Resveratrol in Rodent Models of Parkinson's Disease: A Systematic Review of Experimental Studies.

Parkinson's disease (PD) is a common neurodegenerative disease featured by progressive degeneration of nigrostriatal dopaminergic neurons (DA) accompanied with motor function impairment. Accumulating evidence has demonstrated that natural compounds from herbs have potent anti-PD efficacy in PD models. Among those compounds, resveratrol, a polyphenol found in many common plants and fruits, is more effective against PD. Resveratrol has displayed a potent neuroprotective efficacy in several PD animal models. However, there is still no systematic analysis of the quality of methodological design of these studies, nor of their results. In this review, we retrieved and analyzed 18 studies describing the therapeutic effect of resveratrol on PD animal models. There are 5 main kinds of PD rodent models involved in the 18 articles, including chemical-induced (MPTP, rotenone, 6-OHDA, paraquat, and maneb) and transgenic PD models. The neuroprotective mechanisms of resveratrol were mainly concentrated on the antioxidation, anti-inflammation, ameliorating mitochondrial dysfunction, and motor function. We discussed the disadvantages of different PD animal models, and we used meta-analysis approach to evaluate the results of the selected studies and used SYRCLE's risk of bias tool to evaluate the methodological quality. Our analytical approach minimized the bias of different studies. We have also summarized the pharmacological mechanisms of resveratrol on PD models as reported by the researchers. The results of this study support the notion that resveratrol has significant neuroprotective effects on different PD models quantified using qualitative and quantitative methods. The collective information in our review can guide researchers to further plan their future experiments without any hassle regarding preclinical and clinical studies. In addition, this collective assessment of animal studies can provide a qualitative analysis of different PD animal models, either to guide further testing of these models or to avoid unnecessary duplication in their future research.

Neuroprotective effects of baicalein in animal models of Parkinson's disease: A systematic review of experimental studies.

BACKGROUND: There is an increasing of reports describing the efficacy of neuroprotective small molecule in Parkinson's disease (PD) models. Ideally, the choice of pushing drug candidates to clinical trial should be based on an unbiased assessment of all available data. Systematic review uses a methodical approach to minimize the bias in the selection of studies for inclusion, providing a comprehensive understanding of the drug's effects on multiple animal models with different mechanism. To our knowledge, such assessments of baicalein, which is a candidate neuroprotective drug with efficacy in PD, have not been fully conducted. PURPOSE: To provide a comprehensive understanding of baicalein's effects on different animal models with different mechanism by using a methodical approach to minimize the bias in the selection of studies. METHODS: In this study, we used a systematic review method to comprehensively assess the efficacy of baicalein in animal PD models. By using electronic and manual search for the literatures, we identified studies describing the efficacy of baicalein in animal models of PD. RESULTS: We identified 16 studies describing the efficacy of baicalein in animal models of PD. The methodological quality of all preclinical trials is ranged from 2 to 5. 16 studies involved 4 main kinds of PD animal models. They are MPP+-induced, rotenone-induced, 6-OHDA-induced and acrolein-induced PD models, respectively. The protective effects of baicalein were studied mainly focusing on the anti-oxidative, anti-apoptotic, and anti-inflammatory action. Beyond that, there are 2 articles describing the effects of baicalein on neurotransmitter balance in the basal ganglia, and 2 articles reporting the effects in decreasing synuclein aggregation. CONCLUSIONS: The results demonstrated the neuroprotective effects of baicalein in PD experimental animals and analyzed the pharmacological mechanism. The information will be useful for the further development of baicalein into anti-PD agent and provide unbiased evidence for the conduct of clinical trials. In addition, such evaluation based on animal experiments can give us a general introduction to different animal models of PD, either guiding the further model tests, or avoiding the unnecessary replication.

Reprint of "Animal models of early-stage Parkinson's disease and acute dopamine deficiency to study compensatory neurodegenerative mechanisms".

Parkinson's disease is a common neurodegenerative disease characterized by a widely variety of motor and non-motor symptoms. While the motor deficits are only visible following a severe dopamine depletion, neurodegenerative process and some non-motor symptoms are manifested years before the motor deficits. Importantly, chronic degeneration of dopaminergic neurons leads to the development of compensatory mechanisms that play roles in the progression of the disease and the response to anti-parkinsonian therapies. The identification of these mechanisms will be of great importance for improving our understanding of factors with important contributions to the disease course and the underlying adaptive process. To date, most of the data obtained from animal models reflect the late, chronic, dopamine-depleted states, when compensatory mechanisms have already been established. Thus, adequate animal models with which researchers are able to dissect early- and late-phase mechanisms are necessary. Here, we reviewed the literature related to animal models of early-stage PD and pharmacological treatments capable of inducing acute dopamine impairments and/or depletion, such as reserpine, haloperidol and tetrodotoxin. We highlighted the advantages, limitations and the future prospective uses of these models, as well as their applications in the identification of novel agents for treating this neurological disorder.

Animal models of early-stage Parkinson's disease and acute dopamine deficiency to study compensatory neurodegenerative mechanisms.

Parkinson's disease is a common neurodegenerative disease characterized by a widely variety of motor and non-motor symptoms. While the motor deficits are only visible following a severe dopamine depletion, neurodegenerative process and some non-motor symptoms are manifested years before the motor deficits. Importantly, chronic degeneration of dopaminergic neurons leads to the development of compensatory mechanisms that play roles in the progression of the disease and the response to anti-parkinsonian therapies. The identification of these mechanisms will be of great importance for improving our understanding of factors with important contributions to the disease course and the underlying adaptive process. To date, most of the data obtained from animal models reflect the late, chronic, dopamine-depleted states, when compensatory mechanisms have already been established. Thus, adequate animal models with which researchers are able to dissect early- and late-phase mechanisms are necessary. Here, we reviewed the literature related to animal models of early-stage PD and pharmacological treatments capable of inducing acute dopamine impairments and/or depletion, such as reserpine, haloperidol and tetrodotoxin. We highlighted the advantages, limitations and the future prospective uses of these models, as well as their applications in the identification of novel agents for treating this neurological disorder.

Dopaminergic Neuroprotection with Atremorine in Parkinson´s Disease.

Patients with Parkinson's disease (PD) are looking forward to new therapeutic strategies that may gradually decelerate the rate of neurodegenerative decline, associated with mobility restrictions and related morbidity. Its continuous neurodegenerative process, exacerbated by genetic mutations or environmental toxins, involves a progressive reduction in the dopamine neurotransmission levels, synaptic uptake density, oxidative glucose intake, deficient striatal lactate accumulation and chronic inflammation. Over the last decade, novel bioproducts have received considerable interest due to their unique potential of unifying nutritional, safety and therapeutic natural effects. Some nutraceuticals play a crucial role in the control of the signaling transduction pathways in neurotransmission and inflammation affected in PD, and some natural compounds can beneficially interact with each one of these biological mechanisms to slow down disease progression. Atremorine, a novel plant-derived nutraceutical, probably with a neuroprotective effect in the dopaminergic neurons of the substantia nigra (pars compacta), is a prototype of this new category of bioproducts with potential effects in PD. The major focus of this review will be on the current knowledge and biomedical investigation strategies through a plant-derived neuroprotective approach to improve life quality in PD patients, being of paramount importance for health providers, caregivers and the patients themselves.