Berberine chloride (dual topoisomerase I and II inhibitor) modulate mitochondrial uncoupling protein (UCP1) in molecular docking and dynamic with in-vitro cytotoxic and mitochondrial ATP production

Abstract

Obesity initiates numerous diseases like cardiovascular, metabolic, and type 2 diabetes, and obesity is a vital cause of death worldwide. Plants are necessary to the source of life. Several drug compounds isolated from plants are called phytochemicals which are safe, effective drug moieties to treat several diseases. Berberine chloride is a dual topoisomerase I and II inhibitor, that exhibited potent antitumor activities against several malignancies. However, the effect of Berberine on mitochondria remains unknown. The focus of this study was to determine the role of Berberine on mitochondrial uncoupling protein (UCP1), ATP production, and cytotoxic effect of HEK293T cell at a time and dose-dependent manner analysis by CCK8 assay. The upregulation of mitochondrial UCP1 gene expression reduces adipocyte content by initiating thermogenesis. In this study, berberine chloride significantly up-regulates UCP1 gene expression in brown adipocytes. AT 10 µM concentration of Berberine 48 h treatment demonstrated significant cell death. The decreased level of ATP production leads to mitochondrial uncoupling. Initiate thermogenesis reducing fat droplets in adipocytes. The first time, we used molecular docking and dynamic of Berberine with UCP1 gene in this study and revealed therapeutic potential of Berberine via modulation of mitochondrial UCP1 gene. Further investigation will reveal new insight into mechanisms to treat metabolic-related diseases.

Communicated by Ramaswamy H. Sarma

Keywords:

• Mitochondrial function
• ATP production
• Cell viability
• Molecular docking and Molecular dynamic
• Metabolic diseases
• and Berberine

Acknowledgments

The authors are also grateful to the Department of Endocrinology and Metabolism, Shandong University for giving all kinds of facilities to finish this research work.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Conceptualization, MRF; methodology, MRF; software, MRF, MA; validation, MA., and MRF; formal analysis, MRF; investigation, MRF.; resources, SYF., MRF., and MA.; data curation, MRF., MA; writing—original draft preparation, MRF., writing—review and editing, MRF; visualization, MRF.; supervision, MRF, SYF.; project administration, MRF and SYF; funding acquisition, SYF. All the other authors was involved in the experiment or drafting manuscript. All authors have read and agreed to the published version of the manuscript.

Data availability statement

The available data are presented in the manuscript.

Additional information

Funding

This study was supported by grants from the National Natural Science Foundation (81922016, 81870607) and the Shandong Provincial Natural Science Foundation (ZR2019JQ25) of China.