Obtusifolin ameliorates pancreatic tissue injury and inflammation by modulating the NFκB signaling.

Acute pancreatitis (AP) is a rapid-onset inflammatory disorder of the pancreas, characterized by premature activation of pancreatic digestive enzymes and the development of systemic inflammatory responses. Severe AP is associated with a mortality rate of 10–40%, highlighting the urgent need for effective and targeted therapeutic interventions. Obtusifolin (OBT), a natural compound from Senna obtusifolia, exhibits anti-inflammatory and wound-healing properties. The current study aimed to investigate the effect of OBT against inflammation and tissue injury associated with AP. In vitro, lipopolysaccharide (LPS) and TGF-β-induced differentiation models were employed to investigate the anti-inflammatory and anti-fibrotic effects of OBT in pancreatic stellate cells (PSCs) and PANC-1 cells. In vivo, a cerulein-induced acute pancreatitis mouse model was employed to evaluate the therapeutic potential of OBT through histopathological analysis, ELISA, immunohistochemistry, and western blotting. In vitro results revealed that OBT treatment significantly suppressed the LPS/TGF-β-induced pro-inflammatory and ECM marker expression in PSCs and PANC-1 cells, respectively. In mice, cerulein induction notably increased the pancreatic edema, acinar necrosis, inflammatory infiltration, hemorrhage in tissues of cerulein control, on the other hand, treatment with OBT significantly attenuated the same. Further, OBT treatment significantly reduced the cerulein-induced elevation of inflammatory marker expression (Tnfa, Ccl2, Cxcl10, and Il6), serum α-amylase, β-amylase, and IL-1β levels in a dose-dependent manner. Furthermore, immunohistochemistry and western blot analysis confirmed that OBT ameliorates pancreatitis by modulating the NFκB signaling. These results indicate that obtusifolin attenuates acute pancreatitis by inhibiting inflammatory responses and preserving pancreatic tissue integrity, supporting its potential as a therapeutic candidate for managing acute pancreatitis. Graphical Abstract Similar content being viewed by others Data availability No datasets were generated or analysed during the current study. Abbreviations - AP: - Acute Pancreatitis - CCL2: - Chemokine (C-C motif) ligand 2 - CLN: - Cerulein - COL1α1: - Collagen Type I Alpha 1 Chain - COL3α1: - Collagen Type III Alpha 1 Chain - CXCL10: - Chemokine (C-X-C motif) ligand 10 - CXCL11: - Chemokine (C-X-C motif) ligand 11 - EMT: - Epithelial-to-Mesenchymal Transition - ERCP: - Endoscopic Retrograde Cholangiopancreatography - FBS: - Fetal Bovine Serum - FN1: - Fibronectin 1 - TRAF 6: - TNF receptor-associated factor 6 - LPS: - Lipopolysaccharide - MCP: - 1-Monocyte Chemoattractant Protein-1 - MODS: - Multi-organ Dysfunction Syndrome - MMP1: - Matrix Metalloproteinase 1 - NFκB: - Nuclear Factor kappa B - OBT: - Obtusifolin - PANC-1: - Human Pancreatic Cancer Cell Line-1 - PSCs: - Pancreatic Stellate Cells

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The Authors thank the Director, CSIR-IICT, Hyderabad, India, for providing the facilities and funding necessary to conduct this work. CSIR-IICT manuscript communication number: IICT/Pubs./2025/180. Funding This research received no specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Internal funds from the institute were utilized to complete this work. Author information Authors and Affiliations Contributions Conceptualization: S.B.A.; Methodology: N.S.; *In vitro* cell culture: N.S., S.B.A; RTqPCR, Western-blot analysis: N.S, HW; *In vivo* experiments: N.S., HW; Manuscript 1st draft writing: N.S. Manuscript writing - review and editing: S.B.A.; funding acquisition: S.B.A. Corresponding author Ethics declarations Competing interests The authors declare no competing interests. Additional information Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information Below is the link to the electronic supplementary material. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Sharma, N., Walekar, H.S. & Andugulapati, S.B. Obtusifolin ameliorates pancreatic tissue injury and inflammation by modulating the NFκB signaling. J Mol Histol 57, 21 (2026). https://doi.org/10.1007/s10735-025-10665-3 Received: Accepted: Published: Version of record: DOI: https://doi.org/10.1007/s10735-025-10665-3