Mechanistic Elucidation of the Anti-Ageing Effects of Dendrobium officinale via Network Pharmacology and Experimental Validation

<i>Dendrobium officinale</i> (Orchidaceae) is a commonly used medicinal and edible herb. Although its anti-ageing properties have been demonstrated, the underlying mechanisms remain unclear. We employed network pharmacology and molecular biology techniques to systematically explore its anti-ageing mechanisms. An ageing model was established using D-galactose-induced Kunming mice. <i>D. officinale</i> significantly ameliorated ageing-related symptoms, including behavioural impairment and organ index reduction. It enhanced antioxidant capacity by increasing serum T-AOC levels and restoring renal activities of key antioxidant enzymes (SOD, GSH-Px, CAT) while reducing MDA; it suppressed serum TNF-α levels, indicating anti-inflammatory effects. Histopathological examination revealed that <i>D. officinale</i> alleviated D-galactose-induced renal damage, including tubular cell swelling and glomerular capsule widening. Network pharmacology identified 8 core active compounds (e.g., 5,7-dihydroxyflavone, naringenin) and 10 key targets (e.g., HSP90AA1, EGFR, MAPK3). KEGG analysis highlighted pathways including neuroactive ligand-receptor interaction, cAMP signalling, and calcium signalling. Molecular docking confirmed strong binding affinities between core compounds and key targets. Western blotting and immunohistochemistry validated that <i>D. officinale</i> upregulated EGFR, HSP90AA1, ERK, and GAPDH expression in renal tissues. In summary, <i>D. officinale</i> exerts anti-ageing effects by modulating oxidative stress, suppressing inflammation, and regulating multiple signalling pathways. Our findings provide a scientific rationale for its application in anti-ageing interventions.