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Effect of astragaloside IV on cognitive dysfunction in rats with cerebrally infarcted via TGF-β / Smad signaling pathway
Corresponding Author(s) : Li Li
Cellular and Molecular Biology,
Vol. 66 No. 2: Issue 2
Abstract
Cerebral infarction is an acute cerebrovascular disease caused by abnormal blood circulation in the brain. In the present study, we investigate the effect of astragaloside IV on cognitive dysfunction in cerebrally infarcted rats via transforming growth factor-β (TGF-β) / Smad signaling pathway. For this purpose, 45 rats were divided into three groups including astragaloside, model, and control. 30 of 45 healthy adult male SD rats were randomly selected to establish an acute cerebral infarction model. 15 modeled rats were enrolled as a model and astragaloside group, and another 15 rats as a blank control group. The rats in the astragaloside group were fed with astragaloside IV according to 1.08 g/kg body weight, and those in the blank group and model group were given matching normal saline. The levels of TGF-β, Smad1, Smad3 and Smad7 of TGF-β/Smad signaling transduction pathway at T0 (week 0), T1 (week 3) and T2 (week 6) were determined by enzyme-linked immunosorbent assay (ELISA). The modified neurological severity score (mNSS) was used to evaluate the improvement of cognitive dysfunction in rats. The mNSS of rats with cerebral infarction in the astragaloside group was lower than that in the control group and model group (P< 0.05). While the levels of TGF-β, Smad1, Smad3 and Smad7 in the astragaloside group were higher than those in the control group and model group (P< 0.05). Astragaloside IV plays an important role in improving cognitive dysfunction in rats with cerebral infarction while affecting the levels of TGF-β, Smad1, Smad3 and Smad7 and activating TGF-β / Smad signaling pathway.
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- Gupta A, Giambrone AE, Gialdini G, Finn C, Delgado D, Gutierrez J, Wright C, Beiser AS, Seshadri S, Pandya A, Kamel H. Silent Brain Infarction and Risk of Future Stroke: A Systematic Review and Meta-Analysis. Stroke 2016; 47: 719-725.
- Sandu RE, Buga AM, Balseanu AT, Moldovan M, Popa-Wagner A. Twenty-four hours hypothermia has temporary efficacy in reducing brain infarction and inflammation in aged rats. Neurobiol Aging 2015; 38: 127-140.
- Yan XH, Wu YQ. Study Progress of the Influence of Atrial Fibrillation Treatment on Dementia. Chin Med J (En) 2018; 131: 859-861.
- Cheng WB, Li D, Yang Q, Hou YM. Relationship between ab¬normal vagus nerve tension and basal ganglia cerebral infarction induced paroxysmal atrial fibrillation. Asian Pac J Trop Med 2017; 10: 921-924.
- Numminen H, Kaste M, Aho K, Waltimo O, Kotila M. Decreased severity of brain infarct can in part explain the decreasing case fatality rate of stroke. Stroke 2000; 31: 651-655.
- Cao Y, Wang F, Cheng Q, Jiao X, Lv X. Fasting blood glucose levels affect hospitalization time and relapse and mortality rates of cerebral infarction patients. Int J Clin Exp Med 2015; 8: 11508-11513.
- Zhao J, Tang H, Sun J, Wang B, Chen S, Fu Y. Analysis of cognitive dysfunction with silent cerebral infarction: a prospective study in Chinese patients. Metab Brain Dis 2011; 27: 17-22.
- Davlouros PA, Mplani VC, Koniari I, Tsigkas G, Hahalis G. TGF-β signaling in the brain increases with aging and signals to astrocytes and innate immune cells in the weeks after stroke. J Geriatr Cardiol 2018; 15: 95-104.
- Wood M, Song A, Maslove D, Ferri C, Howes D, Muscedere J, Boyd JG. Brain Tissue Oxygenation in Patients with Septic Shock: a Feasibility Study. Can J Neurol Sci 2015; 43: 65-73.
- Brown PD, Jaeckle K, Ballman KV, Farace E, Cerhan JH, Anderson SK, Carrero XW, Barker FG, Deming R, Burri SH, Ménard C, Chung C, Stieber VW, Pollock BE, Galanis E, Buckner JC, Asher AL. Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases: A Randomized Clinical Trial. JAMA 2016; 316: 401-409.
- Kronenburg A, van den Berg E, van Schooneveld MM, Braun KPJ, Calviere L, van der Zwan A, Klijn CJM. Cognitive Functions in Children and Adults with Moyamoya Vasculopathy: A Systematic Review and Meta-Analysis. J Stroke 2018; 20: 332-341.
- Wang N, Phan K: Cerebral protection devices in transcatheter aortic valve replacement: a clinical meta-analysis of randomized controlled trials. J Thorac Dis 2018; 10: 1927-1935.
- Fatania G, Gilson C, Glover A, Alsafi A, Jackson JE, Patel MC, Shovlin CL. Uptake and radiological findings of screening cerebral magnetic resonance scans in patients with hereditary haemorrhagic telangiectasia. Intractable Rare Dis Res 2018; 7: 236-244.
- Vaidya K, Khandkar C, Celermajer D. Current management aspects in adult congenital heart disease: non-surgical closure of patent foramen ovale. Cardiovasc Diagn Ther 2018; 8: 739-753.
- Ding M, Qiu C. Atrial Fibrillation, Cognitive Decline, and Dementia: an Epidemiologic Review. Curr Epidemiol Rep 2018; 5: 252-261.
- Hsu CY, Chiu SW, Hong KS, Saver JL, Wu YL, Lee JD, Lee M. Folic Acid in Stroke Prevention in Countries without Mandatory Folic Acid Food Fortification: A Meta-Analysis of Randomized Controlled Trials. J Stroke 2018; 20: 99-109.
- Ning X, Zhang K, Wu Q, Liu M, Sun S. Emerging role of Twist1 in fibrotic diseases. J Cell Mol Med 2018; 22: 1383-1391.
- Xu X, Wang B, Ren C, Hu J, Greenberg DA, Chen T, Xie L, Jin K. Recent Progress in Vascular Aging: Mechanisms and Its Role in Age-related Diseases. Aging Dis 2017; 8: 486-505.
- Liu FF, Liu CY, Li XP, Zheng SZ, Li QQ, Liu Q, Song L. Neuroprotective effects of SMADs in a rat model of cerebral ischemia/ reperfusion. Neural Regen Res 2015; 10: 438-444.
- Lou Y, Shi J, Guo D, Qureshi AK and Song L: Function of PD-L1 in antitumor immunity of glioma cells. Saudi J Boil Sci 2017; 24(4): 803-807.
- Guo T, Lin Q, Li X, Nie Y, Wang L, Shi L and Luo F: Octacosanol attenuates inflammation in both RAW264. 7 macrophages and a mouse model of colitis. J Agri Food Chem 2017; 65(18): 3647-3658.
- Li W, Jia MX, Wang JH, Lu JL, Deng J, Tang JX and Liu C: Association of MMP9-1562C/T and MMP13-77A/G polymorphisms with non-small cell lung cancer in southern Chinese population. Biomol 2019; 9(3): 107-119.
- Nie Y, Luo F, Wang L, Yang T, Shi L, Li X, Shen J, Xu W, Guo T and Lin Q: Anti-hyperlipidemic effect of rice bran polysaccharide and its potential mechanism in high-fat diet mice. Food Func 2017; 8(11): 4028-4041.
- Lou Y, Yang J, Wang L, Chen X, Xin X and Liu Y: The clinical efficacy study of treatment to Chiari malformation type I with syringomyelia under the minimally invasive surgery of resection of Submeningeal cerebellar Tonsillar Herniation and reconstruction of Cisterna magna. Saudi J Biol Sci 2019; 26(8): 1927-1931.
- Lou Y, Guo D, Zhang H and Song L: Effectiveness of mesenchymal stems cells cultured by hanging drop vs. conventional culturing on the repair of hypoxic-ischemic-damaged mouse brains, measured by stemness gene expression. Open Life Sci 2016; 11(1): 519-523.
- Finn C, Giambrone AE, Gialdini G, Delgado D, Baradaran H, Kamel H, Gupta A: The Association between Carotid Artery Atherosclerosis and Silent Brain Infarction: A Systematic Review and Meta-analysis. J Stroke Cerebrovasc Dis 26: 1594-1601, 2017.
- Yunzhi C, Jiaxu C, Jie G, Yihui C, Wen L, Zhong Q: Effect of Astragaloside on Vitamin d-Receptor Expression after Endothelin- 1-Induced Cardiomyocyte Injury. Afr J Tradit Complement Altern Med 14: 278-288, 2017.
- Wang L, Chi YF, Yuan ZT, Zhou WC, Yin PH, Zhang XM, Peng W, Cai H: Astragaloside IV inhibits renal tubulointerstitial fibrosis by blocking TGF-β/Smad signaling pathway in vivo and in vitro. Exp Biol Med (Maywood) 239: 1310-1324, 2014.
- Zhang L, Li Z, He W, Xu L, Wang J, Shi J, Sheng M: Effects of astragaloside IV against the TGF-β1-induced epithelial-to-mesenchymal transition in peritoneal mesothelial cells by promoting smad 7 expression. Cell Physiol Biochem 37: 43-54, 2015.
- Zhang S, Wang J, Zhao H, Luo Y: Effects of three flavonoids from an ancient traditional Chinese medicine Radix puerariae on geriatric diseases. Brain Circ 4: 174-184, 2018.
- Ji YD, Luo ZL, Chen CX, Li B, Gong J, Wang YX, Chen L, Yao SL, Shang Y: BML-111 suppresses TGF-β1-induced lung fibroblast activation in vitro and decreases experimental pulmonary fibrosis in vivo. Int J Mol Med 42: 3083-3092, 2018.
- Zhang HY, Wang HL, Zhong GY, Zhu JX: Molecular mechanism and research progress on pharmacology of traditional Chinese medicine in liver injury. Pharm Biol 56: 594-611, 2018.
- Deng F, Magee N, Zhang Y: Decoding the Role of Extracellular Vesicles in Liver Diseases. Liver Res 1: 147-155, 2017.
- Leiting S, Seidl S, Martinez-Palacian A, Muhl L, Kanse SM: Transforming Growth Factor-β (TGF-β) Inhibits the Expression of Factor VII-activating Protease (FSAP) in Hepatocytes. J Biol Chem 291: 21020-21028, 2016.
- Nie Y, Luo F and Lin Q: Dietary nutrition and gut microflora: A promising target for treating diseases. Trends Food Sci Technol 2018;75: 72-80.
- Ren Y, Jiao X and Zhang L: Expression level of fibroblast growth factor 5 (FGF5) in the peripheral blood of primary hypertension and its clinical significance. Saudi J Biol Sci 2018; 25(3): 469-473.
- Liang Y, Lin Q, Huang P, Wang Y, Li J, Zhang L and Cao J: Rice Bioactive Peptide Binding with TLR4 To Overcome H2O2-Induced Injury in Human Umbilical Vein Endothelial Cells through NF-κB Signaling. J Agri Food Chem 2018; 66(2): 440-448.
- Wang L, Lin Q, Yang T, Liang Y, Nie Y, Luo Y and Luo F: Oryza¬nol modifies high fat diet-induced obesity, liver gene expression pro¬file, and inflammation response in mice. J Agri Food Chem 2017; 65(38): 8374-8385.
- Chen X, Xu Y, Meng L, Chen X, Yuan L, Cai Q, Shi W and Huang G: Non-parametric partial least squares–discriminant analysis model based on sum of ranking difference algorithm for tea grade identification using electronic tongue data identify tea grade using e-tongue data. Sens Actuators B Chem 2020; 127924.
References
Gupta A, Giambrone AE, Gialdini G, Finn C, Delgado D, Gutierrez J, Wright C, Beiser AS, Seshadri S, Pandya A, Kamel H. Silent Brain Infarction and Risk of Future Stroke: A Systematic Review and Meta-Analysis. Stroke 2016; 47: 719-725.
Sandu RE, Buga AM, Balseanu AT, Moldovan M, Popa-Wagner A. Twenty-four hours hypothermia has temporary efficacy in reducing brain infarction and inflammation in aged rats. Neurobiol Aging 2015; 38: 127-140.
Yan XH, Wu YQ. Study Progress of the Influence of Atrial Fibrillation Treatment on Dementia. Chin Med J (En) 2018; 131: 859-861.
Cheng WB, Li D, Yang Q, Hou YM. Relationship between ab¬normal vagus nerve tension and basal ganglia cerebral infarction induced paroxysmal atrial fibrillation. Asian Pac J Trop Med 2017; 10: 921-924.
Numminen H, Kaste M, Aho K, Waltimo O, Kotila M. Decreased severity of brain infarct can in part explain the decreasing case fatality rate of stroke. Stroke 2000; 31: 651-655.
Cao Y, Wang F, Cheng Q, Jiao X, Lv X. Fasting blood glucose levels affect hospitalization time and relapse and mortality rates of cerebral infarction patients. Int J Clin Exp Med 2015; 8: 11508-11513.
Zhao J, Tang H, Sun J, Wang B, Chen S, Fu Y. Analysis of cognitive dysfunction with silent cerebral infarction: a prospective study in Chinese patients. Metab Brain Dis 2011; 27: 17-22.
Davlouros PA, Mplani VC, Koniari I, Tsigkas G, Hahalis G. TGF-β signaling in the brain increases with aging and signals to astrocytes and innate immune cells in the weeks after stroke. J Geriatr Cardiol 2018; 15: 95-104.
Wood M, Song A, Maslove D, Ferri C, Howes D, Muscedere J, Boyd JG. Brain Tissue Oxygenation in Patients with Septic Shock: a Feasibility Study. Can J Neurol Sci 2015; 43: 65-73.
Brown PD, Jaeckle K, Ballman KV, Farace E, Cerhan JH, Anderson SK, Carrero XW, Barker FG, Deming R, Burri SH, Ménard C, Chung C, Stieber VW, Pollock BE, Galanis E, Buckner JC, Asher AL. Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases: A Randomized Clinical Trial. JAMA 2016; 316: 401-409.
Kronenburg A, van den Berg E, van Schooneveld MM, Braun KPJ, Calviere L, van der Zwan A, Klijn CJM. Cognitive Functions in Children and Adults with Moyamoya Vasculopathy: A Systematic Review and Meta-Analysis. J Stroke 2018; 20: 332-341.
Wang N, Phan K: Cerebral protection devices in transcatheter aortic valve replacement: a clinical meta-analysis of randomized controlled trials. J Thorac Dis 2018; 10: 1927-1935.
Fatania G, Gilson C, Glover A, Alsafi A, Jackson JE, Patel MC, Shovlin CL. Uptake and radiological findings of screening cerebral magnetic resonance scans in patients with hereditary haemorrhagic telangiectasia. Intractable Rare Dis Res 2018; 7: 236-244.
Vaidya K, Khandkar C, Celermajer D. Current management aspects in adult congenital heart disease: non-surgical closure of patent foramen ovale. Cardiovasc Diagn Ther 2018; 8: 739-753.
Ding M, Qiu C. Atrial Fibrillation, Cognitive Decline, and Dementia: an Epidemiologic Review. Curr Epidemiol Rep 2018; 5: 252-261.
Hsu CY, Chiu SW, Hong KS, Saver JL, Wu YL, Lee JD, Lee M. Folic Acid in Stroke Prevention in Countries without Mandatory Folic Acid Food Fortification: A Meta-Analysis of Randomized Controlled Trials. J Stroke 2018; 20: 99-109.
Ning X, Zhang K, Wu Q, Liu M, Sun S. Emerging role of Twist1 in fibrotic diseases. J Cell Mol Med 2018; 22: 1383-1391.
Xu X, Wang B, Ren C, Hu J, Greenberg DA, Chen T, Xie L, Jin K. Recent Progress in Vascular Aging: Mechanisms and Its Role in Age-related Diseases. Aging Dis 2017; 8: 486-505.
Liu FF, Liu CY, Li XP, Zheng SZ, Li QQ, Liu Q, Song L. Neuroprotective effects of SMADs in a rat model of cerebral ischemia/ reperfusion. Neural Regen Res 2015; 10: 438-444.
Lou Y, Shi J, Guo D, Qureshi AK and Song L: Function of PD-L1 in antitumor immunity of glioma cells. Saudi J Boil Sci 2017; 24(4): 803-807.
Guo T, Lin Q, Li X, Nie Y, Wang L, Shi L and Luo F: Octacosanol attenuates inflammation in both RAW264. 7 macrophages and a mouse model of colitis. J Agri Food Chem 2017; 65(18): 3647-3658.
Li W, Jia MX, Wang JH, Lu JL, Deng J, Tang JX and Liu C: Association of MMP9-1562C/T and MMP13-77A/G polymorphisms with non-small cell lung cancer in southern Chinese population. Biomol 2019; 9(3): 107-119.
Nie Y, Luo F, Wang L, Yang T, Shi L, Li X, Shen J, Xu W, Guo T and Lin Q: Anti-hyperlipidemic effect of rice bran polysaccharide and its potential mechanism in high-fat diet mice. Food Func 2017; 8(11): 4028-4041.
Lou Y, Yang J, Wang L, Chen X, Xin X and Liu Y: The clinical efficacy study of treatment to Chiari malformation type I with syringomyelia under the minimally invasive surgery of resection of Submeningeal cerebellar Tonsillar Herniation and reconstruction of Cisterna magna. Saudi J Biol Sci 2019; 26(8): 1927-1931.
Lou Y, Guo D, Zhang H and Song L: Effectiveness of mesenchymal stems cells cultured by hanging drop vs. conventional culturing on the repair of hypoxic-ischemic-damaged mouse brains, measured by stemness gene expression. Open Life Sci 2016; 11(1): 519-523.
Finn C, Giambrone AE, Gialdini G, Delgado D, Baradaran H, Kamel H, Gupta A: The Association between Carotid Artery Atherosclerosis and Silent Brain Infarction: A Systematic Review and Meta-analysis. J Stroke Cerebrovasc Dis 26: 1594-1601, 2017.
Yunzhi C, Jiaxu C, Jie G, Yihui C, Wen L, Zhong Q: Effect of Astragaloside on Vitamin d-Receptor Expression after Endothelin- 1-Induced Cardiomyocyte Injury. Afr J Tradit Complement Altern Med 14: 278-288, 2017.
Wang L, Chi YF, Yuan ZT, Zhou WC, Yin PH, Zhang XM, Peng W, Cai H: Astragaloside IV inhibits renal tubulointerstitial fibrosis by blocking TGF-β/Smad signaling pathway in vivo and in vitro. Exp Biol Med (Maywood) 239: 1310-1324, 2014.
Zhang L, Li Z, He W, Xu L, Wang J, Shi J, Sheng M: Effects of astragaloside IV against the TGF-β1-induced epithelial-to-mesenchymal transition in peritoneal mesothelial cells by promoting smad 7 expression. Cell Physiol Biochem 37: 43-54, 2015.
Zhang S, Wang J, Zhao H, Luo Y: Effects of three flavonoids from an ancient traditional Chinese medicine Radix puerariae on geriatric diseases. Brain Circ 4: 174-184, 2018.
Ji YD, Luo ZL, Chen CX, Li B, Gong J, Wang YX, Chen L, Yao SL, Shang Y: BML-111 suppresses TGF-β1-induced lung fibroblast activation in vitro and decreases experimental pulmonary fibrosis in vivo. Int J Mol Med 42: 3083-3092, 2018.
Zhang HY, Wang HL, Zhong GY, Zhu JX: Molecular mechanism and research progress on pharmacology of traditional Chinese medicine in liver injury. Pharm Biol 56: 594-611, 2018.
Deng F, Magee N, Zhang Y: Decoding the Role of Extracellular Vesicles in Liver Diseases. Liver Res 1: 147-155, 2017.
Leiting S, Seidl S, Martinez-Palacian A, Muhl L, Kanse SM: Transforming Growth Factor-β (TGF-β) Inhibits the Expression of Factor VII-activating Protease (FSAP) in Hepatocytes. J Biol Chem 291: 21020-21028, 2016.
Nie Y, Luo F and Lin Q: Dietary nutrition and gut microflora: A promising target for treating diseases. Trends Food Sci Technol 2018;75: 72-80.
Ren Y, Jiao X and Zhang L: Expression level of fibroblast growth factor 5 (FGF5) in the peripheral blood of primary hypertension and its clinical significance. Saudi J Biol Sci 2018; 25(3): 469-473.
Liang Y, Lin Q, Huang P, Wang Y, Li J, Zhang L and Cao J: Rice Bioactive Peptide Binding with TLR4 To Overcome H2O2-Induced Injury in Human Umbilical Vein Endothelial Cells through NF-κB Signaling. J Agri Food Chem 2018; 66(2): 440-448.
Wang L, Lin Q, Yang T, Liang Y, Nie Y, Luo Y and Luo F: Oryza¬nol modifies high fat diet-induced obesity, liver gene expression pro¬file, and inflammation response in mice. J Agri Food Chem 2017; 65(38): 8374-8385.
Chen X, Xu Y, Meng L, Chen X, Yuan L, Cai Q, Shi W and Huang G: Non-parametric partial least squares–discriminant analysis model based on sum of ranking difference algorithm for tea grade identification using electronic tongue data identify tea grade using e-tongue data. Sens Actuators B Chem 2020; 127924.