1.Effects of Busheng Huayu Qianggu prescription in elderly patients with osteoporotic lumbar fracture of kidney deficiency and blood stasis type
Guodong QIU ; Lei SUN ; Shuihua XIE
The Journal of Practical Medicine 2024;40(1):114-118
Objective To investigate the application value of Bushen Huayu Qianggu prescription in the treatment of senile osteoporotic lumbar fracture with kidney deficiency and blood stasis type.Methods All elderly patients with osteoporotic lumbar fractures of kidney deficiency and blood stasis were treated in our hospital from September 2021 to March 2023 and randomly divided into 68 cases in both groups.The control group was treated with conventional Western medicine,and the observation group was treated with BushengHuayuQiang Gu prescrip-tion for 12 weeks.Results Serum D-dimer(D-D),interleukin-6(IL-6)and prostaglandin E2(PGE2)were lower in the observation group than in the control group,and vascular endothelial growth factor(VEGF)and β-endorphin(β-EP)were higher(P<0.05);serum osteoprotegerin(OPG)and bone morphogenetic protein-2(BMP-2)were higher in the observation group(P<0.05);total effective rate was as high as 95.59%(65%)(P<0.05);bone mineral density(BMD)was higher in the observation group than in the control group after treatment,and the total symptom score and Cobb angle of Chinese medicine were lower(P<0.05);the total effective rate of the observation group was as high as 95.59%(65/68),higher than that of the control groupwhich was 80.88%(55/68)(P<0.05).Conclusion Combined treatment with BushenHuayuQianggu prescription can reduce inflammation,regulate bone metabolism,promote bone mineral density and improve clinical efficacy for senily-aged lumbar osteoporotic frac-ture caused by kidney deficiency and blood stasis.
2.Wenyang-Shengji ointment regulates GRP78/CHOP pathway to inhibit excessive endoplasmic reticulum stress for facilitating diabetic refractory wound repair
Yarong DING ; Shixu ZHENG ; Jun WANG ; Chenlei XIE ; Shuihua FENG ; Zhongzhi ZHOU ; Li CHEN
Chinese Journal of Pathophysiology 2024;40(3):493-501
AIM:To study the regulation of endoplasmic reticulum stress(ERS)using the glucose regulated protein 78(GRP78)/CCAAT/enhancer binding protein homologous protein(CHOP)pathway and explore the related mech-anism of Wenyang-Shengji ointment in facilitating the repair of diabetic refractory wounds.METHODS:To establish a rat model of diabetic refractory wound repair,Sprague-Dawley(SD)rats were fed a high-fat diet and intraperitoneally in-jected with streptozotocin.Subsequently,full-thickness skin defects were induced in the dorsal region of the rats.The ex-periment included 4 groups:normal,model(diabetic refractory wounds),Wenyang-Shengji ointment,and Beifuxin(re-combinant bovine basic fibroblast growth factor gel)groups.The normal and model groups were treated with normal saline after disinfection.In the Wenyang-Shengji ointment and Beifuxin groups,the wounds were topically treated with the re-spective ointments once daily.After 14 d of treatment,wound healing was assessed and quantified using the wound healing rate.Hematoxylin-eosin(HE)staining was employed to examine the micromorphology of the wound tissue.Western blot analysis was performed to measure GRP78,CHOP and caspase-12 levels in the wound tissue.Immunohistochemical analy-sis was used to detect the expression and distribution patterns of GRP78,CHOP and caspase-12 in the wounds.Transmis-sion electron microscopy was used to observe reticulum numbers and swelling.Enzyme-linked immunosorbent assay was used to determine interleukin-1β(IL-1β)level as a pro-inflammatory factor within the wound.RESULTS:Indexes of each group were assessed 14 d after the corresponding intervention.Compared with normal group,the rats in model group exhibited a significant decrease in the wound healing rate(P<0.01),accompanied by increased inflammatory exudation and poor granulation tissue growth.Additionally,there were increases in the expression levels of GRP78,CHOP and cas-pase-12 proteins(P<0.01),as well as a significant elevation in the content of inflammatory factor IL-1β(P<0.01).In contrast,compared with model group,treatment with Wenyang-Shengji ointment resulted in a significant improvement in wound healing rate(P<0.01),reduction in inflammatory exudation,and enhanced granulation tissue growth(P<0.01).Furthermore,there was a notable decrease in the protein expression of GRP78/CHOP/caspase-12 within the wound tissue following treatment with Wenyang-Shengji ointment(P<0.01).The levels of inflammatory factor IL-1β also showed a sig-nificant decrease(P<0.01).CONCLUSION:Wenyang-Shengji promotes the healing of diabetic refractory wounds,which may be associated with the downregulation of the GRP78/CHOP pathway,inhibition of excessive ERS,and reduc-tion in the level of wound cell apoptosis.
3.Potential Mechanism of Action of Qiangxin Decoction (强心汤) for Chronic Heart Failure Based on Network Pharmacology and Molecular Docking
Meiling MAO ; Jianqi LU ; Liyu XIE ; Yan PANG ; Ding ZHANG ; Weiqi SHI ; Shuihua LIU ; Zongyu CAI ; Shiyu ZHANG ; Min HUANG
Journal of Traditional Chinese Medicine 2023;64(20):2132-2137
ObjectiveTo reveal the targets and molecular mechanisms of the action of Qiangxin Decoction (强心汤) for the treatment of chronic heart failure based on the combination of network pharmacology and molecular docking. MethodsThe active ingredients of Qiangxin Decoction were retrieved from TCMSP database, and the targets of chronic heart failure were screened by searching GeneCards, OMIM, TTD, PharmGkb, and DrugBank databases, and the intersections were taken to obtain the intersecting targets of Qiangxin Decoction for the treatment of chronic heart failure. STRING platform was used to construct the protein-protein interaction network (PPI), Cytoscape 3.8.0 software was used to calculate the network topology to screen the core targets, and R 4.2.3 was used to construct the “active ingredient-target” network by analyzing the GO enrichment analysis and KEGG pathway enrichment analysis. AutoDock 1.5.7 was used for molecular docking to predict the binding performance of active ingredients and core targets. ResultsSeventy-five intersecting targets were identified for the treatment of chronic heart failure with Qiangxin Decoction, among which the core targets were estrogen receptor 1 (ESR1, degree value=7), nuclear receptor coactivator 1 (NCOA1, degree value=8), glucocorticoid receptor (NR3C1, degree value=7), and nuclear receptor coactivator 2 (NCOA2, degree value=7). GO enrichment analysis showed that the top 3 items with the smallest P value in molecular function were G protein-coupled amine receptor activity, postsynaptic neurotransmitter receptor activity, and neurotransmitter receptor activity (P<0.01); the top 3 items with the smallest P value in biological process were adenylyl cyclase-activated adrenergic receptor signaling pathway, adrenergic receptor signaling pathway, and adenylyl cyclase-regulated G protein-coupled receptor signaling pathway (P<0.01); the top 3 items with the smallest P values in cellular composition were components of the postsynaptic membrane, synaptic membrane, and presynaptic membrane (P<0.01). KEGG enrichment analysis showed that the top 5 key signaling pathways were neuroactive ligand-receptor interactions, calcium signaling pathway, dopaminergic synapses, cocaine addiction, and cyclic guanosine monophosphate-protein kinase G (cGMP-PKG) signaling pathway. The molecular docking results showed that lignans and isoflavones had lower binding energies and more structural stability with the four core targets (ESR1, NCOA1, NR3C1, NCOA2). ConclusionThe treatment of chronic heart failure by Qiangxin Decoction was associated with neuroactive ligand-receptor interactions, calcium signaling pathway, dopaminergic synapses, chemoattractant-receptor activation, cGMP-PKG signaling pathway, lipids and atherosclerosis, and cAMP signaling pathway, and lignans and isoflavones may be the core active compounds in its treatment of chronic heart failure.
4.Mechanism of Wenyang Shengji Ointment in treating diabetic wounds based on network pharmacology and animal experiments
DING Yarong ; XIE Chenlei ; FENG Shuihua ; YUAN Zhonghang ; WANG Wei ; LIU Mulin ; ZHOU Zhongzhi ; CHEN Li
Digital Chinese Medicine 2024;7(1):79-89
Objective :
To explore the mechanism of Wenyang Shengji Ointment (温阳生肌膏, WYSJO) in the treatment of diabetic wounds from the perspective of network pharmacology, and to verify it by animal experiments.
Methods:
The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and related literature were used to screen active compounds in WYSJO and their corresponding targets. GeneCards, Online Mendelian Inheritance in Man (OMIM), DrugBank, PharmGkb, and Therapeutic Target Database (TTD) databases were employed to identify the targets associated with diabetic wounds. Cytoscape 3.9.0 was used to map the active ingredients in WYSJO, which was the diabetic wound target network. Search Tool for the Retrieval of Interaction Gene/Proteins (STRING) platform was utilized to construct protein-protein interaction (PPI) network. Kyoto Encyclopedia of Genes and Genomes (KEGG) andGene Ontology (GO) enrichment analyses were performed to identify signaling pathways between WYSJO and diabetic wounds. AutoDock 1.5.6 was used for molecular docking of core components in WYSJO to their targets. Eighteen rats were randomly divided into control, model, and WYSJO groups (n = 6). The model and WYSJO groups were used to prepare the
model of refractory wounds in diabetes rats. The wound healing was observed on day 0, 5, 9, and 14 after treatment, and the wound tissue morphology was observed by hematoxylin-eosin(HE) staining. The expression levels of core genes were detected by quantitative real-timepolymerase chain reaction (qPCR).
Result:
A total of 76 active compounds in WYSJO, 206 WYSJO drug targets, 3 797 diabetic wound targets, and 167 diabetic wound associated WYSJO targets were screened out through network pharmacology. With the use of WYSJO-diabetic wound target network, core targets of seven active compounds encompassing quercetin, daidzein, kaempferol, rhamnetin, rhamnocitrin, strictosamide, and diisobutyl phthalate (DIBP) in WYSJO were found. GO enrichment analysis showed that the treatment of diabetes wounds with WYSJO may involve lipopolysaccharide, bacteria-derived molecules, metal ions, foreign stimuli, chemical stress, nutrient level, hypoxia, and oxidative stress in the biological processes. KEGG enrichment analysis showed that the treatment of diabetes wounds with WYSJO may involve advanced glycation end products (AGE-RAGE), p53, interleukin (IL)-17, tumor necrosis factor (TNF),hypoxia inducible factor-1 (HIF-1), apoptosis, lipid, atherosclerosis, etc. The results of animal experiments showed that WYSJO could significantly accelerate the healing process of diabetic wounds (P < 0.05), alleviate inflammatory response, promote the growth of granulation tissues, and down-regulate the expression levels of eight core genes [histone crotonyltransferase p300 (EP300), protoc gene-oncogene c-Jun (JUN), myelocytomatosis (MYC), hypoxia inducible factor 1A (HIF1A), mitogen-activated protein kinase 14 (MAPK14), specificity protein 1 (SP1), tumor protein p53 (TP53), and estrogen receptor 1 (ESR1)] predicted by the network pharmacology (P < 0.05).
Conclusion
The mechanism of WYSJO in treating diabetes wounds may be closely related to AGE-RAGE, p53, HIF-1, and other pathways. This study can provide new ideas for the pharmacological research of WYSJO, and provide a basis for its further transformation and application.