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Astringin protects LPS-induced toxicity by suppressing oxidative stress and inflammation via suppression of PI3K/AKT/NF-κB pathway for pediatric acute lung injury

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Abstract

Acute lung injury (ALI) is a major pathophysiological problem defined by severe inflammation and acute disease with substantial morbidity and death. It is known that lipopolysaccharide (LPS) induces ALI by causing oxidative stress and inflammation. The goal of this study was to investigate the protective effect of astringin on LPS-induced ALI and probable pathways. Astringin is a stilbenoid, the 3-β-D-glucoside of piceatannol, mainly found in the bark of Picea sitchensis. The findings showed that astringin prevented LPS-induced cellular damage by reducing the generation of oxidative stress in LPS-stimulated A549 lung epithelial cells. Furthermore, astringin extensively decreased the production of inflammatory factors such as TNF-α, IL-1β, and IL-6. In addition, the western blot results revealed that the ability of astringin to reduce oxidative stress and the generation of inflammatory cytokines by inhibiting the ROS-mediated PI3K/AKT/NF-κB pathway could be the reason for its protective effect against LPS-induced ALI. Overall, the results suggest that astringin could be a possible inhibitor of ALI triggered by LPS for pediatric lung injury.

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References

  • An X, Sun X, Hou Y, Yang X, Chen H, Zhang P, Wu J (2019) Protective effect of oxytocin on LPS-induced acute lung injury in mice. Sci Rep 9(1):1–1

    Article  Google Scholar 

  • Aritomi M, Donnelly DM (1976) Stilbene glucosides in the bark of Picea sitchensis. Phytochemistry 15(12):2006–2008

    Article  CAS  Google Scholar 

  • Carlton EF, Flori HR (2019) Biomarkers in pediatric acute respiratory distress syndrome. Ann Transl Med 7(19):505

  • Chang CA, Akinbobuyi B, Quintana JM, Yoshimatsu G, Naziruddin B, Kane RR (2018) Ex-vivo generation of drug-eluting islets improves transplant outcomes by inhibiting TLR4-Mediated NFkB upregulation. Biomaterials 159:13–24

  • Choi YH, Park HY (2012) Anti-inflammatory effects of spermidine in lipopolysaccharide-stimulated BV2 microglial cells. J Biomed Sci 19(1):1–8

  • Dahlem P, Van Aalderen WM, Bos AP (2007) Pediatric acute lung injury. Paediatr Respir Rev 8(4):348–362

    Article  CAS  PubMed  Google Scholar 

  • De Oliveira MT, de Sá CD, De Souza ET, Guterres SS, Pohlmann AR, Silva PM, Martins MA, Bernardi A (2019) Orally delivered resveratrol-loaded lipid-core nanocapsules ameliorate LPS-induced acute lung injury via the ERK and PI3K/Akt pathways. Int J Nanomed 14:5215

    Article  Google Scholar 

  • Deng W, Li CY, Tong J, Zhang W, Wang DX (2012) Regulation of ENaC-mediated alveolar fluid clearance by insulin via PI3K/Akt pathway in LPS-induced acute lung injury. Respir Res 13(1):1–6

    Article  Google Scholar 

  • Deng G, He H, Chen Z, OuYang L, Xiao X, Ge J, Xiang B, Jiang S, Cheng S (2017) Lianqinjiedu decoction attenuates LPS-induced inflammation and acute lung injury in rats via TLR4/NF-κB pathway. Biomed Pharmacother 96:148–152

    Article  PubMed  PubMed Central  Google Scholar 

  • Dhlamini Q, Wang W, Feng G, Chen A, Chong L, Li X, Li Q, Wu J, Zhou D, Wang J, Zhang H (2022) FGF1 alleviates LPS-induced acute lung injury via suppression of inflammation and oxidative stress. Mol Med 28(1):1–4

  • Ding Z, Zhong R, Yang Y, Xia T, Wang W, Wang Y, Xing N, Luo Y, Li S, Shang L, Shu Z (2020) Systems pharmacology reveals the mechanism of activity of Ge-Gen-Qin-Lian decoction against LPS-induced acute lung injury: a novel strategy for exploring active components and effective mechanism of TCM formulae. Pharmacol Res 156:104759

    Article  CAS  PubMed  Google Scholar 

  • Dong Z, Yuan Y (2018) Accelerated inflammation and oxidative stress induced by LPS in acute lung injury: ιnhibition by ST1926. Int J Mol Med 41(6):3405–3421

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fu C, Dai X, Yang Y, Lin M, Cai Y, Cai S (2017) Dexmedetomidine attenuates lipopolysaccharide-induced acute lung injury by inhibiting oxidative stress, mitochondrial dysfunction and apoptosis in rats. Mol Med Rep 15(1):131–138

    Article  CAS  PubMed  Google Scholar 

  • Ge J, Yang H, Zeng Y, Liu Y (2021) Protective effects of wogonin on lipopolysaccharide-induced inflammation and apoptosis of lung epithelial cells and its possible mechanisms. Biomed Eng Online 20(1):1–3

    Article  Google Scholar 

  • George L, Ramasamy T, Sirajudeen KN, Manickam V (2019) LPS-induced apoptosis is partially mediated by hydrogen sulphide in RAW 264.7 murine macrophages. Immunol Investig 48(5):451–65

    Article  CAS  Google Scholar 

  • Gonzales JN, Lucas R, Verin AD (2015) The acute respiratory distress syndrome: mechanisms and perspective therapeutic approaches. Austin J Vasc Med 2(1):1009

  • Gorąca A, Józefowicz-Okonkwo G (2007) Protective effect of an early treatment with lipoic acid in LPS-induced lung injury in rats. J Physiol Pharmacol 58(3):541–549

    PubMed  Google Scholar 

  • Hammerbacher A, Ralph SG, Bohlmann J, Fenning TM, Gershenzon J, Schmidt A (2011) Biosynthesis of the major tetrahydroxystilbenes in spruce, astringin and isorhapontin, proceeds via resveratrol and is enhanced by fungal infection. Plant Physiol 157(2):876–890

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • He YQ, Zhou CC, Yu LY, Wang L, Deng JL, Tao YL, Zhang F, Chen WS (2021) Natural product derived phytochemicals in managing acute lung injury by multiple mechanisms. Pharmacol Res 163:105224

    Article  CAS  PubMed  Google Scholar 

  • Hou L, Zhang J, Liu Y, Fang H, Liao L, Wang Z, Yuan J, Wang X, Sun J, Tang B, Chen H (2021) MitoQ alleviates LPS-mediated acute lung injury through regulating Nrf2/Drp1 pathway. Free Radical Biol Med 165:219–228

    Article  CAS  Google Scholar 

  • Hu X, Fu Y, Lu X, Zhang Z, Zhang W, Cao Y, Zhang N (2017) Protective effects of platycodin D on lipopolysaccharide-induced acute lung injury by activating LXRα–ABCA1 signaling pathway. Front Immunol 7:644

    Article  PubMed  PubMed Central  Google Scholar 

  • Hu X, Qin H, Li Y, Li J, Fu L, Li M, Jiang C, Yun J, Liu Z, Feng Y, Yao Y (2020) Biochanin A protect against lipopolysaccharide-induced acute lung injury in mice by regulating TLR4/NF-κB and PPAR-γ pathway. Microb Pathog 138:103846

    Article  CAS  PubMed  Google Scholar 

  • Jiang W, Luo F, Lu Q, Liu J, Li P, Wang X, Fu Y, Hao K, Yan T, Ding X (2016) The protective effect of Trillin LPS-induced acute lung injury by the regulations of inflammation and oxidative state. Chem Biol Interact 243:127–134

    Article  CAS  PubMed  Google Scholar 

  • Jiang K, Guo S, Yang C, Yang J, Chen Y, Shaukat A, Zhao G, Wu H, Deng G (2018) Barbaloin protects against lipopolysaccharide (LPS)-induced acute lung injury by inhibiting the ROS-mediated PI3K/AKT/NF-κB pathway. Int Immunopharmacol 64:140–150

    Article  CAS  PubMed  Google Scholar 

  • Kim HJ, Lee HS, Chong YH, Kang JL (2006) p38 mitogen-activated protein kinase up-regulates LPS-induced NF-κB activation in the development of lung injury and RAW 264.7 macrophages. Toxicology. 225(1):36–47

    Article  CAS  PubMed  Google Scholar 

  • Kratzer E, Tian Y, Sarich N, Wu T, Meliton A, Leff A, Birukova AA (2012) Oxidative stress contributes to lung injury and barrier dysfunction via microtubule destabilization. Am J Respir Cell Mol Biol 47(5):688–697

  • Kumar V (2020) Pulmonary innate immune response determines the outcome of inflammation during pneumonia and sepsis-associated acute lung injury. Front Immunol 11:1722

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee JW, Fang X, Gupta N, Serikov V, Matthay MA (2009) Allogeneic human mesenchymal stem cells for treatment of E. coli endotoxin-induced acute lung injury in the ex vivo perfused human lung. Proc Natl Acad Sci 106(38):16357–62

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lei J, Wei Y, Song P, Li Y, Zhang T, Feng Q, Xu G (2018) Cordycepin inhibits LPS-induced acute lung injury by inhibiting inflammation and oxidative stress. Eur J Pharmacol 818:110–114

    Article  CAS  PubMed  Google Scholar 

  • Li W, Qiu X, Jiang H, Han Y, Wei D, Liu J (2016) Downregulation of miR-181a protects mice from LPS-induced acute lung injury by targeting Bcl-2. Biomed Pharmacother 84:1375–1382

    Article  CAS  PubMed  Google Scholar 

  • Li PY, Liang YC, Sheu MJ, Huang SS, Chao CY, Kuo YH, Huang GJ (2018) Alpinumisoflavone attenuates lipopolysaccharide-induced acute lung injury by regulating the effects of anti-oxidation and anti-inflammation both in vitro and in vivo. RSC Adv 8(55):31515–31528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li X, Huang R, Liu K, Li M, Luo H, Cui L, Huang L, Luo L (2021) Fucoxanthin attenuates LPS-induced acute lung injury via inhibition of the TLR4/MyD88 signaling axis. Aging (albany NY) 13(2):2655

    Article  CAS  Google Scholar 

  • Liu B, He R, Zhang L, Hao B, Jiang W, Wang W, Geng Q (2021) Inflammatory caspases drive pyroptosis in acute lung injury. Front Pharmacol 12:631256

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Merillon JM, Fauconneau B, Teguo PW, Barrier L, Vercauteren J, Huguet F (1997) Antioxidant activity of the stilbene astringin, newly extracted from Vitis vinifera cell cultures. Clin Chem 43(6):1092–1093

  • Orloff KE, Turner DA, Rehder KJ (2019) The current state of pediatric acute respiratory distress syndrome. Pediatr Allergy Immunol Pulmonol 32(2):35–44

    Article  PubMed  PubMed Central  Google Scholar 

  • Pei X, Zhang XJ, Chen HM (2019) Bardoxolone treatment alleviates lipopolysaccharide (LPS)-induced acute lung injury through suppressing inflammation and oxidative stress regulated by Nrf2 signaling. Biochem Biophys Res Commun 516(1):270–277

  • Peng LY, Shi HT, Yuan M, Li JH, Song K, Huang JN, Yi PF, Shen HQ, Fu BD (2020) Madecassoside protects against LPS-induced acute lung injury via inhibiting TLR4/NF-κB activation and blood-air barrier permeability. Front Pharmacol 11:807

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ribeiro A, Almeida VI, Costola-de-Souza C, Ferraz-de-Paula V, Pinheiro ML, Vitoretti LB, Gimenes-Junior JA, Akamine AT, Crippa JA, Tavares-de-Lima W, Palermo-Neto J (2015) Cannabidiol improves lung function and inflammation in mice submitted to LPS-induced acute lung injury. Immunopharmacol Immunotoxicol 37(1):35–41

    Article  CAS  PubMed  Google Scholar 

  • Shah D, Das P, Acharya S, Agarwal B, Christensen DJ, Robertson SM, Bhandari V (2021) Small immunomodulatory molecules as potential therapeutics in experimental murine models of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Int J Mol Sci 22(5):2573

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shao L, Meng D, Yang F, Song H, Tang D (2017) Irisin-mediated protective effect on LPS-induced acute lung injury via suppressing inflammation and apoptosis of alveolar epithelial cells. Biochem Biophys Res Commun 487(2):194–200

    Article  CAS  PubMed  Google Scholar 

  • Tang J, Xu L, Zeng Y, Gong F (2021) Effect of gut microbiota on LPS-induced acute lung injury by regulating the TLR4/NF-kB signaling pathway. Int Immunopharmacol 91:107272

    Article  CAS  PubMed  Google Scholar 

  • Wang T, Lin S, Liu R, Li H, Liu Z, Zhang X, Xu H, Li Q, Bi K (2020) Metabolomic profile perturbations of serum, lung, bronchoalveolar lavage fluid, spleen and feces in LPS-induced acute lung injury rats based on HPLC-ESI-QTOF-MS. Anal Bioanal Chem 412(5):1215–1234

    Article  CAS  PubMed  Google Scholar 

  • Xie W, Lu Q, Wang K, Lu J, Gu X, Zhu D, Liu F, Guo Z (2018) miR-34b-5p inhibition attenuates lung inflammation and apoptosis in an LPS-induced acute lung injury mouse model by targeting progranulin. J Cell Physiol 233(9):6615–6631

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu M, Cao FL, Zhang YF, Shan L, Jiang XL, An XJ, Xu W, Liu XZ, Wang XY (2015) Tanshinone IIA therapeutically reduces LPS-induced acute lung injury by inhibiting inflammation and apoptosis in mice. Acta Pharmacol Sin 36(2):179–187

    Article  CAS  PubMed  Google Scholar 

  • Xu T, Liu R, Zhu H, Zhou Y, Pei T, Yang Z (2022) The inhibition of LPS-induced oxidative stress and inflammatory responses is associated with the protective effect of (-)-Epigallocatechin-3-Gallate on bovine hepatocytes and murine liver. Antioxidants 11(5):914

  • Xuan TQ, Gong G, Du H, Liu C, Wu Y, Bao G, Ma Q, Zhen D (2022) Protective effect of pteryxin on LPS-induced acute lung injury via modulating MAPK/NF-κB pathway and NLRP3 inflammasome activation. J Ethnopharmacol 286:114924

    Article  CAS  PubMed  Google Scholar 

  • Yang Y, Yang C, Guo YF, Liu P, Guo S, Yang J, Zahoor A, Shaukat A, Deng G (2019) MiR-142a-3p alleviates Escherichia coli derived lipopolysaccharide-induced acute lung injury by targeting TAB2. Microb Pathog 136:103721

    Article  CAS  PubMed  Google Scholar 

  • Yang J, Wang HX, Zhang YJ, Yang YH, Lu ML, Zhang J, Li ST, Zhang SP, Li G (2013) Astragaloside IV attenuates inflammatory cytokines by inhibiting TLR4/NF-кB signaling pathway in isoproterenol-induced myocardial hypertrophy. J Ethnopharmacol 150(3):1062–1070

  • Ye R, Liu Z (2020) ACE2 exhibits protective effects against LPS-induced acute lung injury in mice by inhibiting the LPS-TLR4 pathway. Exp Mol Pathol 113:104350

    Article  CAS  PubMed  Google Scholar 

  • Zeng Z, Gong H, Li Y, Jie K, Ding C, Shao Q, Liu F, Zhan Y, Nie C, Zhu W, Qian K (2013) Upregulation of miR-146a contributes to the suppression of inflammatory responses in LPS-induced acute lung injury. Exp Lung Res 39(7):275–282

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Lang W, Wang S, Li B, Li G, Shi Q (2020) Echinacea polysaccharide alleviates LPS-induced lung injury via inhibiting inflammation, apoptosis and activation of the TLR4/NF-κB signal pathway. Int Immunopharmacol 88:106974

    Article  CAS  PubMed  Google Scholar 

  • Zhao M, Li C, Shen F, Wang M, Jia N, Wang C (2017) Naringenin ameliorates LPS-induced acute lung injury through its anti-oxidative and anti-inflammatory activity and by inhibition of the PI3K/AKT pathway. Exp Ther Med 14(3):2228–2234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhong WT, Wu YC, Xie XX, Zhou X, Wei MM, Soromou LW, Ci XX, Wang DC (2013) Phillyrin attenuates LPS-induced pulmonary inflammation via suppression of MAPK and NF-κB activation in acute lung injury mice. Fitoterapia 90:132–139

    Article  CAS  PubMed  Google Scholar 

  • Zhu DZ, Wang YT, Zhuo YL, Zhu KJ, Wang XZ, Liu AJ (2020) Fucoidan inhibits LPS-induced acute lung injury in mice through regulating GSK-3β-Nrf2 signaling pathway. Arch Pharmacal Res 43(6):646–654

    Article  CAS  Google Scholar 

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LW: conceptualization, performed the experiments, data analysis, and writing—original draft. SJ: performed the experiments, data analysis, and writing—original draft. XL: performed the experiments, data analysis, and writing—original draft. TL: Conceptualization, supervision, data analysis, and reviewing—original draft. TQ: conceptualization, supervision, data analysis, and reviewing—original draft. All authors contributed to the article and approved the submitted version. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Tingting Lin or Tao Qin.

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Wang, L., Jiang, S., Li, X. et al. Astringin protects LPS-induced toxicity by suppressing oxidative stress and inflammation via suppression of PI3K/AKT/NF-κB pathway for pediatric acute lung injury. Naunyn-Schmiedeberg's Arch Pharmacol 396, 2369–2377 (2023). https://doi.org/10.1007/s00210-023-02439-z

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