Natural products against Alzheimer's disease: Pharmaco-therapeutics and biotechnological interventions

Dopamine is a neurotransmitter that is produced in the substantia nigra, ventral tegmental area, and hypothalamus of the brain. Dysfunction of the dopamine system has been implicated in different nervous system diseases. The level of dopamine transmission increases in response to any type of reward and by a large number of strongly additive drugs. The role of dopamine dysfunction as a consequence of oxidative stress is involved in health and disease. Introduce new potential targets for the development of therapeutic interventions based on antioxidant compounds. The present review focuses on the therapeutic potential of antioxidant compounds as a coadjuvant treatment to conventional neurological disorders is discussed.

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The Role of Dopamine and Its Dysfunction as a Consequence of Oxidative Stress

Parkinson disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease and is caused by genetics, environmental factors and aging, with few treatments currently available. Apoptosis and macroautophagy/autophagy play critical roles in PD pathogenesis; as such, modulating their balance is a potential treatment strategy. BCL2 (B cell leukemia/lymphoma 2) is a key molecule regulating this balance. Piperlongumine (PLG) is an alkaloid extracted from Piper longum L. that has antiinflammatory and anticancer effects. The present study investigated the protective effects of PLG in rotenone-induced PD cell and mouse models. We found that PLG administration (2 and 4 mg/kg) for 4 wk attenuated motor deficits in mice and prevented the loss of dopaminergic neurons in the substantia nigra induced by oral administration of rotenone (10 mg/kg) for 6 wk. PLG improved cell viability and enhanced mitochondrial function in primary neurons and SK-N-SH cells. These protective effects were exe...

https://www.tandfonline.com/doi/pdf/10.1080/15548627.2017.1390636

Piperlongumine restores the balance of autophagy and apoptosis by increasing BCL2 phosphorylation in rotenone-induced Parkinson disease models.

Role of the blood-brain barrier in the nutrition of the central nervous system.

The cellular antioxidant system plays key roles in blocking or retarding the pathogenesis of adult neurodegenerative disorders as elevated oxidative stress has been implicated in the pathophysiology of such diseases. Molecules with the ability in enhancing the antioxidant defense thus are promising candidates as neuroprotective agents. We reported herein the synthesis of piperlongumine analogues and evaluation of their cytoprotection against hydrogen peroxide- and 6-hydroxydopamine-induced neuronal cell oxidative damage in the neuron-like PC12 cells. The structure-activity relationship was delineated after the cytotoxicity and protection screening. Two compounds (4 and 5) displayed low cytotoxicity and confer potent protection of PC12 cells from the oxidative injury via upregulation of a panel of cellular antioxidant molecules. Genetically silencing the transcription factor Nrf2, a master regulator of the cellular stress responses, suppresses the cytoprotection, indicating the critical involvement of Nrf2 for the cellular action of compounds 4 and 5 in PC12 cells.

Synthesis of piperlongumine analogues and discovery of nuclear factor erythroid 2-related factor 2 (Nrf2) activators as potential neuroprotective agents.

Identification and simultaneous quantification of five alkaloids in Piper longum L. by HPLC–ESI-MSn and UFLC–ESI-MS/MS and their application to Piper nigrum L.

Context: Alkaloids of Piper longum L. (Piperaceae) (PLA) include piperine and piperlonguminine. Piper longum and piperine have multiple biological properties including antioxidant activity.Objective: The present study investigated the neuroprotective effects of PLA in a MPTP-induced mouse model of Parkinson’s disease.Materials and methods: PLA was prepared by extracting the dry seed of P. longum using 85% ethanol. Adult male C57BL/6 mice were divided into eight groups of 12 rats each. Experimental and control groups received an equivalent volume of saline, 0.5% CMC-Na, and 0.1% Tween 80, treated groups received oral PLA (30, 60, and 120 mg/kg), other groups treated with piperine (60 mg/kg) or Madopar (50 mg/kg). The PLA prevention group (PLA-Pr) administrated PLA (120 mg/kg) for 1 week before MPTP challenged. Except for the PLA-Pr group, others were treated for seven consecutive weeks. Parkinson’s disease was induced by injecting MPTP intraperitoneally (25 mg/kg) twice weekly for five consecutive ...

Neuroprotective effects of alkaloids from Piper longum in a MPTP-induced mouse model of Parkinson’s disease

Tissue distribution profiles of three antiparkinsonian alkaloids from Piper longum L. in rats determined by liquid chromatography–tandem mass spectrometry

Objective To discuss the protective effect of alkaloids from Piper longum (PLA) in rat dopaminergic neuron injury of 6-OHDA-induced Parkinson's disease and its possible mechanism. Method The rat PD model was established by injecting 6-OHDA into the unilateral striatum with a brain solid positioner. The PD rats were divided into the PLA group (50 mg x kg(-1) x d(-1)), the madorpa group (50 mg x kg(-1) x d(-1)) and the model group, with 15 rats in each group. All of the rats were orally given drugs once a day for 6 weeks. Meanwhile, other 15 rats were randomly selected as the sham operation group, and only injected with normal saline in the unilateral striatum. The behavioral changes were observed with the apomorphine (APO)-induced rotation and rotary rod tests. The number of tyrosine hydroxylase (TH)-positive cells in rat substantia nigra and the density of TH-positive fibers in striatum were detected by tyrosine hydroxylase immunohistochemistry. The content of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione (GSH), catalase (CAT), malondialdehyde (MDA), nitric oxide (NO) and nitric oxide synthase (NOS) in rat substantia nigra and striatum were measured by the spectrophotometric method. Result After being induced by APO, PD rats showed obvious rotation behaviors, with decreased time stay on rotary rod and significant reduction in the number of TH-positive cells in sustantia nigra and the density of TH-positive fibers in striatum. The activities of SOD, GSH-Px, CAT, the content of GSH and the total antioxidant capacity significantly decreased, whereas the activities of NOS and the content of MDA, NO significantly increased. PLA could significantly improve the behavioral abnormality of PD rats and increase the number of TH-positive cells in sustantia nigra and the density of TH-positive fibers in striatum. It could up-regulate the activities of SOD, GSH-Px, CAT, the content of GSH and the total antioxidant capacity, and decrease the content of NOS and the content of MDA, NO. Conclusion Alkaloids from P. longum shows the protective effect in substantia nigra cells of 6-OHDA-induced PD model rats. Its mechanism may be related with their antioxidant activity.

Li Zheng

Papers

Identification and simultaneous quantification of five alkaloids in Piper longum L. by HPLC–ESI-MSn and UFLC–ESI-MS/MS and their application to Piper nigrum L.

Neuroprotective effects of alkaloids from Piper longum in a MPTP-induced mouse model of Parkinson’s disease

Tissue distribution profiles of three antiparkinsonian alkaloids from Piper longum L. in rats determined by liquid chromatography–tandem mass spectrometry

[Protective effect of alkaloids from Piper longum in rat dopaminergic neuron injury of 6-OHDA-induced Parkinson's disease].