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Background: Bupleuri Radix is a common Chinese medicinal material in traditional Chinese medicine. Currently, the therapeutic effect of treating schizophrenia is relatively well understood. However, there are fewer studies examining the underlying mechanisms of its treatment. The objective of the study was to investigate the primary mechanisms of Bupleuri Radix in treating schizophrenia through network pharmacology and clinical validation. Method: Network pharmacology revealed possible molecular mechanisms, followed by clinical verification. Sixty-seven schizophrenia patients undergoing treatment at the Hunan Brain Hospital between October and November 2022 were recruited and randomly divided into the olanzapine group and the olanzapine + Bupleuri Radix group. Additionally, 32 healthy people undergoing physical examinations during the same period were included as the control group. The patient’s positive and negative symptom scale scores were compared. qPCR was used to detect the mRNA expression levels of ESR1, mTOR, EIF4E, and SMAD4 in peripheral blood. Results: Through network pharmacological analysis, it was concluded in this study that Bupleuri Radix might regulate the mTOR, PI3K-Akt, and HIF-1 signaling pathways. Clinical experiments indicated that compared with before treatment, the positive and negative symptom scale scores and total scores of the two treatment groups were significantly decreased after treatment (P < 0.01). In addition, the positive and negative symptom scale scores and total scores in the olanzapine + Bupleuri Radix group were significantly decreased (P < 0.01) compared to the olanzapine group after treatment. Before treatment, ESR1 mRNA expression levels in peripheral blood were significantly higher in the two treatment groups than in the control group, whereas the mRNA expression levels of mTOR, EIF4E, and SMAD4 in peripheral blood were significantly lower (P < 0.01). The mRNA expression levels of mTOR, EIF4E, and SMAD4 in peripheral blood were significantly higher after therapy than before treatment, whereas the mRNA expression levels of ESR1 in peripheral blood were significantly lower (P < 0.01). After therapy, the olanzapine + Bupleuri Radix group’s mRNA expression levels of mTOR, EIF4E, and SMAD4 were significantly higher than those of the olanzapine group, whereas the mRNA expression levels of ESR1 were significantly lower (P < 0.01). Conclusion: The mechanism of Bupleuri Radix’s therapeutic efficacy in schizophrenia may involve the up-regulation of mTOR, EIF4E, and SMAD4 mRNA expression and the down-regulation of ESR1 mRNA expression in peripheral blood. [ABSTRACT FROM AUTHOR]

MicroRNAs are consistently reported to regulate gene expression in all cancer cell types by modulating a wide range of biological processes, including cell proliferation, differentiation, and apoptosis, which are associated with tumor development and progression. Previous studies have revealed that miR-490-3p regulates cell proliferation and apoptosis in cancers, such as hepatocellular carcinoma, lung cancer, bladder cancer, and ovarian carcinoma. In this study, we explored the hitherto unrevealed role of miR-490-3p in breast cancer. We tested miR- 490-3p expression in breast cancer tissue and paracarcinoma tissue using reverse transcription- polymerase chain reaction. We also transfected the human breast cancer cell lines MCF-7 and T47D with miR-490-3p; subsequently, we determined the cell phenotype and the expression of Ras homolog gene family member A (RhoA), Bcl-xL, matrix metalloproteinase-9, and P70S6K (P70S6 kinase). Dual-luciferase reporter assay and a xenograft mouse model were used to reveal the roles of miR-490-3p and its target gene RHOA. We found that the levels of miR-490-3p were lower in the breast cancer tissue than in the paracarcinoma tissues. The overexpression of miR-490-3p suppressed breast cancer cell proliferation and promoted early stage apoptosis. Western blotting results revealed that the miR-490-3p overexpression reduced RhoA, Bcl-XL, matrix metalloproteinase-9, and P70S6K protein expression. The dual-luciferase reporter assay confirmed that RhoA is a target of miR-490-3p. The xenograft mouse model confirmed that miR-490-3p overexpression suppressed tumor growth and reduced RhoA expression. Our results indicate that miR-490-3p acts as oncosuppressive microRNA to inhibit breast cancer tumorigenesis and progression by targeting RhoA directly. It may contribute to breast cancer diagnosis and treatment. [ABSTRACT FROM AUTHOR]