Mechanism Of Tao Hong Si Wu Decoction Research Articles

Potential mechanism of Taohong Siwu Decoction in preventing and treating postoperative delirium in intertrochanteric fracture patients based on retrospective analysis and network pharmacology

ObjectiveElderly patients with hip fractures are at a greater risk of developing postoperative delirium (POD), which significantly impacts their recovery and overall quality of life. Neuroinflammation is a pathogenic mechanism of POD. Taohong Siwu Decoction (THSWD), known for its ability to promote blood circulation and remove blood stasis, can effectively reduce inflammation in the nervous system. Therefore, the objective of this article is to provide a comprehensive summary of the clinical efficacy of THSWD in the prevention of POD. Additionally, it aims to investigate the underlying mechanism of THSWD in the prevention and treatment of POD using network pharmacology and molecular docking.MethodsWe conducted a retrospective analysis of patients with intertrochanteric fractures between January 2016 and October 2021. The patients were divided into two groups: the control and THSWD group. We performed a comparative analysis of hemoglobin (HB), albumin (ALB), C-reactive protein (CRP), blood urea nitrogen (BUN), and the blood urea nitrogen to creatinine ratio (BCR) on two different time points: the day before surgery (D0) and the third day after surgery (D3). Furthermore, we examined the incidence and duration of delirium, as well as the Harris Hip Score (HHS) at 3 months and 12 months post-surgery. Network pharmacology was employed to identify the primary targets and mechanisms of THSWD in the management of delirium. Molecular docking was employed to confirm the interaction between active ingredients and COX-2. Inflammatory cytokines, including cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor- (TNF-α), were measured using the enzyme-linked immunosorbent assay (ELISA). The cognitive status of the patients was assessed using the Mini-Mental State Examination (MMSE) scoring system.ResultsRegardless of whether it is in D0 or D3, THSWD treatment can increase HB levels while decreasing BCR. In D3, the THSWD group demonstrated a significant reduction in the expression of CRP and BUN when compared to the control group. However, there were no significant differences in ABL levels, surgery duration, and blood loss between the two groups. Additionally, THSWD treatment requires fewer blood transfusions and can reduce the incidence and duration of POD. The results of the logistic analysis suggest that both CRP levels and BCR independently contribute to the risk of POD. Network pharmacology analysis indicates that THSWD has the potential to prevent and treat POD possibly through inflammatory pathways such as IL-17 signaling pathways and NF-kappa B signaling pathways. Molecular docking validated the interaction between the active ingredient of THSWD and COX-2. Furthermore, THSWD treatment can reduce the levels of COX-2, IL-1β, IL-6, TNF-α, BUN and CRP in the blood of patients with POD, increase HB levels, and enhance MMSE scores. The expression of COX-2 is positively associated with other inflammatory markers (IL-1β, IL-6, TNF-α, and CRP), and inversely associated with MMSE.ConclusionTHSWD has been found to have a preventive and therapeutic effect on POD in intertrochanteric fracture patients possibly through inflammatory pathways. This effect may be attributed to its ability to increase hemoglobin levels and reduce the levels of certain detrimental factors, such as blood urea nitrogen and inflammatory factors.

Applications and Mechanisms of Taohong Siwu Decoction in the Treatment of Ischemic Stroke

Ischemic stroke is a kind of sudden vascular disease of the brain brought on by ischemic hypoxic necrosis of the brain tissue which is becoming a significant global source of death and long-term impairment. Present common treatment options for cerebral ischemia including thrombolytic therapy, mechanical embolization, and intracranial arterioplasty can only benefit a few patients due to the narrow therapeutic time windows. Traditional Chinese Medicine (TCM) prescriptions possess the qualities of multi-ingredients, multi-targets, synergistic and multi-efficacy advantages as a means of treating ischemic stroke. Taohong Siwu Decoction (THSWD) is a famous TCM prescription that promotes blood flow, removes blood clots, adds nourishment, and tonifies blood. Clinical and laboratory research results show the significant advantages of THSWD in ischemic stroke treatment. This review summarizes THSWD’s natural materials and processing methods, pharmacological effects, and related mechanisms to treat ischemic stroke. Its mechanism of action focuses on improving hemorheology, anti-inflammatory response, reducing excitotoxicity, anti-calcium overload, anti-oxidative stress, etc. Moreover, we systematically summarize THSWD and its use in combination with other treatments. Finally, the research obstacles of THSWD in the treatment of ischemic stroke are summarized, and the application prospects in the medical field are prospected.

The Tao Hong Si Wu Decoction ameliorates diabetes-associated cognitive dysfunction by inhibiting the formation of amyloid plaques.

The herbs in Tao Hong Si Wu Decoction (THSWD) are beneficial in the treatment of cognitive impairment. However, the underlying mechanisms of THSWD in treating diabetes-associated cognitive dysfunction (DACD) are not entirely explored. This study is aimed to investigate the therapeutic effects of THSWD in DACD model rats and the underlying mechanism. Ultra-high-phase liquid chromatography was employed to identify the main compounds contained in the THSWD extract. DACD rat model was induced by feeding with a high-sugar and high-fat diet and injecting streptozotocin (35mg/kg). DACD rats were gavaged with THSWD for 1week. The learning and memory abilities of the rats were measured by using the Morris water maze. Western blotting was used to detect the changes in DACD rat targets. Statistical methods were used to evaluate the correlation between proteins. The results show that THSWD effectively reduced the escape latency, hippocampal neuron damage, glycosylated hemoglobin, type A1C, and blood lipid levels in DACD rats. Furthermore, DACD rats showed significantly increased amyloid precursor protein, β-secretase, Aβ1-40 , Aβ1-42 , Tau phosphorylation, and advanced glycation end products (AGEs) expression. However, THSWD treatment can reverse this phenomenon. THSWD can improve the learning and memory abilities of DACD rats by inhibiting the expression of AEGs-AGE receptors pathway, which provides an experimental basis for the clinical application of THSWD. In addition, the experiment combines pharmacological and statistical methods, which offers a new perspective for the study of Chinese herbal medicine.

Exploring the potential mechanism and molecular targets of Taohong Siwu Decoction against deep vein thrombosis based on network pharmacology and analysis docking.

This study aims to investigate the mechanism of Taohong Siwu Decoction (THSWD) against deep vein thrombosis (DVT) using network pharmacology and molecular docking technology. We used the Traditional Chinese Medicine Systems Pharmacology database and reviewed literature to identify the main chemical components of THSWD. To find targets for DVT, we consulted GeneCards, Therapeutic Target Database, and PharmGKB databases. We used Cytoscape 3.8.2 software to construct herb-disease-gene-target networks. Additionally, we integrated drug targets and disease targets on the STRING platform to create a protein-protein interaction network. Then, we conducted Kyoto Encyclopedia of Genes and Genomes and gene ontology analysis. Finally, We employed the molecular docking method to validate our findings. We identified 56 potential targets associated with DVT and found 61 effective components. beta-sitosterol, quercetin, and kaempferol were the most prominent among these components. Our analysis of the protein-protein interaction network revealed that IL6, L1B, and AKT1 had the highest degree of association. Gene ontology analysis showed that THSWD treatment for DVT may involve response to inorganic substances, negative regulation of cell differentiation, plasma membrane protein complex, positive regulation of phosphorylation, and signaling receptor regulator activity. Kyoto Encyclopedia of Genes and Genomes analysis indicated that lipid and atherosclerosis, pathways in cancer, as well as the PI3K-Akt pathway are the main signal pathways involved. Molecular docking results demonstrated strong binding affinity between beta-sitosterol, quercetin, kaempferol, and AKT1 proteins as well as IL1B and IL6 proteins. The main targets for THSWD treatment of DVT may include AKT1, IL1B, and IL6. Beta-sitosterol, quercetin, and kaempferol may be the active ingredients responsible for producing this effect. These compounds may slow down the progression of DVT by regulating the inflammatory response through the PI3K/Akt pathway.

Exploration of the mechanism of Taohong Siwu Decoction for the treatment of ischemic stroke based on CCL2/CCR2 axis.

Taohong Siwu Decoction (THSWD) is a traditional Chinese herbal prescription that is effective for ischemic stroke, Whether THSWD regulates the CCL2/CCR2 axis and thus reduces the inflammatory response induced by ischemic stroke is not known. The aim of this study was to elucidate the mechanism of action of THSWD in the treatment of ischemic stroke using bioinformatics combined with in vitro and in vivo experiments. R language was used to analyze middle cerebral artery occlusion/reperfusion (MCAO/R) rat transcriptome data and to identify differential gene expression following THSWD treatment. Gene set enrichment analysis (GSEA) was used to analyze the gene set enrichment pathway of MCAO/R rats treated with THSWD. PPI networks screened key targets. The Human Brain Microvascular Endothelial Cells (HBMEC) Oxygen Glucose Deprivation/Reoxygenation (OGD/R) model and SD rat models of MCAO/R were established. FITC-dextran, immunofluorescence, flow cytometry, ELISA, immunohistochemistry, Western blotting, and RT-qPCR were performed to identify potential treatment targets. A total of 515 differentially expressed genes of THSWD in MCAO/R rats were screened and 92 differentially expressed genes of THSWD potentially involved in stroke intervention were identified, including Cd68, Ccl2, and other key genes. In vitro, THSWD reversed the increase in permeability of HBMEC cells and M1/M2 polarization of macrophages induced by CCL2/CCR2 axis agonists. In vivo, THSWD improved nerve function injury and blood-brain barrier injury in MCAO/R rats. Further, THSWD inhibited the infiltration and polarization of macrophages, reduced the expression of IL-6, TNF-α, and MMP-9, and increased the expression of IL-4, while reducing the gene and protein expression of CCL2 and CCR2. THSWD may play a protective role in ischemic stroke by inhibiting the CCL2/CCR2 axis, reducing the infiltration of macrophages, and promoting the polarization of M2 macrophages, thereby reducing inflammatory damage, and protecting injury to the blood-brain barrier.

Active components and potential mechanism of Taohong Siwu Decoction in regulating ischemic stroke based on target cell trapping combined with network pharmacology, molecular docking, and experimental validation

The potential anti-stroke active components in Taohong Siwu Decoction(THSWD) were identified by target cell trapping coupled with ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UPLC-Q-TOF-MS). The underlying mechanism of active components in THSWD in the treatment of ischemic stroke(IS) was explored by network pharmacology, molecular docking, and experimental validation. The UPLC-Q-TOF-MS technology combined with the UNIFI data analysis platform was used to analyze the composition of the cellular fragmentation fluid after co-incubation of THSWD with target cells. The targets of potential active components and IS were collected by network pharmacology, and the common targets underwent protein-protein interaction(PPI), Gene Ontology(GO), and Kyoto Encyclopedia of Genes and Genomes(KEGG) signaling pathway enrichment analyses. The target cell trapping component-core target-signaling pathway network was constructed, and the active components were molecularly docked to the top targets in the PPI network, followed by pharmacodynamic validation in vitro. Fifteen active components were identified in the target cellular fragmentation fluid, including bicyclic monoterpenes, cyanoglycosides, flavonols, quinoid chalcones, phenylpropanoids, and tannins. As revealed by the analysis of network pharmacology, THSWD presumably regulated PI3K-AKT, FoxO, MAPK, Jak-STAT, VEGF, HIF-1, and other signaling pathways to affect inflammatory cascade reaction, angiogenesis, oxidative stress, pyroptosis, apoptosis, and other pathological processes via paeoniflorin, butylphthalide, dehydrated safflower yellow B, 3,4-dicaffeoylquinic acid, amygdalin, paeoniflorin, and ligusticolactone. Molecular docking and in vitro pharmacodynamic validation revealed that the target cell trapping active components could promote neovascularization in rat brain microvascular endothelial cells(rBMECs) in the oxygen-glucose deprivation/reoxygenation(OGD/R) model. The application of target cell trapping coupled with UPLC-Q-TOF-MS technology can rapidly screen out the potential active components in THSWD. The active components of THSWD can be predicted to intervene in the pathogenesis of IS through network pharmacology, and molecular docking combined with experimental validation can further clarify the efficacy, thus providing a theoretical basis for research ideas on the pharmacodynamic substance basis of traditional Chinese medicine compounds.

Potential mechanism of Taohong Siwu Decoction in uterine fibroid treatment based on integrated strategy of network pharmacology and experimental verification

BackgroundTaohong Siwu Decoction (THSWD) is a widely prescribed Traditional Chinese Medicine (TCM) for treating gynecological diseases. It is used to treat uterine fibroids (UF) in China, while its potential therapeutic effects and mechanism are unknown.MethodsThe present study used network pharmacology to identify PI3K/AKT as one of the main THSWD signaling pathways that can be targeted to treat UF. The potential binding sites of miR-21-5p to PTEN were predicted using online databases. We were able to establish a UF rat model successfully. We selected the 15% THSWD serum after preparing THSWD drug-containing serum to culture tumor tissue-derived cells. These studies enabled us to assess the role of THSWD in UF improvement.ResultsIn vivo, we observed that low, medium, and high doses of THSWD improved histological changes in UF rats by increasing the expression levels of PTEN and miR-21-5p in their uterus while decreasing the expression levels of p-PI3K, p-AKT, and miR-21-5p. Treatment with THSWD medicated serum (15%) effectively inhibited the proliferation of cells derived from human UF and promoted apoptosis in vitro. PI3K phosphorylation, Akt phosphorylation, and miR-21-5p expression were decreased, while PTEN and cleaved caspase-3 were increased. These findings were reversed by administering 740 Y-P (a PI3K/Akt pathway agonist) and a miR-21-5p mimic. In addition, the double luciferase reporter gene assay confirmed the targeted binding relationship between miR-21-5p and PTEN.ConclusionsTHSWD inhibited the expression and activation of the PI3K/AKT and miR-21-5p/PTEN pathways, resulting in anti-UF activity in leiomyoma cell models. Our findings suggest that THSWD could be used to treat UF.

Taohong siwu decoction ameliorates cognitive dysfunction through SIRT6/ER stress pathway in Alzheimer's disease

Ethnopharmacological relevanceA growing number of people suffer from Alzheimer's disease (AD), but there is currently no effective treatment yet. Taohong Siwu Decoction (TSD) has been proved to take strong neuropharmacological activity on dementia, but the effect and mechanism of TSD against AD are still elusive. Aim of studyTo investigate whether TSD could be effective in ameliorating cognitive deficits through SIRT6/ER stress pathway. Materials and methodsHerein, the APP/PS1 mice, an AD model, and HT-22 cell lines were utilized. Different dosages of TSD (4.25, 8.50 and 17.00 g/kg/d) were administered to the mice for 10 weeks by gavage. Following the behavioral tests, oxidative stress levels were measured using malondialdehyde (MDA) and superoxide dismutase (SOD) kits. Nissl staining and Western blot analyses were used to detect the neuronal function. Then, immunofluorescence and Western blot analysis were applied to evaluate silent information regulator 6 (SIRT6) and ER Stress related protein levels in APP/PS1 mice and HT-22 cells. ResultsBehavioral tests revealed that APP/PS1 mice administered with TSD orally took more time in the target quadrant, crossed more times in the target quadrant, had a higher recognition coefficient, and spent more time in the central region. In addition, TSD could ameliorate oxidative stress and inhibit neuronal apoptosis in APP/PS1 mice. Furthermore, TSD could up-regulate the SIRT6 protein expression and inhibit ER sensing proteins expressions, such as p-PERK and ATF6, in APP/PS1 mice and Aβ1-42-treated HT22 cells. ConclusionAccording to the abovementioned findings, TSD could alleviate cognitive dysfunction in AD by modulating the SIRT6/ER stress pathway.

Exploring the mechanism of Taohong Siwu Decoction on the treatment of blood deficiency and blood stasis syndrome by gut microbiota combined with metabolomics

BackgroundTaohong Siwu Decoction (THSWD) is a prescription which included in the “List of Ancient Classic Prescriptions (First Batch)” issued by the National Administration of Traditional Chinese Medicine (TCM) and the National Medical Products Administration of the People’s Republic of China. THSWD is effective and widely applied clinically for many diseases caused by blood deficiency and stasis syndrome in TCM, such as primary dysmenorrhea, menopausal syndrome, coronary heart disease, angina pectoris, and diabetes.MethodsThe TCM model of blood deficiency and blood stasis syndrome was prepared by ice water bath combined with cyclophosphamide, and the rats were randomly divided into control group, blood deficiency, and blood stasis model group, positive group, and THSWD treatment group. Pharmacodynamics measured the blood routine, blood coagulation, and other related indexes in rats. UHPLC-MS technology was used to analyze the changes in the fingerprints of metabolites in the plasma of rats with blood deficiency and blood stasis syndrome, and combined with mass spectrometry information and public database retrieval, to find potential biomarkers for screening metabolites. At the same time, 16S rDNA sequencing technology was used to identify intestinal flora, and statistical analysis was used to find differences in strain diversity between groups.ResultsTHSWD administration can significantly improve the physical signs, blood routine, and hematopoietic factors caused by the blood deficiency and blood stasis syndrome model, and improve the symptoms of blood deficiency. The results of the general pharmacological studies showed THSWD groups improved changes in blood plasma viscosity and coagulation-related factors caused by modeling, and improved coagulation function significantly. The metabolomic analysis found that compared to the model group, THSWD exerted better effects on β-alanine, taurine, l-tyrosine, l-arginine, Eugenol, sodium deoxycholate, and deethylatrazine. Twenty-three potential differential metabolites showed intervention effects, mainly involved in eight metabolic pathways, including amino acid metabolism, taurine and hypotaurine metabolism, vitamin metabolism, and nucleotide metabolism. Gut microbiota data showed that, compared to the control group, the relative abundance and value of Firmicutes and Bacteroidota of the blood deficiency and blood stasis model group was significantly reduced, while the relative abundance of Actinobacteria, Spirochaetota, Proteobacteria, Campilobacterota, and other pathogenic bacteria was significantly increased. Following THSWD intervention, the abundance of beneficial bacteria increased, and the abundance of pathogenic bacteria decreased. Correlation analysis between the gut microbiota and differential metabolites showed that the two are closely related. THSWD affected the host blood system through mutual adjustment of these two factors, and improved blood deficiency and blood stasis syndrome in rats.ConclusionThe blood deficiency and blood stasis syndrome model of TCM disease caused by ice bath combined with cyclophosphamide lead to changes in the pharmacology, metabolomics, and gut microbiota. The intervention of THSWD can improve the symptoms caused by blood deficiency and blood stasis. The mechanism is mainly through the regulation of platelet function and amino acid metabolism.

Identification of Taohong Siwu Decoction in Treating Chronic Glomerulonephritis Using Network Pharmacology and Molecular Docking

Background: Based on network pharmacology and molecular docking technology, the pharmacological mechanism of Taohong Siwu Decoction (THSWD) in the treatment of chronic glomerulonephritis (CGN) was analyzed to provide a theoretical basis for the subsequent development of new drugs and the clinical application of Traditional Chinese Medicine (TCM). Methods: Active ingredients of drugs and disease target genes were obtained from Traditional Chinese Medicine Database and Analysis Platform (TCMSP) database and GeneCards database. The “drug component target” network of THSWD was constructed using Cytoscape version 3.8.2 software. The protein interaction was analyzed using STRING platform, the protein–protein interaction (PPI) network was constructed, and the potential protein function modules in the network were mined. Metascape platform was used to analyze “drug component target” and its biological processes and pathways. The clusterProfiler R package was called to perform kyoto encyclopedia of genes and genomes (KEGG) pathway and gene ontology (GO) function enrichment analysis on CGN-related targets regulated by THSWD. Molecular docking verification was performed by AutoDock Vina software. Results: THSWD has 205 target genes and 45 active components, 104 of which are cross with the CGN inflammatory gene. Its main active ingredients, stigmasterol, kaempferol, and sitosterol, have positive relationships with the inflammatory targets of CGN, tumor necrosis factor (TNF), IL-6, AKT1, and MAPK14. THSWD modulates the biological pathway of CGN and mainly acts on TNF-α signal pathway, interleukin-17 signal pathway, etc., whose main functions are response to lipid sugar, heme binding, G protein-coupled amine receptor activity, etc. The results of molecular docking showed that the main active compounds could bind to the core targets and showed good affinity. Conclusion: The molecular mechanism of THSWD in the treatment of CGN from the perspective of network pharmacology are components such as beta-sitosterol, kaempferol, and quercetin and key action targets such as TNF, IL-6, AKT1 protein kinase, and MAPK14 protein kinase play a synergistic role in autoimmune, infection, and inflammatory response-related pathways.

Protection of Taohong Siwu Decoction on PC12 cells injured by oxygen glucose deprivation/reperfusion via mitophagy-NLRP3 inflammasome pathway in vitro

Ethnopharmacological relevanceTaohong Siwu Decoction (THSWD) is a traditional Chinese medicine formula used to invigorate blood circulation and resolve blood stasis. It consists of Paeonia lactiflora Pall., Conioselinum anthriscoides (H.Boissieu) Pimenov & Kljuykov, Rehmannia glutinosa (Gaertn.) DC., Prunus persica (L.) Batsch, Angelica sinensis (Oliv.) Diels, and Carthamus creticus L. in the ratio of 3:2:4:3:3:2. THSWD is a common prescription for the treatment of ischemic stroke. Aim of the studyTo study the protective effect and mechanism of Taohong Siwu Decoction (THSWD) on PC12 cells damaged by oxygen glucose deprivation/reperfusion (OGD/R). Materials and methodsOGD/R model of PC12 cells was used to simulate ischemia-reperfusion (I/R) injury of nerve cells in vitro. The experiment was grouped as follows: control, OGD/R and OGD/R + THSWD (5%, 10% and 15%) group. Oxygen and glucose was restored for 24 h after 4–6 h of deprivation. The severity of damage to PC12 cells was evaluated by CCK8, flow cytometry and lactate dehydrogenase (LDH). Mitochondrial morphology and function were examined by transmission electron microscopy (TEM), ATP and mitochondrial membrane potential (MMP) assay kits. Cellular autophagy and NLRP3 inflammasome-associated proteins were detected by Western blot and immunofluorescence staining. ResultsTHSWD treatment improved the survival rate of PC12 cells injured by OGD/R, reduced cell damage and apoptosis. Moreover, ATP, MMP and the expression of autophagy marker proteins (LC3-II/LC3-I, Beclin1, Atg5) and mitophagy marker proteins (Parkin and PINK-1) was significantly elevated. The reactive oxygen species (ROS), NLRP3 inflammasome and pro-inflammatory cytokines induced by OGD/R were distinctly reduced. In contrast, these above beneficial effects of THSWD on mitochondrial autophagy and NLRP3 inflammasome were reversed by mitochondrial division inhibitory factor 1 (Mdivi-1). ConclusionTHSWD protects PC12 cells against OGD/R injury by heightening mitophagy and suppressing the activation of NLRP3 inflammasome.

Taohong Siwu Decoction Promotes Osteo-Angiogenesis in Fractures by Regulating the HIF-1α Signaling Pathway.

Background Vascular damage is a major consequence of bone fracture. Taohong Siwu decoction (TSD) can raise the expression of vascular endothelial growth factor (VEGF) in fracture healing. However, its molecular mechanism in promoting angiogenesis is still unknown. The aim of this study was to investigate the potential mechanisms of TSD in the regulation of osteo-angiogenesis in fracture healing. Methods A rat tibial fracture model was established. After low- (4.5 g·kg−1), medium- (9 g·kg−1), and high-dose TSD (18 g·kg−1) and panax notoginsenoside (25 mg kg−1) treatment, hematoxylin-eosin staining was employed to visualize pathological changes in bone tissues. The levels of cytokines (interleukin (IL)-2, tumor necrosis factor-α (TNF-α), IL-6, and IL-1β), thromboxane B2 (TXB2), and 6 ketone prostaglandin F1α (6-Keto-PGF1α) were quantified by enzyme-linked immunosorbent assay (ELISA). Immunofluorescence was used to identify the rat aortic endothelial cells (RAECs). Control serum, 10% TSD-containing serum, and 10% TSD-containing serum combined with hypoxia-inducible factor-1α (HIF-1α) inhibitor were used to treat the RAECs and rat osteoblasts. Transwell migration assay was utilized to examine the migration of the RAECs. The Matrigel tubulogenesis assay was used for the assessment of angiogenesis. The expression of angiogenesis- (von Hippel-Lindau tumor suppressor (VHL), HIF-1α, VEGF, angiopoietin-2 (Ang-2), and pVHL) and osteogenesis-related (alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), and osteopontin-1 (OPN-1)) protein and gene was detected by western blot and quantitative real-time PCR (qRT-PCR). Results Compared with the model group, TSD increased the trabecular bone areas, numbers, and thicknesses in fractured rats. In the plasma, the levels of cytokines and TXB2 in the middle- and high-dose TSD group were significantly lower than those in the model group (P < 0.01). The 6-keto-PGF1α content was increased by middle- and high-dose TSD intervention (P < 0.01). Compared to the control serum group, the angiogenesis and migration of the RAECs were enhanced in the TSD group (P < 0.001). The expression of HIF-1α, VEGF, and Ang-2 in the TSD group upregulated significantly (P < 0.001). VHL and pVHL were inhibited under TSD-containing serum treatment (P < 0.001). ALP, Runx2, and OPN-1 were increased obviously in the TSD group (P < 0.001). Nevertheless, the HIF-1α inhibitor reversed these changes (P < 0.001). Conclusion TSD promotes angiogenesis and osteogenesis by regulating the HIF-1α signaling pathway. Meanwhile, it can effectively reduce the risk of inflammation and improve blood circulation.

Network pharmacology and experimental validation-based approach to understand the effect and mechanism of Taohong Siwu Decoction against ischemic stroke

Ethnopharmacological relevanceTaohong Siwu Decoction (THSWD) is a classic prescription of traditional Chinese medicine that is mainly used for promoting blood circulation and alleviating blood stasis. THSWD is composed of Prunus persica (L.) Batsch, Carthamus tinctorius L., Ligusticum chuanxiong hort, Angelica sinensis (Oliv.) Diels, Rehmannia glutinosa (Gaertn.) DC, and Paeoniae Radix Alba. This prescription eliminates blood stasis, supplements blood, and dredges the body as an auxiliary treatment. Aim of the studyTo investigate the mechanistic effects of THSWD in the treatment of cerebral ischemia. Materials and methodswe downloaded 39 blood components for THSWD from the PharmMapper database for target prediction studies and identified the targets of cerebral ischemia. We identified the intersection between the components and targets, constructed a protein-protein interaction (PPI) network, carried out GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. a rat model of cerebral ischemia was established in rats, and the results of network pharmacology were verified by in vivo experiments. ResultsEstablished a component-target-pathway network, further transcriptomics analysis identified a total of 11 target genes (Plau, Fabp4, Mmp9, Mmp12, Cfd, Lcn2, Trem1, Lgals3, Hmox1, Selp and Slc6a4), a total of seven pathways (focal adhesion, complement and coagulation cascades, Staphylococcus aureus infection, malaria, transcriptional dysregulation in cancer, progesterone-mediated oocyte maturation, and the PI3K-Akt signaling pathway), because both targets genes and the complement and coagulation cascade signaling pathways mediate inflammatory responses, the signaling pathways associated with the complement and coagulation cascades were selected for experimental verification. We detected inflammatory factors and several key proteins in the complement and coagulation cascade signaling pathway (C1qb, C1qc, C3ar1, C5ar1, and Cfd). Analysis showed that THSWD can reduce the release of inflammatory factors and inhibit activation of the complement signaling pathways, thereby protecting against ischemic stroke disease. ConclusionsOur findings provide preliminary clarification of the predominant mechanism of action of THSWD when used to treat ischemic stroke.

Effects and Mechanisms of Taohong Siwu Decoction on the Prevention and Treatment of Myocardial Injury.

Taohong Siwu decoction (THSWD) is one of the classic prescriptions for promoting blood circulation and removing blood stasis. With the continuous in-depth excavation in basic and clinical research, it has been found that THSWD has made greater progress in the prevention and treatment of cardiovascular diseases. Mechanisms of the current studies have shown that it could prevent and treat the myocardial injury by inhibiting inflammatory reaction, antioxidant stress, inhibiting platelet aggregation, prolonging clotting time, anti-fibrosis, reducing blood lipids, anti-atherosclerosis, improving hemorheology and vascular pathological changes, regulating related signal pathways and other mechanisms to prevent and treat the myocardial injury, so as to protect cardiomyocytes and improve cardiac function. Many clinical studies have shown that THSWD is effective in the prevention and treatment of cardiovascular diseases related to myocardial injuries, such as coronary heart disease angina pectoris (CHD-AP), and myocardial infarction. In clinical practice, it is often used by adding and subtracting prescriptions, the combination of compound prescriptions and combinations of chemicals and so on. However, there are some limitations and uncertainties in both basic and clinical research of prescriptions. According to the current research, although the molecular biological mechanism of various active ingredients needs to be further clarified, and the composition and dose of the drug have not been standardized and quantified, this study still has exploration for scientific research and clinical practice. Therefore, this review mainly discusses the basic mechanisms and clinical applications of THSWD in the prevention and treatment of the myocardial injury caused by CHD-AP and myocardial infarction. The authors hope to provide valuable ideas and references for researchers and clinicians.

Taohong Siwu Decoction exerts anticancer effects on breast cancer via regulating MYC, BIRC5, EGF and PIK3R1 revealed by HTS2 technology

Taohong Siwu Decoction (TSD), a classical gynecological prescription that was firstly reported 600 years ago, has been widely used in the adjuvant treatment of breast cancer (BRCA) in China. However, the mechanism of action of TSD in treating BRCA has remained unclear. Here, high-throughput sequencing-based high-throughput screening (HTS2) technology was used to reveal the molecular mechanism of TSD, combination with bioinformatics and systems pharmacology in this study. Firstly, our results showed that TSD exerts an anticancer effect on BRCA cells by inhibiting cell proliferation, migration and inducing apoptosis as well as cell-cycle arrest. And our results from HTS2 suggested that herbs of TSD could significantly inhibit KRAS pathway and pathway in cancer, and activate apoptosis pathway, p53 pathway and hypoxia pathway, which may lead to the anticancer function of TSD. Further, we found that TSD clearly regulates MYC, BIRC5, EGF, and PIK3R1 genes, which play an important role in the development and progression of tumor and have significant correlation with overall survival in BRCA patients. By molecular docking, we discovered that Pentagalloylglucose, a compound derived from TSD, might directly bind to and inhibit the function of BRD4, which is a reported transcriptional activator of MYC gene, and thus repress the expression of MYC. Taken together, this study explores the mechanism of TSD in anti-BRCA by combining HTS2 technology, bioinformatics analysis and systems pharmacology.

Mechanism of Taohong Siwu Decoction in treating soft tissue injury based on UPLC-Q-TOF-MS,network pharmacology and experimental verification

To explore the action mechanism of Taohong Siwu Decoction(THSWD) in the treatment of soft tissue injury(STI) based on UPLC-Q-TOF-MS technique, network pharmacology and experimental verification method. UPLC-Q-TOF-MS technique was used to identify the chemical constituents of THSWD. The active ingredients and predicted target proteins of THSWD were screened out through TCMSP database. Cytoscape software was used to construct the active component-target-pathway network, and STRING database was used for protein interaction analysis. GeneCards and CTD databases were used to screen out relevant targets of STI. GO function and KEGG pathway enrichment analysis were performed through DAVID database. The rat model of STI was constructed, and Western blot was used to verify the effect of THSWD on key targets of relevant pathways. The results showed 40 active ingredients in THSWD, and 141 potential targets and 20 targets of STI. Target enrichment analysis of the active components produced 128 KEGG pathways, which were mainly concentrated in amino acid synthesis and metabolism, disease signaling pathways, apoptosis, inflammation and other relevant pathways. Western blot showed that THSWD intervention could significantly decrease PTGS2, CASP3, NFKB1, p-CASP3 and p-NFKB1, while enhancing the expression of TP53 protein in the STI samples of rats. According to the results of UPLC-Q-TOF-MS, network pharmacology and experimental verification, active ingredients in THSWD may play anti-inflammatory and antioxidant effects in NF-κB signaling pathway and apoptotic pathway, thus playing a role in the treatment of STI.

Active components and mechanism of Taohong Siwu Decoction in treatment of primary dysmenorrhea based on network pharmacology and molecular docking technology

This paper aimed to investigate the active components and mechanism of Taohong Siwu Decoction in the treatment of primary dysmenorrhea(PD) based on network pharmacology and molecular docking technology. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) was used to search the chemical compositions and targets of six herbs in Taohong Siwu Decoction. The targets for PD treatment were selected through the databases of DrugBank, OMIM, TTD and CTD, and gene annotation of the targets was conducted with UniProt database. Cytoscape 3.7.2 was then used to construct the drug-compound-target network. The protein-protein interaction(PPI) network was constructed based on STRING, and the core targets of Taohong Siwu Decoction in the treatment of PD were selected according to the topological parameters. David database was used for GO enrichment analysis and KOBAS 3.0 was used for KEGG enrichment analysis. The molecular docking technology was used to connect the components with higher medium values in the network with core targets. The results showed that the network contained 36 compounds such as quercetin, kaempferol, luteolin, myricanone and ferulic acid, and 99 targets such as PTGS2, PTGS2, PGR and PPARG. Totally 102 GO terms were obtained by GO functional enrichment analysis(P&lt;0.01), and 228 signal pathways were obtained by KEGG pathway enrichment(P&lt;0.05), mainly involving inflammatory factors, hormone regulation, central analgesia, amino acid metabolism and spasmolysis. The results of molecular docking showed that the main active components can spontaneously bind to the targets. This study preliminarily revealed the mechanism of Taohong Siwu Decoction for treatment of primary dysmenorrheal through multi-components, multi-targets and multi-pathways, providing theoretical references for further researches on mechanism of Taohong Siwu Decoction.

Uterine Metabolomics Reveals Protection of Taohong Siwu Decoction Against Abnormal Uterine Bleeding.

Incomplete abortion, a procedure for terminating pregnancy, will lead to abnormal uterine bleeding (AUB), infections, and even death. Taohong Siwu decoction (TSD) is a traditional Chinese medicine (TCM) formula, which has been developed to treat AUB for hundreds of years. However, the mechanism of the protective effect of TSD against AUB is not clear. We performed mass spectrometry (MS) of uterine samples to observe metabolic profile resulting from the treatment with TSD. An integrated gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry based untargeted metabolomics approach combined with multivariate statistical analyses were used to investigate the metabolic profile of TSD against AUB. There was clear separation between pregnant and incomplete aborting rats as well as incomplete aborting and TSD administered rats. Based on random forest algorithm and receiver operator characteristic analysis, 12 biomarkers were optimized related to TSD administered. The effect of TSD on AUB are related to several pathways, such as AA metabolism, glyoxylate and dicarboxylate metabolism, alanine, aspartate, and glutamate metabolism. To our knowledge, this is the first uterine metabolomics study focusing on TSD on AUB and provide a new perspective for explaining the mechanism of TSD on AUB.

Non-Targeted Metabolomic Profiling of Coronary Heart Disease Patients With Taohong Siwu Decoction Treatment.

Traditional Chinese medicine is one of the complementary and alternative therapies to improve the prognosis of coronary heart disease (CHD). Taohong Siwu Decoction (THSWD), a classical traditional Chinese medication that promotes blood circulation, is clinically beneficial in CHD. However, the underlying mechanism of THSWD is still unclear. To comprehensively understand the material foundation of the “blood”, it is significantly important to study the differential metabolites involved in the treatment of CHD with Chinese medicinal herb promoting blood circulation in TCM theory. Hence, this study investigated the metabolic profiles of the serum in CHD patients to determine the differential metabolites between the THSWD group and the placebo group. Eleven CHD patients were recruited and divided into two groups randomly and double-blindly. Serum samples were determined by performing non-targeted ultra-performance liquid chromatography with tandem mass spectrometry-based metabolomics. Pearson’s correlation analysis was used to assess the association between identified metabolites and clinical serum indexes of CHD. Based on the result, a total of 513 metabolites were found in the serum of CHD patients, of which 27, involved in 29 metabolic pathways, were significantly different between the two groups. Among the differential metabolites, THSWD upregulated succinylcarnitine in fatty acid metabolism and 5′-methylthioadenosine in cysteine and methionine metabolism compared with the placebo group. However, THSWD downregulated pelargonic acid, involved in FA metabolism; succinate, involved in the tricarboxylic acid cycle; gluconic acid, gluconolactone, and d-glucose, involved in pentose phosphate pathway; glycerophosphocholine, involved in glycerophospholipid metabolism; 8,9-dihydroxyeicosatrienoic acid (8,9-DiHETrE), l-lysine, N-acetyl-l-aspartic acid, N-alpha-acetyl-l-asparagine, hippurate, indoxyl sulfate, and 3-ureidopropionate involved in amino acid metabolism compared with the placebo group. Moreover, succinylcarnitine, pelargonic acid, succinate, d-glucose, gluconic acid, l-lysine, N-alpha-acetyl-l-asparagine, 5′-methylthioadenosine, indoxyl sulfate, 8,9-DiHETrE, and 3-ureidopropionate were associated with total cholesterol or low-density lipoprotein. Succinylcarnitine, pelargonic acid, gluconolactone, N-acetyl-l-aspartic acid, N-alpha-acetyl-l-asparagine, hippurate, and 5′-methylthioadenosine were associated with activated partial thromboplastin time. Our findings indicated that glycerophosphocholine, 8,9-DiHETrE, 5′-methylthioadenosine, hippurate, indoxyl sulfate, and 3-ureidopropionate might constitute the partial material foundation of the “blood” in CHD patients treated with THSWD.

Deciphering the intervention mechanism of Taohong Siwu Decoction following the abnormal uterine bleeding rats based on serum metabolic profiles

Abnormal uterine bleeding (AUB), one of the most significant characters of incomplete abortion, is a widespread phenomenon in gynecological that put a woman into a terrible physiological and psychological state. Taohong Siwu Decoction (TSD) is a traditional Chinese medicine (TCM) prescriptions which have treated AUB in China for decades. Our previous study elucidated that TSD reduced the volume of uterine bleedings as well as repaired the endometrium. The present study aims to investigate the mechanisms of TSD on AUB based on serum metabolomics. In this study, serum metabolic profile data was collected using ultra high-performance liquid chromatography with ion trap/time-of-flight mass spectrometry and gas chromatography-mass spectrometry. 23 potential biomarkers (urea, serine, L-proline, L-glutamic acid, palmitic acid, l-acetylcarnitine, LysoPC(16:0), LysoPC(20:4), l-proline, linoleic acid, stearic acid, l-isoleucine, phenylalanine, l-tyrosine, Oleic acid, et al) were eventually identified using multivariate statistical analysis (PCA and OPLS-DA) with VIP > 1, P < 0.05. Correlation analysis, fold-change (FC), area under receiver characteristic (ROC), false discovery rate (FDR) were used for data confirmation to ensure the authenticity of the data. The related-metabolic pathway mainly included amino acid metabolism (Phenylalanine, tyrosine, and tryptophan metabolism; Valine, leucine and isoleucine biosynthesis; Arginine and proline metabolism; Glycine, serine and threonine metabolism) and lipid metabolism (linoleic acid metabolism, glycerophospholipid metabolism). The results show that TSD has a favorable therapeutic effect on AUB by adjusting the metabolic disorders, which could provide dietary guidance for the clinic.