[This corrects the article DOI: 10.1016/j.apsb.2021.07.004.].

Objective To explore the efficacy and mechanism of the aqueous extract of Sauropus spatulifolius in treating constipation based on network pharmacology analysis and experiments.Meth-ods Network pharmacology analysis was conducted using an online platform to investigate the molec-ular mechanism of Sauropus spatulifolius in treating constipation.Loperamide-induced mouse consti-pation models and intestinal epithelial cell(IEC)injury models were constructed.Therapeutic effects were evaluated using indicators such as the time to the first black stool,fecal water content,and gas-trointestinal transit rate.Annexin V-FITC staining was used to assess apoptosis,JC-1 staining was used to detect mitochondrial membrane potential,chemiluminescence was used to measure adenosine triphosphate(ATP)levels,and western blotting was used to detect the expression of relevant proteins.Results Network pharmacology analysis revealed that 29 active components in Sauropus spatulifolius targeted 19 genes associated with constipation,with AKT1 identified as one of the key genes.Exper-imental results demonstrated that the aqueous extract of Sauropus spatulifolius effectively alleviated loperamide-induced constipation symptoms in mice,including weight loss,reduced intestinal motili-ty,prolonged defecation time,and decreased fecal water content.Additionally,the aqueous extract of Sauropus spatulifolius inhibited IEC-6 cell apoptosis,restored mitochondrial membrane potential,and maintained intracellular ATP levels.The therapeutic mechanism involved downregulating the ex-pression of Bel-2-associated X protein(Bax),cytochrome C,Cleaved-Caspase3,and aquaporin 3(AQP3),as well as enhancing protein kinase B(Akt)phosphorylation.Conclusion The aque-ous extract of Sauropus spatulifolius effectively ameliorates constipation symptoms in mouse models,and its mechanism may be related to improving intestinal cell energy metabolism,inhibiting IEC ap-optosis,and reducing AQP3 expression,suggesting that Sauropus spatulifolius could serve as a po-tential drug for the clinical treatment of constipation.

Pancreatic adenocarcinoma (PAAD) is one of the most lethal malignancies. Although gemcitabine (GEM) is a standard treatment for PAAD, resistance limits its application and therapy. Secoemestrin C (Sec C) is a natural compound from the endophytic fungus Emericella, and its anticancer activity has not been investigated since it was isolated. Our research is the first to indicate that Sec C is a broad-spectrum anticancer agent and could exhibit potently similar anticancer activity both in GEM-resistant and GEM-sensitive PAAD cells. Interestingly, Sec C exerted a rapid growth-inhibiting effect (80% death at 6 h), which might be beneficial for patients who need rapid tumor shrinkage before surgery. Liquid chromatography/mass spectrometry and N-acetyl-l-cysteine (NAC) reverse assays show that Sec C sulfates cysteines to disrupt disulfide-bonds formation in endoplasmic reticulum (ER) proteins to cause protein misfolding, leading to ER stress and disorder of lipid biosynthesis. Microarray data and subsequent assays show that ER stress-mediated ER-associated degradation (ERAD) ubiquitinates and downregulates YAP to enhance ER stress via destruction complex (YAP-Axin-GSK-βTrCP), which also elucidates a unique degrading style for YAP. Potent anticancer activity in GEM-resistant cells and low toxicity make Sec C a promising anti-PAAD candidate.

OBJECTIVE: To investigate the therapeutic mechanism of resveratrol (RES) for Alzheimer's disease (AD) in light of network pharmacology. METHODS: We searched PubChem, BATMAN-TCM, Genecards, AD, TTD, String 11.0, AlzData, SwissTargetPrediction, Metascape and other databases for the therapeutic targets of RES and human AD-related targets. The intersection was determined using Venny 2.1 to obtain the therapeutic targets of RES for AD. The protein-protein interaction (PPI) network was constructed, the gene ontology (GO) was enriched and the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG pathway) were analyzed. Cytoscape 3.7.1 software was used to construct a target-signaling pathway network of RES in the treatment of AD. Molecular docking verification was carried out on SwissDock (http://www.swissdock.ch/docking). We examined a 293Tau cell model of AD for changes in protein levels of pS396, pS199, Tau5, CDK5, glycogen synthase kinase 3β (GSK3β) and p-GSK3β in response to RES treatment using Western blotting. RESULTS: We obtained 182 targets of RES, 525 targets related to AD, and 36 targets of RES for AD treatment, among which 34.6% of the targets were protein-modifying enzymes, 27.7% were metabolite invertase, 13.8% were gene-specific transcriptional regulators, and 10.3% were transporters. The core key targets of RES in the treatment of AD included INS, APP, ESR1, MMP9, IGF1R, CACNA1C, MAPT (microtubule- associated protein Tau), MMP2, TGFB1 and GSK3B. Enrichment analysis of GO biological process suggested that the biological function of RES in AD treatment mainly involved the response to β-amyloid protein, positive regulation of transferase activity, the transmembrane receptor protein tyrosine kinase signaling pathway, regulation of behavior, learning or memory, aging, and transmembrane transport. KEGG pathway enrichment analysis showed that the most significantly enriched signaling pathways were AD pathway, PI3K-AKT signaling pathway, cGMP-PKG signaling pathway, and MAPK signaling pathway. Molecular docking results showed that RES had strong binding with ESR1, GSK3B, MMP9, IGF1R, APP and INS. In the cell model of AD, treatment with 50 μmol/L RES for 12 h significantly reduced the levels of pS396 and pS199 by regulating CDK5 and GSK3β activity ( CONCLUSIONS RES produces therapeutic effects on AD by acting on multiple targets and affecting multiple signaling pathways and improves AD-associated pathologies
Alzheimer Disease/genetics* ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases ; Resveratrol/pharmacology*