phytoestrogens and Parkinson-Disease

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive damage of mesencephalic dopaminergic neurons of the substantia nigra and the striatal projections. Recent studies suggest that estrogen and estrogen-like chemicals have beneficial effects on neurodegenerative diseases, particularly PD. Animal studies demonstrate that estrogen influences dopamine's synthesis, release, and metabolism. In vivo studies have also shown the significant beneficial effects of estrogen in shielding the brain from neurodegenerative processes like PD. Moreover, the expression and function of dopamine receptors can be modified by estrogen. Phytoestrogens are non-steroidal compounds derived from plants present in a large spectrum of foods, most specifically soy and in numerous dietary supplements. Phytoestrogens share structural and functional similarities with 17β-estradiol and can be used as an alternative treatment for PD because of estrogen's undesirable effects, such as the increased risk of breast and endometrial cancer, ischemic disorders, and irregular bleeding. Despite the beneficial effects of phytoestrogens, their impact on human health may depend on age, health status, and even the presence or absence of specific gut microflora. In addition to their antioxidant properties, soy products or phytoestrogens also exhibit neuroprotective activity in patients with PD via the interaction with estrogen receptors (ER) α and β, with a higher affinity for ERβ. Phytoestrogens offer a valuable model for fully exploring the biological effects of endocrine disruptors in general. However, observational studies and randomized controlled trials in humans have resulted in inconclusive findings within this domain. This review considered the evidence in animal models and human epidemiological data as to whether developmental exposure to various phytoestrogen classes adversely or beneficially impacts the neurobehavioral programming in PD.

Topics: Animals; Brain; Diet; Humans; Neuroprotection; Neuroprotective Agents; Parkinson Disease; Phytoestrogens

Activation of microglia and consequent release of proinflammatory factors, are believed to contribute to neurodegeneration in Parkinson's disease (PD). Hence, identification of compounds that prevent microglial activation is highly desirable in the search for therapeutic agents for inflammation-mediated neurodegenerative diseases. In this study, we reported that biochanin A, one of the predominant isoflavones in Trifolium pratense, attenuated lipopolysaccharide (LPS)-induced decrease in dopamine uptake and the number of dopaminergic neurons in a dose-dependent manner in rat mesencephalic neuron-glia cultures. Moreover, biochanin A also significantly inhibited LPS-induced activation of microglia and production of tumor necrosis factor-alpha, nitric oxide and superoxide in mesencephalic neuron-glia cultures and microglia-enriched cultures. This study suggested for the first time that biochanin A protected dopaminergic neurons against LPS-induced damage through inhibition of microglia activation and proinflammatory factors generation.

Topics: Animals; Animals, Newborn; Cells, Cultured; Coculture Techniques; Dopamine; Dose-Response Relationship, Drug; Encephalitis; Genistein; Gliosis; Inflammation Mediators; Lipopolysaccharides; Microglia; Neurons; Neuroprotective Agents; Nitric Oxide; Parkinson Disease; Phytoestrogens; Rats; Rats, Sprague-Dawley; Substantia Nigra; Superoxides; Tumor Necrosis Factor-alpha

The protective effect of puerarin on the Parkinson disease (PD) mice with decreased estrogen level was investigated in order to develop a new potential medicine as a substitute for estrogen for preventing and treating PD. By using immunohistochemical method of avidinbiotin peroxidase complex (ABC), the distribution of the cells positive for tyrosine hydroxylase (TH) and fibres in the substantia nigra of the mouse were observed. These mice were divided into three groups randomly: group A, normal-female-mouse models; group B containing three subgroups, B1 (normal saline), B2 (estrogen), B3 (puerarin); group C containing three sub groups, C1 (normal saline), C2 (estrogen), C3 (puerarin). By using TUNEL the numbers of apoptosis cells in every visual field was counted and the difference between the experimental group and control group was compared. The results showed the numbers of the cells positive for TH were more and the numbers of apoptosis cells were less in the normal-female-mouse models group than in the group of model made after ovariosteresis and the group of model made before ovariosteresis (P < 0.05), respectively. However, there was no significant difference, between the group given estrogen/puerarin and the controls, and between the group given estrogen and given puerarin. (P > 0.05). It was suggested that puerarin may have protective effect on the nigral neurons to PD. Moreover, the protective effect might serve as a surrogate of estrogen and be associated with the apoptosis.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Apoptosis; Estrogens; Female; Isoflavones; Mice; Mice, Inbred BALB C; Ovariectomy; Parkinson Disease; Phytoestrogens; Plant Preparations; Random Allocation; Substantia Nigra; Tyrosine 3-Monooxygenase; Vasodilator Agents

In vivo fast cyclic voltammetry (FCV) was used to investigate dopamine (DA) release from amygdala (Amy) of female rats in different phases of estrus cycle, ovaricectomized (OVX) rats and male rats. Tyrosine hydroxylase (TH) immunohistochemistry was employed to measure the numbers of immunoreactive neurons in ventral tegmental area (VTA) of midbrain in the rats. We also observed the effect of intracerebroventricular injection of phytoestrogen-soy isoflavones on DA release from the Amy. The results are as follows: DA release from the Amy of proestrus female rats was apparently higher than that in estrus, metaestrus, diestrus female rats and OVX rats. Amy DA release and the numbers of the TH immunoreactive neurons in VTA showed a significant sex difference. DA release from Amy of female and OVX rats increased significantly within 5 min after i.c.v injection of soy isoflavones, which elicited no effects in male rats. The above-mentioned results suggest that endogenous estrogen may play an important role in regulating the activity of DA neurons in mid-limbic systems, and that soy isoflavones exert an estrogen-like effect on the dopaminergic systems in the Amy.

Topics: Amygdala; Animals; Dopamine; Estrogens; Female; Glycine max; Isoflavones; Male; Neurons; Ovariectomy; Parkinson Disease; Phytoestrogens; Plant Preparations; Rats; Rats, Wistar; Ventral Tegmental Area