<![CDATA[Insulin resistance underlies major metabolic disorders and is driven by chronic low-grade inflammation and oxidative stress that impair insulin signalling in peripheral tissues. Natural compounds with anti-inflammatory properties represent promising strategies to modulate this pathological axis, yet the molecular targets mediating these effects often remain unclear. This study employed an integrative in silico approach combining target fishing and molecular docking to elucidate the potential molecular mechanisms of 6-shogaol, a bioactive constituent of Zingiber officinale, in insulin resistance. Target prediction analysis identified arachidonate 5-lipoxygenase (ALOX5) as the highest-probability molecular target of 6-shogaol. Physicochemical profiling indicated favourable oral bioavailability and drug-likeness properties. Molecular docking analysis against ALOX5 (PDB ID: 6N2W), validated by redocking (RMSD 1.1 Å), demonstrated that 6-shogaol binds effectively within the enzyme active site and exhibits a more favourable binding affinity than the reference inhibitors zileuton and masoprocol. The predicted interaction supports 6-shogaol's ability to suppress leukotriene-mediated inflammatory signalling implicated in insulin resistance. Collectively, these findings suggest that 6-shogaol may act as a multi-target natural modulator of inflammation and oxidative stress, with ALOX5 emerging as a key therapeutic node in insulin resistance.]]>
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