Advances in the pharmacological studies on timosaponins and their sapogenins

CAI Fei; WANG Wei-hong; GAO Shou-hong; CHEN Wan-sheng

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Volume 29 Issue 5

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Article Navigation > Journal of Pharmaceutical Practice and Service > 2011 > 29(5): 331-335

CAI Fei, WANG Wei-hong, GAO Shou-hong, CHEN Wan-sheng. Advances in the pharmacological studies on timosaponins and their sapogenins[J]. Journal of Pharmaceutical Practice and Service, 2011, 29(5): 331-335.

Citation:

CAI Fei, WANG Wei-hong, GAO Shou-hong, CHEN Wan-sheng. Advances in the pharmacological studies on timosaponins and their sapogenins[J]. Journal of Pharmaceutical Practice and Service, 2011, 29(5): 331-335.

Advances in the pharmacological studies on timosaponins and their sapogenins

1.
Department of pharmacy, Command outpatient department, Guangzhou Military District of PLA, Guangzhou 510080, China
2.
Department of pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China

Received Date: 2011-04-12
Rev Recd Date: 2011-07-13

Abstract

Timosaponins and their sapogenins were the major active components from a commonly used Chinese herbal medicine, Anemarrhenae Rhizoma. Studies showed that they had a broad range of pharmacological effects such as improving senile dementia, preventing cerebral ischemia, anti-coagulated blood, anti-oxidant, anti-tumor, anti-osteoporosis, anti-inflammation, lowering blood pressure, lowering blood sugar and lowering blood fat. Recent advances in the above biological activities were reviewed in this paper.
- timosaponin,
- pharmacological effects,
- advance

References

[1]	廖洪利,王伟新,赵福胜,等. 知母化学成分研究进展[J]. 药学实践杂志,2005,23(1):12.
[2]	夏宗勤,胡雅儿,陈曹林. 知母皂苷元及其异构体对老年大鼠学习记忆和脑内M1受体密度的影响[J]. 中国药理学通报,2004,20(5):561.
[3]	Hu Y,Xia Z,Sun Q,et al. A new approach to the pharmacological regulation of memory: Sarsasapogenin improves memory by elevating the low muscarinic acetylcholine receptor density in brains of memory-deficit rat models[J]. Brain Res,2005,1060(1-2):26.
[4]	Hu H,Zhang R,Zhang Y,et al. Role of CREB in the regulatory action of sarsasapogenin on muscarinic M1 receptor density during cell aging[J]. FEBS Lett,2010,584(8):1549.
[5]	王顺宫,徐江平. 知母皂苷对衰老大鼠脑乙酰胆碱受体的调节作用[J]. 解放军药学学报,2001,17(2):71.
[6]	欧阳石,孙莉莎,徐江平. 知母总皂苷对大鼠脑皮质乙酰胆碱酯酶的抑制作用[J]. 中国药学杂志,2006,41(19):1472.
[7]	Lee B,Jung K,Kim DH. Timosaponin A-III,a saponin isolated from Anemarrhena asphodeloides,ameliorates learning and memory deficits in mice[J]. Pharmacol Biochem Behav,2009,93(2):121.
[8]	Ouyang S,Sun L,Guo S,et al. Effects of timosaponins on learning and memory abilities of rats with dementia induced by lateral cerebral ventricular injection of amyloid beta-peptide[J]. 第一军医大学学报,2005,25(2):121.
[9]	钟雷,谭洁,欧阳石,等. 知母皂苷B对大鼠海马注射β-AP (25~35)致tau蛋白磷酸化的影响[J]. 南方医科大学学报,2006,26(8):1106.
[10]	Li TJ,Qiu Y,Yang PY,et al. Timosaponin B-II improves memory and learning dysfunction induced by cerebral ischemia in rats[J]. Neurosci Lett,2007,421(2):147.
[11]	Oh JK,Hyun SY,Oh HR,et al. Effects of Anemarrhena asphodeloides on focal ischemic brain injury induced by middle cerebral artery occlusion in rats[J]. Biol Pharm Bull,2007,30(1):38.
[12]	原源. 知母防治缺血性脑中风的物质基础及品质评价[D]. 上海:第二军医大学,2005.
[13]	邓云,徐秋萍,刘振权,等. 知母皂苷化合物对脑缺血再灌注大鼠的保护作用[J]. 北京中医药大学学报,2005,28(2):33.
[14]	吴非,黎红华,陈文军. 脑缺血再灌注损伤后一氧化氮合酶表达变化及知母总皂苷对其影响[J]. 中华神经医学杂志,2006,5(8):757.
[15]	Niwa A,Takeda O,Ishimaru M,et al. Screening test for platelet aggregation inhibitor in natural products. The active principle of Anemarrhenae Rhizoma[J]. Yakugaku Zasshi,1988,108(6):555.
[16]	李素燕,赵振虎,裴海云,等. 知母皂苷AⅢ抗血栓作用研究[J]. 军事医学科学院院刊,2006,30(004):340.
[17]	Dong JX,Han GY. A new active steroidal saponin from Anemarrhena asphodeloides[J]. Planta Med,1991,57(5):460.
[18]	Zhang J,Meng Z,Zhang M,et al. Effect of six steroidal saponins isolated from Anemarrhenae rhizoma on platelet aggregation and hemolysis in human blood[J]. Clin Chim Acta,1999,289(1-2):79.
[19]	Kaname N,Zhang J,Meng Z,et al. Effect of timosaponin E1 and E2 on superoxide generation induced by various stimuli in human neutrophils and on platelet aggregation in human blood[J]. Clin Chim Acta,2000,295(1-2):129.
[20]	Chen ND,Yue L,Zhang J,et al. One unique steroidal sapogenin obtained through the microbial transformation of ruscogenin by Phytophthora cactorum ATCC 32134 and its potential inhibitory effect on tissue factor (TF) procoagulant activity[J]. Bioorg Med Chem Lett,2010,20(14):4015.
[21]	Meng ZY,Zhang JY,Xu SX,et al. Steroidal Saponins from Anemarrhena asphodeloides and their Effects on Supberoxide Generation[J]. Planta Med,1999,65(7):661.
[22]	邓云,马百平,从玉文,等. 知母皂苷BⅡ对Aβ25-35诱导的原代大鼠神经细胞损伤的保护作用[J]. 中国药理学通报,2009,25(2):244.
[23]	Li PM,Zhong JL,Chen RQ,et al. Zhi-mu saponin inhibits [alpha]-fetoprotein gene expression in developing rat liver[J]. Int J Biochem,1989,21(1):15.
[24]	王丽娟,付勤. 薯蓣皂苷元体内、外的抗肿瘤作用[J]. 中国中药杂志,2002,27(10):777.
[25]	Trouillas P,Corbiere C,Liagre B,et al. Structure-function relationship for saponin effects on cell cycle arrest and apoptosis in the human 1547 osteosarcoma cells: a molecular modelling approach of natural molecules structurally close to diosgenin[J]. Bioorg Med Chem,2005,13(4):1141.
[26]	Ni Y,Gong X,Lu M,et al. Mitochondrial ROS burst as an early sign in sarsasapogenin-induced apoptosis in HepG2 cells[J]. Cell Biol Int,2008,32(3):337.
[27]	Huang XF,Lin YY,Kong LY. Steroids from the roots of Asparagus officinalis and their cytotoxic activity[J]. J Integr Plant Biol,2008,50(6):717.
[28]	Sy LK,Yan SC,Lok CN,et al. Timosaponin A-III induces autophagy preceding mitochondria-mediated apoptosis in HeLa cancer cells[J]. Cancer Res,2008,68(24):10229.
[29]	King FW,Fong S,Griffin C,et al. Timosaponin A-III is preferentially cytotoxic to tumor cells through inhibition of mTOR and induction of ER stress[J]. PloS One,2009,4(9):1221.
[30]	Kang YJ,Chung HJ,Nam JW,et al. Cytotoxic and Antineoplastic Activity of Timosaponin A-III for Human Colon Cancer Cells[J]. J Nat Prod,2011,74(4):701.
[31]	杨茗,季晖,张树平,等. 知母皂苷元对成骨细胞活性和破骨细胞分化及功能的影响[J]. 中国药科大学学报,2009,40(6):544.
[32]	Nian H,Qin L,Chen W,et al. Protective effect of steroidal saponins from rhizome of Anemarrhena asphodeloides on ovariectomy-induced bone loss in rats[J]. Acta Pharmacol Sinica,2006,27(6):728.
[33]	Qin L,Han T,Zhang Q,et al. Antiosteoporotic chemical constituents from Er-Xian Decoction,a traditional Chinese herbal formula[J]. J Ethnopharmacol,2008,118(2):271.
[34]	Lu WQ,Qiu Y,Li TJ,et al. Timosaponin B-II inhibits pro-inflammatory cytokine induction by lipopolysaccharide in BV2 cells[J]. Arch Pharm Res,2009,32(9):1301.
[35]	Kim JY,Shin JS,Ryu JH,et al. Anti-inflammatory effect of anemarsaponin B isolated from the rhizomes of Anemarrhena asphodeloides in LPS-induced RAW 264.7 macrophages is mediated by negative regulation of the nuclear factor-[kappa] B and p38 pathways[J]. Food Chem Toxicol,2009,47(7):1610.
[36]	李泽松,李德良,黄坚,等. 心血管相关基因芯片的制备及其在知母皂苷作用机理研究中的应用[J]. 药学学报,2003,38(7):496.
[37]	赵树进,韩丽萍. 知母皂苷及其苷元对动物模型β肾上腺素受体的调整作用[J]. 中国医院药学杂志,2000,20(2):70.
[38]	Wang GJ,Lin LC,Chen CF,et al. Effect of timosaponin A-III,from Anemarrhenae asphodeloides Bunge (Liliaceae),on calcium mobilization in vascular endothelial and smooth muscle cells and on vascular tension[J]. Life Sci,2002,71(9):1081.
[39]	Xiao S,Xu M,Ge Y,et al. Inhibitory Effects of Saponins From Anemarrhene asphodeloides Bunge on the Growth of Vascular Smooth Muscle Cells[J]. Biomed Environ Sci,2006,19(3):185.
[40]	Nakashima N,Kimura I,Kimura M,et al. Isolation of pseudoprototimosaponin AIII from rhizomes of Anemarrhena asphodeloides and its hypoglycemic activity in streptozotocin-induced diabetic mice[J]. J Nat Prod,1993,56(3):345.
[41]	李春梅,高永林,李敏,等. 知母皂苷对小鼠血糖的影响[J]. 中药药理与临床,2005,21(4):22.
[42]	韩兵,李春梅,李敏,等. 知母皂苷的降脂及抗动脉粥样硬化作用[J]. 上海中医药杂志,2006,40(11):68.
[43]	付宝才,林娟,杨林海. 知母总皂苷对高脂血症大鼠肝脏低密度脂蛋白受体活性的影响[J]. 医学综述,2009,15(14):2226.
[44]	Ren LX,Luo YF,Li X,et al. Antidepressant-Like Effects of Sarsasapogenin from Anemarrhena asphodeloides BUNGE (Liliaceae)[J]. Biol Pharm Bull,2006,29(11):2304.
[45]	Takeda O,Tanaka S,Yamasaki K,et al. Screening for molluscicidal activity in crude drugs[J]. Chem Pharm Bull,1989,37(4):1090.
[46]	Lee B,Trinh HT,Jung K,et al. Inhibitory effects of steroidal timosaponins isolated from the rhizomes of Anemarrhena asphodeloides against passive cutaneous anaphylaxis reaction and pruritus[J]. Immunopharmacol Immunotoxicol,2010,32(3):1.

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通讯作者: 陈斌, [email protected]

1.
沈阳化工大学材料科学与工程学院沈阳 110142

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Advances in the pharmacological studies on timosaponins and their sapogenins

1. Department of pharmacy, Command outpatient department, Guangzhou Military District of PLA, Guangzhou 510080, China

2. Department of pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China

Received Date: 2011-04-12

Rev Recd Date: 2011-07-13

Key words:

Abstract: Timosaponins and their sapogenins were the major active components from a commonly used Chinese herbal medicine, Anemarrhenae Rhizoma. Studies showed that they had a broad range of pharmacological effects such as improving senile dementia, preventing cerebral ischemia, anti-coagulated blood, anti-oxidant, anti-tumor, anti-osteoporosis, anti-inflammation, lowering blood pressure, lowering blood sugar and lowering blood fat. Recent advances in the above biological activities were reviewed in this paper.

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Reference (46)

[1]	廖洪利,王伟新,赵福胜,等. 知母化学成分研究进展[J]. 药学实践杂志,2005,23(1):12.
[2]	夏宗勤,胡雅儿,陈曹林. 知母皂苷元及其异构体对老年大鼠学习记忆和脑内M1受体密度的影响[J]. 中国药理学通报,2004,20(5):561.
[3]	Hu Y,Xia Z,Sun Q,et al. A new approach to the pharmacological regulation of memory: Sarsasapogenin improves memory by elevating the low muscarinic acetylcholine receptor density in brains of memory-deficit rat models[J]. Brain Res,2005,1060(1-2):26.
[4]	Hu H,Zhang R,Zhang Y,et al. Role of CREB in the regulatory action of sarsasapogenin on muscarinic M1 receptor density during cell aging[J]. FEBS Lett,2010,584(8):1549.
[5]	王顺宫,徐江平. 知母皂苷对衰老大鼠脑乙酰胆碱受体的调节作用[J]. 解放军药学学报,2001,17(2):71.
[6]	欧阳石,孙莉莎,徐江平. 知母总皂苷对大鼠脑皮质乙酰胆碱酯酶的抑制作用[J]. 中国药学杂志,2006,41(19):1472.
[7]	Lee B,Jung K,Kim DH. Timosaponin A-III,a saponin isolated from Anemarrhena asphodeloides,ameliorates learning and memory deficits in mice[J]. Pharmacol Biochem Behav,2009,93(2):121.
[8]	Ouyang S,Sun L,Guo S,et al. Effects of timosaponins on learning and memory abilities of rats with dementia induced by lateral cerebral ventricular injection of amyloid beta-peptide[J]. 第一军医大学学报,2005,25(2):121.
[9]	钟雷,谭洁,欧阳石,等. 知母皂苷B对大鼠海马注射β-AP (25~35)致tau蛋白磷酸化的影响[J]. 南方医科大学学报,2006,26(8):1106.
[10]	Li TJ,Qiu Y,Yang PY,et al. Timosaponin B-II improves memory and learning dysfunction induced by cerebral ischemia in rats[J]. Neurosci Lett,2007,421(2):147.
[11]	Oh JK,Hyun SY,Oh HR,et al. Effects of Anemarrhena asphodeloides on focal ischemic brain injury induced by middle cerebral artery occlusion in rats[J]. Biol Pharm Bull,2007,30(1):38.
[12]	原源. 知母防治缺血性脑中风的物质基础及品质评价[D]. 上海:第二军医大学,2005.
[13]	邓云,徐秋萍,刘振权,等. 知母皂苷化合物对脑缺血再灌注大鼠的保护作用[J]. 北京中医药大学学报,2005,28(2):33.
[14]	吴非,黎红华,陈文军. 脑缺血再灌注损伤后一氧化氮合酶表达变化及知母总皂苷对其影响[J]. 中华神经医学杂志,2006,5(8):757.
[15]	Niwa A,Takeda O,Ishimaru M,et al. Screening test for platelet aggregation inhibitor in natural products. The active principle of Anemarrhenae Rhizoma[J]. Yakugaku Zasshi,1988,108(6):555.
[16]	李素燕,赵振虎,裴海云,等. 知母皂苷AⅢ抗血栓作用研究[J]. 军事医学科学院院刊,2006,30(004):340.
[17]	Dong JX,Han GY. A new active steroidal saponin from Anemarrhena asphodeloides[J]. Planta Med,1991,57(5):460.
[18]	Zhang J,Meng Z,Zhang M,et al. Effect of six steroidal saponins isolated from Anemarrhenae rhizoma on platelet aggregation and hemolysis in human blood[J]. Clin Chim Acta,1999,289(1-2):79.
[19]	Kaname N,Zhang J,Meng Z,et al. Effect of timosaponin E1 and E2 on superoxide generation induced by various stimuli in human neutrophils and on platelet aggregation in human blood[J]. Clin Chim Acta,2000,295(1-2):129.
[20]	Chen ND,Yue L,Zhang J,et al. One unique steroidal sapogenin obtained through the microbial transformation of ruscogenin by Phytophthora cactorum ATCC 32134 and its potential inhibitory effect on tissue factor (TF) procoagulant activity[J]. Bioorg Med Chem Lett,2010,20(14):4015.
[21]	Meng ZY,Zhang JY,Xu SX,et al. Steroidal Saponins from Anemarrhena asphodeloides and their Effects on Supberoxide Generation[J]. Planta Med,1999,65(7):661.
[22]	邓云,马百平,从玉文,等. 知母皂苷BⅡ对Aβ25-35诱导的原代大鼠神经细胞损伤的保护作用[J]. 中国药理学通报,2009,25(2):244.
[23]	Li PM,Zhong JL,Chen RQ,et al. Zhi-mu saponin inhibits [alpha]-fetoprotein gene expression in developing rat liver[J]. Int J Biochem,1989,21(1):15.
[24]	王丽娟,付勤. 薯蓣皂苷元体内、外的抗肿瘤作用[J]. 中国中药杂志,2002,27(10):777.
[25]	Trouillas P,Corbiere C,Liagre B,et al. Structure-function relationship for saponin effects on cell cycle arrest and apoptosis in the human 1547 osteosarcoma cells: a molecular modelling approach of natural molecules structurally close to diosgenin[J]. Bioorg Med Chem,2005,13(4):1141.
[26]	Ni Y,Gong X,Lu M,et al. Mitochondrial ROS burst as an early sign in sarsasapogenin-induced apoptosis in HepG2 cells[J]. Cell Biol Int,2008,32(3):337.
[27]	Huang XF,Lin YY,Kong LY. Steroids from the roots of Asparagus officinalis and their cytotoxic activity[J]. J Integr Plant Biol,2008,50(6):717.
[28]	Sy LK,Yan SC,Lok CN,et al. Timosaponin A-III induces autophagy preceding mitochondria-mediated apoptosis in HeLa cancer cells[J]. Cancer Res,2008,68(24):10229.
[29]	King FW,Fong S,Griffin C,et al. Timosaponin A-III is preferentially cytotoxic to tumor cells through inhibition of mTOR and induction of ER stress[J]. PloS One,2009,4(9):1221.
[30]	Kang YJ,Chung HJ,Nam JW,et al. Cytotoxic and Antineoplastic Activity of Timosaponin A-III for Human Colon Cancer Cells[J]. J Nat Prod,2011,74(4):701.
[31]	杨茗,季晖,张树平,等. 知母皂苷元对成骨细胞活性和破骨细胞分化及功能的影响[J]. 中国药科大学学报,2009,40(6):544.
[32]	Nian H,Qin L,Chen W,et al. Protective effect of steroidal saponins from rhizome of Anemarrhena asphodeloides on ovariectomy-induced bone loss in rats[J]. Acta Pharmacol Sinica,2006,27(6):728.
[33]	Qin L,Han T,Zhang Q,et al. Antiosteoporotic chemical constituents from Er-Xian Decoction,a traditional Chinese herbal formula[J]. J Ethnopharmacol,2008,118(2):271.
[34]	Lu WQ,Qiu Y,Li TJ,et al. Timosaponin B-II inhibits pro-inflammatory cytokine induction by lipopolysaccharide in BV2 cells[J]. Arch Pharm Res,2009,32(9):1301.
[35]	Kim JY,Shin JS,Ryu JH,et al. Anti-inflammatory effect of anemarsaponin B isolated from the rhizomes of Anemarrhena asphodeloides in LPS-induced RAW 264.7 macrophages is mediated by negative regulation of the nuclear factor-[kappa] B and p38 pathways[J]. Food Chem Toxicol,2009,47(7):1610.
[36]	李泽松,李德良,黄坚,等. 心血管相关基因芯片的制备及其在知母皂苷作用机理研究中的应用[J]. 药学学报,2003,38(7):496.
[37]	赵树进,韩丽萍. 知母皂苷及其苷元对动物模型β肾上腺素受体的调整作用[J]. 中国医院药学杂志,2000,20(2):70.
[38]	Wang GJ,Lin LC,Chen CF,et al. Effect of timosaponin A-III,from Anemarrhenae asphodeloides Bunge (Liliaceae),on calcium mobilization in vascular endothelial and smooth muscle cells and on vascular tension[J]. Life Sci,2002,71(9):1081.
[39]	Xiao S,Xu M,Ge Y,et al. Inhibitory Effects of Saponins From Anemarrhene asphodeloides Bunge on the Growth of Vascular Smooth Muscle Cells[J]. Biomed Environ Sci,2006,19(3):185.
[40]	Nakashima N,Kimura I,Kimura M,et al. Isolation of pseudoprototimosaponin AIII from rhizomes of Anemarrhena asphodeloides and its hypoglycemic activity in streptozotocin-induced diabetic mice[J]. J Nat Prod,1993,56(3):345.
[41]	李春梅,高永林,李敏,等. 知母皂苷对小鼠血糖的影响[J]. 中药药理与临床,2005,21(4):22.
[42]	韩兵,李春梅,李敏,等. 知母皂苷的降脂及抗动脉粥样硬化作用[J]. 上海中医药杂志,2006,40(11):68.
[43]	付宝才,林娟,杨林海. 知母总皂苷对高脂血症大鼠肝脏低密度脂蛋白受体活性的影响[J]. 医学综述,2009,15(14):2226.
[44]	Ren LX,Luo YF,Li X,et al. Antidepressant-Like Effects of Sarsasapogenin from Anemarrhena asphodeloides BUNGE (Liliaceae)[J]. Biol Pharm Bull,2006,29(11):2304.
[45]	Takeda O,Tanaka S,Yamasaki K,et al. Screening for molluscicidal activity in crude drugs[J]. Chem Pharm Bull,1989,37(4):1090.
[46]	Lee B,Trinh HT,Jung K,et al. Inhibitory effects of steroidal timosaponins isolated from the rhizomes of Anemarrhena asphodeloides against passive cutaneous anaphylaxis reaction and pruritus[J]. Immunopharmacol Immunotoxicol,2010,32(3):1.

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Advances in the pharmacological studies on timosaponins and their sapogenins

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通讯作者: 陈斌, [email protected]

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