Ellagic acid regulates hyperglycemic state through modulation of pancreatic IL-6 and TNF- α immunoexpression

Abstract

Background: Type 2 diabetes (T2DM) is a chronic metabolic disorder. Although therapeutic pharmaceutical agents continue to advance, herbal medicines are potential complementary treatments for the promotion of glucose homeostasis, with minimal adverse effects. Conventionally, ellagic acid (EA) has been utilized for the therapy of a range of pathologies owing to its anti-inflammatory and anti-diabetic actions.

Objective: The aim of this study is to determine the activity of EA on serum α-amylase and lipase titers, and on pancreatic tumor necrosis factor-α (TNF-α), proliferating cell nuclear antigen (PCNA) and interleukin-6 (IL-6) concentrations using the streptozocin-induced T2DM rodent model.

Methods: EA extract synthesized from fresh strawberry fruit was employed for therapy. 50 adults male Wistar rats were randomized into either control, EA, diabetic, co-treated or post- treated cohorts.

Results: EA diminished fasting blood glucose levels, altered lipase, amylase, IL-6, PCNA and TNF- α expression and enhanced islet cell renewal, insulin, and immunoreactivities.

Conclusion: Inflammatory indicators are elevated in the presence of T2DM. Extract of EA has overall tissue reparative and safeguarding properties, as indicated by the augmented β- cell population and enhanced glucose homeostasis. Thus, EA may be an innovative treatment approach for the maintenance of normoglycemia in individuals with T2DM.

Keywords: Ellagic acid; Immunohistochemistry; Pancreas β-cells; Pancreatic enzymes; T2DM.

Fig. 1

FTIR spectra of the ellagic acid.

Fig. 2

Photomicrographs of rat's pancreas sections in the different experimental groups stained with H&E. A&B: Normal structure of the pancreas consisted of exocrine (Acinar cells; AC) and endocrine (islets of Langerhans; L) portions in control and EA groups. C&D: Diabetic rats revealed decreased islets size, decreased β-cells number and degenerated entering connective tissue (arrows) sheet with irregular islets shape. E: Pancreatic sections in co-treated. F: Post treated revealed normal shape and increased β-cells number.

Fig. 3

Photomicrographs of rats pancreas sections in the different experimental groups stained with PCNA. A-C: Strong positive reaction for PCNA immunoreactivity in control and ellagic acid groups. D: Mild to moderate PCNA positive reactions in diabetic group. E: Moderate PCNA positive reactions in co-treated grog. F: Strong PCNA positive reactions in post-treated group.

Fig. 4

Photomicrographs of rat's pancreas (β-cell) sections in the different experimental groups stained with insulin immunoexpression. A&B: Strong positive reaction for insulin immunoreactivity in control and ellagic acid groups. C&D: Mild to moderate insulin positive reactions in diabetic group. E&F: Moderate to strong positive reactions for insulin in co-treated and post-treated groups.

Fig. 5

Photomicrographs of rats pancreas (β-cell) sections in the different experimental groups stained with pro-inflammatory marker TNF-α immunoexpression. A&B: Negative or faint positive reaction for TNF-α immunoreactivity in control and ellagic acid groups. C: Moderate positive reaction for TNF-α immunoreactivity in diabetic group. D&E: Moderate positive reaction for TNF-α immunoreactivity in co-treated and post-treated groups.

Fig. 6

Photomicrographs of rats pancreas (β-cell) sections in the different experimental groups stained with IL-6 immunoexpression. A&B: Mild to moderate positive reaction for IL-6 immunoreactivity in control and ellagic acid group. C&D: strong positive reaction for IL-6 immunoreactivity in diabetic group. E: Moderate positive reaction for IL-6 immunoreactivity in co-treated group. F: Moderate positive reaction for IL-6 immunoreactivity in post-treated group.