As a persistent gastrointestinal disorder, irritable bowel syndrome (IBS) influences the gut-brain connection, leading to abdominal pain and altered bowel irregularities. Baicalein, a flavonoid extracted from Scutellaria baicalensis, is frequently utilized in anti-inflammatory treatments. This study aimed to explore baicalein's effectiveness in mitigating IBS symptoms triggered by both chronic and acute stress (CAS) and to uncover its fundamental mechanisms. Sprague-Dawley rats were employed to develop an IBS rat model by inducing CAS for five weeks. Each rat was randomly allocated to one of four experimental groups: model (M), low-dose baicalein (L), high-dose baicalein (H), and control (C). Baicalein was orally administered throughout the experiment. Behavioral assessments were conducted, including forced swimming, marble-burying, intestinal motility, and visceral sensitivity tests. Colonic tissues were collected for histopathological examination, evaluation of oxidative stress (MDA and SOD levels), and analysis of inflammatory cytokines, and ODC1/NF-κB pathway activation using Western blot assay, ELISA, and immunofluorescence. Baicalein treatment notably ameliorated IBS-like symptoms, such as fecal pellet output and AWR scores, by alleviating stress-induced behavioral changes. Baicalein bolstered antioxidant defenses through boosting SOD activity and lowering MDA levels. Moreover, baicalein inhibited inflammatory responses, targeting IL-6, IL-1β, and TNF-α, while suppressing the expression of ODC1 and restraining NF-κB p65 phosphorylation within the colon. These results indicate that baicalein modulates oxidative stress and inflammation in CAS-associated IBS. Baicalein demonstrates protection against CAS-induced IBS by diminishing intestinal inflammation, oxidative damage, and visceral hypersensitivity via suppression of the ODC1/NF-κB pathway. These findings underscore baicalein's potential as a therapeutic approach for IBS.

The incidence of heart failure was significantly increased in patients with diabetic cardiomyopathy (DCM). The therapeutic effect of triptolide on DCM has been reported, but the underlying mechanisms remain to be elucidated. This study is aimed at investigating the potential targets of triptolide as a therapeutic strategy for DCM using a network pharmacology approach. Triptolide and its targets were identified by the Traditional Chinese Medicine Systems Pharmacology database. DCM-associated protein targets were identified using the comparative toxicogenomics database and the GeneCards database. The networks of triptolide-target genes and DCM-associated target genes were created by Cytoscape. The common targets and enriched pathways were identified by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The gene-gene interaction network was analyzed by the GeneMANIA database. The drug-target-pathway network was constructed by Cytoscape. Six candidate protein targets were identified in both triptolide target network and DCM-associated network: STAT3, VEGFA, FOS, TNF, TP53, and TGFB1. The gene-gene interaction based on the targets of triptolide in DCM revealed the interaction of these targets. Additionally, five key targets that were linked to more than three genes were determined as crucial genes. The GO analysis identified 10 biological processes, 2 cellular components, and 10 molecular functions. The KEGG analysis identified 10 signaling pathways. The docking analysis showed that triptolide fits in the binding pockets of all six candidate targets. In conclusion, the present study explored the potential targets and signaling pathways of triptolide as a treatment for DCM. These results illustrate the mechanism of action of triptolide as an anti-DCM agent and contribute to a better understanding of triptolide as a transcriptional regulator of cytokine mRNA expression.

Background. Aloperine is an active component of Sophora alopecuroides Linn, which has been extensively applied for the treatment of cardiovascular disease (CVD). However, our current understanding of the molecular mechanisms supporting the effects of aloperine on CVD remains unclear. Methods. Systematic network pharmacology was conducted to provide testable hypotheses about pharmacological mechanisms of the protective effects of aloperine against CVD. Detailed structure was obtained from Traditional Chinese Medicines Integrated Database (TCMID). Target genes of aloperine against CVD were collected from SwissTargetPrediction, DrugBank database, and Online Mendelian Inheritance in Man (OMIM) database. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway performance, and network construction were adopted to explore common target genes. Results. Our findings showed that 25 candidate targets were the interacting genes between aloperine and CVD. GO analysis revealed biological process, cellular component, and molecular function of these target genes. More importantly, the majority of enrichment pathways was found to be highly associated with the nitrogen metabolism by KEGG analysis. Core genes particularly in nitrogen metabolism pathway including carbonic anhydrase (CA) III, CA IV, CA VA, CA VB, CA VI, CA VII, CA IX, CA XII, and CA XIV can be modulated by aloperine in the nitrogen metabolism. Conclusion. Our work revealed the pharmacological and molecular mechanisms of aloperine against CVD and provided a feasible tool to identify the pharmacological mechanisms of single active ingredient of traditional Chinese medicines.

Background. Tripterygium wilfordii Hook F (TwHF) has been used in traditional Chinese medicine (TCM) for treating cardiovascular disease (CVD). However, the underlying pharmacological mechanisms of the effects of TwHF on CVD remain elusive. This study revealed the pharmacological mechanisms of TwHF acting on CVD based on a pharmacology approach. Materials and Methods. The active compounds were selected from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database according to the absorption, distribution, metabolism, and excretion (ADME). The potential targets of TwHF were obtained from the SwissTargetPrediction database. The CVD‐related therapeutic targets were collected from the DrugBank, the GeneCards database, and the OMIM database. Protein–protein interaction (PPI) network was generated by the STITCH database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed by R package. The network of drug‐targets‐diseases‐pathways was constructed by the Cytoscape software. Results. The 41 effective ingredients of TwHF and the 178 common targets of TwHF and CVD‐related were collected. Furthermore, AKT1, amyloid precursor protein (APP), mitogen‐activated protein kinase 1 (MAPK), phosphatidylinositol 3‐kinase catalytic subunit alpha (PIK3CA), and cellular tumor antigen p53 (TP53) were identified as the core targets involved in the mechanism of TwHF on CVD. Top ten GO (biological processes, cellular components, and molecular functions) and KEGG pathways were screened with a P value ≤0.01. Finally, we constructed the network of TwHF‐targets‐CVD‐GO‐KEGG. Conclusions. These findings demonstrate that the main active compound of TwHF, the core targets, and pathways maybe provide new insights into the development of a natural therapy for the prevention and treatment of CVD.

Background: Irritable bowel syndrome (IBS) is a chronic disorder of the gut-brain axis with significant morbidity. Triptolide, an active compound extracted from Tripterygium wilfordii Hook F (TwHF), has been widely used as a major medicinal herb in the treatment of inflammatory disease. Methods: The chronic-acute combined stress (CAS) stimulation was used to establish IBS rat model. The model rats were then gavaged with triptolide. Forced swimming, marble-burying, fecal weight and abdominal withdrawal reflex (AWR) score were recorded. Pathologic changes in the ileal and colonic tissues were validated by hematoxylin and eosin staining. The inflammatory cytokines and Ornithine Decarboxylase-1 (ODC1) in the ileal and colonic tissues were performed by ELISA and WB. Results: Triptolide didn’t have antidepressant- and antianxiety- effects in rats caused by CAS, but decreased fecal weight and AWR score. In addition, Triptolide reduced the release of IL-1, IL-6, and TNF-α and the expression of ODC1 in the ileum and colon. Conclusion: The therapeutic efficacy of triptolide for IBS induced by CAS was revealed in this study, which may be related to the reduction of ODC1.

Background Tripterygium wilfordii Hook F (TwHF) has been used in traditional Chinese medicines (TCM) for treating cardiovascular disease (CVD). However, the underlying pharmacological mechanisms of the effects of TwHF against CVD remain elusive. This study revealed the pharmacological mechanisms of TwHF acting on CVD based on a pharmacology approach. Materials and Methods The active compounds were selected by Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) according to the absorption, distribution, metabolism, and excretion (ADME). The potential targets of TwHF were obtained by SwissTargetPrediction database. The CVD-related therapeutic targets were collected by the DrugBank, the GeneCards database and the OMIM database. Protein–protein interaction (PPI) network was generated by STITCH database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed by R package. The network of drug-targets-diseases-pathways was constructed by Cytoscape software. Results The 51 effective ingredients of TwHF and the 178 common targets of TwHF and CVD-related were collected. Furthermore, AKT1, amyloid precursor protein (APP), Mitogen-activated protein kinase 1 (MAPK), phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) and cellular tumor antigen p53 (TP53) was identified the core targets involved in the mechanism of TwHF on CVD. Top ten GO (biological processes, cellular components and molecular functions) and KEGG pathways were screened with a P value ≤ 0.01. Finally, we constructed the network of TwHF-targets-CVD-GO-KEGG. Conclusions These findings demonstrate that the main active compound of TwHF, the core targets and pathways maybe provide new insights into the development of a natural therapy for the prevention and treatment of CVD.