Allium hookeri root extract restores streptozotocin-induced pancreatic β-cells dysfunction in a type 1 diabetic rat model

Abstract

Background: Allium hookeri (AH), a traditional herb in Southeast Asia, has been documented for its significant health benefits in metabolic diseases. This study was to explore the effects of AH root extract (AHRE) on pancreatic β-cell regeneration in streptozotocin (STZ)-induced diabetic rats.

Methods: AHRE (100 mg/kg body weight) was administered daily to STZ-induced diabetic rats for 2 weeks. Serum glucose and insulin levels, total-cholesterol, hemoglobin A1c, alanine transaminase, aspartate transaminase, and pancreatic peroxynitrite and thiobarbituric acid reactive substances were measured. Protein expression associated with pancreatic β-cell apoptosis and regeneration was analyzed through Western blotting.

Results: Diabetic rats exhibited hyperglycemia, insulin deficiency, increased levels of oxidative stress markers, and pancreatic β-cell apoptosis and impairment. AHRE treatment reduced hyperglycemia, insulin insufficiency, and oxidative stress, implying a reduction in pancreatic β-cell apoptosis and restoration of pancreatic β-cell regeneration-associated protein expression.

Conclusions: AHRE can facilitate β-cell regeneration in the impaired pancreatic islets through STZ by reducing oxidative stress markers and apoptosis in pancreatic tissue. Owing to pancreatic β-cells are susceptible to oxidative stress, the protective and enhancing effects of AHRE on the apoptosis and regeneration of these cells may be a significant mechanism for its hypoglycemic effect.

Keywords: Allium hookeri root; apoptosis; diabetes; oxidative stress; β-cell regeneration.

Fig. 1

A photograph of the AH (a) and schematic diagram of STZ-induced diabetic study (b).

Fig. 2

Effects of AHRE on body weight changes, pancreas weight, and food and water intakes in STZ-induced diabetic rats. Body weight (a), food (b), and water intake (c) were measured at every day for the experiment. Data are expressed as mean ± SEM (n = 5). **P < 0.01, ***P < 0.001 versus STZ.

Fig. 3

Effects of AHRE on fasting serum glucose (a), HOMA-IR (b), HbAlc (c), and serum total-cholesterol (d) in STZ-induced diabetic rats. Data are expressed as mean ± SEM (n = 5). *P < 0.05, **P < 0.01, ***P < 0.001 versus STZ.

Fig. 4

Effects of AHRE on serum ALT (a) and AST (b) in STZ-induced diabetic rats. Data are expressed as mean ± SEM (n = 5). *P < 0.05, ***P < 0.001 versus STZ.

Fig. 5

Effects of AHRE on pancreatic ONOO⁻ (a) and TBARS (b) concentrations in STZ-induced diabetic rats. Data are expressed as mean ± SEM (n = 5). *P < 0.05, **P < 0.01, ***P < 0.001 versus STZ.

Fig. 6

Effects of AHRE on pancreatic protein levels of Bax (a), Cytochrome C (b), and Caspase-3 (c) in STZ-induced diabetic rats. Protein level was determined by Western blot and normalized to β-actin. Data are expressed as mean ± SEM (n = 3~5). *P < 0.05, **P < 0.01, ***P < 0.001 versus STZ.

Fig. 7

Effects of AHRE on pancreatic protein levels of PDX-1 (a), p-EGFR (b), and Cyclin E (c) in STZ-induced diabetic rats. Protein level was determined by Western blot and normalized to β-actin. Data are expressed as mean ± SEM (n = 3~5). *P < 0.05, **P < 0.01, ***P < 0.001 versus STZ.

Fig. 8

Heat map of the Spearman ‘r’ correlation between the biochemical parameters and proteins related to pancreatic β-cell functions. S-, serum; HOMA-IR, homeostatic model assessment for insulin resistance; HbA1c, glycated hemoglobin A1c, TC, total-cholesterol; AST, aspartate aminotransferase; ALT, alanine aminotransferase; P-., Pancreatic; ONOO⁻, peroxynitrite; TBARS, thiobarbituric acid reactive substance; Bax, Bcl-2-associated protein x; PDX-1, pancreatic-duodenal homeobox-1; p-EGFR, phospho-epidermal growth factor receptor. *P < 0.05, **P < 0.01, ***P < 0.001 following the Spearman correlation.