Neuroprotective Efficacy of Europinidin in Streptozotocin-Induced Memory Impairment by Modulation of Oxidative Stress, Inflammatory Mediators, and Cholinesterase Activity in Rats

Abstract

Materials and methods: Oral acute toxicity studies were performed to evaluate the toxicological effects of europinidin in animals. In this study, four different animal groups (n = 6) were used. Group I was the normal control, group II was the STZ-induced diabetes control, group III was STZ + europinidin-treated (10 mg/kg), and group IV was STZ + europinidin-treated (10 mg/kg). The efficacy of europinidin at a dose of 10 mg/kg and 20 mg/kg was studied with single-dose administration of streptozotocin, which experimentally induced memory impairments in Wistar male rats for 38 days. The mean body weight and blood glucose levels were recorded at the initial and end of the study. The two behavioural paradigms (Y-maze and Morris water maze) were performed to evaluate spatial and working memory in rats. The biochemical parameters such as acetylcholinesterase, choline acetyltransferase, superoxide dismutase, glutathione transferase, malonaldehyde, catalase, and nitric oxide level as hallmarks of oxidative stress were measured. Additionally, the proinflammatory parameters were also determined to evaluate the neuroinflammatory responses associated with streptozotocin such as tumor necrosis factor-alpha (TNF-α) interleukin-1β (IL-1β), interleukin (IL-6), nuclear factor-kappa B (NF-ƙB), interleukin (IL-10), and nuclear factor-erythroid factor 2-related factor 2 (Nrf2) in the perfused brain.

Results: The rats in the europinidin-treated group exhibited a significant restoration of body weight and blood glucose level as compared with the streptozotocin control group. Furthermore, europinidin significantly modulated the spatial and working memory in rats, when assessed through behavioural paradigms. Streptozotocin caused a significant alteration in biochemical, neuronal enzymatic, and neuroinflammatory parameters, which were significantly restored to normal levels by europinidin.

Conclusion: The present study attributed the neuroprotective efficacy of europinidin in experimental animal models by subsiding the several biomarkers of oxidative stress, neuroinflammation, and neuronal enzymatic activities.

Figure 1

Chemical structure of europinidin.

Figure 2

Mean body weight analysis. In the quantification of statistical data, the present study mean ± S.E.M (n = 6). A one-way analysis of variance, applied to Tukey's post hoc, shows statistically significant results in STZ-group vs. the control group at ^#p < 0.01 and europinidin (20 mg/kg) vs. STZ-treated group (^∗p < 0.05).

Figure 3

Streptozotocin-induced memory impairment in rats. Effects of europinidin on blood glucose levels. In the quantification of statistical data, the present study mean ± S.E.M (n = 6). A one-way analysis of variance, applied to Tukey's post hoc, shows statistically significant results in STZ group vs. the control group at ^#p < 0.001 and europinidin (10 mg/kg) vs. STZ-treated group (^∗p < 0.05; ^∗∗∗p <0.001), also europinidin (20 mg/kg) vs. STZ-treated group (^∗∗p < 0.01; ^∗∗∗p <0.001).

Figure 4

Streptozotocin-induced memory impairment in rats. Effects of europinidin on Y-maze test. Effects of europinidin on blood glucose levels. In the quantification of statistical data, the present study mean ± S.E.M (n = 6). A one-way analysis of variance, applied to the Tukey's post hoc, shows statistically significant results in STZ group vs. the control group at ^#p < 0.001 and europinidin (10 mg/kg) vs. STZ-treated group (^∗p < 0.05), also europinidin (20 mg/kg) vs. STZ-treated group (^∗∗p < 0.001) during spontaneous alteration. Also, during total arm entries, statistically significant results were observed as the STZ group vs. the control group at (^#p < 0.001), europinidin (10 mg/kg) vs. STZ-treated group (^∗P < 0.05; ^∗∗P <0.01), and europinidin (20 mg/kg) vs. STZ-treated group (^∗∗P < 0.01; ^∗∗∗P <0.001).

Figure 5

Streptozotocin-induced memory impairment in rats. Effects of europinidin on Morris water maze test. In the quantification of statistical data, the present study mean ± S.E.M (n = 6). A two-way analysis of variance, applied to the Bonferroni test post hoc, shows statistically significant results vs. the control group at #p < 0.05, ^∗p < 0.05, ^{∗ ∗}p<0.01 and ^{∗ ∗ ∗}p<0.001.

Figure 6

Streptozotocin-induced memory impairment in rats. Effects of europinidin on AChE and ChAT levels. In the quantification of statistical data, the present study mean ± S.E.M (n = 6). A one-way analysis of variance, applied to the Tukey's post hoc, shows statistically significant results in STZ group vs. the control group at ^#p < 0.001 and europinidin (10, and 20 mg/kg) vs. STZ-treated group , ^∗∗p < 0.01, and ^∗∗∗p < 0.001) during different neuroenzyme estimations.

Figure 7

Streptozotocin-induced memory impairment in rats. Effects of europinidin on oxidative parameters. In the quantification of statistical data, the present study mean ± S.E.M (n = 6). A one-way analysis of variance, applied to Tukey's post hoc, shows statistically significant results in STZ group vs. the control group at ^#p < 0.001 and europinidin (10 and 20 mg/kg) vs. STZ-treated group (^∗p < 0.05, ^∗∗p < 0.01, and ^∗∗∗p < 0.001) during different biochemical estimations.

Figure 8

Streptozotocin-induced memory impairment in rats. Effects of europinidin on nitrite levels in the quantification of statistical data; the present study mean ± S.E.M (n = 6). A one-way analysis of variance, applied to Tukey's post hoc, shows statistically significant results in STZ group vs. the control group at ^#p < 0.001 and europinidin (10 and 20 mg/kg) vs. STZ-treated group (^∗p < 0.05 and ^∗∗p < 0.01.

Figure 9

Streptozotocin-induced memory impairment in rats. Effects of europinidin on antiproinflammatory cytokines. In the quantification of statistical data, the present study mean ± S.E.M (n = 6). A one-way analysis of variance, applied to Tukey's post hoc, shows statistically significant results in STZ group vs. the control group at ^#p < 0.001 and europinidin (10, and 20 mg/kg) vs. STZ-treated group (^∗p < 0.05, ^∗∗p < 0.01, and ^∗∗∗p < 0.001) during different proinflammatory marker estimations.