Galangin modulates the NRF2/PPAR-Γ pathway, attenuating sepsis-induced tissue damage in the lungs.

We examined the possible role of galangin, a flavonoid derived from Alpinia officinarum, with anti-inflammatory and anti-fibrotic properties, on the lung via Nrf2 in a CLP-induced sepsis model in rats, biochemically, molecularly and histopathologically. Forty female albino Wistar rats were included in the study. They were divided equally into 5 groups. The treatment groups received galangin orally 1 h before the sepsis model was established. CLP-induced polymicrobial sepsis model was created. Nrf2, PPAR-γ and NF-κB mRNA expressions were measured by RT-PCR in lung tissue samples. The ROS, GSH, GPx, HO-1, TNF-α and IL-6 levels were measured by ELISA. PPAR-γ and NF-κB were analyzed by western blotting. In the lung tissues, the Nrf2 and PPAR-γ mRNA expressions were significantly decreased in the CLP group compared to the healthy group, while the NF-κB mRNA expressions were significantly increased. In the CLP+GAL25, CLP+GAL50 and CLP+GAL100 groups, the Nrf2 and PPAR-γ mRNA expressions were significantly increased and NF-κB mRNA expressions were significantly decreased. The ROS, TNF-α, and IL-6 levels, which increased due to sepsis, decreased in the CLP+GAL25, CLP+GAL50, and CLP+GAL100 groups in a dose-dependent manner. The levels of HO-1, GPx and GSH, which were decreased due to sepsis, increased in the CLP+GAL25, CLP+GAL50 and CLP+GAL100 groups in a dose-dependent manner. Histopathological and immunohistochemical findings for NF-κB, PPAR-γ, Nrf2, and NrfP supported these results. Galangin has been shown to reduce both oxidative stress and inflammatory responses by modulating the Nrf2/PPAR-γ pathway in reducing sepsis-induced tissue damage in the lungs.