Si-Wu-Tang Research Articles

A survey of attitudes toward and experiences with traditional Chinese medicines among people in Taiwan.

Despite numerous surveys on traditional Chinese medicines (TCMs) and their impact on people in Taiwan, only a few directly assessed the perspectives of the users and their experiences with the practice. In this study, we aimed to explore the attitudes, experiences, and understanding of TCMs, and also to identify the TCMs that are commonly preferred among people in Taiwan. We conducted an online survey among people in Taiwan to reflect the views of the general public on TCMs in 2022. Medical-related personnel were excluded. Question topics included experience, impressions, access, and expectations. There were 518 participants. More than 95% of them had taken TCMs. "Work gently" was the most common positive impression, and "Slow to take effect" was the most common negative impression. Among the over-the-counter TCMs that were taken by the participants, "Si Wu Tang," which is used for disorders in women, was the most common. The main expectations for TCMs were to help to improve daily health and prevent diseases. Although the participants were highly aware of TCMs, there was still room for improvement. For example, 30% of the participants still did not know that TCMs may have side effects. The people in Taiwan who participated in the survey had a relatively positive impression of and experience with TCMs, but there were still some cognitive blind spots that need to be filled. It is essential to strengthen the publicity and education about TCMs and improve the public's understanding and correct use of TCMs.

Anti-inflammatory effects of Tao Hong Si Wu Tang in mice with lung cancer and chronic obstructive pulmonary disease.

Lung cancer (LC) combined with chronic obstructive pulmonary disease (COPD) is a common combination of comorbidities. Anti-inflammation and modulation of oxidative/antioxidative imbalance may prevent COPD-induced LC, and are also crucial to the treatment of LC combined with COPD. Modern studies have shown that Tao Hong Si Wu Tang (THSW) has vasodilatory, anti-inflammatory, anti-fatigue, anti-shock, immunoregulatory, lipid-reducing, micronutrient-supplementing, and anti-allergy effects. To observe the effects of THSW on COPD and LC in mice. A total of 100 specific pathogen-free C57/BL6 mice were randomly divided into five groups: Blank control group (group A), model control group (group B), THSW group (group C), IL-6 group (group D), and THSW + IL-6 group (group E), with 20 mice in each group. A COPD mouse model was established using fumigation plus lipopolysaccharide intra-airway drip, and an LC model was replicated by in situ inoculation using the Lewis cell method. The blank control group exhibited a clear alveolar structure. The model control and IL-6 groups had thickened alveolar walls, with smaller alveolar lumens, interstitial edema, and several inflammatory infiltrating cells. Histopathological changes in the lungs of the THSW and THSW + IL-6 groups were less than those of the model control group. The serum IL-1β, IL-6, and TNF-α levels and IL-6R, JAK, p-JAK, STAT1/3, p-STAT1/3, FOXO, p-FOXO, and IL-7R expression levels in lung tissues of mice in the rest of the groups were significantly higher than those of the blank control group (P < 0.01). Compared with the model control group, the IL-6 group demonstrated significantly higher levels for the abovementioned proteins in the serum and lung tissues (P < 0.01), and the THSW group had significantly higher serum IL-1β, IL-6, and TNF-α levels and IL-7R expression levels in lung tissues (P < 0.01) but significantly decreased IL-6R, JAK, p-JAK, STAT1/3, p-STAT1/3, FOXO, p-FOXO, and IL-7R levels (P < 0.01). THSW reduces the serum IL-1β, IL-6, and TNF-α levels in the mouse model with anti-inflammatory effects. Its anti-inflammatory mechanism lies in inhibiting the overactivation of the JAK/STAT1/3 signaling pathway.

Integrating UPLC-QTOF-MS/MS and UPLC-DAD to evaluate the influence of sulfur-fumigated Paeoniae Radix Alba on the overall quality of three Si-Wu-Tang formulations.

Sulfur-fumigation of Paeoniae Radix Alba (PRA) could induce the chemical transformation of its bioactive component paeoniflorin into a sulfur-containing derivative paeoniflorin sulfite, and thus alter the quality, bioactivities, pharmacokinetics, and toxicities of PRA. However, how sulfur-fumigated PRA (S-PRA) affects the quality of PRA-containing complex preparations has not been intensively evaluated. We intend to evaluate the influence of S-PRA on the overall quality of three kinds of Si-Wu-Tang (SWT) formulations, i.e., decoction (SWT-D), granule (SWT-G), and mixture (SWT-M). AnUPLC-DAD multi-components quantification method was used to compare the transfer rates of paeoniflorin sulfite and other 10 bioactive components between S-PRA-containing and NS-PRA-containing SWT formulations. An UPLC-QTOF-MS/MS-based target metabolomics approach was applied to explore the differential sulfur-containing derivatives in S-PRA-containing SWT formulations. The transfer rates of paeoniflorin sulfite in three S-PRA-containing SWT formulations were all higher than 100%. Moreover, S-PRA also increased the transfer rate of 5-hydroxymethylfurfural, 1,2,3,4,6-O-pentagalloylglucose, whereas decreased that of paeoniflorin, albiflorin, and ferulic acid in three SWT formulations. Six pinane monoterpene glucoside sulfites originally identified in S-PRA, were also detectable in three S-PRA-containing SWT formulations. In addition, seven phenolic acid sulfites including (3Z)-6-sulfite-ligustilide, (3E)-6-sulfite-ligustilide, 6,8-disulfite-ligustilide, ferulic acid sulfite, neochlorogenic acid sulfite, chlorogenic acid sulfite, and angelicide sulfite (or isomer) were newly identified in these three S-PRA-containing formulations. S-PRA could differentially affect the transfer rate of paeoniflorin sulfite and other bioactive components during the preparation of three SWT formulations and subsequently the overall quality thereof.

Si-Wu-Tang alleviates metabolic dysfunction-associated fatty liver disease by inhibiting ACSL4-mediated arachidonic acid metabolism and ferroptosis in MCD diet-fed mice

BackgroundMetabolic dysfunction-associated fatty liver disease (MAFLD) is a prevalent chronic liver disease worldwide. Si-Wu-Tang (SWT), a traditional Chinese medicine decoction has shown therapeutic effects on various liver diseases. However, the hepatoprotective effects and underlying mechanism of SWT on MAFLD remain unclear.MethodsFirst, a methionine-choline-deficient (MCD) diet-fed mice model was used and lipidomic analysis and transcriptomic analysis were performed. The contents of total iron ions, ferrous ions, and lipid peroxidation were detected and Prussian blue staining was performed to confirm the protective effects of SWT against ferroptosis. Finally, chemical characterization and network pharmacological analysis were employed to identify the potential active ingredients.ResultsSerological and hepatic histopathological findings indicated SWT's discernible therapeutic impact on MCD diet-induced MAFLD. Lipidomic analysis revealed that SWT improved intrahepatic lipid accumulation by inhibiting TG synthesis and promoting TG transport. Transcriptomic analysis suggested that SWT ameliorated abnormal FA metabolism by inhibiting FA synthesis and promoting FA β-oxidation. Then, ferroptosis phenotype experiments revealed that SWT could effectively impede hepatocyte ferroptosis, which was induced by long-chain acyl-CoA synthetase 4 (ACSL4)-mediated esterification of arachidonic acid (AA). Finally, chemical characterization and network pharmacological analysis identified that paeoniflorin and other active ingredients might be responsible for the regulative effects against ferroptosis and MAFLD.ConclusionIn conclusion, our study revealed the intricate mechanism through which SWT improved MCD diet-induced MAFLD by targeting FA metabolism and ferroptosis in hepatocytes, thus offering a novel therapeutic approach for the treatment of MAFLD and its complications.Graphical

Designing combinational herbal drugs based on target space analysis.

Traditional oriental medicines (TOMs) are a medical practice that follows different philosophies to pharmaceutical drugs and they have been in use for many years in different parts of the world. In this study, by integrating TOM formula and pharmaceutical drugs, we performed target space analysis between TOM formula target space and small-molecule drug target space. To do so, we manually curated 46 TOM formulas that are known to treat Anxiety, Diabetes mellitus, Epilepsy, Hypertension, Obesity, and Schizophrenia. Then, we employed Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties such as human ether-a-go-go related gene (hERG) inhibition, Carcinogenicity, and AMES toxicity to filter out potentially toxic herbal ingredients. The target space analysis was performed between TOM formula and small-molecule drugs: (i) both are known to treat the same disease, and (ii) each known to treat different diseases. Statistical significance of the overlapped target space between the TOM formula and small-molecule drugs was measured using supportvalue. Support value distribution from randomly selected target space was calculated to validate the result. Furthermore, the Si-Wu-Tang (SWT) formula and published literature were also used to evaluate our results. This study tried to provide scientific evidence about the effectiveness of the TOM formula to treat the main indication with side effects that could come from the use of small-molecule drugs. The target space analysis between TOM formula and small-molecule drugs in which both are known to treat the same disease shows that many targets overlapped between the two medications with a support value of 0.84 and weighted average support of 0.72 for a TOM formula known to treat Epilepsy. Furthermore, support value distribution from randomly selected target spacesin this analysis showed that the number of overlapped targets is much higher between TOM formula and small-molecule drugs that are known to treat the same disease than in randomly selected target spaces. Moreover, scientific literature was also used to evaluate the medicinal efficacy of individual herbs. This study provides an evidence to the effectiveness of a TOM formula to treat the main indication as well asside effects associated with the use of pharmaceutical drugs, as demonstrated through target space analysis.

Si-Wu-Tang attenuates hepatocyte PANoptosis and M1 polarization of macrophages in non-alcoholic fatty liver disease by influencing the intercellular transfer of mtDNA

Ethnopharmacological relevanceNon-alcoholic fatty liver disease (NAFLD) represents a burgeoning challenge for public health with potential progression to malignant liver diseases. PANoptosis, an avant-garde conceptualization of cell deaths, is closely associated with mitochondrial damage and linked to multiple liver disorders. Si-Wu-Tang (SWT), a traditional Chinese herbal prescription renowned for regulating blood-related disorders and ameliorating gynecological and hepatic diseases, has been demonstrated to alleviate liver fibrosis by regulating bile acid metabolism and immune responses. Aim of the studyHowever, the mechanisms by which mtDNA is released from PANoptotic hepatocytes, triggering macrophage activation and hepatitis and whether this process can be reversed by SWT remain unclear. Materials and methodsHere, sophisticated RNA-sequencing complemented by molecular approaches were applied to explore the underlying mechanism of SWT against NAFLD in methionine/choline-deficient diet (MCD)-induced mice and relative in vitro models. ResultsWe revealed that SWT profoundly repaired mitochondrial dysfunction, blocked mitochondrial permeability transition and mtDNA released to the cytoplasm, subsequently reversing hepatocyte PANoptosis and macrophage polarization both in MCD-stimulated mice and in vitro. Mechanically, loaded lipids dramatically promoted the opening of mPTP and oligomerization of VDAC2 to orchestrate mtDNA release, which was combined with ZBP1 to promote hepatocyte PANoptosis and also taken by macrophages to trigger M1 polarization via the FSTL1 and PKM2 combination. SWT effectively blocked NOXA signaling and reversed all these detrimental outcomes. ConclusionOur findings show that SWT protects against hepatitis-mediated hepatocyte PANoptosis and macrophage M1 polarization by influencing intrahepatic synthesis, release and intercellular transfer of mtDNA, suggesting a potential therapeutic strategy for ameliorating NAFLD.

Modulation of T Cell Differentiation in Mice with COPD Combined with Lung Cancer Through Key Targets of PD-1 by Tao Hong Si Wu Tang.

The objective is to assess the anti-inflammatory effect of Tao Hong Si Wu Tang combined with anti-PD-1 in a mouse model of COPD combined with lung cancer, elucidating its mechanism through modulation of PD-1/PD-L binding, regulation of Th1/Th2 and Th17/Treg balance, inhibition of IL-4 and IL-17, and promotion of IFN-γ and TGF-β levels in peripheral blood. One hundred male C57/BL6 mice were randomly allocated to five groups: A (blank control), B (model control), C (THSW), D (anti-PD-1), and E (THSW + anti-PD-1), with 20 mice in each group. The COPD model was induced using fumigation and LPS intra-airway drip, followed by the establishment of lung cancer by Lewis cell inoculation. Treatment groups received Tao Hong Si Wu Tang or/and PD-1 monoclonal antibody. Various indicators were assessed, including macroscopic observation, HE staining of lung tissue, ELISA for cytokines, flow cytometry for cell proportions, and immunohistochemistry/western blotting for protein expression. Lung tissue analysis revealed significant differences between groups, with marked tumor formation observed in groups B-E. Serum levels of IL-4, IFN-γ, IL-17, and TGF-β were significantly altered, along with changes in CD4 + T/CD8 + T ratio and cytokine-producing cell populations. Expression levels of key proteins were also significantly affected across treatment groups. Tao Hong Si Wu Tang demonstrated anti-inflammatory effects comparable to anti-PD-1, potentially through modulation of PD-1/PD-L binding, correction of Th1/Th2 and Th17/Treg imbalance, and modulation of cytokine levels. These findings suggest a role for Tao Hong Si Wu Tang in ameliorating inflammation and immune dysregulation in COPD combined with lung cancer.

Prognostic model construction and target identification of Si-Wu-Tang against breast cancer

The targets and mechanisms of Si-Wu-Tang (SWT) against (Breast cancer) BRCA were identified and a survival model and nomogram was construted by network pharmacology, bioinformatic analysis and in vitro experiments. A total of 72 anti-breast cancer SWT targets were selected, among which eleven genes (MAOA、SQLE、CACNA2D1、GLI1、RORB、ITGB3、TACR1、NR3C2、CA3、RBP4 and PTK6) were used to construct a novel prognostic model of breast cancer. The anti-breast cancer activity of SWT was related to the modulation of the receptor tyrosine kinases signaling pathways. Moreover, two compounds, mairin and senkyunone were found to bind directly to ITGB3 and RORB proteins. Finally, mRNA and protein expression of ITGB3 and RORB was observed to be significantly down-regulated after incubation of MCF-7 cells with SWT. Overall, our results indicated that mairin and senkyunone were the key ingredients present in SWT, and ITGB3 as well as RORB proteins were the major targets affected by SWT. The prognostic model can be used to predict the outcome of BRCA patients.

Established UPLC-MS/MS procedure for multicomponent quantitative analysis of rat plasma: Pharmacokinetics of Taohong Siwu Decoction in normal and acute blood stasis models

Ethnopharmacological relevanceAs one of China's 100 classic recipes, Taohong Siwu Decoction (THSWD) consists of Siwu Tang flavored peach kernel and safflower, and is used to nourish and activate blood. Accordingly, THSWD is mainly administered to treat blood deficiency and stasis syndrome. According to prior studies, THSWD induces antioxidant stress, inhibits inflammatory reactions, inhibits platelet aggregation, prevents fibrosis, reduces blood lipids, prolongs clotting time, prevents atherosclerosis and vascular pathology, improves hemorheological changes, and regulates related signaling pathways. Materials and methodsA sensitive analytical method was developed to detect the marker components of THSWD using UPLC-Q-TOF-MS. A rapid and sensitive UPLC-MS/MS analytical method was developed and applied to detect 16 major bioactive components in normal and acute blood stasis (ABS) rats following oral administration of THSWD. The metabolic process of THSWD in vivo was evaluated and the differences in pharmacokinetic parameters between the normal and ABS rat metabolic processes were compared. ResultsThis method was fully validated based on its excellent linearity (r2 < 0.99), satisfactory intra- and inter-day precisions (RSD <15%), and good accuracy (RE within ±14.83%). The stability, matrix effects, and extraction recoveries of the rat plasma samples were also within the acceptable limits (RSD <15%). Compared to normal rats, the pharmacokinetics of the major active constituents (except Senkyunolide G) were significantly different (P < 0.05) in the ABS model rats, indicating that the metabolism of the 16 compounds in vivo may change under disease conditions. ConclusionsIn this study, a sensitive UPLC-Q-TOF-MS method was established to analyze the main components of THSWD, and a UPLC-MS/MS analytical method was developed and applied for the pharmacokinetic parameter detection of the 16 main bioactive components in normal and ABS rats. Our findings lay the foundation for further studies on the pharmacokinetic-pharmacodynamic correlation for THSWD.

Cinnamic aldehyde, an anti-inflammatory component in Du-Huo-Ji-Sheng-Tang, ameliorates arthritis in II collagenase and monosodium iodoacetate induced osteoarthritis rat models.

Du-Huo-Ji-Sheng-Tang (DHJST) is a Chinese herbal formula used for arthralgia and arthritis treatment clinically. This study aims to evaluate the joint-protecting efficacy of DHJST and to identify the active constituents as the evaluation marker. DHJST can be categorized into three recipes: Blood-tonifying-herbs Si-Wu-Tang (SWT), Wind-dampness-dispelling-herbs (WDH) and Qi-tonifying-herbs (TH). All formulas were used to explore the joint-protecting efficacies. s: Firstly, DHJST could decrease the arthritis progression in the monosodium-iodoacetate-induced rat and cure arthritis in the type II collagenase-induced rat. Further, in lipopolysaccharide-stimulated RAW 264.7cells, DHJST, TH and Cinnamomum cassia (CC), an ingredient in TH, were the most potent nitric oxide (NO) and prostaglandin E2 (PGE2) inhibitors. The major components, cinnamic aldehyde, showed the strongest NO and PGE2 inhibition. Up-regulated inducible NO synthase (iNOS) and cyclooxygenase-2 were inhibited by DHJST, TH, CC, and cinnamic aldehyde. In interleukin-1β-stimulated primary chondrocytes, upregulated iNOS was inhibited by DHJST, TH, Cinnamomum cassia, and cinnamic aldehyde. Upregulated matrix metalloprotease-13 was only inhibited by DHJST and TH and Eucommia ulmoides (EU) extract. Results suggest that DHJST presented joint-protective and cure arthritis effects. TH presented equal joint-protective effects as DHJST. The major anti-inflammatory ingredient in TH was Cinnamomum cassia in TH. And cinnamic aldehyde was the potent anti-inflammatory active compound in Cinnamomum cassia. Therefore, this study may facilitate the modern use of DHJST with TH as a simplified version but equally effective anti-osteoarthritic agents with cinnamic aldehyde as a quality control marker of DHJST and TH in osteoarthritis prevention or treatment.

Beneficial Effects of Traditional Chinese Medicine in the Treatment of Premature Ovarian Failure.

Premature ovarian failure (POF) is characterized by hormonal disorders, amenorrhea, and premature loss of fertility potential in women of reproductive age. Several studies have been conducted on the effectiveness of traditional Chinese medicine (TCM) in treating POF. TCM relied primarily on apoptosis, immunity, and aging to treat POF based on the studies of domestic and foreign literature. Zuogui pills inhibited mitochondrial-dependent apoptosis in the treatment of POF. Huyang Yangkun formula regulated the downstream of the Bcl-2 family to resist apoptosis through the aquaporin-1 protein. Modified Bazhen decoction regulated apoptosis in POF by regulating X-linked inhibitors of apoptosis protein. Bushen Tianjing recipe was effective in treating POF by promoting angiogenesis and preventing apoptosis. As for immunity, Bushen Jianpi prescription and Er-Xian decoction cured autoimmunity POF models and increased follicular development-related protein expression. Bushen Huoxue Tang improved ovarian function and reduced ovarian inflammation by regulating the Nrf2/Keap1 signaling pathway and T lymphocytes. Taohong Siwu decoction promoted the proliferation and differentiation of granulosa cells of POF mice by regulating the TGF-β1/Smads signaling pathway. In addition, ginsenoside Rg1 and Jiajian Guisheng formula treated POF by regulating cell aging-related mechanisms. Si Wu Tang treated POF by activating the angiogenesis-related proteins. The goal of this review is to serve as a reference for in-depth research into the treatment of POF with TCM and provide inspiration for new diagnostic methods and treatment options.

Si-Wu-Tang ameliorates bile duct ligation-induced liver fibrosis via modulating immune environment

Si-Wu-Tang (SWT), a traditional Chinese medicine formula firstly recorded from the Tang dynasty, has been reported to alleviate gynecological and liver diseases. We preliminarily demonstrated that SWT could improve liver fibrosis via modulating intestinal microbiota, but little was known about the mechanisms linking its therapeutic effects to the reshaped immune microenvironment within fibrotic livers. Thus, we established a bile duct ligation (BDL)-induced liver fibrosis murine model to evaluate the hepatoprotective effects and potential mechanisms of SWT. The high-performance liquid chromatography, RNA sequencing and other molecular biological techniques were also performed in our study. Our data demonstrated that SWT significantly improved BDL-induced liver fibrosis and inflammatory responses by inhibiting the expression of genes associated with extracellular matrix synthesis and degradation. Combined with the analysis of immune cell infiltration and gene set enrichment analysis (GSEA), we found that SWT remarkably repaired the unbalanced immune microenvironment by modulating the biological functions of different immune cells, especially for macrophages, neutrophils and CD8+ T cells. In addition, SWT significantly inhibited the activation of M2-like macrophages to reduce the release of profibrotic-cytokines and prevented the activation of neutrophils to suppress neutrophil extracellular trap formation. SWT also efficiently promoted the apoptosis of activated hepatic stellate cells via Fas/FasL signaling pathway, which might be mediated by CD8+ tissue-resident memory T cells. In conclusion, our research not only unraveled the intricate mechanisms underlying the hepatoprotective activities of SWT against liver fibrosis but also provided a novel therapeutic strategy for the treatment of liver fibrosis and its relative complications.

Elucidating the pharmacological mechanism by which Si-Wu-Tang induces cellular senescence in breast cancer via multilevel data integration.

Traditional Chinese medicine (TCM) is a promising strategy for effectively treating cancer by inducing cellular senescence with minimal side effects. Si-Wu-Tang (SWT) is a TCM composed of four herbs that is commonly used in China for the treatment of gynecological diseases; SWT can prevent breast cancer (BC), but the molecular mechanism by which SWT induces cellular senescence and its clinical application value remain unknown. We identified 335 differentially expressed genes (DEGs) in SWT-treated MCF-7 cells through Gene Expression Omnibus (GEO) dataset analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed the enrichment of biological processes and key signaling pathways including cellular senescence, the cell cycle, the MAPK signaling pathway, and the p53 signaling pathway. Additionally, SWT induced BC cell senescence by upregulating the expression of 33 aging/senescence-induced genes (ASIGs). According to LASSO regression analysis, NDRG1, ERRFI1, SOCS1, IRS2, IGFBP4, and BIRC3 levels were associated with BC prognosis and were used to develop risk scores. ERRFI1, SOCS1, IRS2, IGFBP4, and BIRC3 were identified as protective factors (P < 0.05, HR < 1), while NDRG1 was identified as a risk factor (P < 0.05, HR > 1). Notably, patients with low risk scores had increased senescence-associated secretory phenotypes (SASPs) and immune cell infiltration. Overall, we systematically integrated biological databases and biocomputational methods to reveal the mechanisms by which SWT induces senescence in breast cancer and its clinical value.

Si-Wu-Tang ameliorates fibrotic liver injury via modulating intestinal microbiota and bile acid homeostasis

BackgroundFibrotic liver injury is a progressive scarring event, which may permanently affect liver function and progress into devastating end-stage liver diseases due to the absence of effective therapies. Si-Wu-Tang (SWT), a traditional Chinese medicine formula used in clinic to treat gynecological disorders for centuries, has been investigated in recent preliminary findings for its role in alleviating chronic liver diseases. Here we aim to elucidate the therapeutic effects and possible mechanisms of SWT against fibrotic liver injury.MethodsUHPLC-MS/MS was performed to investigate the chemical characterization of SWT. After intragastrically administered with carbon tetrachloride (CCl4) every 3 days for 1-week, C57BL/6 mice were orally administered with SWT (5.2, 10.4 and 20.8 g/kg) once daily for 3 weeks along with CCl4 challenge. Liver function was determined by the measurement of serum biomarkers, hematoxylin and eosin (H&E) and Masson’s trichrome staining. Intestinal inflammatory infiltration and the disruption of intestinal barrier were examined by H&E and E-cadherin immunohistochemical staining. The microbial composition of intestinal content was determined by 16S rRNA sequencing. Serum bile acids (BAs) profiling was analyzed by LC–MS/MS. Simultaneously, the expression of genes of interest was determined by qPCR and western blot.ResultsSWT exhibited remarkable therapeutic effects on CCl4-induced liver fibrosis, as indicated by improved collagen accumulation in livers, intestinal barrier injury and hepatic and intestinal inflammatory response. Results of 16S rRNA sequencing revealed that SWT treatment strikingly restructured intestinal microbiota in fibrotic mice by increasing the relative abundances of Bacteroides and Lachnoclostridium and decreasing the relative abundances of Alistipes and Rikenellaceae. UHPLC-MS/MS data suggested that SWT altered the composition of BAs in circulation as evidenced by increased unconjugated BAs like cholic acid and chenodeoxycholic acid but decreased conjugated BAs including taurocholic acid and taurodeoxycholic acid, compared to that in CCl4 mice. Notably, SWT efficiently improved the imbalance of BA homeostasis in livers caused by CCl4 via activating farnesoid X receptor (FXR)-fibroblast growth factor 15 enterohepatic and FXR-small heterodimer partner hepatic pathways.ConclusionSWT decreased inflammatory response, reconstructed gut microbiota-mediated BA homeostasis as well as activated FXR pathways, which eventually protected against CCl4-induced fibrotic liver injury.

Si-Wu-Tang facilitates ovarian function through improving ovarian microenvironment and angiogenesis in a mouse model of premature ovarian failure

Ethnopharmacological relevancePremature ovarian failure (POF) is a severe illness, characterized by premature menopause with a markedly decrease in ovarian function, which leads to infertility. Si-Wu-Tang (SWT), also called “the first prescription of gynecology” by medical experts in China, is widely used as the basic formula in regulating the menstrual cycle and treating infertility. However, the potential effect and underlying mechanisms of action of SWT on the treatment of POF have not yet been elucidated. PurposeThis study aimed to explore the therapeutic effect and underlying molecular mechanism of action of SWT on the treatment of POF in C57BL/6 mice. Materials and methodsThe main compounds of SWT were identified by high-performance liquid chromatography (HPLC). POF model groups were established by a single intraperitoneal injection of cyclophosphamide (Cy, 100 mg/kg). SWT or dehydroepiandrosterone (DHEA) were administered via oral gavage for 28 consecutive days. Ovarian function and pathological changes were evaluated by hormone levels, follicular development, and changes in angiogenesis. Furthermore, statistical analyses of fertility were also performed. ResultsTreatment with SWT significantly improved estrogen levels, the number of follicles, antioxidant defense, and microvascular formation in POF mice. Moreover, SWT significantly activated the Nrf2/HO-1 and STAT3/HIF-1α/VEGF signaling pathways to promote angiogenesis, resulting in a better fertility outcome when compared to the model group. ConclusionsOur findings indicated that SWT protected ovarian function of Cy-induced POF mice by improving the antioxidant ability and promoting ovarian angiogenesis, thereby providing scientific evidence for the treatment of POF using SWT.

Comparison of mechanisms and efficacies of five formulas for improving blood circulation and removing blood stasis

ObjectiveThis study aimed to compare the mechanisms and efficacies of five formulas that improve blood circulation and remove blood stasis. Methods(1) A network pharmacology method was used to determine the targets of five formulas that promote circulation and remove blood stasis. Compounds of the five formulas, namely Danshen Yin (丹参饮, DSY), Huoluo Xiaoling Dan (活络效灵丹, HLXLD), Shixiao San (失笑散, SXS), Taohong Siwu Tang (桃红四物汤, THSWT), and Xuefu Zhuyu Tang (血府逐瘀汤, XFZYT), were retrieved from the Traditonal Chinese Medicine System Pharmacology Database (TCMSP), the Shanghai Institute of Organic Chemistry of CAS, and the TCM Integrated Database. Drug target network was constructed by searching the Swiss Target Prediction database and the STITCH database. The target network of stasis was extracted from the PharmGKB database, the Online Mendelian Inheritance in Man (OMIM) database, the Genetic Association Database (GAD), and the Therapeutic Target Database (TTD). Candidate targets were determined using protein–protein interaction (PPI) network extension and topology selection. Thereafter, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was used to determine the differentiation of the mechanism of the five formulas. (2) Animal experiments were conducted to explore the efficacies of the five formulas in treating blood stasis. Seventy New Zealand rabbits were exposed to high-fat feeding + epinephrine injection to construct a blood stasis syndrome model. The rabbits were evenly divided into control, model, DSY, HLXLD, SXS, THSWT, and XFZYT groups. The latter five groups were orally administered the corresponding formulas [DSY: 3.92 g/(kg·d), XFZYT: 7.10 g/(kg·d), SXS: 1.12 g/(kg·d), HLXLD: 5.60 g/(kg·d), THSWT: 4.48 g/(kg·d)]. Serum lipid and blood rheology were analyzed, and pathology slices were observed. Results(1) A total of 269, 358, 288, 370, and 376 candidate targets of DSY, HLXLD, SXS, THSWT, and XFZYT were obtained among which were 232 shared candidate targets. Fluid shear stress and atherosclerosis were the biological processes common to the five formulas. HLXLD, SXS, DSY, and THSWT regulated lipolysis in adipocytes, and XFZYT, HLXLD, SXS, and THSWT regulated the AGE-RAGE signaling pathway and complement and coagulation cascades. HLXLD, SXS, and XFZYT regulated the HIF-1 signaling pathway, DSY regulated the cGMP-PKG signaling pathway, HLXLD reduced platelet activation, SXS regulated the calcium signaling pathway, and XFZYT regulated the PPAR signaling pathway. (2) In the animal experiments, the values of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), TC/HDL, and TG/HDL in each group decreased, among which the ones seen in XFZYT, HLXLD, and SXS groups were statistically significant (P < 0.05). XFZYT presented the best effect, followed by HLXLD and SXS. XFZYT and HLXLD decreased apolipoprotein B100 (apoB100) and increased apolipoprotein A1/apoB100 (P < 0.05). XFZYT decreased all the values of hematocrit (HCT), plasma viscosity, whole blood viscosity (WBV); HLXLD and SXS affected HCT; and DSY and THSWT regulated WBV (P < 0.05). All the five formulas decreased the values of optical density and area of plaque, among which XFZYT and HLXLD showed statistical significance (P < 0.05). ConclusionAdjusting fluid shear stress and alleviating the injury of endothelial cells might be the common mechanisms by which the five formulas promote blood circulation and remove blood stasis. Different formulas also have unique targets, which may provide guidance for clinical drug selection. By regulating different indices, the five formulas can regulate blood lipid and hemorheology, improve the state of blood stasis, and decrease the degree of aortic plaque in the blood stasis model rabbits. XFZYT and HLXLD had higher efficacies than DSY, THSWT, and SXS.

Can traditional Chinese medicine formulas treat BMI-associated hypertension effectively?

The tradition of Chinese Medicine (TCM) has been in use and development for thousands of years, where it has been applied in some form for the treatment of nearly every common illness. TCM is currently undergoing a resurgence in interest and in providing an adjunct to allopathic medical care virtually worldwide. TCM therapeutics may be administered in many forms from capsules, to powders, homogenates, tinctures and decoctions. Si Wu Tang, a derivative of the traditional Chinese including Formulas, is a combination of substances that may function in a synergistic manner to promote a calming effect and an amelioration of symptoms of hypertension. Such formulas are often used in TCM to treat or alleviate a wide range of the common illness and disorders of both Eastern and Western society. Reported beneficial effects include improvements in circulatory, cardiovascular, mood, endocrine metabolic and reproductive disorders. One such TCM formula commonly recommended is the Wu Cao Si Wu Tang [SWT]formula, used to treat the hypertension of obesity and a variety of other disorders. Hypertension is a key risk factor for cardiovascular morbidity and mortality and is a leading cause of end-stage renal disease; over 7 million US deaths per year may be directly attributed to pathophysiologic complications resulting from poor control of blood pressure. While numerous advances in the diagnosis and treatment of hypertension have had a major impact on decreasing the overall risks and an improved management of this chronic disease, a definitive cure for all causes of hypertension has remained elusive to date. To determine the comparative effectiveness of conventional Western treatment vs. drug free Traditional Oriental Therapy for hypertension, we reviewed the data from independent studies. Wu Cao Si Wu Tang was found to be as effective as allopathic medications in controlling blood pressure in a group of moderately hypertensive patients

Evaluating the Therapeutic Efficacy of Si-Wu-Tang Decoction and Concentrated Extract in Follicular Maldevelopment-Related Menstrual Disorders Through Pharmacokinetic/Pharmacodynamic Studies.

Si-Wu-Tang (SWT), a traditional Chinese formula, is commonly used to relieve menstrual discomfort and climacteric syndrome. Water decoction (WD) and concentrated herbal extract (CHE) are the two most common formulations of traditional Chinese medicine (TCM). However, few studies have reported the equivalency of these two formulations. In this study, 23 healthy volunteers were included to determine the pharmacokinetic (PK) equivalent dosage of WD and CHE, and 25 infertile women with follicular maldevelopment to evaluate the pharmacodynamic (PD) effects on menstrual disorders. The randomized, two-way crossover comparative PK study of SWT-WD and SWT-CHE analyzed the active component, ferulic acid. The results showed that clinical doses of 170 mL SWT-WD and 18 g SWT-CHE produced the same amount of ferulic acid in the blood. The PD study showed that patients who took both of these formulations had an initial luteinizing hormone/follicle-stimulating hormone ratio of <1; however, the value returned to normal and their symptoms all improved after taken SWT. Our results showed that WD and CHE, both prepared from 40 g of SWT, displayed bioequivalence upon PK/PD analysis.

Herbal medicine (Taohong Siwu Tang) for the treatment of primary dysmenorrhea: A systematic review and meta-analysis

ObjectivesThis systematic review aimed to evaluate the efficacy and safety of Tao-Hong Siwu Tang (TST) for the treatment of primary dysmenorrhea. MethodsWe searched four English databases (MEDLINE, EMBASE, Allied and Complementary Medicine Database, and Cochrane Central Register of Controlled Trials [CENTRAL, Cochrane Library]), three Chinese databases (China National Knowledge Infrastructure, Wanfang, and Chinese Science and Technology Periodical Database), two Korean databases (Oriental Medicine Advanced Searching Integrated System and Korean traditional Knowledge Portal), and one Japanese database (Citation Information by NII). All randomized controlled trials (RCTs) using TST or modified TST (MTST) were included. Three independent reviewers extracted the data, assessed the risk of bias according to the Cochrane criteria, and performed a meta-analysis. ResultsA total of 85 possibly relevant articles were identified, and five trials met our inclusion criteria. The meta-analysis showed a favorable effect of MTST compared to non-steroidal anti-inflammatory drugs (NSAIDs) (n = 486, risk ratio [RR] = 1.53, 95% confidence interval [95% CI] = 1.37–1.72, I2 = 39%). Among the included trials, one RCT showed superior effects of MTST on primary dysmenorrhea recurrence rate compared to NSAIDs (n = 246, RR = 0.31, 95% CI = 0.15–0.63, P = 0.001). Another RCT revealed a beneficial impact of oral contraceptives (OCs) used in combination with TST compared to OCs alone (n = 60, RR = 1.35, 95% CI = 1.02–1.79, P = 0.04). ConclusionThis systematic review and meta-analysis provides moderate quality evidence for the superiority of MTST over NSAIDs as well as that of TST plus OCs over OCs in the treatment of primary dysmenorrhea.

Study on the Antibreast Cancer Mechanism and Bioactive Components of Si-Wu-Tang by Cell Type-Specific Molecular Network.

Si-Wu-Tang (SWT), a traditional Chinese herbal formula, has shown an effect on antibreast cancer. However, the mechanisms and bioactive components of SWT are still unclear. Fortunately, cell type-specific molecular network has provided an effective method. This study integrated the data of formula components, all types of biomolecules in the human body, and nonexpressed protein in breast cancer cells and constructed the breast cancer cell network and the biological network that SWT acted on the breast cancer-related targets by Entity Grammar System (EGS). Biological network showed 59 bioactive components acting on 15 breast cancer-related targets. The antibreast cancer mechanisms were summarized by enrichment analysis: regulation of cell death, response to hormone stimulation, response to organic substance, regulation of phosphorylation of amino acids, regulation of cell proliferation, regulation of signal transmission, and affection of gland development. In addition, we discovered that verbascoside played the role of antibreast cancer by inhibiting cell proliferation, but there was not a report on this effect. The results of CCK8 and western blot were consistent with the antibreast cancer effect of verbascoside based on biological network. Biological network modeling by EGS and network analysis provide an effective way for uncovering the mechanism and identifying the bioactive components of SWT.