mg/mL, 24 h） and non-treated groups using cDNA microarray analysis. We selected genes downregulated in cDNA microarray and investigated mRNA levels of the genes by RT- PC R. RESULTS： Microarray showed that amygdalin downregulated especially genes belonging to cell cycle category： exonuclease 1 （EXO1）, ATP-binding cassette, sub-family F, member 2 （ABCF2）, MRE11 meiotic recombination 11 homolog A （MRE11A）, topoisomerase （DNA） Ⅰ （TOP1）, and FK506 binding protein 12-rapamycin-associated protein 1 （FRAP1）. RT-PCR analysis revealed that mRNA levels of these genes were also decreased by amygdalin treatment in SNU-C4 human colon cancer cells. CONCLUSION： These results suggest that amygdalin have an anticancer effect via downregulation of cell cycle-related genes in SNU-C4 human colon cancer cells, and might be used for therapeutic anticancer drug.
文摘Summary: The pathogenesis of hyperoxia lung injury and the mechanism of amygdalin on type 2 alveolar epithelial cells (AEC2) isolated from premature rat lungs in vitro were investigated. AEC2 were obtained by primary culture from 20-days fetal rat lung and hyperoxia-exposed cell model was established. Cell proliferating viability was examined by MTT assay after treatment of amygdalin at various concentrations. DNA content and the proliferating cell nuclear antigen (PCNA) protein expression of AEC2 were measured by using flow cytometry and immunocytochemistry respectively after 24 h of hyperoxia exposure or amygdalin treatment. The results showed that hyperoxia inhibited the proliferation and decreased PCNA protein expression in AEC2 of premature rat in vitro. Amygdalin at the concentration range of 50-200 μmol/L stimulated the proliferation of AEC2 in a dose-dependent manner, however, 400 μmol/L amygdalin inhibited the proliferation of AEC2. Amygdalin at the concentration of 200 μmol/L played its best role in facilitating proliferation of AEC2s in vitro and could partially ameliorated the changes of proliferation in hyperoxia exposed AEC2 of premature rat. It has been suggested that hyperoxia inhibited the proliferation of AEC2s of premature rat, which may contribute to hyperoxia lung injury. Amygdalin may play partial protective role in hyperoxia-induced lung injury.
基金Supported by the Science and Technology Major Projects for Major New Drugs(Research on innovation of Majiepingchuan effective components cataplasm of transdermal drug delivery system),No.2012ZX09103201-007
文摘OBJECTIVE:To analyze the transdermal profile of pseudoephedrine and amygdalin in the Traditional Chinese Medicine majiepingchuan in rat skin and to reveal their interaction.METHODS:A Franz diffusion cell was used in vitro to evaluate the transdermal parameters of cumulative transdermal flux(Q_(tot)),cumulative transmission(T_(tot)),and mean penetration rate(Kp)of pseudoephedrine and amygdalin in majiepingchuan.Linear regression analyses of Q_(tot)over time of pseudoephedrine vs amygdalin and their ratios was adopted for correlation evaluation.RESULTS:At 1,2,4,6,and 8 h,the Q_(tot),T_(tot)and Kp of pseudoephedrine showed a good correlation with that of amygdalin.CONCLUSION:There was a small difference in theratios of Q_(tot),T_(tot)and Kp between pseudoephedrine and amygdalin,and a correlation between them.
基金Supported by National Natural Science Foundation of China(Nos.81530101,81973613 and 81603681)Shanghai Rising-Star Program(No.19QA1408900)。
文摘Objective:To observe the effect of amygdalin on liver fibrosis in a liver fibrosis mouse model,and the underlying mechanisms were partly dissected in vivo and in vitro.Methods:Thirty-two male mice were randomly divided into 4 groups,including control,model,low-and high-dose amygdalin-treated groups,8 mice in each group.Except the control group,mice in the other groups were injected intraperitoneally with 10%carbon tetrachloride(CCl4)-olive oil solution 3 times a week for 6 weeks to induce liver fibrosis.At the first 3 weeks,amygdalin(1.35 and 2.7 mg/kg body weight)were administered by gavage once a day.Mice in the control group received equal quantities of subcutaneous olive oil and intragastric water from the fourth week.At the end of 6 weeks,liver tissue samples were harvested to detect the content of hydroxyproline(Hyp).Hematoxylin and eosin and Sirius red staining were used to observe the inflammation and fibrosis of liver tissue.The expressions of collagenⅠ(Col-Ⅰ),alpha-smooth muscle actin(α-SMA),CD31 and transforming growth factorβ(TGF-β)/Smad signaling pathway were detected by immunohistochemistry,quantitative real-time polymerase chain reaction and Western blot,respectively.The activation models of hepatic stellate cells,JS-1and LX-2 cells induced by TGF-β1 were used in vitro with or without different concentrations of amygdalin(0.1,1,10μmol/L).The effect of different concentrations of amygdalin on the expressions of liver sinusoidal endothelial cells(LSECs)dedifferentiation markers CD31 and CD44 were observed.Results:High-dose of amygdalin significantly reduced the Hyp content and percentage of collagen positive area,and decreased the mRNA and protein expressions of Col-Ι,α-SMA,CD31 and p-Smad2/3 in liver tissues of mice compared to the model group(P<0.01).Amygdalin down-regulated the expressions of Col-Ⅰandα-SMA in JS-1 and LX-2 cells,and TGFβR1,TGFβR2 and p-Smad2/3 in LX-2 cells compared to the model group(P<0.05 or P<0.01).Moreover,1 and 10μmol/L amygdalin inhibited the mRNA and protein expressions of CD31 in LSECs and increased CD44 expression compared to the model group(P<0.05 or P<0.01).Conclusions:Amygdalin can dramatically alleviate liver fibrosis induced by CCl4 in mice and inhibit TGF-β/Smad signaling pathway,consequently suppressing HSCs activation and LSECs dedifferentiation to improve angiogenesis.
文摘苦杏仁苷是存在于苦杏仁等蔷薇科植物中的一种含氰基糖苷化合物。近年研究显示苦杏仁苷具有较好的抗纤维化作用,主要与调控相关细胞凋亡、控制有关胶原蛋白表达等密切相关。此外,苦杏仁苷抗肿瘤、抗炎等药理作用也取得明显进展,其通过抑制细胞周期、诱导肿瘤细胞凋亡、调节免疫反应等抑制肿瘤生长,通过抑制炎症介质[白细胞介素-17(IL-17)、肿瘤坏死因子-α(TNF-α)]表达,调节MAPK/NF-κB等信号通路,减轻炎症反应。但苦杏仁苷被β-葡萄糖苷代谢分解后形成有害物质氢氰酸,导致其临床应用受到限制。为解决苦杏仁苷生物利用度低、稳定性差限制其应用的问题,有研究将其开发成新型制剂,如自微乳化药物递送系统、纳米制剂、凝胶等,实现靶向递送并调控代谢路径,有效提高其稳定性和安全性,对提升苦杏仁苷的临床用药疗效具有重要的应用价值。该文基于国内外对苦杏仁苷的研究现状,通过检索中国知网、维普、PUBMED、Web of Science等国内外数据库,综述苦杏仁苷的药理作用及其制剂的研发进展,为苦杏仁苷的研究开发和临床应用提供科学依据。
