Flavonoids from Scutellaria baicalensis Georgi Stems and Leaves Regulate the Brain Tau Hyperphosphorylation at M|ultiple Sites Induced by Composited Aβ in Rats

Background: Neurofibrillary tangles (NFTs), formed by hyperphosphorylation of Tau protein in Alzheimer's disease (AD) are the main pathomechanisms of neuronal degeneration, which can be used as a sign of brain disorder. It is positively correlated with the degree of cognitive impairment in AD. Objective: The objective of this study is to investigate the effect of Scutellaria baicalensis Georgi stems and leaves flavonoids (SSF) on the hyperphosphorylated expression levels at multiple sites of Tau protein induced by β-amyloid protein 25-35 (Aβ25-35) in combined with aluminum trichloride (AlCl3) and recombinant human transforming growth factor-β1 (RHTGF-β1) (composited Aβ) in rats. Methods: The model of rats for AD was established by intracerebroventricular injection of Aβ25-35 and AlCl3 combined with RHTGF-β1. On day 45 after the operation, the Morris water maze was used to screen the rats’ memory impairment model for AD. The successful model rats were randomly divided into the model group and three-dose of drug group. The drug group rats were daily and orally SSF administrated for 38 days. Western blotting was used to detect the protein expression of P-Tau (Thr181), P-Tau (Thr217), P-Tau (Thr231), P-Tau (Ser199), P-Tau (Ser235), P-Tau (Ser396) and P-Tau (Ser404) in the hippocampus and cerebral cortex of rats. Results: Compared with the sham group, the protein expression of P-Tau (Thr181), P-Tau (Thr217), P-Tau (Thr231), P-Tau (Ser199), P-Tau (Ser235), P-Tau (Ser396) and P-Tau (Ser404) was significantly increased in the hippocampus and cerebral cortex in the model group (P < 0.01). However, the three doses of 35, 70 and 140 mg/kg SSF regulated the expression of phosphorylated Tau protein at the above sites to varying degrees in the hippocampus and cerebral cortex (P < 0.01) induced by composited Aβ. Conclusion: SSF can significantly reduce the protein expression levels of P-Tau (Thr181), P-Tau (Thr217), P-Tau (Thr231), P-Tau (Ser199), P-Tau (Ser235), P-Tau (Ser396) and P-Tau (Ser404) in rats’ brain induced by the intracerebroventricular injection of composited Aβ. These results demonstrated that the neuro-protection and the impaired memory improvement of SSF were due to the inhibition for the hyperphosphorylation of Tau protein at multiple sites.

The Molecular Mechanism of Scutellaria baicalensis Georgi Stems and Leaves Flavonoids in Promoting Neurogenesis and Improving Memory Impairment by the PI3K-AKT-CREB Signaling Pathway in Rats

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207324666210506152320 ◽

2021 ◽

Vol 24 ◽

Author(s):

Qian-qian Liu ◽

Sheng-kai Ding ◽

Hui Zhang ◽

Ya-zhen Shang

Keyword(s):

Cerebral Cortex ◽

Protein Expression ◽

Signaling Pathway ◽

Molecular Mechanism ◽

Memory Impairment ◽

Model Group ◽

Memory Errors ◽

Protein Expressions ◽

Aim: The aim of this study was to investigate the effect, and molecular mechanism of Scutellaria Baicalensis Georgi stems and leaves flavonoids (SSF) in promoting neurogenesis and improving memory impairment induced by the PI3K-AKT-CREB signaling pathway. Methods: Alzheimer's disease (AD) was induced in the male Wistar rats by intracerebroventricular injection of amyloid beta-peptide 25-35 (Aβ25-35) in combination with aluminum trichloride (AlCl3) and recombinant human transforming growth factor-β1(RHTGF-β1) (composited Aβ). The Morris water maze was used to screen the successful establishment of the memory impairment model of rats. The screened successful model rats were randomly divided into a model group and three groups of three different doses of the drug (SSF). Rats in the drug group were treated with 35, 70, and 140 mg/kg of SSF for 43 days. The Eight-arm maze was used to measure the spatial learning and memory abilities of the rat, including working memory errors (WME) and reference memory errors (RME). Immunohistochemistry was used to detect the expression of BrdU, an indicator of neuronal proliferation, in the hippocampal gyrus of rats. The mRNA and protein expressions of TRKB, PI3K, AKT, P-AKT, and IGF2 in the PI3K-AKT-CREB signaling pathway in the hippocampus and cerebral cortex of the rats were determined by quantitative real-time PCR (qPCR) and Western blotting methods. Results: Compared to the sham group, the spatial memory ability of rats with composited Aβ was decreased, the number of WME and RME (P < 0.01) was increased, the expression of BrdU protein (P < 0.01) in the hippocampal gyrus was reduced, the mRNA and protein expression levels of TRKB, AKT, and IGF2 (P < 0.01, P < 0.05) in the hippocampus and cerebral cortex were lowered, and the mRNA expression level of PI3K (P < 0.01) in the cerebral cortex and the protein expression level of PI3K (P < 0.01) in the hippocampus were augmented. However, compared to the model group, the three-doses of SSF improved memory disorder induced by composited Aβ, reduced the number of WME and RME, increased the expression of BrdU protein in the hippocampal gyrus, and differently regulated the mRNA and protein expressions in composited Aβ rats. Conclusions: SSF improved memory impairment and neurogenesis disorder induced by composited Aβ in rats by activating the PI3K-AKT-CREB signaling pathway and up-regulating the mRNA and protein expressions of TRKB, PI3K, AKT, CREB, and IGF2.

The Effects and Regulative Mechanism of Scutellaria Baicalensis Georgi Stems and Leaves Flavonoids in Promoting Neurogenesis and Improving Memory Impairment Mediated by BDNF-ERK-CREB Signal Pathway in Rats

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527320666210827112048 ◽

2021 ◽

Vol 20 ◽

Author(s):

Yazhen Shang ◽

Shengkai Ding ◽

Qianqian Liu

Keyword(s):

Cerebral Cortex ◽

Protein Expression ◽

Signaling Pathway ◽

Memory Impairment ◽

Signal Pathway ◽

Scutellaria Baicalensis ◽

Mrna And Protein Expression ◽

Stems And Leaves ◽

Regulative Mechanism

Background: It is well known that Alzheimer's disease (AD) is a degenerative disease, and accompanied by memory impairment and main pathological changes of the extracellular senile plaque (SP) and intracellular neurofibrillary tangles (NFTs). However, there are many evidences showing that the disorders of neurogenesis are also regarded as a new opinion in AD. Objective: To investigate the effects and regulative mechanism of Scutellaria baicalensis Georgi stems and leaves flavonoids in promoting neurogenesis and improving memory impairment mediated by BDNF-ERK-CREB signal pathway in rats. Methods: Male Wistar rats were intracerebroventricularly injected with amyloid-beta protein 25-35 (Aβ25-35) in combination with aluminum trichloride (AlCl3) and recombinant human transforming growth factor-β1 (RHTGF-β1) (composited Aβ), to establish an AD model. Morris water maze was used to screen AD model of rats and measure the rats’ learning and memory ability. The expression of cell neurogenesis related molecule Ki67 protein in the hippocampal gyrus of rats was detected by the immunohistochemical method. The expression of mRNA and protein of Grb2, SOS1, Ras, ERK and BDNF in the BDNF-ERK-CREB signaling pathway, in the hippocampus and cerebral cortex were assayed by the Quantitative real-time PCR (qPCR) and Western blotting methods, respectively. Results: Intracerebroventricular injection of composited Aβ could produce the rats’ memory impairment, decrease the protein expression of Ki67 in the hippocampal gyrus, and increase the mRNA and protein expression levels of Grb2, SOS1, Ras, ERK and BDNF in the hippocampus and cerebral cortex. However, SSF could significantly ameliorate the rats’ memory impairment, lower the reduction of Ki67 protein expression in the hippocampal gyrus and regulate the mRNA and protein expression abnormal levels of Grb2, SOS1, Ras, ERK and BDNF in the hippocampus and cerebral cortex induced by composited Aβ. Conclusion: Composited Aβ can result in memory impairment, decrease neurogenesis and regulate the mRNA and protein abnormal expression of Grb2, SOS1, Ras, ERK and BDNF in BDNF-ERK-CREB signaling pathway. The effects of SSF in promoting neurogenesis and improving memory impairment may be related to the regulation in Grb2, SOS1, Ras, ERK and BDNF molecules’ expression of the BDNF-ERK-CREB signaling pathway.

Effect of Scutellaria Baicalensis Georgi Stems and Leaves Flavonoids on Multisite Phosphorylation of tau Protein Induced by Composited Aβ in Rats

International Journal of Medicinal Plants and Natural Products ◽

10.20431/2454-7999.0604001 ◽

2020 ◽

Vol 6 (4) ◽

Keyword(s):

Tau Protein ◽

Scutellaria Baicalensis ◽

Multisite Phosphorylation ◽

The Protecting Effects and Mechanisms of Baicalin and Octreotide on Heart Injury in Rats with SAP

Mediators of Inflammation ◽

10.1155/2007/19469 ◽

2007 ◽

Vol 2007 ◽

pp. 1-11 ◽

Cited By ~ 12

Author(s):

Zhang Xiping ◽

Tian Hua ◽

Chen Hanqing ◽

Chen Li ◽

Wang Zhiwei ◽

...

Keyword(s):

Protein Expression ◽

Caspase 3 ◽

Treated Group ◽

Myocardial Cell ◽

Sham Operation ◽

Model Group ◽

Expression Levels ◽

Sham Operation Group ◽

Heart Injury ◽

Operation Group

Purpose.To observe the protecting effects and mechanisms of Baicalin and Octreotide on heart injury in rats with severe acute pancreatitis (SAP).Methods.The SAP rat models were randomly divided into the model group, Baicalin-treated group, Octreotide treated group, and sham operation group. The contents of some inflammatory indexes in blood were determined. The rat mortality, pathological changes of heart, the changes ofNF-κB, P-Selectin, Bax, Bcl-2, and Caspase-3 protein expression levels as well as apoptotic index were observed in all groups, respectively, at 3 hours, 6 hours, and 12 hours after operation.Results.The survival rate of model group was less than treated groups at 12 hours, difference was significant. The contents of some inflammatory indexes of the treated groups were lower than those of the model group to various degrees at different time points. The pathological myocardial changes under light microscope were milder in treated groups than in model group. The changes ofNF-κB, P-Selectin, Bax, Bcl-2, and Caspase-3 protein expression levels in all groups were different. There was only a case of myocardial cell apoptosis in an Octreotide-treated group at 6 hours.Conclusion.Baicalin and Octreotide have protecting effects on heart injury of rats with SAP.

Okadaic Acid Induces the Rats’ Memory Impairment and Tau Protein Hyperphosphorylation And Intervened by Flavonoids from Stem and Leaf of Scutellaria Baicalensis Georgi

Biomedical Journal of Scientific & Technical Research ◽

10.26717/bjstr.2018.09.001842 ◽

2018 ◽

Vol 9 (4) ◽

Author(s):

Shang Yazhen

Keyword(s):

Okadaic Acid ◽

Tau Protein ◽

Memory Impairment ◽

Scutellaria Baicalensis ◽

Scutellaria Baicalensis Georgi

Yiqi Dingxuan Yin improves cerebral ischaemic injury in rats by inhibiting apoptosis and promoting angiogenesis

10.21203/rs.3.rs-885692/v1 ◽

2021 ◽

Author(s):

Fei Liu ◽

Liuyang Xie ◽

Chunhua Liu ◽

Guilian He ◽

Chunyun Yuan ◽

...

Keyword(s):

Protein Expression ◽

Cerebral Ischaemia ◽

Neurological Function ◽

Neural Function ◽

Sham Operation ◽

Nerve Function ◽

Model Group ◽

Expression Levels ◽

Sham Operation Group ◽

Operation Group

Abstract Background Clinically, Yiqi Dingxuan Yin promotes nerve function recovery and improves nerve function defect symptoms; however, the underlying molecular pathways remain unknown. In this study, we established a rat model of cerebral ischaemia induced by middle cerebral artery occlusion (MCAO). The effects of Yiqi Dingxuan Yin on the neurological function and local neuron morphology were compared with those of butylphthalide, which is used to treat ischemic stroke, and the possible mechanisms of action were explored. Methods Of 97 healthy adult male Sprague‒Dawley rats, 20 were randomly assigned to the sham operation group. The remaining rats underwent MCAO. Model generation was successful in 60 rats, which were randomly divided into a model group, butylphthalide group, and Yiqi Dingxuan Yin group (n = 20/group) administered distilled water, butylphthalide capsule, and Yiqi Dingxuan Yin, respectively. Zea-Longa scores were used to assess the neurological function of the rats at 1, 3, 7, and 14 days. Haematoxylin and eosin staining of brain sections was used to observe morphological changes in the rat hippocampus. Apoptosis of nerve cells was detected using TUNEL staining. The expression levels of erythropoietin/erythropoietin receptor (EPO/EPOR), vascular endothelial growth factor (VEGF), and brain-derived neurotrophic factor/tyrosine receptor kinase B (BDNF/TrkB) protein in the ischaemic brain tissue were detected using immunohistochemistry. Results The apoptosis rate, and EPO/EPOR, VEGF, and BDNF/TrkB expression levels were higher in the model group than in the sham operation group (P < 0.05). Among MCAO groups, the nerve function deficit score and cell apoptosis rate were lower (P < 0.05), whereas the EPO/EPOR, VEGF, and BDNF/TrkB protein expression levels were higher (P < 0.05) in both the butylphthalide and Yiqi Dingxuan Yin groups than in the model group. Conclusions Yiqi Dingxuan Yin can improve the neural function and morphology of neurons after cerebral ischaemia injury in rats, with a more significant effect at 14 days. This may be related to the upregulation of EPO/EPOR, VEGF, and BDNF/TrkB protein expression, which may promote angiogenesis to improve cerebral blood flow and oxygen supply, thereby protecting the form and function of neurons and promoting the restoration of impaired neural function.

Mechanisms underlying attenuation of apoptosis of cortical neurons in the hypoxic brain by flavonoids from the stems and leaves of Scutellaria baicalensis Georgi

Neural Regeneration Research ◽

10.4103/1673-5374.141784 ◽

2014 ◽

Vol 9 (17) ◽

pp. 1592 ◽

Cited By ~ 10

Author(s):

Yazhen Shang ◽

Guangxin Miao ◽

Hongxiang Zhao ◽

Ke Guo ◽

Jianjun Cheng ◽

...

Keyword(s):

Cortical Neurons ◽

Scutellaria Baicalensis ◽

Hypoxic Brain ◽

Identification of flavonoids in the stems and leaves of Scutellaria baicalensis Georgi

Journal of Chromatography B ◽

10.1016/j.jchromb.2011.02.050 ◽

2011 ◽

Vol 879 (13-14) ◽

pp. 1023-1028 ◽

Cited By ~ 48

Author(s):

Guozhu Liu ◽

Nautiyal Rajesh ◽

Xiaosong Wang ◽

Mingshan Zhang ◽

Qin Wu ◽

...

Keyword(s):

Scutellaria Baicalensis ◽

Changes in Expressions of HSP27, HSP70 and Soluble Glycoprotein in Heart Failure Rats Complicated with Pulmonary Edema and Correlations with Cardiopulmonary Functions Running title: Expressions of HSP27, HSP70 and Soluble Glycoprotein in Heart Failure

Tobacco Regulatory Science ◽

10.18001/trs.7.5.1.206 ◽

2021 ◽

Vol 7 (5) ◽

pp. 4286-4295

Author(s):

Yan Tan ◽

Bo Gao ◽

Dongming Gu ◽

Shuyun Wang ◽

Zhinua Wang

Keyword(s):

Heart Failure ◽

Protein Expression ◽

Pulmonary Edema ◽

Airway Resistance ◽

Lung Compliance ◽

Left Ventricular ◽

Normal Group ◽

Model Group ◽

Expression Levels ◽

Gene And Protein Expression

Objective: The study aimed to investigate the changes in expressions of heat shock protein 27 (HSP27), HSP70 and soluble glycoprotein (SGP) in heart failure (HF) rats complicated with pulmonary edema, and explore their potential correlations with cardiopulmonary functions. Methods: The rat model of HF was established, and the rats were divided into HF model group (model group, n=15) and normal group (n=15). After successful modeling, MRI and ECG were applied to detect the cardiac function indexes of the rats. The myocardial function indexes were determined, the injury of myocardial tissues was observed via hematoxylin and eosin (HE) staining, and the content of myeloperoxidase (MPO), matrix metalloproteinase-9 (MMP-9) and tumor necrosis factor-alpha (TNF-a) in the blood was measured. The partial pressure of oxygen (Pa02) and oxygenation index (01) were observed, and the airway resistance and lung compliance were examined. Moreover, quantitative polymerase chain reaction (qPCR) and Western blotting assay were performed to detect the gene and protein expression levels of HSP27, HSP70 and SGP130. Results: The levels of serum creatine kinase (CK), creatine (Cr) and blood urea nitrogen (BUN) were increased markedly in model group (p<0.05). Model group had notably decreased fractional shortening (FS) and ejection fraction (EF) compared with normal group (p<0.05), while the opposite results of left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) were detected. In model group, the content of serum MPO, MMP-9 and TNF-a was raised remarkably (p<0.05), 01 and Pa02were reduced notably (p<0.05), the airway resistance was increased (p<0.05), and the lung compliance was decreased (p<0.05). Obviously elevated gene and protein expression levels of HSP27, HSP70 and SGP130 were detected in model group (p<0.05). Conclusion: The expressions of HSP27, HSP70 and SGP130 are increased in HF rats complicated with pulmonary edema, seriously affecting the cardiopulmonary functions of the rats.