Effects of Buyang Huanwu Decoction on Intestinal Barrier, Intestinal Flora, and Trimethylamine Oxide in Rats with Heart Failure / 中国结合医学杂志

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 sham-operation 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 enhancing the intestinal barrier structure, and regulating intestinal flora and TAMO.

Mechanism of Buyang Huanwu Decoction glycosides against atherosclerotic inflammation through NF-κB signaling pathway / 中国中药杂志

This study aims to explore the effect of Buyang Huanwu Decoction glycosides on the inflammatory response of apolipoprotein E~(-/-)(ApoE~(-/-)) mice and RAW264.7 cells through nuclear factor kappa-B(NF-κB) signaling pathway. In the in vivo experiment, ApoE~(-/-) mice were fed with high-fat diets for 12 weeks to induce the animal model of atherosclerosis, and 75 μg·mL~(-1) oxidized low-density lipoprotein(Ox-LDL) incubated RAW264.7 cells for 24 h to establish the atherosclerosis cell model. Automatic biochemical analyzer, hematoxylin-eosin(HE) staining, enzyme-linked immunosorbent assay(ELISA), Western blot, and droplet digital polymerase chain reaction(PCR) were used to determine the blood lipid levels, aortic intimal thickness, inflammatory factor content, NF-κB pathway-related proteins, and mRNA expression levels, and evaluate arterial atherosclerotic lesions and anti-atherosclerotic mechanisms of the drug. The model of atherosclerosis was successfully established in ApoE~(-/-) mice after 12 weeks of feeding with high-fat diets. In the model group, the plasma levels of total cholesterol(TC), triglyceride(TG), and low-density lipoprotein cholesterol(LDL-C) were increased(P<0.01), the intima of the blood vessels was thickened, the levels of inflammatory factors tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) were increased, and the protein and mRNA expressions of NF-κB and inhibitor of NF-κB(IκBα) were significantly increased as compared with the control group. Compared with the model group, the high-dose Buyang Huanwu Decoction glycoside group decreased the plasma levels of TC, TG, and LDL-C, reduced the plaque area and thickness and the content of inflammatory factor TNF-α, and inhibited the protein and mRNA expressions of NF-κB and IκBα, with the effect same as Buyang Huanwu Decoction. In the in vivo experiment, 75 μg·mL~(-1) Ox-LDL stimulated RAW264.7 cells for 24 h to successfully establish a foam cell model. As compared with the control group, the nuclear amount of NF-κB and the protein and mRNA expressions of IκBα in the model group increased. Compared with the model group, the middle-dose and high-dose Buyang Huanwu Decoction glycoside groups decreased the nuclear amount of NF-κB and the protein and mRNA expressions of IκBα. The above results show that the glycosides are the main effective substances of Buyang Huanwu Decoction against atherosclerosis, which inhibit the NF-κB pathway and reduce the inflammatory response, thus playing the role against atherosclerotic inflammation same as Buyang Huanwu Decoction.

Improving mechanism of Buyang huanwu decoction on idiopathic pulmonary fibrosis model rats / 中国药房

OBJECTIVE To study the improving mechanism of Buyang huanwu decoction （BYHW） on idiopathic pulmonary fibrosis （IPF） model rats. METHODS Ninety-six Wistar rats were randomly divided into blank group， model group， positive control group， and BYHW low-dose， middle-dose and high-dose groups， with 16 rats in each group. Except for the blank group， the IPF model was induced in other groups by intratracheal instillation of bleomycin （5 mg/kg）. Starting from the day of modeling， the blank group and model group were given normal saline （10 mL/kg） intragastrically， while the rats in the positive control group were given dexamethasone solution （5 mg/kg） intragastrically， BYHW low-dose， middle-dose and high-dose groups were treated with BYHW （2.5， 5， 10 g/kg， by crude drug） intragastrically， once a day， for 28 consecutive days. The body mass of rats in each group was measured on days 0， 7， 14， 21 and 28 after modeling. The number of adherent white blood cells in pulmonary veins was observed by a dynamic visualization system. The contents of TNF-α and IL-6 in serum and TNF-α， IL-6， HYP and TGF-β1 in lung tissue were detected； the protein expression of ZO-1 was also detected. The pathomorphological changes in lung tissue were observed. RESULTS Compared with the model group， the body weight of rats all increased significantly in BYHW high-dose and middle-dose groups， positive control group， while the number of adherent white blood cells in pulmonary veins was decreased significantly； the contents of TNF-α （except for serum in BYHW middle-dose group） and IL-6 in serum and lung tissue， the contents of HYP and TGF-β1 in lung tissue were decreased significantly， while the protein expression of ZO-1 in the lung tissue was increased significantly （P＜0.05 or P＜0.01）. The pathological changes of lung tissue were improved to varying degrees. CONCLUSIONS BYHW may play anti-pulmonary fibrosis role by improving leukocyte adhesion， anti-inflammatory， anti-fibrosis， and other aspects of pulmonary microcirculation.

Optical coherence tomography angiography quantitative analysis of the effect of modified Buyang Huanwu Decoction on blood flow to the optic disc in patients with non-proliferative diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To observe the clinical efficacy of modified Buyang Huanwu Decoction in treating non-proliferative diabetic retinopathy(NPDR)of qi and yin deficiency and stagnation of collaterals, and to quantitatively analyze the changes in peripapillary vessel density before and after treatment using optical coherence tomography angiography(OCTA).METHODS:A randomized controlled trial was used to collect a total of 58 patients(99 eyes)with qi and yin deficiency and stagnation of collaterals NPDR who visited our hospital from June 2022 to November 2022, and patients were randomly divided into an observation group(n=29, 51 eyes)and a control group(n=29, 48 eyes). The control group received basic treatment according to the recommendations for DR published by the American Academy of Ophthalmology in 2019(blood glucose control, diabetes health education, and regular follow-up for patients with mild NPDR; and add local/grid-like laser photocoagulation if necessary for patients with moderate NPDR), while the observation group received modified Buyang Huanwu Decoction in addition to the basic treatment for 1mo. The best-corrected visual acuity(BCVA), traditional Chinese medicine(TCM)efficacy, peripapillary telangiectasia vessel density(ppVD), and changes in peripapillary retinal nerve fiber layer(pRNFL)thickness were compared between the two groups before and after treatment.RESULTS:The BCVA(LogMAR)of the observation group was 0.20(0.10, 0.30)after 1mo of treatment, which was significantly improved compared with that of the control group of 0.30(0.20, 0.40; P&#x003C;0.05). The TCM efficacy in the observation group after 1mo of treatment was better than that in the control group(P&#x003C;0.05). The ppVD in all quadrants of the observation group showed a significant improvement at 1mo after treatment, and the ppVD in all quadrants of the observation group was higher than that of the control group(P&#x003C;0.05). The pRNFL thickness in the superior, temporal, and average peripapillary areas of the observation group increased after 1mo of treatment, and the pRNFL thickness in the superior, temporal, inferior quadrants, and average peripapillary area of the observation group was higher than that of the control group(P&#x003C;0.05).CONCLUSION:Modified Buyang Huanwu Decoction can improve visual acuity and enhance TCM efficacy in patients with NPDR of qi and yin deficiency and stagnation of collaterals. It may be related to its ability to improve ppVD and reduce damage to the pRNFL.

Comparative study on brain pharmacokinetics of Buyang Huanwu Decoction in normal and cerebral ischemia rats using brain microdialysis combined with LC-MS/MS / 中草药·英文版

Objective: To conduct a comparative study on the brain pharmacokinetics of seven ingredients (i. e. senkyunolide A, ferulic acid, formononetin, calycosin, ononin, calycosin-O-β-D-glucopyranoside, and paeoniflorin), which were the compounds of Buyang Huanwu Decoction (BHD), in normal and cerebral ischemia rats administrated intragastrically with BHD. Methods: The samples of normal and permanent middle cerebral artery occlusion (pMCAO) rats were collected by using brain microdialysis technique. The concentrations of seven ingredients were determined by the HPLC-MS/MS method. After the BHD were administrated intragastrically to the rats for seven consecutive days, brain microdialysis probes were inserted into the hippocampus of rats, and then the brain microdialysates were collected at 20 min time intervals for 5 h. The separation of the seven ingredients and internal standard (IS) was carried out on an ACQUITY UPLC BEH C

Efficacy of addition and subtraction of Buyang Huanwu decoction in the adjuvant treatment of non-proliferative diabetic retinopathy of Qi-Yin deficiency and blood stasis / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To observe the efficacy of addition and subtraction of Buyang Huanwu decoction in the adjuvant treatment of non-proliferative diabetic retinopathy of Qi-Yin deficiency and blood stasis and its effects on traditional Chinese medicine(TCM)syndromes and visual function level. <p>METHODS: A total of 110 patients with non-proliferative diabetic retinopathy of Qi-Yin deficiency and blood stasis in our hospital between January 2017 and December 2019 were selected and divided into observation group(55 cases, 110 eyes)and control group(55 cases, 110 eyes). Patients in control group received conventional treatment according to the condition of patients with reference to relevant guidelines, and patients in observation group were combined with addition and subtraction of Buyang Huanwu decoction adjuvant therapy on this basis. The clinical efficacy after 3mo of treatment, and TCM syndromes scores, clinical indicators(macular edema score, macular retinal volume, macular foveal retinal thickness), visual function(best corrected visual acuity, average visual field sensitivity)and serum biochemical indicators \〖vascular endothelial growth factor(VEGF), hypoxia-inducible factor-1(HIF-1)\〗 before treatment and 3mo after treatment were compared between the two groups.<p>RESULTS: After 3mo of treatment, the total effective rate of treatment in observation group was significantly higher than that in control group(<i>P</i><0.05). After 3mo of treatment, the TCM syndromes scores in the two groups were decreased compared with those before treatment, and the scores in observation group were lower than those in control group(<i>P</i><0.05). After 3mo of treatment, the macular edema score, macular retinal volume and macular foveal retinal thickness in the two groups were reduced compared with those before treatment, and the indexes in observation group were smaller than those in control group(<i>P</i><0.05). After 3mo of treatment, the best corrected visual acuity and average visual field sensitivity in the two groups were improved compared with those before treatment, and the indexes in observation group were higher than those in control group(<i>P</i><0.05). After 3mo of treatment, the levels of serum VEGF and HIF-1 in the two groups were decreased compared with those before treatment, and the levels in observation group were lower than those in control group(<i>P</i><0.05). <p>CONCLUSION: Addition and subtraction of Buyang Huanwu decoction has an exact efficacy in the adjuvant treatment of non-proliferative diabetic retinopathy of Qi-Yin deficiency and blood stasis, and it can improve symptoms and promote visual function recovery by reducing the expressions of VEGF and HIF-1.

The Yijing Buyang Huanwu Decoction combined with timolol maleate in the treatment of POAG / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To discuss the effect of Yijing Buyang Huanwu Decoction combined with timolol maleate eye drop on the blood supply and intraocular pressure in patients with primary open angle glaucoma(POAG). <p>METHODS:The 120 patients with POAG in our hospital from February 2018 to February 2020 were selected, they were divided into decoction group(<i>n</i>=60)and eye drop group(<i>n</i>=60)according to the randomly table. The eye drop group was treated with timolol maleate eye drop, and the decoction group was treated with Yijing Buyang Huanwu Decoction on the basis of the eye drop group, the eye blood supply \〖end diastolic velocity(EDV), peak systolic velocity(PSA), resistance index(RI)of central retinal artery(CRA)and posterior ciliary artery(PCA)\〗, intraocular pressure, visual acuity, visual field \〖mean sensitivity(MS), mean deviation(MD)\〗, efficacy and adverse reactions were compared between the two groups. <p>RESULTS: The EDV and PSA of the CRA and PCA and the visual acuity, MS in the Decoction group and eye drop group after treatment were significantly higher than those in the before treatment, the RI of the CRA and PCA and the intraocular pressure, MD in the Decoction group and eye drop group after treatment were significantly lower than those in the before treatment, the EDV and PSA of the CRA and PCA and the visual acuity, MS in the Decoction group after treatment were significantly higher than those in the eye drop group, the RI of the CRA and PCA and the intraocular pressure, MD in the Decoction group after treatment were significantly lower than those in the eye drop group(<i>P</i><0.05). The effective rate in the Decoction group was significantly higher than that in eye drop group(<i>P</i><0.05). There was no significant difference in adverse reactions between the Decoction group and eye drop group(<i>P</i>>0.05).<p>CONCLUSION: Yijing Buyang Huanwu Decoction combined with timolol maleate eye drop can effectively improve the blood supply, intraocular pressure and visual acuity, visual field of patients with POAG, it can improve the efficacy, and it has the good safety, it's worth for further clinical promotion.

Effects of Buyang Huanwu Decoction on Hemorheology and Platelet Related Biological Indexes in Hyperlipidemia Model Rats / 中国药房

OBJECTIVE：To investigate the effe cts of Buyang huanwu decoction on hemorheology and platelet related biological indexes of hyperlipidemia model rats. METHODS ：Male Wistar rats were randomly divided into blank control group （10 rats）and model group （40 rats）. Blank control group was given normal diet ，and model group was given high-lipid diet for 6 weeks at least to induce hypelipidemia model. After modeling ，rats were randomly divided into model control group ，positive control group （simvastatin，0.004 g/kg），Buyang huanwu decoction low-dose and medium-dose groups （3.5，14.0 g/kg，by crude drug），with 10 rats in each group. Blank control group and model control group were given normal saline intragastrically ， administration groups were given relevant drug intragastrically ，0.01 mL/g，once a day ，for consecutive 4 weeks. Thirty min after last medication ，hemorheological indexes （whole blood viscosity ，plasma viscosity ），platelet adhesion related indexes [adhesion rate，von Willebrand factor （vWF），fibronectin（FN）]，platelet release related indexes [ β-thromboglobulin（β-TG），platelet factor 4 （PF4）] and platelet fibrinolytic system related indexes [tissue plasminogen activator （t-PA），plasminogen activator inhibitor （PAI-1）]，platelet parameters （PLT，PDW，MPV，PCT，PLCR），4 kinds of coagulation parameters （APTT，TT，PT，FIB）were detected. RESULTS ：Compared with blank control group ，the whole blood viscosity （low，medium and high shear rate ），plasma viscosity，platelet adhesion rate ，the contents or levels of vWF ，FN，β-TG，PAI-1，PLT，MPV，PCT，PLCR and FIB in model control group were increased significantly （P＜0.05 or P＜0.01），and t-PA content was significantly decreased （P＜0.05）. Compared with model control group ，the whole blood viscosity （except for whole blood viscosity of high shear rate in Buyang huanwu decoction high-dose group ），plasma viscosity ，platelet adhesion rate ，the contents or levels of vWF ，FN，β-TG，PAI-1， PLT，PDW（except for Buyang huanwu decoction low-dose and high-dose groups ），MPV，PCT，PLCR（except for Byang huanwu decoction low-dose group ）and FIB were decreased significantly （P＜0.05 or P＜0.01），while t-PA content （except for positive control group ） was increased significantly （P＜0.05）. CONCLUSIONS ：Buyang huanwu decoction can significantly improve the pathological state in hyperlipidemia model rats by reducing blood viscosity and FN content ，improving platelet adhesion，enhancing fibrinolytic activity ，improving platelet aggregation ，inhibiting hypercoagulability and hyperplatelet release.

Effects of Buyang Huanwu Decoction on neurovascular units after cerebral ischemia: a review / 中国中药杂志

Buyang Huanwu Decoction, a representative prescription in traditional Chinese medicine(TCM) for tonifying Qi and activating blood, has been proved to be effective in preventing and treating acute cerebral infarction(ACI). It consists of Astragali Radix, Angelicae Sinensis Radix, Paeoniae Radix Rubra, Pheretima, Chuanxiong Rhizoma, Carthami Flos, and Persicae Semen, possessing multiple active ingredients. The neurovascular unit is a functionally and structurally interdependent multicellular complex composed of neurons-glial cells-blood vessels. It plays an important role in the pathological changes of cerebral ischemia and the permeability variation of the blood-brain barrier. In recent years, Buyang Huanwu Decoction has been found to protect the integrity of neurovascular units and improve the permeability of the blood-brain barrier, thereby alleviating stroke and other diseases caused by cerebral ischemia. This paper collated and summarized the protective effects of Buyang Huanwu Decoction on neurovascular units.

Effects and Mechanism of Buyang Huanwu Decoction and the like on Oxygen Deprivation and Reoxygenation of Hippocampal Neurons in Vitro / 中国药学杂志

OBJECTIVE: To investigate the effects and mechanism of Buyang Huanwu Decoction and the like on primary cultured neonate hippocampal neurons induced by oxygen deprivation and reoxygenation. METHODS: The primary cultured hippocampal neurons cell model was established, oxygen sugar deprivation/reoxygenation (OGD/R) model was established in vitro. CCK-8 was used to determine the concentration of Buyang Huanwu Decoction and the like drug-containing serum to protect hippocampal neurons cell. The experimental groups were divided into control group, model group, Buyang Huanwu Decoction drug-containing serum group(10%), Naoxintong Capsule drug-containing serum group(10%), Yangyin Tongnao Granules drug-containing serum group(10%), Buyang Huanwu Decoction drug-containing serum+TAK-242 group(10%,1 μmol•L-1), Naoxintong Capsule drug-containing serum+TAK-242 group(10%,1 μmol•L-1), Yangyin Tongnao Granules drug-containing serum+TAK-242 group(10%,1 μmol•L-1). The morphology of hippocampal neuron was observed under inverted microscope. The expression of tumor necrosis factor-α(TNF-α) and interleukin 1(IL-1β) in the cell supernatant was detected by ELISA kit. The neuronal cell apoptosis was observed by Hoechst 33358 staining fluorescence microscope and the expression of TLR4/NF-κB signaling pathway proteins was detected by Western blot. RESULTS: The results showed that hgher purity neuronal cells can be obtained by primary culture. Compared with model group, Buyang Huanwu Decoction and the like all can reduce the release of TNF-α and IL-1β in hippocampal neurons, significantly reduced the number of apoptosis. At the same time, the three traditional Chinese medicine compounds all can inhibit the expression of TLR4 and NF-κB protein in TLR4/NF-κB signaling pathway, and protect the inflammatory response of oxygenated sugar deprivation and reoxygenated hippocampal neurons. The addition of TLR4-specific inhibitor TAK-242 blocked the conduction of this signaling pathway and reduced the protective effect of Buyang Huanwu Decoction and the like. CONCLUSION: Buyang Huanwu Decoction and the like have protective effects on OGD/R-induced inflammatory response in hippocampal neurons, its mechanism may be related to TLR4/NF-κB signaling pathway, and the anti-inflammatory protective effect of Naoxintong Capsule is relatively obvious.

Regulation of Buyang Huanwu Decoction extracts on apoptosis and autophagy of PC12 cells model with oxidative stress injury / 中草药

Objective: To explore the underlying mechanism of Buyang Huanwu Decoction extracts on apoptosis and autophagy in PC12 cells model with oxidative stress injury. Methods: Different level oxidative stress injury models with H2O2 at various concentrations were established. The effective concentrations of Buyang Huanwu Decoction extracts were determined by MTT method in the initial stage and the intensifying period after oxidative stress injury. The apoptosis of PC12 cells were evaluated by FCM and TUNNEL, the autophagy situations were observed by TEM and mRFP-GFP-LC3. Furthermore, the proteins of Bax, Bcl-2, Beclin1, LC3A, and LC3B related to apoptosis were determined by Western blotting. Results: The initial stage and the intensifying period of oxidative stress injury cell models were established by H2O2 at the concentration of 1.5 and 2.0 mmol/L, respectively. Compared with the control group, model group appeared increasing apoptosis and autophagy levels, and model group had higher expressions of Bax/Bcl-2, Beclin1, LC3B and lower expression of LC3A (P < 0.05). Compared with the initial stage of oxidative stress injury cell models, Buyang Huanwu Decoction extracts could reduce the Bax/Bcl-2 and restrain apoptosis rates, while the autophagy was activated by up-regulation Beclin1 and LC3B/LC3A (P < 0.05). When the serious apoptosis and excessive autophagy were observed in the intensifying period of oxidative stress injury cells, the extracts could play the protective effect by apoptosis restraining and autophagy alleviating. Conclusion: Buyang Huanwu Decoction extracts can play the protective effects on oxidative stress injury cell models in different period by regulating apoptosis and autophagy.

Chinese medicine Buyang Huanwu decoction promotes neurogenesis and angiogenesis in ischemic stroke rats by upregulating miR-199a-5p expression / 浙江大学学报·医学版

OBJECTIVE@#To investigate the mechanism of Chinese medicine Buyang Huanwu decoction (BYHWD) promoting neurogenesis and angiogenesis in ischemic stroke rats.@*METHODS@#Male SD rats were randomly divided into sham operation group, model group, BYHWD group, antagonist group and antagonist control group with 14 rats in each. Focal cerebral ischemia was induced by occlusion of the right middle cerebral artery for 90 min with intraluminal filament and reperfusion for 14 d in all groups except sham operation group. BYHWD (13 g/kg) was administrated by gastrogavage in BYHWD group, antagonist group and antagonist control group at 24 h after modeling respectively, and BrdU (50 mg/kg) was injected intraperitoneally in all groups once a day for 14 consecutive days. miR-199a-5p antagomir or NC (10 nmol) was injected into the lateral ventricle at d5 after ischemia in antagonist and antagonist control groups, respectively. The neurological deficits were evaluated by the modified neurological severity score (mNSS) and the corner test, and the infract volume was measured by toluidine blue staining. Neurogenesis and angiogenesis were detected by immunofluorescence double labeling method. The expression level of miR-199a-5p was tested by real-time RT-PCR, and the protein expressions of vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) were determined by Western blotting.@*RESULTS@#BYHWD treatment significantly promoted the recovery of neurological function (@*CONCLUSIONS@#Buyang Huanwu decoction promotes neurogenesis and angiogenesis in rats with cerebral ischemia, which may be related to increased protein expression of VEGF and BDNF through upregulating miR-199a-5p.

Interaction between components of Buyang Huanwu Decoction and targets associated with ischemic stroke based on molecular docking method / 中草药

Objective: To investigate the interaction between the components of Buyang Huanwu Decoction (BYHWD) and the targets associated with ischemic stroke by using molecular docking technique, and explore the effective material basis and main targets of BYHWD. Methods: A total of 46 key protein targets associated with cerebral infarction of the human body were selected, 204 components of BYHWD were screened from the TCMSP database, and these components and targets were docked using molecular docking technology, thereby to get the Total Score. Cytoscape3.7.1 software was applied to establish network model of component-protein targets. At the same time, total quantum statistical moment similarity method was used to analyze the imprinting behaviors of these targets. Results: From molecular docking results, 22 components had good interactions with 40 or more protein targets, and 22 protein targets had good interactions with 80 or more components for the treatment of cerebral infarction. Conclusion: Molecular docking method can be used to find the active ingredients and main targets of BYHWD in treating ischemic stroke, providing certain reference for further study on the mechanism of BYHWD in treating ischemic stroke.

Establishment of fingerprint of Buyang Huanwu Decoction based on core-shell chromatography and its Q-Orbitrap HRMS/MS analysis / 中草药

Objective: To establish the fingerprint of Buyang Huanwu Decoction (BHD) based on core-shell column for its quality control. Methods: The extract of BHD was separated on an Agilent Poroshell 120 SB-C18 (150 mm × 4.6 mm, 2.7 μm) with a gradient elution. The mobile phase consisted of acetonitrile-0.1% formic acid. The detection wavelength was 280 nm. The similarity evaluation of 15 batches of BHD was carried out by the “Similarity Evaluation System for Chromatographic Fingerprints of TCM”. HPLC-Q-Orbitrap HRMS/MS was used to characterize the 21 chemical compounds of the extract of BHD. Results: The chromatographic fingerprints of 15 batches of BHD were generated 21 common peaks (P1-P21), belonging to all seven medicinal herbs in 38 min. Methyl quinate (P4), calycosin-7-O-β-D-glucoside (P11), calycosin-7-O-β-D-glucoside-6″-O-malonate (P13), ononin (P15), (6αR, 11αR)-9,10-dimethoxypterocarpan-3-O-β-D-glucoside (P16), isomucronulatol-7-O-β-D-glucoside (P17), calycosin (P18), formononetin (P19), (6αR,11αR)-9,10-dimethoxypterocarpan (P20), and isomucronulatol (P21) were from Astragali Radix. Succinyl adenosine (P3), 6-hydroxykaempferol-3,6-diglucoside (P5), and kaempferol-3-O-sophoroside (P10) were from Carthami Flos. Gallic acid (P2) and paeoniflorin (P9) were from Paeoniae Radix Rubra. Vanillic acid (P7) was from Angelicae Sinensis Radix. Guanoside (P1) was from Pheretima. Amygdalin (P6) and prunasin (P8) were from Persicae Semen. Ferulic acid (P12) and senkyunolide H (P14) were from Angelicae Sinensis Radix and Chuanxiong Rhizoma. A total of 21 components were identified by UHPLC-Q-Orbitrap HRMS/MS. It was the first time to establish the UHPLC fingerprint of BHD by core-shell chromatography technology. Conclusion: The method is simple and accurate with a good reproducibility and time consuming, which will provide a basis for the further research on effective constituents in BHD.

Effects of Buyang Huanwu Decoction on Endothelial-mesenchymal Transformation of Lung Tissue in Idiopathic Pulmonary Fibrosis Model Rats and Mechanism Study / 中国药房

OBJECTIVE： To investigate the effects of Buyang huanwu decoction on endothelial-mesenchymal transformation （EndMT） of lung tissue in idiopathic pulmonary fibrosis （IPF） model rats， and to explore its potential mechanism. METHODS： Male SD rats were randomly divided into normal group， model gorup， dexamethasone group [0.405 mg/（kg·d）]， Buyang huanwu decoction low-dose， medium-dose and high-dose groups [6.435， 12.87， 25.74 g/（kg·d）， by raw material]， with 8 rats in each group. Except for normal group， other groups were given endotracheal injection of bleomycin to induce IPF model. On the second day after modeling， normal group and model group were given water intrgastrically [10 mL/（kg·d）]； administration groups were given relevant medicine intragastrically， once a day， for consecutive 28 days. 24 h after last medication， the expression of endothelial cell markers [platelet endothelial cell adhesion molecule 1， vascular endothelial cell cadherin] and interstitial cell markers [α-smooth muscle actin， fibroblast specific protein 1] were detected by immunohistochemistry method. The expression of Notch4 and DLL4 in lung tissue of rats were detected by Western blotting assay. RESULTS： Compared with normal group， the expression of endothelial cell markers were decreased significantly in lung tissue of model group， while the expressipon of interstitial cell markers， Notch4 and DLL4 were increased significantly （P＜0.01）. Compared with model group， the expression of endothelial cell markers in lung tissue of rats were increased significantly in administration groups， while Buyang huanwu decoction low-dose group was significantly lower than dexamethasone group； the expression of interstitial cell markers， Notch4 and DLL4 were decreased significantly， while Buyang huanwu decoction low-dose group was significantly higher than dexamethasone group （P＜0.05 or P＜0.01）. CONCLUSIONS： Buyang huanwu decoction can relieve IPF of model rats by intervening in EndMT， the mechanism of which may be associated with inhibiting DLL4/Notch4 singaling pathway.

Effects of Buyang Huanwu Decoction on the Expression of MMPs and TIMPs in Cardiac Tissue of Viral Myocarditis Model Mice / 中国药房

OBJECTIVE： To investigate the effects of Buyang huanwu decoction on the expression of MMPs and TIMPs in cardiac tissue of viral myocarditis （VMC） model mice. METHODS： Male BALb/c mice were randomly divided into control group， model group， positive control group [captopril， 100 mg/（kg·d）]， Buyang huanwu decoction low-dose， medium-dose and high-dose groups [6， 18， 36 g/（kg·d）]， with 24 mice in each group. Except for control group， other groups were given Coxsackie virus B3 once intraperitoneally to induce VMC model. After modeling， control group and model group were given constant volume of normal saline intragastrically； administration groups were given relevant medicine intragastrically； once a day， for consecutive 30 days. The general situation of mice in each group was observed. The day of inoculation was set at 0 d， heart mass to body mass ratio （HW/BW） was measured at 4， 10， 20， 30 d after inoculation. The morphological characteristics of myocardium were observed by HE staining， and the myocardial histopathological scores of myocardium were evaluated. The distribution of type Ⅰ and Ⅲ collagen in myocardium was observed by Abcam picrosirius red staining， and the ratio of type Ⅰ to Ⅲ collagen was calculated. At 30 d， relative expressions of MMP-1， MMP-3， MMP-9 and TIMP-1 in cardiac tissue were detected by Western blotting assay， and the ratio of MMPs to TIMPs was calculated. RESULTS： Compared with control group， mice in model group suffered from irritability， arch back， alleviation of stimulation response， reduction of body mass and even mental depression. Typical inflammatory changes and local interstitial hyperemia were observed in the myocardium， accompanied by a large number of lymphocyte infiltration and distribution of type Ⅰ and Ⅲ collagen. HW/BW （at different time points of 10-30 d）， myocardial histopathological score （at different time points of 4-30 d）， ratio of type Ⅰ and Ⅲ collagen （at different time points of 4-30 d）， the expression of MMP-1 and MMP-9， ratio of MMPs to TIMPs were increased significantly， while the expression of MMP-3 and TIMP-1 were decreased significantly （P＜0.05）. Compared with model group， above symptoms of mice in administration groups were improved to different extents. HW/BW [at different time points of 10-30 d in administration groups （except for 10 d in Buyang huanwu decoction low-dose group）]， myocardial histopathological score （at different time points of 10-30 d in administration groups）， ratio of type Ⅰand Ⅲ collagen （at different time points of 4-10 d in positive control group and Buyang huanwu decoction high-dose group， at different time points of 20-30 d in Buyang huanwu decoction low-dose and medium-dose groups）， the expression of MMP-1 （positive control group and Buyang huanwu decoction high-dose group） and MMP-9 （administration groups）， ratio of MMPs to TIMPs （administration groups） were decreased significantly， while the expression of MMP-3 （positive control group， Buyang huanwu decoction low-dose and high-dose groups） and TIMP-1 （administration groups） were increased significantly （P＜0.05）. CONCLUSIONS： Buyang huanwu decoction can inhibit myocardial fibrosis of VMC model mice by inhibiting myocardial collagen hyperplasia， regulating the expression of MMPs and TIMPs， improving MMPs/TIMPs imbalance.

Dynamic chromatopharmacokinetics model for components in Chinese medicine and validation in Buyang Huanwu Decoction / 中国中药杂志

The Chinese medicine is mostly derived from plants or animals, highly polymorphic, with dynamic components which are reflected by the characteristic peaks and fingerprint peaks in chromatographic fingerprints. The chromatopharmacokinetics method for determined components is not applicable due to dynamic changes of chromatopharmacokinetics. Based on the preliminary study, dynamic pharmacokinetics mathematical model for multiple components in Chinese medicine was set up and verified by Buyang Huanwu Decoction as the model drug, applying the principle of the total quantum statistical moment(TQSM), superimposing or subtracting the relevant statistical parameters in blood samples and blank samples. This provided a new method for the chromatopharmacokinetic study of Chinese medicine. HPLC was used to determine the TQSM parameters in blood and blank sample fingerprints of Buyang Huanwu Decoction at each point, and the overall TQSM parameters of drug-containing blood sample and blank samples were obtained with addition calculation of TQSM; while the initial TQSM of the pure drug can be obtained with subtraction calculation. The metabolic and absorption equilibrium constants were calculated iteratively to a steady state using the estimated metabolic equilibrium constants, then the metabolic chromatopharmacokinetic parameters in rats were obtained: VUC_T 1.262×10~8 mAu·s, MRT_T 37.48 h, VRT_T 9.016×10~2 h~2, CL_T 25.79 mL·h~(-1)·kg~(-1), Vs 1.586×10~2 mL·kg~(-1), t_(T,0.5) 6.15 h, respectively. This suggested that 95% of the compounds in whole recipe were metabolized and secreted from the body after 0-96.33 h. The experiment verified that the established mathematical model and the total quantum moment statistics parameters can represent the dose-time relationship of Buyang Huanwu Decoction, which can be used to study on in vivo metabolism dynamics for Chinese medicine.

Effect of modified Buyang Huanwu Decoction on hemorrhagic transformation after rt-PA intravenous thrombolysis in patients with super early cerebral infarction / 中国中药杂志

To study the effect of modified Buyang Huanwu Decoction on the hemorrhagic transformation after intravenous thrombolysis of recombinant tissue type plasminogen activator(rt-PA) in patients with super early(onset time<4. 5 h) cerebral infarction. From March 2016 to July 2018,at the brain disease zone of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,212 cases of super early cerebral infarction were selected and divided into two group according to the randomized complete blocks designs: control group(106 cases) and traditional Chinese medicine group(106 cases). The control group was treated with rt-PA intravenous thrombolysis,while the traditional Chinese medicine group was treated with modified Buyang Huanwu Decoction in addition to the therapy of the control group. Both groups were treated for 14 days. Neurological deficit score,serum matrix metalloproteinase-9(MMP-9),neuron specific enolase(NSE),vascular endothelial growth factor(VEGF) and plasma cellular fibronectin(c-FN) levels,the incidence of hemorrhagic transformation,clinical efficacy and adverse drug reactions before and after treatment were compared between the two groups. According to the findings,at the 14 thday after treatment,the rank sum test of the grade data showed that the clinical efficacy of the traditional Chinese medicine group was better than that of the control group(Z =-2. 033,P = 0. 042); on the basis of χ2 test,the total efficiency of the traditional Chinese medicine group was higher than that of the control group(χ2= 4. 895,P =0. 027); the hemorrhagic transformation rate of the traditional Chinese medicine group was lower than that of the control group within14 days of treatment(χ2= 3. 962,P = 0. 047). MMP-9 levels in the traditional Chinese medicine group were lower than those in the control group at the 3 rd,5 th,7 th,10 th,14 thd after treatment(t =-2. 474,-3. 022,-5. 163,-6. 998,-9. 821; P = 0. 014,0. 003,0,0,0). The improvement of c-FN,NSE,VEGF and NIHSS scores in the traditional Chinese medicine group was superior to that of the control group after 14 days of treatment(t =-2. 343,-3. 187,-2. 129,-3. 105; P = 0. 020,0. 002,0. 034,0. 002). No obvious adverse reactions of modified Buyang Huanwu Decoction were observed during 14 days of treatment. Modified Buyang Huanwu Decoction could reduce the expressions of MMP-9,c-FN,NSE and VEGF after rt-PA intravenous thrombolysis in patients with super early cerebral infarction,and decrease the hemorrhagic transformation rate after thrombolysis,with high safety.

Effect of Yijing Buyang Huanwu Decoction on intraocular pressure and prognosis of open angle glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To study the effect of Yijing Buyang Huanwu Decoction on intraocular pressure control and prognosis in patients with open angle glaucoma. <p>METHODS: Totally 93 patients(186 eyes)with open angle glaucoma admitted to our hospital from July 2015 to July 2017 were selected. All patients were divided into two groups according to the random number table method. In the observation group, 47 cases(94 eyes)were treated with timolol eye drop combined with Yijing Buyang Huanwu Decoction, and in the control group, 46 cases(92 eyes)were treated with timolol eye drop only. The clinical effect, visual acuity, intraocular pressure, central retinal artery blood flow, mean defect area, visual field average photosensitivity and image evoked visual potential were observed and compared before and after treatment. <p>RESULTS: The total effective rate of the observation group after treatment was significantly higher than that of the control group(85.1% <i>vs</i> 63.0%, <i>P</i><0.01). After treatment, the intraocular pressure in the observation group was significantly lower than that in the control group(<i>P</i><0.01). After treatment, RI values of central retinal artery blood flow in observation group were significantly lower than those in control group(<i>P</i><0.01). PSA and EDV values were significantly higher than those in control group(<i>P</i>=0.011,<0.01). After treatment, the average photosensitivity of the observation group was significantly higher than that of the control group(<i>P</i>=0.001), and the average defect area was significantly less than that of the control group(<i>P</i>=0.011). <p>CONCLUSION: Yijing Buyang Huanwu Decoction is effective in the treatment of open angle glaucoma. It can effectively control the level of intraocular pressure, enlarge the visual field, promote blood circulation and improve the prognosis.

Efficacy and safety of Buyang Huanwu Decoction for early-stage diabetic nephropathy: a Meta-analysis / 中国中药杂志

Buyang Huanwu Decoction(BHD) has the effect in benefiting Qi and activating blood circulation,and is the representative prescription for benefiting Qi and activating blood. At present,it is used for treatment of early diabetic nephropathy. However,its efficacy and safety remained to be verified. Therefore,this study aims to systematically evaluate the efficacy and safety of Buyang Huanwu Decoction for early-stage diabetic nephropathy. Data of randomized controlled trials(RCTs) of Buyang Huanwu Decoction for earlystage diabetic nephropathy were collected through the retrieval of electronic databases,including PubMed,EMbase,the Cochrane Library,CBM,CNKI,VIP and Wan Fang Data from inception to September 16,2018. Two reviewers independently screened out literatures,extracted data,and assessed the risk of bias. And then Meta-analysis was conducted by Rev Man 5. 3 software. A total of 15 RCTs involving 1 402 patients were included. The results of Meta-analysis indicated that Buyang Huanwu Decoction and conventional treatment group(combination treatment group) were superior to conventional treatment group in reducing 24 h urinary albumin excretion rates(MD =-40. 23,95% CI[-71. 25,-9. 21],P = 0. 01) and total cholesterol(MD =-0. 75,95% CI[-1. 02,-0. 48],P <0. 000 01). The effects of the two groups in reducing serum creatinine were similar(MD =-1. 48,95%CI[-4. 48,1. 53],P = 0. 34).However,the reduction of triglyceride was affected by the course of treatment. The effects were similar in less than or equal to eight weeks(MD =-0. 33,95%CI[-0. 97,0. 31],P = 0. 31),whereas the combination group was superior to the conventional treatment group in 12 weeks(MD =-0. 30,95%CI[-0. 58,-0. 22],P = 0. 03) and more than or equal to 16 weeks(MD =-0. 49,95% CI[-0. 9,-0. 08],P= 0. 02). There were no significant difference in adverse events between the two groups(OR= 1. 38,95%CI[0. 28,6. 8],P = 0. 69). The results showed that combination treatment group has a significantly higher efficacy on early diabetic nephropathy.The above conclusion shall be verified with more high-quality RCTs because of the low quality of the included studies.