Department of Biochemistry, Faculty of Pharmacy, October 6 University, Giza 12585, Egypt.
Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
Biomed Pharmacother. 2024 Jul;176:116854. doi: 10.1016/j.biopha.2024.116854. Epub 2024 Jun 1.
Acute pancreatitis (APS) is a prevalent acute pancreatic inflammation, where oxidative stress, inflammatory signaling pathways, and apoptosis activation contribute to pancreatic injury.
Pinocembrin, the predominant flavonoid in propolis, was explored for its likely shielding effect against APS provoked by two intraperitoneal doses of L-arginine (250 mg / 100 g) in a rat model.
Pinocembrin ameliorated the histological and immunohistochemical changes in pancreatic tissues and lowered the activities of pancreatic amylase and lipase that were markedly elevated with L-arginine administration. Moreover, pinocembrin reinstated the oxidant/antioxidant equilibrium, which was perturbed by L-arginine, and boosted the pancreatic levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Pinocembrin markedly reduced the elevation in serum C-reactive protein (CRP) level induced by L-arginine. Additionally, it decreased the expression of high motility group box protein 1 (HMGB1), toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and NOD-like receptor (NLR) Family Pyrin Domain Containing 3 (NLRP3) inflammasome in the pancreas. Furthermore, it also reduced myeloperoxidase (MPO) activity. Pinocembrin markedly downregulated miR-34a-5p expression and upregulated the protein levels of peroxisome proliferator-activated receptor alpha (PPAR-α) and Sirtuin 1 (SIRT1) and the gene expression level of the inhibitor protein of NF-κB (IκB-α), along with normalizing the Bax/Bcl-2 ratio.
Pinocembrin notably improved L-arginine-induced APS by its antioxidant, anti-inflammatory, and anti-apoptotic activities. Pinocembrin exhibited a protective role in APS by suppressing inflammatory signaling via the TLR4/NF-κB/NLRP3 pathway and enhancing cytoprotective signaling via the miR-34a-5p/SIRT1/Nrf2/HO-1 pathway.
急性胰腺炎（APS）是一种常见的急性胰腺炎症，其中氧化应激、炎症信号通路和细胞凋亡的激活导致胰腺损伤。
在大鼠模型中，使用两种腹腔内剂量的 L-精氨酸（250mg/100g）来研究白杨素，一种蜂胶中的主要类黄酮，是否具有对抗 APS 的潜在屏蔽作用。
白杨素改善了胰腺组织的组织学和免疫组织化学变化，并降低了 L-精氨酸给药后明显升高的胰腺淀粉酶和脂肪酶的活性。此外，白杨素恢复了由 L-精氨酸扰乱的氧化还原平衡，并增加了核因子红细胞 2 相关因子 2（Nrf2）和血红素加氧酶-1（HO-1）在胰腺中的水平。白杨素显著降低了 L-精氨酸引起的血清 C 反应蛋白（CRP）水平的升高。此外，它还降低了高迁移率族蛋白 B1（HMGB1）、Toll 样受体 4（TLR4）、核因子 kappa B（NF-κB）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和 NOD 样受体（NLR）家族含吡啶结构域蛋白 3（NLRP3）炎性体在胰腺中的表达。此外，它还降低了髓过氧化物酶（MPO）活性。白杨素显著下调 miR-34a-5p 的表达，上调过氧化物酶体增殖物激活受体α（PPAR-α）和 Sirtuin 1（SIRT1）的蛋白水平，以及 NF-κB 抑制剂蛋白（IκB-α）的基因表达水平，并使 Bax/Bcl-2 比值正常化。
白杨素通过其抗氧化、抗炎和抗凋亡作用显著改善了 L-精氨酸诱导的 APS。白杨素通过抑制 TLR4/NF-κB/NLRP3 通路的炎症信号，通过 miR-34a-5p/SIRT1/Nrf2/HO-1 通路增强细胞保护信号，在 APS 中发挥保护作用。
