Abstract
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.
Highlights
Diabetes mellitus is a chronic endocrine metabolic disorder that takes place because of absolute or partially deficient insulin secretory response by pancreatic cells or sometimes due to developed insulin resistance by the body (De Fronzo et al, 1997)
We investigated the antidiabetic potential of a bioactive leaf extract of S. aqueum in the STZ diabetes model by exploring the effects of the extract on a wide array of biochemical and molecular markers such as pancreatic malondialdehyde (MDA), reduced glutathione (GSH), tumor necrosis factor-alpha (TNF-α), nuclear factor-erythroid factor 2 (Nrf-2), toll-like receptor 4 (TLR-4), tumor necrosis factor receptor-associated factor (TRAF6), myeloid differentiation factor (MYD88), and heme oxygenase isozyme-1 (HO-1) along with glucose, fructosamine, and insulin levels in plasma
We investigated the possible antidiabetic effects of the leaf extract of S. aqueum in a rat model of type 2 diabetes compared to glibenclamide, a well-known oral hypoglycemic drug used to treat this type of diabetes
Summary
Diabetes mellitus is a chronic endocrine metabolic disorder that takes place because of absolute or partially deficient insulin secretory response by pancreatic cells or sometimes due to developed insulin resistance by the body (De Fronzo et al, 1997). Diabetes involves mainly disrupted carbohydrates metabolism, which translates into impaired glucose usage by body cells resulting in elevated blood sugar level (hyperglycemia). There are four types of diabetes: insulin-dependent diabetes mellitus (IDDM, type 1), an autoimmune disease characterized by absolute insulin deficiency and affects mainly children and young adults; non-insulin-dependent diabetes mellitus (NIDDM, type 2), known as adult-onset diabetes and characterized by partial insulin deficiency and/or cells-acquired insulin resistance; gestational diabetes mellitus (GDM), a kind of glucose intolerance during pregnancy; monogenic types of diabetes comprising disorders of genetic defects of beta cells (Alberti and Zimmet 1998). Managed diabetes can cause many complications over the whole body such as renal failure, neuropathy and nerve damage, retinopathy and vision loss, foot ulcers, and infections that might lead to limb amputation, peripheral artery disease, and about 2- to 3-fold increased risk of cardiac attacks and strokes (Harris 1993; Papatheodorou et al, 2018)
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