Eupatilin mitigates Gestational diabetes in streptozotocin-induced diabetic pregnant rats through the Regulation of inflammation and oxidative stress

Abstract

Gestational diabetes mellitus (GDM) is a common metabolic disease that is typically diagnosed in pregnant women. The current study was aimed at disclosing the salutary activities of eupatilin against streptozotocin (STZ)-induced GDM in rats. The pregnant rats were induced with GDM and then treated with eupatilin for 20 days. The bodyweight, pup numbers and survival, glucose, and insulin levels were estimated. The levels of biochemical markers, antioxidants, and lipid profiles were measured using kits. The histopathological analysis was done on the pancreas and liver tissues. The eupatilin effectively reduced glucose and boosted insulin levels in the GDM rats. The pup numbers and their survival index were increased by the eupatilin treatment. The lipase, creatinine, AST, ALT, and urea levels were effectively reduced by the eupatilin in the GDM rats. Eupatilin treatment also decreased oxidative stress by increasing antioxidant levels and reducing inflammatory cytokine levels in the GDM rats. The cholesterol, LDL, and triglyceride levels were effectively decreased, and HDL was elevated by eupatilin. The results of histopathological analysis of both liver and pancreatic tissues also demonstrated the therapeutic properties of eupatilin. In conclusion, the current results prove that eupatilin can be an effective salutary candidate to treat GDM.

Keywords: Dyslipidemia; Eupatilin; Hyperglycemia; Inflammation; Malondialdehyde.

Fig. 1

Effect of eupatilin on the bodyweight and FBG level in the experimental rats Each bar shows the mean ± SD of three separate measurements, which is statistically analyzed using GraphPad Prism software. Values are analyzed by one-way ANOVA and Tukey's post hoc assay. ‘*’ reveals p < 0.01 compared with control; ‘#’ reveals p < 0.05 compared with STZ-induced GDM group. A): Fasting blood glucose level; B): Body weight.

Fig. 2

Effect of eupatilin on the glucose, lipase, and insulin levels in the experimental rats Each bar shows the mean ± SD of three separate measurements, which is statistically analyzed using GraphPad Prism software. Values are analyzed by one-way ANOVA and Tukey's post hoc assay. ‘*’ reveals p < 0.01 compared with control; ‘#’ reveals p < 0.05 compared with STZ-induced GDM group. A): Insulin level; B): Lipase activity; C): Glucose level.

Fig. 3

Effect of eupatilin on the levels of biochemical parameters in the experimental rats Each bar shows the mean ± SD of three separate measurements, which is statistically analyzed using GraphPad Prism software. Values are analyzed by one-way ANOVA and Tukey's post hoc assay. ‘*’ reveals p < 0.01 compared with control; ‘#’ reveals p < 0.05 compared with STZ-induced GDM group. A): ALT and AST activities in the serum; B): Albumin level; C): Creatinine level; D): Urea level.

Fig. 4

Effect of eupatilin on the levels of lipid profiles in the experimental rats Each bar shows the mean ± SD of three separate measurements, which is statistically analyzed using GraphPad Prism software. Values are analyzed by one-way ANOVA and Tukey's post hoc assay. ‘*’ reveals p < 0.01 compared with control; ‘#’ reveals p < 0.05 compared with STZ-induced GDM group. A): Total cholesterol level; B): Triglycerides level; C): Low density lipoprotein (LDL) level; D): High density lipoprotein (HDL) level.

Fig. 5

Effect of eupatilin on the oxidative stress markers in the liver tissues of experimental rats Each bar shows the mean ± SD of three separate measurements, which is statistically analyzed using GraphPad Prism software. Values are analyzed by one-way ANOVA and Tukey's post hoc assay. ‘*’ reveals p < 0.01 compared with control; ‘#’ reveals p < 0.05 compared with STZ-induced GDM group. A): Malondialdehyde (MDA); B): Total antioxidant capacity (TAC); C): Superoxide dismutase (SOD); D): Catalase (CAT); E): Glutathione peroxidase (GPx); F): Glutathione S-transferases (GST).

Fig. 6

Effect of eupatilin on the inflammatory cytokine levels in the liver tissues of experimental rats Each bar shows the mean ± SD of three separate measurements, which is statistically analyzed using GraphPad Prism software. Values are analyzed by one-way ANOVA and Tukey's post hoc assay. ‘*’ reveals p < 0.01 compared with control; ‘#’ reveals p < 0.05 compared with STZ-induced GDM group. A): Tumor necrosis factor-α (TNF-α); B): Interleukin-1β (IL-1β).

Fig. 7

Effect of eupatilin on the pancreas histopathology of experimental rats Group I: The pancreas tissues from healthy pregnant rats showed no evidence of inflammation and displayed normal cellular architecture. Group II: The pancreatic tissues of STZ-induced GDM rats showed inflammation, inflammatory cell infiltrations (black arrows), pancreatic islet cell contraction (yellow arrows), and increased adipose size (blue arrows). Group III and IV: The histological alterations caused by STZ in the pancreas tissues were significantly mitigated by the treatment of 10 and 20 mg/kg eupatilin, respectively. A): Normal control (Group I) B): STZ-induced GDM rats (Group II); C): STZ-induced GDM + 10 mg/kg of eupatilin-treated rats (Group III); D): STZ-induced GDM + 20 mg/kg of eupatilin-treated rats (Group III).

Fig. 8

Effect of eupatilin on the liver histopathology of experimental rats Group I: The liver tissues from healthy pregnant rats revealed no signs of inflammation and demonstrated intact cellular arrangements. Group II: The liver tissues of the GDM rats exhibited the extensive inflammatory cell infiltrations (black arrows) and hepatocyte damages (yellow arrows). Group III and IV: The histological damages induced by STZ in the liver tissues were considerably ameliorated by the 10 and 20 mg/kg eupatilin treatment, respectively. A): Normal control (Group I) B): STZ-induced GDM rats (Group II); C): STZ-induced GDM + 10 mg/kg of eupatilin-treated rats (Group III); D): STZ-induced GDM + 20 mg/kg of eupatilin-treated rats (Group III).

Fig. 9

Graphical representation of the mode of action of eupatilin.