EGb761 improves the cognitive function of elderly db/db−/− diabetic mice by regulating the beclin-1 and NF-κB signaling pathways

Abstract

To assess whether EGb761 could protect elderly diabetic mice with cognitive disorders and explore the role of beclin-1-mediated autophagy in these protective effects. Two-month-old male db/db−/− mice and wild-type C57/BL6 mice were randomly divided into six groups: db/db−/− control, db/db−/− 50 mg, db/db−/− 100 mg, wild-type (WT) control, WT 50 mg, and WT 100 mg. EGb761 (50 mg/kg or 100 mg/kg of bodyweight) was given by gavage once a day for 1 month from the age of 6 months. Y-maze and social choice tests were performed at 8th months. The blood pressure was measured. The imaging changes in the brain were measured using magnetic resonance imaging (MRI). The expression and distribution of beclin-1, LC3, and NF-κB were detected using immunohistochemistry staining and western blotting. Ultrastructure alterations in the hippocampus were observed using transmission electron microscopy. Compared with WT mice, the learning ability, memory and overall cognitive function of db/db−/− mice decreased (P < 0.05), and EGb761 could significantly improve the learning and memory function of db/db−/− mice (P < 0.05). EGb761 significantly improved systolic blood pressure in db/db−/− mice (P < 0.01). In addition, fMRI-bold showed a decline in the hippocampus of mice in the db/db−/− group compared with WT. EGb761 could improve these above changes. Immunohistochemistry staining and western blotting confirmed that EGb761 significantly increased beclin-1 and reduced LC3-II/I levels in the brains of db/db−/− mice (P < 0.05). NF-κB levels were obviously higher in the db/db−/− group than that in the WT group, and EGb761 significantly reduced NF-κB levels in db/db−/− mice (P < 0.05). There was a trend of increased autophagosomes in db/db−/− mice, but EGb761 did not change obviously the number of autophagosomes. Compared with normal aged WT mice, aging db/db−/− mice had more common complications of cerebral small vessel disease and cognitive dysfunction. EGb761 could significantly improve the cognitive function of aging db/db−/− mice via a mechanism that may involve the regulation of beclin-1, LC3, and NF-κB.

Medicinal plants for diabetes associated neurodegenerative diseases: A systematic review of preclinical studies

“…Guan et al (2018) during a study on diabetic mice demonstrated that treatment with EGb761 causes improvement of diabetic neurological disorders identified by MRI. The extract also causes normalization of blood pressure and improvement of learning and memory during Y‐maze test.…”

“…Beclin‐1 and LC3 genes expression increase in autophagy; so that EGb761 can inhibit autophagy in brain nerve cells. Generally, EGb761 can help to improve neurological disorders in diabetic mice by inhibition of autophagy and inflammation (Guan et al, 2018).…”

Overexpression of MicroRNA-133a Inhibits Apoptosis and Autophagy in a Cell Model of Parkinson’s Disease by Downregulating Ras-Related C3 Botulinum Toxin Substrate 1 (RAC1)

“…The overactivation of autophagy during neuron loss is involved in PD pathogenesis [ 30 ]. According to a new study, Beclin-1 has important functions in autophagy that are mediated by the formation of the Beclin-1-Bcl2 complex [ 31 ]. LC3II is considered a marker of autophagy in cells and tissues [ 32 ].…”

Long non‐coding RNA TNRC6C‐AS1 promotes methylation of STK4 to inhibit thyroid carcinoma cell apoptosis and autophagy via Hippo signalling pathway

“…31 A new study has noted that Beclin1 works in autophagy via complexes like the Beclin1-PI3KC3 or Beclin1-Bcl-2 complex. 32 LC3II was considered as an autophagy-linked marker in cell tissues. 33 YAP plays a role in the processes of autophagy and apoptosis 34 and silencing YAP increased the ratio of LC3-I and LC3-II, accompanied by the autophagy-related protein Beclin1.…”