Novel Amphibian Bowman–Birk-Like Inhibitor with Antioxidant and Anticoagulant Effects Ameliorates Pancreatitis Symptoms in Mice

Acute
pancreatitis (AP) is a serious inflammatory disorder and
still lacks effective therapy globally. In this study, a novel Ranacyclin
peptide, Ranacin, was identified from the skin of Pelophylax
nigromaculatus frog. Ranacin adopted a compact β-hairpin
conformation with a disulfide bond (Cys5–Cys15). Ranacin was
also demonstrated effectively to inhibit trypsin and have anticoagulant
and antioxidant activities in vitro. Furthermore, the severity of
pancreatitis was significantly alleviated in l-Arg-induced
AP mice after treatment with Ranacin. In addition, structure–activity
studies of Ranacin analogues confirmed that the sequences outside
the trypsin inhibitory loop (TIL), especially at the C-terminal side,
might be closely associated with the efficacy of its trypsin inhibitory
activity. In conclusion, our data suggest that Ranacin can improve
pancreatic injury in mice with severe AP through its multi-activity.
Therefore, Ranacin is considered a potential drug candidate in AP
therapy.