Inhibition of γH2AX, COX-2 and regulation of antioxidant enzymes in MPP+-exposed SH-SY5Y cells pre-treated with rutin

Enogieru, Adaze Bijou; Haylett, William; Hiss, Donavon C; Ekpo, Okobi Eko

doi:10.1007/s11011-021-00746-z

Cited by 9 publications

(8 citation statements)

References 53 publications

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“…Further exploration of this exciting field in this model may elucidate the mechanisms of pathogenesis in PD. Because exploration of the new and reliable biomarkers of PD can eventually lead to the development of new treatment strategies (Enogieru et al, 2021), those manipulations such as using of inhibitor of DNA damage targeting the activation of DDR have potential intervention for the treatment of PD.…”

Section: Discussionmentioning

confidence: 99%

“…The neural-specific vesicular monoamine transporter 2 (VMAT2) is a transmembrane protein and is a key regulator of monoamine homeostasis by implication in monoamine storage, protection of neurotransmitters from oxidation, and control of quantal secretion of these neurotransmitters (Erickson et al, 1992). Therefore, functional failure of VMAT2 has been recognized as a contributor to the pathology of PD (Lotharius & Brundin, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Upregulated DNA Damage-Linked Biomarkers in Parkinson's Disease Model Mice

et al. 2023

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Oxidative stress-induced DNA damage has been considered to constitute a unifying pathogenesis in the development of Parkinson's disease (PD). In the present study, multiple measurement methods were applied to examine the expression of DNA damage markers in the brain of the vesicular monoamine transporter 2 transgenic mice (VMAT2 Lo), a PD animal model. The results demonstrated that mainly in the substantia nigra (SN) and locus coeruleus (LC) of VMAT2 Lo mice at the ages of 18 and 23 months, there was a significant increase in the protein levels of phosphor-ataxia telangiectasia mutated (pATM), as well as ATM and RAD 3-related (pATR) two DNA damage sensors, and γ-H2A histone family member X (γ-H2AX), a DNA damage marker of double-strand breaks (DSBs). Furthermore, these alterations were accompanied by a significant elevation of mRNA and protein levels of Cav1.2 and Cav1.3, two voltage-gated Ca2+ channel proteins, and modulator of calcium homeostasis in the SN and LC. Finally, the measurements of TUNEL assay and immunostaining in the brain regions confirmed the presence of apoptosis and a marked increase of immunoreactive 8-oxo-7,8-dihydro-2′dihydroguanosine (8-OHdG) and p53-binding protein 1 (53BP1), two DNA lesion indicators induced by oxidative stress. These novel findings are coincident with the observations previously reported in PD patients and PD animal models, and provide the evidence for the features of DNA damage involved in pathogenesis of PD and feasibility of this model for investigation of PD. Summary Statement The present study examined expression of DNA damage markers in VMAT2 Lo PD model mice. The results demonstrate there is a significant increase in these DNA damage markers mostly in the brain regions of 18- and 23-month-old model mice, indicating oxidative stress-induced DNA lesion is an important pathologic feature of this mouse model.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Upregulated DNA Damage-Linked Biomarkers in Parkinson's Disease Model Mice

et al. 2023

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“…In an earlier study, psoralen isolated from Dystaenia takeshimana was reported to inhibit COX-2/5-LOX in mouse bone marrow-derived mast cells [33]. A few studies suggest that psoralen derivatives [34,35] and rutin [36][37][38] possess COX-2 inhibitory activity. For instance, 5-methoxy-8-(2-hydroxy-3-buthoxy-3-methylbutyloxy)-psoralen from Angelica dahurica was reported to inhibit induction of COX-2 in bone marrow-derived mast cells [34].…”

Section: Discussionmentioning

confidence: 99%

Himalayan Ficus palmata L. Fruit Extract Showed In Vivo Central and Peripheral Analgesic Activity Involving COX-2 and Mu Opioid Receptors

Tewari

Gupta

Bawari

et al. 2021

Plants

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Analgesic drugs like morphine and non-steroidal anti-inflammatory drugs exhibit several harmful effects. Here, we show for the first time the analgesic activity of Ficus palmata L. fruit extract (FPFE) on different analgesic rat models along with the in silico studies of some of the main phytochemicals of this plant. We performed in vivo pain models, along with in silico docking studies against the active site of COX-2 protein and mu-opioid receptors. A significant (p < 0.05) analgesic effect of FPFE was observed, and it was found that rutin has good pose and score as compared to diclofenac and morphinan antagonist (X-ligand), and psoralen has binding affinity almost equal to diclofenac, but a lower binding affinity as compared to rutin. The results proved that F. palmata fruits have the potential to ameliorate painful conditions.

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“…Recent studies have claimed how 1-methyl-4-phenylpyridinium (MPP + )has been used in the induction of dopaminergic cell death [32]. In this study, 0.5 mmol of MPP + was induced to the SHSY5Y cell line to cause toxicity to the cells at 20 C, and the treatment was provided by the top % cell viability compounds HBU-2, and HBU-4 with a dose selectivity of 125 µg/ml.…”

Section: Neuroprotection Of Hbu-2 and Hbu-4mentioning

confidence: 99%

In Silico, Preparation and in Vitro Studies of Benzylidene-Based Hydroxy Benzyl Urea Derivatives as Free Radical Scavengers in Parkinson’s Disease

CHAND,

KANDY,

PRASAD

et al. 2024

Int J App Pharm

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Objective: The study focuses on the benzylidene-based hydroxy benzyl urea derivative as free radical scavengers in PD. Methods: The derivatives were designed, synthesized, and characterized using FTIR, 1H, 13C-NMR, and Mass spectrometry. Further in vitro studies were performed on the SHSY-5Y cell lines. Molecular docking and molecular dynamic studies were performed at 100 ns to predict the binding affinity and stability of the ligand/protein complex. Results: Among the nine derivatives, compounds HBU-2, and HBU-4were found to have the highest binding affinity-9.699 kcal/mol, and-9.020 kcal/mol with the amino acid interactions SER 149, PHE 157, ARG 158, SER 159, ILE 230, and ASP 231. Further, this HBU-1 to HBU-9 derivatives were produced using a synthesis route. The neurotoxicity studies were performed on the SHSY-5Y cells, where the % cell viability for the compound HBU-2, and HBU-4 was 91.22 %, and 90.42 %at a minimal concentration of 125 µg/ml with a p-value<0.011. Further, the cell counts and LDH assay for the compound HBU-2, and HBU-4 with MPP+treatment predicted 0.72-fold change and 0.66-fold change. The ROS % activity was also measured for compounds HBU-2 and HBU-4 in conjunction with the MPP+induction. In the SHSY-5Y cell line, compound HBU-2 downregulated the ROS level to 45%. Conclusion: The synthesized compounds were found to have good free radical scavenging properties on SHSY-5Y neuroblastoma cell lines, considering these derivatives could be further assessed using appropriate PD models.

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Inhibition of γH2AX, COX-2 and regulation of antioxidant enzymes in MPP+-exposed SH-SY5Y cells pre-treated with rutin

Cited by 9 publications

References 53 publications

Upregulated DNA Damage-Linked Biomarkers in Parkinson's Disease Model Mice

Upregulated DNA Damage-Linked Biomarkers in Parkinson's Disease Model Mice

Himalayan Ficus palmata L. Fruit Extract Showed In Vivo Central and Peripheral Analgesic Activity Involving COX-2 and Mu Opioid Receptors

In Silico, Preparation and in Vitro Studies of Benzylidene-Based Hydroxy Benzyl Urea Derivatives as Free Radical Scavengers in Parkinson’s Disease

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