AUTHOR=Mahmoud Mona F. , Abdelaal Shimaa , Mohammed Heba Osama , El-Shazly Assem M. , Daoud Rachid , Abdelfattah Mohamed A. O. , Sobeh Mansour TITLE=Syzygium aqueum (Burm.f.) Alston Prevents Streptozotocin-Induced Pancreatic Beta Cells Damage via the TLR-4 Signaling Pathway JOURNAL=Frontiers in Pharmacology VOLUME=Volume 12 - 2021 YEAR=2021 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.769244 DOI=10.3389/fphar.2021.769244 ISSN=1663-9812 ABSTRACT=Although several treatments are available for treatment of type 2 diabetes mellitus, adverse effects and cost burden impose the search for safe, efficient and cost-effective alternative herbal remedies. Syzygium aqueum (Burm.f.) Alston, a natural anti-inflammatory, antioxidant herb may suppress diabetes-associated inflammation and pancreatic beta cell death. Here, we tested the ability of the bioactive leaf extract (SA) to prevent streptozotocin (STZ)-induced oxidative stress and inflammation in pancreatic beta cells in rats and the involvement of TLR-4 signaling pathway. Non-fasted rats pretreated with 100 or 200 mg·kg−1 SA two days prior to STZ challenge and for 14 days later had up to 52% and 39% reduction in the glucose levels respectively, while glibenclamide, the reference standard drug (0.5 mg·kg−1) results in 70% reduction. Treatment with SA extract was accompanied by increased insulin secretion, restoration of Langerhans islets morphology and decreased collagen deposition as demonstrated from ELISA measurement, H&E and Mallory staining. Both glibenclamide and SA extract significantly decreased levels of TLR-4, MYD88, pro-inflammatory cytokines TNF-α and TRAF-6 in pancreatic tissue homogenates, which correlated well with minimal pancreatic infiltration. Pre-treatment with SA or glibenclamide decreased malondialdehyde, a sensitive biomarker of ROS-induced lipid peroxidation, and restored depleted reduced glutathione in pancreas. All together, these data indicate that S. aqueum is efficacious in improving STZ -induced pancreatic damage, which could be beneficial in the treatment of type 2 diabetes mellitus.