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.