In-vivo Studies and Molecular Docking of Modeled Mus musculas 8S Lipoxygenase Protein Using Some Natural Bioactive Compounds

Abstract

Mus musculus 8S Lipoxygenase (8SLOX) is expressed in suprabasal keratinocytes, and the massive accumulation of 8-HETE, the product of 8SLOX, plays a significant role in epidermal tumor development in papillomas and induces chromosomal alterations in basal keratinocytes. It has also been observed to be unregulated in inflammatory dermatoses. In an attempt to discover potent 8S LOX inhibitors, 5 bioactive compounds, viz., anthraquinone, celastrine, curcumin, gilloin and tinosporide, derived from different medicinal plants, were selected for the molecular docking study against 8S LOX protein. NDGA, a known lipoxygenase inhibitor was used as a standard. A 3D structure of Mus musculus Arachidonate 8S LOX protein (PMDB ID: PM0078979) was predicted using comparative homology modeling with homologous template (PDB ID: 3V98), retrieved from PDB resources. Conserved active site residues Gln109 and Asn174 were found to be involved in interaction with all drugs including NDGA. Docking studies revealed that celastrine has the best interaction followed by gilloin and curcumin, all of which performed much better than NDGA. Gene expression pattern in the skin of the control mice, IMQ-treated and phytocompound-treated psoriasis-like dermatitis inducedmice revealed that the curcumin and gillion compound were more influential in downregulating 8S lipoxygenase gene than the other compound used in this study. The results suggested that these potent compounds can efficiently inhibit 8S LOX protein and therefore can prove to be promising candidates in drug development for the treatment of inflammatory disorders of skin like psoriasis. © 2021, The National Academy of Sciences, India.