Tetrahydroxy stilbene glucoside rejuvenates aging hematopoietic stem cells with predilection for lymphoid differentiation via AMPK and Tet2.

INTRODUCTION: Aging of hematopoietic stem cells (HSCs) has emerged as an important challenge to human health. Recent advances have raised the prospect of rejuvenating aging HSCs via specific medical interventions, including pharmacological treatments. Nonetheless, efforts to develop such drugs are still in infancy until now. OBJECTIVES: We aimed to screen the prospective agents that can rejuvenate aging HSCs and explore the potential mechanisms. METHODS: We screened a set of natural anti-aging compounds through oral administration to sub-lethally irradiated mice, and identified 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside (TSG) as a potent rejuvenating agent for aging HSCs. Then naturally aged mice were used for the follow-up assessment to determine the HSC rejuvenating potential of TSG. Finally, based on the transcriptome and DNA methylation analysis, we validated the role of the AMP-activated protein kinase (AMPK)-ten-eleven-translocation 2 (Tet2) axis (the AMPK-Tet2 axis) as the underlying mechanisms of TSG for ameliorating HSCs aging. RESULTS: TSG treatment not only significantly increased the absolute number of common lymphoid progenitors (CLPs) along with B lymphocytes, but also boosted the HSCs/CLPs repopulation potential of aging mice. Further elaborated mechanism research demonstrated that TSG supplementation restored the stemness of aging HSCs, as well as promoted an epigenetic reprograming that was associated with an improved regenerative capacity and an increased rate of lymphopoiesis. Such effects were diminished when the mice were co-treated with an AMPK inhibitor, or when it was performed in Tet2 knockout mice as well as senescent cells assay. CONCLUSION: TSG is effective in rejuvenating aging HSCs by modulating the AMPK- Tet2 axis and thus represents a potential candidate for developing effective HSC rejuvenating therapies.

Scutellaria baicalensis Georgi alleviates Clostridium difficile associated diarrhea and its modulatory effects on the gut microbiota.

The growing incidence of Clostridium difficile associated diarrhea (CDAD) underscores the urgency for potent treatments. This research delves into the therapeutic potential of Scutellaria baicalensis Georgi (Lamiaceae) root (SR) in addressing CDAD and its influence on gut microbiota. Using a CDAD mouse model and fidaxomicin as a control, SR's impact was measured through diarrhea symptoms, colonic histopathology, and C. difficile toxin levels. Employing the PacBio platform, 16S rRNA full-length gene sequencing analyzed the gut microbial composition and the effect of SR. Results revealed SR considerably alleviated diarrhea during treatment and restoration phases, with a marked decrease in colonic inflammation. C. difficile toxin levels dropped significantly with SR treatment (P < 0.001). While SR didn't augment gut microbiota's overall abundance, it enhanced its diversity. It restored levels of Proteobacteria and Bacteroidetes, reduced Akkermansia spp. and Enterococcus spp. proportions, and modulated specific bacterial species' abundance. In essence, SR effectively mitigates CDAD symptoms, curtails inflammatory reactions, and beneficially restructures gut microbiota, suggesting its potential in advanced CDAD clinical intervention.

Integrated serum pharmacochemistry and metabolomics reveal potential effective components and mechanisms of Shengjiang Xiexin decoction in the treatment of Clostridium difficile infection.

Shengjiang Xiexin Decoction (SXD) is a widely recognized formula in Traditional Chinese Medicine (TCM) for treating diarrhea and is commonly used in clinical practice. Clostridium difficile infection (CDI) is a type of antibiotic-associated diarrhea with a rising incidence rate that has severe consequences for humans. Recent clinical applications have found significant efficacy in using SXD as an adjunct to CDI treatment. However, the pharmacodynamic substance basis and therapeutic mechanism of SXD remain unclear. This study aimed to systematically analyze the metabolic mechanisms and key pharmacodynamic components of SXD in CDI mice by combining non-targeted metabolomics of Chinese medicine and serum medicinal chemistry. We established a CDI mouse model to observe the therapeutic effect of SXD on CDI. We investigated the mechanism of action and active substance composition of SXD against CDI by analyzing 16S rDNA gut microbiota, untargeted serum metabolomics, and serum pharmacochemistry. We also constructed a multi-scale, multifactorial network for overall visualization and analysis. Our results showed that SXD significantly reduced fecal toxin levels and attenuated colonic injury in CDI model mice. Additionally, SXD partially restored CDI-induced gut microbiota composition. Non-targeted serum metabolomics studies showed that SXD not only regulated Taurine and hypotaurine metabolism but also metabolic energy and amino acid pathways such as Ascorbate and aldarate metabolism, Glycerolipid metabolism, Pentose and glucuronate interconversions, as well as body and other metabolite production in the host. Through the implementation of network analysis methodologies, we have discerned that Panaxadiol, Methoxylutcolin, Ginsenoside-Rf, Suffruticoside A, and 10 other components serve as critical potential pharmacodynamic substance bases of SXD for CDI. This study reveals the metabolic mechanism and active substance components of SXD for the treatment of CDI mice using phenotypic information, gut microbiome, herbal metabolomics, and serum pharmacochemistry. It provides a theoretical basis for SXD quality control studies.

Shengjiang Xiexin Decoction ameliorates antibiotic-associated diarrhea by altering the gut microbiota and intestinal metabolic homeostasis.

BACKGROUND: Antibiotic-associated diarrhea (AAD) has had a significant increase in the last years, with limited available effective therapies. Shengjiang Xiexin Decoction (SXD), a classic traditional Chinese medicine formula for treating diarrhea, is a promising alternative for reducing the incidence of AAD. PURPOSE: This study aimed to explore the therapeutic effect of SXD on AAD and to investigate its potential therapeutic mechanism by integrated analysis of the gut microbiome and intestinal metabolic profile. METHODS: 16S rRNA sequencing analysis of the gut microbiota and untargeted-metabolomics analysis of feces were performed. The mechanism was further explored by fecal microbiota transplantation (FMT). RESULTS: SXD could effectively ameliorate AAD symptoms and restore intestinal barrier function. In addition, SXD could significantly improve the diversity of the gut microbiota and accelerate the recovery of the gut microbiota. At the genus level, SXD significantly increased the relative abundance of Bacteroides spp (p < 0.01) and decreased the relative abundance of Escherichia_Shigela spp (p < 0.001). Untargeted metabolomics showed that SXD significantly improved gut microbiota and host metabolic function, particularly bile acid metabolism and amino acid metabolism. CONCLUSION: This study demonstrated that SXD could extensively modulate the gut microbiota and intestinal metabolic homeostasis to treat AAD.

Targeted delivery of triptolide by dendritic cell-derived exosomes for colitis and rheumatoid arthritis therapy in murine models.

BACKGROUND AND PURPOSE: Triptolide (TP) elicits a beneficial effect in the treatment of autoimmune diseases, such as ulcerative colitis (UC) and rheumatoid arthritis (RA). However, its multiorgan toxicity needs to be resolved. Dendritic cells (DCs) are the primary target of TP, which induces immunosuppression, and DC-derived exosomes (DEX) can selectively enter DCs in vivo. Here, we encapsulated TP with DEX (DEXTP) to generate TP-targeted delivery to reduce toxicity. EXPERIMENTAL APPROACH: The effect of DEXTP was evaluated in murine colitis and RA models. Toxicity was examined by haematoxylin and eosin staining and serum biochemical marker detection. Affinity of DEXs for DCs was tracked by fluorescent labelling. The immune environment was evaluated and mimicked in vitro for further analysis of the mechanism. KEY RESULTS: DEXTP effectively carried TP to DCs in vivo, and alleviated local inflammation and damage in colitis and RA mice with no obvious toxicity. Additionally, DEXTP reshaped the immune milieu by decreasing CD4+ T-cell levels and increasing regulatory T-cell levels in vivo. Furthermore, consistent T-cell differentiation was observed in vitro, and DC activation was inhibited by alterations in surface factors and secrete cytokines, and by induction of apoptosis or other form of death. CONCLUSIONS AND IMPLICATIONS: Encapsulating TP with DEX is a new method that both reduces the toxicity of TP and induces immunosuppression in UC and RA mice. The underlying immune mechanism involves DEXTP targeting DCs in vivo, to inhibit DC activation and induce DC apoptosis, which further induces T-cell immunosuppression.

[Modulation of gut microbiota during alleviation of antibiotic-associated diarrhea with Zingiberis Rhizoma].

This study was aimed to explore the effect of Zingiberis Rhizoma extract on rats with antibiotic-associated diarrhea(AAD), and reveal the modulation of gut microbiota during alleviation of AAD. AAD rat model was successfully established by exposing rats to appropriate antibiotic mixed solution. Peficon(70 mg·kg~(-1)·d~(-1)) was used as positive control, then rats were treated with 200 mg·kg~(-1)·d~(-1) and 400 mg·kg~(-1)·d~(-1) of Zingiberis Rhizoma extract for low and high dosage groups of Zingiberis Rhizoma extract, respectively. The weight changes of the rats were observed, and the degree of diarrhea were evaluated by fecal score, 120 min fecal weight and fecal water content. Colon tissues for histopathological examination were stained with hematoxylin and eosin(HE), and 16 S rRNA sequencing analysis of gut microbiota was performed. The results showed that compared with the model group, the degree of diarrhea, indicated by fecal water content, fecal score, and 120 min fecal weight of positive control group, Zingiberis Rhizoma low-dose group and Zingiberis Rhizoma high-dose group were significantly ameliorated. And the treatment of Zingiberis Rhizoma could significantly improve the pathological condition of colon tissue in AAD rats, especially the high dose of Zingiberis Rhizoma. In addition, 16 S rRNA sequencing analysis of gut microbiota showed that the diversity and abundance of gut microbiota were significantly improved and the reco-very of gut microbiota was accelerated after given high-dose of Zingiberis Rhizoma, while no significant changes of alterations were observed after given Pefikon. Of note, compared with the pefikon group, the abundance and diversity of gut microbiota in Zingi-beris Rhizoma high-dose group were significantly elevated. At the phylum level, the abundance of Firmicutes in AAD rats increased and the abundance of Proteobacteria was decreased after the Zingiberis Rhizoma intervention. At the genus level, the abundance of Bacillus spp., Lachnoclostridium and Escherichia coli-Shigella were decreased, and the abundance of Lactobacillus spp., Trichophyton spp., and Trichophyton spp., etc., were increased. While compared with the AAD model group, there was no significant difference of gut microbiota after given Peficon. The results showed that Zingiberis Rhizoma exerted beneficial health effects against AAD, and positively affected the microbial environment in the gut of rats with AAD.

RNA-seq based transcriptome analysis of ethanol extract of saffron protective effect against corticosterone-induced PC12 cell injury.

BACKGROUND: At present, oral antidepressants are commonly used in the clinical treatment of depression. However, the current drug treatment may lead to more serious adverse reactions. Therefore, we focus on Chinese traditional medicine, trying to find an effective and safe alternative or complementary medicine. Crocus sativus (saffron) is a traditional Chinese herbal medicine, which is typically used in the clinic to regulate anxiety, insomnia, amnesia, and other mental disorder. The study aimed to explore the neuroprotective effect of ethanol extract of saffron (EES) on corticosterone (CORT)- induced injury in PC12 cells and further explored its potential mechanism. METHODS: The authenticity of saffron and the active components of EES were identified by a water test and ultra-performance liquid chromatography-time of flight mass spectrometry system. The screening of cytotoxicity for PC12 cells was incubated with EES in different concentrations for 24 h, and the protective efficacy of EES on CORT (500 µM) -induced PC12 cell injury, cell viability was assessed by Cell Counting Kit-8 (CCK-8) assay. The differentially expressed genes (DEGs) of EES-protected PC12 cells were analyzed using the RNA-seq method, and the results were analyzed for GO and KEGG enrichment. The results of RNA-seq were verified by qPCR analysis. RESULTS: The saffron was initially identified as authentic in the water test and 10 compounds were identified by Ultra Performance Liquid Chromatography (UPLC)- Mass Spectrometry (MS). The results of CCK-8 demonstrated that EES at concentrations above 640 µg/mL exerted a certain cytotoxic effect, and PC12 cells pretreated with EES (20, 40, and 80 µg/mL) significantly reversed the 500 µM CORT-induced cell death. RNA-seq analysis showed that EES regulated 246 differential genes, which were mainly enriched in the MAPK signaling pathway. Dusp5, Dusp6, Gadd45b, Gadd45G, and Pdgfc were further validated by qPCR. Experimental data showed that the results of qPCR were consistent with RNA-seq. CONCLUSIONS: These findings provide an innovative understanding of the molecular mechanism of the protective effect of EES on PC12 cells at the molecular transcription level, and Dusp5, Dusp6, Gadd45b, Gadd45g, and Pdgfc may be potential novel targets for antidepressant treatment.

Dendritic cell combination therapy reduces the toxicity of triptolide and ameliorates colitis in murine models.

Triptolide (TP) exerts a promising effect in the treatment of ulcerative colitis (UC). However, its toxicity seriously hinders its application in the clinic. Previous studies indicated that dendritic cells (DCs) are the main target through which TP exerts its immunoregulatory effect. Thus, we designed an approach to target DCs in vitro to avoid the direct exposure of organs to TP. Our results revealed that DCs pretreated with TP (DCTP) exerted satisfactory therapeutic effects in mice with colitis, resulting in improved colonic inflammation and alleviated local lesion damage. In addition, no obvious toxicity was observed. DCTP also reshaped the immune milieu by decreasing CD4+ T cell numbers and increasing regulatory T cell numbers in the spleen, mesenteric lymph nodes, peripheral blood and colon; these effects were further confirmed in vitro. Downregulation of CD80/86, ICAM-1, MHCI, TLR2/4, TNF-α, and IL-6 expression and upregulation of programmed cell death ligand 1 (PDL1) and IL-10 expression were observed, indicating that DCs were converted into tolerogenic DCs. In conclusion, DCTP can effectively reduce toxicity and alleviate colonic inflammation and local lesion damage in mice with colitis. The immune mechanism underlying the effects of DCTP included the conversion of DCs into tolerogenic DCs and the alteration of T cell differentiation to produce immunoinhibitory rather than immunostimulatory T cells.

Shuangshen granules attenuate lung metastasis by modulating bone marrow differentiation through mTOR signalling inhibition.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine Shuangshen granules (SSG) have been used to treat lung cancer patients with Qi deficiency and blood stasis for decades. According to clinical experience, SSG indeed improve the quality of life and prolong the survival time of patients with lung cancer after surgery. Each of the components herbs was proved to be effective in anti-cancer therapy. Both the American ginseng and notoginseng belong to genus Panax of the family Araliaceae. Preclinical and clinical studies demonstrated that ginsenosides of them have anti- or preventive activities to various tumors, including cancers of gastric, breast, liver, lung, ovarian, colon, melanoma and leukemia. PDS, such as ginsenoside Rb1, and PTS, such as ginsenoside Rg1 are the main anticancer compositions. Cordyceps sinensis had also been found effective in inhibiting tumour growth and metastasis, especially on tumour associated immune cells, such as macrophages. However, limited information is available regarding potential mechanisms of SSG. Myeloid-derived suppressor cell (MDSC)-mediated immunosuppression, which is closely associated with poor clinical outcomes in cancer patients, may be the target of SSG, which regulate immune function. AIM OF THE STUDY: The present study aimed to explore whether SSG attenuate the differentiation of bone marrow cells (BMCs) into MDSCs by blocking the mTOR signalling, leading to the suppression of lung metastasis. MATERIALS AND METHODS: First, we observed the differentiation of BMCs into MDSCs in vitro and in vivo. BMCs were cultured alone or co-cultured with Lewis lung carcinoma (LLC) cell supernatant in vitro. The effects of different concentrations of SSG, or LLC cell supernatant as a control, on BMC differentiation were detected by flow cytometry and western blotting. Male C57BL/6J mice were subcutaneously implanted with LLC cells, and SSG were administered by gavage twice daily before and after implantation for 7 or 14 days, respectively. The tumour weight, proportion of MDSCs, presence of CD11b+Ly6C+Ly6G- and CD11b+Ly6C+Ly6G+ cells in the bone marrow, blood, and lungs, as well as the expression levels of differentiation-related proteins in the bone marrow and lungs were evaluated. RESULTS: SSG attenuated the differentiation of BMCs into MDSCs, and reduced the fraction of CD11b+Ly6C+Ly6G+ cells by inhibiting the mTOR/S6K1/Myc signalling pathway. In vivo, SSG attenuated differentiation-associated protein markers and reduced the fractions of MDSCs and CD11b+Ly6C+Ly6G+ cells in the bone marrow, blood, and lungs. In addition, SSG administration reduced the tumour weight and inhibited lung metastasis. CONCLUSIONS: SSG may reduce lung metastasis by attenuating BMC differentiation into CD11b+Ly6C+Ly6G+ cells by inhibiting mTOR signalling in vitro and in vivo.

Modulation of gut microbiota and intestinal barrier function during alleviation of antibiotic-associated diarrhea with Rhizoma Zingiber officinale (Ginger) extract.

Antibiotic-associated diarrhea (AAD) is typically mediated by antibiotic therapy, which has increased in prevalence in recent years. Previous studies have suggested that ginger, a common spice and herbal medicine, can modulate the composition of gut microbiota and is beneficial against gastrointestinal disease. This study investigates the therapeutic effects of fresh ginger extract on AAD in a rat model. Gut microbiota and intestinal barrier function were also studied. Ginger was administered to rats with AAD. Diarrhea symptoms were assessed, and 16s rRNA sequencing analysis of gut microbiota was performed. An AAD model was successfully established, and ginger was found to effectively ameliorate AAD-related diarrhea symptoms. After the intervention of ginger decoction, the diversity (rather than richness) of gut microbiota was significantly improved, and the gut microbiota recovery was accelerated. At the genus level, Escherichia_Shigella and Bacteroides levels decreased and increased the most, respectively. Additionally, these changes were demonstrated to be coincidental with the moderate restoration of intestinal barrier function, especially the restoration of tight junction protein ZO-1. Our data indicate that ginger could restore gut microbiota and intestinal barrier function during alleviation of AAD.

Modulatory effects of Xihuang Pill on lung cancer treatment by an integrative approach.

Lung cancer has a rapidly increasing incidence and remains the highest ranked cancer in terms of mortality worldwide. Xihuang Pill(XHW), a famous four-herb traditional Chinese formulation, has been used to treat lung cancer in China for more than 100 years. It is usually prescribed as a complementary and alternative medicine for cancer therapy. However, the main active ingredients of XHW that treat lung cancer and their regulatory effects remain unclear. Here, we revealed modulatory effects effects of XHW on lung cancer in a mouse model of Lewis lung cancer (LLC) by a comprehensive strategy combining network pharmacology with metabolomics. The results demonstrated that XHW inhibited tumour growth in this model. Additionally, 11 differentially expressed metabolites were identified in the XHW group compared to those in the model group or normal group by untargeted metabolomics. They were enriched in amino acid-related metabolic pathways, and the top three pathways were phenylalanine metabolism; phenylalanine, tyrosine and tryptophan biosynthesis; and aminoacyl-tRNA biosynthesis. A total of 107 active components derived from Niuhuang, Shexiang, Ruxiang and Moyao, directly acted on 13 important targets (NR3C2, AKR1D1, MPO, PNP, NT5E, TAAR1, ADRB2, ADRB1, ADRA1A, ADRA2B, ADRA2A, MAOA and MAOB) to regulate 4 metabolites (L-phenylalanine, l-adrenaline, corticosterone and guanosine). Our results suggested that the key metabolites of XHW involved in the treatment of lung cancer were regulated by a multi-component and multi-target interaction network. This research elucidated the modulatory effect and therapeutic advantages of XHW treatment for lung tumours through an integrated approach.

Identification of a Pharmacological Biomarker for the Bioassay-Based Quality Control of a Thirteen-Component TCM Formula (Lianhua Qingwen) Used in Treating Influenza A Virus (H1N1) Infection.

As chemical analysis for quality control (QC) of traditional Chinese medicine (TCM) formula is difficult to guarantee the effectiveness, a bioassay method that combines QC with evaluation of therapeutic effects has been developed to assess the TCM quality. Here, we chose a thirteen-component TCM formula, Lianhua Qingwen capsule (LHQW), as a representative sample, to explore the pivotal biomarkers for a bioassay and to investigate close association between QC and pharmacological actions. Initially, our results showed that chemical fingerprinting could not effectively distinguish batches of LHQW. Pharmacological experiments indicated that LHQW could treat influenza A virus (H1N1) infection in the H1N1 mouse model, as claimed in clinical trials, by improving pathologic alterations and bodyweight loss, and decreasing virus replication, lung lesions and inflammation. Furthermore, by using serum metabolomics analysis, we identified two important metabolites, prostaglandin F2α and arachidonic acid, and their metabolic pathway, arachidonic acid metabolism, as vital indicators of LHQW in treatment of influenza. Subsequently, macrophages transcriptomics highlighted the prominent role of cyclooxygenase-2 (COX-2) as the major rate-limiting enzyme in the arachidonic acid metabolism pathway. Finally, COX-2 was validated by in vivo gene expression and in vitro enzymatic activity with 43 batches of LHQW as a viable pharmacological biomarker for the establishment of bioassay-based QC. Our study provides systematic methodology in the pharmacological biomarker exploration for establishing the bioassay-based QC of LHQW or other TCM formulas relating to their pharmacological activities and mechanism.

Metabolomics coupled with integrative pharmacology reveals the therapeutic effect of l-borneolum against cerebral ischaemia in rats.

OBJECTIVES: This study aimed to investigate metabolic biomarker changes and related metabolic pathways before and after treatment with l-borneolum in cerebral ischaemic rats. METHODS: Rats were subjected to pMCAO surgery. The Zea-Longa scoring method was used to evaluate neurological deficits. TTC staining was used to observe cerebral infarction. HE staining was used to observe the pathological changes in brain tissue. The metabolomics method was used to analyse the changes in metabolism. RESULTS: The pharmacology changes of the H-B group were significantly different from those of the vehicle group. Moreover, according to the metabolomics method, identification of potential biomarkers in cerebral ischaemia treatment showed that the levels of l-valine and l-arginine were increased while the levels of N-succinyl-L,L-2,6-diaminopimelate and LysoPC (18 : 1(9Z)) were reduced, which were related to energy metabolism. Simultaneously, thermogenesis and bile secretion levels were inhibited by l-borneolum. Furthermore, elevated level of methotrexate might be related to an anti-inflammatory effect. CONCLUSIONS: The therapeutic effect of l-borneolum on cerebral ischaemia might be associated with the regulation of energy metabolism, thermogenesis and bile secretion. These metabolic changes and the core target changes, as well as the metabolic-target pathway network, help to elucidate the mechanisms governing the effect of l-borneolum on cerebral ischaemia.

Exploration in the mechanism of rhubarb for the treatment of hyperviscosity syndrome based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Hyperviscosity syndrome (HVS) is a major risk factor for thrombotic diseases. Rhubarb, well-known as a traditional Chinese medicine, exhibits multiple pharmacological activities, especially for promoting blood circulation to remove blood stasis (PBRB), which has been become a functional health food for decreasing the risk of cardiovascular diseases. However, due to the complexity of rhubarb components, it is still difficult to clarify the specific targets of effective substances in PBRB, and the pharmacodynamic mechanism needs to be further probed. MATERIALS AND METHODS: The "compound-target-cell-disease" network analysis was initially used to predict potential targets and bioactive compounds. The effect of rhubarb for the treatment of HVS was examined by histopathology and biochemical assays based on the HVS rat model. RESULTS: Through the "compound-target-cell-disease" network analysis, eight potential therapeutic targets were eventually screened out, and platelets were predicted as the main effector cells of rhubarb in PBRB. Among targets coagulation factor II (prothrombin, F2) and fibrinogen gamma chain (FGG) were closely related to platelets, and five compounds associated with F2 and FGG were predicted including emodin-8-O-beta-D-glucopyranoside (Emo), physcion-8-O-beta-D-glucopyranoside (Phy), procyanidin B-5,3'-O-gallate, torachrysone-8-O-beta-D-(6'-oxayl)-glucoside and epicatechin. Furthermore, thoracic aorta histopathology and biochemical examinations showed middle dose of rhubarb (0.42 g/kg/day) significantly ameliorated pathological changes, hemorheology parameters, as well as levels of representative biomarkers such as plasma P-selectin (P-sel) and thromboxane (TXB2) in platelet activation compared to HVS rat model, whose effects were comparable to the positive drug aspirin or even better. Finally, it was further validated F2 and FGG as the major effective targets of rhubarb as well as its two active ingredients Emo and Phy in PBRB. CONCLUSIONS: This study may provide an innovative way and scientific information to further understand the main effective components of rhubarb and its mechanisms about targets of F2 and FGG in PBRB, especially the new therapeutic target FGG, which also provide a basis for establishing a quality control for rhubarb by bioassays that could correlate the clinical efficacy and its mechanism.

[Anti-inflammatory and immunomodulatory effects of Tripterygium wilfordii processed with licorice on mice model of ulcerative colitis].

The aim of this paper was to investigate the anti-inflammatory effect of Tripterygium wilfordii processed with licorice on DSS-induced ulcerative colitis( UC) mice and its regulation on intestinal immune system. In this study,a DSS-induced animal model of UC mice was established,with mesalazine( Mes) as a positive drug. The pharmacodynamic effects of low( PT1) and high( PT2)doses of T. wilfordii processed with licorice were analyzed by disease activity index( DAI),colon length and colon histopathological score in mice. By detecting the expression levels of TNF-α and IL-6 cytokines in the serum of mice,immunohistochemical CD3+T and Fox P3+Treg staining in the colon of mice,the anti-inflammatory and immunoregulatory effects of T. wilfordii processed with licorice on UC mice were analyzed. The hepatotoxicity of each dose of T. wilfordii processed with licorice was also analyzed by HE staining in liver tissue of mice and ALT and AST levels in serum. The results showed that the colitis symptoms of the mice in the PT1 group and the PT2 group were alleviated,the inflammatory cell infiltration was reduced. And the expression of inflammatory factors was decreased,the difference was statistically significant compared with the model group( P<0. 05). The HE staining and ALT and AST levels in the high dose group and low dose group were not significantly different from those in the normal group. The results showed that T. wilfordii processed with licorice has the anti-inflammatory and immunomodulatory effects on UC mice,and the dose did not show significant hepatotoxicity.

[Therapeutic window analysis of Tripterygium wilfordii processed by liquorice: an instantiation using allergic contact dermatitis].

The present study was aimed to explore the dose-toxicity-effect relationship of Tripterygium wilfordii Hook f( TW) processed by liquorice,to establish the safe and effective therapeutic window,and further to provide scientific reference for the clinical use of TW. The toxicity and anti-inflammatory effect of six doses of raw TW and TW processed by liquorice( 0. 78,1. 56,3. 12,6. 24,12. 48,15. 60 g·kg-1) in 1-fluoro-2,4-dinitrobenzene( DNFB)-induced allergic contact dermatitis( ACD) model were mainly examined by histopathology and serum biochemistry. The liver biochemical parameters including ALT and AST,related inflammatory factors including TNF-α and IL-2,together with liver index,kidney index and the other pharmacodynamic indicators,were examined and compared. The results showed that compared with the control group,the serum levels of TNF-α and IL-2 of the model group were significantly increased( P<0. 01),which proved that the ACD model was successful. The comprehensive analysis of liver biochemical indexes,serum inflammatory factors and the other indexes showed that the safe and effective therapeutic window of TW processed by liquorice was 3. 12-12. 48 g·kg-1. The results showed the therapeutic window of TW processed by liquorice was much broader than that of raw TW. And it could provide scientific reference for the clinical rational use of TW.

Quality assessment of Astragali Radix from different production areas by simultaneous determination of thirteen major compounds using tandem UV/charged aerosol detector.

To identify more chemical markers for improving the quality standard and evaluate producing areas differentiation of Astragali Radix (AR), a simple, low-cost and reliable chromatography method based on a high performance liquid chromatography (HPLC) coupled with ultraviolet (UV) detector and charged aerosol detector (CAD) for separation of 13 major chemical components, including 8 flavonoids and 5 astragalosides in AR extract, was developed. The contents of 13 compounds in total of 27 herb samples, collected from different cultivating regions, were determined and compared. Moreover, chemometric analysis techniques with principal component constituent analysis (PCA) and cluster analysis (CA) were performed to discriminate the samples from different producing areas. As a result, an obvious linkage between the content of components and collecting areas was found. Results showed that the content of astragaloside III and astragaloside IV could be used to differentiate samples collected from Northeast China, Inner Mongolia and Shanxi Province, suggesting that they should be added as the chemical marker for further investigation on the pharmacological actions and the quality control of AR.

Effect of Triptolide on Dextran Sodium Sulfate-Induced Ulcerative Colitis and Gut Microbiota in Mice.

Triptolide is beneficial for the treatment of ulcerative colitis (UC), which is closely related to the gut microbiota. However, whether the therapeutic effects of triptolide involve the regulation of the gut microbiota is still unclear. In the present study, animal models of UC mice induced by dextran sodium sulfate (DSS) were established, the changes of gut microbiota in mice were detected by high-throughput sequencing. The effects of triptolide on DSS-induced UC mouse and its gut microbiota were studied. As a result, we found that triptolide exerted anti-inflammatory and therapeutic effects on UC mice. Sequencing results for the gut microbiota showed that the composition of the gut microbiota from DSS group was disordered as compared with that from the control group, consistent with a decrease in the abundance of flora. Triptolide treatment accelerated the recovery of the population of the gut microbiota and significantly improved the microbial diversity. At the phylum level, the population of Bacteroidetes decreased and that of Firmicutes increased. At the genus level, Bacteroides and Lachnospiraceae counts decreased. Thus, triptolide could regulate the composition of the gut microbiota, accelerate the recovery of microbiota, and exert good therapeutic effects in UC mice. Our results also revealed that fecal transplantation from triptolide-treated mice could relieve UC. This study provides a reference for the rational use of triptolide for the treatment of UC.