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Ginsenoside Rb1 has been demonstrated to protect dopaminergic (DA) neurons from death in vitro. However, the neuroprotective effects and underlying mechanism of Rb1 in treating Parkinson's disease (PD) remain uncharacterized. In this study, we explored the effects of Rb1 on the movement disorder and the underlying mechanisms based on the glutamatergic transmission and excitotoxicity in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Here, for the first time, we report that Rb1 treatment ameliorates motor deficits, prevents DA neuron death, and suppresses α-synuclein expression and astrogliosis in the MPTP mouse model of PD. Rb1 attenuates glutamate excitotoxicity by upregulating glutamate transporter expression and function, and modulating the nigrostriatal and cortico-nigral glutamatergic transmission pathways. Our results demonstrate that Rb1 increases glutamate transporter expression via nuclear translocation of nuclear factor-kappa B, regulates glutamate receptor expression and promotes synaptic protein expression. These results indicate that Rb1 suppresses glutamate excitotoxicity and modulates synaptic transmission to improve the impairments in motor functions of the MPTP model of PD, suggesting that Rb1 may serve as a potential therapeutic agent for PD.

Background: Working memory impairment is a common non-motor symptom in the progression of Parkinson's disease (PD). Ginsenoside Rb1, an extract from the Ginseng root, has been demonstrated to ameliorate motor deficits and prevent dopaminergic neuron death in PD. However, whether Rb1 can attenuate the PD-associated deficits in working memory and its underlying mechanism of action are still unclear. Methods: Behavioral tests were used to examine the effect of Rb1 on the working memory deficits in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Gamma-aminobutyric acid (GABA)-chemical exchange saturation transfer (CEST) magnetic resonance imaging and electrophysiology were used to identify the effect of Rb1 on the GABA content and GABAergic synaptic transmission in the prefrontal cortex. Immunofluorescence and western blotting were used to explore the expression of the different GABA receptors. Findings: We found that Rb1 attenuated the impairment in spatial working memory in the MPTP mouse model of PD, and this neuroprotective mechanism involved the regulation of prefrontal cortical GABAergic content and transmission. We demonstrated that Rb1 increased GABA content in the prefrontal cortex, and Rb1 prevented the MPTP-induced decrease of presynaptic GABA release and postsynaptic GABA receptor expression and function. Furthermore, Rb1's promotion of GABA current may be associated with the regulation of GABAA receptor trafficking from the postsynaptic density to the membrane, as well as with the modulation of postsynaptic GABAB receptors to enhance GABAA receptor function. Interpretation: Rb1 may serve as a potential drug candidate for the treatment of cognitive impairments in PD. Funding: The National Natural Science Foundation of China (No. 81704130 to YZ, No. 81774377 and No. 81373999 to LW), the Natural Science Foundation of Fujian Province of China (No. 2017J05139 to YZ), the Natural Science Foundation of Guangdong Province of China (No. 2017A030310643 to YZ), the China Postdoctoral Science Foundation (No. 2016M590598 to YZ), the National Key Research and Development Program of China (No. 2016YFC1305903 to LW), and the Program for New Century Excellent Talents in University of Ministry of Education of China (No. NCET-13-0505 to LW). Declaration of Interest: The authors declare no conflicts of interest. Ethical Approval: All experiments were conducted according to the National Institute of Health guidelines on the care and use of animals (NIH Publications No. 8023, revised 1978) and approved by the Institutional Animal Care and Use Committee of Guangzhou Medical University.

An in vivo rat model of myocardial contrast echocardiography (MCE) was defined and used to examine the dose range response of microvascular permeabilization and premature ventricular contractions (PVCs) with respect to method of imaging, peak rarefactional pressure amplitude (PRPA) and agent dose. A left ventricular short axis view was obtained on anesthetized rats at 1.7 MHz using a diagnostic ultrasound system with simultaneous ECG recording. Evans blue dye, a marker for microvascular leakage, and a bolus of Optison were injected i.v. Counts of PVCs were made from video tape during the 3 min of MCE. Hearts were excised 5 min after imaging and petechial hemorrhages, Evans blue colored area and Evans blue content were determined. No PVCs or microvascular leakage were seen in rats imaged without contrast agent followed by contrast agent injection without imaging. When PVCs were detected during MCE, petechial hemorrhages and Evans blue leakage were also found in the myocardium. Triggering 1:4 at end-systole produced the most PVCs per frame and most microvascular leakage, followed by end-systole 1:1, continuous scanning and end-diastole triggering 1:1. All effects increased with increasing Optison dosage in the range 25 to 500 microL kg(-1). Ultrasound PRPA was important, with apparent thresholds for PVCs at 1.0 MPa and for petechiae at 0.54 MPa. PVCs, petechial hemorrhages and microvascular leakage in the myocardium occur as a result of MCE in rats.