Academic Journal
Προβολή σε EDS
Συνδεδεμένο Πλήρες Κείμενο

Salvianolic Acid A Relieves Acute Lung Injury by Promoting the Expression of FOXO1 and Activating Autophagy Through the Inhibition of miR-217-5p.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Salvianolic Acid A Relieves Acute Lung Injury by Promoting the Expression of FOXO1 and Activating Autophagy Through the Inhibition of miR-217-5p.
Συγγραφείς: Liu X; Department of Rehabilitation Medicine, Yunnan Qujing Central Hospital (Qujing No.1 Hospital), Qujing, 655000, Yunnan, China., Shi Y; Department of Rehabilitation Medicine, Yunnan Qujing Central Hospital (Qujing No.1 Hospital), Qujing, 655000, Yunnan, China., Huang L; Department of Rehabilitation Medicine, Yunnan Qujing Central Hospital (Qujing No.1 Hospital), Qujing, 655000, Yunnan, China., Chen H; Department of Rehabilitation Medicine, Yunnan Qujing Central Hospital (Qujing No.1 Hospital), Qujing, 655000, Yunnan, China., Fan R; Department of Rehabilitation Medicine, Yunnan Qujing Central Hospital (Qujing No.1 Hospital), Qujing, 655000, Yunnan, China., Zhang H; Department of Rehabilitation Medicine, Yunnan Qujing Central Hospital (Qujing No.1 Hospital), Qujing, 655000, Yunnan, China., Li Q; Department of Rehabilitation Medicine, Yunnan Qujing Central Hospital (Qujing No.1 Hospital), Qujing, 655000, Yunnan, China., Yan N; Department of Rehabilitation Medicine, Yunnan Qujing Central Hospital (Qujing No.1 Hospital), Qujing, 655000, Yunnan, China., He M; Department of Rehabilitation Medicine, Yunnan Qujing Central Hospital (Qujing No.1 Hospital), Qujing, 655000, Yunnan, China. hemaiding@kmmu.edu.cn., Yang Y; Department of Rehabilitation Medicine, Yunnan Qujing Central Hospital (Qujing No.1 Hospital), Qujing, 655000, Yunnan, China. yangyonghua@kmmu.edu.cn.
Πηγή: Biochemical genetics [Biochem Genet] 2026 Aug; Vol. 64 (4), pp. 5225-5244. Date of Electronic Publication: 2025 Nov 15.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Kluwer Academic/Plenum Publishers Country of Publication: United States NLM ID: 0126611 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-4927 (Electronic) Linking ISSN: 00062928 NLM ISO Abbreviation: Biochem Genet Subsets: MEDLINE
Imprint Name(s): Publication: 1999- : New York : Kluwer Academic/Plenum Publishers
Original Publication: New York, Plenum Press.
Ιατρικοί όροι (MeSH): Acute Lung Injury*/drug therapy , Acute Lung Injury*/metabolism , Acute Lung Injury*/pathology , Acute Lung Injury*/chemically induced , MicroRNAs*/genetics , MicroRNAs*/metabolism , Forkhead Box Protein O1*/genetics , Forkhead Box Protein O1*/metabolism , Autophagy*/drug effects , Lactates*/pharmacology , Caffeic Acids*/pharmacology, Gene Expression Regulation/drug effects ; Animals ; Mice ; Cell Line ; Lipopolysaccharides ; Male
Περίληψη: Acute lung injury (ALI) is a severe respiratory syndrome for which there is still a lack of effective treatment. Salvianolic acid A (Sal A) is a bioactive polyphenol extracted from Salvia miltiorrhiza Bunge, which has anti-inflammatory and antioxidant effects, but its role in ALI is unclear. We injected 50 µL LPS into the trachea of mice, and treated MLE-12 cells with 1 µg/mL LPS to construct ALI mouse and cell model. The levels of genes and proteins was identified using RT‒qPCR, western blot and immunofluorescence. The damage of MLE-12 cells and mouse lung tissue was evaluated by CCK-8, ELISA, TUNEL and HE staining. Sal A treatment can significantly inhibit LPS-induced inflammation and apoptosis, and then inhibit MLE-12 cell damage and ALI progression. From a mechanistic standpoint, Sal A promotes the expression of LC3 II/I and Beclin1, suppresses p62 expression, increases cell autophagy, and suppresses LPS-induced inflammatory cytokines IL-6, IL-1β, and TNF-α expression, ultimately reducing LPS-induced inflammation in lung epithelial cells and alleviating ALI progression. The main function of Sal A is to achieve this by inhibiting the expression of miR-217-5p and thereby promoting the expression of FOXO1. Our research results may provide a new target for the treatment of ALI with Sal A.
(© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Competing Interests: Declarations. Competing Interests: The authors declare no competing interests. Ethical Approval: All the experimental protocols were approved by the Animal Ethics Committee of Qujing No.1 Hospital (2019-68), and the animals were handled according to the management requirements of the Animal Management Association of Qujing No.1 Hospital.
References: ANDRADE J, SHI C, COSTA AS et al (2021) Control of endothelial quiescence by FOXO-regulated metabolites. Nat Cell Biol 23(4):413–423. (PMID: 10.1038/s41556-021-00637-6337958718032556)
Artham S, Gao F, Verma A et al (2019) Endothelial stromelysin1 regulation by the forkhead box-O transcription factors is crucial in the exudative phase of acute lung injury. Pharmacol Res 141:249–263. (PMID: 10.1016/j.phrs.2019.01.006306118536532785)
Bagam P, Kaur G, Singh DP et al (2021) In vitro study of the role of FOXO transcription factors in regulating cigarette smoke extract-induced autophagy. Cell Biol Toxicol 37(4):531–553. (PMID: 10.1007/s10565-020-09556-y33146789)
Cui Y, Wang X, Lin F et al (2022) Mir-29a-3p improves acute lung injury by reducing alveolar epithelial cell PANoptosis. Aging Dis 13(3):899–909. (PMID: 10.14336/AD.2021.1023356561159116916)
Deretic V, Saitoh T (2013) Autophagy in infection, inflammation and immunity. Nat Rev Immunol 13(10):722–737. (PMID: 10.1038/nri3532240645185340150)
Du Y, Ding Y, Shi T et al (2022) Long noncoding RNA GAS5 attenuates cigarette smoke-induced airway remodeling by regulating miR-217-5p/PTEN axis. Acta Biochim Biophys Sin 54(7):931–939. (PMID: 10.3724/abbs.2022074358805729828483)
FU M, ZHANG F, SONG Y et al (2025) Salvianolic acid A alleviates sciatic nerve injury in rats via inhibiting NLRP3 inflammasome through the activation of Schwann cells autophagy. Neurochem Res 50(3):152. (PMID: 10.1007/s11064-025-04402-140279045)
Hayes M, Curley G, Ansari B et al (2012) Clinical review: stem cell therapies for acute lung injury/acute respiratory distress syndrome - hope or hype? Crit Care 16(2):205. (PMID: 10.1186/cc10570224241083681334)
HE C, KLIONSKY DJ (2009) Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet 43:67–93. (PMID: 10.1146/annurev-genet-102808-114910196538582831538)
HU Y, LOU J, MAO Y Y et al (2016) Activation of MTOR in pulmonary epithelium promotes LPS-induced acute lung injury. Autophagy 12(12):2286–2299. (PMID: 10.1080/15548627.2016.1230584276580235173285)
Jiang Y, Luo W, Zhou F et al (2023) The role of FOXO1-mediated autophagy in the regulation of bone formation. Cell Cycle 22(7):829–840. (PMID: 10.1080/15384101.2022.215544336510368)
Kong X, Lu L, Lin D et al (2022) FGF10 ameliorates lipopolysaccharide-induced acute lung injury in mice via the BMP4-autophagy pathway. Front Pharmacol 13:1019755. (PMID: 10.3389/fphar.2022.1019755366189119813441)
Kurakazu I, Akasaki Y, Tsushima H et al (2021) TGFβ1 signaling protects chondrocytes against oxidative stress via FOXO1-autophagy axis. Osteoarthritis Cartilage 29(11):1600–1613. (PMID: 10.1016/j.joca.2021.07.015344196038789330)
LEVITT JE, CALFEE CS, GOLDSTEIN BA et al (2013) Early acute lung injury: criteria for identifying lung injury prior to the need for positive pressure ventilation*. Crit Care Med 41(8):1929–1937. (PMID: 10.1097/CCM.0b013e31828a3d99237829663748809)
Li ZM, Xu SW, Liu PQ (2018) Salvia miltiorrhizaBurge (Danshen): a golden herbal medicine in cardiovascular therapeutics. Acta Pharmacol Sin 39(5):802–824. (PMID: 10.1038/aps.2017.193296983875943903)
LI S, FANG J, SI T et al (2021a) Salvianolic acid A inhibits the growth of diffuse large B-cell lymphoma through MAPK pathways. Exp Hematol 94:60-8e2. (PMID: 10.1016/j.exphem.2020.11.00733278489)
Li C, Wang P, Li M et al (2021b) The current evidence for the treatment of sepsis with xuebijing injection: bioactive constituents, findings of clinical studies and potential mechanisms. J Ethnopharmacol 265:113301. (PMID: 10.1016/j.jep.2020.11330132860891)
Li J, Deng SH, LI J et al (2022) Obacunone alleviates ferroptosis during lipopolysaccharide-induced acute lung injury by upregulating Nrf2-dependent antioxidant responses. Cell Mol Biol Lett 27:29. (PMID: 10.1186/s11658-022-00318-8353055608933916)
Liu Q, Zhu CL, Li HR et al (2022) Salvianolic acid A protects against lipopolysaccharide-induced acute lung injury by inhibiting neutrophil NETosis. Oxid Med Cell Longev 2022:7411824. (PMID: 10.1155/2022/7411824359108499334034)
LU TX, ROTHENBERG ME (2018) MicroRNA. J Allergy Clin Immunol 141(4):1202–1207. (PMID: 10.1016/j.jaci.2017.08.03429074454)
Lu Q, Yu S, Meng X et al (2022) MicroRNAs: important regulatory molecules in acute lung injury/acute respiratory distress syndrome. Int J Mol Sci. https://doi.org/10.3390/ijms23105545. (PMID: 10.3390/ijms23105545366140109820753)
Menghini R, Casagrande V, Cardellini M et al (2009) Microrna 217 modulates endothelial cell senescence via silent information regulator 1. Circulation 120(15):1524–1532. (PMID: 10.1161/CIRCULATIONAHA.109.86462919786632)
MIZUMURA K, CLOONAN SM, HASPEL JA et al (2012) The emerging importance of autophagy in pulmonary diseases. Chest 142(5):1289–1299. (PMID: 10.1378/chest.12-0809231319373494477)
Mizumura K, Cloonan S, Choi ME et al (2016) Autophagy: friend or foe in lung disease? Ann Am Thorac Soc 13(Suppl 1):S40–S47. (PMID: 10.1513/AnnalsATS.201507-450MG270279515466160)
NAKAHIRA K, HASPEL JA, RATHINAM VA et al (2011) Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat Immunol 12(3):222–230. (PMID: 10.1038/ni.198021151103)
Nosaka N, Martinon D, Moreira D et al (2020) Autophagy protects against developing increased lung permeability and hypoxemia by down regulating inflammasome activity and IL-1β in LPS plus mechanical ventilation-induced acute lung injury. Front Immunol 11:207. (PMID: 10.3389/fimmu.2020.00207321173187033480)
Qi Y, Zhang K, Li P et al (2021) Down-regulating miR-217-5p protects cardiomyocytes against ischemia/reperfusion injury by restoring mitochondrial function via targeting SIRT1. Inflammation 44(1):383–396. (PMID: 10.1007/s10753-020-01343-533064238)
RANIERI VM, RUBENFELD GD, THOMPSON BT et al (2012) Acute respiratory distress syndrome: the Berlin definition. JAMA 307(23):2526–2533. (PMID: 22797452)
Saitoh T (2016) Regulation of inflammasomes by autophagy. J Allergy Clin Immunol 138(1):28–36. (PMID: 10.1016/j.jaci.2016.05.00927373323)
Shi X, Sun R, Zhao Y et al (2018) Promotion of autophagosome-lysosome fusion via Salvianolic acid A-mediated SIRT1 up-regulation ameliorates alcoholic liver disease. RSC Adv 8(36):20411–20422. (PMID: 10.1039/C8RA00798E355416579080827)
Wang J, Xu C, Zhang K et al (2021) Inhibition of ASC enhances the protective role of Salvianolic acid A in traumatic brain injury via inhibition of inflammation and recovery of mitochondrial function. Folia Neuropathol 59(1):50–66. (PMID: 10.5114/fn.2021.10513133969677)
Wang X, Qian J, Meng Y et al (2022) Salidroside alleviates severe acute pancreatitis-triggered pancreatic injury and inflammation by regulating miR-217-5p/YAF2 axis. Int Immunopharmacol 111:109123. (PMID: 10.1016/j.intimp.2022.10912335963157)
Wang P, Sun Y, Zhang R et al (2025) Salvianolic acid A attenuates lipopolysaccharide-induced acute lung injury by activating AMPK/SIRT1/Nrf2 signaling pathway. J Biochem Mol Toxicol 39(5):e70282. (PMID: 10.1002/jbt.7028240272051)
Wei X, Yi X (2020) Microrna-377-3p released by mesenchymal stem cell exosomes ameliorates lipopolysaccharide-induced acute lung injury by targeting RPTOR to induce autophagy. Cell Death Dis 11(8):657. (PMID: 10.1038/s41419-020-02857-4328147657438519)
Xie J, Li S, Ma X et al (2022) MiR-217-5p inhibits smog (PM2.5)-induced inflammation and oxidative stress response of mouse lung tissues and macrophages through targeting STAT1. Aging 14(16):6796–6808. (PMID: 10.18632/aging.204254360403879467388)
XING JJ, CHEN X, TU PF et al (2006) Effects of salvianolic acids on erythrocyte deformability in oleic acid induced acute lung injury in rabbits. Clin Hemorheol Microcirc 34(4):507–517. (PMID: 16687790)
Xing YQ, Li A, Yang Y et al (2018) The regulation of FOXO1 and its role in disease progression. Life Sci 193:124–131. (PMID: 10.1016/j.lfs.2017.11.03029158051)
XIONG X, DOU J, SHI J et al (2023) RAGE Inhibition alleviates lipopolysaccharides-induced lung injury via directly suppressing autophagic apoptosis of type II alveolar epithelial cells. Respir Res 24(1):24. (PMID: 10.1186/s12931-023-02332-6366910129872382)
Yi Z, Shi Y, Zhao P et al (2020) Overexpression of miR-217-5p protects against oxygen-glucose deprivation/reperfusion-induced neuronal injury via inhibition of PTEN. Hum Cell 33(4):1026–1035. (PMID: 10.1007/s13577-020-00396-w32683553)
Yoshida T, Fujino Y, Amato MB et al (2017) Fifty years of research in ARDS. Spontaneous breathing during mechanical ventilation. Risks, mechanisms, and management. Am J Respir Crit Care Med 195(8):985–992. (PMID: 10.1164/rccm.201604-0748CP27786562)
YOU T, ZHANG B (2022) CircWDR33 alleviates human pulmonary microvascular endothelial cell injury in sepsis-associated acute lung injury by targeting miR-217-5p/SERP1 axis. Int Immunopharmacol 113:109440. (PMID: 10.1016/j.intimp.2022.10944036417821)
Zeng X, Chen X (2020) Preventive effects of a natural anti-inflammatory agent Salvianolic acid A on acute kidney injury in mice. Food Chem Toxicol 135:110901. (PMID: 10.1016/j.fct.2019.11090131654708)
Zhang LC, Wu XY, Yang RB et al (2021) Recombinant protein schistosoma japonicum-derived molecule attenuates dextran sulfate sodium-induced colitis by inhibiting miRNA-217-5p to alleviate apoptosis. World J Gastroenterol 27(46):7982–7994. (PMID: 10.3748/wjg.v27.i46.7982350466258678816)
Zhang J, Zheng Y, Wang Y et al (2022) YAP1 alleviates sepsis-induced acute lung injury via inhibiting ferritinophagy-mediated ferroptosis. Front Immunol 13:884362. (PMID: 10.3389/fimmu.2022.884362359793599376389)
Zhao H, Chen H, Xiaoyin M et al (2019) Autophagy activation improves lung injury and inflammation in sepsis. Inflammation 42(2):426–439. (PMID: 10.1007/s10753-018-00952-530645707)
Zhou Z (2016) Mesenchymal stem cells alleviate LPS-induced acute lung injury in mice by MiR-142a-5p-controlled pulmonary endothelial cell autophagy. Cell Physiol Biochem 38(1):258–266. (PMID: 10.1159/00043862726784440)
Grant Information: 2023Y0701 the Yunnan Provincial Department of Education Science Research Fund Project
Contributed Indexing: Keywords: Acute lung injury; Autophagy; FOXO1; Inflammation; MiR-217-5p; Salvianolic acid A
Substance Nomenclature: 0 (MicroRNAs)
0 (Forkhead Box Protein O1)
51622542XO (salvianolic acid A)
0 (Lactates)
0 (Foxo1 protein, mouse)
0 (Caffeic Acids)
0 (Lipopolysaccharides)
Entry Date(s): Date Created: 20251115 Date Completed: 20260721 Latest Revision: 20260721
Update Code: 20260721
DOI: 10.1007/s10528-025-11288-9
PMID: 41240169
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1573-4927
DOI:10.1007/s10528-025-11288-9