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Article: Xiao-Xu-Ming

Wang, Yue-Hua / Yang, Ying-Lin / Cheng, Xiao / Zhang, Jun / Li, Wan / Du, Guan-Hua

2018 Volume 14, Issue 3, Page(s) 470–479

Abstract: Xiao-Xu-Ming decoction has been widely used to treat stroke and sequelae of stroke. We have ... previously shown that the active fractions of Xiao-Xu-Ming decoction attenuate cerebral ischemic injury ... However, the global protein profile and signaling conduction pathways regulated by Xiao-Xu-Ming decoction are still ...

Abstract	Xiao-Xu-Ming decoction has been widely used to treat stroke and sequelae of stroke. We have previously shown that the active fractions of Xiao-Xu-Ming decoction attenuate cerebral ischemic injury. However, the global protein profile and signaling conduction pathways regulated by Xiao-Xu-Ming decoction are still unclear. This study established a two-vessel occlusion rat model by bilateral common carotid artery occlusion. Rats were intragastrically administered 50 or 150 mg/kg Xiao-Xu-Ming decoction for 4 consecutive weeks. Learning and memory abilities were measured with Morris water maze. Motor ability was detected with prehensile test. Coordination ability was examined using the inclined screen test. Neuronal plasticity was observed by immunofluorescent staining. Differentially expressed proteins of rat hippocampus were analyzed by label-free quantitative proteomics. Real time-polymerase chain reaction and western blot assay were used to identify the changes in proteins. Results showed that Xiao-Xu-Ming decoction dramatically alleviated learning and memory deficits, and motor and coordination dysfunction, and increased the expression of microtubule-associated protein 2. Xiao-Xu-Ming decoction extract remarkably decreased 13 upregulated proteins and increased 39 downregulated proteins. The regulated proteins were mainly involved in oxidation reduction process, intracellular signaling cascade process, and protein catabolic process. The signaling pathways were mainly involved in ubiquitin mediated proteolysis and the phosphatidylinositol signaling system. Furthermore, there was an interaction among Rab2a, Ptpn1, Ppm1e, Cdk18, Gorasp2, Eps15, Capza2, Syngap1 and Mt-nd1. Protein analyses confirmed the changes in expression of MT-ND1. The current findings provide new insights into the molecular mechanisms of Xiao-Xu-Ming decoction extract's effects on chronic cerebral hypoperfusion.
Language	English
Publishing date	2018-12-14
Publishing country	India
Document type	Journal Article
ZDB-ID	2388460-5
ISSN	1876-7958 ; 1673-5374
ISSN (online)	1876-7958
ISSN	1673-5374
DOI	10.4103/1673-5374.245471
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Metabolomics-based study of the potential interventional effects of Xiao-Xu-Ming Decoction on cerebral ischemia/reperfusion rats.

Wu, Ziqian / Qian, Shiyan / Zhao, Liangcai / Zhang, Zaiheng / Song, Chengcheng / Chen, Ling / Gao, Hongchang / Zhu, Wenzong

Journal of ethnopharmacology

2022 Volume 295, Page(s) 115379

Abstract: Ethnopharmacological relevance: Xiao-Xu-Ming Decoction (XXMD) is a classical Chinese medicinal ...

Abstract	Ethnopharmacological relevance: Xiao-Xu-Ming Decoction (XXMD) is a classical Chinese medicinal compound for the treatment of ischemic stroke, which has good efficacy in clinical studies and also plays a neuroprotective role in pharmacological studies. Aim of the study: The purpose of this study is to investigate the potential and integral interventional effects of XXMD on cerebral ischemia/reperfusion rat model. Materials and methods: In this study, Results: It's observed that XXMD treatment could improve the neurological deficit scores and reduce the cerebral infarct areas on cerebral ischemia/reperfusion rat model. The pathological staining results performed that XXMD treatment could improve the decrease of Nissl bodies and the expression of NeuN and MCT2, reduce the high expression of TUNEL. In Conclusion: Our findings indicated that XXMD has positive effect on neuroprotection and improvement of metabolism targeting cerebral ischemic injury in rats, which showed great potential for ischemic stroke.
MeSH term(s)	Animals ; Brain Ischemia/drug therapy ; Brain Ischemia/metabolism ; Cerebral Infarction/drug therapy ; Drugs, Chinese Herbal ; Ischemia/drug therapy ; Ischemic Stroke ; Metabolomics ; Neuroprotective Agents/pharmacology ; Neuroprotective Agents/therapeutic use ; Rats ; Reperfusion ; Reperfusion Injury/metabolism
Chemical Substances	Drugs, Chinese Herbal ; Neuroprotective Agents ; xiao-xu-ming
Language	English
Publishing date	2022-05-18
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	134511-4
ISSN	1872-7573 ; 0378-8741
ISSN (online)	1872-7573
ISSN	0378-8741
DOI	10.1016/j.jep.2022.115379
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Article ; Online: Xiao-Xu-Ming decoction extracts promotes mitochondrial biogenesis and improves neurobehavioral deficits in cerebral ischemia/reperfusion rats

Xiao Cheng / Ying-Lin Yang / Wei-Han Li / Man Liu / Shan-Shan Zhang / Dong-Ni Liu / Li-Da Du / Yue-Hua Wang / Guan-Hua Du

Pharmacological Research - Modern Chinese Medicine, Vol 5, Iss , Pp 100192- (2022)

2022

Abstract: ... Traditional Chinese medicine plays an important role in preventing and treatment of stroke. Xiao-Xu-Ming decoction (XXM) is ...

Abstract	Introduction: Stroke is one of the leading causes of death and disability in the worldwide. Traditional Chinese medicine plays an important role in preventing and treatment of stroke. Xiao-Xu-Ming decoction (XXM) is an effective traditional Chinese prescription for the treatment of stroke and its sequelae. Previous studies have reported the extracts of XXM has a good therapeutic effect on experimental animal stroke. However, the mechanism is unclear. Our present study focused on metabolic remodeling in cerebral ischemia-reperfusion to investigate the mechanism of XXM on cerebral ischemia/reperfusion (I/R). Methods: The cerebral I/R rat model was established by 90 min middle cerebral artery occlusion following reperfusion. XXM at doses of 37.5, 75 and 150 mg/kg was administered for the continuous 7 day after cerebral I/R. Behavioral testing, cerebral infarction detected by TTC staining, Nissl staining, NeuN immunohistochemical staining, and MAP2 immunofluorescence staining were conducted to evaluate the effect of XXM treatment on cerebral I/R of rats. TUNEL staining was used to detect DNA damage. The expression of related proteins was detected by qPCR and western blotting. Results: 7 day XXM treatment improved neurological and behavioral deficits, regulated the biogenesis and dynamic process of mitochondria, promoted the recovery of mitochondrial function, and improved the energy metabolism disorder after cerebral I/R. Furthermore, XXM also had an improving effect on mitochondrial-dependent apoptosis after cerebral I/R. Conclusion: we found that XXM regulated metabolic remodeling in cerebral ischemia-reperfusion and improve neurological deficits.
Keywords	Xiao-Xu-Ming decoction ; Cerebral Ischemia ; Metabolic remodeling ; Mitochondrial function ; Apoptosis ; Other systems of medicine ; RZ201-999 ; Therapeutics. Pharmacology ; RM1-950
Subject code	610
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Metabolomics-based study of the potential interventional effects of Xiao-Xu-Ming Decoction on cerebral ischemia/reperfusion rats

Wu, Ziqian / Qian, Shiyan / Zhao, Liangcai / Zhang, Zaiheng / Song, Chengcheng / Chen, Ling / Gao, Hongchang / Zhu, Wenzong

Journal of ethnopharmacology. 2022 Sept. 15, v. 295

2022

Abstract: Xiao-Xu-Ming Decoction (XXMD) is a classical Chinese medicinal compound for the treatment ...

Abstract	Xiao-Xu-Ming Decoction (XXMD) is a classical Chinese medicinal compound for the treatment of ischemic stroke, which has good efficacy in clinical studies and also plays a neuroprotective role in pharmacological studies. The purpose of this study is to investigate the potential and integral interventional effects of XXMD on cerebral ischemia/reperfusion rat model. In this study, ¹H NMR metabolomics was used, combined with neurological functional assessments, cerebral infarct area measurements, and pathological staining including Nissl staining, immunofluorescence staining of NeuN and TUNEL, and immunohistochemical staining of MCT2, to analyze the metabolic effects of XXMD in the treatment of an ischemia/reperfusion rat model. It's observed that XXMD treatment could improve the neurological deficit scores and reduce the cerebral infarct areas on cerebral ischemia/reperfusion rat model. The pathological staining results performed that XXMD treatment could improve the decrease of Nissl bodies and the expression of NeuN and MCT2, reduce the high expression of TUNEL. In ¹H NMR study, it revealed that the metabolic patterns among three experimental groups were different, the level of lactate, acetate, NAA, glutamate, and GABA were improved to varying degrees in different brain area. Our findings indicated that XXMD has positive effect on neuroprotection and improvement of metabolism targeting cerebral ischemic injury in rats, which showed great potential for ischemic stroke.
Keywords	acetates ; animal models ; brain ; fluorescent antibody technique ; glutamic acid ; immunohistochemistry ; infarction ; ischemia ; lactic acid ; metabolism ; metabolomics ; neuroprotective effect ; traditional medicine
Language	English
Dates of publication	2022-0915
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	134511-4
ISSN	1872-7573 ; 0378-8741
ISSN (online)	1872-7573
ISSN	0378-8741
DOI	10.1016/j.jep.2022.115379
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Article: Network Pharmacology-Based Analysis of Xiao-Xu-Ming Decoction on the Treatment of Alzheimer's Disease.

Shen, Yanjia / Zhang, Baoyue / Pang, Xiaocong / Yang, Ran / Chen, Miao / Zhao, Jiaying / Wang, Jinhua / Wang, Zhe / Yu, Ziru / Wang, Yuehua / Li, Li / Liu, Ailin / Du, Guanhua

Frontiers in pharmacology

2020 Volume 11, Page(s) 595254

Abstract: ... a heavy economic burden to healthcare system. Xiao-Xu-Ming Decoction (XXMD) has been widely used to treat ...

Abstract	Alzheimer's disease (AD) has become a worldwide disease that is harmful to human health and brings a heavy economic burden to healthcare system. Xiao-Xu-Ming Decoction (XXMD) has been widely used to treat stroke and other neurological diseases for more than 1000 years in China. However, the synergistic mechanism of the constituents in XXMD for the potential treatment of AD is still unclear. Therefore, the present study aimed to predict the potential targets and uncover the material basis of XXMD for the potential treatment of AD. A network pharmacology-based method, which combined data collection, drug-likeness filtering and absorption, distribution, metabolism, excretion and toxicity (ADME/T) properties filtering, target prediction and network analysis, was used to decipher the effect and potential targets of XXMD for the treatment of AD. Then, the acetylcholinesterase (AChE) inhibitory assay was used to screen the potential active constituents in XXMD for the treatment of AD, and the molecular docking was furtherly used to identify the binding ability of active constituents with AD-related target of AChE. Finally, three
Language	English
Publishing date	2020-12-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2020.595254
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Article: Perturbed Lipidomic Profiles in Rats With Chronic Cerebral Ischemia Are Regulated by Xiao-Xu-Ming Decoction.

Jia, Zhixin / Tie, Cai / Wang, Caihong / Wu, Caisheng / Zhang, Jinlan

Frontiers in pharmacology

2019 Volume 10, Page(s) 264

Abstract: ... occlusion of rat bilateral common carotid arteries, and then the rats were treated with a Xiao-Xu-Ming ...

Abstract	Chronic cerebral ischemia (CCI) is a serious human health condition with lacking therapeutic agents. Moreover, its mechanism of action remains elusive, and thus novel treatment options are required. Lipid metabolism disorder are closely related to CCI. In this study, a CCI-rats model was established by the permanent occlusion of rat bilateral common carotid arteries, and then the rats were treated with a Xiao-Xu-Ming decoction (XXMD). Lipidomic profiling was conducted in both plasma and brain o determine the effects of the injury and therapy on lipid metabolism. Sphingolipid (particularly long acyl chain and total ceramides), glyceryl phosphatide, and glyceride profiles significantly changed in the brain after model induction and again after dosing. A total of 35 potential biomarkers were found in the brain and four were found in the plasma, representing both CCI injury and XXMD action. Correlations between endogenous lipids and exogenous XXMD compounds were analyzed using linear regression. Two exogenous compounds (cimifugin and 5-
Language	English
Publishing date	2019-03-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2019.00264
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Article ; Online: Xiao-Xu-Ming Decoction Reduced Mitophagy Activation and Improved Mitochondrial Function in Cerebral Ischemia and Reperfusion Injury.

Lan, Rui / Zhang, Yong / Wu, Tao / Ma, Yun-Zhi / Wang, Bao-Qi / Zheng, Hai-Zhong / Li, Ya-Na / Wang, Yan / Gu, Chun-Qing / Wu, Ji-Tao

Behavioural neurology

2018 Volume 2018, Page(s) 4147502

Abstract: We investigated whether Xiao-Xu-Ming decoction reduced mitophagy activation and kept mitochondrial ...

Abstract	We investigated whether Xiao-Xu-Ming decoction reduced mitophagy activation and kept mitochondrial function in cerebral ischemia-reperfusion injury. Rats were randomly divided into 5 groups: sham, ischemia and reperfusion (IR), IR plus XXMD (60 g/kg/day) (XXMD60), IR plus cyclosporin A (10 mg/kg/day) (CsA), and IR plus vehicle (Vehicle). Focal cerebral ischemia and reperfusion models were induced by middle cerebral artery occlusion (MCAO). Cerebral infarct areas were measured by triphenyl tetrazolium chloride staining. Cerebral ischemic injury was evaluated by hematoxylin and eosin staining (HE) and Nissl staining. Ultrastructural features of mitochondria and mitophagy in the penumbra of the ischemic cortex were observed by transmission electron microscopy. Mitophagy was detected by immunofluorescence labeled with LC3B and VDAC1. Autophagy lysosome formation was observed by immunofluorescence labeled with LC3B and Lamp1. The expression of LC3B, Beclin1, and Lamp1 was analyzed by Western blot. The rats subjected to MCAO showed worsened neurological score and cell ischemic damage. These were all significantly reversed by XXMD or CsA. Moreover, XXMD/CsA notably downregulated mitophagy and reduced the increase in LC3, Beclin1, and Lamp1 expression induced by cerebral ischemia and reperfusion. The findings demonstrated that XXMD exerted neuroprotective effect via downregulating LC3, Beclin1, Lamp1, and mitochondrial p62 expression level, thus leading to the inhibition of mitophagy.
MeSH term(s)	Animals ; Apoptosis/drug effects ; Brain Ischemia/drug therapy ; Disease Models, Animal ; Drugs, Chinese Herbal/pharmacology ; Male ; Medicine, Chinese Traditional ; Mitochondria/drug effects ; Mitochondrial Degradation/drug effects ; Neuroprotective Agents/pharmacology ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury/drug therapy
Chemical Substances	Drugs, Chinese Herbal ; Neuroprotective Agents ; xiao-xu-ming
Language	English
Publishing date	2018-06-19
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1001896-7
ISSN	1875-8584 ; 0953-4180
ISSN (online)	1875-8584
ISSN	0953-4180
DOI	10.1155/2018/4147502
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Article ; Online: Pharmacokinetics of 21 active components in focal cerebral ischemic rats after oral administration of the active fraction of Xiao-Xu-Ming decoction.

Wang, Caihong / Jia, Zhixin / Wang, Zhe / Hu, Ting / Qin, Hailin / Du, Guanhua / Wu, Caisheng / Zhang, Jinlan

Journal of pharmaceutical and biomedical analysis

2016 Volume 122, Page(s) 110–117

Abstract: The Xiao-Xu-Ming decoction (XXMD) is a traditional Chinese medicine prescription that is clinically ...

Abstract	The Xiao-Xu-Ming decoction (XXMD) is a traditional Chinese medicine prescription that is clinically used for the treatment of stroke. The active fraction of XXMD (AF-XXMD) exhibits pharmacological effects that are similar to those of XXMD. In this study, 21 primary compounds of AF-XXMD with potential anti-ischemic-stroke activities were selected as effective candidates to perform comparisons of their pharmacokinetic differences between control and cerebral ischemic rats and to characterize their pharmacokinetic behaviors in cerebral ischemic rats. After oral administration of AF-XXMD to control and cerebral ischemic rats, plasma and brain were harvested and analyzed using liquid chromatography coupled with tandem mass spectrometry. Reverse molecular docking results indicate that 21 AF-XXMD-derived compounds exert potential neuroprotection, anti- inflammation, and vascular dilation effects via interaction with multiple targets in stroke-related pathways. The blood-brain permeability, cerebral exposure and brain region distribution of these compounds were found to change in cerebral ischemic models. Flavonoids were identified as the predominant form in plasma, whereas chromones were found to be the major form in the brain, and alkaloids possessed moderate blood-brain permeability. Collectively, the cerebral pharmacokinetic behaviors of chromones, flavonoids and alkaloids were found to change under pathological conditions. The efficacy of AF-XXMD against cerebral ischemia is relevant to the synergistic effects of these compounds in targeting different receptors and pathways. Chromones exhibit relatively high brain permeability, and their activity and mechanism warrant further investigation.
MeSH term(s)	Administration, Oral ; Alkaloids/pharmacokinetics ; Alkaloids/pharmacology ; Animals ; Blood-Brain Barrier/metabolism ; Brain/drug effects ; Brain/metabolism ; Brain Ischemia/drug therapy ; Brain Ischemia/metabolism ; Chromatography, High Pressure Liquid/methods ; Drugs, Chinese Herbal/pharmacokinetics ; Drugs, Chinese Herbal/pharmacology ; Flavonoids/pharmacokinetics ; Flavonoids/pharmacology ; Male ; Medicine, Chinese Traditional/methods ; Permeability ; Rats ; Rats, Wistar ; Stroke/drug therapy ; Tandem Mass Spectrometry/methods
Chemical Substances	Alkaloids ; Drugs, Chinese Herbal ; Flavonoids ; xiao-xu-ming
Language	English
Publishing date	2016-04-15
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604917-5
ISSN	1873-264X ; 0731-7085
ISSN (online)	1873-264X
ISSN	0731-7085
DOI	10.1016/j.jpba.2016.01.052
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Article ; Online: Xiao-Xu-Ming decoction preserves mitochondrial integrity and reduces apoptosis after focal cerebral ischemia and reperfusion via the mitochondrial p53 pathway.

Lan, Rui / Zhang, Yong / Xiang, Jun / Zhang, Wen / Wang, Guo-Hua / Li, Wen-Wei / Xu, Li-Li / Cai, Ding-Fang

Journal of ethnopharmacology

2014 Volume 151, Issue 1, Page(s) 307–316

Abstract: Ethnopharmacological relevance: Xiao-Xu-Ming decoction (XXMD) has been used to treat stroke and ...

Abstract	Ethnopharmacological relevance: Xiao-Xu-Ming decoction (XXMD) has been used to treat stroke and other neurological diseases for more than 1000 years. The purpose of this study was to investigate the effects of XXMD on mitochondrial damage and apoptosis after cerebral ischemia and reperfusion. Materials and methods: Male Sprague-Dawley rats were randomly divided into 3 groups: sham, cerebral ischemia and reperfusion (I/R), and cerebral ischemia and reperfusion plus XXMD (60 g/kg/day) (XXMD60). Focal cerebral ischemia and reperfusion models were induced by middle cerebral artery occlusion. Cerebral ischemic injury was evaluated by hematoxylin and eosin staining. Ultrastructural features of mitochondria in the penumbra of the ischemic cortex were analyzed by transmission electron microscopy. Apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick end labeling (TUNEL) staining and cleaved caspase 3 immunohistochemistry. Proteins in the mitochondrial p53 pathway were detected by western blot and immunofluorescence. Results: The results showed that XXMD treatment markedly attenuated ischemic changes, preserved mitochondrial integrity, and significantly reduced apoptosis. In addition, we found that XXMD treatment reduced p53 and Bax levels and increased Bcl-2 levels in mitochondrial fractions. XXMD significantly blocked the release of cytochrome c and Smac/Diablo from mitochondria, and inhibited activation of caspase 9 and caspase 3 in cytoplasmic fractions. Increased expression of c-IAP1 was observed in the XXMD60 group. Conclusions: The findings demonstrated that XXMD protected mitochondria from ischemic injury and inhibited apoptosis. The mitochondrial p53 pathway could be partially involved in the protective effects.
MeSH term(s)	Animals ; Apoptosis/drug effects ; Brain Ischemia/pathology ; Drugs, Chinese Herbal/pharmacology ; Gene Expression Regulation/drug effects ; Male ; Mitochondria/drug effects ; Mitochondria/metabolism ; Mitochondria/ultrastructure ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury/prevention & control ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism
Chemical Substances	Drugs, Chinese Herbal ; Tumor Suppressor Protein p53 ; xiao-xu-ming
Language	English
Publishing date	2014
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	134511-4
ISSN	1872-7573 ; 0378-8741
ISSN (online)	1872-7573
ISSN	0378-8741
DOI	10.1016/j.jep.2013.10.042
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Article: PI3K/Akt Pathway Contributes to Neurovascular Unit Protection of Xiao-Xu-Ming Decoction against Focal Cerebral Ischemia and Reperfusion Injury in Rats.

Lan, Rui / Xiang, Jun / Zhang, Yong / Wang, Guo-Hua / Bao, Jie / Li, Wen-Wei / Zhang, Wen / Xu, Li-Li / Cai, Ding-Fang

Evidence-based complementary and alternative medicine : eCAM

2013 Volume 2013, Page(s) 459467

Abstract: ... the protective effects of Xiao-Xu-Ming decoction (XXMD) on neurovascular unit and to examine the role of PI3K ...

Abstract	In the present study, we used a focal cerebral ischemia and reperfusion rat model to investigate the protective effects of Xiao-Xu-Ming decoction (XXMD) on neurovascular unit and to examine the role of PI3K (phosphatidylinositol 3-kinase)/Akt pathway in this protection. The cerebral ischemia was induced by 90 min of middle cerebral artery occlusion. Cerebral infarct area was measured by tetrazolium staining, and neurological function was observed at 24 h after reperfusion. DNA fragmentation assay, combined with immunofluorescence, was performed to evaluate apoptosis of neuron, astrocyte, and vascular endothelial cell which constitute neurovascular unit. The expression levels of proteins involved in PI3K/Akt pathway were detected by Western blot. The results showed that XXMD improved neurological function, decreased cerebral infarct area and neuronal damage, and attenuated cellular apoptosis in neurovascular unit, while these effects were abolished by inhibition of PI3K/Akt with LY294002. We also found that XXMD upregulated p-PDKl, p-Akt, and p-GSK3 β expression levels, which were partly reversed by LY294002. In addition, the increases of p-PTEN and p-c-Raf expression levels on which LY294002 had no effect were also observed in response to XXMD treatment. The data indicated the protective effects of XXMD on neurovascular unit partly through the activation of PI3K/Akt pathway.
Language	English
Publishing date	2013-05-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2171158-6
ISSN	1741-4288 ; 1741-427X
ISSN (online)	1741-4288
ISSN	1741-427X
DOI	10.1155/2013/459467
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