Syzygium aqueum (Burm.f.) Alston Prevents Streptozotocin-Induced Pancreatic Beta Cells Damage via the TLR-4 Signaling Pathway

Although several treatments are available for the 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 suppres...

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Autores principales: Mona F. Mahmoud, Shimaa Abdelaal, Heba Osama Mohammed, Assem M. El-Shazly, Rachid Daoud, Mohamed A. O. Abdelfattah, Mansour Sobeh
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Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/1438a8bf00aa4ba798f8035a799f9263
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spelling oai:doaj.org-article:1438a8bf00aa4ba798f8035a799f92632021-12-01T13:36:06ZSyzygium aqueum (Burm.f.) Alston Prevents Streptozotocin-Induced Pancreatic Beta Cells Damage via the TLR-4 Signaling Pathway1663-981210.3389/fphar.2021.769244https://doaj.org/article/1438a8bf00aa4ba798f8035a799f92632021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.769244/fullhttps://doaj.org/toc/1663-9812Although several treatments are available for the 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 the TLR-4 signaling pathway. Non-fasted rats pretreated with 100 or 200 mg kg−1 SA 2 days prior to the 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 and 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 inflammatory cell infiltration. Pre-treatment with SA or glibenclamide decreased malondialdehyde, a sensitive biomarker of ROS-induced lipid peroxidation, and restored depleted reduced glutathione in the pancreas. Altogether, these data indicate that S. aqueum is effective in improving STZ-induced pancreatic damage, which could be beneficial in treating type 2 diabetes mellitus.Mona F. MahmoudShimaa AbdelaalHeba Osama MohammedAssem M. El-ShazlyRachid DaoudMohamed A. O. AbdelfattahMansour SobehFrontiers Media S.A.articleSyzygium aqueumTLR-4TRAF-6MyD88HO-1diabetesTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Syzygium aqueum
TLR-4
TRAF-6
MyD88
HO-1
diabetes
Therapeutics. Pharmacology
RM1-950
spellingShingle Syzygium aqueum
TLR-4
TRAF-6
MyD88
HO-1
diabetes
Therapeutics. Pharmacology
RM1-950
Mona F. Mahmoud
Shimaa Abdelaal
Heba Osama Mohammed
Assem M. El-Shazly
Rachid Daoud
Mohamed A. O. Abdelfattah
Mansour Sobeh
Syzygium aqueum (Burm.f.) Alston Prevents Streptozotocin-Induced Pancreatic Beta Cells Damage via the TLR-4 Signaling Pathway
description Although several treatments are available for the 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 the TLR-4 signaling pathway. Non-fasted rats pretreated with 100 or 200 mg kg−1 SA 2 days prior to the 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 and 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 inflammatory cell infiltration. Pre-treatment with SA or glibenclamide decreased malondialdehyde, a sensitive biomarker of ROS-induced lipid peroxidation, and restored depleted reduced glutathione in the pancreas. Altogether, these data indicate that S. aqueum is effective in improving STZ-induced pancreatic damage, which could be beneficial in treating type 2 diabetes mellitus.
format article
author Mona F. Mahmoud
Shimaa Abdelaal
Heba Osama Mohammed
Assem M. El-Shazly
Rachid Daoud
Mohamed A. O. Abdelfattah
Mansour Sobeh
author_facet Mona F. Mahmoud
Shimaa Abdelaal
Heba Osama Mohammed
Assem M. El-Shazly
Rachid Daoud
Mohamed A. O. Abdelfattah
Mansour Sobeh
author_sort Mona F. Mahmoud
title Syzygium aqueum (Burm.f.) Alston Prevents Streptozotocin-Induced Pancreatic Beta Cells Damage via the TLR-4 Signaling Pathway
title_short Syzygium aqueum (Burm.f.) Alston Prevents Streptozotocin-Induced Pancreatic Beta Cells Damage via the TLR-4 Signaling Pathway
title_full Syzygium aqueum (Burm.f.) Alston Prevents Streptozotocin-Induced Pancreatic Beta Cells Damage via the TLR-4 Signaling Pathway
title_fullStr Syzygium aqueum (Burm.f.) Alston Prevents Streptozotocin-Induced Pancreatic Beta Cells Damage via the TLR-4 Signaling Pathway
title_full_unstemmed Syzygium aqueum (Burm.f.) Alston Prevents Streptozotocin-Induced Pancreatic Beta Cells Damage via the TLR-4 Signaling Pathway
title_sort syzygium aqueum (burm.f.) alston prevents streptozotocin-induced pancreatic beta cells damage via the tlr-4 signaling pathway
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/1438a8bf00aa4ba798f8035a799f9263
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