OBJECTIVE The inhibitory effect of active ingredients of Tripterygium wilfordii Hook.F.(TWHF)(celastrol,triptolide,triptonide,wilforlide A,wilforgine and wilforine)on human carboxylester⁃ase 1(CES1)and CES2 was detect...OBJECTIVE The inhibitory effect of active ingredients of Tripterygium wilfordii Hook.F.(TWHF)(celastrol,triptolide,triptonide,wilforlide A,wilforgine and wilforine)on human carboxylester⁃ase 1(CES1)and CES2 was detected to investigate the herb-drug interactions(HDIs)of TWHF.METHODS Human liver microsomes catalysed hydrolysis of 2-(2-benzoyl-3-methoxyphenyl)benzothi⁃azole(BMBT)and fluorescein diacetate(FD)were used as the probe reaction to phenotype the activity of CES1 and CES2,respectively.The residual activities of CES1 and CES2 were detected by ultrahigh performance liquid chromatography(UPLC)after intervention with celastrol,triptolide,triptonide,wilforlide A,wilforgine and wilforine(100μmol·L^(-1)).Kinetics analysis,involving half inhibitory concentra⁃tion(IC_(50)),inhibition type and kinetic parameter(Ki),and in vitro-in vivo extrapolation(IVIVE),was carried out to predict the HDIs between these compounds and CES-metabolizing drugs.Molecular docking was performed to analyze the ligand-enzyme interaction.RESULTS Out of the six main con⁃stituents of TWHF,only celastrol exhibited strong inhibition towards both CES1 and CES2,with the inhibitory rates of 97.45%(P<0.05)and 95.62%(P<0.05),respectively.The IC_(50)was 9.95 and 4.02 mol·L^(-1),respectively,and the types of inhibition were all non-competitive inhibition.Based on the kinetics analysis,the Ki values were calculated to be 5.10 and 10.55μmol·L^(-1)for the inhibition of celastrol on CES1 and CES2,respectively.IVIVE indicated that celastrol might disturb the metabolic hydrolysis of clinical drugs in vivo by inhibiting CES1.Molecular docking results showed that hydrogen bonds and hydrophobic contacts contributed to the interaction of celastrol and CESs.CONCLUSION The inhibitory effect of celastrol on CES1 and CES2 might cause HDIs with clinical drugs hydrolysed by CESs.展开更多
Safety of a compound Lonicera rupicola Hook. f. et & Thomson injection was evaluated by local irritation experiments including conjunctiva,skin and muscle irritant experiments,and the effect on weight gain was stu...Safety of a compound Lonicera rupicola Hook. f. et & Thomson injection was evaluated by local irritation experiments including conjunctiva,skin and muscle irritant experiments,and the effect on weight gain was studied. The results showed that the compound L. rupicola Hook. f. et & Thomson injection had no irritation to rabbit eyes and weak irritation to rabbit ears,and had relatively strong irritation to the leg muscles of the mice. Its metabolism in mice had no abnormal toxicity.展开更多
The physical properties and chemical components of three oil samples extracted from Illicium verum Hook. f. by steam distillation （SD）, solvent extraction （SE） and supercritical fluid extraction （SFE） were compa...The physical properties and chemical components of three oil samples extracted from Illicium verum Hook. f. by steam distillation （SD）, solvent extraction （SE） and supercritical fluid extraction （SFE） were compared with one another and analyzed by Gas Chromatography-Mass Spectrometry （GC-MS）. The quality parameters of star anise essential oil from SFE were close to that of those came from SD and SE. Although the extraction yield of star anise by SFE （9.2 %） was close to the value from SE （9.3%）, it was yet higher than that came from SD （8.2%）. For sensory evaluation, however, three oils were significantly different. The odor and taste of the products from SFE and SE were generally more natural and vivid than that came from distilled oil. The volatile compound revealed that significant differences of the composition existed in the distilled oil and the oleoresins prepared by SFE and SE.展开更多
Sixty-nine specimens from Tripterygium Wilfordii Hook.f. (TWH) users were investigated by electron microscopy. No macrophages were demonstrated in the 21 specimens collected prior to the administration of TWH. However...Sixty-nine specimens from Tripterygium Wilfordii Hook.f. (TWH) users were investigated by electron microscopy. No macrophages were demonstrated in the 21 specimens collected prior to the administration of TWH. However, it was found in 23 out of the 48 semen specimens obtained following the TWH administration. The macrophages were functionally active as shown by the presence of a large number of cytoplasmic processes and pseudopodia on the surface, and primary and secondary lysosomes in the cytoplasm. The macrophages phagocytized sperm debris and degenerated or dead spermatids with formation of specific phagosomes. Around those macrophages, lymphocytes were commonly noted. The cytoplasmic processes of the two cell types could come into contact or even fuse with each other, leading to tight junction-like structure; in some of the contacts, the plasma membranes were found dissolved so as to form direct cytoplasmic linkage.展开更多
Prostate cancer(PCa)is one of the most common malignant tumours and a leading cause of cancer deaths.Treatment failure of PCa is often due to bone-metastasis.Celastrol,an active constituent of the roots of Tripterygiu...Prostate cancer(PCa)is one of the most common malignant tumours and a leading cause of cancer deaths.Treatment failure of PCa is often due to bone-metastasis.Celastrol,an active constituent of the roots of Tripterygium wilfordii,has shown antitumour effects in previous studies in accordance with its use in TCM.Here we report for the first time an in-depth study of the effects of celastrol on展开更多
目的探讨雷公藤Tripterygium wilfordii抑制三阴性乳腺癌(triple-negative breast cancer,TNBC)增殖及骨转移的作用及机制。方法通过MTT、细胞划痕、结晶紫染色及克隆形成实验,评估雷公藤对4T1细胞增殖、迁移及克隆形成的抑制作用;采用W...目的探讨雷公藤Tripterygium wilfordii抑制三阴性乳腺癌(triple-negative breast cancer,TNBC)增殖及骨转移的作用及机制。方法通过MTT、细胞划痕、结晶紫染色及克隆形成实验,评估雷公藤对4T1细胞增殖、迁移及克隆形成的抑制作用;采用Western blotting分析雷公藤对4T1细胞铁死亡相关蛋白表达的影响。体内构建小鼠乳腺癌骨转移模型,利用活体成像、CT扫描及TRAP染色观察雷公藤对骨转移的干预作用。结果雷公藤显著抑制4T1细胞的增殖、迁移和克隆形成(P<0.05、0.01、0.001),同时诱导铁死亡并降低核因子E2相关因子2(nuclear factor E2-related factor 2,Nrf2)、溶质载体家族7成员11(solute carrier family 7 member 11,SLC7A11)、谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)蛋白的表达(P<0.05、0.01、0.001)。体内实验结果显示,雷公藤可抑制乳腺癌骨转移模型小鼠肿瘤的进展,降低继发性肺转移的发生;通过离体骨组织3D重建发现,雷公藤显著缓解了肿瘤诱导的骨质流失;TRAP染色证实雷公藤通过抑制破骨细胞过度分化和募集,阻断了肿瘤-破骨细胞的恶性循环,有效维持了胫骨和股骨的骨微结构完整性。结论雷公藤体外可抑制TNBC细胞增殖,体内可有效干预TNBC骨转移,显示出其潜在的治疗价值。展开更多
文摘OBJECTIVE The inhibitory effect of active ingredients of Tripterygium wilfordii Hook.F.(TWHF)(celastrol,triptolide,triptonide,wilforlide A,wilforgine and wilforine)on human carboxylester⁃ase 1(CES1)and CES2 was detected to investigate the herb-drug interactions(HDIs)of TWHF.METHODS Human liver microsomes catalysed hydrolysis of 2-(2-benzoyl-3-methoxyphenyl)benzothi⁃azole(BMBT)and fluorescein diacetate(FD)were used as the probe reaction to phenotype the activity of CES1 and CES2,respectively.The residual activities of CES1 and CES2 were detected by ultrahigh performance liquid chromatography(UPLC)after intervention with celastrol,triptolide,triptonide,wilforlide A,wilforgine and wilforine(100μmol·L^(-1)).Kinetics analysis,involving half inhibitory concentra⁃tion(IC_(50)),inhibition type and kinetic parameter(Ki),and in vitro-in vivo extrapolation(IVIVE),was carried out to predict the HDIs between these compounds and CES-metabolizing drugs.Molecular docking was performed to analyze the ligand-enzyme interaction.RESULTS Out of the six main con⁃stituents of TWHF,only celastrol exhibited strong inhibition towards both CES1 and CES2,with the inhibitory rates of 97.45%(P<0.05)and 95.62%(P<0.05),respectively.The IC_(50)was 9.95 and 4.02 mol·L^(-1),respectively,and the types of inhibition were all non-competitive inhibition.Based on the kinetics analysis,the Ki values were calculated to be 5.10 and 10.55μmol·L^(-1)for the inhibition of celastrol on CES1 and CES2,respectively.IVIVE indicated that celastrol might disturb the metabolic hydrolysis of clinical drugs in vivo by inhibiting CES1.Molecular docking results showed that hydrogen bonds and hydrophobic contacts contributed to the interaction of celastrol and CESs.CONCLUSION The inhibitory effect of celastrol on CES1 and CES2 might cause HDIs with clinical drugs hydrolysed by CESs.
基金Supported by Project of Science and Technology Department of Sichuan Province,China(2016KZ0007)Innovative Scientific Research Project for Postgraduates of Southwest Minzu University(CX2018SZ44)
文摘Safety of a compound Lonicera rupicola Hook. f. et & Thomson injection was evaluated by local irritation experiments including conjunctiva,skin and muscle irritant experiments,and the effect on weight gain was studied. The results showed that the compound L. rupicola Hook. f. et & Thomson injection had no irritation to rabbit eyes and weak irritation to rabbit ears,and had relatively strong irritation to the leg muscles of the mice. Its metabolism in mice had no abnormal toxicity.
基金Supported by the Science and Technology Key Project of Guangxi Province (0424008-1C)
文摘The physical properties and chemical components of three oil samples extracted from Illicium verum Hook. f. by steam distillation （SD）, solvent extraction （SE） and supercritical fluid extraction （SFE） were compared with one another and analyzed by Gas Chromatography-Mass Spectrometry （GC-MS）. The quality parameters of star anise essential oil from SFE were close to that of those came from SD and SE. Although the extraction yield of star anise by SFE （9.2 %） was close to the value from SE （9.3%）, it was yet higher than that came from SD （8.2%）. For sensory evaluation, however, three oils were significantly different. The odor and taste of the products from SFE and SE were generally more natural and vivid than that came from distilled oil. The volatile compound revealed that significant differences of the composition existed in the distilled oil and the oleoresins prepared by SFE and SE.
基金The work reported in this paper was supported by the State Family Planning commission
文摘Sixty-nine specimens from Tripterygium Wilfordii Hook.f. (TWH) users were investigated by electron microscopy. No macrophages were demonstrated in the 21 specimens collected prior to the administration of TWH. However, it was found in 23 out of the 48 semen specimens obtained following the TWH administration. The macrophages were functionally active as shown by the presence of a large number of cytoplasmic processes and pseudopodia on the surface, and primary and secondary lysosomes in the cytoplasm. The macrophages phagocytized sperm debris and degenerated or dead spermatids with formation of specific phagosomes. Around those macrophages, lymphocytes were commonly noted. The cytoplasmic processes of the two cell types could come into contact or even fuse with each other, leading to tight junction-like structure; in some of the contacts, the plasma membranes were found dissolved so as to form direct cytoplasmic linkage.
文摘Prostate cancer(PCa)is one of the most common malignant tumours and a leading cause of cancer deaths.Treatment failure of PCa is often due to bone-metastasis.Celastrol,an active constituent of the roots of Tripterygium wilfordii,has shown antitumour effects in previous studies in accordance with its use in TCM.Here we report for the first time an in-depth study of the effects of celastrol on
