Morroniside interaction with poly (ADP-ribose) polymerase accentuates metabolic mitigation of alloxan-induced genotoxicity and hyperglycaemia: a molecular docking based in vitro and in vivo experimental therapeutic insight

J Biomol Struct Dyn. 2023 Aug 17:1-18. doi: 10.1080/07391102.2023.2246585. Online ahead of print.

Abstract

The present study tends to evaluate the possible potential of bio-active Morroniside (MOR), against alloxan (ALX)-induced genotoxicity and hyperglycaemia. In silico prediction revealed the interaction of MOR with Poly (ADP-ribose) polymerase (PARP) protein which corroborated well with experimental in vitro L6 cell line and in vivo mice models. Data revealed the efficacy of MOR in the selective activation of PARP protein and modulating other stress proteins NF-κB, and TNF-α to initiate protective potential against ALX-induced genotoxicity and hyperglycaemia. Further, the strong interaction of MOR with CT-DNA (calf thymus DNA) analyzed through CD spectroscopy, UV-Vis study and ITC data revealed the concerted action of bio-factors involved in inhibiting chromosomal aberration and micronucleus formation associated with DNA damage. Finally, MOR does not play any role in microbial growth inhibition which often occurs due to hyperglycemic dysbiosis. Thus, from the overall findings, we may conclude that MOR could be a potential drug candidate for the therapeutic management of induced-hyperglycaemia and genotoxicity.Communicated by Ramaswamy H. Sarma.

Keywords: Morroniside; PARP; alloxan; genotoxicity; in vitro model; molecular docking.