Sijunzi Tang Research Articles

Study on the anti-skin aging effect and mechanism of Sijunzi Tang based on network pharmacology and experimental validation

Ethnopharmacological relevanceSi Jun Zi Tang (SJZT) is a famous traditional Chinese medicine formula composing of 4 herbal medicines (Ginseng Radix et Rhizoma, Atractylodis macrocephalae Rhizoma, Poria, and Glycyrrhizae Radix et Rhizoma) with tonifying spleen and anti-aging effects. It is also known that SJZT can be used to tone, nourish the skin and accelerate wound healing. However, due to the complexity of the formulation, the anti-aging especially anti-skin aging mechanisms as well as the key components of SJZT have not been fully investigated. Therefore, further in vitro and in vivo experimental studies are particularly needed to investigate the anti-skin ageing efficacy of SJZT. Aim of the studyThe purpose of this article was to explore the therapeutic effect and possible pharmacological mechanism of SJZT in the treatment of skin aging by topical application using network pharmacology and to validate the findings using in vitro and in vivo tests. Materials and methodsNetwork pharmacology method was applied to predict the underlying biological function and mechanism involved in the anti-skin aging effect of SJZT. Molecular docking was used to preliminarily predict the active components of SJZT-Skin Aging. UPLC QTOF MS/MS was carried out to analyze the chemical compounds. Finally, to confirm the anti-skin aging effort of SJZT, a mouse skin-aging model and UVB-induced EpiSCs (epidermal stem cells) senescence model were established. ResultsPPI network analysis and KEGG studies indicated that TP53, CDKN2A, TNF, IL6, and IL1B might be parts of the core targets associated with EpiSCs senescence. Furthermore, molecular docking suggested the top active components, glycyrrhizin, ginsenoside Rg5, ginsenoside Rh2, liquiritin, polyporenic acid C and atractylenolide II showed strong affinity to the key proteins involved in cellular senescence signaling. UPLC QTOF MS/MS analysis of SJZT confirmed the presence of these key components. In-vivo experiments revealed that SJZT could improve UVB-induced skin thickening, increase the number of collagen fibers, strengthen the structure of elastin fibers, and decrease the expression of MDA, as well as increase the expression of CAT and T-SOD in the skin tissue of mouse. And, in-vitro experiments indicated that SJZT could reduce ROS generation and oxidative stress, increase mitochondrial membrane potential, and upregulate the expression of stem cell markers. Moreover, SJZT could suppress the expression of p53, p-p53 and p21, downregulated p38 phosphorylation. Furthermore, the anti-cellular senescence effect of SJZT on EpiSCs disappeared after treatment with the p38 inhibitor adesmapimod. Taken all together, the regulation of senescence signaling in EpiSCs is an important mechanism of SJZT in combating skin aging. ConclusionThe research results indicate that SJZT has anti-skin aging effects on UVB-induced skin-aging model, possibly by mediating p38/p53 signaling pathway. These findings strongly demonstrate the great potential of SJZT as an active composite for anti-skin aging and cosmeceutical applications.

Synergistic Therapeutic Effects and Immunoregulatory Mechanism of Maxing Shigan Decoction Combined with Sijunzi Decoction on Viral Pneumonia in Mice.

Influenza is defined in traditional Chinese medicine (TCM) as an epidemic febrile illness and is usually treated with herbal compound formulas under the guidance of the "Qu Xie and Fu Zheng" theories. Ma Xing Shi Gan Tang (MXSGD) is a prominent remedy for clearing heat and detoxifying toxins in the clinical treatment of influenza in TCM, playing the role of "Qu Xie." Si Jun Zi Tang (SJZD) is recognized as one of the "Fu Zheng" formulas for strengthening the spleen and nourishing the stomach, with immunomodulatory effects. In this study, we followed the principles of "Qu Xie and Fu Zheng" to explore the effects of MXSGD combined with SJZD on viral pneumonia and its mechanism. Results showed that the couse of MXSGD and SJZD was effective in reducing the mortality rates and severity of lung pathology in lethally infected FM1 mice compared to the use of either drug alone. Moreover, further research demonstrated that the combined use suppressed TLRs and NLRP3 inflammatory signaling pathways at 4 dpi while promoting them at 7 dpi. At 10 dpi, there was a significant increase in CD11c+ and CD103+ DCs in the lungs. Together, SJZD improved the therapeutic effectiveness of MXSGD in treating influenza virus pneumonia than when used alone. MXSGD and SJZD exhibit synergistic effects in the treatment of influenza, as evidenced by the inhibition of TLR7 and NLRP3 inflammatory pathways early in the infection and facilitation of the response later. They also increase CD11c+ and CD103+ DC levels, as well as balancing Th1/Th2 cytokines.

Sijunzi Tang improves gefitinib resistance by regulating glutamine metabolism

Lung cancer is a major health concern and significant barrier to human well-being and social development. Although targeted therapy has shown remarkable progress in the treatment of lung cancer, the emergence of drug resistance has limited its clinical efficacy. Sijunzi Tang (SJZ) is a classical Chinese herbal formula known for tonifying qi and nourishing the lungs, has been recognized for its potential in lung cancer management. However, the underlying mechanism of its combined use with anti-cancer drugs remains unclear. Here, we investigated the anti-lung cancer efficacy and underlying mechanisms of the combination of gefitinib and SJZ in gefitinib-resistant human lung adenocarcinoma cells (PC-9/GR). We conducted in vitro and in vivo experiments using histopathology and targeted metabolomics approaches. Our results demonstrated that the combination of SJZ and gefitinib exhibited synergistic effects on tumor growth inhibition in PC-9/GR-bearing nude mice. Notably, the co-administration of SJZ and gefitinib synergistically promoted tumor cell apoptosis, potentially through the regulation of BAX and BCL-2 expression. Immunohistochemistry and western blot analysis found down-regulation of GLS, GS, and SLC1A5 expression in the co-administration group compared to the control and the individual treatment groups. Targeted metabolomics revealed significant alterations in the plasma glutamine metabolic markers glutamine, alanine, succinate, glutamate, and pyruvate. Of the glutamine metabolism markers measured in tumor tissues, glutamine and pyruvate demonstrated significant differences across the treatment groups. These findings suggest that administration of SJZ improves gefitinib resistance in the treatment of lung cancer without toxic effects. Moreover, SJZ may affect glutamine metabolism by regulating key targets involved in glutamine metabolism (SLC1A5, GLS, and GS) and modulating the levels of related metabolic markers, ultimately reducing gefitinib resistance.

Elucidating the anti-aging mechanism of Si Jun Zi Tang by integrating network pharmacology and experimental validation in vivo.

Si Jun Zi Tang (SJZT) is a classic Traditional Chinese Medicine (TCM) prescription used to treat aging-related diseases. However, the potential molecular mechanisms of the anti-aging effects of the bioactive compounds and their targets remain elusive. In this study, we combined network pharmacology and molecular docking with in vivo experiments to elucidate the anti-aging molecular mechanism of SJZT. A series of network pharmacology strategies were used to predict potential targets and therapeutic mechanisms of SJZT, including compound screening, pathway enrichment analysis and molecular docking studies. Based on the network pharmacology predictions and observation of outward signs of aging, the expression levels of selected genes and proteins and possible key targets were subsequently validated and analysed using qRT-PCR and immunoblotting. Using a data mining approach, 235 effective targets of SJZT and aging were obtained. AKT1, STAT3, JUN, MAPK3, TP53, MAPK1, TNF, RELA, MAPK14 and IL6 were identified as core genes in the Protein-Protein Interaction Networks (PPI) analysis. The results of the effective target Gene Ontology (Go) functional enrichment analysis suggested that SJZT may be involved aging and antiapoptotic biological processes. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that the anti-aging mechanism of SJZT may be associated with the PI3K-AKT and P38 MAPK signalling pathways. Molecular docking analysis suggested that kaempferol and quercetin could fit in the binding pockets of the core targets. In addition, SJZT alleviated the aging symptoms of mice such as osteoporosis and hair loss. In conclusion, the anti-aging effect of SJZT was associated with the inhibition of the PI3K-AKT and P38 MAPK signalling pathways, and these findings were consistent with the network pharmacology prediction.

High-Throughput Sequencing Reveals the Differential MicroRNA Expression Profiles of Human Gastric Cancer SGC7901 Cell Xenograft Nude Mouse Models Treated with Traditional Chinese Medicine Si Jun Zi Tang Decoction.

Objective. The present study aimed to investigate the potential mechanism underlying the antitumor effect of Si Jun Zi Tang (SJZT) decoction on gastric cancer. Methods. Twelve human gastric cancer SGC7901 cell xenograft nude mouse models were established. The mice were randomly divided into the Model group and SJZT group. SJZT exerted significant antitumor effects after 21 days of decoction administration. High-throughput sequencing was used to analyze the microRNA (miRNA) expression profiles of tumor tissues. Bioinformatics analysis was performed to provide further information regarding the differentially expressed miRNAs. Five representative differentially expressed miRNAs and four predicted target genes were further validated using quantitative real-time reverse transcription PCR (qRT-PCR). Results. We identified 33 miRNAs that were differentially expressed in the SJZT group compared with the Model group. Among them, 32 miRNAs were upregulated and 1 miRNA was downregulated. Bioinformatic analysis showed that most of miRNAs acted as tumor suppressors and their target genes participated in multiple signaling pathways, including the PI3K/Akt signaling pathway, microRNAs in cancer, and Wnt signaling pathway. The qRT-PCR result confirmed that miR-223-3p, miR-205-5p, miR-147b-3p, and miR-223-5p were overexpressed and their respective paired target genes FUT9, POU2F1, MUC4, and RAB14 mRNA were obviously downregulated in the SJZT group compared with those in the Model group. Network analysis revealed that miR-223-3p and miR-205-5p shared two targets POU2F1 (encoding POU class 2 homeobox 1) and FUT9 (encoding fucosyltransferase 9), suggesting they have a common role in certain pathways. Conclusion. This study provided novel insights into the anticancer mechanism of SJZT against gastric cancer, which might be partly related to the modulation of miRNA expression and their target pathways in tumors.

Effect of Single-Dose and Short-Term Administration of Si Jun Zi Tang on the Pharmacokinetics of Gefitinib in Rats.

Background Si Jun Zi Tang (SJZ), a four-herb Chinese medicine formula that has been described for approximately one thousand years, is often prescribed for cancer patients as a complementary therapy in China. However, the mechanism by which Si Jun Zi Tang enhances the efficacy of gefitinib is unclear. Methods We investigated how Si Jun Zi Tang affected the pharmacokinetics of gefitinib in rats. A rapid, specific, and reliable ultra-performance liquid chromatography method with mass spectrometry was established to determine the plasma concentration of gefitinib. Results The results showed that a single intragastrically administered dose of Si Jun Zi Tang increased the pharmacokinetic parameters of gefitinib (Cmax, 3156.13 μg/L; A UC, 46281.5 μg/L/h) by 3 folds in rats compared with the administration of gefitinib alone (Cmax, 1352.07 μg/L; AUC, 11823.7 μg/L/h). Si Jun Zi Tang could also alter the pharmacokinetics of gefitinib by prolonging the time to reach Cmax. Conclusions Potential pharmacokinetic interactions between gefitinib and SJZ were evaluated, and SJZ extended Tmax and T1/2 and increased the Cmax and AUC of gefitinib. Long-term administration of gefitinib in combination with Si Jun Zi Tang would improve the efficacy of gefitinib.

Efficacy and safety of Si-Jun-Zi-Tang-based therapies for functional (non-ulcer) dyspepsia: a meta-analysis of randomized controlled trials

BackgroundThe traditional Chinese medicine formula Si-Jun-Zi-Tang (SJZT) has a long history of application in the treatment of functional dyspepsia (non-ulcer dyspepsia, FD)-like symptoms. SJZT-based therapies have been claimed to be beneficial in managing FD. This study aimed to assess the efficacy and safety of SJZT-based therapies in treating FD by meta-analysis.MethodsSystematic searches for RCTs were conducted in seven databases (up to February 2019) without language restrictions. Data were analyzed using Cochrane RevMan software version 5.3.0 and Stata software version 13.1, and reported as relative risk (RR) or odds ratio (OR) with 95% confidence intervals (CIs). The primary outcome was response rate and the secondary outcomes were gastric emptying, quality of life, adverse effects and relapse rate. The quality of evidence was evaluated according to criteria from the Cochrane risk of bias.ResultsA total of 341 potentially relevant publications were identified, and 12 RCTs were eligible for inclusion. For the response rate, there was a statically significant benefit in favor of SJZT-based therapies (RR = 1.23; 95% CI 1.17 to 1.30). However, the benefit was limited to modified SJZT (MSJZT). The relapse rate of FD patients received SJZT-based therapies was lower than that of patients who received conventional medicines (OR = 0.23; 95% CI 0.10 to 0.51). No SJZT-based therapies-related adverse effect was reported.ConclusionSJZT-based prescriptions may be effective in treating FD and no serious side-effects were identified, but the effect on response rate appeared to be limited to MSJZT. The results should be interpreted with caution as all the included studies were considered at a high risk of bias. Standardized, large-scale and strictly designed RCTs are needed to further validate the benefits of SJZT-based therapies for FD management.Trial registrationSystematic review registration: [PROSPERO registration: CRD42019139136].

Professor YANG Jun's clinical characteristics in the treatment of chronic diarrhea with acupuncture and herbal medicine based on qi activity theory in Huangdi Neijing

Professor YANG Jun believes that chronic diarrhea is located in the "intestine" and its pathogenesis focuses on the dysfunction of the spleen and the stomach which results in the impairment of qi activity. In the treatment, the comprehensive therapy is adopted, including acupuncture, moxibustion, herbal medicine, cupping method, etc. Regarding acupuncture therapy, Tianshu (ST 25) is selected specially for regulating the spleen and stomach function, Xiabai (LU4) for dispersing the lung qi to stop diarrhea, as well as Yintang (GV 29), Shuigou (GV 26), Chengjiang (CV 24), Qihai (CV 6), Guanyuan (CV 4) and Zhongwan (CV 12) for promoting the circulation of the conception vessel and the governor vessel. Regarding moxibustion therapy, moxibustion is exerted at the abdominal region to regulate qi and blood circulation and unblocking the meridians. Moreover, the retained cupping method is used at Shenque (CV 8) to consolidate the primary qi and the modified sijunzi tang, the herbal decoction is supplemented to tonify the acquired foundation for assisting the congenital one. All of these therapies co-work on promoting and regulating qi activity so as to stop diarrhea.

Spectrum-Effect Relationship between UPLC Fingerprints and Antilung Cancer Effect of Si Jun Zi Tang.

Nowadays, an increasing number of patients are seriously affected by lung cancer. Si Jun Zi Tang (SJZ), a four-herb Chinese medicine formula first described approximately one thousand years ago, is often prescribed for cancer patients as a complementary therapy. But the research on the effective materials for treating cancer using SJZ was rarely reported. To solve this problem, we evaluate the inhibitory effect of 10 samples of SJZ from different origins on PC9 cells. Ultraperformance liquid chromatography (UPLC) and hierarchical cluster analysis (HCA) along with canonical correlation analysis (CCA) and bioactivity validation were used to investigate the underlying correlation between the chemical ingredients and the antiproliferative effect of SJZ on PC9 cells. The evaluation indicated that 10 batches of SJZ could inhibit proliferation of PC9 cells and there was a notable difference in pharmacological activity between the different SJZ samples. The results of CCA and multivariate statistical analysis indicated that ginsenoside Ro and ginsenoside Rg1 might be active constituents of the antiproliferative effect as determined by spectrum-effect relationships. The results showed that bioassay and spectrum-effect relationships are suitable to associate sample quality with the active ingredient associated with clinical efficacy. And our finding would provide foundation and further understanding of the quality evaluation of traditional Chinese medicine decoction.

Metabolomic Study on Nude Mice Models of Gastric Cancer Treated with Modified Si Jun Zi Tang via HILIC UHPLC-Q-TOF/MS Analysis.

Recently, metabolomic methods have been used to explore the complex pathogenesis of cancer and the mechanism of action of traditional Chinese medicine (TCM) formulae. In this study, first, modified Si Jun Zi Tang (MSJZT) was prepared with strict quality control using the instrument method of ultra performance liquid chromatography and photodiode array detector (UPLC-PDA). Subsequently, in vivo experiments with tumour-bearing nude mice demonstrated that MSJZT exerted good antitumour effects. MSJZT not only significantly increased mouse body weight but also shrank the tumour volume. Then, the HILIC UHPLC-Q-TOF/MS-based metabolomics approach was used for exploring the pathogenesis of gastric cancer and the molecular mechanism of MSJZT. A total of 59 potential biomarkers in plasma were identified, and 6 pathways were found to be disturbed in gastric cancer. In contrast, after 3 weeks of MSJZT intervention, 32 potential biomarkers were identified, and 4 altered pathways were detected. The changes in glycolytic, amino acid, and lipid metabolisms could be partially regulated by MSJZT through decreasing the content of lactic dehydrogenase (LDH), glutamine synthetase (GS), phosphocholine cytidylyltransferase (PCYT2) mRNA, and protein level. In conclusion, we established a HILIC UHPLC-Q-TOF/MS metabolomic analysis method to demonstrate a complex metabolic profile of gastric cancer. The disordered metabolism could be partially regulated by MSJZT. These findings not only establish a solid foundation for TCM to treat gastric cancer but also provide a basis for further exploration of the precise mechanism of MSJZT activity.

Modified Si-Jun-Zi-Tang Attenuates Airway Inflammation in a Murine Model of Chronic Asthma by Inhibiting Teff Cells via the mTORC1 Pathway.

Background: Modified Si–Jun–Zi–Tang (MSJZT), a multi-herb formulation, is frequently used in traditional Chinese medicine for patients during the remission stage of asthma. However, the pharmacological basis underlying the effects of MSJZT on asthma has yet to be elucidated. This study aims at evaluating the anti-asthmatic effects of MSJZT and investigating its possible mechanism.Methods: A chronic murine model of asthma was established by sensitization and repeated challenge with ovalbumin (OVA) in female BALB/c mice, followed with oral administration of MSJZT during remission, and then mouse were re-challenged by OVA. The chemical profile of MSJZT was analyzed by high-performance liquid chromatography. The characteristic features of allergic asthma, including airway hyperreactivity, histopathology, cytokine levels (IL-4, -5, -13, -17, and INF-γ), T regulatory (Treg) lymphocytes (Foxp3+CD4+CD25+), and T effector (Teff) lymphocytes (Foxp3-CD25+CD4+) in bronchoalveolar lavage fluid (BALF), and downstream proteins of mTORC1/2 signaling pathway were examined.Results: MSJZT markedly suppressed airway hyper-responsiveness to aerosolized methacholine, and reduced levels of IL-4, IL-5, and IL-13 in the BALF. Histological studies showed that MSJZT significantly reduced inflammatory infiltration in lung tissues. The percentage and absolute number of Teff cells were suppressed to a remarkable level by MSJZT without affecting Treg cells. Furthermore, MSJZT effectively inhibited the mTORC1 activity, but exerted limited effects on mTORC2, as assessed by the phosphorylation of the mTORC1 and mTORC2 substrates, S6 ribosomal protein, p70 S6 kinase, mTOR S2481, and Akt, respectively.Conclusion: MSJZT attenuated chronic airway inflammation in a mouse model of asthma by inhibiting Teff cells, which occurred, at least in part, via modulation of the mTORC1 signaling pathway.

The modulatory properties of Si Jun Zi Tang enhancing anticancer of gefitinib by an integrating approach

Lung cancer remains the leading cause of cancer death worldwide, and the current therapy seems to have reached a plateau due to toxicities and acquired resistance. Therefore, exploration of novel therapeutic avenues may be useful. Si Jun Zi Tang (SJZ), a four-herb Chinese medicine formula first described approximately one thousand years, is often prescribed for cancer patients as a complementary therapy. However, whether SJZ benefits cancer patients as well as the main active constituents and its regulatory mechanism in combination with anticancer drugs remains unknown. Here, we investigated the anti-lung cancer potency and underlying mechanisms of the combination of gefitinib plus SJZ in mice with Lewis lung carcinoma (LLC), using histopathology and an integrated strategy of metabolomics and network pharmacology. The results showed that SJZ significantly enhanced gefitinib suppressing tumor growth and inhibiting LLC metastasis in LLC-bearing mice. Furthermore, 9 potential metabolomics biomarkers that differentially expressed in the SJZ/gefitinib group compared to the SJZ group or gefitinib group were identified by untargeted metabolomics, mainly involved three pathways: tricarboxylic acid cycle, tyrosine and tryptophan biosynthesis metabolism and linoleic acid metabolism. Five active ingredients, kaempferol, ginsenoside Rf, caprylic acid, lauric acid and naringenin, acted directly on 9 targets and regulated 4 out of 9 metabolites. Our results indicated that SJZ enhanced the anti-lung cancer effects of gefitinib via the key targets ABCG2, ABCC1, ABAT, GSR, CYP1A2, ALOX5, CYP3A4, PLA2G1B and PLA2G2A and the key metabolites 2-oxoglutarate, taurocholic acid, oxidized glutathione and linoleic acid. This work illustrated the modulatory properties of SJZ, which enhanced the anticancer effects of gefitinib, using metabolomics and network pharmacology analyses, and provided insights into underlying the mechanism the active ingredients of SJZfor the treatment of lung cancer in combination with gefitinib.

Feasibility of Sijunzi Tang (Chinese medicine) to enhance protein disulfide isomerase activities for reactivating malate dehydrogenase deactivated by polycyclic aromatic hydrocarbons.

The objective of this research is to investigate the enzymatic activities between protein disulfide isomerase (PDI) found in animals and plants and the properties found in a commonly used Chinese medicine called Sijunzi Tang. During the investigation, PDI, which is a monomer with a molecular mass of 57.0kDa, was used to reactivate malate dehydrogenase (MDH). However, with the interference of polycyclic aromatic hydrocarbons (PAHs), evidence indicates that such chemicals are carcinogenic, mutagenic, and toxic to humans. The enzymatic activity of PDI found in animal's liver and plant was 1657 folds of purification; 0.284 unit/mg of enzyme activity, and 5694.4 folds of purification; 1.00 unit/mg of enzyme activity, respectively. PDI extracted in treated animal and plant tissue revealed 2.40% and 80.44% of regaining MDH enzymatic activity, respectively. Although in its initial phase of investigation, it is assumed that the properties found in Sijunzi Tang can help regain enzymatic activity in those affected by xenobiotic substances, thus, making it a potential ingredient in assisting with PDI functions.

Effects of three Wenyang Jianpi Tang on cell proliferation and apoptosis of nonalcoholic fatty liver cells

To investigate the effects of Sijunzi Tang, Lizhong Tang and Fuzi Lizhong Tang on the cell proliferation and apoptosis of nonalcoholic fatty liver cells through the nonalcoholic fatty liver cell model established by inducing L02 cells with oleic acid. Different concentrations of oleic acid were added into L02 cells to induce the nonalcoholic fatty liver cell model. Oil red O staining was used to observe fatty droplets of fatty liver cells. Automatic biochemical analyzer was used to detect the levels of aspartic transaminase(AST), alanine aminotransferase(ALT), total cholesterol(TC), and triglyceride(TG) in the cell supernatants. There were five groups, namely normal group, model group, model and Sijunzi Tang group, model and Lizhong Tang group, and model and Fuzi Lizhong Tang group. The cell proliferation and apoptosis of the five groups were detected by MTT colorimetry test and flow cytometer. The expressions of PCNA, cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, Bax and Bcl-2 proteins of the five groups were detected by Western blot. The oil red O staining results showed that the optimum concentration of oleic acid that was used to induce nonalcoholic fatty liver cell models was 80 mg•L-1. The levels of AST, ALT, TC and TG in the nonalcoholic fatty liver cell supernatants were higher than that in normal liver cell supernatants(P<0.01). MTT colorimetry test and flow cytometer results showed that all of Sijunzi Tang, Lizhong Tang and Fuzi Lizhong Tang could effectively promote the cell proliferation, and inhibit the cellular apoptosis of nonalcoholic fatty liver cells(P<0.01). And Fuzi Lizhong Tang showed the best effect. Western blot results showed that Sijunzi Tang, Lizhong Tang and Fuzi Lizhong Tang could down-regulate the expressions of cleaved caspase-3, cleaved caspase-8, cleaved caspase-9 and Bax proteins, and up-regulate the expressions of PCNA and Bcl-2 proteins of nonalcoholic fatty liver cells. And Fuzi Lizhong Tang showed the best effect. In conclusion, all of Sijunzi Tang, Lizhong Tang and Fuzi Lizhong Tang could effectively promote the cell proliferation, and inhibit the cellular apoptosis of nonalcoholic fatty liver cells. And Fuzi Lizhong Tang showed the best effect. The pharmacodynamic mechanism may be related to the expressions of key factors in pathways related with proliferation and apoptosis mediated by the three decoctions.

To Unveil the Molecular Mechanisms of Qi and Blood through Systems Biology-Based Investigation into Si-Jun-Zi-Tang and Si-Wu-Tang formulae.

Traditional Chinese Medicine (TCM) is increasingly getting clinical application worldwide. But its theory like QI-Blood is still abstract. Actually, Qi deficiency and blood deficiency, which were treated by Si-Jun-Zi-Tang (SJZT) and Si-Wu-Tang (SWT) respectively, have characteristic clinical manifestations. Here, we analyzed targets of the ingredients in SJZT and SWT to unveil potential biologic mechanisms between Qi deficiency and blood deficiency through biomedical approaches. First, ingredients in SWT and SJZT were retrieved from TCMID database. The genes targeted by these ingredients were chosen from STITCH. After enrichment analysis by Gene Ontology (GO) and DAVID, enriched GO terms with p-value less than 0.01 were collected and interpreted through DAVID and KEGG. Then a visualized network was constructed with ClueGO. Finally, a total of 243 genes targeted by 195 ingredients of SWT formula and 209 genes targeted by 61 ingredients of SJZT were obtained. Six metabolism pathways and two environmental information processing pathways enriched by targets were correlated with 2 or more herbs in SWT and SJZT formula, respectively.

Neuroprotection and antioxidative effects of Sijunzi Tang Decoction in the nematode Caenorhabditis elegans

IntroductionKnowledge about the pharmacological properties of traditional TCM formulas is scarce as is their impact on aging. This study evaluated the potential effects of Sijunzi Tang Decoction (SJZTD), Si-Wu-Tang Decoction (SWTD), and Liuwei Dihuang Decoction (LWDHD) against oxidative stress and glucotoxic stress-induced neuronal dysfunction and lifespan reduction. MethodsNematodes (C. elegans) were cultivated under 10mmol/L paraquat or 400mmol/L glucose to assess the protective effects of a systemic Traditional Chinese Medicine (TCM) treatment. Lifespan was determined by calculation of Kaplan-Meier survival curves, formation of reactive oxygen species was quantified by hydroethidine staining, and neuronal functions were evaluated by worm tracking analysis. ResultsA 10% SJZTD solution largely normalized nematode survival under both oxidative stress (increased 3-day-survival rate by 143%) and glucotoxic stress (extended mean lifespan from 19.90 to 23.71 days). Under high glucose conditions we demonstrated both antioxidative effects (reduced Reactive Oxygen Species (ROS) formation by 71%) and neuroprotective effects (improved whole nematode motility by 179%). SWTD and LWDHD failed to confer protection in our model system. ConclusionsThe neuroprotective effects for SJZT decoction against glucotoxic stress due to pronounced antioxidant properties were demonstrated. Future studies should be extended to protection of the neurovascular system in higher organisms.

Efficient inhibition of growth of metastatic cancer cells after resection of primary colorectal cancer by soluble Flt-1.

Removal of primary tumors often leads to increases in growth of metastatic tumor cells. Thus, development of an efficient treatment to inhibit the growth of metastatic tumor cells after resection of primary tumors appears to be critical for cancer therapy. Here, we reported that administration of a Chinese medicine Shiquandabutao (SQDBT) after removal of the primary cancer significantly inhibited the growth of metastatic cancer cells in mouse liver. Further analyses showed that the effect of SQDBT resulted from one of its main component, Siwutang (SWT), rather than from another main component, Sijunzitang (SJZT). Moreover, we found that the soluble Flt-1 from SWT neutralized the increased placental growth factor (PLGF) secreted by the metastatic cancer cells after primary cancer resection and subsequently inhibited the cancer neovascularization to suppress the metastatic cancer growth. Thus, our study reveals an essential role of SQDBT in inhibiting the growth of metastatic cancer after removal of primary cancer and further highlights PLGF as a potential target for metastatic cancer treatment.

Qualitative and Quantitative Analysis of Constituents in Si-jun-zi Tang Decoction by HPLC-DAD-ELSD and HPLC-ESI-MS

Aim: The purpose of this study is to explore a convenient, accurate and reliable method for quality control of Si-jun-zi Tang (SJZT) decoction. Methods: A high-performance liquid chromatography coupled with diode array and evaporative light scattering detectors (HPLC-DAD-ELSD) method and a HPLC coupled with electrospray ionization tandem mass spectrometry (HPLC-ESI-MS) method were developed for the qualitative and quantitative analysis of multiple constituents in SJZT. The chromatographic separation of multiple constituents was performed on a Boston pHlex ODS column and a C18 guard column with a gradient elution program consisting of 0.1% aqueous formic acid and acetonitrile at a flow rate of 0.7 mL/min. Results: A total of 23 constituents (7 ginsenosides, 9 licorice flavonoids, 5 licorice saponins and 2 atractylenolides) were verified based on peak retention time, ultraviolet-visible (UV) spectrum and MS data of HPLC-DAD-ELSD and HPLCESI- MS methods. The HPLC-DAD-ELSD method was successfully applied to quantify 11 major constituents (liquiritin apioside, liquiritin, Re/Rg1, isoliquiritin apioside, isoliquiritin, ononin, Rb1, Rg2, glycyrrhizic acid, and atractylenolide III) in SJZT with good linearity (R2 > 0.9990), acceptable precision (RSD < 3.0%) and high recovery (93.4%-101.7%). Conclusion: The combined methods of HPLC-DAD-ELSD and HPLC-ESI-MS proved to be convenient, accurate and reliable methods for qualitative and quantitative analysis of SJZT. Keywords: Ingredient, HPLC-DAD-ELSD, HPLC-ESI-MS, quantitative analysis, quantify, Si-jun-zi Tang (SJZT).

Evaluation of the teratogenic effects of three traditional Chinese medicines, Si Jun Zi Tang, Liu Jun Zi Tang and Shenling Baizhu San, during zebrafish pronephros development.

The aim of this study was to evaluate the teratogenic effects of three common Chinese medical prescriptions, Si Jun Zi Tang (SJZT), Liu Jun Zi Tang (LJZT) and Shenling Baizhu San (SLBS), during zebrafish pronephros development. We used the transgenic zebrafish line Tg(wt1b:EGFP) to assess the teratogenic effects using 12 different protocols, which comprised combinations of 4 doses (0, 25, 250, 1,250 ng/mL) and 3 exposure methods [methods I, 12–36 hours post fertilization (hpf), II, 24–48 hpf, and III, 24–36 hpf]. As a result, few defects in the kidneys were observed in the embryos exposed to 25 ng/mL of each medical prescription. The percentage of kidney malformation phenotypes increased as the exposure concentrations increased (25 ng/mL, 0–10%; 250 ng/mL, 0–60%; 1,250 ng/mL, 80–100%). Immunohistochemistry for α6F, which is a basolateral and renal tubular differentiation marker, revealed no obvious defective phenotypes in either SJZT- or LJZT-treated embryos, indicating that these Chinese medical prescriptions had minimal adverse effects on the pronephric duct. However, SLBS-treated embryos displayed a defective phenotype in the pronephric duct. According to these findings, we suggest (1) that the Chinese medical prescriptions induced kidney malformation phenotypes that are dose dependent and (2) that the embryonic zebrafish kidney was more sensitive to SLBS than SJZT and LJZT.

Coptidis rhizome and Si Jun Zi Tang can prevent Salmonella enterica serovar Typhimurium infection in mice.

Salmonella, a common zoonotic pathogen, causes gastroenteritis in both humans and animals. Traditional Chinese Medicine (TCM) has been used to improve gastrointestinal dysfunction and to modify the immune response to inflammation for centuries. This study used six herbal plants and four TCM formulae to rate their efficacy in preventing S. Typhimurium infection via mouse model. Minimum bactericidal concentration (MBC) of Coptidis rhizome (CR) against the reference strain tallied 12.5 mg/ml and against clinical isolate ST21 was 25 mg/ml. MBCs of other herbal extracts and formulae on Salmonella Typhimurium strains were above 50 mg/ml. In the mice model, CR and Si Jun Zi Tang (SJZT) could significantly decrease the bacterial load in organs and blood after being challenged, along with body weight loss due to the infection. CR and SJZT alleviated infection-induced interferon-gamma levels in the serum and tissues, and tumor necrosis factor-alpha (TNF-α) levels in intestinal tissues. CR and SJZT serum metabolites could suppress S. Typhimurium invasion and TNF-α expression in RAW264.7 cells. The therapeutic activity of CR and SJZT may involve berberine, ginsenoside Rb1, and glycyrrhizin, interfering with Salmonella when invading macrophages. CR and SJZT has shown potential in preventing S. Typhimurium infection through the regulation of the immune response.