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Protective Effects of Eugenia uniflora Red Fruit on Brain in a Rat Model of Type 2 Diabetes: Mechanistic Insights
Imtiaz Ahmad1, Juliane de Souza Cardoso1, Julia Eisenhardt de Mello2
1Laboratório de Biomarcadores, Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Pelotas, RS, Brazil.
Abstract:
The current study aimed to evaluate the in-vitro toxicity and in-vivo antidiabetic effects of a standardized extract from Eugenia uniflora (E. uniflora) fruit, comparing its efficacy to metformin (Met), a widely used anti-hyperglycemic drug. First, toxicity of the extract was determined by MTT assay in 3T3 cell line and primary astrocyte culture. Then Wistar rats were divided into four groups: I- Control, II- type 2 diabetes mellitus (T2DM), III- T2DM + Met and IV- T2DM + E. uniflora. To induce T2DM, groups II, III and IV received a high fat diet (HFD) for 3 weeks followed by a single intraperitoneal (i.p.) dose of streptozotocin (STZ, 35 mg/kg). Animals of group I received normal diet and vehicle (i.p.). Group III received Met (250 mg/kg) and group IV received E. uniflora (200 mg/kg) intragastric pathway, once a day, throughout all experimental protocol. Animals from the groups I and II received water in the same volume. Results showed that cell viability was not affected. In-vivo, E. uniflora and Met prevented the change in serum levels of glucose, cholesterol, LDL, triglyceride and interleukin-6. Furthermore, extract and Met improved oxidative stress markers and antioxidant enzyme activity in the brain (cerebral cortex, hippocampus, striatum). Furthermore, extract enhanced the downstream insulin signaling pathway, including insulin receptor substrate 1, forkhead box protein O-3a, as well as activated the nuclear factor erythroid 2-related factor 2 in the cerebral cortex. This study indicates that E. uniflora extract may have potential in preventing complications associated with T2DM; nevertheless, additional studies are required to confirm these effects and establish their clinical significance.
Insights
Eugenia uniflora fruit extract shows no in-vitro toxicity and demonstrates in-vivo antidiabetic effects comparable to metformin. The extract effectively manages blood glucose and improves brain oxidative stress in type 2 diabetes models.
Area of Science:
- Pharmacology
- Biochemistry
- Toxicology
Background:
- Type 2 diabetes mellitus (T2DM) is a growing global health concern.
- Metformin is a first-line anti-hyperglycemic drug, but its efficacy and side effects necessitate exploration of alternative treatments.
- Natural products, like Eugenia uniflora fruit, are increasingly investigated for their therapeutic potential in managing T2DM and its complications.
Purpose of the Study:
- To evaluate the in-vitro toxicity of a standardized Eugenia uniflora (E. uniflora) fruit extract.
- To assess the in-vivo antidiabetic effects of E. uniflora extract in a rat model of T2DM.
- To compare the efficacy of E. uniflora extract with metformin (Met) in managing T2DM-related metabolic and oxidative stress markers.
Main Methods:
- In-vitro toxicity was assessed using MTT assays on 3T3 cell line and primary astrocyte cultures.
- Type 2 diabetes mellitus was induced in Wistar rats using a high-fat diet and streptozotocin (STZ).
- Animals were treated with E. uniflora extract (200 mg/kg) or metformin (250 mg/kg) daily via oral gavage.
Main Results:
- E. uniflora extract exhibited no significant in-vitro toxicity.
- Both E. uniflora extract and metformin prevented adverse changes in serum glucose, cholesterol, LDL, and triglyceride levels.
- The extract and metformin improved oxidative stress markers and antioxidant enzyme activity in the brain, with E. uniflora enhancing insulin signaling pathways.
Conclusions:
- Eugenia uniflora fruit extract demonstrates promising antidiabetic properties and neuroprotective effects.
- The extract may help prevent T2DM complications by modulating glucose metabolism, lipid profiles, and oxidative stress.
- Further research is warranted to confirm these findings and explore the clinical significance of E. uniflora in T2DM management.
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