Effects of Ficus exasperata on neurotransmission and expression of BDNF, tau, ACHE and BACE in diabetic rats

Abstract

Diabetes mellitus, a chronic metabolic disorder, has significant global health implications, particularly due to its neurological complications, such as diabetic neuropathy. This condition increases the risk of neurodegenerative diseases by affecting peripheral nerves and cognition. Ficus exasperata, known for its neuroprotective properties, shows promise as a therapeutic option for addressing these complications. This study evaluates the effects of methanol extract of Ficus exasperata (MEFE) on neurotransmission and the expression of Tau, brain-derived neurotrophic factor (BDNF), acetylcholinesterase (ACHE), and Beta-Site Amyloid Precursor Protein Cleaving Enzyme (BACE) in alloxan-induced diabetic Wistar rats. The controlled experimental design involved 20 Wistar rats divided into four groups (n = 5): control, diabetic untreated, diabetes + MEFE (200 mg/kg), and diabetes + insulin (0.3 IU). The methanol extract was prepared using cold maceration, and an aliquot was subjected to gas chromatography-mass spectrometry. Constituents of MEFE were docked with neurologic receptors. Blood glucose levels were measured using the glucose oxidase method, and neurotransmitter levels, antioxidants, oxidative stress markers, and the expression of Tau, BDNF, ACHE, and BACE were assessed using standard procedures and qRT-PCR. Data were analyzed using one-way ANOVA at P < 0.05. Results indicated that MEFE significantly reduced fasting blood glucose levels compared to untreated diabetic rats. In silico docking identified kaur-16-ene, a constituent of MEFE, as having the highest binding affinity for NMDA, TrkB, mAchR and nAchR receptors, indicating its neuroprotective potential. MEFE also enhanced antioxidant enzyme levels (SOD, GPx, catalase) while reducing oxidative stress markers (MDA, 8-OHdG). Gene expression analysis revealed that MEFE modulates the expression of Tau, BDNF, ACHE, and BACE, suggesting its potential to influence neurodegenerative pathways associated with diabetic neuropathy. Ficus exasperata demonstrates significant therapeutic potential in managing diabetic neuropathy and related cognitive impairments by modulating neurotransmission, protein expression, and antioxidant defenses.

Keywords: Diabetes mellitus; Ficus exasperata, neurotransmission; Kaur-16-ene; Neuroprotective properties.

Graphical abstract

Fig. 1

Shows Ficus exasperata Vahl leaves (White fig).

Fig. 2

Shows the effect of methanol extract of Ficus exasperata on blood glucose concentration. Data were expressed as mean ± SEM (n = 5, all groups) and analyzed using one-way ANOVA followed by Tukey multiple comparism Post-hoc test. Values are considered significant at p < 0.05∗, p < 0.01∗∗, p < 0.001∗∗∗ and p < 0.0001∗∗∗∗.

Fig. 3

Show the effect of methanol extract of Ficus exasperata on antioxidant activities (a) Superoxide dismutase (b) Glutathione peroxidase (c) Catalase (d) Glutathione Reductase (e) Malondialdehyde (f) 8-hydroxy-2′-deoxyguanosine Data were expressed as mean ± SEM (n = 5, all groups) and analyzed using one-way ANOVA followed by Tukey multiple comparism Post-hoc test. Values are considered significant at p < 0.05∗, p < 0.01∗∗, p < 0.001∗∗∗ and p < 0.0001∗∗∗∗.

Fig. 4

Show the effect of methanol extract of Ficus exasperata on mRNA expression of (a) Acetylcholine (b) Glutamate (c) Total protein (d) Dopamine (e) Gaba-aminobutyric acid (f) Serotonin. A (Control), B (Diabetes untreated), C (Diabetes + MEFE (200 mg/kg), D (Diabetes + Insulin (0.3 IU) Data were expressed as mean ± SEM (n = 5, all groups) and analyzed using one-way ANOVA followed by Tukey multiple comparism Post-hoc test. Values are considered significant at p < 0.05∗, p < 0.01∗∗, p < 0.001∗∗∗ and p < 0.0001∗∗∗∗.

Fig. 5

Show the effect of methanol extract of Ficus exasperata on mRNA expression of (a) Brain Derived Neurotrophic Factor (b) Tau protein (c) Acetylcholinesterase (d) Beta-Site Amyloid Precursor Protein Cleaving Enzyme Data were expressed as mean ± SEM (n = 5, all groups) and analyzed using one-way ANOVA followed by Tukey multiple comparism Post-hoc test. Values are considered significant at p < 0.05∗, p < 0.01∗∗, p < 0.001∗∗∗ and p < 0.0001∗∗∗∗.

Fig. 6

Show the molecular interaction between a. Kaur-16-ene and TrkB Receptor b. Caryophyllene oxide and Muscarinic Acetylcholine Receptor (mAChR) c. Acetylcholine and Muscarinic Acetylcholine Receptor (mAChR) d. Kaur-16-ene and Nicotinic Acetylcholine Receptor (nAChR) e. Kaur-16-ene and N-methyl-D-aspartate receptor (NMDA) and f. Glutamate and N-methyl-D-aspartate receptor (NMDA).

Fig. 7

The photomicrograph of the brain tissue. A (Control) showed normal architecture of the brain tissue with dark stained nucleus B (Diabetic untreated) showed brain tissue with deeply stained cytoplasm and vacuolation (Green colour), C (diabetes + 200 mg/kg of MEFE) showed brain tissue with small vacuolation of the cytoplasm (Yellow Arrow), and D (diabetes + 0.3 IU of insulin) showed normal architecture of brain tissue. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)