Astragaloside IV protects against tacrolimus-induced nephrotoxicity by inhibiting mTOR to activate TFEB and restore autophagy, identifying the mTOR-TFEB-GADD45alpha axis as a calcineurin-independent therapeutic target in TICN.
| Evidence tier | D Mechanistic / in vitro / review |
| Study type | 5 - Mechanistic / In Vitro |
| Model system | In vitro (renal cell lines) |
| Journal | Journal of Agricultural and Food Chemistry |
| Year | 2026 |
| Peer reviewed | Yes |
| Source | DOI 10.1021/acs.jafc.5c17921 · PMID 42438242 |
Tacrolimus-induced chronic nephrotoxicity (TICN) is mediated in part through calcineurin-dependent TFEB phosphorylation. Astragaloside IV (AS-IV) significantly reactivated TFEB and restored tacrolimus-impaired renal function, autophagy flux, and DNA repair. TFEB knockdown reversed AS-IV effects. AS-IV does not affect calcineurin but inhibits mTOR (which phosphorylates TFEB Ser211), thereby activating TFEB via the mTOR-TFEB-GADD45alpha axis.
| Intervention | Astragaloside IV |
| Target | mTOR / TFEB / GADD45alpha / autophagy |
| Model | In vitro (renal cells) |
| Effect | TFEB reactivation, restored autophagy flux, improved renal function markers, attenuation of nephrotoxicity |