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buyang huanwu decoction increases vascular endothelial growth factor expression and promotes angiogenesis in a rat model of local cerebral ischemia

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Neural Regeneration Research 2010年第22期5卷 1733-1738页

作者： Guangxian Cai Baiyan Liu Key Laboratory of Internal Medicine Hunan University of Traditional Chinese Medicine Changsha 410007 Hunan Province China

Angiogenesis in the infarct periphery can improve blood flow. Vascular endothelial growth factor （VEGF） has been considered a potential therapeutic target for stroke. buyang huanwu decoction （BYHWD） is a classic traditional formula in traditional Chinese medicine and is used to treat stroke; in addition, the promotion effects on VEGF protein expression have been confirmed. However, little is known about how BYHWD regulates angiogenesis, or about the effects of BYHWD on VEGF mRNA expression. For this reason, the present study measured microvessel density in rats with cerebral ischemia using immunohistochemistry. In addition, VEGF expression was measured by re-verse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay to determine the effects of BYHWD on angiogenesis and VEGF expression in rats with cerebral ischemia. Results demonstrated that microvessel density, as well as VEGF mRNA and protein expression, increased after 7 and 14 days of BYHWD treatment, which suggests that BYHWD promoted angiogenesis following cerebral ischemia and upregulated VEGF mRNA and protein expression in ischemic cerebral regions.

关键词： buyang huanwu decoction cerebral ischemia angiogenesis vascular endothelial growth factor Chinese medicine neural regeneration

buyang huanwu decoction regulates neural stem cell behavior in ischemic brain

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Neural Regeneration Research 2013年第25期8卷 2336-2342页

作者： Baiyan Liu Guangxian Cai Jian Yi Xuemei Chen Key Laboratory of Internal Medicine Hunan University of Traditional Chinese Medicine

The traditional Chinese medicine buyang huanwu decoction has been shown to improve the neu- rological function of patients with stroke. However, the precise mechanisms underlying its effect remain poorly understood. In this study, we established a rat model of cerebral ischemia by middle cerebral artery occlusion and intragastrically administered 5 g/kg buyang huanwu decoction, once per day, for 1, 7, 14 and 28 days after cerebral ischemia. Immunohistochemical staining revealed a number of cells positive for the neural stem cell marker nestin in the cerebral cortex, the subven- tricular zone and the ipsilateral hippocampal dentate gyrus in rat models of cerebral ischemia. buyang huanwu decoction significantly increased the number of cells positive for 5-bromodeoxyuridine （BrdU）, a cell proliferation-related marker, microtubule-associated protein-2, a marker of neuronal differentiation, and growth-associated protein 43, a marker of synaptic plasticity in the ischemic rat cerebral regions. The number of positive cells peaked at 14 and 28 days after intragastric administration of buyang huanwu decoction. These findings suggest that buyang huanwu decoction can promote the proliferation and differentiation of neural stem cells and en- hance synaptic plasticity in ischemic rat brain tissue.

关键词： neural regeneration traditional Chinese medicine buyang huanwu decoction cerebral ischemia nestin BrdU microtubule-associated protein-2 growth-associated protein 43 neural stem cells proliferation differentiation cerebral cortex subventricular zone dentate gyrus grants-supportedpaper neuroregeneration

buyang huanwu decoction Ameliorates Damage of Erectile Tissue and Function Following Bilateral Cavernous Nerve Injury

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Chinese Journal of Integrative Medicine 2023年第9期29卷 791-800页

作者： YE Miao-yong ZHAO Fan MA Ke YAO Li-juan ZHOU Kang MA Jian-xiong LYU Bo-dong XU Zeng-bao Department of Urology the First People’s Hospital of WenlingWenlingZhejiang Province317500China Department of Urology Affiliated Hospital of Nantong UniversityNantongJiangsu Province226001China The Second Clinical Medical College Zhejiang Chinese Medical UniversityHangzhou310053China Department of Urology Huzhou Hospital of Traditional Chinese MedicineHuzhouZhejiang Province313000China Andrology Laboratory on Integration of Chinese and Western Medicine Zhejiang Provincial Key Laboratory of Traditional Chinese MedicineHangzhou310053China

Objective To verify the effect of buyang huanwu decoction(BHD)in ameliorating erectile dysfunction(ED)after radical prostatectomy(RP).Methods The composition of BHD was verified by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry(UPLC-QTOF-MS/MS)*** cavernous nerve crush injury(BCNI)in rats was used to mimic the neurovascular injury occurring after *** the envelope method,forty rats were randomly divided into 4 groups as follows:sham(cavernous nerves exposed only),model(BCNI),low-dosage BHD[LBHD,12.8 g/(kg·d)],and high-dosage BHD[HBHD,51.2 g/(kg·d)]groups,10 rats in each group,feeding for 3 weeks *** function was evaluated by measuring intracavernosal pressure(ICP).Changes in the histopathology of corpus cavernosum(CC)were examined by hematoxylin-eosin ***,the fibrosis of CC was measured by Masson’s trichrome staining and Western blot was used to detect the expressions of collagen I,transforming growth factor beta 1(TGF-β1)andα-smooth muscle actin(α-SMA).Apoptosis index was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL)and Western blot for determining the expressions of B-cell lymphoma 2(Bcl-2)and Bcl-2-associated X(Bax).The oxidative stress in the CC were assessed by the superoxide dismutase(SOD),malondialdehyde(MDA)and reactive oxygen species(ROS)*** proteins expression of c-Jun N-terminal kinase(JNK)and c-Jun were detected by Western *** addition,the expression ofα-SMA and p-c-Jun in the CC was observed by double immunofluorescence *** The UPLC-QTOF-MS/MS analysis showed that BHD contained calycosin-7-O-β-D-glucoside,ononin,calycosin and *** with the model group,LBHD and HBHD treatment improved the ICP and the circumference,area,and weight of CC(P<0.05 or P<0.01).Furthermore,LBHD and HBHD treatments increased CC smooth muscle content and decreased apoptosis index(P<0.05 or P<0.01).LBHD and HBHD also e

关键词： buyang huanwu decoction erectile dysfunction cavernous nerve injury Chinese medicine Jun N-terminal kinase

buyang huanwu decoction ameliorates ischemic stroke by modulating multiple targets with multiple components: In vitro evidences

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Chinese Journal of Natural Medicines 2018年第3期16卷 194-202页

作者： ZHANG Wei-Wei XU Feng WANG Ding YE Jia CAI Shao-Qing Department of Molecular and Cellular Pharmacology School of Pharmaceutical Sciences Peking University Department of Clinical Pharmacy Beijing Tsinghua Changgung Hospital Medical Center Tsinghua University State Key Laboratory of Natural and Biomimetic Drugs Peking University

buyang huanwu decoction （BYHWD） is a well-known traditional Chinese medicine prescription which is used to treat ischaemic stroke and stroke-induced disabilities. However, the exact mechanism underlying BYHWD＇s amelioration of ischaemic stroke and its effective constituents remain unclear. The present study aimed to identify the effective constituents of BYHWD and to further explore its action mechanisms in the amelioration of ischaemic stroke by testing the activities of 15 absorbable chemical constituents of BYHWD with the same methods under the same conditions. The following actions of these 15 compounds were revealed： 1） Ferulic acid, calycosin, formononetin, astrapterocarpan-3-O-β-D-glucoside, paeonol, calycosin-7-O-β-D-glucoside, astraisofla- van-7-O-β-D-glucoside, ligustrazine, and propyl gallate significantly suppressed concanavalin A （Con A）-induced T lymphocyte proliferation; 2） Propyl gallate, calycosin-7-O-β-D-glucoside, paeonol, and ferulic acid markedly inhibited LPS-induced apoptosis in RAW264.7 cells; 3） Propyl gallate and formononetin significantly inhibited LPS-induced NO release; 4） Hydroxysaffior yellow A and inosine protected PC12 cells against the injuries caused by glutamate; and 5） Formononetin, astragaloside IV, astraisofiavan-7-O-β-D- glucoside, inosine, paeoniflorin, ononin, paeonol, propyl gallate, ligustrazine, and ferulic acid significantly suppressed the constriction of the thoracic aorta induced by KCI in rats. In conclusion, the results from the present study suggest that BYHWD exerts its ischaemic stroke ameliorating activities by modulating multiple targets with multiple components.

关键词： buyang huanwu decoction Chemical constituents Ischemic stroke Anti-inflammatory-immunity Neuroprotection Vasodilation

buyang huanwu decoction promotes angiogenesis and improves hemorheological parameters after cervical spinal cord injury

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Journal of Traditional Chinese Medical Sciences 2024年第4期11卷 456-465页

作者： Luchun Xu Yongdong Yang Guozheng Jiang Yushan Gao Jiawei Song Yukun Ma Jiaojiao Fan Guanlong Wang Xing Yu Xiangsheng Tang Department of Orthopedics Dongzhimen HospitalBeijing University of Chinese MedicineBeijing100700China School of Traditional Chinese Medicine Beijing University of Chinese MedicineBeijing 102488China Department of Orthopedics China-Japan Friendship HospitalBeijing 100029China

Objective:To explore the effects of buyang huanwu decoction(BYHWD)on vascular neogenesis and hemorheological parameters following cervical spinal cord injury(SCI).Methods:An acute cervical SCI model was established using 84 female SpragueeDawley *** recovery of the rats was evaluated using the forelimb locomotor scale score,forelimb grip strength test,and Basso-Beattie-Bresnahan *** animals were subsequently euthanized at days 7 and 28 *** gross morphology,neuronal survival,and myelin sheath in the injured area were evaluated using hematoxylin and eosin(HE),Nissl,and luxol fast blue(LFB)staining,*** staining was used to observe CD31 expression 7 days ***,the expression of CD31,neuronal nuclear protein(NeuN),and myelin basic protein(MBP)were evaluated 28 days ***,vascular endothelial growth factor A(VEGFA)and VEGF receptor-2(VEGFR-2)expression was evaluated using western ***-blood viscosity,plasma viscosity,and red blood cell aggregation were measured using a ***:From postoperative days 3e28,motor function in the BYHWD group began to recover consid-erably compared to the SCI *** effectively restored spinal cord *** addition,the number of NeuN-positive cells,and fluorescence intensity of CD31at 7 and 28 days and MBP significantly increased in the BYHWD group compared with the SCI group(all Pdecoction significantly upregulated the expression of VEGFA and VEGFR-2(all P<0.05).BYHWD improved the hemorheology results(i.e.,except erythrocyte aggregation index in the low-dose group),revealing statistically significant differences compared with the SCI group(all P<0.05).Conclusion:BYHWD effectively promoted angiogenesis,improved hemorheological parameters,and protected neurons and myelin sheaths,ultimately promoting the recovery of neurological function after cervical SCI in *** findings suggest

关键词： Cervical spinal cord injury buyang huanwu decoction Angiogenesis Hemorheology Neuroprotection

Microvessel changes in the gerbil hippocampus after cerebral ischemia and reperfusion by buyang huanwu decoction pretreatment

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Neural Regeneration Research 2011年第9期6卷 656-660页

作者： Xiaoguang Wu Yixue Li Haixia Liu Yuhua Yin Shumin Zhao Yuanyuan Guo Institute of Basic Medicine Chengde Medical College Chengde 067000 Hebei Province China Depatement of Ultrasonography Affiliated Hospital of Chengde Medical College Chengde 067000 Hebei Province China Depatement of Obstetrics and Gynecology Second Affiliated Hospital Chengde Medical College Chengde 067000 Hebei Province China

buyang huanwu decoction （BYHWD） is a classic recipe for the prevention and treatment of ischemic cerebrovascular disease. Gerbils were pretreated with BYHWD, and then subjected to cerebral ischemia and reperfusion. Microvascular changes were determined with laser Doppler monitoring, tannic acid-ferric chloride mordant, and electron microscopy. Results showed that BYHWD pretreatment could enhance the function of hippocampal microvessels, prevent injury, and increase microvasular density and microvasular area density. Thus, these results suggest that BYHWD pretreatment could prevent microvascular occlusion, enhance the capacity of microvascular reperfusion, increase cerebral blood flow, and inhibit neuronal damage, and may be an effective therapy against brain ischemic injury.

关键词： buyang huanwu decoction pretreatment cerebral ischemia and reperfusion microvascular density microvessel area density traditional Chinese medicine

Neuroprotective effects of buyang huanwu decoction on cerebral ischemia-induced neuronal damage

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Neural Regeneration Research 2014年第17期9卷 1621-1627页

作者： Qingchun Mu Pengfei Liu Xitong Hu Haijun Gao Xu Zheng Haiyan Huang First Hospital of Bethune Jilin University Hongqi Hospital of Mudanjiang Medical University

Among the various treatment methods for stroke, increasing attention has been paid to tradi- tional Chinese medicines. buyang huanwu decoction is a commonly used traditional Chinese medicine for the treatment of stroke. This paper summarizes the active components of the Chinese herb, which is composed of Huangqi （Radix Astragali seu Hedysari）, Danggui （Radix Angelica sinensis）, Chishao （Radix Paeoniae Rubra）, Chuanxiong （Rhizoma Ligustici Chuanx- iong）, Honghua （Flos Carthami）, Taoren （Semen Persicae） and Dilong （Pheretima）, and identifies the therapeutic targets and underlying mechanisms that contribute to the neuroprotective prop- erties of buyang huanwu decoction.

关键词： nerve regeneration buyang huanwu decoction traditional Chinese medicine cerebral ischemia clinical application neuroprotection review neural regeneration

Effects of buyang huanwu decoction on Intestinal Barrier, Intestinal Flora, and Trimethylamine Oxide in Rats with Heart Failure

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Chinese Journal of Integrative Medicine 2023年第2期29卷 155-161页

作者： WENG Jie-qiong LI Jie-bai YUAN Meng-fei YAO Ting-ting ZHANG Jing-fang ZENG Yuan-yuan ZHAO Jing LI Ying XU Ke SHEN Xiao-xu Department of Cardiology Dongzhimen Hospital of Beijing University of Chinese MedicineBeijing 100700China Department of Nuclear Medicine Dongzhimen Hospital of Beijing University of Chinese MedicineBeijing 100700China Peking University Sixth Hospital Beijing 100700China

Objective: To explore the mechanisms of buyang huanwu decoction(BYHWD) modulating the gut microbiome and trimethylamine oxide(TAMO) to exert cardioprotective effects. Methods: Ligation of the left anterior descending coronary artery was performed in rats to induce heart failure(HF). Except for the shamoperation group(n=10), 36 operation-induced models were randomized into 3 groups using a random number table(n=12 in each group): the model group, the BYHWD group(15.02 g/kg BYHWD), and the positive group(4.99 g/kg metoprolol succinate). After 4-week treatment(once daily by gavage), echocardiography was applied to evaluate the cardiac function and the Tei index(the ratio of ventricular isovolumic contraction time(IVCT)and isovolumic diastolic time(IVRT) to ejection time(ET)) was calculated;hematoxylin-eosin(HE) staining was observed to characterize the pathology of the myocardium and small intestinal villi. D-lactic acid was detected by an enzyme-linked immunosorbent assay(ELISA). Expressions of occludin, claudin-1, and zonula occludens(ZO-1) were detected by Western blot. 16S ribosomal ribonucleic acid(16S rRNA) sequencing was used to explore the changes in the intestinal flora. TMAO was detected via liquid chromatography-tandem mass spectrometry(LC-MS/MS). Results: In the echocardiography, the Tei index was considerably lower in the positive and BYHWD groups compared with the model group(P<0.05). Besides, BYHWD improved the pathology of myocardium and small intestine of HF rats and lowered the D-lactic acid content in the serum, when compared with the model group(P<0.05). BYHWD also improved the expression of occludin and claudin-1(P<0.05);in the gut microbiota analysis, BYHWD slowed down modifications in the structure distribution of gut microbiota and regulated the diversity of intestinal flora in HF rats. The content of TMAO in the serum was significantly lowered by BYWHT compared with the model group(P<0.05). Conclusion: BYHWD may delay progression of HF by enhan

关键词： buyang huanwu decoction heart failure intestinal flora trimethylamine oxide

Mitogen activated protein kinase signaling pathways participate in the active principle region of buyang huanwu decoction-induced differentiation of bone marrow mesenchymal stem cells

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Neural Regeneration Research 2012年第18期7卷 1370-1377页

作者： Jinghui Zheng Jian Liang Xin Deng Xiaofeng Chen Fasheng Wu Xiaofang Zhao Yuan Luo Lei Fu Zuling Jiang Ruikang Hospital Attached to Guangxi Traditional Chinese Medicine College Level-3 Laboratory of Cell Molecular Biology of StateAdministration of Traditional Chinese Medicine of the People's Republic of ChinaNanning 530011Guangxi Zhuang Autonomous Region China

Our preliminary studies confirmed that an active principle region of buyang huanwu decoction, comprising alkaloid, polysaccharide, aglycon, glucoside and volatile oil, can induce bone marrow mesenchymal stem cell differentiation into neurons. Mitogen-activated protein kinase signaling was identified as one of the key pathways underlying this differentiation process. The present study shows phosphorylated extracellular signal-regulated protein kinase and phosphorylated p38 protein expression was increased after differentiation. Cellular signaling pathway blocking agents, PD98059 and SB203580, inhibited extracellular signal-regulated protein kinase and p38 in mitogen-activated protein kinase signaling pathways respectively, mRNA and protein expression of the neuronal marker, neuron specific enolase, and neural stem cell marker, nestin, were decreased in bone marrow mesenchymal stem cells after treatment with the active principle region of buyang huanwu decoction. Experimental findings indicate that, extracellular signal-regulated protein kinase and p38 in mitogen-activated protein kinase signaling pathways participate in bone marrow mesenchymal stem cell differentiation into neuron-like cells, induced by the active principle region of buyang huanwu decoction.

关键词： buyang huanwu decoction bone marrow mesenchymal stem ceils extracellular signal-regulatedprotein kinase mitogen-activated protein kinase signaling pathway neuron specific enolase nestin cell signal transduction pathway neural regeneration