Metabolomics investigation reveals metabolic mediators associated with Ligusticum wallichii-relieving experimental acute pancreatitis

Background: Acute pancreatitis (AP) is a typical destructive inflammation of the pancreas. The direct effect of L. wallichii on AP remains unknown.Methods: AP animal model was constructed by intraperitoneal injection of caerulein in male Sprague–Dawley rats. L. wallichii extracts were used to treat rats with AP. Then, tissue injury was evaluated by hematoxylin and eosin staining. Serum indicators, including amylase, lipase, KL-6, creatinine and urea, were measured by commercial kits. GC/MS-based metabolomics was utilized to characterize the metabolome.Results: Intraperitoneal injection of L. wallichii extracts protected against lung, liver, and kidney injury in rats with caerulein-induced AP. GC/MS-based metabolomics analysis revealed that L. wallichii treatment could restore caerulein-induced alteration of the abundance of most metabolites. These differential metabolites enriched twelve metabolic pathways that were able to be reprogramed by L. wallichii administration. L. wallichii impacted arginine metabolism by inhibiting arginase expression and activity. Inhibition of arginase by S-(2-boronoethyl)-L-cysteine (BEC) could relieve caerulein-induced AP, suggesting that suppression of arginase is a potential mechanism for L. wallichii to ameliorate AP.Conclusion: Our data provide the inter-relationship between metabolic reprograming and anti-AP effects of L. wallichii extracts in rats, and highlight the potential of metabolic reprograming against AP pathogenesis.