Tephrosia purpurea, with (-)-Pseudosemiglabrin as the Major Constituent, Alleviates Severe Acute Pancreatitis-Mediated Acute Lung Injury by Modulating HMGB1 and IL-22

Abstract

Ischemia-reperfusion (IR) injury is a major cause of multiple organ failure. The purpose of this study was to look into the role of Tephrosia purpurea (TEP) and its active constituent pseudosemiglabrin (PS) in alleviating severe acute pancreatitis and its associated acute lung injury. We established a rat pancreatic IR model, and the rats were treated with TEP (200 mg/kg and 400 mg/kg) and PS (20 and 40 mg/kg), in addition to the IR control and sham groups. The results showed that the respiratory parameters, including inspiratory time (Ti), expiratory time (Te), duration (Dr), and respiratory rate (RR), were comparable among all groups, while peak inspiratory flow (PIF), forced vital capacity (FVC), and forced expiratory volume at 0.1 s (FEV0.1) were significantly impaired. Notably, PS at 40 mg/kg showed normal PIF, FVC, and FEV0.1/FVC compared to the IR group, indicating an improved lung function. Additionally, TEP and PS showed protective effects on pancreatic and lung tissues compared to the IR control group, with the following effects: alleviating pathological damage; reducing serum levels of trypsinogen activation peptide (TAP), lipase, and amylase; decreasing oxidative stress markers such as MDA and MPO; restoring antioxidant enzyme activity (GPx); suppressing inflammatory markers TNF-α, IL-6, and NF-κB; downregulating HMGB1 gene in pancreatic tissue; and upregulating the IL-22 gene in lung tissues. In conclusion, the obtained findings demonstrate that oral supplementation of TEP and PS to rats with pancreatic IR alleviates pancreatic and lung injuries by reducing oxidative stress and modulating inflammatory processes, which offers an attractive therapeutic option for severe acute pancreatitis and its associated acute lung injury.