Study on the effect of ginsenoside Rb1 on MPTP induced neuronal damage and behavioral abnormalities in mice
Parkinson’s disease (PD) is the second most common neurodegenerative disease affecting the central nervous system (CNS) after Alzheimer’s disease (AD). The main pathological feature is progressive death of dopaminergic neurons, accompanied by a decrease in tyrosine hydroxylase (TH); The main clinical symptoms include movement disorders (including rigidity, decreased motor function, resting tremors, etc.) and non movement disorders (sleep deprivation, memory impairment, etc.). Dopaminergic neurons in the substantia nigra release dopamine in a calcium dependent manner from the axon terminals in the dorsal striatum, as well as from the cell bodies and dendrites in the midbrain. Their production and metabolism in the body are regulated by the coordinated function of different ion channels, such as iron, zinc, copper, and calcium. About 1% of the world’s 10 million 60 year olds suffer from this disease, and with the rising living standards of the whole country and the aging of the global population, the number of people suffering from Parkinson’s disease is also gradually increasing. So far, no complete treatment for Parkinson’s disease has been discovered, and the currently available drugs can only improve the symptoms of Parkinson’s disease but cannot completely cure it. This makes research on the treatment of Parkinson’s disease an urgent problem to be solved.
Ginsenoside Rb1 is the main active ingredient in ginseng and Panax notoginseng. Ginseng has calming and cognitive effects, while Panax notoginseng has a protective effect against brain damage and can improve memory. Ginsenoside Rb1 can improve hypoxia induced apoptosis of brain nerve cells and repair central nervous system damage, and has great potential for application and development. Studies have shown that ginsenoside Rb1 improves motor dysfunction and prevents DA neuron death by upregulating the glutamate transporter GLT-1 in MPTP mouse models. This article mainly explores whether ginsenoside Rb1 can improve the damage caused by MPTP induced PD model through FP1, CaMKII, and anti apoptotic protein Bcl-2, in order to provide assistance for the prevention and treatment of Parkinson’s disease.

 

PD is the second largest neurodegenerative disease in the world, posing a threat to people’s health. The neurochemical abnormalities in PD are the degeneration of dopaminergic neurons in the substantia nigra, leading to a decrease in striatal dopamine (DA) levels. Primary culture is one of the most relevant models for studying the characteristics and features of dopaminergic neurons. These cultures can be placed in various stress agents and neuroprotective compounds that simulate PD pathology to prevent or slow down neuronal degeneration. Therefore, we cultured dopaminergic neurons in vitro and observed the morphology of neurons through MPTP damage. In addition, the sports injuries caused by PD and the reduction of TH tyrosine positive kinase are its main characteristics. MPTP is a neurotoxin and the “best” model for studying Parkinson’s disease to date. Therefore, in this study, we used open field experiments and pole climbing experiments to detect the motor disorders induced by MPTP in PD models. We found that the MPTP model group exhibited significant motor function impairment. In addition, the detection of striatal proteins in MPTP induced mouse models showed a significant decrease in TH expression in the MPTP model group.

Ionic homeostasis plays a crucial role in Parkinson’s disease. Calcium and iron homeostasis are mentioned more frequently, and they also interact with each other. Imbalanced iron or calcium levels can promote harmful crosstalk between iron and calcium, leading to neuronal dysfunction and death. Ca2+may be a key participant in coordinating complex organelle networks to ultimately achieve metabolic interactions, intracellular signaling, cell maintenance, and cell survival regulation. It is a fundamental element for cell adaptation to the environment, and its disruption of homeostasis plays a crucial role in MPP+toxicity. MPTP can cause an increase in intracellular Ca2+, leading to the activation of Ca2+- dependent enzymes such as protein kinases and calpain I and II, thereby interfering with normal cellular function and causing cellular damage. In this study, the expression level of CaMKII was detected after MPTP injury, and it was found that there was no significant difference in the expression level of CaMKII. Iron deposition is one of the key factors in the etiology of Parkinson’s disease (PD). Iron homeostasis is maintained through the interaction between iron transporters and iron storage proteins. Damage to iron transportation or changes in iron storage may disrupt the steady-state equilibrium of iron. Studies have shown that MPTP induced PD model mice have increased iron levels. Ferroportin-1 (FP1) is a newly discovered iron efflux protein, and its decreased expression in the substantia nigra can explain the increase in iron levels. In this study, the expression level of FP1 was detected after MPTP injury, and it was found that the expression level of FP1 showed a significant decrease. In addition, Bcl-2 is an anti apoptotic protein, and studies have shown that the expression of Bcl-2 in MPTP treated mice is reduced. Apoptosis and autophagy are important intracellular processes that maintain homeostasis and promote survival. Their imbalance is related to neurodegenerative diseases, such as PD and B-cell lymphoma, where Bcl-2 family members participate in maintaining the balance between autophagy and apoptosis. Restoring the balance between autophagy and apoptosis is a promising strategy for treating PD. Therefore, in this study, we also detected the expression level of Bcl-2 after MPTP injury and found that the expression level of Bcl-2 was significantly reduced.

Ginsenoside Rb1 has been proven to have neuroprotective effects on several central nervous system diseases. Studies have found through immunohistochemistry, immunoblotting, PCR, electrophysiological experiments, etc. that Rb1 improves motor disorders in PD animal models and can upregulate the glutamate transporter GLT-1 to terminate glutamate excitotoxicity in the nigrostriatal and corticosterone systems. In a report, a PD model mouse was induced by MPTP, and the inhibition of MPTP induced hippocampal memory changes by ginsenoside Rb1 through regulating the α – synuclein/PSD-95 pathway was detected in water maze, open field experiments, electrophysiology, immunoblotting, immunofluorescence, and other aspects. Our research mainly focuses on MPTP induced dopaminergic neuron damage and PD mouse models to explore the improvement effect of ginsenoside Rb1 on behavioral abnormalities and its relationship with anti apoptotic protein Bcl-2.

Our results show that ginsenoside Rb1 can restore the motor injury caused by MPTP and significantly improve the reduction of TH tyrosine positive kinase caused by MPTP. This provides relevant methods for further treatment of Parkinson’s disease and the development and use of active ingredients in traditional Chinese medicine. Our study also showed that ginsenoside Rb1 exhibited significant differences in the anti apoptotic protein Bcl-2; Although ginsenoside Rb1 did not show significant differences in the expression levels of FP1 and CaMKII, MPTP did cause a decrease in FP1 expression, which can provide some ideas for related research. In addition, other mechanisms of ginsenoside Rb1 besides anti apoptotic proteins still need to be studied.