The liver regenerative capacity is crucial for patients with end-stage liver disease following partial hepatectomy (PHx). The specific bacteria and mechanisms regulating liver regeneration post-PHx remain unclear. This study demonstrated dynamic changes in the abundance of Parabacteroides distasonis (P. distasonis) post-PHx, correlating with hepatocyte proliferation. Treatment with live P. distasonis significantly promoted hepatocyte proliferation and liver regeneration after PHx. Targeted metabolomics revealed a significant positive correlation between P. distasonis and β-hydroxybutyric acid (BHB), as well as hyodeoxycholic acid and 3-hydroxyphenylacetic acid in the gut after PHx. Notably, treatment with BHB, but not hyodeoxycholic acid or 3-hydroxyphenylacetic acid, significantly promoted hepatocyte proliferation and liver regeneration in mice after PHx. Moreover, STAT3 inhibitor Stattic attenuated the promotive effects of BHB on cell proliferation and liver regeneration both in vitro and in vivo. Mechanistically, P. distasonis upregulated the expression of fatty acid oxidation-related proteins, and increased BHB levels in the liver, and then BHB activated the STAT3 signaling pathway to promote liver regeneration. This study, for the first time, identifies the involvement of P. distasonis and its associated metabolite BHB in promoting liver regeneration after PHx, providing new insights for considering P. distasonis and BHB as potential strategies for promoting hepatic regeneration.

[This corrects the article DOI: 10.1016/j.apsb.2024.03.030.].

This study aims to investigate the effects of Pulsatilla powder(PP)on colonic intestinal flora and tryptophan metabolism in piglets with diarrhea.Twenty-four weaned piglets were ran-domly divided into the normal control group,model group,self-healing group,and PP group.The model of piglet diarrhea was established by the compound factor of external evil+internal injury+epi-demic virus,and treated with PP.During the modeling period,the body weight,mental status and fecal patterns of piglets were monitored daily.After the experiment,the colon tissues were collect-ed for histopathological observation,and the inflammatory factors IL-1β and IL-6 in the colon tis-sue was detected by ELISA,16S rRNA was used to analyze colonic intestinal flora and RT-qPCR was used to determine the expression of genes related to tryptophan metabolism in the colon.The results showed that,compared with the model group,PP significantly improved the pathological status of the colon in piglets with diarrhea,with elevated body mass and a significant increase in goblet cells(P＜0.05);and significantly reduced the levels of IL-1β and IL-6 in the colon of diar-rhea piglets(P＜0.05).The results of intestinal flora showed that PP increased the abundance of Firmicutes(P＜0.01),Spirochaeota(P＜0.01)and Lactobacillus(P＜0.05),reduced the abun-dance of Bacteroidota(P＜0.05)、Prevotella_NK3B31_group(P＜0.05)and Clostridium_sensu_stricto 1(P＜0.01).Meanwhile,PP significantly reduced the expression level of TPH1 mRNA(P＜0.05),increased the expression levels of AhR(P＜0.05)and IL-22 mRNA in the co-lon of diarrhea piglets.These results indicates that PP may alleviate diarrhea in piglets by regula-ting colonic intestinal flora and genes related to intestinal tryptophan metabolism.This study pro-vides data support for the subsequent investigation of piglet diarrhea prevention and treatment.

This study aims to explore the mechanism of Shenling Baizhu San(SLBZS)in the treat-ment of ulcerative colitis(UC)based on systematic network pharmacology and in vivo experimen-tal verification.Systematic network pharmacology was used to predict the core targets and key pathways of the SLBZS in the treatment of UC,it was further validated in UC model of BALB/c mice which were established with DSS[3.5％(w/v)],and SLBZS was given orally for treatment at the same time.Network analysis of SLBZS identified 153 active compounds and 68 compound-re-lated targets correlated with UC.Additionally,5 core active compounds were obtained,such as rob-inin,luteolin,kaempferol,quercetin,denudatin B.Most of the compounds have proven to have phar-macological activities.Based on PPI network and pathway enrichment studies,SLBZS may exert anti-inflammatory,immunological regulation,and participate in the process of apoptosis through regulating IL6,TNF,IL1B,PTGS2,TP53,STAT3,CASP3,IL10,CXCL8,IL2,PPARG,PTPRC,IFNG,MTOR,MMP9,so as to affect cell differentiation,TNF signaling,cancer signaling,IL-17 signaling,NF-Kappa B signaling of Th17 cell.The results of in vivo animal experiments showed that SBP could significantly improve the clinical symptoms and colonic pathological changes of UC mice,regulate the abnormal changes of blood routine indexes,increase the serum inflammatory factors IL-4 and IL-10,and reduce the contents of IL-6,IL-2,IL-1β and TNF-α.These results indi-cates that SBP can treat ulcerative colitis through TNF signaling pathway and NF-Kappa B signa-ling pathway.

This study aims to investigate the medication rules of patented traditional Chinese medi-cine(TCM)compound formulas and molecular mechanisms of core drugs for treating sepsis using data mining and network pharmacology approaches.In the present study,we first searched the PubMed database,Web of Science database,and the China National Knowledge Infrastructure(CNKI)since the establishment of the library to April 30,2024 for the relevant literature on the treatment of sepsis by traditional Chinese medicine.The prescriptions were then statistically ana-lyzed for drug frequency and association analysis to obtain the core drugs.Then we screened the ef-fective active ingredients of the core drugs by TCMSP and other database platforms,obtained sep-sis-related genes in GeneCards and other databases,and statistically intersected targets,and predic-ted the mechanism of action of the core TCMs by subjecting the intersected targets to PPI analy-sis,GO function and KEGG pathway enrichment analysis.Finally,the relationship between key tar-gets and herbal components was examined in reverse by molecular docking method.The results showed that 64 compound formulas were obtained,with a total of 150 Chinese medicines,which were mostly sweet in taste,cold in nature,and belonged to the spleen,stomach and intestinal me-ridians.According to the association rules,the core drugs were identified as"mirabilite-peach ker-nel-rheum officinale".There were 79 intersecting targets between the core drugs and sepsis,with core targets such as IL-1β,EGFR and SRC.MAPK,TNF,IL-17 and other signaling pathways are involved to mediate inflammatory responses,apoptosis and other biological processes to exert ther-apeutic effects on sepsis.The molecular docking results indicated that the docking activity of the key targets with the main components of the drug,and sennoside E_qt has the lowest binding ener-gy and the best docking activity with SRC.In conclusion,this study showed that the prescription of Chinese medicine for sepsis is mostly based on tonifying the spleen and clearing heat.The mecha-nism of action of the core drug"mirabilite-peach kernel-rheum officinale"in the treatment of sep-sis is multilevel and multifaceted,which provides a certain theoretical basis for the treatment of sepsis by traditional Chinese medicine.

Danggui Buxue decoction(DBD)is a classic prescription with immunomodulatory and hematopoietic effects.Previous studies have shown the DBD has potential to be used as an oral im-mune booster.However,its immunomodulatory effects and mechanism of action have not been thoroughly studied,especially the protective mechanism of immunomodulatory regulation in the state of immunosuppressive is still unclear.The aim of this study was to explore the protective mechanism of DBD in the immunosuppressive state using network pharmacology combined with animal experiments verification.The active components,core targets and signaling pathways of DBD in treating immunosuppression were obtained using network pharmacology tools.On this ba-sis,the active components of DBD were identified using HPLC-MS,and in vivo studies were con-ducted at the same time.The key active components of DBD obtained using network pharmacology included quercetin,kaempferol and formononetin.The core targets included TP53,RELA,TNF,AKT1,and IL-6.KEGG pathway enrichment analysis showed that phosphoinositide 3-kinase(PI3K)-protein kinase B(AKT)may play an important role in the treatment of immunosuppres-sive diseases using DBD.Molecular docking confirmed that each core target had good binding activ-ity with its corresponding compounds.Animal experiments showed that after DBD intervention,the mRNA gene and protein expression of RELA,TNF,and IL-6 in the serum was significantly down-regulated.The mRNA expression of PI3K and AKT in the ileum and PI3K protein expression were also downregulated.In conclusion,DBD exerts its role in treating immunosuppressive diseases by regulating the PI3K-AKT signaling pathway.

To observe the effect of penthorum chinense pursh(PCP)on diarrhea in weaned pig-lets,and to explore its mechanism through network pharmacology and in vivo animal experiments.Animal experiment 1 A total of 160 1-day-old piglets were randomly divided into control group,low-dose prevention group(0.25％),medium-dose prevention group(0.50％)and high-dose pre-vention group(1.00％).Starting from the 14 th day,0.25％,0.50％and 1.00％PCP were added to the basal diet of the three prevention groups and weaned.PCP was stopped on the 29th day,and the diarrhea rate of piglets was recorded for 35 d.In animal experiment 2,35 4-week-old male Kunming mice were randomly divided into 5 groups(control group,LPS group,low-dose group,medium-dose group and high-dose group)for 8 d.The low-dose group,the medium-dose group and the high-dose group were intragastrically administered with 200,400 and 800 mg/kg PCP for 7 consecutive days,respectively.The control group and the LPS group were intragastrically administered with the same amount of sterile saline.On the 8th day of the experiment,except that the Control group was intraperitoneally injected with sterile normal saline,the other groups were intraperitoneally injec-ted with the same amount of LPS(15 mg/kg)to establish an intestinal injury model.HE staining was used for ileal histopathological observation,and fluorescence quantitative PCR was used to de-tect the expression levels of inflammatory factors and tight junction protein mRNA.The TCMSP database was used to screen the active components and targets of PCP,and the GeneCards database was used to obtain the targets of diarrhea.The targets of PCP and diarrhea were imported into Li-anchuan biological cloud platform,and the Venn diagram was obtained after intersection.The pro-tein-protein interaction(PPI)network was constructed by combining Cytoscape 3.7.1 and STRING database,and GO and KEGG enrichment analysis was performed by KOBAS-i platform.The results showed that compared with the control group,the diarrhea rate of weaned piglets in the low-dose prevention group(0.25％),the medium-dose prevention group(0.50％),and the high-dose prevention group(1.00％)was significantly reduced at 28-62 d(P＜0.05).According to the prediction of network pharmacology,there were 32 corresponding targets of 145 potential com-ponents of PCP,6 332 targets of diarrhea,and 118 intersection targets.The protective mechanism of PCP in the treatment of diarrhea may be related to NF-κB and PI3k-Akt signaling pathways.Further experiments confirmed that compared with the LPS group,PCP can significantly improve the pathological state of ileum in mice,the mRNA expression level of intestinal tight junction pro-tein Occludin(P＜0.05)was reversed.At the same time,PCP also significantly down-regulated the mRNA level of NF-κB.The results showed that PCP may alleviate diarrhea in piglets through multiple targets and multiple pathways.The main mechanism may be related to the inhibition of Akt-NF-κB signaling pathway.This study is conducive to providing a theoretical basis for the clini-cal application of PCP.

To observe the effect of penthorum chinense pursh(PCP)on diarrhea in weaned pig-lets,and to explore its mechanism through network pharmacology and in vivo animal experiments.Animal experiment 1 A total of 160 1-day-old piglets were randomly divided into control group,low-dose prevention group(0.25％),medium-dose prevention group(0.50％)and high-dose pre-vention group(1.00％).Starting from the 14 th day,0.25％,0.50％and 1.00％PCP were added to the basal diet of the three prevention groups and weaned.PCP was stopped on the 29th day,and the diarrhea rate of piglets was recorded for 35 d.In animal experiment 2,35 4-week-old male Kunming mice were randomly divided into 5 groups(control group,LPS group,low-dose group,medium-dose group and high-dose group)for 8 d.The low-dose group,the medium-dose group and the high-dose group were intragastrically administered with 200,400 and 800 mg/kg PCP for 7 consecutive days,respectively.The control group and the LPS group were intragastrically administered with the same amount of sterile saline.On the 8th day of the experiment,except that the Control group was intraperitoneally injected with sterile normal saline,the other groups were intraperitoneally injec-ted with the same amount of LPS(15 mg/kg)to establish an intestinal injury model.HE staining was used for ileal histopathological observation,and fluorescence quantitative PCR was used to de-tect the expression levels of inflammatory factors and tight junction protein mRNA.The TCMSP database was used to screen the active components and targets of PCP,and the GeneCards database was used to obtain the targets of diarrhea.The targets of PCP and diarrhea were imported into Li-anchuan biological cloud platform,and the Venn diagram was obtained after intersection.The pro-tein-protein interaction(PPI)network was constructed by combining Cytoscape 3.7.1 and STRING database,and GO and KEGG enrichment analysis was performed by KOBAS-i platform.The results showed that compared with the control group,the diarrhea rate of weaned piglets in the low-dose prevention group(0.25％),the medium-dose prevention group(0.50％),and the high-dose prevention group(1.00％)was significantly reduced at 28-62 d(P＜0.05).According to the prediction of network pharmacology,there were 32 corresponding targets of 145 potential com-ponents of PCP,6 332 targets of diarrhea,and 118 intersection targets.The protective mechanism of PCP in the treatment of diarrhea may be related to NF-κB and PI3k-Akt signaling pathways.Further experiments confirmed that compared with the LPS group,PCP can significantly improve the pathological state of ileum in mice,the mRNA expression level of intestinal tight junction pro-tein Occludin(P＜0.05)was reversed.At the same time,PCP also significantly down-regulated the mRNA level of NF-κB.The results showed that PCP may alleviate diarrhea in piglets through multiple targets and multiple pathways.The main mechanism may be related to the inhibition of Akt-NF-κB signaling pathway.This study is conducive to providing a theoretical basis for the clini-cal application of PCP.

This study aims to investigate the effects of Pulsatilla powder(PP)on colonic intestinal flora and tryptophan metabolism in piglets with diarrhea.Twenty-four weaned piglets were ran-domly divided into the normal control group,model group,self-healing group,and PP group.The model of piglet diarrhea was established by the compound factor of external evil+internal injury+epi-demic virus,and treated with PP.During the modeling period,the body weight,mental status and fecal patterns of piglets were monitored daily.After the experiment,the colon tissues were collect-ed for histopathological observation,and the inflammatory factors IL-1β and IL-6 in the colon tis-sue was detected by ELISA,16S rRNA was used to analyze colonic intestinal flora and RT-qPCR was used to determine the expression of genes related to tryptophan metabolism in the colon.The results showed that,compared with the model group,PP significantly improved the pathological status of the colon in piglets with diarrhea,with elevated body mass and a significant increase in goblet cells(P＜0.05);and significantly reduced the levels of IL-1β and IL-6 in the colon of diar-rhea piglets(P＜0.05).The results of intestinal flora showed that PP increased the abundance of Firmicutes(P＜0.01),Spirochaeota(P＜0.01)and Lactobacillus(P＜0.05),reduced the abun-dance of Bacteroidota(P＜0.05)、Prevotella_NK3B31_group(P＜0.05)and Clostridium_sensu_stricto 1(P＜0.01).Meanwhile,PP significantly reduced the expression level of TPH1 mRNA(P＜0.05),increased the expression levels of AhR(P＜0.05)and IL-22 mRNA in the co-lon of diarrhea piglets.These results indicates that PP may alleviate diarrhea in piglets by regula-ting colonic intestinal flora and genes related to intestinal tryptophan metabolism.This study pro-vides data support for the subsequent investigation of piglet diarrhea prevention and treatment.

This study aims to explore the mechanism of Shenling Baizhu San(SLBZS)in the treat-ment of ulcerative colitis(UC)based on systematic network pharmacology and in vivo experimen-tal verification.Systematic network pharmacology was used to predict the core targets and key pathways of the SLBZS in the treatment of UC,it was further validated in UC model of BALB/c mice which were established with DSS[3.5％(w/v)],and SLBZS was given orally for treatment at the same time.Network analysis of SLBZS identified 153 active compounds and 68 compound-re-lated targets correlated with UC.Additionally,5 core active compounds were obtained,such as rob-inin,luteolin,kaempferol,quercetin,denudatin B.Most of the compounds have proven to have phar-macological activities.Based on PPI network and pathway enrichment studies,SLBZS may exert anti-inflammatory,immunological regulation,and participate in the process of apoptosis through regulating IL6,TNF,IL1B,PTGS2,TP53,STAT3,CASP3,IL10,CXCL8,IL2,PPARG,PTPRC,IFNG,MTOR,MMP9,so as to affect cell differentiation,TNF signaling,cancer signaling,IL-17 signaling,NF-Kappa B signaling of Th17 cell.The results of in vivo animal experiments showed that SBP could significantly improve the clinical symptoms and colonic pathological changes of UC mice,regulate the abnormal changes of blood routine indexes,increase the serum inflammatory factors IL-4 and IL-10,and reduce the contents of IL-6,IL-2,IL-1β and TNF-α.These results indi-cates that SBP can treat ulcerative colitis through TNF signaling pathway and NF-Kappa B signa-ling pathway.