Quantitative analysis of the therapeutic effect of magnolol on MPTP-induced mouse model of Parkinson’s disease using in vivo 18F-9-fluoropropyl-(+)-dihydrotetrabenazine PET imaging

Abstract

18F-9-Fluoropropyl-(+)-dihydrotetrabenazine [18F-FP-(+)-DTBZ] positron emission tomography (PET) has been shown to detect dopaminergic neuron loss associated with Parkinson’s disease (PD) in human and neurotoxin-induced animal models. A polyphenol compound, magnolol, was recently proposed as having a potentially restorative effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- or 6-hydroxydopamine-treated animal models. In this study, 18F-FP-(+)-DTBZ PET was used to determine the therapeutic efficacy of magnolol in an MPTP–PD mouse model that was prepared by giving an intraperitoneally (i.p.) daily dose of 25 mg/kg MPTP to male C57BL/6 mice for 5 consecutive days. Twenty-minute static 18F-FP-(+)-DTBZ PET scans were performed before MPTP treatment and 5 days after the termination of MPTP treatment to set up the baseline control. Half of the MPTP-treated mice then received a daily dose of magnolol (10 mg/kg dissolved in corn oil, i.p.) for 6 days. 18F-FP-(+)-DTBZ PET imaging was performed the day after the final treatment. All 18F-FP-(+)-DTBZ PET images were analysed and the specific uptake ratio (SUr) was calculated. Ex vivo autoradiography (ARG) and corresponding immunohistochemistry (IHC) studies were conducted to confirm the distribution of dopaminergic terminals in the striatum. The striatal SUr ratios of 18F-FP-(+)-DTBZ PET images for the Sham, the MPTP, and the MPTP + Magnolol-treated groups were 1.25 ± 0.05, 0.75 ± 0.06, and 1.00 ± 0.11, respectively (n = 4 for each group). The ex vivo 18F-FP-(+)-DTBZ ARG and IHC results correlated favourably with the PET imaging results. 18F-FP-(+)-DTBZ PET imaging suggested that magnolol post-treatment may reverse the neuronal damage in the MPTP-lesioned PD mice. In vivo imaging of the striatal vesicular monoamine transporter type 2 (VMAT2) distribution using 18F-FP-(+)-DTBZ animal PET is a useful method to evaluate the efficacy of therapeutic drugs i.e., magnolol, for the management of PD.

Characterization of 18F-PM-PBB3 (18F-APN-1607) Uptake in the rTg4510 Mouse Model of Tauopathy

“…All PET images were processed and analyzed by using the PMOD image analysis software (v3.5, PMOD Technologies Ltd., Zurich, Switzerland). To lower the possible bias from manual VOIs (volume of interests) drawing, an early phase PET template was created with the first 10 min mean PET image acquisition from each animal based on the rigid matching function of to the PMOD built-in mouse T2 MRI template (the procedure for the PET image template creation is shown in Figure S2) [40,41]. Then all other PET images were spatially normalized to this early phase PET template and the different VOIs, including the hippocampus, striatum, cortex, midbrain, and cerebellum from the MRI template were applied for image quantitation (the representative VOI selection image is shown in Figure 7).…”

“…To further evaluate the tracer deposition in the transgenic mouse animal model, the 6-mo-old animals were sacrificed immediately after in vivo PET imaging procedure and applied for the ex vivo autoradiography as in our previous work [41]. Briefly, the animal was sacrificed with cervical dislocation and then the brain was quickly removed and frozen in dry ice.…”

Insights on the Multifunctional Activities of Magnolol

“…Dopaminergic neurons degeneration is one of the main pathological characteristics of Parkinson's disease (PD). Magnolol has been shown the neuroprotective activity to reverse the damage induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) using 18 F-FP-(+)-DTBZ animal positron emission tomography (PET) [13]. Cholinergic deficits and neuronal dysfunction contribute to Alzheimer's disease (AD).…”

“…Both magnolol and honokiol are isolated from the stem bark of a traditional Chinese herbal medicine Magnolia officinalis , which has been used for management of nervous disturbance, abdominal distention or disorders, gastrointestinal food stagnancy, and coughing and dyspnea [1]. Magnolol has showed a wide spectrum of beneficial activities, including anti-inflammation [2, 3], antimicroorganism [4, 5], antioxidation [6, 7], antiangiogenesis [8, 9], anticancer [10–12], neuroprotection [13, 14], cardiovascular protection [15, 16], and lipolysis activities [17, 18]. However, there are still some differences between magnolol and honokiol in safety and toxicology, which have been reviewed by Sarrica et al (2018)[19].…”

A Mini Review on the Protective Effect of Lignans for the Treatment of Neurodegenerative Disorders

“…A group of investigators claimed that schisantherin A (a dibenzocyclooctadiene lignan) from Schisandra chinensis fruit protects against 6-hydroxydopamine (6-OHDA) (a PD model) induced dopaminergic neuronal damage in Zebrafish and cytotoxicity in SHSY5Y cells by regulating intracellular ROS accumulation and inhibiting NO production [128]. Weng et al, showed that 6 days daily intraperitonial injection of 10 mg/kg magnolol reversed the neuronal damage associated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced dopaminergic neurotoxicity (the toxin which produces symptoms like PD) in male C57BL/6 mice [129].…”