ASTRAGALOSIDE IV
Astragaloside IV (ASIV) is a glycoside (sugar-bound molecule) from the astragalus plant. Astragalus is used in traditional Chinese medicine (TCM); like many “traditional” plants, the actual effects from the dried or whole plant are not strong enough pharmacologically to merit scientific inquiry for modern medicinal use. However, the glycoside astragaloside IV holds potential to heal wounds, improve immune function, assist in recovery from cardiovascular events, reverse endothelial dysfunction due to hyperaminoacidemia (a major contributor to cardiovascular disease), promotes mesenchymal stem cell proliferation in vitro, reduced induced left ventricular hypertrophy in a rat model, inhibited proliferation of basal-like human breast cancer lines in vitro, and attenuated 6-OHDA induced loss of dopaminergic neurons in a culture.
The glycoside astragaloside IV is not the only compound from the astragalus plant with healing potential; many of the traits are shared with other chemicals from the plant, in various forms, such as cycloastraganol:
Cycloartane-type saponins are the principal constituents responsible for wound healing activities of the roots of Astragalus species substantiating its use in traditional medicine.[1]
Astragaloside IV thus far (primarily in non-human models) has displayed a variety of different effects, including tissue-specific cellular healing of various types (such as heart tissue, below):
Astragaloside IV significantly reduced infarct size in dogs subjected to coronary ligation in vivo. Astragaloside IV also improved post-ischemic heart function and ameliorated reperfusion arrhythmias in rat hearts in vitro. The cardioprotection of astragaloside IV was accompanied by a significant increase in coronary flow both in vivo and in vitro.[2]
ASIV also increased lymphocyte production (specifically T and B cell) and antibody production in vitro and in vivo.[3]
ASIV not only increases endogenous antioxidant activity (specifically SOD) as demonstrated in vivo, but attenuates homocysteine-induced endothelial dysfunction:
In human umbilical vein endothelial cells culture experiment, exposure to astragaloside IV significantly ameliorated the homocysteine-induced inactivation of nitric oxide-nitric oxide synthase signal pathway via reducing oxygen species and increasing the activity of superoxide dismutase. Additionally, pretreatment with superoxide dismutase showed a similar effect to astragaloside IV on attenuation of the homocysteine-induced endothelial dysfunction. These data support the view that astragaloside IV might be advantageous in the treatment of endothelial dysfunction induced by disturbed nitric oxide-nitric oxide synthase pathway due to oxidative stress in hyperhomocysteinemia.[4]
Mesenchymal stem cells, or MSCs, are multipotent stem cells that can differentiate into a variety of cell types,[1] including: osteoblasts (bone cells), chondrocytes (cartilage cells) and adipocytes (fat cells).
MSCs or mesenchymal stem cells are a type of multi-function stem cell that can differentiate into several different cell types, usually chondrocytes (cartilage cells), adipocytes (fat cells), or osteoblasts (bone cells). ASIV was demonstrated to promote MSC proliferation in vitro (which could itself be useful for certain applications); macrophase stimulating colony factor (SCF) secretion in particular was elevated, which could provide a partial explanation for the immunomodulatory properties of ASIV:
[The purpose of the] study the effect of astragaloside IV on the expression of cytokines in bone mesenchymal stem cells (MSCs) in rats.
METHODS: MSCs were isolated from Wistar rats by the method of adhesive cultiration and clone, and then their biological activities were assessed using indirect immunofluorescence. Proliferation of MSCs stimulated with astragaloside IV was ascertained by the MTT method. Expression of cytokines was ascertained using RT-PCR in MSCs with astragaloside IV stimulation or not. RESULTS: MSCs were effectively isolated and purified in vitro, and had expression of many cytokines except IL-3, such as stem cell factor (SCF), thrombopoietin (TPO), granulocyte macrophage colony stimulating factor (GM-CSF) and transforming growth factor (TGF-beta1). Astragaloside IV stimulation promoted MSCs proliferation, and 200 mg/mL astragaloside IV treatment produced a peak effect 72 hrs after culture. The SCF expression in MSCs stimulated with astragaloside IV increased significantly compared with that in MSCs without astragaloside IV stimulation. CONCLUSIONS: Astragaloside IV may promote MSCs proliferation and increase SCF secretion in vitro.
Induced left ventricle hypertrophy (LVH) in rats was reduced after administration of ASIV; other measurable associated factors were also reduced:
Left ventricle hypertrophy was induced by abdominal aorta banding between bilateral renal aortas for 12 weeks. Rats were given astragaloside … After treatment, the left ventricular mass index (LVMI)was calculated by morphometry methods. Plasma and cardiac tissue angiotensin II, and plasma aldosterone were measured by ELISA method. Gene expressions of ACE, AT1 and AT2 in cardiac tissue were detected by real time PCR. Protein expressions of AT1 and AT2 in cardiac tissue were detected by Western blot…. Compared with model rats, LVMI was decreased by astragaloside IV treatment. Biochemical results indicated that the contents of angiotensin II in plasma and cardiac tissue as well as aldosterone in plasma were all increased in abdominal aorta banding rats comparing with sham-operated rats, then, decreased by astragaloside IV treatment. …CONCLUSION: Excessive activated rennin-angiotensin system in rats with pressure-overload induced cardiac hypertrophy is inhibited by astragaloside IV treatment.
ASIV halts proliferation of at least certain lines of breast cancer cells in vivo, likely through the Akt-phosphorylation pathway:
The effects of different concentrations of Astragalus injection, astragaloside IV and formononetin on proliferation of breast cancer cell lines were assayed by methyl thiazolyl tetrazolium (MTT) assay, and their effects on phospho-Akt were assayed by in-cell Western blot method…Astragalus injection, astragaloside IV and formononetin can inhibit proliferation of breast cancer cell lines MDA-MB-468 and MDA-MB-231, and the antiproliferation effects vary according to their concentrations. And the antiproliferation mechanisms may be related to their down-regulation effects on Akt phosphorylation[7]
Another cell-specific regenerative process induced by ASIV may be useful for treating Parkinson’s in humans:
Parkinson's disease (PD) is caused by a progressive degeneration of dopaminergic neurons in the substantia nigra. Oxidative stress and neural degeneration are suggested to be involved in the pathogenesis of Parkinson's disease. In the present study, Astragaloside IV (AS-IV) extracted from the dried root of Astragalus membranaceus, a well-known Chinese medicine used for the treatment of neurodegenerative diseases, was investigated for its capacity to protect dopaminergic neurons in experimental Parkinson's disease. By examining the effect of AS-IV on 6-hydroxydopamine (6-OHDA)-induced loss of dopaminergic neurons in primary nigral culture, we found that AS-IV pretreatment significantly and dose-dependently attenuated 6-OHDA-induced loss of dopaminergic neurons. Neuronal fiber length studies showed that massive neuronal cell death with degenerated neurons was observed in those cultures incubated with 6-OHDA, whereas in AS-IV co-treatments most dopaminergic neurons were seen to be intact and sprouting…. Besides the neuroprotective effect, AS-IV alone promoted neurite outgrowth and increased TH and NOS immunoreactive of dopaminergic neurons. The neuroprotective and neurosprouting effects of AS-IV are specific for dopaminergic neurons and it has therapeutic potential in the treatment of PD.[8]
Citations
[1] Sevimli-Gür C, Onbaşılar I, Atilla P, Genç R, Cakar N, Deliloğlu-Gürhan I, Bedir E. In vitro growth stimulatory and in vivo wound healing studies on cycloartane-type saponins of Astragalus genus. J Ethnopharmacol. 2011 Apr 12;134(3):844-50.
[2] Wei-Dong Zhang, Hong Chen, Chuan Zhang, Run-Hui Liu, Hui-Liang Li, Hong-Zhuan Chen. Astragaloside IV from Astragalus membranaceus Shows Cardioprotection during Myocardial Ischemia in vivo and in vitro. Planta Med 2006; 72(1): 4-8.
[3] Wang YP, Li XY, Song CQ, Hu ZB. Effect of astragaloside IV on T, B lymphocyte proliferation and peritoneal macrophage function in mice. Acta Pharmacol Sin. 2002 Mar;23(3):263-6.
[4] Qiu LH, Xie XJ, Zhang BQ. Astragaloside IV improves homocysteine-induced acute phase endothelial dysfunction via antioxidation. Biol Pharm Bull. 2010;33(4):641-6.
[5] Tan YF, Yin XC, Xiong YJ, Wang Y [Stem cell factor secretion by bone mesenchymal stem cells stimulated with astragaloside IV]. Zhongguo Dang Dai Er Ke Za Zhi. 2010 Apr;12(4):290-2.
[6] Shi H, Ma C, Liu Y, Zhou J, Hu Z, Wu D [Inhibitory effect on activated renin-angiotensin system by astragaloside IV in rats with pressure-overload induced cardiac hypertrophy]. Zhongguo Zhong Yao Za Zhi. 2009 Dec;34(24):3242-6.
[7] Deng Y, Chen HF. [Effects of Astragalus injection and its ingredients on proliferation and Akt phosphorylation of breast cancer cell lines]. Zhong Xi Yi Jie He Xue Bao. 2009 Dec;7(12):1174-80.
[8] Chan WS, Durairajan SS, Lu JH, Wang Y, Xie LX, Kum WF, Koo I, Yung KK, Li M. Neuroprotective effects of Astragaloside IV in 6-hydroxydopamine-treated primary nigral cell culture. Neurochem Int. 2009 Nov;55(6):414-22. Epub 2009 May 4.
Astragaloside IV (ASIV) is a glycoside (sugar-bound molecule) from the astragalus plant. Astragalus is used in traditional Chinese medicine (TCM); like many “traditional” plants, the actual effects from the dried or whole plant are not strong enough pharmacologically to merit scientific inquiry for modern medicinal use. However, the glycoside astragaloside IV holds potential to heal wounds, improve immune function, assist in recovery from cardiovascular events, reverse endothelial dysfunction due to hyperaminoacidemia (a major contributor to cardiovascular disease), promotes mesenchymal stem cell proliferation in vitro, reduced induced left ventricular hypertrophy in a rat model, inhibited proliferation of basal-like human breast cancer lines in vitro, and attenuated 6-OHDA induced loss of dopaminergic neurons in a culture.
The glycoside astragaloside IV is not the only compound from the astragalus plant with healing potential; many of the traits are shared with other chemicals from the plant, in various forms, such as cycloastraganol:
Cycloartane-type saponins are the principal constituents responsible for wound healing activities of the roots of Astragalus species substantiating its use in traditional medicine.[1]
Astragaloside IV thus far (primarily in non-human models) has displayed a variety of different effects, including tissue-specific cellular healing of various types (such as heart tissue, below):
Astragaloside IV significantly reduced infarct size in dogs subjected to coronary ligation in vivo. Astragaloside IV also improved post-ischemic heart function and ameliorated reperfusion arrhythmias in rat hearts in vitro. The cardioprotection of astragaloside IV was accompanied by a significant increase in coronary flow both in vivo and in vitro.[2]
ASIV also increased lymphocyte production (specifically T and B cell) and antibody production in vitro and in vivo.[3]
ASIV not only increases endogenous antioxidant activity (specifically SOD) as demonstrated in vivo, but attenuates homocysteine-induced endothelial dysfunction:
In human umbilical vein endothelial cells culture experiment, exposure to astragaloside IV significantly ameliorated the homocysteine-induced inactivation of nitric oxide-nitric oxide synthase signal pathway via reducing oxygen species and increasing the activity of superoxide dismutase. Additionally, pretreatment with superoxide dismutase showed a similar effect to astragaloside IV on attenuation of the homocysteine-induced endothelial dysfunction. These data support the view that astragaloside IV might be advantageous in the treatment of endothelial dysfunction induced by disturbed nitric oxide-nitric oxide synthase pathway due to oxidative stress in hyperhomocysteinemia.[4]
Mesenchymal stem cells, or MSCs, are multipotent stem cells that can differentiate into a variety of cell types,[1] including: osteoblasts (bone cells), chondrocytes (cartilage cells) and adipocytes (fat cells).
MSCs or mesenchymal stem cells are a type of multi-function stem cell that can differentiate into several different cell types, usually chondrocytes (cartilage cells), adipocytes (fat cells), or osteoblasts (bone cells). ASIV was demonstrated to promote MSC proliferation in vitro (which could itself be useful for certain applications); macrophase stimulating colony factor (SCF) secretion in particular was elevated, which could provide a partial explanation for the immunomodulatory properties of ASIV:
[The purpose of the] study the effect of astragaloside IV on the expression of cytokines in bone mesenchymal stem cells (MSCs) in rats.
METHODS: MSCs were isolated from Wistar rats by the method of adhesive cultiration and clone, and then their biological activities were assessed using indirect immunofluorescence. Proliferation of MSCs stimulated with astragaloside IV was ascertained by the MTT method. Expression of cytokines was ascertained using RT-PCR in MSCs with astragaloside IV stimulation or not. RESULTS: MSCs were effectively isolated and purified in vitro, and had expression of many cytokines except IL-3, such as stem cell factor (SCF), thrombopoietin (TPO), granulocyte macrophage colony stimulating factor (GM-CSF) and transforming growth factor (TGF-beta1). Astragaloside IV stimulation promoted MSCs proliferation, and 200 mg/mL astragaloside IV treatment produced a peak effect 72 hrs after culture. The SCF expression in MSCs stimulated with astragaloside IV increased significantly compared with that in MSCs without astragaloside IV stimulation. CONCLUSIONS: Astragaloside IV may promote MSCs proliferation and increase SCF secretion in vitro.
Induced left ventricle hypertrophy (LVH) in rats was reduced after administration of ASIV; other measurable associated factors were also reduced:
Left ventricle hypertrophy was induced by abdominal aorta banding between bilateral renal aortas for 12 weeks. Rats were given astragaloside … After treatment, the left ventricular mass index (LVMI)was calculated by morphometry methods. Plasma and cardiac tissue angiotensin II, and plasma aldosterone were measured by ELISA method. Gene expressions of ACE, AT1 and AT2 in cardiac tissue were detected by real time PCR. Protein expressions of AT1 and AT2 in cardiac tissue were detected by Western blot…. Compared with model rats, LVMI was decreased by astragaloside IV treatment. Biochemical results indicated that the contents of angiotensin II in plasma and cardiac tissue as well as aldosterone in plasma were all increased in abdominal aorta banding rats comparing with sham-operated rats, then, decreased by astragaloside IV treatment. …CONCLUSION: Excessive activated rennin-angiotensin system in rats with pressure-overload induced cardiac hypertrophy is inhibited by astragaloside IV treatment.
ASIV halts proliferation of at least certain lines of breast cancer cells in vivo, likely through the Akt-phosphorylation pathway:
The effects of different concentrations of Astragalus injection, astragaloside IV and formononetin on proliferation of breast cancer cell lines were assayed by methyl thiazolyl tetrazolium (MTT) assay, and their effects on phospho-Akt were assayed by in-cell Western blot method…Astragalus injection, astragaloside IV and formononetin can inhibit proliferation of breast cancer cell lines MDA-MB-468 and MDA-MB-231, and the antiproliferation effects vary according to their concentrations. And the antiproliferation mechanisms may be related to their down-regulation effects on Akt phosphorylation[7]
Another cell-specific regenerative process induced by ASIV may be useful for treating Parkinson’s in humans:
Parkinson's disease (PD) is caused by a progressive degeneration of dopaminergic neurons in the substantia nigra. Oxidative stress and neural degeneration are suggested to be involved in the pathogenesis of Parkinson's disease. In the present study, Astragaloside IV (AS-IV) extracted from the dried root of Astragalus membranaceus, a well-known Chinese medicine used for the treatment of neurodegenerative diseases, was investigated for its capacity to protect dopaminergic neurons in experimental Parkinson's disease. By examining the effect of AS-IV on 6-hydroxydopamine (6-OHDA)-induced loss of dopaminergic neurons in primary nigral culture, we found that AS-IV pretreatment significantly and dose-dependently attenuated 6-OHDA-induced loss of dopaminergic neurons. Neuronal fiber length studies showed that massive neuronal cell death with degenerated neurons was observed in those cultures incubated with 6-OHDA, whereas in AS-IV co-treatments most dopaminergic neurons were seen to be intact and sprouting…. Besides the neuroprotective effect, AS-IV alone promoted neurite outgrowth and increased TH and NOS immunoreactive of dopaminergic neurons. The neuroprotective and neurosprouting effects of AS-IV are specific for dopaminergic neurons and it has therapeutic potential in the treatment of PD.[8]
Citations
[1] Sevimli-Gür C, Onbaşılar I, Atilla P, Genç R, Cakar N, Deliloğlu-Gürhan I, Bedir E. In vitro growth stimulatory and in vivo wound healing studies on cycloartane-type saponins of Astragalus genus. J Ethnopharmacol. 2011 Apr 12;134(3):844-50.
[2] Wei-Dong Zhang, Hong Chen, Chuan Zhang, Run-Hui Liu, Hui-Liang Li, Hong-Zhuan Chen. Astragaloside IV from Astragalus membranaceus Shows Cardioprotection during Myocardial Ischemia in vivo and in vitro. Planta Med 2006; 72(1): 4-8.
[3] Wang YP, Li XY, Song CQ, Hu ZB. Effect of astragaloside IV on T, B lymphocyte proliferation and peritoneal macrophage function in mice. Acta Pharmacol Sin. 2002 Mar;23(3):263-6.
[4] Qiu LH, Xie XJ, Zhang BQ. Astragaloside IV improves homocysteine-induced acute phase endothelial dysfunction via antioxidation. Biol Pharm Bull. 2010;33(4):641-6.
[5] Tan YF, Yin XC, Xiong YJ, Wang Y [Stem cell factor secretion by bone mesenchymal stem cells stimulated with astragaloside IV]. Zhongguo Dang Dai Er Ke Za Zhi. 2010 Apr;12(4):290-2.
[6] Shi H, Ma C, Liu Y, Zhou J, Hu Z, Wu D [Inhibitory effect on activated renin-angiotensin system by astragaloside IV in rats with pressure-overload induced cardiac hypertrophy]. Zhongguo Zhong Yao Za Zhi. 2009 Dec;34(24):3242-6.
[7] Deng Y, Chen HF. [Effects of Astragalus injection and its ingredients on proliferation and Akt phosphorylation of breast cancer cell lines]. Zhong Xi Yi Jie He Xue Bao. 2009 Dec;7(12):1174-80.
[8] Chan WS, Durairajan SS, Lu JH, Wang Y, Xie LX, Kum WF, Koo I, Yung KK, Li M. Neuroprotective effects of Astragaloside IV in 6-hydroxydopamine-treated primary nigral cell culture. Neurochem Int. 2009 Nov;55(6):414-22. Epub 2009 May 4.
