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Salvianic acid A alleviates hepatic fibrosis by inhibiting the AKT1/NF-κB axis.

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Τίτλος: Salvianic acid A alleviates hepatic fibrosis by inhibiting the AKT1/NF-κB axis.
Συγγραφείς: Hu J; State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, 122 Luoshi Road, Wuhan, 430070, China; Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases, School of Chemistry, Chemical Engineering and Life Science, Wuhan Univ ersity of Technology, 122 Luoshi Road, Wuhan, 430070, China., Zhang J; Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases, School of Chemistry, Chemical Engineering and Life Science, Wuhan Univ ersity of Technology, 122 Luoshi Road, Wuhan, 430070, China., Ge X; Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases, School of Chemistry, Chemical Engineering and Life Science, Wuhan Univ ersity of Technology, 122 Luoshi Road, Wuhan, 430070, China., Li S; Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases, School of Chemistry, Chemical Engineering and Life Science, Wuhan Univ ersity of Technology, 122 Luoshi Road, Wuhan, 430070, China., Li X; Wuhan Guangxing Scientific Research Co., LTD, 388 Gaoxin 2 Road, Wuhan, 430206, China., Zhang T; Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases, School of Chemistry, Chemical Engineering and Life Science, Wuhan Univ ersity of Technology, 122 Luoshi Road, Wuhan, 430070, China., Li X; Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases, School of Chemistry, Chemical Engineering and Life Science, Wuhan Univ ersity of Technology, 122 Luoshi Road, Wuhan, 430070, China., He M; Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases, School of Chemistry, Chemical Engineering and Life Science, Wuhan Univ ersity of Technology, 122 Luoshi Road, Wuhan, 430070, China. Electronic address: menghe@whut.edu.cn., Gao G; State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, 122 Luoshi Road, Wuhan, 430070, China; Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases, School of Chemistry, Chemical Engineering and Life Science, Wuhan Univ ersity of Technology, 122 Luoshi Road, Wuhan, 430070, China. Electronic address: gbgao@whut.edu.cn., Sun T; State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, 122 Luoshi Road, Wuhan, 430070, China; Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases, School of Chemistry, Chemical Engineering and Life Science, Wuhan Univ ersity of Technology, 122 Luoshi Road, Wuhan, 430070, China. Electronic address: suntl@whut.edu.cn.
Πηγή: European journal of pharmacology [Eur J Pharmacol] 2026 Oct 28; Vol. 1034, pp. 179304. Date of Electronic Publication: 2026 Sep 03.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 1254354 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0712 (Electronic) Linking ISSN: 00142999 NLM ISO Abbreviation: Eur J Pharmacol Subsets: MEDLINE
Imprint Name(s): Publication: 2005- : Amsterdam : Elsevier Science
Original Publication: Amsterdam, North Holland Pub. Co.
Ιατρικοί όροι (MeSH): Proto-Oncogene Proteins c-akt*/metabolism , Proto-Oncogene Proteins c-akt*/antagonists & inhibitors , NF-kappa B*/metabolism , NF-kappa B*/antagonists & inhibitors , Lactates*/pharmacology , Lactates*/therapeutic use , Liver Cirrhosis*/drug therapy , Liver Cirrhosis*/pathology , Liver Cirrhosis*/chemically induced , Liver Cirrhosis*/metabolism , Antifibrotic Agents*/pharmacology , Antifibrotic Agents*/therapeutic use, Signal Transduction/drug effects ; Hepatic Stellate Cells/drug effects ; Hepatic Stellate Cells/pathology ; Hepatic Stellate Cells/metabolism ; Liver/drug effects ; Liver/pathology ; Transforming Growth Factor beta1/pharmacology ; Animals ; Mice ; Male ; Carbon Tetrachloride ; Humans ; Mice, Inbred C57BL ; Cell Line ; Molecular Docking Simulation
Περίληψη: Hepatic fibrosis (HF) is a crucial and reversible stage, yet there is a paucity of effective clinical antifibrotic drugs. Salvianic acid A (SAA) has shown antifibrotic potential in preliminary studies; however, its molecular mechanisms and potential targets remain incompletely understood. To evaluate the therapeutic efficacy and mechanisms of SAA in mitigating HF, we employed a carbon tetrachloride (CCl4)-induced HF mouse model. In parallel, we used transforming growth factor beta 1 (TGF-β1)-stimulated LX-2 cells and primary mouse hepatic stellate cells (HSCs) for in vitro studies. In CCl4-induced mice, SAA markedly improved liver function and suppressed HF, as evidenced by significant reduction in α-smooth muscle actin and collagen I expression and alleviation of inflammatory response. Similar antifibrotic and anti-inflammatory effects were observed in vitro. To investigate the targets and mechanism of SAA in HF, we employed network pharmacology, molecular docking, molecular dynamics simulations, and microscale thermophoresis. We found that SAA was predicted to interact with the allosteric pocket of RAC-alpha serine/threonine-protein kinase 1 (AKT1), accompanied by inhibition of AKT1 phosphorylation and the downstream nuclear factor-kappa B (NF-κB) signaling. To further explore the involvement of AKT1 in SAA's antifibrotic effects, we used the AKT activator SC79. In CCl4-induced mice, SC79 partly reversed the antifibrotic effects of SAA. Consistently, we observed that SC79 partially restored the inflammatory and fibrotic markers in TGF-β1-simulated HSCs, counteracting the inhibitory efficacy of SAA. Our findings suggest that SAA exerts antifibrotic effects in part through suppression of the AKT1/NF-κB axis and may represent a promising therapeutic candidate for HF.
(Copyright © 2026 Elsevier B.V. All rights reserved.)
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Contributed Indexing: Keywords: AKT1 inhibitor; Hepatics fibrosis; NF-κB signaling; Salvianic acid A
Substance Nomenclature: EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
0 (NF-kappa B)
0 (Lactates)
4GF33A5PAJ (3,4-dihydroxyphenyllactic acid)
CL2T97X0V0 (Carbon Tetrachloride)
EC 2.7.11.1 (Akt1 protein, mouse)
0 (Antifibrotic Agents)
0 (Transforming Growth Factor beta1)
Entry Date(s): Date Created: 20260903 Date Completed: 20260919 Latest Revision: 20260919
Update Code: 20260920
DOI: 10.1016/j.ejphar.2026.179304
PMID: 42692281
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1879-0712
DOI:10.1016/j.ejphar.2026.179304