Astragaloside IV Mitigates Tacrolimus-Induced Chronic Nephrotoxicity by Regulating the mTOR-TFEB-GADD45alpha Pathway

Ping Gao, Xinwei Cheng, Rui Xu, Xinyu Huang, Jianqiao Wang, Maochang Liu, Xiuxun Wu, Xinlei Guan, Yunzhou Chen, Zhenpeng Qiu · 2026 · Journal of Agricultural and Food Chemistry · Atlas ID GAO2026

What this study shows

Astragaloside IV protects against tacrolimus-induced nephrotoxicity by inhibiting mTOR to activate TFEB and restore autophagy, nominating the mTOR-TFEB-GADD45alpha axis as a calcineurin-independent candidate therapeutic target (preclinical; no human data) in TICN.

Abstract

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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.

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At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: In vitro (renal cell lines)) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
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
Record last updated	2026-07-29
Source	DOI 10.1021/acs.jafc.5c17921 · PMID 42438242

Extracted findings

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

In the Atlas

Cite this paper

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Ping Gao, Xinwei Cheng, Rui Xu, Xinyu Huang, Jianqiao Wang, Maochang Liu, Xiuxun Wu, Xinlei Guan, Yunzhou Chen, & Zhenpeng Qiu (2026). Astragaloside IV Mitigates Tacrolimus-Induced Chronic Nephrotoxicity by Regulating the mTOR-TFEB-GADD45alpha Pathway. Journal of Agricultural and Food Chemistry. https://doi.org/10.1021/acs.jafc.5c17921

@article{GAO2026,
  author       = {Ping Gao and Xinwei Cheng and Rui Xu and Xinyu Huang and Jianqiao Wang and Maochang Liu and Xiuxun Wu and Xinlei Guan and Yunzhou Chen and Zhenpeng Qiu},
  title        = {{Astragaloside IV Mitigates Tacrolimus-Induced Chronic Nephrotoxicity by Regulating the mTOR-TFEB-GADD45alpha Pathway}},
  journal      = {Journal of Agricultural and Food Chemistry},
  year         = {2026},
  doi          = {10.1021/acs.jafc.5c17921},
  note         = {PMID: 42438242},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record GAO2026) [Data set]. https://mtor-atlas.org/study/GAO2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_GAO2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record GAO2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/GAO2026/},
  doi          = {10.5281/zenodo.22059963}
}