Nanostructure lipid carriers enhance alpha-mangostin neuroprotective efficacy in mice with rotenone-induced neurodegeneration

Abstract

Neurodegenerative disease, for instance, Parkinson's disease (PD), is associated with substantia nigra dopaminergic neuronal loss with subsequent striatal dopamine reduction, leading to motor de cits. Currently, there is no available effective therapy for PD; thus, novel therapeutic agents such as natural antioxidants with neuroprotective effects are emerging. Alpha-mangostin (αM) is a xanthone derivative compound from mangosteen peel with a cytoprotective effect depicted in neurodegenerative disease models. However, αM has low aqueous solubility and low biodistribution in the brain. Nanostructured lipid carriers (NLC) have been used to encapsulate bioactive compounds delivered to target organs to improve the oral bioavailability and effectiveness. This study aimed to investigate the effect of αM and αM encapsulated in NLC (αM-NLC) in mice with rotenone-induced PD-like neurodegeneration. Forty male ICR mice were divided into normal, PD, PD+αM, and PD+ αM-NLC groups. Vehicle, αM (25 mg/kg/48 h), and αM-NLC (25 mg/kg/48 h) were orally administered, along with PD induction by intraperitoneal injection of rotenone (2.5 mg/kg/48 h) for 4 consecutive weeks. Motor abilities were assessed once a week using rotarod and hanging wire tests. Biochemical analysis of brain oxidative status was conducted, and neuronal populations in substantia nigra par compacta (SNc), striatum, and motor cortex were evaluated using Nissl staining. Tyrosine hydroxylase (TH) immunostaining of SNc and striatum was also evaluated. Results showed that rotenone signi cantly induced motor de cits concurrent with signi cant SNc, striatum, and motor cortex neuronal reduction and signi cantly decreased TH intensity in SNc (p < 0.05).The signi cant reduction of brain superoxide dismutase activity (p < 0.05) was also detected.Administrations of αM and αM-NLC signi cantly reduced motor de cits, prevented the reduction of TH intensity in SNc and striatum, and prevented the reduction of neurons in SNc (p < 0.05). Only αM-NLC signi cantly prevented the reduction of neurons in both striatum and motor cortex (p < 0.05). These were found concurrent with signi cantly reduced malondialdehyde level and increased catalase and superoxide dismutase activities (p < 0.05). Therefore, this study depicted the neuroprotective effect of αM and αM-NLC against rotenone-induced PD-like neurodegeneration in mice. We indicated an involvement of NLC, emphasizing the protective effect of αM against oxidative stress. Moreover, αM-NLC exhibited broad protection against rotenone-induced neurodegeneration that was not limited to nigrostriatal structures and emphasized the bene t of NLC in enhancing αM neuroprotective effects.

Neuroprotective effect of gallic acid in mice with rotenone-induced neurodegeneration

“…We observed the brain's oxidative status (Figure 1b) which indicated that only SOD activity was significantly reduced by rotenone exposure when comparing PD-veh with sham-veh (p = 0.0219). The effect of rotenone on SOD activity was similar to the previous studies that indicated the inhibition effect of rotenone on SOD activity appeared from the fourth week [12] and continued in the sixth week of rotenone exposure [13]. The present study observed these effects in the fifth week of rotenone exposure and the same result was observed.…”

“…Hanging tests were conducted once per week, consisting of three trials with the time extended to 180 seconds. The hanging test time was adapted to increase the intensity based on our previous studies that used the ICR mice model of rotenone-induced neurodegeneration [11][12][13].…”

“…Absorbance was read every 30 seconds at 240 nm for 3 minutes. CAT activity was calculated with reference to the extinction coefficient of H2O2 and presented as U/mg of protein [12].…”

Oxidative response to accumulation of trace metals in tissue of two bivalves, the Asian green mussel Perna viridis and the blood cockle Tegillarca granosa, living in Pattani Bay, Thailand

“…Standard SOD activity was 6150 U/mg of protein (Merck). Catalase activity (U/mg of protein) was determined by dynamic absorbance reading at 240 nm; calculation of CAT activity was referenced to the extinction coefficient of H 2 O 2 (Sakamula and Thong-Asa 2018;Thong-Asa et al 2020Sakamula et al 2022).…”

Lipid Carrier Nanostructured Astilbin Ameliorates Rotenone-Induced Neurodegeneration in Mice Brain via Modulation of GSK3β-Nrf2 Signaling Pathways

“…In the PD mouse model, the dual drug-loaded lipid nanoparticles greatly improved the regulation of the αS protein and reduced rotenone-induced neurotoxicity, oxidative stress, and apoptotic neurodegeneration 15) . NLC-encapsulated α-mangostin applied in mice with PD-like neurodegeneration caused by rotenone showed potent antioxidant effects that protected against neurodegeneration 16) . Thus, the utilization of NLCs for drug delivery, particularly in neurodegenerative illnesses, is quite intriguing.…”