Allicin suppresses TNF/NF-κB pathway, inhibiting kidney stone formation in rat model

Nephrolithiasis, or kidney stone disease, is a highly prevalent urological disorder marked by significant incidence and frequent recurrence, posing a substantial burden on healthcare systems. Current treatments often focus on symptom management or surgical intervention, but lack effective strategies to prevent recurrence by addressing underlying mechanisms. Inflammatory responses and crystal aggregation are recognized as critical factors in stone pathogenesis. Allicin, a compound derived from garlic, possesses diverse pharmacological properties, yet its precise role and mechanisms in mitigating kidney stone formation have remained largely unexplored, representing a key gap this research addresses.

Researchers employed a multi-pronged approach, starting with network pharmacology to identify potential targets and pathways. Molecular docking simulations were then used to assess binding affinities. In vitro experiments utilized calcium oxalate-damaged HK-2 cells, treated with Allicin 200 µmol/L, to evaluate cellular responses such as viability and inflammatory factor levels. For in vivo validation, an ethylene glycol-induced nephrolithiasis rat model was established. Animals were treated with Allicin, and primary endpoints included assessments of kidney damage and calcium oxalate deposition, comparing treated groups to control arms.

Integrated network pharmacological screening revealed 46 overlapping targets shared by allicin and nephrolithiasis. Among these, TNF was identified as the central effector target, with the TNF/NF-κB signaling axis determined to be the dominant pathway mediating allicin's protective effects against renal crystal formation. Molecular docking confirmed that allicin moderately binds to TNF with a binding energy of -2.05 kcal/mol. In vitro, treatment with Allicin 200 µmol/L significantly improved the viability of injured HK-2 cells and decreased the levels of inflammatory factors. The most impactful finding from the in vivo studies was:

Allicin treatment effectively reduced kidney damage and calcium oxalate deposition in the ethylene glycol-induced nephrolithiasis rat model, providing strong preclinical evidence for its efficacy. These results collectively indicate that allicin alleviates kidney stones by inhibiting the TNF/NF-κB pathway.