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Background. Heart failure represents the terminal stage of various cardiovascular diseases. This study aims to explore the pharmacological mechanisms underlying the protective effect of Ginsenoside Rg3 against heart failure. Methods. Potential targets of Ginsenoside Rg3 were identified using SwissTargetPrediction and the Comparative Toxicogenomics Database, while heart failure‐related genes were retrieved from the Comparative Toxicogenomics Database, Therapeutic Target Database, DisGeNET, and PharmGKB. Overlapping of Ginsenoside Rg3 targets with heart failure‐related genes identified drug‐disease interaction genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on the drug‐disease interaction genes to elucidate their biological functions. A protein‐protein interaction network was constructed using the drug‐disease interaction genes, and the hub genes were identified by topological analysis. Additionally, we validate the expression of IL‐6 and TNF by real‐time PCR. Results. The intersection of Ginsenoside Rg3 targets and heart failure‐related genes yielded 15 drug‐disease interaction genes. Enrichment analysis highlighted the involvement of inflammation‐related GO terms and KEGG pathways, such as positive regulation of interleukin‐8 and ‐6 production, regulation of immune effector process, cytokine receptor binding, cytokine activity, adipocytokine signaling pathway, and IL‐17 signaling pathway, which are implicated in the cardioprotective effect. Topological analysis revealed four hub genes: STAT3, CASP3, TNF, and IL-6. The application of Ginsenoside Rg3 significantly reversed the elevated levels of IL‐6 and TNF in the isoproterenol‐treated H9c2 cell line. Conclusions. Our findings suggest that the cardioprotective effect of Ginsenoside Rg3 may be mediated through its anti‐inflammation properties. Further research is required to elucidate and validate the detailed cardioprotective mechanisms of Ginsenoside Rg3. [ABSTRACT FROM AUTHOR]

Introduction: Restricted repetitive behaviors (RRBs), which are associated with many different neurological and mental disorders, such as obsessive‐compulsive disorder (OCD) and autism, are patterns of behavior with little variation and little obvious function. Paired Box 2 (Pax2) is a transcription factor that is expressed in many systems, including the kidney and the central nervous system. The protein that is encoded by Pax2 has been implicated in the development of the nervous system and neurodevelopmental disorders. In our previous study, Pax2 heterozygous gene knockout mice (Pax2+/− mice) showed abnormally increased self‐grooming and impaired learning and memory abilities. However, it remains unclear which cell type is involved in this process. In this study, we deleted Pax2 only in the nervous system to determine the regulatory mechanism of Pax2 in RRBs. Methods: In this study, Pax2 nervous system‐specific knockout mice (Nestin‐Pax2 mice) aged 6–8 weeks and Pax2 flox mice of the same age were recruited as the experimental group. Tamoxifen and vehicle were administered via intraperitoneal injection to induce Pax2 knockout after gene identification. Western blotting was used to detect Pax2 expression. After that, we assessed the general health of these two groups of mice. The self‐grooming test, marble burying test and T‐maze acquisition and reversal learning test were used to observe the lower‐order and higher‐order RRBs. The three‐chamber test, Y‐maze, and elevated plus‐maze were used to assess social ability, spatial memory ability, and anxiety. Neural circuitry tracing and transcriptome sequencing (RNA‐seq) were used to observe the abnormal neural circuitry, differentially expressed genes (DEGs) and signaling pathways affected by Pax2 gene knockout in the nervous system and the putative molecular mechanism. Results: (1) The Nestin‐Pax2 mouse model was successfully constructed, and the Nestin‐Pax2 mice showed decreased expression of Pax2. (2) Nestin‐Pax2 mice showed increased self‐grooming behavior and impaired T‐maze reversal behavior compared with Pax2 flox mice. (3) An increased number of projection fibers can be found in the mPFC projecting to the CA1 and BLA, and a reduction in IGFBP2 can be found in the hippocampus of Nestin‐Pax2 mice. Conclusion: The results demonstrated that loss of Pax2 in the nervous system leads to restricted repetitive behaviors. The mechanism may be associated with impaired neural circuitry and a reduction in IGFBP2. [ABSTRACT FROM AUTHOR]