Identification of potential sclerostin inhibiting flavonoids from Oroxylum indicum: an insilico approach

Abstract

Flavonoids are secondary metabolites that are widely found in various medicinal plants. They are known for their medicinal benefits and have been extensively used in healthcare industries and in the management of age-related diseases. This paper focuses on flavonoids from Oroxylum indicum, a significant medicinal tree in the practice of traditional Indian medicine. O. indicum has been utilized in a variety of polyherbal formulations for the management of musculoskeletal disorders, however the mechanism of action of its bioactive flavonoids remains unknown. The present study aimed to identify the flavonoids of O. indicum with the potential to target sclerostin, an antagonist of canonical Wnt signaling pathway for the treatment of bone-related disorders. Molecular docking, coarse-grained and molecular dynamics simulations were performed to screen the major flavonoids and investigate their interaction with sclerostin. Flavonoids with highest binding affinity and interacting with at least one of the amino acids of the PNAIG motif residues were selected from docking studies and subjected to further drug likeness and ADMET screening. Further screening from coarse-grained and molecular dynamic simulations results showed that baicalein, compared to other screened flavonoids, stably binds with the important residues of the LRP6 binding site of sclerostin, resulting in pronounced structural changes in the protein. These findings suggest that baicalein from O. indicum can potentially inhibit sclerostin and can elicit skeletal protective effects, providing an insight for further in vitro and in vivo studies.

Communicated by Ramaswamy H. Sarma

Keywords:

• Sclerostin inhibitor
• flavonoids
• Oroxylum indicum
• in silico drug screening
• canonical wnt signaling
• bone-related disorders

Acknowledgement

The author (RM) sincerely thanks Vellore Institute of Technology (VIT), Vellore for providing Teaching cum research assistant (TRA) fellowship as the financial support.

Disclosure statement

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

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.