Berberine Suppresses Inflammatory Response in Severe Pneumonia by Specifically Targeting Upregulation of SIRT1 to Activate Nrf2 Signaling Pathway.

OBJECTIVE: To investigate the key role of berberine (BER) in severe pneumonia progression, and analyze its potential mechanisms. METHODS: Genes associated with pneumonia and their expression profiles were analyzed in patients with severe pneumonia compared with healthy controls, thereby identifying core targets. In vitro, RLE-6TN cells were stimulated with Klebsiella pneumoniae (KP) and treated with BER to investigate cellular responses and sirtuin 1/nuclear factor erythroid 2-related factor 2 (SIRT1/Nrf2) pathway activation. Additionally, an in vivo study was conducted in KP-infected rats to evaluate lung tissue pathology and gene expression. RESULTS: In vitro experiments demonstrated that KP treatment of RLE-6TN cells significantly elevated lactate dehydrogenase activity, reduced cell viability and proliferation, and increased apoptosis (P<0.01). The expression levels of inflammatory markers (Bax, SIRT1, and Nrf2) were upregulated, whereas those of Bcl-2, Kiel proliferation index-67 (Ki-67), and proliferating cell nuclear antigen (PCNA) were downregulated (P<0.01). BER treatment mitigated these changes (P<0.01); however, sh-SIRT1 reversed the effects of BER, and sulforaphane (SFN, Nrf2 activator) counteracted the influence of sh-SIRT1 (P<0.05 or P<0.01). In vivo studies demonstrated that BER improved survival rates in KP-infected rats, alleviated lung injury, reduced pathological changes in lung tissue, and restored SIRT1 and Nrf2 to baseline levels (P<0.01). These advantageous effects were negated by sh-SIRT1 and subsequently restored by SFN (P<0.05 or P<0.01). CONCLUSION: BER promoted the viability and proliferation of KP-treated RLE-6TN cells, inhibited cell apoptosis and inflammatory responses, and alleviated severe pneumonia through the SIRT1/Nrf2 signaling pathway activation.