Ginkgolide B restores pancreatic β-cell identity and attenuates oxidative stress in streptozotocin-induced diabetic rats via Nrf2/Keap1 pathway activation

Abstract

Objective: To investigate the efficacy of ginkgolide B, a major active constituent isolated from Ginkgo biloba, on pancreatic β-cell integrity and Nrf2/Keap1 signaling in a streptozotocin (STZ)-induced diabetes model of rats.
Methods: Sprague-Dawley rats were injected with STZ along with nicotinamide. After confirmation of hyperglycemia, diabetic rats (n=8/group) received no treatment, or ginkgolide B (10 or 30 mg/kg). Healthy rats served as normal control. After 21 days of treatment, rats were sacrificed, and plasma samples was obtained to assess the biochemical, hepatic, renal, oxidative stress, lipid profile, apoptotic, and inflammatory parameters. Pancreatic tissue was used for histopathological observation and detection of gene expression of NFE2L2, KEAP1, NQO1, HO-1, Ins1, MAFA, Ngn3, Pdx1, and Pax4.
Results: Ginkgolide B-treated rats showed significant improvement in diabetes markers, i.e., fasting plasma glucose, insulin, and glucagon. It also significantly improved oxidative stress, inflammation, as well as lipid profile, antiapoptotic, liver, and kidney function markers as compared with the model group. Ginkgolide B improved β-cell function, activated Nrf2 signaling, and upregulated β-cell-related genes Ins1, Pdx1, MAFA, Ngn3, and Pax4. Histopathological results showed nearly normal islet architecture in ginkgolide B-treated groups.
Conclusions: Ginkgolide B shows antidiabetic effect. It can alleviate oxidative damage and inflammation, and upregulate genes related to regeneration and insulin signaling.

Keywords

Ginkgo biloba / Ginkgolide B / Diabetes mellitus / Nrf2/Keap1 pathway / Oxidative stress / β-cell regeneration

References

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