Batryticatus Bombyx Protects Dopaminergic Neurons Against MPTP-Induced Neurotoxicity by Inhibiting Oxidative Damage

Abstract

Oxidative stress plays an important role in the degeneration of dopaminergic neurons in Parkinson's disease (PD). Altered redox homeostasis in neurons interferes with several biological processes, ultimately leading to neuronal death. Oxidative damage has been identified as one of the principal mechanisms underlying the progression of PD. Several studies highlight the key role of superoxide radicals in inducing neuronal toxicity. Batryticatus Bombyx (BB), the dried larva of Bombyx mori L. infected by Beauveria bassiana (Bals.) Vuill., has been used in traditional medicine for its various pharmacological effects. In the present study, BB showed a beneficial effect on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity by directly targeting dopaminergic neurons. Treatment with BB improved behavioral impairments, protected dopaminergic neurons, and maintained dopamine levels in PD mouse models. Here, we investigated the protective effects of BB on MPTP-induced PD in mice and explored the underlying mechanisms of action, focusing on oxidative signaling. In MPTP-induced PD, BB promoted recovery from impaired movement, prevented dopamine depletion, and protected against dopaminergic neuronal degradation in the substantia nigra pars compacta (SNpc) or the striatum (ST). Moreover, BB upregulated mediators of antioxidative response such as superoxidase dismutase (SOD), catalase (CAT), glutathione (GSH), Heme oxygenase 1 (HO-1), and NAD(P)H (nicotinamide adenine dinucleotide phosphate) dehydrogenase (NQO1). Thus, treatment with BB reduced the oxidative stress, improved behavioral impairments, and protected against dopamine depletion in MPTP-induced toxicity.

Keywords: Batryticatus Bombyx; Parkinson’s disease; dopaminergic neuron; neuroprotection.

Figure 1

Effects of Batryticatus Bombyx (BB) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced behavior impairment. One day after MPTP treatment, the retention time on the rotating rod was recorded (A). On days 5 and 7 after MPTP treatment, time to turn (T-T) completely downward and time to fall off the rod onto the floor (T-LA) were recorded (B). Values represent means ± standard error of the mean (S.E.M.). * p < 0.05, ** p < 0.01, and *** p < 0.001 compared with the control group, and # p < 0.05 and ## p < 0.01 compared with the MPTP-treated group.

Figure 2

Effects of BB on MPTP-induced dopamine contents. Dopamine contents in the striatum (ST) of mice brain was measured using enzyme-linked immunosorbent assay (ELISA). Values represent means ± S.E.M. * p < 0.05 compared with the control group, and # p < 0.05 and ## p < 0.01 compared with the MPTP-treated group or control group.

Figure 3

Effects of BB on MPTP-induced dopaminergic neuronal damage. Dopaminergic neurons were visualized by tyrosine hydroxylase (TH)-specific Immunohistochemistry (IHC). The TH-positive neurons in the substantia nigra pars compacta (SNpc) were counted (A) and the optical density in the striatum (ST) was measured (B). Representative photomicrographs were taken of the SNpc and ST (C). Values are presented as means ± S.E.M. ** p < 0.01 and *** p < 0.001 compared with the control group. Scale bar: 200 µm.

Figure 4

Effects of BB on MPTP-induced antioxidant enzyme levels. Levels of antioxidant enzymes such as superoxidase dismutase (SOD; A), catalase (CAT; B) and glutathione (GSH; C) in SNpc were measured using ELISA kits. Values represent means ± S.E.M. ** p < 0.01 compared with the control group, and # p < 0.05 and ## p < 0.01 compared with the MPTP-treated group.

Figure 5

Effects of BB on MPTP-induced Heme oxygenase 1 (HO-1) and NAD(P)H dehydrogenase (NQO1) expression. Bar graphs represent the relative proteins expression of HO-1 (A) and NQO1 (B) adjusted to β-actin expression. The cellular proteins were used for the detection of HO-1 and NQO1 by Western blot (C). Values represent means ± S.E.M. ** p < 0.01 and *** p < 0.001 compared with the control group, and ## p < 0.01 and ### p < 0.001 compared with the MPTP-treated group.