Shenling Baizhu San Research Articles

Integrated strategy for mechanism of Shenling Baizhu San in treating ulcerative colitis based on colonic metabolomics and network pharmacology

Shenling Baizhu San(SLBZS) is a commonly used medicine for the treatment of ulcerative colitis(UC). This study aims to explore the mechanism of SLBZS in treating UC by using colonic metabolomics and network pharmacology. BALB/c mice were randomly divided into four groups: a blank group, a model group, an SLBZS group, and a sulfasalazine group. UPLC-Q-TOF-MS/MS technology was utilized to analyze the metabolic profiles of colonic tissue in mice, and differential metabolites and related metabolic pathways were screened. Based on the online database, active ingredients, action targets, and UC disease targets of SLBZS were screened. The protein-protein interaction(PPI) network of core targets of SLBZS in treating UC was constructed using STRING and Cytoscape 3.9.1. Gene Ontology(GO) functional and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were performed using the DAVID database. A "metabolite-reaction-enzyme-gene" network was constructed to conduct a combined analysis of metabolomics and network pharmacology. SLBZS reversed the levels of 25 metabolites involved in various pathways such as D-glutamine and D-glutamate metabolism, caffeine metabolism, sphingolipid metabolism, arginine biosynthesis, lysine degradation, alanine, aspartate, and glutamate metabolism, glycerophospholipid metabolism, and pyrimidine metabolism in UC colonic tissue. 47 core targets of SLBZS in treating UC were involved in pathways including the MAPK signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway, lipid and atherosclerosis, inflammatory bowel disease, and Th17 cell differentiation. Integrated analysis showed that glycerophospholipid metabolism and pyrimidine metabolism were key metabolic pathways in the treatment of UC with SLBZS. The results suggested that SLBZS improved colonic mucosal morphology by regulating colonic metabolites, down-regulated the expression of inflammation-related core target genes to reduce inflammation levels, and alleviated lipid metabolism disorders, thereby exerting a therapeutic effect on UC.

Effects of Lactobacillus plantarum fermented Shenling Baizhu San on gut microbiota, antioxidant capacity, and intestinal barrier function of yellow-plumed broilers.

The current study focused on the effects of Shenling Baizhu San (SLBZS) fermented by Lactobacillus plantarum (L. plantarum) on gut microbiota, antioxidant capacity, and intestinal barrier function of yellow-plumed broilers. Our results showed that the content of ginsenoside Rb1 was the highest when SLBZS were inoculated with 3% L. plantarum and fermented at 28°C for 24 h. One-day-old male broilers were divided into five treatment groups. Treatment consisted of a basal diet as a control (Con), 0.1% unfermented SLBZS (U-SLBZS), 0.05% fermented SLBZS (F-SLBZS-L), 0.1% fermented SLBZS (F-SLBZS-M), and 0.2% fermented SLBZS (F-SLBZS-H). On days 14, 28, and 42, six chickens from each group were randomly selected for blood collection and tissue sampling. The results showed that the addition of 0.1% fermented SLBZS could significantly increase average daily feed intake (ADFI) and average daily gain (ADG), and decrease feed conversion ratio (FCR) of broilers. The addition of 0.1 and 0.2% fermented SLBZS significantly increased the lymphoid organ index of broilers on day 28 and 42. The addition of 0.1 and 0.2% fermented SLBZS could improve the antioxidant capacity of broilers. Moreover, the addition of 0.1 and 0.2% fermented SLBZS could significantly increase the villus height/crypt depth of the ileum, and significantly increase the expression of tight junction. In addition, fermentation of SLBZS increase the abundance of Coprococcus, Bifidobacterium and Bilophila in the gut of broilers. These results indicate that the supplementation of fermented SLBZS in the diet could improve the growth performance, lymphoid organ index, antioxidant capacity, and positively affect the intestinal health of broilers.

Transcriptome profiling Revealed the potential mechanisms of Shen Lin Bai Zhu San n-butanol extract on DSS induced Colitis in Mice and LC-MS analysis

BackgroundInflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disorder in gastrointestinal tract. Shen Ling Bai Zhu San (SLBZS), which has a long history of use in Traditional Chinese Medicine (TCM), has been widely used to treat gastrointestinal diseases. The isolated fractions of TCM have also been proved to possess an important potential for treating diseases, which are due to their effective components. PurposeIn this study, we examined the possibility that SLBZS and its isolated active fractions may prevent DSS-induced colitis, and investigated the potential mechanisms by regulating genetic profile of colon. MethodsColitis mice were induced by 2.5% DSS for 7 days, and then SLBZS and different SLBZS extracts were administrated to protect the mice for 7 days. Body weight, diarrhea, bleeding in stool, colon length, spleen weight, cytokines of serum and colon and pathology of colon were assessed. The level of Ginsenoside Rg1, Re and Rb1 in different SLBZS extracts and qualitative analysis of n-butanol extract of SLBZS (S-Nb) was performed by HPLC and LC-MS, respectively. And the effects of S-Nb on the transcriptome in colitis were investigated. ResultsOur results showed that SLBZS and S-Nb significantly regained body weight, reduced DAI, splenomegaly and the length of colon and attenuated histological damage of the colon. Meanwhile, SLBZS and S-Nb markedly reduced the levels of TNF-α, IL-1β and IL-6 and increased the level of IL-10 in serum and colon. These effects may be associated with the high levels of Ginsenoside Rg1, Re and Rb1 and rich variety of compounds in S-Nb including 6 ginsenosides, glycyrrhizin, L-tryptophan, and so on. Transcriptome analysis revealed that S-Nb selectively regulated 103 differentially expressed genes (DEGs), 36 of which were changed in DSS-induced mice. And the genes of Per2, Per3, Npy and Serpina3m were closely related to colitis and also restored by S-Nb with different extent. Remarkably, these DEGs modulated the biological functions of colitis mice, including extracellular region, response to external stimulus, MAPK signaling pathway and arginine and proline metabolism. ConclusionsThese data indicated that SLBZS and S-Nb blunted DSS-induced colitis by modulating differentially expression gene profile and biological functions based on their ginsenosides and rich compounds.

Shen-Ling-Bai-Zhu-San Enhances the Antipneumonia Effect of Cefixime in Children by Ameliorating Gut Microflora, Inflammation, and Immune Response.

Objective Shen-Ling-Bai-Zhu-San (SLBZS) is used for treating gastrointestinal disorders. However, the role of SLBZS in treating pneumonia in children is still unclear. Methods In this study, children (≥2 and <9 years) with pneumonia were treated with 0.1 g cefixime (cefixime group) or 0.1 g cefixime + 9 g SLBZS (SLBZS + cefixime). The drugs were administered twice daily for 10 days. The therapeutic effects of the two groups were compared. The white blood cell (WBC), neutrophil, and lymphocyte counts; neutrophil-lymphocyte ratio (NLR); serum inflammatory factor levels; and gut microflora were assessed. Results The clinical efficacy of SLBZS + cefixime treatment of pneumonia in children was higher than that of cefixime alone (93.3% vs. 86.7%). Both cefixime and SLBZS + cefixime treatments decreased the area of pulmonary inflammatory lesions, reduced white blood cell and neutrophil counts, neutrophil-lymphocyte ratio, inflammation, and increased lymphocyte count in children with pneumonia compared with those before treatment. Moreover, SLBZS enhanced the anti-inflammation and immunity-enhancing effects of cefixime in children with pneumonia. SLBZS + cefixime treatment decreased Enterobacter, Enterococcus, Bacteroides, and Fusobacterium counts and increased Bifidobacterium and Lactobacillus counts. Compared with the cefixime treatment group, the count of the six bacterial strains in the SLBZS + cefixime treatment group was closer to the normal level. Conclusion SLBZS enhanced the antipneumonia effect of cefixime in children with pneumonia by ameliorating gut microflora, inflammation, and immune response.

Chinese herbal formula shen-ling-bai-zhu-san to treat chronic gastritis: Clinical evidence and potential mechanisms.

BACKGROUNDChronic gastritis (CG) is an inflammatory disease of the gastric mucosa. Shen-ling-bai-zhu san (SLBZS), a traditional Chinese medicine formula, is widely used for treating CG. Nevertheless, its effects are currently unclear.AIMTo determine the clinical evidence and potential mechanisms of SLBZS for the treatment of CG.METHODSWe systematically searched 3 English (PubMed, Embase, Medline) and 4 Chinese databases (Cochrane Library Central Register of Controlled Trials, China National Knowledge Infrastructure database, Wanfang Data Knowledge Service Platform, and the VIP information resource integration service platform) without language or publication bias restriction. Qualified studies were selected according to pre-set inclusion and exclusion criteria. RevMan 5.3 software was used for meta-analysis and literature quality assessment, Stata 14.0 software was used for sensitivity analysis, GRADE profiler 3.6 was used to evaluate the quality of evidence. And then, network pharmacology analysis was applied to primary research the mechanisms of action of SLBZS on CG.RESULTSFourteen studies were finally included, covering 1335 participants. Meta-analysis indicated that: (1) SLBZS was superior to conventional therapies [risk ratio (RR): 1.29, 95% confidence interval (CI): 1.21 to 1.37, P < 0.00001]; (2) SLBZS was better than conventional therapies [RR: 0.24, 95% confidence interval (95%CI): 0.11 to 0.55, P = 0.0007] in terms of recurrence rate and reversal of Helicobacter pylori positivity (RR: 1.20, 95%CI: 1.11 to 1.30, P < 0.00001); and (3) The safety of SLBZS for CG remains unclear. According to the GRADE method, the quality of evidence was not high. Besides, SNZJS might treat CG by acting on related targets and pathways such as EGFR tyrosine kinase inhibitor resistance, the PI3K-Akt signaling pathway, and others.CONCLUSIONSLBZS might be useful in treating CG, but long-term effects and specific clinical mechanisms of it maintain unclear. More samples and high-quality clinical experiments should be assessed and verified in the next step.

Shen-Ling-Bai-Zhu-San (SL) and SL Derived-Polysaccharide (PL) Ameliorate the Severity of Diarrhea-Induced by High Lactose via Modification of Colonic Fermentation.

In our previous study, we demonstrated that Shen-ling-bai-zhu-san (SL), a classical Chinese herbal formula, could alleviate lactose-induced diarrhea. However, little is known about the mechanism underlying SL action or the efficacy of the polysaccharide (PL) derived from SL. In this study, we investigated the effect of SL and PL on improving the dysregulated luminal and mucosal microbiota in rats with high lactose diet using 16S rRNA analysis. The concentrations of lactose, lactic acid in cecum and short-chain fatty acids (SCFAs) in cecum and portal vein were measured, meanwhile the expression of ion transporters were ascertained. Our data suggest that the SL, PL and cecal microbiota transplantation (CMT) significantly decreased fecal water content and water intake. In the luminal microbiota there was a significant increase in Akkermansia, Bifidobacterium and Blautia and a lower abundance of Lactobacillus, Escherichia-Shigella, and Dubosiella, while the mucosal microbiota showed a significant increase in Bifidobacterium, Akkermansia, Albaculum, Bilophila, and Coriobacteriaceae_UCG-002 and a lower abundance of Enterococcus, Helicobacter, Dubosiella, and Collinsella. Furthermore, the treatments enhanced lactose fermentation and SCFA production, which may be related to the modulation of the luminal microbial community. A lower ratio of phosphorylation Na/H exchanger3/Na/H exchanger3 (pNHE3/NHE3) and a higher sodium monocarboxylate1 (sMCT1) expression were found in the treatment group than in the model group, which may be related to the changes in the mucosal microbial community. Also, the treatments may restore the impacted metabolic pathways of gut microbiota. These results provide an important foundation for mechanism of SL action and developing PL-based treatment for lactose-induced diarrhea.

Effect of Shenling Baizhu San on Intestinal Flora in a Rat Model of Ulcerative Colitis with Spleen Deficiency and Dampness.

Objective Shenling Baizhu San (SLBZS) is reported as an effective drug for ulcerative colitis (UC); however, its effect on intestinal flora remains unknown. In this study, we investigated the effect of SLBZS on intestinal flora in a rat model of UC with spleen deficiency and dampness. Methods UC was induced in rats using 2,4,6-trinitrobenzene sulfonic acid on the basis of a model of spleen deficiency and dampness. The 16S rDNA sequencing was used to detect structural changes in the intestinal flora; the phylogenetic investigation of communities by reconstruction of unobserved state (PICRUSt) analysis was used to predict the altered pathways. Results Compared with the model group, rats in the SLBZS group exhibited decreased levels of TNF-α(P < 0.05), and increased abundance and diversity of the intestinal flora. The abundance of Actinobacteria (P < 0.001) and Bacteroides (P < 0.01) increased and that of Firmicutes decreased (P < 0.001), and the abundance of Bifidobacterium(P < 0.05) and Allobaculum increased. PICRUSt analysis showed that the altered pathways between the groups were those of fatty acid and antibiotic biosynthesis, amino acid metabolism, and the pentose phosphate pathway. Conclusions SLBZS can regulate the structure and function of the intestinal flora, alter expression levels of certain metabolic pathways, and has the potential to treat UC.

Herbal Formula Shenling Baizhu San for Chronic Diarrhea in Adults: A Systematic Review and Meta-analysis.

Background:Shenling Baizhu San (SBS), a well-known Chinese medicine herbal formula, has been widely used for treating chronic diarrhea for thousands of years. However, the efficacy and safety of SBS in treating chronic diarrhea have not been fully assessed.Objective:This study evaluates the efficacy and safety of the herbal formula SBS in symptomatic relief of chronic diarrhea.Methods:English and Chinese language databases (PubMed, Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Data, and SinoMed electronic databases) were searched through April 2020 for relevant randomized controlled trials (RCTs). The outcomes in these RCTs included stool frequency, stool consistency, patient-reported satisfaction of chronic diarrhea treatment, quality of life and adverse events. Paired reviewers independently extracted data and conducted qualitative and quantitative analyses. The Cochrane revised risk of bias RoB-2 tool was applied to assess the risk of bias for each trial whereas the RevMan 5.3 software was used for outcomes data synthesis and meta-analysis. Mean difference (MD) and the 95% confidence interval (CI) were used to measure continuous data. The dichotomous data were analyzed via the relative risk (RR) with 95% CIs.Results:Fourteen RCTs including 1158 participants (54% males) with chronic diarrhea were included. Shenling Baizhu San combined with or without conventional medicine (CM) was associated with greater patient-reported satisfaction than CM alone. There was no increased risk of adverse events (AEs) during treatment.Conclusion:Treatment with SBS was associated with significant improvement in patient-reported satisfaction, irrespective of conventional medicine use. Rigorous and powered RCTs with objective outcome measures are needed to confirm the effects of SBS in specific gastrointestinal disease populations with chronic diarrhea symptoms.Systematic review registration number (PROSPERO):CRD42020178073

Abstracts from Society for Acupuncture ResearchPandemics, Pain, &amp; Public Health:Roles and Relevance of Traditional East Asian MedicineJune 14–17, 2021

Abstracts from Society for Acupuncture ResearchPandemics, Pain, &amp; Public Health:Roles and Relevance of Traditional East Asian Medicine<i>June 14–17, 2021</i>

Effects of ShenLing BaiZhu San Supplementation on Gut Microbiota and Oxidative Stress in Rats with Ulcerative Colitis.

The aim of this study was to evaluate the effect of gut microbiota and antioxidation of Shenling Baizhu San (SLBZS) as a supplement in a rat model of ulcerative colitis (UC) induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). Acute intestinal inflammation was induced in 40 male SD rats aged 4 weeks with 100 mg/kg TNBS, and then three dosages of SLBZS (0.5 g/kg, 1 g/kg, and 1.5 g/kg) were administered for eight days, respectively. Faecal microbiome composition was assessed by 16S rRNA high-throughput sequencing. The result indicated that SLBZS could reduce the diversity of gut microbiota and increased its abundance. At the genus level, the relative abundance of SCFAs producing bacteria including Prevotella and Oscillospira increased, while the relative abundance of opportunistic pathogens including Desulfovibrio and Bilophila decreased. Meanwhile, SLBZS could improve the lesions of colon and significantly reduce the level of MPO, increase the levels of SOD and CAT in rats' serum. These findings revealed that SLBZS was effective and possessed anticolitic activities in a rat model of UC by reducing macroscopical and microscopical colon injury, enhancing antioxidant capacity, and regulating gut microbiota.

Predicting the Molecular Mechanism of Shenling Baizhu San in Treating Convalescent Patients With COVID-19 Based on Network Pharmacology and Molecular Docking

Objective: Shenling Baizhu San (SBS) was selected as the regimen for the treatment of COVID-19 in Guangdong Province. It is mainly used for the convalescent treatment of COVID-19 patients with deficiency of both lung and spleen. In this study, we aimed to explore the mechanism of SBS in the treatment of COVID-19 through network pharmacology combined with molecular docking. Methods: The targets of active components of SBS were collected through Traditional Chinese Medicine Systems Pharmacology (TCMSP) and ETCM databases. Using the Genecards, TTD, OMIM and other databases, the targets of COVID-19 were determined. The next step was to use a string database to build a protein–protein interactions (PPI) network between proteins, and use David database to perform gene ontology (GO) function enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on core targets. Then we used Cytoscape software to construct the active ingredients-core target-signaling pathway network, and finally the active ingredients of SBS were molecularly docked with the core targets to predict the mechanism of SBS in the treatment of COVID-19. Results: A total of 177 active compounds, 43 core targets and 58 signaling pathways were selected. Molecular docking results showed that the binding energies of the top six active components and the targets were all less than −5 kcal/MOL. Conclusion: The potential mechanism of action of SBS in the treatment of COVID-19 may be associated with the regulation of genes co-expressed with IL6, DPP4, PTGS2, PTGS1 and TNF.

Efficacy and safety of Shen-Ling-Bai-Zhu-San combined with chemotherapy for lung cancer: A protocol for systematic review and meta-analysis.

Background:Lung cancer (LC), with the high incidence in malignant tumors in the world, and seriously affects people's lives and brings a great economic burden. Previous clinical studies on Shen-Ling-Bai-Zhu-San (SLBZS) combined with chemotherapy for the treatment of lung cancer have been increasing, but there are no systematic reviews. This study aims to systematically study the efficacy and safety of SLBZS combined with chemotherapy in the treatment of LC.Methods:The Chinese and English databases will be searched by us for related documents, and the search time limit is January 2021. Databases including PubMed, Embase, Web of Science, the Cochrane Library, Chinese databases include China National Knowledge Infrastructure, Wanfang Data, ChongqingVIP Information Resource Integration Service Platform, China Biomedical Literature. The international clinical trial registration platform and the Chinese clinical trial registration platform will be searched by us to find ongoing or unpublished trials. After screening the literature based on inclusion and exclusion criteria, 2 researchers independently extracted data. The primary outcomes were the treatment efficiency. RevMan 5.3.5 software will be used for statistical analysis. The Recommendation, Assessment, Development, and Evaluation (GRADE) system will be used to evaluate the quality evidence of each result.Results:This study will provide the latest evidence for the SLBZS combined with chemotherapy for LC.Conclusion:The efficacy and safety of SLBZS combined with chemotherapy for LC will be evaluated.Unique INPLASY number:INPLASY202110025.

Shen-Ling-Bai-Zhu-San Improves Dextran Sodium Sulfate-Induced Colitis by Inhibiting Caspase-1/Caspase-11-Mediated Pyroptosis.

The traditional Chinese medicine Shen-ling-bai-zhu-san (SLBZS) is described in “Tai Ping Hui Min He Ji Ju Fang.” SLBZS has been shown to be effective against many gastrointestinal diseases. The present study aimed to investigate the effect of SLBZS on experimental colitis in mice and to define the potential mechanisms. Our data suggest that compared to the model group, SLBZS treatment increases mouse body weight and colon length, decreases the DAI score, and improves colonic injury. SLBZS reduces the production of cytokines (IL-1β, IL-18, and TNF-α) in colon tissue and mouse colonic mucosal epithelial (MCME) cells. Mechanistically, SLBZS inhibits inflammation by inhibiting the MAPK and NF-κB signaling pathways. Further mechanistic analyses showed that SLBZS attenuates the expression levels of pyroptosis-related genes, including NLRP3, ASC, and GSDMD-N in the colons of mice. In addition, SLBZS restores the levels of the colon tight junction proteins ZO-1 and occludin, suggesting that it protects colonic barrier integrity and ameliorates the progression of colitis. In this paper, we demonstrate that SLBZS attenuates DSS-induced ulcerative colitis injury in mice via the MAPK/NF-κB and pyroptosis signaling pathway. These results indicate that SLBZS is a potential drug for the treatment of UC.

Shenling Baizhu San improves functional dyspepsia in rats as revealed by 1H-NMR based metabolomics.

Functional dyspepsia (FD), a common gastrointestinal disorder around the world, is driven by multiple factors, making prevention and treatment a major challenge. Shenling Baizhu San (SBS), a classical prescription of traditional Chinese medicine, has been proven to be effective in gastrointestinal disorders. However, studies on SBS improving FD are few. Thus, our study aimed to evaluate the effect of SBS on FD and further to explore the mechanism underlying the interactions between FD and SBS by the metabolomics approach. A FD rat model was induced by multiple forms of mild stimulation, and proton nuclear magnetic resonance (1H-NMR) spectroscopy and multivariate data analysis were used to profile the fecal and urinary metabolome in the FD rats during SBS intervention. Significant dyspeptic symptoms such as weight loss, poor appetite, reduced gastrointestinal motility and decreased absorptive capacity were observed in the FD rats, which were subsequently improved by SBS. Additionally, the levels of citrate, branched chain acids and pyruvate decreased, and the levels of choline, trimethylamine and taurine increased in the FD rats. Furthermore, the metabolic disorders were amended with SBS intervention mainly by modulating the metabolic pathways involved in energy metabolism, amino acid metabolism, and gut microbiota and host co-metabolism. Overall, our study highlighted the effect of SBS on the disturbed metabolic pathways in the FD rats, providing new insight into the mechanism of SBS treatment for FD from the perspective of metabolomics.

Deep-Fried Atractylodis Rhizoma Protects against Spleen Deficiency-Induced Diarrhea through Regulating Intestinal Inflammatory Response and Gut Microbiota.

According to the theories of traditional Chinese medicine, spleen deficiency often leads to diarrhea, and deep-fried Atractylodis Rhizoma (DAR) is commonly used for the treatment. However, the association between spleen deficiency and diarrhea remains unclear. The present study aimed to investigate the therapeutic effect of DAR for the treatment of diarrhea caused by spleen deficiency and analyze the related mechanisms. It was found that a high dose group of an ethanolic extract of deep-fried Atractylodis Rhizoma (EEDAR-H) significantly inhibited weight loss, diarrhea, and pathological changes in colon tissue induced by rhubarb. EEDAR-H was found to significantly reduce the level of intestinal inflammatory cytokines and increase the expression of gastrointestinal motility hormones. In addition, EEDAR-H significantly increased the expression of aquaporin 3 (AQP3) and aquaporin 8 (AQP8) and restored abnormal water metabolism; Shen-Ling-Bai-Zhu-San (SLBZS) induced the same effect as EEDAR-H. Additional tests on the mechanism found that EEDAR-H and SLBZS promoted the integrity of the intestinal barrier. Both significantly increased the expression of the tight junction protein ZO-1 and Occludin, inhibited the phosphorylation of p38MAPK and MLC, and significantly reduced the expression levels of PAR-2. Analysis of the gut microbiota indicated that overall changes in its structure were reversed after treatment with EEDAR-H or SLBZS, in addition to significant modulation of the abundance of different phyla. At the genus level, EEDAR-H or SLBZS significantly reduced the levels of potential pathogens and increased those of beneficial bacteria.

Chinese Herbal Medicine Formula Shenling Baizhu San Ameliorates High-Fat Diet-Induced NAFLD in Rats by Modulating Hepatic MicroRNA Expression Profiles.

Objective The purpose of present study was to investigate the potential mechanism underlying the protective effect of Shenling Baizhu San (SLBZS) on nonalcoholic fatty liver disease (NAFLD) by microRNA (miRNA) sequencing. Methods Thirty male Wistar rats were randomly divided into a normal control (NC) group, a high-fat diet (HFD) group, and an SLBZS group. After 12 weeks, the biochemical parameters and liver histologies of the rats were assessed. The Illumina HiSeq 2500 sequencing platform was used to analyse the hepatic miRNA expression profiles. Representative differentially expressed miRNAs were further validated by qRT-PCR. The functions of the differentially expressed miRNAs were analysed by bioinformatics. Results Our results identified 102 miRNAs that were differentially expressed in the HFD group compared with the NC group. Among those differentially expressed miRNAs, the expression levels of 28 miRNAs were reversed by SLBZS administration, suggesting the modulation effect of SLBZS on hepatic miRNA expression profiles. The qRT-PCR results confirmed that the expression levels of miR-155-5p, miR-146b-5p, miR-132-3p, and miR-34a-5p were consistent with those detected by sequencing. Bioinformatics analyses indicated that the target genes of the differentially expressed miRNAs reversed by SLBZS were mainly related to metabolic pathways. Conclusion This study provides novel insights into the mechanism of SLBZS in protecting against NAFLD; this mechanism may be partly related to the modulation of hepatic miRNA expression and their target pathways.

Lipidomic Analysis of the Protective Effects of Shenling Baizhu San on Non-Alcoholic Fatty Liver Disease in Rats.

Shenling Baizhu San (SLBZS), a famous traditional Chinese medicine, has been demonstrated to exert protective effects against non-alcoholic fatty liver disease (NAFLD), but its exact mechanisms have not been well understood. The aim of this study was to investigate the mechanisms underlying the protective effects of SLBZS in a rat model of NAFLD using lipidomics and to evaluate the role of Sirtuin 1 (SIRT1) in the mechanism of SLBZS against NAFLD. The rat model of NAFLD was induced by high-fat feeding. An ultra-performance liquid chromatography-mass spectrometry (UHPLC-MS)-based untargeted lipidomics approach was applied to analyze hepatic lipid alterations, and the SIRT1-selective inhibitor EX 527 was used to inhibit SIRT expression in the liver. The results of body and biochemical parameters, as well as histological changes, indicated that SLBZS administration exerted protective effects against NAFLD. Lipidomic analysis showed that 30 lipid species were effectively regulated by SLBZS administration in rats fed a high-fat diet. Pathway analysis indicated that glycerophospholipid metabolism and glycerolipid metabolism were potential target pathways closely involved in the mechanism of SLBZS against NAFLD. Moreover, the beneficial effects of SLBZS on hepatic steatosis, some biochemical parameters and hepatic lipid species were partly diminished by SIRT1 inhibition. In conclusion, our results suggested that SLBZS administration could effectively alter some hepatic lipid species in rats fed a high-fat diet, which was mainly associated with the regulation of glycerophospholipid and glycerolipid metabolism. Furthermore, the beneficial effects of SLBZS on hepatic lipid metabolism may be at least partly attributed to SIRT1 activation in the liver.

Shen-Ling-Bai-Zhu-San alleviates functional dyspepsia in rats and modulates the composition of the gut microbiota

The pathogenesis of functional dyspepsia (FD) is multifactorial, and the gut microbiota may play a significant role. Shen-Ling-Bai-Zhu-San (SLBZS), a traditional Chinese herbal medicine, has been widely used in the treatment of FD, and appears to influence the gut microbiota. Therefore, we hypothesized that SLBZS would alleviate dyspeptic symptoms by adjusting the composition of the gut microbiota. To test this hypothesis, we aimed to evaluate the effects of SLBZS on FD and elucidate the mechanism that underlies the interactions between gut microbiota and FD during SLBZS treatment. We employed a rat model of FD induced by multiple forms of chronic mild stimulation. 16S rRNA gene sequencing and shotgun metagenomic sequencing were used to analyze the microbial communities in fecal samples from the rats. We found that the SLBZS improved dyspeptic symptoms in FD rats, such as weight loss, decreased intestinal motility, reduced absorptive capacity. Moreover, the SLBZS treatment reversed gut dysbiosis in FD. With SLBZS treatment, FD biomarkers including Prevotella, Mucispirillum and Akkermansia were decreased while SCFA-producing bacteria such as Adlercreutzia and Clostridium, and sulfate-reducing bacteria Desulfovibrio were enriched. Additionally, SLBZS normalized the dysregulated function of the microbiome, upregulating the pathways of energy metabolism and decreasing the oxidative stress as well as bacterial pathogenesis. Our study demonstrated that SLBZS could ameliorate dyspepsia, and amend the dysregulated composition and function of the gut microbial community, providing insight into the mechanism of SLBZS treatment for FD from the perspective of gut microbiota.

Systems Pharmacology and Microbiome Dissection of Shen Ling Bai Zhu San Reveal Multiscale Treatment Strategy for IBD.

Generally, inflammatory bowel disease (IBD) can be caused by psychology, genes, environment, and gut microbiota. Therefore, IBD therapy should be improved to utilize multiple strategies. Shen Ling Bai Zhu San (SLBZS) adheres to the aim of combating complex diseases from an integrative and holistic perspective, which is effective for IBD therapy. Herein, a systems pharmacology and microbiota approach was developed for these molecular mechanisms exemplified by SLBZS. First, by systematic absorption-distribution-metabolism-excretion (ADME) analysis, potential active compounds and their corresponding direct targets were retrieved. Then, the network relationships among the active compounds, targets, and disease were built to deduce the pharmacological actions of the drug. Finally, an “IBD pathway” consisting of several regulatory modules was proposed to dissect the therapeutic effects of SLBZS. In addition, the effects of SLBZS on gut microbiota were evaluated through analysis of the V3-V4 region and multivariate statistical methods. SLBZS significantly shifted the gut microbiota structure in a rat model. Taken together, we found that SLBZS has multidimensionality in the regulation of IBD-related physiological processes, which provides new sights into herbal medicine for the treatment of IBD.

Polysaccharides from radix astragali exert immunostimulatory effects to attenuate the dampness stagnancy due to spleen deficiency syndrome

Pharmacognosy Magazine ,2019,15,63,500-506.DOI:10.4103/pm.pm_503_18Published:May 2019Type:Original Article Authors:Wenxiao Zhao, Lijun Chen, Ning Cui, Xuming Ji, Haiqiang Jiang, Tiantian Deng, and Shijun Wang Author(s) affiliations:Wenxiao Zhao1, Lijun Chen2, Ning Cui3, Xuming Ji4, Haiqiang Jiang5, Tiantian Deng3, Shijun Wang6 1School of Nursing, Shandong University of Traditional Chinese Medicine; Shandong Co-Innovation Center of Classic Traditional Chinese Medicine Formula, Jinan, Shandong, China 2School of Nursing, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China 3School of Traditional Chinese Medical, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China. 4College of Basic Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China 5Key Laboratory of Traditional Chinese Medicine Basic Research, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China 6Shandong Co-Innovation Center of Classic Traditional Chinese Medicine Formula; School of Traditional Chinese Medical, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China Abstract:Background: Radix Astragali is an herb with tonifying qi or adaptogenic effects and commonly used for spleen-qi deficiency in traditional Chinese medicine. Astragalus polysaccharides (APS) is one of the major bioactive ingredients, and little is known on APS in attenuating the dampness stagnancy due to spleen deficiency (DSSD). Objective: The objective of the study is to investigate the potential mechanism of action of APS underlying attenuating water and fluid retention of rats with the DSSD syndrome in order to provide novel insights into the application of APS on modulating the DSSD syndrome. Materials and Methods: Four-week-old Wistar rats were fed with one high-fat and low-protein diet and subjected to exhaustive swimming to induce the DSSD model for 8 weeks. APS (300, 600, and 1200 mg/kg) and Shen Ling Bai Zhu San (SLBZS) (2.5 g/kg) were administrated starting at 9 weeks for 2 weeks. Results: APS increased the body weight, decreased the water load index, and attenuated symptoms of the DSSD syndrome. APS also increased spleen and thymus indices, the percentage of CD3+, the percentage of CD3+ CD4+, and CD3+ CD4+ to CD3+ CD8+ ratio and decreased levels of serum interleukin (IL)-6, IL-10, and tumor necrosis factor-α in DSSD rats. Significant effects were seen for toll-like receptor 4 (TLR4) at both protein and gene expression levels with amelioration of expression levels in APS groups. Conclusion: These findings suggest that APS may be used to attenuate the fluid retention of the DSSD syndrome through the immunoregulatory effect, which is driven in part by the modulation of TLR4. Keywords:Astragalus polysaccharides, cytokine secretion, dampness stagnancy due to spleen deficiency, immunostimulatory effects, toll-like receptor 4View:PDF (1.85 MB)