Prospective insight into the role of benzyl propylene glycoside as a modulator of the cGAS-STING signaling pathway in the management of nonalcoholic fatty pancreas animal model.

Autor: Albadawy R; Department of Gastroenterology, Hepatology & Infectious Disease, Faculty of Medicine, Benha University, Benha, 13518, Egypt. reda.albadawy@fmed.bu.edu.eg., Hasanin AH; Clinical Pharmacology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt., Agwa SHA; Clinical Pathology and Molecular Genomics Unit, Medical Ain Shams Research Institute (MASRI), Faculty of Medicine, Ain Shams University, Cairo, 11382, Egypt., Hamady S; Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, 11566, Egypt., Mohamed RH; Clinical Pharmacology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt., Gomaa E; Histology and Cell Biology Department, Faculty of Medicine, Ain Shams University, Giza, Egypt., Othman M; Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, TX, 77030, USA., Yahia YA; Chemistry Department, School of Science and Engineering, American University in Cairo, New Cairo, 11835, Egypt.; Biochemistry Department, Faculty of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, Giza, Egypt., Ghani AMA; Clinical Pathology, Faculty of Medicine, Ain Shams University, Cairo, 11566, Egypt., Matboli M; Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, Cairo, 11566, Egypt. DrMarwa_Matboly@med.asu.edu.eg.
Jazyk: angličtina
Zdroj: Biological research [Biol Res] 2023 Mar 13; Vol. 56 (1), pp. 11. Date of Electronic Publication: 2023 Mar 13.
DOI: 10.1186/s40659-023-00423-8
Abstrakt: Background: Nonalcoholic fatty pancreatitis (NAFP) is one of the metabolic syndrome manifestations that need further studies to determine its molecular determinants and find effective medications. We aimed to investigate the potential effect of benzyl propylene glycoside on NAFP management via targeting the pancreatic cGAS-STING pathway-related genes (DDX58, NFκB1 & CHUK) and their upstream regulator miRNA (miR-1976) that were retrieved from bioinformatics analysis.
Methods: The rats were fed either normal chow or a high-fat high-sucrose diet (HFHS), as a nutritional model for NAFP. After 8 weeks, the HFHS-fed rats were subdivided randomly into 4 groups; untreated HFHS group (NAFP model group) and three treated groups which received 3 doses of benzyl propylene glycoside (10, 20, and 30 mg/kg) daily for 4 weeks, parallel with HFHS feeding.
Results: The molecular analysis revealed that benzyl propylene glycoside could modulate the expression of the pancreatic cGAS-STING pathway-related through the downregulation of the expression of DDX58, NFκB1, and CHUK mRNAs and upregulation of miR-1976 expression. Moreover, the applied treatment reversed insulin resistance, inflammation, and fibrosis observed in the untreated NAFP group, as evidenced by improved lipid panel, decreased body weight and the serum level of lipase and amylase, reduced protein levels of NFκB1 and caspase-3 with a significant reduction in area % of collagen fibers in the pancreatic sections of treated animals.
Conclusion: benzyl propylene glycoside showed a potential ability to attenuate NAFP development, inhibit pancreatic inflammation and fibrosis and reduce the pathological and metabolic disturbances monitored in the applied NAFP animal model. The detected effect was correlated with modulation of the expression of pancreatic (DDX58, NFκB1, and CHUK mRNAs and miR-1976) panel.
(© 2023. The Author(s).)
Databáze: MEDLINE
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