Effects of Shenling Baizhu powder on endoplasmic reticulum stress related signaling pathway in liver tissues of nonalcoholic fatty liver disease rats

Background:According to our previous studies,Shenling Baizhu powder has an excellent preventive and therapeutic effect on nonalcoholic fatty liver disease,but the prevention mechanism is still not clear.In this study,we intended to explore the effects of Shenling Baizhu powder on the endoplasmic reticulum stress related signaling pathway in nonalcoholic fatty liver disease rats’liver tissues.Methods:After 16 weeks,the levels of serum total cholesterol,triglyceride,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,alanine transaminase and aspartate transaminase were evaluated by an automatic biochemical analyzer,and the levels of serum free fatty acid and hepatic total cholesterol and triglyceride were evaluated by commercial kits.Then,histological changes of the liver were observed by hematoxylin and eosin and oil red-O staining.Protein expression related to the liver unfolded protein response signalling pathway was assessed using Western blot analysis.Results:The results showed that Shenling Baizhu powder supplementation reduced serum total cholesterol,triglyceride,free fatty acid,alanine transaminase,and aspartate transaminase(P<0.05 or P<0.01),as well as the levels of hepatic total cholesterol and triglyceride(P<0.01).Pathological examination showed that Shenling Baizhu powder improved hepatic steatosis and lipid accumulation.The results of biochemical parameters and histological changes indicated that Shenling Baizhu powder administration exerted protective effects against nonalcoholic fatty liver disease.In addition,Shenling Baizhu powder decreased the protein expression levels of binding immunoglobulin protein,activating transcription factor 6,phosphorylation of eukaryotic initiation factor 2 alpha,protein kinase RNA-like endoplasmic reticulum kinase and X-box binding protein 1s in the liver(P<0.05 or P<0.01).Conclusion:Shenling Baizhu powder can ameliorate high-fat diet-induced liver lipid metabolism disorder in nonalcoholic fatty liver disease rats.The mechanisms may be related to the inhibition of the expression of proteins related to unfolded protein response signaling pathways in endoplasmic reticulum stress.

Mechanism of Shenling Baizhu powder in treating dextran sulfate sodium-induced colitis in rats

Objective: To investigate whether Shenling Baizhu powder can inhibit the inflammatory response of dextran sulfate sodium-induced colitis in rats by protecting the intestinal mucosal barrier. Methods: A total of 40 SD rats were randomly divided into normal control group (group A), dextran sulfate sodium model group (group B), middle-dose Shenling Baizhu powder group (group C), high-dose Shenling Baizhu powder group (group D) and sulfasalazine group (group E), with 8 rats in each group. In addition to group A, dextran sulfate sodium solution (40 g/L) was added to the drinking water of rats for free drinking. The treatment groups were also given the corresponding dose of Shenling Baizhu powder/sulfasalazine. Body weight, disease activity index(DAI), colon length and intestinal mucosal permeability were measured to evaluate the effect of Shenling Baizhu powder on colitis induced by dextran sulfate sodium. The content of interleukin-10(IL-10), interleukin-6(IL-6) and tumor necrosis factor(TNF-ɑ) in rat colonic homogenate were analyzed by using enzyme-linked immunosorbent assay. The protective effect of Shenling Baizhu powder on intestinal mucosa was discussed. Results: The levels of IL-6 and TNF-ɑ in group B were higher than those in group A (P<0.05), while IL-10 level of group B was lower than that of group A (P<0.05). The levels of TNF-ɑ in groups C, D and E were significantly lower than those in group B (P<0.01), and showed concentration dependence in groups C and D. The levels of IL-6 in groups D and E were significantly lower than those in group B (P<0.05). The levels of IL-10 in groups C, D and E were significantly higher than those in group B (P<0.01), and concentration dependence was observed in groups B and C. Conclusion: Shenling Baizhu powder can protect the intestinal mucosal barrier by regulating the function of cytokines such as IL-10, IL-6 and TNF-ɑ, which alleviate the inflammatory response in rats with dextran sulfate sodium-induced colitis.

Study on the mechanism of Shenling Baizhu Powder in the treatment of diarrhea-type irritable bowel syndrome based on network pharmacology and molecular docking

Objective:Explore the possible intervention mechanism of Shenling Baizhu Powder on IBS-D from network data through network pharmacology and molecular docking simulation technology.Methods:Establish a complete regulatory network of Shenling Baizhu powder on IBS-D after obtaining the active components and drug targets of Shenling Baizhu Powder on the TCMSP platform and obtaining the disease targets of IBS-D from GeneCards and OMIM databases.Then screen out the potential best target of Shenling Baizhu Powder in IBS-D intervention network combining with the PPI network constructed in the STRING database,and screen the potential core of compounds through the molecular docking simulation and comparison with pivecurium bromide.After that,the related gene ontology functions and pathways of Shenling Baizhu Powder in treating IBS-D will be obtained though gene ontology(GO)enrichment analysis through DAVID database and Kyoto encyclo-pedia of genes and genomes(KEGG)pathways enrichment analysis through Bioconductor database.Results:The number of IBS-D disease-related targets was 2,724.And there were 184 active compounds in Shenling Baizhusan,among which 175 could act on IBS-D.After screening,four potential best targets of PTGS2,ESR1,AR and MAPK14 were obtained,and four core compounds of quercetin,luteolin,kaempferol and isorhamnetin were obtained by molecular docking simulation.GO enrichment analysis results showed that there were 92 biological processes,18 cellular components and 21 molecular functions associated with shenling Baizhu Powder intervention IBS-D process.The results of KEGG pathway enrichment analysis showed that shenling Baizhu Powder had 172 pathways involved in the intervention of IBS-D.Conclusion:The intervention effect of Shenling Baizhu powder on IBS-D was better than pivecurium bromide in terms of the number of targets and the ease of binding to the targets.Its intervention process of IBS-D may be closely related to inflammation,cancer,endocrine disorders and other related reactions and pathways,among which quercetin,luteolin,kaempferol and isorrine are the most potential core compounds in the intervention network,and the four target proteins of PTGS2,ESR1,AR and MAPK14 are the potential best target options in the intervention network.

Therapeutic Effect of Shenling Baizhu Powder on Primary Nephrotic Syndrome Featuring Damp Abundance Due to Splenic Asthenia

[Objectives]To observe the clinical efficacy of Shenling Baizhu Powder in the treatment of primary nephrotic syndrome(PNS)featuring damp abundance due to splenic asthenia.[Methods]40 patients with PNS were randomly divided into treatment group(n=19)and control group(n=21).In the treatment group and the control group,methylprednisolone tablets were taken orally and cytoxan(CTX)was given intravenously for treatment;in the treatment group,based on oral administration of methylprednisolone tablets and intravenous drip of cytoxan(CTX),oral administration of traditional Chinese medicine(addition and subtraction of Shenling Baizhu Powder)was added.Urine routine,24-hour urinary protein,renal function and serum albumin were re-examined after 4 weeks of treatment.[Results]The total effective rate of the treatment group was significantly higher than that of the control group(89.47%vs 61.90%,P<0.05).After treatment,both groups could effectively reduce the levels of 24-hour urinary protein(P<0.05),serum creatinine(P<0.05)and urea nitrogen(P<0.05),and increase the level of serum albumin(P<0.05),but the degree of improvement in the treatment group was significantly higher than that in the control group(P<0.05),and the difference was statistically significant(P<0.05).[Conclusions]Methylprednisolone combined with addition and subtraction of Shenling Baizhu Powder could effectively reduce urinary protein,improve edema symptoms,shorten the course of hormone use and reduce adverse reactions in the treatment of PNS featuring damp abundance due to splenic asthenia.

Clinical observation of Shenling Baizhu Powder combined with triamcinolone acetonide in treating macular edema induced by retinal vein occlusion

Objective:to observe the clinical effica-cy of Shenling Baizhu Powder(SLBZP)combined with a subconjunctival injection of triamcinolone acetonide(TA)in treating macular edema(ME)induced by retinal vein occlusion(RVO).Method:there were 62 patients(62 eyes)with ME induced by RVO that were selected and divided into two groups in accordance with the ran-dom number table.Each group had 31 eyes.Group one,the control group,was treated with a single subconjunc-tival injection of TA;group two,the observation group,was treated with a single subconjunctival injection of TA(20 mg/0.5 mL)per eye and one month of SLBZP.To evaluate the clinical efficacy,both groups were checked(3×)with the best corrected-visual acuity(BCVA),cen-ter macular thickness(CMT),and intraocular pressure(IOP).The checks were before treatment,one month af-ter injection,and three months after injection.Results:there were 26 eyes(83.87%)in the observation group,and 17 eyes(54.84%)in the control group in which the BCVA was significantly improved.The ME obviously de-creased in 27 eyes(87.10%)the observation group and in 19 eyes(61.29%)the control group.The clinical effica-cy of the observation group was significantly better than that of the control group(P<0.05).Conclusion:as one method to treat ME induced by RVO,SLBZP combined with subconjunctival injection of TA is significantly more effective than a single subconjunctival injection of TA.Besides,the SLBZP had less side-effects.Based on the above,this method deserves in-depth research.

Shenling Baizhu Powder (参苓白术散) Ameliorates Pi (Spleen)-Deficiency-Induced Functional Diarrhea in Rats

Objective To explore the mechanism of Pi(Spleen)-deficiency-induced functional diarrhea(FD)model rats treated by Shenling Baizhu Powder(参苓白术散,SBP).Methods Thirty male Sprague-Dawley rats were randomly divided into 5 groups including control,model,low-,medium-,and high-dose SBP groups(SBPLDG,SBPMDG,SBPHDG),6 rats in each group,respectively.Pi-deficiency-induced FD rats model was developed through Radix et Rhizoma Rhei gavage for 7 days.After modeling,the rats were treated with 3 doses of SBP[0.93,1.86,and 3.72 g/(kg·d)],and the rats in the control and model groups were given pure water for 7 days.The diarrhea index was calculated.On the 7th and 14th days,the traveled distance of rat was measured by the open field test.Serum D-xylose content was determined by the phloroglucinol method and interleukin(IL)-10 and IL-17 levels were measured using an enzyme-linked immunosorbent assay kit.The content of Treg cells was determined by flow cytometry.Results Compared with the control group,the diarrhea index and IL-17 level in the model group were significantly higher and the total exercise distance and D-xylose content significantly decreased(P>0.05).The expression of IL-10 in the SBPHDG group was significantly up-regulated,and serum D-xylose level and Treg cells increased significantly compared with the model group(P>0.05).Conclusion High-dose SBP exhibited ameliorating effects against Pi-deficiency induced FD,which might be attributed to its modulations on intestinal absorption function as well as adaptive immunity in mesenteric lymph nodes of rat.

Hepatic protective effects of Shenling Baizhu powder, a herbal compound, against inflammatory damage via TLR4/NLRP3 signalling pathway in rats with nonalcoholic fatty liver disease

Objective: High-fat diet(HFD) and inflammation are two key contributors to nonalcoholic fatty liver disease(NAFLD). Shenling Baizhu powder(SLBZP), a classical herbal compound, has been successfully used to alleviate NAFLD. However, its specific mechanisms are not fully understood. In this study, we assessed the anti-NAFLD effect of SLBZP in vivo.Methods: Rats were fed an HFD with or without SLBZP or with probiotics. At the end of week 16, an echo magnetic resonance imaging(EchoMRI) body composition analyser was used to quantitatively analyse body composition;a micro-computed tomography(micro-CT) imaging system was used to evaluate whole body and liver fat;and the Moor full-field laser perfusion imager 2 was used to assess liver microcirculation, after which, all rats were sacrificed. Then, biochemical indicators in the blood and the ultrastructure of rat livers were evaluated. Protein expression related to the liver Toll-like receptor 4(TLR4)/Nod-like receptor family pyrin domain-containing 3(NLRP3) signalling pathway was assessed using Western blot analysis. Further, high-throughput screening of 29 related inflammatory factors in liver tissue was performed using a cytokine array.Results: SLBZP supplementation reduced body weight, serum free fatty acid, and insulin resistance index(P<0.05). It also ameliorated liver microcirculation and ultrastructural abnormalities. EchoMRI and micro-CT quantitative analyses showed that treatment with SLBZP reduced fat mass and visceral fat(P<0.05 and P<0.01, respectively). In addition, SLBZP decreased the expression of lipopolysaccharide(LPS)-activated TLR4/NLRP3 signalling pathway-related proteins and altered the expression levels of some inflammatory cytokines in liver tissues.Conclusion: SLBZP can inhibit NLRP3 inflammasome activation and interleukin-1 b release by suppressing LPS-induced TLR4 expression in rats with HFD-induced NAFLD. Thus, SLBZP may be beneficial for the prevention and treatment of inflammatory damage and associated diseases.