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

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posted on 2023-08-23, 13:07 authored by Jinwei Chai, Jiena Wu, Jinqiao Li, Hang Liao, Wancheng Lu, Ruiyin Guo, Zuoyan Shao, Mohamed Amine Jmel, Larissa Almeida Martins, Tilman Hackeng, Hans Ippel, Ingrid Dijkgraaf, Michail Kotsyfakis, Xueqing Xu
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.