Estrogenic Plants: to Prevent Neurodegeneration and Memory Loss and Other Symptoms in Women After Menopause.

In mammals, sexual hormones such as estrogens play an essential role in maintaining brain homeostasis and function. Estrogen deficit in the brain induces many undesirable symptoms such as learning and memory impairment, sleep and mood disorders, hot flushes, and fatigue. These symptoms are frequent in women who reached menopausal age or have had ovariectomy and in men and women subjected to anti-estrogen therapy. Hormone replacement therapy alleviates menopause symptoms; however, it can increase cardiovascular and cancer diseases. In the search for therapeutic alternatives, medicinal plants and specific synthetic and natural molecules with estrogenic effects have attracted widespread attention between the public and the scientific community. Various plants have been used for centuries to alleviate menstrual and menopause symptoms, such as Cranberry, Ginger, Hops, Milk Thistle, Red clover, Salvia officinalis, Soy, Black cohosh, Turnera diffusa, Ushuva, and Vitex. This review aims to highlight current evidence about estrogenic medicinal plants and their pharmacological effects on cognitive deficits induced by estrogen deficiency during menopause and aging.

In Silico Identification of Novel Interactions for FABP5 (Fatty Acid-Binding Protein 5) with Nutraceuticals: Possible Repurposing Approach.

Fatty Acid Binding-Protein 5 (FABP5) is a cytoplasmic protein, which binds long-chain fatty acids and other hydrophobic ligands. This protein is implicated in several physiological processes including mitochondrial ß-oxidation and transport of fatty acids, membrane phospholipid synthesis, lipid metabolism, inflammation and pain. In the present study, we used molecular docking tools to determine the possible interaction of FABP5 with six selected compounds retrieved form Drugbank. Our results showed that FABP5 binding pocket included 31 polar and non-polar amino acids, and these residues may be related to phosphorylation, acetylation, ubiquitylation, and mono-methylation. Docking results showed that the most energetically favorable compounds are NADH (-9.12 kcal/mol), 5'-O-({[(Phosphonatooxy)phosphinato]oxy}phosphinato)adenosine (-8.62 kcal/mol), lutein (-8.25 kcal/mol), (2S)-2-[(4-{[(2-Amino-4-oxo-1,4,5,6,7,8-hexahydro-6-pteridinyl)methyl]amino}benzoyl)amino]pentanedioate (-7.17 kcal/mol), Pteroyl-L-glutamate (-6.86 kcal/mol) and (1S,3R,5E,7Z)-9,10-Secocholesta-5,7,10-triene-1,3,25-triol (-6.79 kcal/mol). Common interacting residues of FABP5 with nutraceuticals included SER16, LYS24, LYS34, LYS40 and LYS17. Further, we used the SwissADME server to determine the physicochemical and pharmacokinetic characteristics and to predict the ADME parameters of the selected nutraceuticals after molecular analysis by docking with the FABP5 protein. Amongst all compounds, pteroyl-L-glutamate is the only one meeting the Lipinski's rule of five criteria, demonstrating its potential pharmacological use. Finally, our results also suggest the importance of FABP5 in mediating the anti-inflammatory activity of the nutraceutical compounds.

Extracts of Physalis peruviana Protect Astrocytic Cells Under Oxidative Stress With Rotenone.

The use of medicinal plants to counteract the oxidative damage in neurodegenerative diseases has steadily increased over the last few years. However, the rationale for using these natural compounds and their therapeutic benefit are not well explored. In this study, we evaluated the effect of different Physalis peruviana extracts on astrocytic cells (T98G) subjected to oxidative damage induced by rotenone. Extracts of fresh and dehydrated fruits of the plant with different polarities were prepared and tested in vitro. Our results demonstrated that the ethanolic extract of fresh fruits (EF) and acetone-dehydrated fruit extract (AD) increased cell viability, reduced the formation of reactive oxygen species (ROS) and preserved mitochondrial membrane potential. In contrast, we observed a significant reduction in mitochondrial mass when rotenone-treated cells were co-treated with EF and AD. These effects were accompanied by a reduction in the percentage of cells with fragmented/condensed nuclei and increased expression of endogenous antioxidant defense survival proteins such as ERK1/2. In conclusion, our findings suggest that ethanolic and acetone extracts from P. peruviana are potential medicinal plant extracts to overcome oxidative damage induced by neurotoxic compounds.

Inhibiting Effect of Zinc Oxide Nanoparticles on Advanced Glycation Products and Oxidative Modifications: a Potential Tool to Counteract Oxidative Stress in Neurodegenerative Diseases.

Advanced glycation end products (AGEs) are implicated in several central nervous system (CNS) pathologies including Alzheimer and Parkinson's diseases. In the face-off of AGE menace, we have attempted to investigate the zinc oxide nanoparticle (ZnONP) role in inhibition of AGE formation. Synthesized ZnONPs were used to investigate the inhibitory effects on AGE formation. The inhibitory effects of ZnONPs on AGE formation were determined by biophysical immunological and biochemical techniques. The results showed that ZnONP is a potential anti-glycating agent inhibiting AGE formation as well as protecting the protein structure from change. Therefore, our findings suggest ZnONPs may be used as a therapeutic in resolving the AGE role in CNS-related complications.

Medicinal Plants as Protective Strategies Against Parkinson's Disease.

Parkinson's disease is a neurodegenerative disease caused by the loss of dopaminergic neurons in the substantia nigra pars compacta region. An important mechanism contributing to its development is oxidative stress, induced by the imbalance between the endogenous antioxidant defenses and free radicals production. Naturally occurring bioactive compounds exhibit high antioxidant capacity that may help reducing oxidative stress and even reverse the damage induced by ROS. Fruits are particularly rich in phytochemicals with antioxidant effect, and their properties against the development of neurodegenerative diseases are of great interest. This review discusses how the fruits bioactive compounds and synthetic analogs have been assessed for their ability to regulate molecular pathways involved in neuronal survival such as MAPK, Nrf2, and NF-κB, thus elucidating the possible therapeutic and neuroprotective actions of these compounds.

Advances in Medicinal Plants with Effects on Anxiety Behavior Associated to Mental and Health Conditions.

BACKGROUND: Many mental health conditions including psychiatric disorders and neurodegenerative conditions are poorly responsive for actual medications or have low patient adherence to treatment due to the side effects or costs associated with these treatments. OBJECTIVE: The main goal of this review is to provide clinical providers and patients with actualized information about the efficacy of selected herbal medicines for anxiety disorders derived from mental and/or health conditions, and their associated side effects. METHODS: In this review, actual scientific advances about the use of medicinal plants for anxiety disorders are presented. RESULTS: In recent years, the herbal therapies have reemerged as a source of efficacious natural treatments, at a lower cost and most of the time reduced side effects than currently prescribed pharmaceutical drugs. The herbs described mainly correspond to plants of traditional medicine from the American continent and near islands and Asia. CONCLUSION: Current evidence confirms the therapeutic effects of traditional medicine. Further clinical investigation is required to confirm these findings. The current understanding of the molecular mechanisms involved in psychiatric disorders, as well as the new advances in brain imaging permit a rapid and serious evaluation of anxiolytic compounds.

Ginkgo biloba as an Alternative Medicine in the Treatment of Anxiety in Dementia and other Psychiatric Disorders.

BACKGROUND: Mental disorders are the most common health problems in the worldwide population. Current medicines against these conditions have undesired side effects or limited effectiveness. These disadvantageous pharmacological and therapeutic characteristics provoke a low adherence to treatment in an important percentage of patients with mental disorders. Since ancient times, ethnically different groups have been using plants extracts as medicines for the treatment of mental conditions including dementia, depression and anxiety disorders. Among them are extracts of Ginkgo biloba, a tree in the division Gingophyta, that has been used by millions of people worldwide. OBJECTIVE: This review aims to discuss current scientific evidence of efficacy, neuroprotective and antioxidant effects as mechanism of action, side effects and potential interaction with other commonly prescribed anxiolytic drugs. METHODS: A PubMed search of preclinical studies as well as individual clinical trials and meta-analysis were scrutinized. RESULTS: Various preclinical and clinical studies have shown a positive effect of Ginkgo biloba to improve cognitive abilities in impaired individuals and reducing anxiety under pathological conditions. CONCLUSION: A more advanced clinical research is needed to confirm the efficacy of Gingko biloba for the treatment of anxiety in different health conditions.

Implication of Green Tea as a Possible Therapeutic Approach for Parkinson Disease.

Green tea is a beverage consumed around the world that is believed to have substantial health benefits such as reducing the risk of cancer, cardiovascular diseases, diabetes and neurodegeneration. This beverage is prepared from the leaves (steamed and dried) of the Camellia sinesis plant and contains strong antioxidant and neuroprotective phenolic compounds from which the most important is (-)-Epigallocatechin-3-gallate. Parkinson's disease (PD) is the second more common neurodegenerative disorders, after Alzheimer's disease and is characterized by degeneration of dopaminergic neurons in the pars compact of the substantia nigra of the basal ganglia. It has been shown in pre-clinical and clinical studies that green tea may be able to prevent PD, but its optimal dose or a possible mechanism explaining its health benefit in PD has not been properly established. In this review, we discuss the potential role of green tea's phenolic compounds and their therapeutic effectin modulating key signaling pathways in the PD brain.

Raf inhibitors as therapeutic agents against neurodegenerative diseases.

The active form of the serine/threonine kinase cRaf-1 is upregulated postmortem in the brains of Alzheimer's disease (AD) patients and in transgenic mouse models of AD pathology. The persistent activation of cRaf-1 can activate the proinflammatory factor NFkappaB and consequently, upregulate the expression of several of its downstream factors such as the amyloid precursor protein (APP), Cox-2 and iNOS. These factors have been found upregulated in numerous neurodegenerative conditions including AD, epilepsy, brain trauma, and psychological stress. The Raf kinase inhibitors, GW5074 and ZM336372, are neuroprotective against many different neurotoxic insults in vitro, including the Abeta peptide, glutamate and glutathione depletion. Recently, we have reported that the multi-kinase and potent Raf inhibitor sorafenib reversed memory impairment and reduced the expression of APP, Cox-2, and iNOS in the brain of the transgenic mouse model of AD, APPswe. Similar improvement of behavioral outcome was attained after acute treatment with GW5074 in a mouse model of Huntington's disease. Several Raf inhibitors have been developed to treat aggressive forms of cancer showing an upregulation of Raf kinases. These Raf inhibitors offer a great promise as therapeutic tools against neurological disorders. The negative and positive aspects of these inhibitors as anti-neurodegenerative agents are discussed.