A protein-miRNA biomic analysis approach to explore neuroprotective potential of nobiletin in human neural progenitor cells (hNPCs)

Sadaf Jahan; Uzair Ahmad Ansari; Ankur Kumar Srivastava; Sahar Aldosari; Nessrin Ghazi Alabdallat; Arif Jamal Siddiqui; Andleeb Khan; Hind Muteb Albadrani; Sana Sarkar; Bushra Khan; Mohd Adnan; Aditya Bhushan Pant

doi:10.3389/fphar.2024.1343569

A protein-miRNA biomic analysis approach to explore neuroprotective potential of nobiletin in human neural progenitor cells (hNPCs)

Front Pharmacol. 2024 Jan 25:15:1343569. doi: 10.3389/fphar.2024.1343569. eCollection 2024.

Authors

Sadaf Jahan^#^{1

2}, Uzair Ahmad Ansari^#^{3

4}, Ankur Kumar Srivastava^#³, Sahar Aldosari^{1

2}, Nessrin Ghazi Alabdallat^{1

2}, Arif Jamal Siddiqui⁵, Andleeb Khan⁶, Hind Muteb Albadrani⁷, Sana Sarkar³, Bushra Khan³, Mohd Adnan⁵, Aditya Bhushan Pant^{3

4}

Affiliations

¹ Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Majmaah, 11952, Saudi Arabia.
² Health and Basic Sciences Research Center, Majmaah University, 11952 Majmaah, Saudi Arabia.
³ Developmental Toxicology Laboratory, Systems Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhavan, 31, Mahatma Gandhi Marg, P.O. Box No. 80, Lucknow 226001, Uttar Pradesh, India.
⁴ Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
⁵ Department of Biology, College of Science, University of Hail, Hail, Saudi Arabia.
⁶ Department of Biosciences, Faculty of Science, Integral University, Lucknow, Uttar Pradesh 226026, India.
⁷ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Imam Abdulrahman Bin Faisal University, Dammam, Eastern Province 34212, Saudi Arabia.

^# Contributed equally.

Abstract

Chemical-induced neurotoxicity is increasingly recognized to accelerate the development of neurodegenerative disorders (NDs), which pose an increasing health burden to society. Attempts are being made to develop drugs that can cross the blood-brain barrier and have minimal or no side effects. Nobiletin (NOB), a polymethoxylated flavonoid with anti-oxidative and anti-inflammatory effects, has been demonstrated to be a promising compound to treat a variety of NDs. Here, we investigated the potential role of NOB in sodium arsenate (NA)-induced deregulated miRNAs and target proteins in human neural progenitor cells (hNPCs). The proteomics and microRNA (miRNA) profiling was done for different groups, namely, unexposed control, NA-exposed, NA + NOB, and NOB groups. Following the correlation analysis between deregulated miRNAs and target proteins, RT-PCR analysis was used to validate the selected genes. The proteomic analysis showed that significantly deregulated proteins were associated with neurodegeneration pathways, response to oxidative stress, RNA processing, DNA repair, and apoptotic process following exposure to NA. The OpenArray analysis confirmed that NA exposure significantly altered miRNAs that regulate P53 signaling, Wnt signaling, cell death, and cell cycle pathways. The RT-PCR validation studies concur with proteomic data as marker genes associated with autophagy and apoptosis (HO-1, SQSTM1, LC-3, Cas3, Apaf1, HSP70, and SNCA1) were altered following NA exposure. It was observed that the treatment of NOB significantly restored the deregulated miRNAs and proteins to their basal levels. Hence, it may be considered one of its neuroprotective mechanisms. Together, the findings are promising to demonstrate the potential applicability of NOB as a neuroprotectant against chemical-induced neurotoxicity.

Keywords: human neural progenitor cells; miRNA; neurodegeneration; neuroprotection; nobiletin; proteomics; sodium arsenate.

Grants and funding

The authors extend their appreciation to the deputyship for research & innovation, ministry education in Saudi Arabia for funding this research work through the project number (IFP-2022-03).