Clinical study of modified photodynamic therapy combined with Taohong Siwu Decoction in treating hypertrophic scar after severe burn

Abstract Objective: The aim of this study was to study the curative effect and the relative mechanism of modified photodynamic therapy combined with Taohong Siwu Decoction in the treatment of hyperplastic scar after severe burn, in order to provide a stable, safe and satisfactory scheme for scar repair. Methods: Forty cases with hyperplastic scars after severe burns admitted to the plastic surgery department from May 2021 to May 2022 were divided into a control group and an observation group by means of the random number table method. The control group was treated with ordinary laser therapy combined with Taohong Siwu Decoction, while the observation group was treated with modified photodynamic therapy combined with Taohong Siwu Decoction. The Vancouver Scar Scale (VSS) was assessed in both groups, and the clinical effectiveness of both groups was compared. HE-staining was performed on the scar tissue of the same patient before and after treatment to observe the changes in the arrangement of fibroblasts. The Vascular Endothelial Growth Factor (VEGF), β-Transforming Growth Factor (TGF-β), and Platelet-Derived Growth Factor (PDGF) in the tissue samples of both groups were detected by quantitative real-time PCR. The patients were followed up for 6 months, and their satisfaction, side effects, and scar recurrence were observed. Results: Compared with the control group, the VSS score in the observation group was lower (p < 0.05). The therapeutic effect of the observation group was superior to the control group after 3 months (p < 0.05). After 3-months of therapy, the arrangement of fibroblasts in the scar became looser in two groups, and the observation group was more looser. The VEGF, TGF-β and PDGF levels in tissue samples of the observation group were lower than those in the control group after 3 months of treatment (p < 0.05). The satisfaction of the observation group was higher than that of the control group (p < 0.05). The adverse reactions between the two groups showed no difference (p > 0.05), while the recurrence rate was lower in the observation group (p < 0.05). Conclusion: Modified photodynamic therapy combined with Taohong Siwu Decoction shows remarkable efficacy in patients with hyperplastic scars after severe burns. It can improve the color, thickness, vascular distribution, and softness of the scar, and reduce the level of cytokines related to tissue repair. At the same time, it can improve patients' satisfaction with the aesthetic appearance and reduce the recurrence rate, providing a new comprehensive therapy that is safer and more effective, simple and quick, and easy to promote in the clinic.

Study on the mechanism of Taohong siwu decoction improving peripheral nerve injury induced by paclitaxel in rats / 中国药房

OBJECTIVE To explore the mechanism of Taohong siwu decoction （THD） improving peripheral nerve injury induced by paclitaxel （PTX） in rats. METHODS The effects of THD （1 g/mL drug-containing serum） and PTX （0.1 μmol/L） alone or in combination on the proliferation rate of Schwann cells line RSC96 as well as the expressions of lysosomal-associated membrane protein-2 （LAMP2）， autophagy marker protein yeast Atg 6 homolog （Beclin1）， phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， and mammalian target of rapamycin （mTOR） were investigated， and then compared with autophagy promoter rapamycin and autophagy inhibitor 3-methyladenine （3-MA）. The effects of high-dose and low-dose THD on the expressions of myelin basic protein （MBP） and myelin protein zero （MPZ）， S100 calcium-binding protein （S100）， LAMP2， Beclin1， PI3K， Akt and mTOR were tested at the end of the experiment. RESULTS After treatment of THD+PTX， the proliferation rate of RSC96 cells was significantly higher than those treated with PTX alone. After treatment of THD+PTX or THD+ 3-MA， the protein expressions of LAMP2 and Beclin1 in RSC96 cells were significantly higher than those treated with PTX or 3- MA alone， while the protein expressions of PI3K， Akt and mTOR were significantly lower than those treated with PTX or 3-MA alone （P＜0.05）. Compared with model group， the protein expressions of MBP， MPZ， S100， LAMP2 and Beclin1 in sciatic nerve of rats were increased significantly in THD high-dose and low-dose groups， while the protein expressions of PI3K， Akt and mTOR were significantly decreased （P＜0.05）. CONCLUSIONS THD may activate Schwann cell autophagy by inhibiting the PI3K/Akt/ mTOR signaling pathway， thereby improving peripheral nerve injury caused by PTX.

Therapeutic effect of Taohong Siwu decoction on a mouse model of carbon tetrachloride-induced liver fibrosis and its mechanism / 临床肝胆病杂志

Objective To investigate the therapeutic effect of Taohong Siwu decoction on a mouse model of carbon tetrachloride (CCl 4 )-induced liver fibrosis and its mechanism of action. Methods A total of 24 male C57BL/6 mice were randomly divided into normal group, model group, and Taohong Siwu decoction group, with 8 mice in each group. The mice in the model group and the Taohong Siwu decoction group were given intraperitoneal injection of 10% CCl 4 , and Taohong Siwu decoction was given by gavage since week 3 for 4 consecutive weeks. Liver function [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] was measured, and liver pathomorphology was observed. Real-time PCR was used to measure the mRNA expression of α-smooth muscle actin (α-SMA), hyaluronic acid synthase-2 (HAS-2), and collagen type Ⅰ(Col1), and Western blotting was used to measure the protein expression of α-SMA, Col1, and HAS-2. Primary hepatic stellate cells (HSCs) were isolated, and HAS-2 was silenced by siRNA to observe its influence on HSC activation. The t -test was used for comparison of continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the SNK or least significant difference t -test was used for further comparison between two groups. Results Compared with the normal group, the model group had significant increases in serum liver function parameters (ALT, AST) and the Taohong Siwu decoction group had significant reductions in the serum levels of ALT and AST (all P < 0.01). Pathological staining showed that the model group had marked inflammatory cell infiltration and formation of fibrous septa by proliferated collagen fibers, and the Taohong Siwu decoction group had loose fibrous septa and alleviated inflammatory cell infiltration. Compared with the model group, the Taohong Siwu decoction group had significant reductions in the mRNA and protein expression of α-SMA and Col1(all P < 0.001). Compared with the normal group, the model group had a significant increase in the mRNA expression level of HAS-2 in liver tissue ( t =6.14, P < 0.05), and compared with the model group, the Taohong Siwu decoction group had a significant reduction in the protein expression level of HAS-2 (0.29±0.10 vs 1.00±0.12, t =70.73, P < 0.001). After HAS-2 was silenced by siRNA, the Si HAS-2+transforming growth factor β (TGFβ) group (treated with TGFβ) had significant reductions in the mRNA expression levels of α-SMA and Col-Ⅰ compared with the NC+TGFβ group ( P < 0.01). Conclusion Taohong Siwu decoction exerts a marked therapeutic effect on CCl 4 -induced liver fibrosis in mice by inhibiting HAS-2.

Efficacy and Safety Evaluation of Taohong Siwu Decoction () for Patients with Angina Pectoris: A Meta-Analysis of Randomized Controlled Trials / 中国结合医学杂志

OBJECTIVE@#To assess the efficacy and safety of Taohong Siwu Decoction (, TSD), a Chinese herbal compound prescription, in patients with angina pectoris (AP).@*METHODS@#Randomized clinical trials (RCTs) comparing TSD plus conventional treatment (CT) with CT plus placebo or CT only in the patients with AP were searched in PubMed, Cochrane Library, Excerpta Medica Database, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wanfang Database, Chinese Scientific Journal Database, Chinese Clinical Trial Registry and International Clinical Trial Registry from their inception to March 2017. The primary outcomes include a composite event of death, acute myocardial infarction (AMI), and target vessel revascularization. The secondary outcomes include angina symptom, electrocardiogram (ECG) improvement and serum high-sensitivity C-reactive protein (hs-CRP), endothelin-1 (ET-1), triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels. The methodological quality of included studies and extracted available data were assessed. RevMan 5.3 software was used to conduct statistical analysis. The relative risk (RR) and standardized mean difference (SMD) with 95% confidence interval (CI) was calculated. A funnel plot was used to evaluate the publication bias.@*RESULTS@#Among 204 studies identified in the literature search, 12 trials including 959 patients with AP met the inclusion criteria. No studies reported the primary outcome including death, AMI and target vessel revascularization. TSD combined with CT showed significant improvement in relieving angina symptom [RR=3.70, 95% CI (2.42, 5.67)] and ECG [RR=3.20, 95% CI (2.20, 4.65)] compared with CT alone. TSD combined with CT reduced the serum hs-CRP, TG, TC and LDL-C levels compared with CT alone. No serious adverse events were reported in TSD combined with CT.@*CONCLUSIONS@#TSD combined with CT has a potential benefit on relieving AP without significant adverse events. However, the efficacy on the cardiovascular events needs to be assessed by more rigorously-designed, largescale, and multi-center RCTs in future.

Analysis on quality value transfer of substance benchmarks of Taohong Siwu Decoction / 中国中药杂志

By preparing 15 batches of substance benchmarks of Taohong Siwu Decoction, the methodology of the characteristic spectrums of substance benchmarks was established. The paste-forming rate range, the contents and the transfer rate range of the index components, hydroxy safflower yellow A, ferulic acid and paeoniflorin, the characteristic peaks and the similarity range of the characteristic spectrums of Taohong Siwu Decoction were determined to define key quality attributes of substance benchmarks of Taohong Siwu Decoction.In the 15 batches of substance benchmarks of Taohong Siwu Decoction, the similarity of characteristic spectrums was higher than 0.9. Furthermore, based on summarization of the characteristic peak information, there were 13 characteristic peaks in the whole decoction. Baishao had three characteristic peaks, Honghua had seven characteristic peaks, and Chuanxiong and Danggui had three characteristic peaks. The paste-forming rate of the 15 batches of substance benchmarks was controlled at 33.11%-40.62%. The content of hydroxy safflower yellow A was 0.129%-0.203%, with the average transfer rate of 16.596%±0.669%.The content of ferulic acid was 0.043%-0.055%, with the average transfer rate of 20.489%±1.772%.The content of paeoniflorin was 0.676%-0.943%, with the average transfer rate of 29.112%±3.273%.The quality value transfer of substance benchmarks of classical prescription Taohong Siwu Decoction was analyzed by the combination of characteristic spectrums, paste-forming rate and the content of index components. The established substance benchmark quality evaluation method was stable and feasible, and could provide a basis for quality control and subsequent development of relevant preparations of Taohong Siwu Decoction.

Repair Effect and Mechanism of Taohong Siwu Decoction on Rotator Cuff Injury in Rabbits / 中国药房

OBJECTIVE：To study the repa ir effect and mechanism of Taohong siwu decoction on rotator cuff injury in rabbits. METHODS：New Zealand rabbits were randomly divided into blank control group ，model group ，Taohong siwu decoction low-dose，medium-dose and high-dose groups （2.75，5.5，11 g/kg），and Taohong siwu decoction+LY 294002 group [ 5.5 g/kg Taohong siwu decoction+ 6.4 μg/kg LY294002（pathway inhibitor ）]，with 11 rabbits in each group. Except for blank control group ， other groups underwent right subscapularis muscle detachment to establish rotator cuff injury model. After modeling ，blank control group and model group were given normal saline intragastrically ；Taohong siwu decoction groups were given relevant medicine intragastrically；Taohong siwu decoction+LY 294002 group was given Taohong siwu decoction intragastrically ，and then injected with LY 294002 at the ear edge ，once a day ，for 12 weeks. After last intragastric administration （injection），the pathological changes of tendon-bone interface was observed ；the levels of TNF-α，IL-10 and IL- 6 in serum were detected ；mRNA and protein expressions of PI 3K，Akt and mTOR in tendon-bone interface were detected ；the expression of autophagy related protein （Beclin1， LC3Ⅱ）were detected. RESULTS ：Compared with blank control group ，the tendon-bone interface was uneven and the intima was swollen in model group. Serum levels of TNF-α and IL-6，mRNA and protein expressions of PI 3K，Akt and mTOR in tendon-bone interface were increased significantly （P＜0.05 or P＜0.01），while the level of IL- 10 and protein expression of Beclin 1 and LC 3Ⅱ were decreased significantly （P＜0.01）. Compared with model group ，the tendon-bone interface of rabbits in Taohong siwu decoction low-dose and medium-dose groups still had certain intimal damage ，while the tendon-bone interface of rabbits in high-dose group was smooth and flat without an obvious intimal tear ；the levels of most indexes in serum and tendon-bone interface of rabbits were significantly reversed in each dose group （P＜0.05 or P＜0.01）. Swollen tendon-bone interface and obvious intimal tear were obse rved in Taohong siwu decoction + LY group；compared with model group ，there w as no significant difference in above indexes of serum and tendon-bone interface （P＞0.05）. CONCLUSIONS ：Taohong siwu decoction may repair the rotator cuff injury of rabbits ，the mechanism of which may be associated with inhibiting PI3K/Akt/mTOR signaling pathway，activating autophagy and inhibiting inflammatory response.

Mechanism of Taohong Siwu Decoction in treating soft tissue injury based on UPLC-Q-TOF-MS,network pharmacology and experimental verification / 中国中药杂志

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 / 中国中药杂志

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<0.01), and 228 signal pathways were obtained by KEGG pathway enrichment(P<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.

Prescription compatibility connotation and action mechanism of Siwu Decoction in treating primary dysmenorrhea / 中国中药杂志

The aim of this paper was to study the prescription compatibility connotation in the treatment of primary dysmenorrhea(PD) and verify the mechanism as predicted by network pharmacology of Siwu Decoction(SWD). Mice PD model was constructed by using estradiol benzoate-oxytocin. PD mice were randomly divided into 8 groups, namely normal group, model group, positive group, complete formula group, Rehmanniae Radix Praeparata-free group, Paeoniae Radix Alba-free group, volatile oil-free group, Chuan-xiong Rhizoma and Angelicae Sinensis Radix-free group. Latent time, writhing times, inhibition rate, prostaglandin F_2_α(PGF_2_α) and prostaglandin E_2(PGE_2) levels in serum, endothelin-1, Ca~(2+), expression levels of prostaglandin synthase 2 G/H(PTGS2), estrogen receptor(ESR1), glucocorticoid receptor gene(NR3 C1) mRNA and protein expression levels in the uterus homogenate and pathological changes of uterine tissue were index to explore the prescription compatibility connotation and verify the mechanism of SWD in the treatment of PD. Compared with the extraction liquid of the whole recipe, the effect of Rehmanniae Radix Praeparata-free group and Paeoniae Radix Alba-free group with volatile oil were slightly lower, the effect of essential oil-free group was significantly lower, and the effect of Chuanxiong Rhizoma and Angelicae Sinensis Radix-free group was worse than that of the whole recipe. The relative expression levels of PTGS2 protein and mRNA were significantly reduced by the SWD. The relative expressions of protein and mRNA of ESR1, NR3 C1 were significantly increased. SWD treats PD by regulating the expression of key proteins PTGS2, ESR1 and NR3 C1.Its main medicinal herbs were Angelicae Sinensis Radix and Chuanxiong Rhizoma. Active components were mainly in volatile oil, but Paeo-niae Radix Alba and Rehmanniae Radix Praeparata also had some contributions.

Comparative Study in Situ on Rat Intestinal Absorption Mechanism of Paeoniflorin in Single Herb, Herb-pair, and Complicated Chinese Herbal Formula / 中国药学杂志

OBJECTIVE: To investigate the absorption mechanism of paeoniflorin in Radix Paeoniae Alba, both of Radix Paeoniae Alba and Radix Angelica Sinensis and Siwu Decoction. METHODS: The circulatory perfusion technique was used in this study, the concentrations of paeoniflorin and phenol red in intestinal absorption circulation were respectively determined by HPLC and UV. The effects of pH value, drug concentration, absorption site and P-gp on the absorption of paeoniflorin were investigated separately. RESULTS: By comparing the absorption of paeoniflorin in Radix Paeoniae Alba, both of Radix Paeoniae Alba and Radix Angelica Sinensis, and Siwu Decoction, it was found that in the sample solution at the same absorption site, pH value and concentration (based on the concentration of paeoniflorin), the absorption, Ka and cumulative absorption of paeoniflorin in compound Siwu decoction group were significantly increased compared with the other groups (P<0.05), while t1/2 was significantly decreased (P<0.05). When combined with the inhibitor and inducer of P-gp, the absorption of paeoniflorin showed significant increase or decrease in the amount of absorption, Ka and cumulative absorption% compared with the control group (P<0.05), and t1/2 also showed significant decrease or increase (P<0.05). CONCLUSION: The absorption of paeoniflorin could be affected by P-gp, and under the same conditions, the absorption of paeoniflorin in complicated Chinese herbal formula is better than that in the single herb and herb-pair.

Underlying targets and mechanism of taohong siwu decoction in prosthetic joint infection on network pharmacology / 中国组织工程研究

BACKGROUND: Taohong Siwu Decoction has a good effect in the treatment of periprosthetic infection after joint replacement, and can improve the function of joint movement. However, most present studies focus on the antibacterial effect of single drug and its components in the prescription, and there is little research on the compound and other mechanisms. OBJECTIVE: To explore the mechanism of Taohong Siwu Decoction in the treatment of periprosthetic joint infection. METHODS: Ingredients and target genes of Semen Persicae, Carthami Flos, Rehmanniae Radix Praeparata, Paeoniae Radix Alba, Angelicae Sinensis Radixand and Chuanxiong Rhizoma were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Periprosthetic joint infection-related target genes were obtained from the human gene database (GeneCards). Cytoscape3.7.2 was used for constructing a “Drug-Ingredient-Target-Disease” network. The key target genes were introduced into the STRING to construct protein-protein interaction network. We analyzed the mechanism by Kyoto Encyclopedia of Genes and Genomes and Gene Ontology biological enrichment analysis. RESULTS AND CONCLUSION: (1) Totally 15 active components, such as quercetin, luteolin and kaempferol, were screened from Taohong Siwu Decoction, which acted on 34 key genes, such as vascular endothelial growth factor A, tumor necrosis factor, and interleukin-6. (2) Gene Ontology function enrichment showed that the biological process and function of Taohong Siwu Decoction were concentrated in positive regulation of biological process, response to chemical stimulus, response to stress, and regulation of apoptosis. (3) Kyoto Encyclopedia of Genes and Genomes pathway enrichment showed that the treatment of periprosthetic joint infection by Taohong Siwu Decoction mainly involved pathways in cancer, AGE-RAGE signaling pathway, fluid shear stress and atherosclerosis, inflammatory bowel disease and cytokine-cytokine receptor interaction pathway. (4) Through the study of network pharmacology, it is found that Taohong Siwu Decoction could treat periprosthetic joint infection by inhibiting bacterial growth and improving hemorheology, which provided a preliminary theoretical basis for the application of “activating circulation and removing blood stasis” in periprosthetic joint infection and a new idea for subsequent experiments.

Network pharmacology-based study on mechanism of Siwu Decoction in treatment of primary dysmenorrhea / 中国中药杂志

This paper aimed to predict and explore the mechanism of multiple components, targets and pathways of Siwu decoction for treatment of primary dysmenorrhea, and to establish a network pharmacological model of "compound-target-pathway-disease". According to the active ingredients in Siwu Decoction, Swiss Target Prediction server was used to predict the active component targets based on the reverse pharmacodynamic group matching method, and the primary dysmenorrhea targets approved by FDA were selected by database including DrugBank, OMIM and TTD. According to the enrichment analysis of the target pathways by using KEGG, the Cytoscape software was used to construct the network of "compound-target-pathway-disease" of Siwu Decoction. Network analysis showed that there were 20 active components involved in 114 pathways. And 16 components, 16 target proteins and 24 pathways were related to primary dysmenorrhea. Siwu Decoction may play a role in treating primary dysmenorrhea by acting on protein targets and pathways related to hormone regulation, central analgesia, spasmolysis,inflammation and immunity. This study revealed the potential active compounds and possible mechanism of Siwu Decoction for treatment of primary dysmenorrhea, providing theoretical references for further systematic laboratory experiments on effective compounds and action mechanism of Siwu Decoction.

Anti-oxidative effect of siwu decoction on aged mice / 预防医学

Objective To evaluate the anti-oxidative function of siwu decoction.Methods Using aged mice model and setting three dose groups(0.58 g/kg BW, 1.17 g/kg BW, 3.50 g/kg BW), negative control group, after feeding four groups for 30 days with the lyophilized powder of the siwu decoction product, removing accessories, the content of lipid oxidation product malondialdehyde(MDA), glutathione(GSH)and protein carbonyl, the activity of superoxide dismutase(SOD)were tested. Results In the control group, the activity of SOD was(33.0±3.4)U/mgprot, and the content of GSH and protein carbonyl were(5.56±0.73)mg/gprot,(2.30±0.22)nmol/mgprot, respectively. Compared with the control group, the activity of SOD in the high dose group(39.2±6.3 U/mgprot)and the content of GSH in the medium and high dose group[(7.04±0.86) mg/gprot,(6.81±1.02)mg/gprot, respectively]was significantly higher(P<0.05); the content of protein carbonyl notably in the high dose group[(1.78±0.32)nmol/mgprot]significantly decreased(P<0.05). No obvious difference in the content of MDA were observed between each dose group and the control group (P>0.05). Conclusion Siwu decoction has obvious antioxidant effect on aged mice.

Study on biopharmaceutical properties of active fraction from Xiangfu Siwu Decoction by composite phospholipid liposome-based artificial skin membrane / 中草药

Objective: To evaluate the feasibility of the application of composite phospholipid liposome-based artificial skin membrane (CPLASM) for measuring biopharmaceutical properties of active fraction extracted from Xiangfu Siwu Decoction (XSD) via transdermal administration. Methods: The HPLC method was established for the determination of active ingredients (ferulic acid, tetrahydrocolumbamine, tetrahydropalmatine, senkyunolide I, and senkyunolide H) in active fraction of XSD. The oil/water partition coefficient values of these active ingredients were measured. The CPLASM was prepared to determine the in vitro permeability parameters of active fraction of XSD. The obtained parameters were further compared with those obtained by porcine ear skin. Results: The oil-water partition coefficients of ferulic acid, tetrahydrocolumbamine, tetrahydropalmatine, senkyunolide I, and senkyunolide H in active fraction of XSD (pH 5.5) were measured to be 1.220 ± 0.280, 0.670 ± 0.085, 0.920 ± 0.110, 1.040 ± 0.092, 1.030 ± 0.093 (n = 3), respectively. The permeability parameters of the active ingredients through porcine ear skin and CPLASM indicated a significant correlation (r > 0.9). Compared with the classical oil-water partition coefficients, the 6 h- cumulative permeation ratio of five active ingredients through CPLASM can be characterized as effectively predicting permeability parameters through porcine ear skin. Conclusion: The biopharmaceutical properties of active fractions from Chinese material medica can be effectively characterized by the application of CPLASM for the determination of in vitro permeability parameters of active ingredients.

Effects of traditional herbal formulae on human CYP450 isozymes / 中国结合医学杂志

<p><b>OBJECTIVE</b>To assess the effects of traditional herbal formulae Sijunzi Decoction (, Sagunja-tang, SJZD), Siwu Decoction (, Samul-tang, SWD), Bawu Decoction (, Palmul-tang, BWD) and Shiquan Dabu Decoction (, Sipjeondaebo-tang, SDD) on the activities of human cytochrome P450 (CYP450), a drug-metabolizing enzyme.</p><p><b>METHODS</b>Herbal formula water extracts were filtered and lyophilized after the powder extracts were dissolved in distilled water. The activities of major human CYP450 isozymes (CYP3A4, CYP2C19, CYP2D6 and CYP2E1) were measured using in vitro fluorescence-based enzyme assays. The inhibitory effects of the herbal formulas on the activities of CYP450 were characterized as half maximal inhibition concentration (IC) values.</p><p><b>RESULTS</b>All the tested herbal formulae inhibited CYP2C19 activity (IC: SJZD, 83.28 μg/mL; SWD, 235.54 μg/mL; BWD, 166.82 μg/mL; SDD, 178.19 μg/mL); SJZD (IC= 196.46 μg/mL), SWD (IC= 333.42 μg/mL) and SDD (IC= 163.42 μg/mL) inhibited CYP2E1-mediated metabolism; whereas BWD exhibited comparatively weak inhibition of CYP2E1 (IC= 501.78 μg/mL). None of the four herbal formulas significantly affected CYP3A4 or CYP2D6.</p><p><b>CONCLUSIONS</b>These results suggest that SJZD, SWD, BWD and SDD could potentially inhibit the metabolism of co-administered synthetic drugs whose primary route of elimination is via CYP2C19. In addition, clinically relevant pharmacokinetic interactions could occur when SJZD, SWD or SDD is co-administered with drugs metabolized by CYP2E1. Our findings provide information for the safety and effective clinical use of these four classic herbal formulas.</p>

Siwu decoction improves iron deficiency anemia in infant rats and regulates iron metabolism / 中国中药杂志

To investigate the effect of Siwu decoction on improving iron deficiency anemia in infant rats and observe its regulatory effects on iron metabolism. SD rats were fed with low iron fodder for 2 weeks, and then the rats with hemoglobin level less than 75 g•L ⁻¹ were screened out and randomly divided into model group, Ferrous succinate 50 mg•kg ⁻¹ group, Siwu decoction 4 g•kg ⁻¹, 8 g•kg ⁻¹ and 16 g•kg ⁻¹ groups. After 4 weeks' gavage administration, Wright-Giemsa's staining of blood smear and HE staining of the livers were conducted, and all rats were tested for blood routine, serum iron, total iron binding capacity, serum ferritin, serum hepcidin and liver hepcidin. The expression levels of liver ferritin, transferrin and transferrin receptor 1 were also detected. The results showed that as compared with normal group, the activity level of model group was decreased, and the color and lustre of auricles and toes were pale white; the number of red blood cells was decreased; the volume was smaller, with an increased zone of central pallor; the body weight and blood routine parameters were decreased significantly; the livers were pale red, and the hepatic cords around thecentral veins were unclear and misaligned; the serum iron, serum ferritin, liver iron levels and the expression of liver ferritin were decreased significantly; the total iron binding capacity, serum hepcidin, liver hepcidin, the expression levels of liver transferrin and transferrin receptor 1 were significantly increased, indicating successful establishment of models. As compared with the model group, activity was increased in Siwu decoction group; the color and lustre of auricles and toes were ruddy; the number of red blood cells was increased; the volume was larger, with a decreased zone of central pallor; the body weight and blood routine parameters were increased significantly; the livers were red, hepatic cords around the central veins were clear and aligned;the serum iron, serum ferritin, liver iron levels and the expression of liver ferritin were significantly increased, the total iron binding capacity, serum hepcidin, liver hepcidin, the expression of liver transferrin and transferrin receptor 1 were decreased significantly. The results demonstrated that Siwu decoction had a certain effect on improving iron deficiency anemia in infant rats, and the mechanism may be associated with the regulatory effect of hepcidin iron metabolism.

Clinical Efficacy of Modified Taohong Siwu Decoction in Adjuvant Therapy of Traumatic Fracture: A Systematic Review / 中国药房

OBJECTIVE:To systematically review the therapeutic efficacy and safety of modified Taohong siwu decoction in adjuvant therapy of traumatic fracture,and to provide evidence-based reference in clinic.METHODS:Retrieved from CJFD,CBM,Wanfang database and PubMed,related studies about fracture restitution combined with modified Taohong siwu decoction (trial group) vs.fracture restitution alone (control group) in the treatment of traumatic fracture were collected.Meta-analysis was conducted by using Rev Man 5.3 statistical software after data extraction and quality evaluation according to Cochrane systematic review.RESULTS:A total of 6 RCTs and 3 clinical control trials were included,involving 929 patients.Meta-analysis showed that clinical total response rate [RR =1.35,95 ％ Cl (1.24,1.47),P ＜ 0.001] and the incidence of gastrointestinal ADR [RR =5.59,95 ％ Cl (1.30,24.14),P=0.02] in trial group were significantly higher than control group;symptom and sign score [MD =-5.50,95 ％ Cl(-6.45,-4.54),P＜0.001],erythrocyte sedimentation [MD=-13.78,95％ Cl(-15.97,-11.60),P＜0.01],whole blood viscosity [MD=-1.03,95％Cl(-1.11,-0.95),P＜0.001],plasma viscosity [MD=-0.24,95％Cl(-0.27,-0.21),P＜0.01],hematocrit [MD=-12.12,95％Cl(-13.37,-10.86),P＜0.01] and erythrocyte electrophoresis time [MD=-7.12,95％Cl(-7.88,-6.35),P＜ 0.01] of trial group were significantly lower than those of control group,with statistical significance.CONCLUSIONS:For adjunctive therapy of traumatic fracture,modified Taohong siwu decoction can improve clinical efficacy,reduce the inflammatory reaction, improve blood rheology but aggravate gastrointestinal reaction.

Preventive effect of Taohong Siwu decoction on the formation of lower extremity deep vein thrombosis in patients with cerebral hemorrhage / 中国中西医结合急救杂志

Objective To observe the preventive effect of Taohong Siwu decoction on the formation of lower extremity deep vein thrombosis (DVT) in patients with cerebral hemorrhage.Methods Eighty patients with cerebral hemorrhage admitted to the Department of Neurosurgery in Huzhou First People's Hospital from November 2014 to January 2016 were enrolled, and they were divided into an observation group and a control group according to the difference in treatment methods, each group 40 cases. Both groups were given routine treatment and nursing care, the patients of observation group were additionally given Taohong Siwu decoction (composition:Radix Angelicae Sinensis (stir-fried with wine) 10 g,Radix Rehmanniae Preparata 10 g,Radix Paeoniae Alba10 g,Ligusticum Chuanxiong Hort 6 g,Semen Persicae 6 g,Carthami Flos 4 g), once a day for consecutive 2 weeks.Results The D-dimer level in the observation group was significantly lower than that in the control group (mg/L: 1.47±0.91 vs. 1.88±0.79,t = 1.991,P = 0.035); the incidence of DVT in the observation group was obviously lower than that in the control group [5.0% (2/40) vs. 20.0% (8/40), χ2 = 4.114,P = 0.043].Conclusion Taohong Siwu decoction can effectively reduce the incidence of DVT in patients with cerebral hemorrhage.

Effects of Siwu Decoction on Memory and Spatial Learning in Mice with Blood Deficiency and Related Mechanisms / 医药导报

Objective To investigate the effects of Siwu decoction on the learning and memory abilities in mice with blood deficiency and the related mechanism.Methods The mice were randomly divided into five groups:normal control group,model control group,high-,medium-,and low-dose group of Siwu decoction.Blood deficiency mouse model was established by continuously cuttingtailand bleedingin model control group,high-,medium-,and low-dose group of Siwu decoction.The mice in high-,medium-,and low-dose group were intragastrically administrated with Siwu decoction of 2.5,5.0,10.0 g·kg-1 for 14 days,respectively.The erythrocyte counts (RBC),hemoglobin (HGB),red blood cell hematocrit (HCT) were detected before modeling,7 and 14 days after administration.The spatial learning and memory abilities were assessed using the T maze test.The spontaneous activities were assessed using locomotors activity detector.The levels of erythropoietin (EPO) content in serum and acetylcholinesterase (AChE) in hippocampal tissue were detected by enzyme-linked immunousorbent assay.Results 5.0 and 10.0 g·kg-1Siwu decoction could increase RBC,HGB,HCT on the 7th and 14th day,2.5 g.kg-1Siwu decoction could increase RBC,HCT on 14th day,and each dosage of Siwu decoction could significantly increase the spontaneous activities of model mice with blood deficiency on the 7th and 14th day as compared with model control group (P ＜0.05 or P ＜0.01).Compared with model control group,the number of errorsin T Maze test were decreased significantly in high-,medium-,and low-dose groups (P ＜ 0.01).And the Siwu decoction had a tendency to reduce the hippocampal AChE levels,but when compared with the model control group there were no statistical differences (P ＞ 0.05).Conclusion Siwu decoction is benefit formemory and spatial learning in mice with blood deficiency,which may be related with higher serun EPO and lower hippocampal AChE expression.

Screening for differentially-expressed proteins in ovary of primary dysmenorrheal mice with Xiangfu Siwu decoction administration using nano LC-LTQ-Orbitrap-MS/MS / 中国中药杂志

To study the mechanism of Xiangfu Siwu decoction in treating primary dysmenorrhea, differentially-expressed proteins in ovary of primary dysmenorrheal mice with Xiangfu Siwu decoction administration were screened based on proteome technology using nano LC-LTQ-Orbitrap-MS/MS. Estradiol benzoate and oxytocin were used to produce dysmenorrheal mice model. The model mice were orally administrated with Xiangfu Siwu decoction for 3 days, and 1 h after the last administration, the ovary samples were collected. After protein denaturation, reduction, alkylation, desalination and enzymatic hydrolysis, identification was carried out by nano LC-LTQ-Orbitrap-MS/MS technology. The obtained data was processed by using Thermo Proteome discoverer 1.4 software. The differentially-expressed proteins were screened and identified, and their biological information was also analyzed. The significant differentially-expressed protein was checked using Western blot technology in ovary samples. A total of 106 differentially-expressed proteins were identified during the normal, model and administration group. Most of them participate cellular processes. Adherens junction and focal adhesion pathways play a regulatory role in various cell signaling pathways. Protein ADRM1 was validated. Compared to the normal group, it was up-regulated expression in the model group. After administration, the expression of ADRM1 was down-regulated. Through the comparative analysis, a series of differentially-expressed proteins involved in primary dysmenorrheal mice with Xiangfu Siwu decoction administration were obtained. Protein ADRM1 may become a target for Xiangfu Siwu decoction.