Potential therapeutics against neurological disorders: Natural products-based drugs

Rauf, Abdur; Rahman, Md. Mominur

doi:10.3389/fphar.2022.950457

Cited by 8 publications

(4 citation statements)

References 10 publications

(9 reference statements)

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“…[17] Till now, many agents of natural origin with robust antiinflammatory and antioxidant properties have been identified to exhibit beneficial effects in PD. [18,19] Therefore, it is under great urgency to develop more natural drugs to mitigate oxidative stress and neuroinflammation, which will help counteract dopaminergic neurodegeneration and alleviate PD progression.…”

Section: Introductionmentioning

confidence: 99%

Vincamine alleviates brain injury by attenuating neuroinflammation and oxidative damage in a mouse model of Parkinson's disease through the NF‐κB and Nrf2/HO‐1 signaling pathways

Wang,

Chen,

Shan

2024

J Biochem & Molecular Tox

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Parkinson's disease (PD) is a neurodegenerative disease featured by progressive loss of nigrostriatal dopaminergic neurons, the etiology of which is associated with the existence of neuroinflammatory response and oxidative stress. Vincamine is an indole alkaloid that was reported to exhibit potent anti‐inflammatory and antioxidant properties in many central and/or peripheral diseases. Nevertheless, the specific role of vincamine in PD development remains unknown. In our study, dopaminergic neuron loss was determined through immunohistochemistry staining and western blot analysis of tyrosine hydroxylase (TH) expression in the substantia nigra (SN) of PD mice. Reactive oxygen species (ROS) production and malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) levels were detected through DHE staining and commercially available kits to assess oxidative stress. Pro‐inflammatory cytokine (TNF‐α, IL‐1β, and IL‐6) levels in the SN were measured via RT‐qPCR and western blot analysis. Microglial and astrocyte activation was examined through immunofluorescence staining of Iba‐1 (microglia marker) and GFAP (astrocyte marker) in the SN. The regulation of vincamine on the NF‐κB and Nrf2/HO‐1 pathway was estimated through western blot analysis. Our results showed that vincamine treatment decreased TNF‐α, IL‐1β, and IL‐6 mRNA and protein levels, reduced GFAP and Iba‐1 expression, decreased ROS production and MDA level, and increased SOD activity and GSH level in the SN of PD mice. Mechanically, vincamine repressed the phosphorylation levels of p65, IKKβ, and IκBα but enhanced the protein levels of Nrf2 and HO‐1 in PD mice. Collectively, vincamine plays a neuroprotective role in PD mouse models by alleviating neuroinflammation and oxidative damage via suppressing the NF‐κB pathway and activating the Nrf2/HO‐1 pathway.

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Section: Introductionmentioning

confidence: 99%

Vincamine alleviates brain injury by attenuating neuroinflammation and oxidative damage in a mouse model of Parkinson's disease through the NF‐κB and Nrf2/HO‐1 signaling pathways

Wang,

Chen,

Shan

2024

J Biochem & Molecular Tox

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“…Only in the USA and Europe, the annual cost of treating mental disorders is USD 1.7 trillion [1]. More than 50 million and 322 million individuals suffer from epilepsy and depression, respectively [2]. Multiple investigations have indicated that anxiety and depression might simultaneously occur [3].…”

Section: Introductionmentioning

confidence: 99%

In Vivo Neuropharmacological Effects of Neophytadiene

et al. 2023

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Neophytadiene (NPT) is a diterpene found in the methanolic extracts of Crataeva nurvala and Blumea lacera, plants reported with anxiolytic-like activity, sedative properties, and antidepressant-like actions; however, the contribution of neophytadiene to these effects is unknown. This study determined the neuropharmacological (anxiolytic-like, antidepressant-like, anticonvulsant, and sedative) effects of neophytadiene (0.1–10 mg/kg p.o.) and determined the mechanisms of action involved in the neuropharmacological actions using inhibitors such as flumazenil and analyzing the possible interaction of neophytadiene with GABA receptors using a molecular docking study. The behavioral tests were evaluated using the light–dark box, elevated plus-maze, open field, hole-board, convulsion, tail suspension, pentobarbital-induced sleeping, and rotarod. The results showed that neophytadiene exhibited anxiolytic-like activity only to the high dose (10 mg/kg) in the elevated plus-maze and hole-board tests, and anticonvulsant actions in the 4-aminopyridine and pentylenetetrazole-induced seizures test. The anxiolytic-like and anticonvulsant effects of neophytadiene were abolished with the pre-treatment with 2 mg/kg flumazenil. In addition, neophytadiene showed low antidepressant effects (about 3-fold lower) compared to fluoxetine. On other hand, neophytadiene had no sedative or locomotor effects. In conclusion, neophytadiene exerts anxiolytic-like and anticonvulsant activities with the probable participation of the GABAergic system.

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“…Neurological disorders (NDs) are increasingly prevalent and represent the leading cause of disability-adjusted life years [ 1 ]. They account for over 6% of the global disease burden [ 2 ], are the second most common cause of death worldwide with nine million deaths annually, and are exacerbated by severe health disparities.…”

Section: Introductionmentioning

confidence: 99%

Influence of Metabolic, Transporter, and Pathogenic Genes on Pharmacogenetics and DNA Methylation in Neurological Disorders

Martínez-Iglesias,

Naidoo,

Carrera

et al. 2023

Biology

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Pharmacogenetics and DNA methylation influence therapeutic outcomes and provide insights into potential therapeutic targets for brain-related disorders. To understand the effect of genetic polymorphisms on drug response and disease risk, we analyzed the relationship between global DNA methylation, drug-metabolizing enzymes, transport genes, and pathogenic gene phenotypes in serum samples from two groups of patients: Group A, which showed increased 5-methylcytosine (5mC) levels during clinical follow-up, and Group B, which exhibited no discernible change in 5mC levels. We identified specific SNPs in several metabolizing genes, including CYP1A2, CYP2C9, CYP4F2, GSTP1, and NAT2, that were associated with differential drug responses. Specific SNPs in CYP had a significant impact on enzyme activity, leading to changes in phenotypic distribution between the two patient groups. Group B, which contained a lower frequency of normal metabolizers and a higher frequency of ultra-rapid metabolizers compared to patients in Group A, did not show an improvement in 5mC levels during follow-up. Furthermore, there were significant differences in phenotype distribution between patient Groups A and B for several SNPs associated with transporter genes (ABCB1, ABCC2, SLC2A9, SLC39A8, and SLCO1B1) and pathogenic genes (APOE, NBEA, and PTGS2). These findings appear to suggest that the interplay between pharmacogenomics and DNA methylation has important implications for improving treatment outcomes in patients with brain-related disorders.

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Potential therapeutics against neurological disorders: Natural products-based drugs

Cited by 8 publications

References 10 publications

Vincamine alleviates brain injury by attenuating neuroinflammation and oxidative damage in a mouse model of Parkinson's disease through the NF‐κB and Nrf2/HO‐1 signaling pathways

Vincamine alleviates brain injury by attenuating neuroinflammation and oxidative damage in a mouse model of Parkinson's disease through the NF‐κB and Nrf2/HO‐1 signaling pathways

In Vivo Neuropharmacological Effects of Neophytadiene

Influence of Metabolic, Transporter, and Pathogenic Genes on Pharmacogenetics and DNA Methylation in Neurological Disorders

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