Danggui-Shaoyao-San (DSS) ameliorating cognitive impairment in ischemia–reperfusion vascular dementia mice through miR-124 regulating PI3K/Akt signaling pathway

Article

Author: Qin, Yuyun ; Wang, Qi ; Ye, Xinyi ; Lin, Chaozhan ; Liu, Meng ; Liu, Xian ; Chen, Xiaotong ; Zhao, Wei ; Jiang, Qiyao ; Yao, Liwei ; Li, Weirong ; Chen, Shuyun ; Zhu, Chenchen

Vascular dementia (VD) is a disease characterized by cognitive impairment and memory loss due to brain cell damage caused by cerebral vascular ischemia. Danggui-Shaoyao-San (DSS) has been used clinically to treat diseases for centuries. The VD model was established by bilateral common carotid artery (BCCA) repeated ischemia-reperfusion (I/R) and caudal bleeding. Target prediction of DSS and miR-124 in PI3K/Akt signaling pathway by network pharmacology. The effect of DSS on cognitive dysfunction were evaluated through methods such as behavioral experiments, cerebral blood flow monitoring, HE and Nissl staining, western blot, and q-PCR. Prediction result showed that both DSS and miR-124 could target Akt1. DSS treatment significantly reduced hippocampal cell damage, improved learning and memory ability. Mechanically, DSS treatment up-regulated the expression levels of PI3K and Akt protein, and its gene. Bcl-2/Bax index is up-regulated and cell apoptosis reduced. LC3II/LC3I index decreased and autophagy of brain cells increased. Moreover, DSS down-regulated the expression level of miR-124. And inhibition of miR-124 up-regulate the expression of PI3K, Akt. These results suggested that DSS can reduce the content of miR-124 in the hippocampus of VD mice, thus regulating the PI3K/Akt signaling pathway and improving the learning and memory ability of VD mice.

01 Nov 2024·Brain and Behavior

Correlation Between Regulation of Intestinal Flora by Danggui‐Shaoyao‐San and Improvement of Cognitive Impairment in Mice With Alzheimer's Disease

Article

Author: Wang, Ya‐Han ; Xu, Xiang‐Qing ; Ding, Peng‐Li ; Zhang, Kai‐Xin ; Li, He

ABSTRACTPurposeThe abnormal central glucose metabolism in Alzheimer's disease (AD) is related to the brain–gut axis. This study aims to explore the target of Danggui‐Shaoyao‐San (DSS) in improving cognitive impairment.MethodThis study analyzed the differences in mice intestinal flora by 16S rRNA sequencing. The cognitive protective effects of DSS were observed through the Morris water maze and the new object recognition. The mitigation effects of DSS on Aβ and p‐tau, regulatory effects on glucose metabolism targets, and intestinal structure effects were observed through brain and colon slices staining. The differences in neural ultrastructure were compared by transmission electron microscopy.FindingThe results showed that DSS affected the composition of intestinal dominant bacteria and bacteria genera and regulated the abundance of intestinal bacteria in AD mice. DSS improved the behavior of AD mice, alleviated the deposition of AD pathological products in the brain and colon, regulated the expression of glycometabolism‐related proteins, and improved the colon barrier structure and neural ultrastructure in the brain of mice with AD.ConclusionOur findings suggest that DSS may affect AD central glucose metabolism and improve cognition by regulating the gut–brain axis.

01 Oct 2024·Brain and Behavior

Danggui Shaoyao San Alleviates Early Cognitive Impairment in Alzheimer's Disease Mice Through IRS1/GSK3β/Wnt3a‐β‐Catenin Pathway

Article

Author: Xu, Xiang‐Qing ; Zhang, Ji‐Wei ; Zhang, Kai‐Xin ; Ding, Peng‐Li ; Wang, Ya‐Han ; Sheng, Ning

ABSTRACTIntroductionAlzheimer's disease (AD) is a neurodegenerative disease characterized by Amyloid plaques and neurofibrillary tangles. We explored the potential mechanism by which Danggui Shaoyao San (DSS) modulates central glucose metabolism via the insulin receptor substrate 1 (IRS1)/glycogen synthase kinase‐3β (GSK3β)/Wnt3a‐β‐catenin pathway, thereby exerting protective effects on cognitive functions.MethodsIn vitro, HT22 cells were induced with streptozotocin (STZ) to investigate the impact of GSK3β on pathway transduction. The active components in the DSS stock solution were validated using mass spectrometry. Subsequently, an AD model in C57BL/6J mice was established through STZ injection into both ventricles. The success of the model was validated behaviorally and pathologically. The Morris Water Maze (MWM) test, immunohistochemistry, Western blotting, quantitative reverse transcription‐PCR, and 18F‐fluorodeoxyglucose‐positron emission tomography (FDG‐PET) were employed to evaluate the influence of DSS on memory and pathological changes in AD.ResultsThe DSS stock solution, rich in active components, ameliorated the memory deficits in AD mice in the MWM. In vitro, GSK3β exhibited regulatory control over Wnt and β‐catenin, with GSK3β inhibition mitigating β‐amyloid and tau redundancies at protein and gene levels, facilitating signal transduction. In vivo, DSS impacted key targets in the IRS1/GSK3β/Wnt3a‐β‐catenin pathway, mitigated senile plaques resulting from amyloid β (Aβ) deposition and neurofiber tangles induced by tau hyperphosphorylation, and alleviated the decline in central glucose metabolism observed in FDG‐PET.ConclusionsOur findings suggest that DSS potentially confers cognitive protection by alleviating central hypoglycemia through the IRS1/GSK3β/Wnt3a‐β‐catenin pathway. This may serve as a promising therapeutic avenue for AD.

100 Deals associated with Danggui Shaoyao Granules Jia Fuzi

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Indication	Country/Location	Organization	Date
Abdominal Pain	JP	Sanwa Shoyaku Co., Ltd.	18 Jul 1986
Andropause	JP	Sanwa Shoyaku Co., Ltd.	18 Jul 1986
Dysmenorrhea	JP	Sanwa Shoyaku Co., Ltd.	18 Jul 1986
Headache	JP	Sanwa Shoyaku Co., Ltd.	18 Jul 1986
Hemorrhoids	JP	Sanwa Shoyaku Co., Ltd.	18 Jul 1986
Nephritis	JP	Sanwa Shoyaku Co., Ltd.	18 Jul 1986
Neuralgia	JP	Sanwa Shoyaku Co., Ltd.	18 Jul 1986
Pollakisuria	JP	Sanwa Shoyaku Co., Ltd.	18 Jul 1986
postpartum complications	JP	Sanwa Shoyaku Co., Ltd.	18 Jul 1986
Pregnancy Complications	JP	Sanwa Shoyaku Co., Ltd.	18 Jul 1986

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