Deciphering the molecular mechanism of Bu Yang Huan Wu Decoction in interference with diabetic pulmonary fibrosis via regulating oxidative stress and lipid metabolism disorder.

BACKGROUND: Diabetes mellitus type 2 and pulmonary fibrosis have been found to be closely related in clinical practice. Diabetic pulmonary fibrosis (DPF) is a complication of diabetes mellitus, but its treatment has yet to be thoroughly investigated. Bu Yang Huan Wu Decoction (BYHWD) is a well-known traditional Chinese prescription that has shown great efficacy in treating pulmonary fibrosis with hypoglycemic and hypolipidemic effects. METHODS: The active ingredients of BYHWD and the corresponding targets were retrieved from the Traditional Chinese Medicine Systematic Pharmacology Database (TCMSP) and SymMap2. Disease-related targets were obtained from the GeneCard, OMIM and CTD databases. GO enrichment and KEGG pathway enrichment were carried out using the DAVID database. AutoDock Vina software was employed to perform molecular docking. Molecular dynamics simulations of proteinligand complexes were conducted by Gromacs. Animal experiments were further performed to validate the effects of BYHWD on the selected core targets, markers of oxidative stress, serum lipids, blood glucose and pulmonary fibrosis. RESULTS: A total of 84 active ingredients and 830 target genes were screened in BYHWD, among which 56 target genes intersected with DPF-related targets. Network pharmacological analysis revealed that the active ingredients can regulate target genes such as IL-6, TNF-α, VEGFA and CASP3, mainly through AGE-RAGE signaling pathway, HIF-1 signaling pathway and TNF signaling pathway. Molecular docking and molecular dynamics simulations suggested that IL6-astragaloside IV, IL6-baicalein, TNFα-astragaloside IV, and TNFα-baicalein docking complexes could bind stably. Animal experiments showed that BYHWD could reduce the expression of core targets such as VEGFA, CASP3, IL-6 and TNF-α. In addition, BYHWD could reduce blood glucose, lipid, and MDA levels in DPF while increasing the activities of SOD, CAT and GSH-Px. BYHWD attenuated the expression of HYP and collagen I, mitigating pathological damage and collagen deposition within lung tissue. CONCLUSIONS: BYHWD modulates lipid metabolism disorders and oxidative stress by targeting the core targets of IL6, TNF-α, VEGFA and CASP3 through the AGE-RAGE signaling pathway, making it a potential therapy for DPF.

Anti-inflammatory effects of powdered product of Bu Yang Huan Wu decoction: Possible role in protecting against Transient Focal Cerebral Ischemia.

Bu Yang Huan Wu decoction (BYHW) is a traditional Chinese medicine (TCM) that consists of several herbs and has been used in patients with ischemic stroke for centuries. Although powdered formula of BYHW has widely been prescribed in clinic nowadays, evidence-based effectiveness and mechanism of action of BYHW powdered product in stroke remain to be characterized. Adult male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 90 min followed by reperfusion for 24 h (ischemia/reperfusion; I/R) or sham surgery. After I/R, the rats were then given low dose (0.5 g/kg) and high dose (2.5 g/kg) of BYHW or vehicle by oral gavage twice a day for seven consecutive days. The results showed that I/R induced obvious cerebral infarction and neurobehavioral defects, in parallel with histological aberrations and extensive signaling of proinflammatory cytokines, including tumor necrosis factor (TNF-α) and interleukin-6 (IL-6), in the stroke model. Post-I/R treatment with BYHW powdered product significantly reduced the infarct area and ameliorated neurofunctional defects in a dose-dependent manner. The dose dependence was associated with TNF-α downregulation and interleukin-10 (IL-10) induction. In summary, the present findings demonstrated that BYHW powdered product exhibited therapeutic efficacy for experimental stroke and a higher dose treatment may strengthen the effectiveness via inflammatory modulation.

Analysis on Effect and Mechanism of Bu-Yang Huan-Wu Decoction of Alzheimer's Disease Mice / 世界科学技术-中医药现代化

This study was aimed to investigate the effects of Bu-Yang Huan-Wu (BYHW) decoction to the learning and memory ability of APP/PS1 double transgenic mice through two behavior tests,in order to observe the Alzheimer's disease (AD) treatment effect of BYHW decoction.A total of 60 APP/PS1 double transgenic mice were randomly divided into five groups,which were the model group,the hydrochloride group,the high-,middle-,and low-dose BYHW decoction group,with ten rats in each group.The C57BL/6J mice were used as the control group.After 30 days of drug administration,all mice were subjected to behavior tests,including new object recognition experiment and step-through task.Western blot was used to detect changes of inflammatory factors,including IL-6 and TNF-α,in hippocampus of mice.The results showed that compared with the model group,the high-and middle-dose BYHW decoction can significantly decrease inflammatory factors of IL-6 and TNF-α expression in hippocampus of APP/PS1 mice.It can also obviously improve the learning and memory ability of APP/PS1 mice.It was concluded that BYHW decoction can significantly decrease the inflammatory factor expression in APP/PS 1 double transgenic AD model mice.It can obviously improve its learning and memory ability,which can be used in the treatment of AD.

Therapeutic Observation of Acupoint Application for Stroke Due to Qi Deficiency and Blood Stagnation / 上海针灸杂志

Objective To observe the clinical efficacy of acupoint application based on the formula ofBu Yang Huan Wu decoction in treating stroke due to qi deficiency and blood stagnation.Method Totally 109 patients with stroke due to qi deficiency and blood stagnation were randomized into a treatment group of 55 cases and a control group of 54 cases. In addition to the basic treatment, the treatment group was intervened by acupoint application based on formula ofBu Yang Huan Wu decoction at Dazhui (GV 14), Zusanli (ST 36), and Xuanzhong (GB ), while the control group received relevant health education. The symptom and syndrome score of traditional Chinese medicine (TCM), National Institute of Health Stroke Scale (NIHSS), and Barthel Index (BI) were observed before and after treatment, and the clinical efficacies and relapse rates were compared.Result The symptom and syndrome score of TCM, NIHSS score, and BI score were significantly different from that before treatment in both groups (P0.05).Conclusion Acupoint application is an effective method in treating stroke due to qi deficiency and blood stagnation.

Study on Volatile Ingredient and GC-MS Fingerprint of Bu-yang Huan-wu Decoction / 世界科学技术-中医药现代化

This study was aimed to establish GC-MS fingerprint of Bu-yang Huan-wu (BYHW) decoction. The 5HP-MS quartz capillary column was used. The temperature program carrier gas was He. The velocity was 1.0 mL·min-1. The injection volume was 1 μL. The split ratio was 1:20. The MS conditions were electron impact (EI) ion source with the transmission line temperature at 280oC, ion source temperature at 230oC, and quadrupole temperature at 150oC. The mass scan range was m/z 50~550. And the results were contrasted with ChemStation and NIST 05a. The results showed that nine common peaks were obtained in the fingerprint of eleven batches of BYHW decoction by peaks matched with the Similarity Evaluation System for Chromatographic Fingerprint (2004 A Version). The similari-ty of fingerprints was calculated more than 0.93. It was concluded that fingerprinting can be used as a method of quality control and provide evidence for the research of volatile ingredient of BYHW decoction.

Effect of Bu Yang Huan Wu decoction(补阳还五汤) on basic fibroblast growth factor in rats with cerebral ischemia / 中国中西医结合急救杂志

Objective To investigate the effect of Bu Yang Huan Wu decoction(BYHWD,补阳还五汤) on the expression of basic fibroblast growth factor(bFGF) and its mechanism of anti-cerebral ischemia.Methods Eighty-five Sprague-Dawley rats(body weight 280-300 g) were randomly divided into five groups: normal control group(n=5),sham-operated group,model group(n=20),traditional BYHWD group and ultra-fine powder BYHWD group.Then the latter four groups were further divided into four subgroups of 1,3,5 and 7 days(each n=5).The cerebral ischemic rat model was made by occluding the middle cerebral artery(MCA) with a thread.The traditional decoction and ultra-fine powder decoction groups were ingested with the liquid medicine of BYHWD after 2 hours of the operation(2 ml per rat per day,according to the surface area,it was equivalent to three times the dosage of 70 kg adult(human)).All groups were executed at the 1,3,5 and 7 days after the operation.At the same time there were 5 rats as the normal control group.The brain tissue was taken for the preparation of specimens.The distribution and expression difference of bFGF in the ischemic brain tissues of rats in different groups had been investigated with immuohistochemistry technique.The contents of bFGF in the brain tissue were detected with enzyme linked immunosorbent assay(ELISA).Results The positive expression of bFGF at peri-infarct area after ischemia increased obviously,but at central-infarct area there was less such positive expression.There was no expression at contra-lateral side to the ischemic area.The expression of bFGF immune positive cell increased at 1 day,peaked at 3 days,and returned to baseline at 7 days.The positive cells of bFGF in tradition decoction and ultra-fine powder decoction groups were obviously more than those in the model group at 3,5 and 7 days(all P

The protecting effects of Jia Wei Bu Yang Huan Wu decoction on the injury of 16 Hz,130 dB infrasound / 中华物理医学与康复杂志

Objective To study the effects of Jia Wei Bu Yang Huan Wu decoction on learning and memory abilities, superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities and the contents of malondialdehyde (MDA) in mice exposed to 16 Hz,130 dB infrasound. Methods Fifty BALB/c mice were divided into a control group (group C), an infrasound-control group (IC group), an infrasound and drug-treated group (ID group). Learning and memory abilities,SOD and GSH-PX activities and MDA contents were measured 14 d after corresponding treatment. Results Compared with those in group C, learning and memory abilities was significantly decreased(P0.05)in IC group. Compared with those in IC group, learning and memory abilities was increased(P