Toosendanin(TSN),a tetracyclic triterpenoid derived from Melia toosendan and M.azedarach,demonstrates broad application prospects in cancer treatment.Although previously employed as a pesticide,recent studies have rev...Toosendanin(TSN),a tetracyclic triterpenoid derived from Melia toosendan and M.azedarach,demonstrates broad application prospects in cancer treatment.Although previously employed as a pesticide,recent studies have revealed its potential therapeutic value in treating various types of cancer.TSN exerts an anticancer effect via mechanisms including proliferation inhibition,apoptosis induction,migration suppression,and angiogenesis inhibition.However,TSN's toxicity,particularly its hepatotoxicity,significantly limits its therapeutic application.This review explored the dual nature of TSN,evaluating both its anticancer potential and toxicological risks,emphasizing the importance of balancing these aspects in therapeutic applications.Furthermore,we investigated the incorporation of TSN into novel therapeutic strategies,such as Proteolysis-targeting chimeras(PROTAC)technology and nanotechnology-based drug delivery systems(DDS),which enhance treatment efficacy while mitigating toxicity in normal tissues.展开更多
To investigate the effect on central nervous transmission of toosendanin (TSN), a presynaptic blocker, rat striatum was perfused in vivo with a TSN-containing artificial cere-brospinal fluid (ACSF) and the level of do...To investigate the effect on central nervous transmission of toosendanin (TSN), a presynaptic blocker, rat striatum was perfused in vivo with a TSN-containing artificial cere-brospinal fluid (ACSF) and the level of dopamine (DA) as well as related metabolites in the collected dialysates has been determined by a microbore HPLC with electrochemical detection (mi-crobore HPLC-ECD). The results are as follows: ( i ) TSN induced a biphasic change of DA from its basal level;( ii ) the basal contents of two metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) increased in turn and stayed at a higher level than basal control for a long period. The basal level of 5-hydroxyindoleacetic acid (5-HIAA), a metabolite of 5-hydroxytryptamine(5-HT), had a change similar to that of HVA; (iii) after per-fusion with TSN-containing ACSF, high K+-evoked DA release was inhibited. These results show that TSN does not selectively affect acetylcholine (ACh) release, but probably acts on a common展开更多
Toosendanin (TSN), a triterpenoid derivative extracted from the bark of Melia toosendan Seib et Zucc and used in Chinese traditional medicine as an anthelmintic against ascaris, is a presynaptic neuromuscular blocker....Toosendanin (TSN), a triterpenoid derivative extracted from the bark of Melia toosendan Seib et Zucc and used in Chinese traditional medicine as an anthelmintic against ascaris, is a presynaptic neuromuscular blocker. Without affecting the nerve conduction, the muscle resting potential as well as acetylcholine (ACh) sensitivity of the muscle membrane at the end-plate region, TSN blocks the neuromuscular transmission selectively by inhibiting ACh release from the motor nerve terminals. It was interesting to notice展开更多
建立高效液相串联电雾式检测器法(HPLC-CAD)测定川楝子中川楝素含量的方法。利用C18固相萃取小柱对样本进行除杂和净化制备供试品溶液:将川楝子甲醇提取物溶解于5 m L 30%甲醇上柱,6 m L 30%甲醇、6 m L甲醇分别洗脱,收集甲醇洗脱液制...建立高效液相串联电雾式检测器法(HPLC-CAD)测定川楝子中川楝素含量的方法。利用C18固相萃取小柱对样本进行除杂和净化制备供试品溶液:将川楝子甲醇提取物溶解于5 m L 30%甲醇上柱,6 m L 30%甲醇、6 m L甲醇分别洗脱,收集甲醇洗脱液制备供试品溶液;供试品溶液采用Agilent ZOBAX SB C18(4.6 mm×250 mm,5μm)色谱柱进行分离,流动相为乙腈-水(33∶67),柱温30℃。以CAD为检测器,雾化气为氮气,雾化气压力为55 psi,雾化室温度35℃。结果显示,HPLC-CAD法测定川楝子中川楝素,其色谱表征清晰、干扰较小、色谱峰分离度好;方法学考察结果表明,该方法灵敏、准确、稳定可靠,定量限为24.0 ng,精密度、重复性、稳定性RSD均小于5.0%,高、中、低三个浓度的回收率为95.9%~99.7%;利用该方法测定10批次川楝子中川楝素的含量并利用Pearson相关性分析,将该结果与LC-MS法测定结果比较,表明两种检测方法结果相近且总体呈强正相关(相关系数为0.9950,P<0.001)。本研究建立了HPLC-CAD结合固相萃取测定川楝子中川楝素含量的方法,该方法简便、可靠,为川楝子质量控制与质量评价提供测定方法和参考依据。展开更多
来自楝属中药材提取的川楝素可配制成农田杀虫剂,为验证其安全性,本论文对0.3%楝素可溶液剂在甘蓝及土壤中的残留消解动态和最终残留进行了研究。残留消解动态研究表明,以2倍推荐使用剂量7.5 g a.i./hm^(2)对甘蓝及土壤喷雾施药1次,分...来自楝属中药材提取的川楝素可配制成农田杀虫剂,为验证其安全性,本论文对0.3%楝素可溶液剂在甘蓝及土壤中的残留消解动态和最终残留进行了研究。残留消解动态研究表明,以2倍推荐使用剂量7.5 g a.i./hm^(2)对甘蓝及土壤喷雾施药1次,分别采用IC-ELISA和HPLC对样品中川楝素的残留量进行检测,降解过程符合一级动力学数学模型。川楝素在甘蓝中的半衰期分别为1.2 d和1.6 d,在土壤中的半衰期为0.71 d。最终残留试验表明,分别按推荐剂量3.75 g a.i./hm^(2)和7.5 g a.i./hm^(2)兑水喷施3到4次后,施药间隔期为7 d,采收期距最后一次施药7 d时,IC-ELISA检测出川楝素的最终残留分别为0.009 mg/kg和0.015 mg/kg,HPLC未检测出川楝素;与此同时,两种分析方法在土壤中均未检测出川楝素的残留量。结果证明0.3%楝素可溶液剂释放到环境中较为安全,极容易降解,是一种安全的新型植物源农药。展开更多
基金supported by the National Natural Science Foundation of China(Nos.82322073,82304790,and 82173846)China Postdoctoral Innovative Talent Support Program(BX20220213)+10 种基金Shanghai Rising-Star Program(No.22QA1409100)Oriental Scholars of Shanghai(No.TP2022081)Jiangxi Province Thousand Talents Program(No.jxsq2023102168)Young Talent Lifting Project of China Association of Chinese Medicine[No.CACM-(2021-QNRC2-A08)]Shanghai Science and Technology Innovation Action Plan(No.21S11902800)Three-year Action Plan for Shanghai TCM Development and Inheritance Program[Nos.ZY(2021-2023)-0401 and ZY(2021-2023)-0208]Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No.ZYYCXTD-D-202004)CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2023-I2M-3-009)Shanghai Sailing Program(Nos.22YF1445000 and 23YF1442600)the National Key R&D Program of China(No.2022YFC3502000)High-level Key Discipline of National Administration of Traditional Chinese Medicine,Innovation team of high-level local universities in Shanghai:Strategic Innovation Team of TCM Chemical Biology,Organizational Key Research and Development Program of Shanghai University of Traditional Chinese Medicine(No.2023YZZ02)。
文摘Toosendanin(TSN),a tetracyclic triterpenoid derived from Melia toosendan and M.azedarach,demonstrates broad application prospects in cancer treatment.Although previously employed as a pesticide,recent studies have revealed its potential therapeutic value in treating various types of cancer.TSN exerts an anticancer effect via mechanisms including proliferation inhibition,apoptosis induction,migration suppression,and angiogenesis inhibition.However,TSN's toxicity,particularly its hepatotoxicity,significantly limits its therapeutic application.This review explored the dual nature of TSN,evaluating both its anticancer potential and toxicological risks,emphasizing the importance of balancing these aspects in therapeutic applications.Furthermore,we investigated the incorporation of TSN into novel therapeutic strategies,such as Proteolysis-targeting chimeras(PROTAC)technology and nanotechnology-based drug delivery systems(DDS),which enhance treatment efficacy while mitigating toxicity in normal tissues.
文摘To investigate the effect on central nervous transmission of toosendanin (TSN), a presynaptic blocker, rat striatum was perfused in vivo with a TSN-containing artificial cere-brospinal fluid (ACSF) and the level of dopamine (DA) as well as related metabolites in the collected dialysates has been determined by a microbore HPLC with electrochemical detection (mi-crobore HPLC-ECD). The results are as follows: ( i ) TSN induced a biphasic change of DA from its basal level;( ii ) the basal contents of two metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) increased in turn and stayed at a higher level than basal control for a long period. The basal level of 5-hydroxyindoleacetic acid (5-HIAA), a metabolite of 5-hydroxytryptamine(5-HT), had a change similar to that of HVA; (iii) after per-fusion with TSN-containing ACSF, high K+-evoked DA release was inhibited. These results show that TSN does not selectively affect acetylcholine (ACh) release, but probably acts on a common
基金This work was supported by National Institute for Physiological Science, Japan and the National Natural Science Foundation of China. Partial experiments were performed in Okazaki, Japan
文摘Toosendanin (TSN), a triterpenoid derivative extracted from the bark of Melia toosendan Seib et Zucc and used in Chinese traditional medicine as an anthelmintic against ascaris, is a presynaptic neuromuscular blocker. Without affecting the nerve conduction, the muscle resting potential as well as acetylcholine (ACh) sensitivity of the muscle membrane at the end-plate region, TSN blocks the neuromuscular transmission selectively by inhibiting ACh release from the motor nerve terminals. It was interesting to notice
文摘建立高效液相串联电雾式检测器法(HPLC-CAD)测定川楝子中川楝素含量的方法。利用C18固相萃取小柱对样本进行除杂和净化制备供试品溶液:将川楝子甲醇提取物溶解于5 m L 30%甲醇上柱,6 m L 30%甲醇、6 m L甲醇分别洗脱,收集甲醇洗脱液制备供试品溶液;供试品溶液采用Agilent ZOBAX SB C18(4.6 mm×250 mm,5μm)色谱柱进行分离,流动相为乙腈-水(33∶67),柱温30℃。以CAD为检测器,雾化气为氮气,雾化气压力为55 psi,雾化室温度35℃。结果显示,HPLC-CAD法测定川楝子中川楝素,其色谱表征清晰、干扰较小、色谱峰分离度好;方法学考察结果表明,该方法灵敏、准确、稳定可靠,定量限为24.0 ng,精密度、重复性、稳定性RSD均小于5.0%,高、中、低三个浓度的回收率为95.9%~99.7%;利用该方法测定10批次川楝子中川楝素的含量并利用Pearson相关性分析,将该结果与LC-MS法测定结果比较,表明两种检测方法结果相近且总体呈强正相关(相关系数为0.9950,P<0.001)。本研究建立了HPLC-CAD结合固相萃取测定川楝子中川楝素含量的方法,该方法简便、可靠,为川楝子质量控制与质量评价提供测定方法和参考依据。
文摘来自楝属中药材提取的川楝素可配制成农田杀虫剂,为验证其安全性,本论文对0.3%楝素可溶液剂在甘蓝及土壤中的残留消解动态和最终残留进行了研究。残留消解动态研究表明,以2倍推荐使用剂量7.5 g a.i./hm^(2)对甘蓝及土壤喷雾施药1次,分别采用IC-ELISA和HPLC对样品中川楝素的残留量进行检测,降解过程符合一级动力学数学模型。川楝素在甘蓝中的半衰期分别为1.2 d和1.6 d,在土壤中的半衰期为0.71 d。最终残留试验表明,分别按推荐剂量3.75 g a.i./hm^(2)和7.5 g a.i./hm^(2)兑水喷施3到4次后,施药间隔期为7 d,采收期距最后一次施药7 d时,IC-ELISA检测出川楝素的最终残留分别为0.009 mg/kg和0.015 mg/kg,HPLC未检测出川楝素;与此同时,两种分析方法在土壤中均未检测出川楝素的残留量。结果证明0.3%楝素可溶液剂释放到环境中较为安全,极容易降解,是一种安全的新型植物源农药。
