Unlocking the wound-healing potential: An integrative in silico proteomics and in vivo analysis of Tacorin, a bioactive protein fraction from Ananas comosus (L.) Merr. Stem

Abstract

Tacorin, a bioactive protein fraction derived from pineapple stem (Ananas comosus), has emerged as a promising therapeutic agent for wound healing. This study employs an integrated approach, combining in silico proteomics and in vivo investigations, to unravel the molecular mechanisms underlying Tacorin's wound healing properties. In the domain of in silico proteomics, the composition of Tacorin is elucidated through LC/MS-MS protein sequencing, revealing ananain (23.77 kDa) and Jacalin-like lectin (14.99 kDa) as its predominant constituents. Molecular protein-protein docking simulations unveil favorable interactions between Tacorin's components and key regulators of wound healing, including TGF-β, TNF-α, and MMP-2. The calculated free binding energies indicate strong binding affinities between Tacorin proteins and their target receptors. Specifically, ananain demonstrates a binding affinity of −12.2 kcal/mol with TGF-β, suggesting its potential as a potent activator of TGF-β-mediated signaling, while Jacalin-like lectin exhibits the most favorable binding affinity of −8.7 kcal/mol with TNF-α. Subsequent 100 ns molecular dynamics (MD) simulations provide insights into the dynamic behavior and stability of Tacorin-receptor complexes, shedding light on the molecular determinants of Tacorin's therapeutic effects. Complementing the in silico analyses, in vivo studies evaluate Tacorin's efficacy in wound healing using skin and uterine incision models. Tacorin treatment accelerates wound closure and promotes tissue repair in both models, as evidenced by macroscopic observations and histological assessments. Overall, this study provides compelling evidence of Tacorin's therapeutic potential in wound healing and underscores the importance of elucidating its molecular mechanisms for further development and clinical translation.