Pharmacological properties of Ensete glaucum seed extract: Novel insights for antidiabetic effects via modulation of oxidative stress, inflammation, apoptosis and MAPK signaling pathways

Abstract

Ethnophamacological relevance: Medicinal plants are increasingly making important contributions to diabetic treatment. Ensete glaucum seeds have been widely used in folk medicine to treat diabetes.

Aim of the study: The study was aimed to investigate the protective effect and active mechanisms of E. glaucum seed extract (EGSE) against streptozotocin (STZ)-induced hyperglycemia.

Materials and methods: Hyperglycemic mice were treated with EGSE (25 and 50 mg/kg) or glibenclamide (5 mg/kg) once daily for 7 d. The effects of these treatments on changes in blood biochemical parameters, pancreatic, liver, and kidney histopathology, oxidative stress and inflammatory marker levels in pancreatic, hepatic, and renal tissues were assessed. Expression of several proteins in MAPK signaling pathway related to apoptosis in pancreatic tissue were investigated. Furthermore, ex vivo, in vitro, and in silico biological activities of EGSE and its compounds were also examined.

Results: EGSE and glibenclamide increased notably insulin, reduced significantly glucose, AST, ALT, BUN and creatinine levels in blood. Pancreatic islets, hepatic and renal tissue structure were restored by EGSE or glibenclamide. EGSE showed significant anti-oxidative stress and anti-inflammatory effects by enhancing GSH level and dropping MDA, NF-κB, TNF-α and IL-6 levels in these tissues. Particularly, EGSE exhibited pancreatic protective effect against STZ-induced apoptosis through the MAPK signaling pathway by down-regulation of p-p38 MAPK, ERK1/2, JNK1, p-AMPK, Bax, Bax/Bcl-2, cytochrome c, cleaved-caspase 3 and PARP expression, and slight up-regulation of Bcl-2 expression. Moreover, EGSE inhibited intestinal glucose absorption, PTP1B, α-amylase, and α-glucosidase activities. Its isolated compounds (Afzelechin and coniferaldehyde) showed PTP1B and α-glucosidase inhibitory activities, and potent structure-activity relationships.

Conclusion: These findings indicated the hypoglycemic and protective effects of E. glaucum seed extract against the STZ diabetogenic action. E. glaucum seed is a potential candidate for further studies to confirm its activities as a therapeutic agent for diabetic patients.

Keywords: Anti-apoptosis; Ensete glaucum seeds; Hypoglycemia; MAPK signaling pathway; Natural compounds; Pancreatic protection.