Academic Journal
Salvianolic acid C alleviates acute kidney injury by restoring fructose-1,6-bisphosphatase 1-mediated gluconeogenesis.
| Τίτλος: | Salvianolic acid C alleviates acute kidney injury by restoring fructose-1,6-bisphosphatase 1-mediated gluconeogenesis. |
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| Συγγραφείς: | Chen J; Department of Nephrology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China., Li Y; Department of Nephrology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China., Zhou P; Department of Nephrology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China., Zou S; Department of Nephrology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China., Zhao J; Department of Nephrology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China., Wu M; Key Laboratory of Liver and Kidney Diseases, Ministry of Education, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, TCM Institute of Kidney Disease of Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China., Wang L; Department of Nephrology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China. |
| Πηγή: | Renal failure [Ren Fail] 2026 Dec; Vol. 48 (1), pp. 2629902. Date of Electronic Publication: 2026 Mar 08. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Informa Healthcare Country of Publication: England NLM ID: 8701128 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1525-6049 (Electronic) Linking ISSN: 0886022X NLM ISO Abbreviation: Ren Fail Subsets: MEDLINE |
| Imprint Name(s): | Publication: London : Informa Healthcare Original Publication: New York, N.Y. : M. Dekker, c1987- |
| Ιατρικοί όροι (MeSH): | Acute Kidney Injury*/drug therapy , Acute Kidney Injury*/pathology , Acute Kidney Injury*/chemically induced , Acute Kidney Injury*/metabolism , Fructose-Bisphosphatase*/metabolism , Gluconeogenesis*/drug effects , Reperfusion Injury*/drug therapy , Reperfusion Injury*/complications , Polyphenols*/pharmacology , Alkenes*/pharmacology , Lactates*/pharmacology, Cisplatin/toxicity ; Forkhead Box Protein O1/metabolism ; Apoptosis/drug effects ; Kidney/pathology ; Kidney/drug effects ; Drugs, Chinese Herbal/pharmacology ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism ; Salvia miltiorrhiza/chemistry ; Animals ; Male ; Mice ; Mice, Inbred C57BL ; Disease Models, Animal ; Molecular Docking Simulation ; Benzofurans |
| Περίληψη: | This research was targeted to investigate the pharmacological effects and mechanisms of Salvianolic acid C (SAC), a natural compound extracted from the Chinese traditional herbal Danshen (Salviae Miltiorrhizae Radix et Rhizoma), in acute kidney injury (AKI). Male C57BL/6J mice were used to create animal models and SAC (10 mg/kg, i.p.) or saline was administered 24 h before modeling. In both ischemia reperfusion injury (IRI) induced AKI and cisplatin (Cis) induced AKI models, SAC significantly alleviated the decline of renal function and destruction of renal pathological structure, which were correlated with reduced expression of renal injury markers and inhibited renal cell apoptosis. Non-targeted metabolomics sequencing revealed that the gluconeogenesis pathway was downstream of the renal protective effect of SAC in AKI. Further experiments revealed that the expression of key gluconeogenic enzyme fructose-1,6-bisphosphatase 1 (FBP1) was significantly decreased in AKI kidneys. AKI induced the reduction in glucose levels from serum and increase in lactate levels from serum and renal tissue. All of these metabolic changes were improved after the SAC treatment. The protective effects of SAC were reversed by an FBP1 inhibitor. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and forkhead box O1 (FOXO1), identified as gluconeogenesis promoting factor, were decreased after injection of cisplatin, which were reversed by SAC. Finally, molecular docking and SPR experiments revealed the direction interaction between FBP1 and SAC. Collectively, SAC possibly exerts its effect through a dual regulatory mechanism: by modulating the FOXO1/PGC1α/FBP1 signaling axis and via direct interaction with FBP1. |
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| Contributed Indexing: | Keywords: Acute kidney injury; cisplatin; fructose-1, 6-bisphosphatase 1; gluconeogenesis; ischemia reperfusion injury; salvianolic acid C Local Abstract: [plain-language-summary] SAC alleviates both IRI and Cisplatin induced AKI.SAC improves cisplatin-induced AKI through FBP1-mediated gluconeogenesis.SAC modulates FBP1-mediated gluconeogenesis through a dual regulatory mechanism. |
| Substance Nomenclature: | EC 3.1.3.11 (Fructose-Bisphosphatase) Q20Q21Q62J (Cisplatin) I16H9Z53ZL (salvianolic acid C) 0 (Forkhead Box Protein O1) 0 (Polyphenols) 0 (Drugs, Chinese Herbal) 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha) 0 (Foxo1 protein, mouse) 0 (Alkenes) 0 (Ppargc1a protein, mouse) 0 (Lactates) 0 (Benzofurans) |
| Entry Date(s): | Date Created: 20260308 Date Completed: 20260710 Latest Revision: 20260813 |
| Update Code: | 20260813 |
| PubMed Central ID: | PMC12973791 |
| DOI: | 10.1080/0886022X.2026.2629902 |
| PMID: | 41795894 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1525-6049 |
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| DOI: | 10.1080/0886022X.2026.2629902 |