bakuchiol and Sepsis

Bakuchiol (BAK) is a prenylated phenolic mono-terpene extracted from the fruit of Psoralea corylifolia L., which exerts a protective effect on organs. However, whether BAK has a protective effect on sepsis-induced acute kidney injury (S-AKI) is not clear. In our study we have demonstrated for the first time that pretreatment with BAK significantly reduced bacterial load, inflammation and renal oxidative stress in caecal ligation and puncture (CLP)-induced sepsis. Moreover, CLP-induced renal histological damage, mortality and clinical signs were markedly attenuated by BAK. Additionally, BAK inhibited sepsis-induced activation of NF-κB and p38 MAPK signaling in the kidneys. The evidence presented here has confirmed that BAK exerts multifunctional activity in protection against S-AKI. This action of BAK is probably due to the blockade of the NF-κB and p38 MAPK signaling pathways. Our findings offer a novel potential for BAK in protection against sepsis and S-AKI.

Topics: Acute Kidney Injury; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antioxidants; Bacterial Load; Disease Models, Animal; Kidney; Male; Mice, Inbred C57BL; NF-kappa B; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Phenols; Psoralea; Sepsis

Sepsis is a systemic inflammatory reaction that may lead to multiple organ damage and acute lung injury (ALI). Bakuchiol (Bak) has been reported to confer protection against inflammation and oxidative stress. However, its effect on sepsis-induced acute lung injury remains unclear. In the present study, male C57BL/6 mice were subjected to cecal ligation and puncture (CLP), and Bak (15, 30, 60 mg/kg) was administered intragastrically after 0 and 3 h of surgery. Lung water content was detected. Pathologic changes in lung tissues were evaluated via hematoxylin and eosin (H&E) staining. The levels of myeloperoxidase (MPO), IL-1β, IL-6, and TNF-α were evaluated using ELISA. In addition, expression levels of phosphorylated (p)-IκB, ICAM-1, HMGB1, nitrotyrosine (3-NT), claudin-1, and VE-cadherin were detected using Western blot. Further, IL-1β expression was evaluated using immunofluorescence. SOD activity, contents of MDA, and 8-OHdG were detected to determine the level of oxidative stress. Our results suggested that Bak (60 mg/kg) treatment significantly attenuated pathologic changes and edema in lung tissues and attenuated inflammation and oxidative stress in the lung following sepsis. Additionally, Bak treatment alleviated sepsis-induced lung endothelial barrier disruption. In conclusion, Bak treatment attenuates ALI following sepsis by suppressing inflammation, oxidative stress, and endothelial barrier disruption. Our study indicates that Bak is a potential candidate to treat sepsis-induced ALI.

Topics: Acute Lung Injury; Animals; Edema; Endothelium; Inflammation; Lung; Male; Mice; Mice, Inbred C57BL; Oxidative Stress; Phenols; Protective Agents; Sepsis