Skip to content
2000
image of Aloperine Protects Against Cisplatin-Induced Injury in Kidney Cells Via Modulating PI3K/AKT/Nfκb-Mediated NLRP3 Inflammasome

Abstract

Background

Aloperine (ALO) is a vital alkaloid present in the traditional Chinese herb Sophora alopecuroides, which has demonstrated effective anti-inflammatory activity. However, the effects and the mechanism of action of ALO on cisplatin (CDDP)-induced nephrotoxicity remain unclear.

Objective

This study aimed to investigate the effects of ALO on CDDP-induced nephrotoxicity and its potential mechanism of action .

Methods

Cell viability, lactate dehydrogenase cytotoxicity, apoptosis, activity of Caspase-Glo 3/7 and 1, in-cell western blotting, immunohistochemical staining, and enzyme-linked immunosorbent assay (ELISA) were performed to assess the influence of ALO on CDDP-treated kidney cells. Inhibitors of phosphatidylinositol 3-kinase (PI3K, LY294002), protein kinase B (Akt, AKT inhibitor VIII), and nuclear factor kappa B (NFκB, BAY 11-7082) were used to determine their potential mechanisms of action.

Results

The results indicated that ALO significantly reversed the inhibition of cell viability, cytotoxicity, apoptosis, and the release of inflammatory factors induced by CDDP in kidney cells. ALO attenuated the PI3K/AKT/NFκB-mediated pathway activated by CDDP treatment and downregulated the CDDP-induced nucleotide-binding domain, leucine-rich-containing family, pyrin domain–containing-3 (NLRP3) inflammasome. Furthermore, the PI3K and AKT inhibitors diminished the effects of ALO on CDDP-treated kidney cells. Additionally, NFκB inhibitors reversed the effects of the PI3K and AKT inhibitors on ALO in CDDP-treated kidney cells.

Conclusion

These results suggest that ALO protects against CDDP-induced injury in kidney cells by modulating the PI3K/AKT/NFκB-mediated NLRP3 inflammasome.

© Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/ppl/10.2174/0109298665334965251007043325
2025-11-03
2025-11-29

  • From This Site

    /content/journals/ppl/10.2174/0109298665334965251007043325
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Romani A.M.P. Cisplatin in cancer treatment. Biochem. Pharmacol. 2022 206 115323 10.1016/j.bcp.2022.115323 36368406
    [Google Scholar]
  2. Dasari S. Bernard Tchounwou P. Cisplatin in cancer therapy: Molecular mechanisms of action. Eur. J. Pharmacol. 2014 740 364 378 10.1016/j.ejphar.2014.07.025 25058905
    [Google Scholar]
  3. Zhang J. Ye Z.W. Tew K.D. Townsend D.M. Cisplatin chemotherapy and renal function. Adv. Cancer Res. 2021 152 305 327 10.1016/bs.acr.2021.03.008 34353441
    [Google Scholar]
  4. Tang C. Livingston M.J. Safirstein R. Dong Z. Cisplatin nephrotoxicity: New insights and therapeutic implications. Nat. Rev. Nephrol. 2023 19 1 53 72 10.1038/s41581‑022‑00631‑7 36229672
    [Google Scholar]
  5. Wang R. Deng X. Gao Q. Wu X. Han L. Gao X. Zhao S. Chen W. Zhou R. Li Z. Bai C. Sophora alopecuroides L.: An ethnopharmacological, phytochemical, and pharmacological review. J. Ethnopharmacol. 2020 248 112172 10.1016/j.jep.2019.112172 31442619
    [Google Scholar]
  6. Zhou H. Li J. Sun F. Wang F. Li M. Dong Y. Fan H. Hu D. A review on recent advances in aloperine research: Pharmacological activities and underlying biological mechanisms. Front. Pharmacol. 2020 11 538137 10.3389/fphar.2020.538137 33536900
    [Google Scholar]
  7. Qiu M. Li J. Zhang S. Liang J. Wang X. Liu J. Aloperine attenuates UVB-induced damage in skin fibroblasts via activating TFE3/beclin-1-mediated autophagy. Protein Pept. Lett. 2024 31 11 884 893 10.2174/0109298665335370241017055831 39558499
    [Google Scholar]
  8. Tahir M. Ali S. Zhang W. Lv B. Qiu W. Wang J. Aloperine: A potent modulator of crucial biological mechanisms in multiple diseases. Biomedicines 2022 10 4 905 10.3390/biomedicines10040905 35453655
    [Google Scholar]
  9. Lin W.H. Jiang W.P. Chen C.C. Lee L.Y. Tsai Y.S. Chien L.H. Chou Y.N. Deng J.S. Huang G.J. Renoprotective effect of Pediococcus acidilactici GKA4 on cisplatin-induced acute kidney injury by mitigating inflammation and oxidative stress and regulating the MAPK, AMPK/SIRT1/NF-κB, and PI3K/AKT pathways. Nutrients 2022 14 14 2877 10.3390/nu14142877 35889833
    [Google Scholar]
  10. Guan T. Zheng Y. Jin S. Wang S. Hu M. Liu X. Huang S. Liu Y. Troxerutin alleviates kidney injury in rats via PI3K/AKT pathway by enhancing MAP4 expression. Food Nutr. Res. 2022 66 10 10.29219/fnr.v66.8469 35844954
    [Google Scholar]
  11. Fahmy M.I. Khalaf S.S. Yassen N.N. Sayed R.H. Nicorandil attenuates cisplatin-induced acute kidney injury in rats via activation of PI3K/AKT/mTOR signaling cascade and inhibition of autophagy. Int. Immunopharmacol. 2024 127 111457 10.1016/j.intimp.2023.111457 38160566
    [Google Scholar]
  12. Fu Y. Xiang Y. Wang Y. Liu Z. Yang D. Zha J. Tang C. Cai J. Chen G. Dong Z. The STAT1/HMGB1/NF-κB pathway in chronic inflammation and kidney injury after cisplatin exposure. Theranostics 2023 13 9 2757 2773 10.7150/thno.81406 37284446
    [Google Scholar]
  13. Chien L.H. Wu C.T. Deng J.S. Jiang W.P. Huang W.C. Huang G.J. Salvianolic acid c protects against cisplatin-induced acute kidney injury through attenuation of inflammation, oxidative stress and apoptotic effects and activation of the camkk–ampk–sirt1-associated signaling pathway in mouse models. Antioxidants 2021 10 10 1620 10.3390/antiox10101620 34679755
    [Google Scholar]
  14. Thompson L.E. Joy M.S. Understanding cisplatin pharmacokinetics and toxicodynamics to predict and prevent kidney injury. J. Pharmacol. Exp. Ther. 2024 391 3 399 414 10.1124/jpet.124.002287 39322416
    [Google Scholar]
  15. Elmorsy E.A. Saber S. Hamad R.S. Abdel-Reheim M.A. El-kott A.F. AlShehri M.A. Morsy K. Salama S.A. Youssef M.E. Advances in understanding cisplatin-induced toxicity: Molecular mechanisms and protective strategies. Eur. J. Pharm. Sci. 2024 203 106939 10.1016/j.ejps.2024.106939 39423903
    [Google Scholar]
  16. Chen H. Wang S. Chen Q. Yu W. Nie H. Liu L. Zheng B. Gong Q. Aloperine ameliorates acetaminophen‐induced acute liver injury through HMGB1/TLR4/NF‐ κ B and NLRP3/Inflammasome Pathway. Mediators Inflamm. 2024 2024 1 3938136 10.1155/2024/3938136 39381066
    [Google Scholar]
  17. Ren D. Ma W. Guo B. Wang S. Aloperine attenuates hydrogen peroxide-induced injury via anti-apoptotic activity and suppression of the nuclear factor-κB signaling pathway. Exp. Ther. Med. 2017 13 1 315 320 10.3892/etm.2016.3962 28123508
    [Google Scholar]
  18. Fu Y. Xiang Y. Li H. Chen A. Dong Z. Inflammation in kidney repair: Mechanism and therapeutic potential. Pharmacol. Ther. 2022 237 108240 10.1016/j.pharmthera.2022.108240 35803367
    [Google Scholar]
  19. Kimura T. Isaka Y. Yoshimori T. Autophagy and kidney inflammation. Autophagy 2017 13 6 997 1003 10.1080/15548627.2017.1309485 28441075
    [Google Scholar]
  20. Chen X. Wei W. Li Y. Huang J. Ci X. Hesperetin relieves cisplatin-induced acute kidney injury by mitigating oxidative stress, inflammation and apoptosis. Chem. Biol. Interact. 2019 308 269 278 10.1016/j.cbi.2019.05.040 31153982
    [Google Scholar]
  21. Kim J.Y. Park J.H. Kim K. Jo J. Leem J. Park K.K. Pharmacological inhibition of caspase-1 ameliorates cisplatin-induced nephrotoxicity through suppression of apoptosis, oxidative stress, and inflammation in mice. Mediators Inflamm. 2018 2018 1 10 10.1155/2018/6571676 30670928
    [Google Scholar]
  22. Dadkhah M. Sharifi M. The NLRP3 inflammasome: Mechanisms of activation, regulation, and role in diseases. Int. Rev. Immunol. 2025 44 2 98 111 10.1080/08830185.2024.2415688 39402899
    [Google Scholar]
  23. Luo S. Yang M. Han Y. Zhao H. Jiang N. Li L. Chen W. Li C. Yang J. Liu Y. Liu C. Zhao C. Sun L. β-Hydroxybutyrate against cisplatin-induced acute kidney injury via inhibiting NLRP3 inflammasome and oxidative stress. Int. Immunopharmacol. 2022 111 109101 10.1016/j.intimp.2022.109101 35940076
    [Google Scholar]
  24. Gao H. Wang X. Qu X. Zhai J. Tao L. Zhang Y. Song Y. Zhang W. Omeprazole attenuates cisplatin-induced kidney injury through suppression of the TLR4/NF-κB/NLRP3 signaling pathway. Toxicology 2020 440 152487 10.1016/j.tox.2020.152487 32418911
    [Google Scholar]
  25. Hazem S.H. Saad K.M. Samaha M.M. Protective effects of BTK inhibition by acalabrutinib on cisplatin-induced renal and testicular injury in mice: Modulation of mTOR/AMPK, NLRP3/GSDMD-N, and apoptotic pathways. Int. Immunopharmacol. 2025 149 114256 10.1016/j.intimp.2025.114256 39938312
    [Google Scholar]
  26. Jafari M. Ghadami E. Dadkhah T. Akhavan-Niaki H. PI3k/AKT signaling pathway: Erythropoiesis and beyond. J. Cell. Physiol. 2019 234 3 2373 2385 10.1002/jcp.27262 30192008
    [Google Scholar]
  27. Zhang X. Shi M. Ye R. Wang W. Liu X. Zhang G. Han J. Zhang Y. Wang B. Zhao J. Hui J. Xiong L. Zhao G. Ginsenoside Rd attenuates tau protein phosphorylation via the PI3K/AKT/GSK-3β pathway after transient forebrain ischemia. Neurochem. Res. 2014 39 7 1363 1373 10.1007/s11064‑014‑1321‑3 24792734
    [Google Scholar]
  28. Amable G. Martínez-León E. Picco M.E. Di Siervi N. Davio C. Rozengurt E. Rey O. Metformin inhibits β-catenin phosphorylation on Ser-552 through an AMPK/PI3K/Akt pathway in colorectal cancer cells. Int. J. Biochem. Cell Biol. 2019 112 88 94 10.1016/j.biocel.2019.05.004 31082618
    [Google Scholar]
  29. Ashayeri Ahmadabad H. Mohammadi Panah S. Ghasemnejad-Berenji H. Ghojavand S. Ghasemnejad-Berenji M. Khezri M.R. Metformin and the PI3K/AKT signaling pathway: Implications for cancer, cardiovascular, and central nervous system diseases. Naunyn Schmiedebergs Arch. Pharmacol. 2025 398 2 1035 1055 10.1007/s00210‑024‑03358‑3 39225830
    [Google Scholar]
  30. Zeng Y. Yuan W. Feng C. Peng L. Xie X. Peng F. Li T. Lin M. Zhang H. Dai H. Trametinib alleviates lipopolysaccharide-induced acute kidney injury by inhibiting macrophage polarization through the PI3K/Akt pathway. Transpl. Immunol. 2025 89 102183 10.1016/j.trim.2025.102183 39892762
    [Google Scholar]
  31. Hu J. Pang X. Liang X. Shao X. Xia Q. Sun J. Wang Y. Wang G. Li S. Zha L. Guo J. Peng C. Huang P. Ding Y. Jin C. He N. Huang Y. Gui S. Raspberry ameliorates renal fibrosis in rats with chronic kidney disease via the PI3K/Akt pathway. Phytomedicine 2025 140 156589 10.1016/j.phymed.2025.156589 40056634
    [Google Scholar]
  32. Chou Y.N. Lee M.M. Deng J.S. Jiang W.P. Lin J.G. Huang G.J. Water Extract from Brown Strain of Flammulina velutipes Alleviates Cisplatin-Induced Acute Kidney Injury by Attenuating Oxidative Stress, Inflammation, and Autophagy via PI3K/AKT Pathway Regulation. Int. J. Mol. Sci. 2023 24 11 9448 10.3390/ijms24119448 37298398
    [Google Scholar]
  33. Shen Q. Zhang X. Li Q. Zhang J. Lai H. Gan H. Du X. Li M. TLR2 protects cisplatin‐induced acute kidney injury associated with autophagy via PI3K/Akt signaling pathway. J. Cell. Biochem. 2019 120 3 4366 4374 10.1002/jcb.27722 30387162
    [Google Scholar]
  34. Jędrzejewski T. Sobocińska J. Maciejewski B. Slovakova M. Wrotek S. Enhanced anti-cancer potential: Investigating the combined effects with Coriolus versicolor extract and phosphatidylinositol 3-kinase inhibitor (LY294002) in vitro. Int. J. Mol. Sci. 2025 26 4 1556 10.3390/ijms26041556 40004020
    [Google Scholar]
  35. Hsieh H.J. Urak R. Clark M.C. Kwak L.W. Forman S.J. Wang X. Capivasertib enhances chimeric antigen receptor T cell activity in preclinical models of B cell lymphoma. Mol. Ther. Methods Clin. Dev. 2025 33 1 101421 10.1016/j.omtm.2025.101421 40008088
    [Google Scholar]
  36. Lai X. Liu B. Wan Y. Zhou P. Li W. Hu W. Gong W. Metformin alleviates colitis-associated colorectal cancer via inhibition of the TLR4/MyD88/NFκB/MAPK pathway and macrophage M2 polarization. Int. Immunopharmacol. 2025 144 113683 10.1016/j.intimp.2024.113683 39602956
    [Google Scholar]
  37. Xie Y. Fang C. Lu L. Wang J. Wu L. Wang S. Guo Q. Yan W. Wei J. Duan F. Huang L. Extract of Tinospora sinensis alleviates LPS-induced neuroinflammation in mice by regulating TLR4/NF-κB/NLRP3 signaling pathway. J. Ethnopharmacol. 2025 337 Pt 1 118807 10.1016/j.jep.2024.118807 39245241
    [Google Scholar]
  38. Wu X.Y. Dong Q.W. Zhang Y.B. Li J.X. Zhang M.Q. Zhang D.Q. Cui Y.L. Cimicifuga heracleifolia kom. Attenuates ulcerative colitis through the PI3K/AKT/NF-κB signaling pathway. J. Ethnopharmacol. 2025 337 Pt 3 118892 10.1016/j.jep.2024.118892 39395768
    [Google Scholar]
  39. Yu H. Lin L. Zhang Z. Zhang H. Hu H. Targeting NF-κB pathway for the therapy of diseases: Mechanism and clinical study. Signal Transduct. Target. Ther. 2020 5 1 209 10.1038/s41392‑020‑00312‑6 32958760
    [Google Scholar]
  40. Moon J. Moon I.J. Hyun H. Yoo J.M. Bang S.H. Song Y. Chang S.E. Bay 11‐7082, an NF‐κB inhibitor, prevents post‐inflammatory hyperpigmentation through inhibition of inflammation and melanogenesis. Pigment Cell Melanoma Res. 2025 38 1 e13207 10.1111/pcmr.13207 39462815
    [Google Scholar]
/content/journals/ppl/10.2174/0109298665334965251007043325
Loading
Aloperine Protects Against Cisplatin-Induced Injury in Kidney Cells Via Modulating PI3K/AKT/Nfκb-Mediated NLRP3 Inflammasome
Bentham Science Publishers ; https://doi.org/10.2174/0109298665334965251007043325
/content/journals/ppl/10.2174/0109298665334965251007043325
/content/journals/ppl/10.2174/0109298665334965251007043325
Loading

Data & Media loading...


  • Article Type:     Research Article
Keywords: Aloperine ; CDDP-induced injury ; sophora alopecuroides ; PI3K/AKT/NFκB ; NLRP3 inflammasome ; kidney cells

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test