Effect of intestinal function-recovering decoction on treatment of multiple organ dysfunction syndrome in rats

Objective:To analyze the effect of intestinal function-recovering decoction on multiple organ dysfunction syndrome in rats,and to investigate a novel solution to multiple organ dysfunction syndrome.Methods:Multiple organ dysfunction syndrome was induced in 60 Sprague-Dawley rats by intestinal ischemia-reperfusion combined with cecal ligation and puncture.Then these rats were intragastrically administered physiological saline(group Ⅰ,n=20),ampicillin(group Ⅱ,n=20) or intestinal function-recovering decoction(group Ⅲ,n=20).After treatment, serum malondialdehyde and superoxide dismutase levels were compared among three groups. Simultaneously,bacterial culture of various organ tissues was performed and bacterial and endotoxin translocation were observed.Results:Compared with group 1,serum malondialdehyde, alanine aminotransferase and aspartate aminotransferase levels were significantly decreased(all P<0.05) and serum superoxide dismutase level was significantly increased(P<0.05) in the group Ⅲ. However,there were no significant differences in these indices between groups Ⅱ and Ⅲ(P>0.05). The rate of bacterial translocation in the groups Ⅱ and Ⅲ was significantly lower than in the group Ⅰ(P<0.05),and no significant difference was observed between groups Ⅱ and Ⅲ(P>0.05). Conclusions:Intestinal function-recovering decoction can significantly reduce endotoxin and bacterial translocation and stabilize enteral oxidative-antioxidative balance.

Pharmacodynamic Experiment of Dachengqi Decoction and Separated Decoction on Incomplete Intestinal Obstruction in Rats

[Objectives]To investigate the effect and mechanism of Dachengqi Decoction and separated decoction on incomplete intestinal obstruction in rats.[Methods]80 healthy SD rats were selected to establish incomplete intestinal obstruction model by silk ligation.The dosage was 20 mL/kg for 3 d,and the damage index of ileocecal mucosa was analyzed;the morphology of ileocecal mucosa was observed by HE staining;the serum levels of IL-1α,IL-1β,IL-6,IL-18,Ach,NO,ET,IL-1,TNF-αand ultra-micro Na+-K+-ATPase were detected by ELISA.[Results]Compared with the model group,the mucosal damage index of Dachengqi Decoction and each separated decoction group decreased significantly(P<0.05);compared with the normal group and sham operation group,the serum level of IL-1,IL-6,TNF-αand other factors in the model group increased significantly(P<0.05);compared with the model group,the serum IL-1,IL-6 and TNF-αsecretion levels of rats in Dachengqi Decoction group and separated decoction group decreased(P<0.01).[Conclusions]Dachengqi Decoction and each separated decoction can effectively improve intestinal tissue pathological damage in the incomplete intestinal obstruction model rats,and reduce the inflammatory reaction in the rat body.

Dajianzhong decoction:a review of its phytochemistry and therapeutic potential for gastrointestinal disease

Dajianzhong decoction(DJZD)is one of the traditional herbal prescriptions originated from Synopsis of Golden Chamber,which clinically used for the treatment of various gastrointestinal(GI)disease.This paper was aimed to provide a systematic review on the phytochemistry of DJZD and its therapeutic potential for GI disease and the mechanism.Finally,the possible development and perspectives for future research on this prescription were also discussed.To date,over 60 compounds have been identified form DJZD,including unsaturated fatty acid,saponins,and polyphenols,with hydroxy-sanshool and ginsenoside compounds as the predominant ones.DJZD possessed widely pharmacological activities on the GI disease from the Eastern Han Dynasty to the present,such as intestinal obstruction,colitis,and irritable bowel syndrome.Especially for the intestinal obstruction,it had demonstrated the efficacy of DJZD treatment for relief of postoperative ileus in patients undergoing surgery for GI cancer.The detailed mechanism was mainly related with NF-ᴋB signaling pathway.However,further research elucidating the protective effects of DJZD on GI disease,exploring new clinical effects,as well as establishing criteria for quality control for DJZD should be studied.

Effect of Rhubarb Decoction on the Isolated Intestinal Movement of Ophicephalus argus

[Objective] The aim of this study was to investigate effects of rhubarb decoction with different concentrations on the isolated intestinal movement performance of Ophicephalus argus,and to discuss its pharmacological mechanism.[Method] With RM6240C biological signal collection and processing system,tension values of the isolated intestine before and after the treatment by rhubarb decoction with different concentrations were recorded by the isolated organ method.[Result] Rhubarb decoction with concentration of 0.062 and 0.125 g/ml showed obvious enhancement on the isolated intestinal contraction of Ophicephalus argus,while rhubarb decoction with concentration of 0.250 and 0.500 g/ml showed inhibition on the isolated intestinal contraction of Ophicephalus argus.There was an extremely significant difference in rhubarb decoction with concentration of lower than 0.500 g/ml and more than 0.500 g/ml.With the increase of rhubarb concentration,the intestinal movement of Ophicephalus argus enhanced,but the contraction frequency did not change obviously.[Conclusion] Rhubarb decoction has remarkable effects on the contraction of smooth muscle in the isolated intestines of Ophicephalus argus.

Therapeutic effect of Qingyi decoction in severe acute pancreatitis-induced intestinal barrier injury

AIM: To investigate the effect of Qingyi decoction onthe expression of secreted phospholipase A2(s PLA2) in intestinal barrier injury.METHODS: Fifty healthy Sprague-Dawley rats were randomly divided into control, severe acute pancreatitis(SAP), Qingyi decoction-treated(QYT), dexamethasonetreated(DEX), and verapamil-treated(VER) groups. The SAP model was induced by retrograde infusion of 1.5% sodium deoxycholate into the biliopancreatic duct of the rats. All rats were sacrificed 24 h post-SAP induction. Arterial blood, intestine, and pancreas from each rat were harvested for investigations. The levels of serum amylase(AMY) and diamine oxidase(DAO) were determined using biochemical methods, and serum tumor necrosis factor(TNF)-α level was measured by an enzyme linked immunosorbent assay. Pathologic changes in the harvested tissues were investigated by microscopic examination of hematoxylin and eosinstained tissue sections. The expressions of s PLA2 at m RNA and protein levels were detected by reverse transcriptase PCR and Western blot, respectively. A terminal deoxynucleotidyl transferase-mediated d UTP nick-end labeling assay was used to investigate apoptosis of epithelial cells in the intestinal tissues. RESULTS: Compared to the control group, the expression of s PLA2 at both the m RNA and protein levels increased significantly in the SAP group(0.36 ± 0.13 vs 0.90 ± 0.38, and 0.16 ± 0.05 vs 0.64 ± 0.05, respectively; P s < 0.01). The levels of AMY, TNF-α and DAO in serum were also significantly increased(917 ± 62 U/L vs 6870 ± 810 U/L, 59.7 ± 14.3 ng/L vs 180.5 ± 20.1 ng/L, and 10.37 ± 2.44 U/L vs 37.89 ± 5.86 U/L, respectively; P s < 0.01). The apoptosis index of intestinal epithelial cells also differed significantly between the SAP and control rats(0.05 ± 0.02 vs 0.26 ± 0.06; P < 0.01). The serum levels of DAO and TNF-α, and the intestinal apoptosis index significantly correlated with s PLA2 expression in the intestine(r = 0.895, 0.893 and 0.926, respectively; Ps < 0.05). Thelevels of s PLA2, AMY, TNF-α, and DAO in the QYT, VER, and DEX groups were all decreased compared with the SAP group, but not the control group. Qingyi decoction intervention, however, gave the most therapeutic effect against intestinal barrier damage, although the onset of its therapeutic effect was slower. CONCLUSION: Qingyi decoction ameliorates acute pancreatitis-induced intestinal barrier injury by inhibiting the overexpression of intestinal s PLA2. This mechanism may be similar to that of verapamil.

Jianpi Qingchang decoction regulates intestinal motility of dextran sulfate sodium-induced colitis through reducing autophagy of interstitial cells of Cajal

AIM To investigate the underlying effect of Jianpi Qingchang decoction(JQD) regulating intestinal motility of dextran sulfate sodium(DSS)-induced colitis in mice. METHODS C57BL/6 mice were randomly divided into four groups: the control group, the DSS group, the JQD group, and the 5-aminosalicylic acid group. Except for the control group, colitis was induced in other groups by giving distilled water containing 5% DSS. Seven days after modeling, the mice were administered corresponding drugs intragastrically. The mice were sacrificed on the 15^(th) day. The disease activity index, macroscopic and histopathologic lesions, and ultrastructure of colon interstitial cells of Cajal(ICC) were observed. The levels of tumor necrosis factor-alpha(TNF-α), interleukin(IL)-1β, IL-10 and interferon gamma(IFN-γ), the expression of nuclear factor-kappa B(NF-κB) p65, c-kit, microtubule-associated protein 1 light chain 3(LC3-Ⅱ) and Beclin-l m RNA, and the colonic smooth muscle tension were assessed. RESULTS Acute inflammation occurred in the mice administered DSS. Compared with the control group, the levels of IL-1β, TNF-α, IL-10 and IFN-γ, the expression of LC3-Ⅱ, Beclin-1 and NF-κB p65 m RNA, and the contractile frequency increased(P < 0.05), the expression of c-kit m RNA and the colonic smooth muscle contractile amplitude decreased in the DSS group(P < 0.05). Compared with the DSS group, the levels of IL-10 and IFN-γ, the expression of c-kit m RNA, and the colonic smooth muscle contractile amplitude increased(P < 0.05), the levels of TNF-α and IL-1β, the expression of LC3-Ⅱ, Beclin-1 and NF-κB p65 m RNA, and the contractile frequency decreased in the JQD group(P < 0.05).CONCLUSION JQD can regulate the intestinal motility of DSS-induced colitis in mice through suppressing intestinal inflammatory cascade reaction, reducing autophagy of ICC, and regulating the network path of ICC/smooth muscle cells.

Effect of Dachengqi Decoction on NF-κB p65 Expression in Lung of Rats with Partial Intestinal Obstruction and the Underlying Mechanism

To investigate the effect of Dachengqi decoction on NF-κB p65 expression in lung of rats with partial intestinal obstruction and the underlying mechanism, 30 SD rats were randomly divided into three groups： sham-operation group, model group and Dachengqi decoction treatment group （Dachengqi group）, with 10 animals in each group. The models were made by partially ligating their large intestines outside the body. The pathological changes were analyzed by HE staining. The expression of NF-κB p65 in rats lung were measured by using real-time polymerase chain reaction and immunohistochemistry respectively. Moreover, the expression of caveolin-1 in rats lung was also measured to. Increased edema, interstitial thickening, hemorrhage, and infiltration of inflammatory cells were found in the model group. In contrast, this change was significantly reduced in Dachengqi group as compared with model group. In addition, the up-regulated caveolin-1 and NF-κB p65 were also suppressed by Dachengqi decoction in lung of rats with partial intestinal obstruction. We are led to concluded that the caveolin-l-NF-κB pathway plays an important role in the development of lung injury of rats with partial intestinal obstruction and Dachengqi decoction could down-regulate the expression of caveolin-1 and NF-κB p65 in lung of rats with partial intestinal obstruction.

Gegen Qinlian decoction enhances immunity and protects intestinal barrier function in colorectal cancer patients via gut microbiota

BACKGROUND We previously showed,using the Traditional Chinese Medicine System Pharmacology Database,that Gegen Qinlian decoction(GQD)had a direct antitumor effect,and was combined with programmed cell death protein(PD)-1 inhibitors to treat microsatellite stable(MSS)tumor-bearing mice.However,the effect of GQD on patients with colorectal cancer(CRC)is not clear.AIM To determine the therapeutic mechanism of GQD in improving immune function,reducing inflammation and protecting intestinal barrier function.METHODS Seventy patients with CRC were included in this study:37 in the control group and 33 in the treatment group.The proportions of CD4+T,CD8+T,natural killer(NK),NKT and T regulatory cells were measured by flow cytometry.Levels of the cytokines tumor necrosis factor(TNF)-α,interferon(IFN)-γ,interleukin(IL)-2,IL-6,IL-10 and serotonin(5-hydroxytryptamine;5-HT)in serum were assessed by enzyme-linked immunosorbent assay(ELISA).The expression of zonula occludens(ZO)-1,occludin,nuclear factor(NF)-κB and TNF-αin tumor and normal tissues was measured by immunohistochemistry.The composition of gut microbiota from patients in the treatment group was assessed using 16S rDNA analysis.RESULTS There were no adverse events in the treatment group.The proportion of CD4+T cells and NKT cells in the post-treatment group was significantly higher than that in the pre-treatment and control groups(P<0.05).The level of TNF-αin the posttreatment group was significantly lower than that in the pre-treatment and control groups(P<0.05).The concentration of 5-HT in the post-treatment group was significantly lower than that in the pre-treatment group(P<0.05).The expression of ZO-1 and occludin in tumor tissues in the treatment group was significantly higher than that in the control group(P<0.05).The expression of ZO-1 in normal tissues of the treatment group was significantly higher than that in the control group(P=0.010).Compared with the control group,expression of NF-κB and TNF-αin tumor tissues of the treatment group was significantly decreased(P<0.05).Compared with the pre-treatment group,GQD decreased the relative abundance of Megamonas and Veillonella.In addition,GQD increased the relative abundance of Bacteroides,Akkermansia and Prevotella.CONCLUSION GQD enhances immunity and protects intestinal barrier function in patients with CRC by regulating the composition of gut microbiota.

Qingyi decoction attenuates intestinal epithelial cell injury via the calcineurin/nuclear factor of activated T-cells pathway

BACKGROUND Recent studies have demonstrated that dysfunction of the intestinal barrier is a significant contributing factor to the development of severe acute pancreatitis(SAP).A stable intestinal mucosa barrier functions as a major anatomic and functional barrier,owing to the balance between intestinal epithelial cell(IEC)proliferation and apoptosis.There is some evidence that calcium overload may trigger IEC apoptosis and that calcineurin(CaN)/nuclear factor of activated Tcells(NFAT)signaling might play an important role in calcium-mediated apoptosis.AIM To investigate the potential mechanisms underlying the therapeutic effect of Qingyi decoction(QYD)in SAP.METHODS A rat model of SAP was created via retrograde infusion of sodium deoxycholate.Serum levels of amylase,tumor necrosis factor(TNF-α),interleukin(IL)-6,D-lactic acid,and diamine oxidase(DAO);histological changes;and apoptosis of IECs were examined in rats with or without QYD treatment.The expression of the two subunits of CaN and NFAT in intestinal tissue was measured via quantitative realtime polymerase chain reaction and western blotting.For in vitro studies,Caco-2 cells were treated with lipopolysaccharide(LPS)and QYD serum,and then cell viability and intracellular calcium levels were detected.RESULTS Retrograde infusion of sodium deoxycholate increased the severity of pancreatic and intestinal pathology and the levels of serum amylase,TNF-α,and IL-6.Both the indicators of intestinal mucosa damage(D-lactic acid and DAO)and the levels of IEC apoptosis were elevated in the SAP group.QYD treatment reduced the serum levels of amylase,TNF-α,IL-6,D-lactic acid,and DAO and attenuated the histological findings.IEC apoptosis associated with SAP was ameliorated under QYD treatment.In addition,the protein expression levels of the two subunits of CaN were remarkably elevated in the SAP group,and the NFATc3 gene was significantly upregulated at both the transcript and protein levels in the SAP group compared with the control group.QYD significantly restrained CaN and NFATc3 gene expression in the intestine,which was upregulated in the SAP group.Furthermore,QYD serum significantly decreased the LPS-induced elevation in intracellular free Ca^(2+)levels and inhibited cell death.CONCLUSION QYD can exert protective effects against intestinal mucosa damage caused by SAP and the protective effects are mediated,at least partially,by restraining IEC apoptosis via the CaN/NFATc3 pathway.

Dahuang Fuzi decoction reduces inflammation levels and alleviates intestinal mucosal barrier damage in septic rats

Objective:To investigate the protective effect of Dahuang Fuzi Decoction(DHFZD),a traditional Chinese prescription,at alleviating sepsis-induced inflammation and gut barrier damage in rats.Methods:Forty clean-grade male Sprague-Dawley rats were divided randomly into three groups:normal control group(NCG,n?10),model control group(MCG,n?15)and DHFZD-treated group(DHFZDG,n?15).NCG rats were sham operated on and used as the controls,whereas MCG and DHFZDG rats were used to replicate the rat sepsis model using cecal ligation and puncture(CLP).The DHFZDG rats received DHFZD by gavage(4.5 mg/g of body weight)2 h prior to CLP and after its successful induction,while the NCG and MCG rats received equivalent amounts of sterilized water by gavage.All rat groups were starved and had free access to water.At 24 h post-experimental set up,the mortality of rats in each group was recorded,and peritoneal inflammation assessment and pathological changes related to the intestinal mucosal injury index(IMII)in the surviving rats were evaluated.D-lactic acid,tumor necrosis factor(TNF)-a,interleukin(IL)-6 and IL-10 peripheral blood concentrations,along with secretory immunoglobulin A(sIgA)in the intestinal mucosa were evaluated by enzyme-linked immunosorbent assays.Gut microbes were detected using 16S rRNA gene sequencing.Results:DHFZD reduced sepsis-related mortality in the rats.Moreover,it alleviated peritoneal inflammation and pathological changes according to the IMII.DHFZD reduced serum procalcitonin,TNF-a and IL-6 concentrations,but not the IL-10 concentration.It also reduced serum D-lactic acid and increased sIgA concentrations in intestinal mucosa.Notably,DHFZDG restored gut microbiota diversity and regulated the decrease in Bacteroidetes induced by sepsis,compared with the MCG rats.Conclusion:DHFZDG may play a protective role in sepsis by alleviating sepsis-induced inflammation and gut barrier damage in rats.

Study on the Mechanism of Fu Zi Li Zhong Decoction in Treating Gastric Ulcer and its Effect on Gastrointestinal Microecology

Objective To explore the pharmacodynamic mechanism of Fu Zi Li Zhong Decoction(FZLZD)in treating gastric ulcer and its effect on gastrointestinal microecology.Methods Rat gastric ulcer model was established by continuous vinegar gavage.The experiment included normal group,model group,ranitidine group and FZLZD group.The animals were handled after intragastricing administration of corresponding clinical isodose drugs for 7 d.The rats’gastrointestinal histopathology was observed by HE staining.The expression of ZO-1 and Occludin mRNA in rat gastric tissue was detected by RT-PCR.The diversity of intestinal flora was analyzed by 16SrDNA sequencing.Results FZLZD can effectively improve gastric mucosal destruction,epithelial exfoliation,inflammatory cell infiltration,inflammatory substance exudation and edema in rats with gastric ulcer.FZLZD can effectively up-regulate the expression levels of ZO-1 and Occludin mRNA in gastric tissue of rats with gastric ulcer.The results of intestinal flora diversity showed that the diversity of intestinal flora in FZLZD group was significantly higher than that of model group.Conclusions FZLZD can regulate gastric ulcer by promoting the expression of ZO-1 and Occludin and improving the diversity of intestinal flora.

Effects of Zhenren Yangzang Decoction Combined with Modified Shenling Baizhu Powder on Immune Function and Intestinal Microecology of Diarrhea Patients with Deficiency and Cold Syndrome

OBJECTIVE: To observe the effects of Zhenren Yangzang Decoction combined with modified Shenling Baizhu Powder on the immune function and intestinal microecology of diarrhea patients with deficiency and cold syndrome. METHODS: A total of 60 diarrhea patients with deficiency and cold syndrome were randomly divided into observation group and control group, with 30 cases in each group. The control group was treated with conventional western medicine. The observation group was given the treatment of Zhenren Yangzang Decoction combined with modified Shenling Baizhu Powder on the basis of the same treatment for 4 weeks. The clinical symptoms, fecal flora and immunoglobulin content of the 2 groups were observed and the clinical efficacy was evaluated. RESULTS: After treatment, the symptoms scores of fecal diarrhea, aversion to cold, cold limbs, loss of appetite, cold and painful waist and knee, abdominal fullness, abdominal distension and abdominal pain, and intestinal bacilli contents were significantly decreased(P < 0.05). The contents of lactobacillus, bifidus bacilli, IgG, IgM and IgA were significantly increased(P < 0.05), and the improvement of the above indexes in the observation group was significantly better than that in the control group(P < 0.05). The total effective rate after treatment in the observation group was 93.3%, which was significantly higher than 73.3% of the control group(P < 0.05). CONCLUSION: The treatment of diarrhea patients with deficiency and cold syndrome with Zhenren Yangzang Decoction and modified Shenling Baizhu Powder can effectively improve the intestinal micro-ecological environment, improve the immune function of patients and promote the rapid recovery of patients.

Progress of Bai He Di Huang decoction on intestinal flora of mouse with depression

Depression is a recurrent,common,and potentially life-threatening psychiatric disease.Intestinal flora is a large number of microbial communities that are parasitic in the human digestive tract.Current evidence suggests that the occurrence of depression may be related to intestinal flora.Long time ago,Bai He Di Huang decoction was used to treat the depression.Recently,researchers found that Bai He Di Huang decoction could affect the the intestinal flora of patients with depression.This review focuses on the clinical progress of Bai He Di Huang decoction in the treatment of depression,and explores the effect and mechanism of Bai He Di Huang decoction on the intestinal flora of depressive mouse.

Qixue Shuangbu decoction and acupuncture combined with Western medicine in acute severe stroke patients

BACKGROUND Stroke is a common and frequently occurring disease of the nervous system and one of the three major diseases leading to human death.The incidence and mortality of stroke in China increase with age.Overall,70%of patients with stroke have serious disability,which results in heavy burden to their families and the society.AIM To analyze the effects of Qixue Shuangbu decoction and acupuncture combined with Western medicine on immune indexes and digestive tract function in patients with acute severe stroke.METHODS A total of 68 patients with acute severe stroke admitted to Lanzhou Second People’s Hospital between March 2018 and September 2021 were selected and divided into the control and observation groups according to a random number table method.The control group was administered routine Western medicine treatment,such as dehydration,lowering intracranial pressure,anticoagulation,improving cerebral blood circulation and cerebral nerve protection according to the“Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke in China.”The observation group was administered Qixue Shuangbu decoction via nasal feeding tube on the basis of the routine Western medicine treatment with simultaneous acupuncture.The two groups were compared.RESULTS The acute physiology and chronic health evaluation II,organ dysfunction syndrome score,National Institutes of Health Stroke Scale,and traditional Chinese medicine syndrome scores of the two groups were significantly decreased compared with those measured before treatment,and the complements C3 and C4,and immunoglobulins(Ig)M and G were significantly increased compared with those observed before treatment(P<0.05).After treatment,the scores of the observation group were lower than those of the control group,and the complement and Ig levels were higher than those of the control group(P<0.05).The levels of diamine oxidase(DAO),Dlactic acid(D-LA),and calcitonin gene-related peptide(CGRP)in the two groups were significantly higher than those before treatment,while the levels of lipopolysaccharide,ubiquitin carboxyl-terminal hydrolase 1(UCH-L1),tumor necrosis factor-α(TNF-α),interleukin(IL)-2,and IL-8 were significantly lower than those before treatment(P<0.05).After treatment,DAO,D-LA,and CGRP were higher in the observation group than in the control group,while lipopolysaccharide,UCH-L1,TNF-α,IL-2,and IL-8 were lower than in the control group(P<0.05).The hospitalization time of individuals in the observation group was shorter than that of the control group(P<0.05).CONCLUSION Qixue Shuangbu decoction and acupuncture combined with Western medicine for the treatment of acute severe stroke can regulate intestinal flora,reduce inflammation,improve intestinal mucosal barrier function and immune function related indicators,and promote recovery.

Banxia Xiexin Decoction Alleviated Cerebral Glucose Metabolism Disorder by Regulating Intestinal Microbiota in APP/PS1 Mice

Objective To identify whether Banxia Xiexin Decoction(BXD)alleviates cerebral glucose metabolism disorder by intestinal microbiota regulation in APP/PS1 mice.Methods Forty-five 3-month-old male APP/PS1 mice were divided into 3 groups using a random number table(n=15 per group),including a model group(MG),a liraglutide group(LG)and a BXD group(BG).Fifteen 3-month-old male C57BL/6J wild-type mice were used as the control group(CG).Mice in the BG were administered BXD granules by gavage at a dose of 6 g/(kg·d)for 3 months,while mice in the LG were injected intraperitoneally once daily with Liraglutide Injection(25 nmol/kg)for 3 months.Firstly,liquid chromatography with tandem-mass spectrometry was used to analyze the active components of BXD granules and the medicated serum of BXD.Then,the cognitive deficits,Aβpathological change and synaptic plasticity markers,including synaptophysin(SYP)and postsynaptic density protein 95(PSD95),were measured in APP/PS1 mice.Brain glucose uptake was detected by micropositron emission tomography.Intestinal microbial constituents were detected by 16S rRNA sequencing.The levels of intestinal glucagon-like peptide 1(GLP-1)and cerebral GLP-1 receptor(GLP-1R),as well as the phosphoinositide-3-kinase/protein kinase B/glycogen synthase kinase-3β(PI3K/Akt/GSK3β)insulin signaling pathway were determined by immunohistochemical(IHC)staining and Western blot analysis,respectively.Results BXD ameliorated cognitive deficits and Aβpathological features(P<0.01).The expressions of SYP and PSD95 in the BG were higher than those in the MG(P<0.01).Brain glucose uptake in the BG was higher than that in the MG(P<0.01).The intestinal microbial composition in the BG was partially reversed.The levels of intestinal GLP-1 in the BG were higher than those in the MG(P<0.01).Compared with the MG,the expression levels of hippocampal GLP-1R,Akt,PI3K and p-PI3K in the BG were significantly increased(P<0.01),while the levels of GSK3βwere reduced(P<0.01).Conclusion BXD exhibited protective effects against Alzheimer’s disease by regulating the gut microbiota/GLP-1/GLP-1R,enhancing PI3K/Akt/GSK3βinsulin signaling pathway,and improving brain glucose metabolism.

Systems pharmacology approach reveals protective mechanisms of Jian-Pi Qing-Chang decoction on ulcerative colitis

BACKGROUND Given the complex pathogenesis of ulcerative colitis (UC), the conventional therapeutic methods are not fully curative. As a sort of systematic complementary and alternative medicine, traditional Chinese medicine (TCM) provides new options for the standard therapy. Nevertheless, there are still numerous problems with the promotion of TCM attributed to its complexity, and consequently, new research approaches are urgently needed. Thus, we explored the protective effects of Jian-Pi Qing-Chang (JPQC) decoction on UC based on systems pharmacology approach, which might fill the current innovation gap in drug discovery and clinical practice pertaining to TCM. AIM To investigate the protective mechanisms of JPQC decoction on UC based on systems pharmacology approach. METHODS We performed systems pharmacology to predict the active ingredients, the matched targets, and the potential pharmacological mechanism of JPQC on UC. In vivo, we explored the effects of JPQC in a colitis model induced by dextran sulfate sodium. In vitro, we adopted the bone marrow-derived macrophages (BMDMs) as well as BMDMs co-cultured with Caco2 cells to verify the underlying mechanisms and effects of JPQC on UC under TNF-α stimulation. RESULTS Systems pharmacology revealed 170 targets for the 107 active ingredients of JPQC and 112 candidate targets of UC. Protein-protein interaction networks were established to identify the underlying therapeutic targets of JPQC on UC. Based on enrichment analyses, we proposed our hypothesis that JPQC might have a protective effect on UC via the NF-κB/HIF-1α signalling pathway. Subsequent experimental validation revealed that treatment with TNFα activated the NF-κB/HIF-1α signalling pathway in BMDMs, thereby damaging the epithelial barrier permeability in co-cultured Caco2 cells, while JPQC rescued this situation. The findings were also confirmed in a dextran sulfate sodium-induced colitis model. CONCLUSION JPQC could improve the mucosal inflammatory response and intestinal epithelial barrier function via the NF-κB/HIF-1α signalling pathway, which provides new perspectives on the pharmaceutical development and clinical practice of TCM.

Effects of Buyang Huanwu Decoction on Intestinal Barrier, Intestinal Flora, and Trimethylamine Oxide in Rats with Heart Failure

Objective: To explore the mechanisms of Buyang Huanwu Decoction(BYHWD) modulating the gut microbiome and trimethylamine oxide(TAMO) to exert cardioprotective effects. Methods: Ligation of the left anterior descending coronary artery was performed in rats to induce heart failure(HF). Except for the shamoperation group(n=10), 36 operation-induced models were randomized into 3 groups using a random number table(n=12 in each group): the model group, the BYHWD group(15.02 g/kg BYHWD), and the positive group(4.99 g/kg metoprolol succinate). After 4-week treatment(once daily by gavage), echocardiography was applied to evaluate the cardiac function and the Tei index(the ratio of ventricular isovolumic contraction time(IVCT)and isovolumic diastolic time(IVRT) to ejection time(ET)) was calculated;hematoxylin-eosin(HE) staining was observed to characterize the pathology of the myocardium and small intestinal villi. D-lactic acid was detected by an enzyme-linked immunosorbent assay(ELISA). Expressions of occludin, claudin-1, and zonula occludens(ZO-1) were detected by Western blot. 16S ribosomal ribonucleic acid(16S rRNA) sequencing was used to explore the changes in the intestinal flora. TMAO was detected via liquid chromatography-tandem mass spectrometry(LC-MS/MS). Results: In the echocardiography, the Tei index was considerably lower in the positive and BYHWD groups compared with the model group(P<0.05). Besides, BYHWD improved the pathology of myocardium and small intestine of HF rats and lowered the D-lactic acid content in the serum, when compared with the model group(P<0.05). BYHWD also improved the expression of occludin and claudin-1(P<0.05);in the gut microbiota analysis, BYHWD slowed down modifications in the structure distribution of gut microbiota and regulated the diversity of intestinal flora in HF rats. The content of TMAO in the serum was significantly lowered by BYWHT compared with the model group(P<0.05). Conclusion: BYHWD may delay progression of HF by enhancing the intestinal barrier structure, and regulating intestinal flora and TAMO.

16S rRNA Technology Approach to Explore Mechanism of Qishen Decoction in Improving Nonalcoholic Fatty Liver Fibrosis

Objective: To explore the mechanism of Qishen Decoction in the treatment of nonalcoholicfatty liver fibrosis (NAFLF) by 16S rRNA technology. Methods: NAFLF rat model was established by intraperitoneal injection of carbon tetrachloride combined with high fat diet. During the modeling period, each group was given corresponding drug intervention treatment for 8 weeks. The changes of liver histopathology, serum liver function, lipid and liver fibrosis were analyzed and compared after treatment in each group. The contents of cecum end were collected and the intestinal flora was sequenced by Illumina Miseq platform. Results: Compared with the model group, Qishen Decoction could significantly improve the pathological changes of liver tissue in NALFL rats, and reduce the NAS score, oil red staining area, collagen staining area, ALT, AST, TC, TG, HA, LN, PIIINP and C-IV levels, with significant differences (P<0.05). In addition, compared with the control group, the intestinal flora abundance and diversity of the rats in the model group were significantly reduced (P<0.05), Qishen decoction could significantly increase the abundance and diversity of the intestinal flora of NAFLF rats (P<0.05), and upregulated the abundance of Bacteroidales_S24-7_group_unclassified, Bifidobacterium, Lactobacillu s, Turicibacter, Parabacteroides, Phascolarctobacterium, Lachnospiraceae_NK4A136_group, Coriobacteriaceae_UCG-002, Parasutterella, Odoribacter, Anaerostipes, Ruminococcaceae_unclassified, Allobaculum, Romboutsia, Holdemanella, and Haem ophilus, the difference was statistically significant (P<0.05). Conclusion: Qishen Decoction inhibits liver fibrosis in NAFLF rats by restore the diversity of intestinal flora and increase the abundance of probiotics in intestinal tract.

玉屏风煎剂对德化黑鸡生长性能、免疫调节、血清生化指标的影响

【目的】探讨玉屏风煎剂对德化黑鸡生长性能、免疫调节、血清生化指标的影响,并对其安全性进行观察。【方法】黄芪、白术、防风按质量比2:2:1混合煎制,浓缩成含生药1 g·mL^(-1)的玉屏风煎剂。将30日龄体重相近的德化黑鸡160头随机分为低剂量组(1.25 mL·头^(-1)·天^(-1))、中剂量组(1.875 mL·头^(-1)·天^(-1))、高剂量组(2.5mL·头^(-1)·天^(-1))和空白对照组(0 mL·头^(-1)·天^(-1)),每组4个重复,每个重复10头,煎制玉屏风饮水给药,饲喂试验为期25 d;试验第25 d采血及十二指肠,检测生长性能、十二指肠形态结构、免疫功能、抗氧化能力、血清生化等相关指标。【结果】与对照组相比,1)中、高剂量组日增重分别提高16.77%(P<0.05)、27.58%(P<0.01),3个剂量组饲料转化率分别提高8.30%、14.61%、21.92%;2)3个剂量组血清IL-2含量,中、高剂量组十二指肠黏膜SIgA水平显著提高(P<0.05或P<0.01);3个剂量组血清IFN-γ、TNF-α含量显著降低(P<0.05或P<0.01)。3)3个剂量组MDA浓度极显著降低(P<0.01),GSH-Px、SOD活性极显著升高(P<0.01),高剂量组T-AOC、CAT活性显著升高(P<0.05或P<0.01)。4)中、高剂量组隐窝深度显著降低(P<0.05),绒隐比显著增加(P<0.05或P<0.01);5)3个剂量组总胆红素浓度、甘油三酯浓度、总胆固醇浓度、谷草转氨酶活性、谷丙转氨酶活性、碱性磷酸酶活性、肌酐浓度、肌酸激酶活性差异均不显著(P>0.05)。【结论】玉屏风煎剂可以提高德化黑鸡的生长性能,改善肠道形态结构,强化抗氧化能力,增强免疫功能,具有抗炎、维持免疫平稳态的作用,使用安全,最适剂量为2.5 mL·头^(-1)·天^(-1)。

青柏溃结汤灌肠治疗溃疡性结肠炎的优势研究

目的研究青柏溃结汤灌肠治疗溃疡性结肠炎的效果及对患者疾病相关因子的影响。方法选取本院2020年12月-2022年12月收治的78例溃疡性结肠炎患者,依据随机数字表法划分为对照组与试验组,各39例。对照组给予美沙拉嗪缓释颗粒治疗,试验组在对照组基础上给予青柏溃结汤灌肠治疗。14 d为1个疗程,2组均持续治疗2个疗程。比较2组治疗2个疗程后的临床疗效及不同时间点(治疗前、治疗2个疗程后)中医证候积分、肠道菌群、免疫功能及血清白细胞介素(IL-6)、肠型脂肪酸结合蛋白(I-FABP)、核周型抗中性粒细胞抗体(p-ANCA)、C反应蛋白(CRP)水平。结果试验组总有效率(92.31%)高于对照组(71.79%)(P<0.05);治疗2个疗程后2组各项中医证候积分、Th17细胞比例、血清IL-6、CRP、I-FABP、p-ANCA水平均呈现降低的趋势(P<0.05),且试验组低于对照组(P<0.05);治疗2个疗程后2组乳酸杆菌、双歧杆菌的数量与治疗前相比均增加,且试验组多于对照组(P<0.05);治疗2个疗程后2组大肠埃希菌的数量与治疗前相比均减少,且试验组少于对照组(P<0.05);2组Treg细胞比例、血清CD3^(+)、CD4^(+)与治疗前相比,均呈现升高的趋势,且试验组高于对照组(P<0.05)。结论青柏溃结汤灌肠可调节溃疡性结肠炎患者肠道菌群变化,可辅助减轻机体炎性损伤、改善免疫功能。