lignans and Parkinson-Disease

Neurodegenerative Diseases (NDs) are characterized by progressive neuronal deterioration as a result of several pathogenesis mechanisms. Phytochemicals, including sesamin with multitarget activities, have been studied widely.. In this review, we aim to survey the neuroprotective effects of sesamin on NDs and its mechanisms of action.. Searching GoogleScholar, PubMed, and Science Direct databases, we reviewed original English language articles on sesamin effects against NDs, specifically Alzheimer's Disease (AD) and Parkinson's Disease (PD), either in vivo or in vitro settings, with no time limitation.. Sesamin has been reported to interfere with NDs progression through its antioxidative, antiinflammatory, and antiapoptotic actions in most of the retrieved studies. Sesamin also can prevent amyloid-β aggregation in AD models and elevate dopamine levels in PD-induced models.. The results of this study revealed the beneficial effects of sesamin in the prevention and management of NDs, including AD and PD; however, no clinical data supporting these effects in humans is available, which highlights the need for designing clinical trials to evaluate the efficacy, proper dosage, pharmacokinetics aspects, and possible side effects of sesamin in humans.

Topics: Alzheimer Disease; Dioxoles; Humans; Lignans; Parkinson Disease

Neuronal apoptosis and oxidative stress have the most crucial influence on neurodegenerative diseases, including Parkinson's disease. Rat adrenal pheochromocytoma cells (PC-12) induced by H. This study aimed to evaluate the neuroprotective effects of lignans in E. ulmoides leaves and to explore the underlying mechanism.. Cell viability was measured using the CCK-8 assay. Apoptosis was assessed by calcein/PI staining. The release levels of ROS and LDH were assessed using a commercial assay kit. The enzyme activities of SOD and GPx were measured using kits. The establishment of the compound-target-pathway-disease network was performed using a database and computer software. Antioxidant proteins (HO-1, NQO-1, and Cat) and related regulatory proteins (Nrf2, GSK-3β, p-GSK 3β (Ser 9), Akt, p-Akt (Tyr326), PI3K) were detected by western blotting. Apoptosis in the zebrafish head was assessed using acridine orange (AO) staining.. Our experiments first propose that the diepoxylignans from E. ulmoides leaves exert neuroprotective effects via activation of the PI3K/Akt/GSK-3β/Nrf2 signaling pathway. These findings further indicate that lignans could be the primary components of E. ulmoides Oliver as agents for the prevention and treatment of neurodegenerative diseases. Collectively, Eucommia ulmoides leaves with important research value may be a potential candidate for traditional Chinese medicine for treating oxidative stress-related neurodegenerative diseases.

Topics: Animals; Antioxidants; Eucommiaceae; Glycogen Synthase Kinase 3 beta; Hydrogen Peroxide; Lignans; Neuroprotective Agents; NF-E2-Related Factor 2; Parkinson Disease; PC12 Cells; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; Reactive Oxygen Species; Signal Transduction; Superoxide Dismutase; Zebrafish

Topics: Acanthaceae; Animals; Autophagy; Humans; Lignans; Mice; Mice, Knockout; Parkinson Disease; PC12 Cells; Rats

Parkinson's disease (PD) is a neurodegenerative disease characterized by loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNc). The proinflammatory response can occur early in the disease, contributing to nigrostriatal degeneration. Identification of the new molecules, which are able to slow down the degenerative process associated with PD, represents one of the main interests. Recently, natural polyphenols, especially lignans, have raised attention for their anti-inflammatory, antioxidant, and estrogenic activity at a peripheral level. The aim of this study was to evaluate the central effects of chronic treatment with lignan 7-hydroxymatairesinol (HMR/lignan) on neurodegenerative, neuroinflammatory processes and motor deficits induced by a unilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA) in rats to evaluate the potential neuroprotective properties of this compound.. Sprague-Dawley male rats underwent lignan (10 mg/kg) or vehicle treatment (oral) for 4 wk starting from the day of 6-OHDA injection. The degree of nigrostriatal damage was evaluated by immunohistochemistry. Moreover, we performed a quantitative and qualitative assessment of neuroinflammatory process, including phenotypic polarization of microglia and astrocytes. The motor performance was assessed by behavioral tests.. We demonstrated that chronic treatment with HMR/lignan was able to slow down the progression of degeneration of striatal dopaminergic terminals in a rat model of PD, with a consequent improvement in motor performance. Nevertheless, the anti-inflammatory effect of HMR/lignan observed in SNc was not sufficient to protect dopaminergic cells bodies.. These results suggest intriguing properties of HMR/lignan at neuroprotective and symptomatic levels in the context of PD.

Topics: Animals; Corpus Striatum; Disease Models, Animal; Dopaminergic Neurons; Lignans; Male; Neuroprotective Agents; Oxidopamine; Parkinson Disease; Parkinson Disease, Secondary; Rats; Rats, Sprague-Dawley

Parkinson's disease is the second most common neurodegenerative disease. Its main pathological feature is the substantial nigra-striatum dopaminergic neuronal dysfunction, which causes insufficient release of DA, induces motor symptoms, and is accompanied by nonmotor symptoms. Schisandrol A belongs to lignan components and has anti-inflammatory, antioxidant and neuroprotective effects. In this experiment, we injected 6-OHDA into medial forebrain bundle of C57BL/6J male mice to establish the model. The motor function of mice was examined by open field test and pole test, the depression-like behavior of mice was examined by sucrose preference test and the memory function was examined by Y maze. We found that schisandrol A (20 mg/kg/d) could significantly improve the motor symptoms, and alleviate the depression-like symptoms and memory dysfunction of PD mice induced by 6-OHDA. Then we studied the neuroprotective mechanism of schisandrol A by H.E., ELISA assay kits and Western blot. Results showed that schisandrol A may enhance the PI3K/AKT pathway, inhibit the IKK/IκBα/NF-κB pathway, reduce neuronal inflammation and oxidative stress, and enhance the survival of DA neurons in the brain of mice. These results indicate that schisandrol A is expected to be a potential drug for improving Parkinson's disease.

Topics: Animals; Corpus Striatum; Cyclooctanes; I-kappa B Kinase; Lignans; Male; Mice; Mice, Inbred C57BL; Neuroprotective Agents; NF-kappa B; NF-KappaB Inhibitor alpha; Oxidative Stress; Oxidopamine; Parkinson Disease; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction

Parkinson's disease (PD) is a profound neurodegenerative disorder with gradual loss of dopamine nigrostriatal neurons linked to serious behavioral symptoms. While the current treatment strategies present limitations on halting the progression of PD, this study aimed to investigate the therapeutic potential of honokiol, as a partial peroxisome proliferator-activated receptor-gamma (PPARγ) mimic, on the proceeding behavioral and biochemical alterations in hemiparkinsonian mice. Results showed that unilateral striatal 6-hydroxydopamine (6-OHDA)-lesioned mice exhibited motor impairment, reflecting the contralateral rotation induced by apomorphine at 1-3 weeks post-lesion. Subchronic honokiol administration for 1-2 weeks, beginning 7 days after 6-OHDA-lesion, dose-dependently ameliorated motor dysfunction in hemiparkinsonian mice. Recovery of motor function was correlated with reversal of nigrostriatal dopaminergic neuronal loss, accompanied by higher tyrosine hydroxylase (TH) density, dopamine transporter (DAT) expression and vesicular monoamine transporter-2 (VMAT2) levels. Furthermore, honokiol attenuated oxidative stress and reactive astrocyte induction via decreasing NADPH-oxidase and glial fibrillary acidic protein (GFAP) expressions in 6-OHDA-lesioned striatum. The reversal effects of honokiol on behavioral impairment and striatal PPARγ expression were impeded by PPARγ antagonist GW9662. Notably, subchronic honokiol treatment extended the lifespan of these hemiparkinsonian mice. The present findings demonstrate the therapeutic activities of honokiol in ameliorating motor impairment and progressive dopaminergic damage that could be associated with regulating PPARγ signaling. Therefore, honokiol may potentially exert as a novel therapeutic candidate through PPARγ activation for management of motor symptoms and progressive neurodegeneration in PD.

Topics: Animals; Biphenyl Compounds; Gliosis; Lignans; Longevity; Male; Mice; Motor Activity; NADPH Oxidases; Neostriatum; Nerve Degeneration; Oxidation-Reduction; Oxidopamine; Parkinson Disease; PPAR gamma

18F-9-Fluoropropyl-(+)-dihydrotetrabenazine [18F-FP-(+)-DTBZ] positron emission tomography (PET) has been shown to detect dopaminergic neuron loss associated with Parkinson's disease (PD) in human and neurotoxin-induced animal models. A polyphenol compound, magnolol, was recently proposed as having a potentially restorative effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- or 6-hydroxydopamine-treated animal models. In this study, 18F-FP-(+)-DTBZ PET was used to determine the therapeutic efficacy of magnolol in an MPTP-PD mouse model that was prepared by giving an intraperitoneally (i.p.) daily dose of 25 mg/kg MPTP to male C57BL/6 mice for 5 consecutive days. Twenty-minute static 18F-FP-(+)-DTBZ PET scans were performed before MPTP treatment and 5 days after the termination of MPTP treatment to set up the baseline control. Half of the MPTP-treated mice then received a daily dose of magnolol (10 mg/kg dissolved in corn oil, i.p.) for 6 days. 18F-FP-(+)-DTBZ PET imaging was performed the day after the final treatment. All 18F-FP-(+)-DTBZ PET images were analysed and the specific uptake ratio (SUr) was calculated. Ex vivo autoradiography (ARG) and corresponding immunohistochemistry (IHC) studies were conducted to confirm the distribution of dopaminergic terminals in the striatum. The striatal SUr ratios of 18F-FP-(+)-DTBZ PET images for the Sham, the MPTP, and the MPTP + Magnolol-treated groups were 1.25 ± 0.05, 0.75 ± 0.06, and 1.00 ± 0.11, respectively (n = 4 for each group). The ex vivo 18F-FP-(+)-DTBZ ARG and IHC results correlated favourably with the PET imaging results. 18F-FP-(+)-DTBZ PET imaging suggested that magnolol post-treatment may reverse the neuronal damage in the MPTP-lesioned PD mice. In vivo imaging of the striatal vesicular monoamine transporter type 2 (VMAT2) distribution using 18F-FP-(+)-DTBZ animal PET is a useful method to evaluate the efficacy of therapeutic drugs i.e., magnolol, for the management of PD.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Biphenyl Compounds; Corpus Striatum; Disease Models, Animal; Fluorine Radioisotopes; Humans; Lignans; Mice; Neurons; Parkinson Disease; Parkinson Disease, Secondary; Positron-Emission Tomography; Tetrabenazine; Vesicular Monoamine Transport Proteins

Topics: Administration, Oral; Animals; Brain; Cyclooctanes; Dioxoles; Disease Models, Animal; Drug Compounding; Lignans; Male; Nanoparticles; Parkinson Disease; Rats, Sprague-Dawley; Zebrafish

Dibenzocyclooctadiene lignans represent a unique group of natural chemical structures, are considered as protectants against neuronal cell death and cognitive impairment in neurological disorders. Among the family of dibenzocyclooctadiene lignan analogs from the fruit of Schisandra chinensis (Turcz.) Baill, neuroprotective potential of schisantherin A (StA) has not yet been characterized. In this study, 1-methyl-4-phenylpyridinium ion (MPP(+))-incubated SH-SY5Y cells and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice were used to study the neuroprotection of StA. Pretreatment with StA significantly inhibited MPP(+)-induced cytotoxicity in SH-SY5Y cells. Moreover, StA conferred significant protection against MPTP-induced loss of TH-positive dopaminergic neurons in a Parkinson's disease (PD) mice model. Structure activity relationship analysis suggested that methylenedioxy, benzoyloxy and methoxyl groups, in the dibenzocyclooctadiene lignan of StA, were probably functionally important to its neuroprotective activity. In addition, Western blotting analysis demonstrated that StA exhibited neuroprotection against MPP(+) through the regulation of two distinct pathways including increasing CREB-mediated Bcl-2 expression and activating PI3K/Akt survival signaling suggesting that StA might be a promising neuroprotective agent for the prevention of PD.

Topics: 1-Methyl-4-phenylpyridinium; Animals; Antiparkinson Agents; Brain; Cell Line, Tumor; Cell Survival; Cyclic AMP Response Element-Binding Protein; Cyclooctanes; Dioxoles; Dopaminergic Neurons; Humans; Lignans; Male; Mice, Inbred C57BL; Neuroprotective Agents; Parkinson Disease; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Signal Transduction

The potential protective effects of arctigenin on 1-methyl-4-phenylpyridinium ion and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyride-induced neurotoxicity were examined, and the results indicated that arctigenin could improve the movement behaviors and upregulate dopamine and γ-aminobutyric acid levels in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyride-induced neurotoxicity mouse model. A further in vitro experiment showed that the pretreatment with arctigenin on cultured human neuroblastoma SH-SY5Y cells could obviously attenuate the decrease of cell survival rates caused by treatment with 1-methyl-4-phenylpyridinium ion by way of acting against cell apoptosis through the decrease of Bax/Bcl-2 and caspase-3, and by antioxidative action through reduction of the surplus reactive oxygen species production and downregulation of mitochondrial membrane potential. It is for the first time that a neuroprotective activity of arctigenin in both in vitro and in vivo experiments was reported, enlightening that arctigenin could be useful as a potential therapeutic agent for Parkinson's disease.

Topics: 1-Methyl-4-phenylpyridinium; Animals; Apoptosis; bcl-2-Associated X Protein; Behavior, Animal; Brain; Cell Line, Tumor; Cell Survival; Dopamine; Furans; gamma-Aminobutyric Acid; Humans; Lignans; Male; Membrane Potential, Mitochondrial; Mice; Mice, Inbred C57BL; MPTP Poisoning; Neuroblastoma; Neuroprotective Agents; Neurotoxicity Syndromes; Parkinson Disease

An efficient synthesis of honokiol with Suzuki-Miyaura cross coupling obtained an overall yield of 45%. The proposed approach successfully synthesized several structurally similar alkyl, alkenyl and alkynyl analogues, seven of which showed potential neuropreventive activity against MPP(+)-induced and CHP/TBHP oxidative stress induced neuroblastoma cell death.

Topics: Biphenyl Compounds; Catalysis; Cell Death; Cell Line, Tumor; Cell Survival; Chemistry, Pharmaceutical; Drug Design; Humans; Lignans; Models, Chemical; Neuroblastoma; Neuroprotective Agents; Oxidative Stress; Parkinson Disease; Reactive Oxygen Species; Time Factors

Advances in understanding the neurodegenerative pathologies are creating new opportunities for the development of neuroprotective therapies, such as antioxidant food factors, lifestyle modification and drugs. However, the biomarker by which the effect of the agent on neurodegeneration is determined is limited. We here address hexanoyl dopamine (HED), one of novel dopamine adducts derived from brain polyunsaturated acid, referring to its in vitro formation, potent toxicity to SH-SY5Y cells, and application to assess the neuroprotective effect of antioxidative food factors. Dopamine is a neurotransmitter, and its deficiency is a characterized feature in Parkinson's disease (PD); thus, HED provides a new insight into the understanding of dopamine biology and pathophysiology of PD and a novel biomarker for the assessment of neuroprotective therapies. We have established an analytical system for the detection of HED and its toxicity to the neuroblstoma cell line, SH-SY5Y cells. Here, we discuss the characteristics of the system and its applications to investigate the neuroprotective effect of several antioxidants that originate from food.

Topics: Antioxidants; Cell Line, Tumor; Cell Survival; Chromatography, High Pressure Liquid; Curcumin; Dioxoles; Dopamine; Humans; Lignans; Neuroblastoma; Parkinson Disease; Tandem Mass Spectrometry; Tocopherols; Tocotrienols; Xanthophylls

Advances in understanding the neurodegenerative pathologies are creating new opportunities for the development of neuroprotective therapies, such as antioxidant food factors, lifestyle modification, and drugs. However, the biomarker by which to determine the effect of the agent on neurodegeneration is limited. We here address hexanoyl dopamine (HED), one of novel dopamine adducts derived from brain polyunsaturated acid, referring to its in vitro formation, potent toxicity to SH-SY5Y cells, and application to assess the neuroprotective effect of antioxidative food factors. Dopamine is a neurotransmitter and its deficiency is a characterized feature in Parkinson's disease (PD), thereby HED represents a new addition to understanding of dopamine biology and pathophysiology of PD and a novel biomarker for the assessment of neuroprotective therapies. We have established an analytical system using for the detection of HED and its toxicity to the neuroblstoma cell line, SH-SY5Y cells. Here, we discuss the characteristics of the system and its applications to investigate the neuroprotective effect of several antioxidants that originate from food.

Topics: Antioxidants; Cell Line, Tumor; Cell Survival; Chromatography, High Pressure Liquid; Curcumin; Dioxoles; Dopamine; Food; Humans; Lignans; Neuroprotective Agents; Oxidative Stress; Parkinson Disease; Tandem Mass Spectrometry; Tocopherols; Tocotrienols; Xanthophylls