Investigation on the antitumor effects of paeonol against renal cell carcinoma based on network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Renal cell carcinoma (RCC) is the most common cancer of the urinary system, the current treatments for RCC are unsatisfactory. Paeonol is the main pharmacologically active ingredient of the traditional Chinese medicine (TCM) moutan cortex (Paeonia suffruticosa Andrews) and Paeonia albiflora Pall, and has been used in TCM to treat various diseases including cancer. However, the underlying therapeutic mechanisms of paeonol in RCC have not been investigated yet. AIM OF THE STUDY: This study aimed to explore the potential antitumor effects and mechanisms of paeonol on RCC based on network pharmacology and experimental validation. MATERIALS AND METHODS: Network pharmacological analysis was performed to predict the potential targets and mechanism of paeonol against RCC. The antitumor effects and the priority targets of paeonol against RCC were further assessed by in vitro experiments. RESULTS: 104 intersection targets shared by paeonol and RCC were collected, 15 hub genes were obtained, among these genes, VEGFA expression was higher in RCC, and the higher expression of IL-6 or lower expression of AKT1, JUN, MAPK1, and MAPK8 were correlated to the shorter overall survival (OS) in RCC patients. GO and KEGG analyses suggested that the genes were mainly enriched in the positive regulation of cell death and apoptosis pathway. In vitro experiments showed that paeonol inhibited 786-O cell proliferation, migration, invasion, and promoted apoptosis. When 786-O cells were treated with paeonol, the expression of Bax increased while Bcl-2 and VEGFA decreased. CONCLUSION: The present study demonstrated that paeonol might play an essential role in RCC by regulating cell proliferation, apoptosis, metastasis, and invasion through the Bcl-2/Bax signaling pathway and VEGFA, providing a theoretical and experimental scientific basis for future investigations of the antitumor effects of paeonol against RCC.

Anti­IL­39 (IL­23p19/Ebi3) polyclonal antibodies ameliorate autoimmune symptoms in lupus­like mice.

The interleukin (IL)­12 family cytokines have been examined as therapeutic targets in the treatment of several autoimmune diseases. Our previous study showed that a novel IL­12 family cytokine, IL­39 (IL­23p19/Ebi3) mediates inflammation in lupus­like mice. In the present study, the effect of anti­mouse IL­39 polyclonal antibodies on autoimmune symptoms in lupus­like mice was investigated. Rabbit anti­mouse IL­39 polyclonal antibodies were produced by immunization with recombinant mouse IL­39, and purified using protein A chromatography. These antibodies were subsequently used to treat lupus­like mice. Flow cytometry, captured images, ELISA and H&E staining were used to determine the effect of anti­IL­39 polyclonal antibodies on inflammatory cells, autoantibody titers, proteinuria, infiltrating inflammatory cells and the structure of the glomerular region. The anti­IL­39 polyclonal antibodies effectively reduced the numbers of inflammatory cells, splenomegaly, autoantibody titers, proteinuria, infiltrating inflammatory cells, and restored the structure of the glomerular region in MRL/lpr mice. Taken together, these results suggested that anti­IL­39 polyclonal antibodies ameliorated autoimmune symptoms in lupus­like mice. Therefore, IL­39 may be used as a possible target for the treatment of systemic lupus erythematosus.