Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Acteoside-containing caffeic acid is bioactive functional group of antifibrotic effect by suppressing inflammation via inhibiting AHR nuclear translocation in chronic kidney disease

Acta Pharmacologica Sinica (2025)Cite this article

Abstract

Chronic kidney disease (CKD) is a common disorder with increasing prevalence and morbidity worldwide. However, the present agents do not effectively inhibit pathological processes. Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediated various diseases. Acteoside (ATS) is a commercial ATP-competitive inhibitor of protein kinase C. Clinical study showed ATS mitigated Th22 cell disorder and proteinuria in patients with immunoglobulin A nephropathy. This study analyzed AHR and nuclear factor kappa B (NF-κB) p65 expression in CKD patients. We compared the effects of ATS and its isomer isoacteoside (IAT) on renal function to identify their active functional group of antifibrosis in adenine-induced CKD rats. We further determined the effects of their active functional group on AHR signalling and inflammation pathway. The results showed increasing intrarenal AHR and NF-κB p65 expression in CKD patients. ATS improved renal function and fibrosis while IAT did not significantly improve fibrosis in CKD rats. Both ATS and IAT inhibited intrarenal mRNA expression of AHR and its downstream genes while ATS not IAT significantly inhibited nuclear AHR protein expression. Structure-activity analysis indicated that ATS-containing caffeic acid group by ester bond binding is transformed from C-11 to C-15 becoming IAT leads to a weakened inhibition of fibrosis and AHR nuclear translocation, indicating that caffeic acid group is bioactive functional group of ATS. Furthermore, ATS not IAT significantly regulated protein expression of NF-κB p65 and nuclear factor erythroid 2-related factor 2 (Nrf2) as well as their downstream gene products. Similar results were observed in indole-3-acetic acid (IAA)-induced NRK-52E cells. However, IAT did not show a significant effect. The inhibitory effects of ATS on NF-κB and Nrf2 pathways were partially abolished in IAA-stimulated NRK-52E cells treated with CH223191. However, ATS did not affect AHR expression in IAA-induced NRK-52E cells treated with BAY 11-7082. Therefore, ATS was identified as an AHR antagonist that ameliorated CKD by improving NF-κB/Nrf2 signalling axis. Conclusively, ATS holds promise as a chemical scaffold for the development of new antifibrotic agents.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Acteoside not isoacteoside ameliorate renal fibrosis in rats with adenine-induced CKD.
Fig. 2: Both ATS and IAT inhibited transcription levels of intrarenal AHR and its downstream target genes in rats with adenine-induced CKD.
Fig. 3: ATS inhibited hyperactive NF-κB pathway in rats with adenine-induced CKD.
Fig. 4: ATS activated impaired Nrf2 pathway in rats with adenine-induced CKD.
Fig. 5: Acteoside not isoacteoside inhibited profibrotic protein expression in IAA-induced NRK-52E cells.
Fig. 6: Both ATS and IAT inhibited transcription levels of intrarenal AHR and its downstream target genes in IAA-induced NRK-52E cells.
Fig. 7: ATS suppressed hyperactive NF-κB pathway in IAA-induced NRK-52E cells.
Fig. 8: ATS improved impaired Nrf2 pathway in IAA-induced NRK-52E cells.
Fig. 9: ATS inhibited renal fibrosis through modulating NF-κB and Nrf2 pathways via suppressing AHR signalling.

Similar content being viewed by others

References

  1. Francis A, Harhay MN, Ong ACM, Tummalapalli SL, Ortiz A, Fogo AB, et al. Chronic kidney disease and the global public health agenda: an international consensus. Nat Rev Nephrol. 2024;20:473–85.

    Article  PubMed  Google Scholar 

  2. Khandpur S, Mishra P, Mishra S, Tiwari S. Challenges in predictive modelling of chronic kidney disease: a narrative review. World J Nephrol. 2024;13:97214.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Balakumar P. Unleashing the pathological role of epithelial-to-mesenchymal transition in diabetic nephropathy: the intricate connection with multifaceted mechanism. World J Nephrol. 2024;13:95410.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Wang YN, Miao H, Yu XY, Guo Y, Su W, Liu F, et al. Oxidative stress and inflammation are mediated via aryl hydrocarbon receptor signalling in idiopathic membranous nephropathy. Free Radic Biol Med. 2023;207:89–106.

    Article  CAS  PubMed  Google Scholar 

  5. Liu D, Chen X, He W, Lu M, Li Q, Zhang S, et al. Update on the pathogenesis, diagnosis, and treatment of diabetic tubulopathy. Integr Med Nephrol Androl. 2024;11:e23–00029.

    Article  Google Scholar 

  6. Miao H, Liu F, Wang YN, Yu XY, Zhuang S, Guo Y, et al. Targeting Lactobacillus johnsonii to reverse chronic kidney disease. Signal Transduct Target Ther. 2024;9:195.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Wang YN, Zhang ZH, Liu HJ, Guo ZY, Zou L, Zhang YM, et al. Integrative phosphatidylcholine metabolism through phospholipase A2 in rats with chronic kidney disease. Acta Pharmacol Sin. 2023;44:393–405.

    Article  CAS  PubMed  Google Scholar 

  8. Correa-Rotter R, Maple-Brown LJ, Sahay R, Tuttle KR. Ulasi II. New and emerging therapies for diabetic kidney disease. Nat Rev Nephrol. 2024;20:156–60.

    Article  CAS  PubMed  Google Scholar 

  9. Rothhammer V, Quintana FJ. The aryl hydrocarbon receptor: an environmental sensor integrating immune responses in health and disease. Nat Rev Immunol. 2019;19:184–97.

    Article  CAS  PubMed  Google Scholar 

  10. Miao H, Cao G, Wu XQ, Chen YY, Chen DQ, Chen L, et al. Identification of endogenous 1-aminopyrene as a novel mediator of progressive chronic kidney disease via aryl hydrocarbon receptor activation. Br J Pharmacol. 2020;177:3415–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Cao G, Miao H, Wang YN, Chen DQ, Wu XQ, Chen L, et al. Intrarenal 1-methoxypyrene, an aryl hydrocarbon receptor agonist, mediates progressive tubulointerstitial fibrosis in mice. Acta Pharmacol Sin. 2022;43:2929–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Miao H, Wang YN, Yu XY, Zou L, Guo Y, Su W, et al. Lactobacillus species ameliorate membranous nephropathy through inhibiting aryl hydrocarbon receptor pathway via tryptophan-produced indole metabolites. Br J Pharmacol. 2024;181:162–79.

    Article  CAS  PubMed  Google Scholar 

  13. Miao H, Wu XQ, Wang YN, Chen DQ, Chen L, Vaziri ND, et al. 1-Hydroxypyrene mediates renal fibrosis through aryl hydrocarbon receptor signalling pathway. Br J Pharmacol. 2022;179:103–24.

    Article  CAS  PubMed  Google Scholar 

  14. Hu Q, Jiang L, Yan Q, Zeng J, Ma X, Zhao Y. A natural products solution to diabetic nephropathy therapy. Pharmacol Ther. 2023;241:108314.

    Article  CAS  PubMed  Google Scholar 

  15. Guo ZY, Wu X, Zhang SJ, Yang JH, Miao H, Zhao YY. Poria cocos: traditional uses, triterpenoid components and their renoprotective pharmacology. Acta Pharmacol Sin. 2024;46:836–51.

    Article  PubMed  Google Scholar 

  16. Ruan Z, Liu J, Liu W, Huang W. Qufeng tongluo decoction may alleviate podocyte injury induced by high glucose and hydrogen peroxide by regulating autophagy. Integr Med Nephrol Androl. 2024;11:e24–00023.

    Article  Google Scholar 

  17. Zou TF, Liu ZG, Cao PC, Zheng SH, Guo WT, Wang TX, et al. Fisetin treatment alleviates kidney injury in mice with diabetes-exacerbated atherosclerosis through inhibiting CD36/fibrosis pathway. Acta Pharmacol Sin. 2023;44:2065–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Xiao Y, Ren Q, Wu L. The pharmacokinetic property and pharmacological activity of acteoside: A review. Biomed Pharmacother. 2022;153:113296.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Nishizuka Y. Studies and perspectives of protein kinase C. Science. 1986;233:305–12.

    Article  CAS  PubMed  Google Scholar 

  20. Herbert JM, Maffrand JP, Taoubi K, Augereau JM, Fouraste I, Gleye J. Verbascoside isolated from Lantana camara, an inhibitor of protein kinase C. J Nat Prod. 1991;54:1595–600.

    Article  CAS  PubMed  Google Scholar 

  21. Cheimonidi C, Samara P, Polychronopoulos P, Tsakiri EN, Nikou T, Myrianthopoulos V, et al. Selective cytotoxicity of the herbal substance acteoside against tumor cells and its mechanistic insights. Redox Biol. 2018;16:169–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Hsieh PF, Yu CC, Chu PM, Hsieh PL. Verbascoside protects gingival cells against high glucose-induced oxidative stress via PKC/HMGB1/RAGE/NFκB pathway. Antioxidants (Basel). 2021;10:1445.

    Article  CAS  PubMed  Google Scholar 

  23. Seo ES, Oh BK, Pak JH, Yim SH, Gurunathan S, Kim YP, et al. Acteoside improves survival in cecal ligation and puncture-induced septic mice via blocking of high mobility group box 1 release. Mol Cells. 2013;35:348–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Wang HQ, Xu YX, Zhu CQ. Upregulation of heme oxygenase-1 by acteoside through ERK and PI3 K/Akt pathway confer neuroprotection against beta-amyloid-induced neurotoxicity. Neurotox Res. 2012;21:368–78.

    Article  PubMed  Google Scholar 

  25. Zhang Y, Yuan Y, Wu H, Xie Z, Wu Y, Song X, et al. Effect of verbascoside on apoptosis and metastasis in human oral squamous cell carcinoma. Int J Cancer. 2018;143:980–91.

    Article  CAS  PubMed  Google Scholar 

  26. Gan L, Li X, Zhu M, Chen C, Luo H, Zhou Q. Acteoside relieves mesangial cell injury by regulating Th22 cell chemotaxis and proliferation in IgA nephropathy. Ren Fail. 2018;40:364–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Mao Y, Yu J, Da J, Yu F, Zha Y. Acteoside alleviates UUO-induced inflammation and fibrosis by regulating the HMGN1/TLR4/TREM1 signaling pathway. PeerJ. 2023;11:e14765.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Gao W, Zhou Y, Li C, Liu T, Zhao H, Wang M, et al. Studies on the metabolism and mechanism of acteoside in treating chronic glomerulonephritis. J Ethnopharmacol. 2023;302:115866.

    Article  CAS  PubMed  Google Scholar 

  29. Wang Q, Dai X, Xiang X, Xu Z, Su S, Wei D, et al. A natural product of acteoside ameliorate kidney injury in diabetes db/db mice and HK-2 cells via regulating NADPH/oxidase-TGF-β/Smad signaling pathway. Phytother Res. 2021;35:5227–40.

    Article  CAS  PubMed  Google Scholar 

  30. Bai YH, Yang M, Feng ZJ, Zheng S. Acteoside ameliorates diabetic kidney disease via regulating the activation of the PPARγ/β-catenin pathway. ScienceAsia. 2021;47:293–302.

    Article  CAS  Google Scholar 

  31. Choi CG, Lee DJ, Chung N, Joo YH. Anti-obesity effects of isoacteoside on 3T3-L1 adipocytes. Appl Biol Chem. 2022;65:33.

    Article  CAS  Google Scholar 

  32. Wang B, Li XH, Song Z, Li ML, Wu XW, Guo MX, et al. Isoacteoside attenuates acute kidney injury induced by severe acute pancreatitis. Mol Med Rep. 2021;23:287.

    Article  CAS  PubMed  Google Scholar 

  33. Wang YN, Miao H, Hua MR, Yang JZ, Pei M, Yu HX, et al. Moshen granule ameliorates membranous nephropathy by blocking intrarenal renin-angiotensin system signalling via the Wnt1/β-catenin pathway. Phytomedicine. 2023;114:154763.

    Article  CAS  PubMed  Google Scholar 

  34. Miao H, Wang YN, Su W, Zou L, Zhuang SG, Yu XY, et al. Sirtuin 6 protects against podocyte injury by blocking the renin-angiotensin system by inhibiting the Wnt1/β-catenin pathway. Acta Pharmacol Sin. 2023;45:137–49.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Kishi S, Nagasu H, Kidokoro K, Kashihara N. Oxidative stress and the role of redox signalling in chronic kidney disease. Nat Rev Nephrol. 2024;20:101–19.

    Article  PubMed  Google Scholar 

  36. Webster AC, Nagler EV, Morton RL, Masson P. Chronic kidney disease. Lancet. 2017;389:1238–52.

    Article  PubMed  Google Scholar 

  37. Rashid I, Tiwari P, D’Cruz S, Jaswal S. Prognostic importance of neutrophil-lymphocyte ratio in non-dialysis chronic kidney disease patients—a hospital-based prospective cohort. Explor Med. 2023;4:299–313.

    Article  CAS  Google Scholar 

  38. Kalantar-Zadeh K, Jafar TH, Nitsch D, Neuen BL, Perkovic V. Chronic kidney disease. Lancet. 2021;398:786–802.

    Article  CAS  PubMed  Google Scholar 

  39. Ndongo M, Nehemie LM, Coundoul B, Diouara AAM, Seck SM. Prevalence and outcomes of polycystic kidney disease in African populations: a systematic review. World J Nephrol. 2024;13:90402.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Mullowney MW, Duncan KR, Elsayed SS, Garg N, van der Hooft JJJ, Martin NI, et al. Artificial intelligence for natural product drug discovery. Nat Rev Drug Discov. 2023;22:895–916.

    Article  CAS  PubMed  Google Scholar 

  41. Shao YF, Tang BB, Ding YH, Fang CY, Hong L, Shao CX, et al. Kaempferide ameliorates cisplatin-induced nephrotoxicity via inhibiting oxidative stress and inducing autophagy. Acta Pharmacol Sin. 2023;44:1442–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Zhong X, Jia J, Tan R, Wang L. Hederagenin improves adriamycin-induced nephropathy by inhibiting the JAK/STAT signaling pathway. Integr Med Nephrol Androl. 2024;11:e22–00016.

    Article  Google Scholar 

  43. Wang B, Yang LN, Yang LT, Liang Y, Guo F, Fu P, et al. Fisetin ameliorates fibrotic kidney disease in mice via inhibiting ACSL4-mediated tubular ferroptosis. Acta Pharmacol Sin. 2024;45:150–65.

    Article  PubMed  Google Scholar 

  44. Vagopoulou A, Theofilis P, Karasavvidou D, Haddad N, Makridis D, Tzimikas S, et al. Pilot study on the effect of flavonoids on arterial stiffness and oxidative stress in chronic kidney disease. World J Nephrol. 2024;13:95262.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Du W, Di Martino L, Li J. Natural polysaccharides-based postbiotics and their potential applications. Explor Med. 2024;5:444–58.

    Article  CAS  Google Scholar 

  46. Uddin MJ, Çiçek SS, Willer J, Shulha O, Abdalla MA, Sönnichsen F, et al. Phenylpropanoid and flavonoid glycosides from the leaves of Clerodendrum infortunatum (Lamiaceae). Biochem Syst Ecol. 2020;92:104131.

    Article  CAS  Google Scholar 

  47. Jiang X, Wang J, Lin L, Du L, Ding Y, Zheng F, et al. Macrophages promote pre-metastatic niche formation of breast cancer through aryl hydrocarbon receptor activity. Signal Transduct Target Ther. 2024;9:352.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Sládeková L, Mani S, Dvořák Z. Ligands and agonists of the aryl hydrocarbon receptor AhR: Facts and myths. Biochem Pharmacol. 2023;213:115626.

    Article  PubMed  Google Scholar 

  49. Salminen A. Aryl hydrocarbon receptor (AhR) impairs circadian regulation: Impact on the aging process. Ageing Res Rev. 2023;87:101928.

    Article  CAS  PubMed  Google Scholar 

  50. Pinto CJG, Ávila-Gálvez M, Lian Y, Moura-Alves P, Nunes Dos Santos C. Targeting the aryl hydrocarbon receptor by gut phenolic metabolites: a strategy towards gut inflammation. Redox Biol. 2023;61:102622.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Vogel CFA. Van Winkle LS, Esser C, Haarmann-Stemmann T. The aryl hydrocarbon receptor as a target of environmental stressors - Implications for pollution mediated stress and inflammatory responses. Redox Biol. 2020;34:101530.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Dong F, Perdew GH. The aryl hydrocarbon receptor as a mediator of host-microbiota interplay. Gut Microbes. 2020;12:1859812.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Zhao H, Chen L, Yang T, Feng YL, Vaziri ND, Liu BL, et al. Aryl hydrocarbon receptor activation mediates kidney disease and renal cell carcinoma. J Transl Med. 2019;17:302.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Ying Y, Song LY, Pang WL, Zhang SQ, Yu JZ, Liang PT, et al. Astragalus polysaccharide protects experimental colitis through an aryl hydrocarbon receptor-dependent autophagy mechanism. Br J Pharmacol. 2024;181:681–97.

    Article  CAS  PubMed  Google Scholar 

  55. Mo Y, Hu D, Yu W, Ji C, Li Y, Liu X, et al. Astragaloside IV attenuates indoxyl sulfate-induced injury of renal tubular epithelial cells by inhibiting the aryl hydrocarbon receptor pathway. J Ethnopharmacol. 2023;308:116244.

    Article  CAS  PubMed  Google Scholar 

  56. Li MZ, Zhao Y, Wang HR, Talukder M, Li JL. Lycopene preventing DEHP-induced renal cell damage is targeted by aryl hydrocarbon receptor. J Agric Food Chem. 2021;69:12853–61.

    Article  CAS  PubMed  Google Scholar 

  57. Liu X, Deng R, Chen Y, Huang S, Lu J, Zheng L, et al. Jian-Pi-Yi-Shen formula improves adenine-induced chronic kidney disease via regulating tryptophan metabolism and aryl hydrocarbon receptor signaling. Front Pharmacol. 2022;13:922707.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Mo Y, Jie X, Wang L, Ji C, Gu Y, Lu Z, et al. Bupi Yishen formula attenuates kidney injury in 5/6 nephrectomized rats via the tryptophan-kynurenic acid-aryl hydrocarbon receptor pathway. BMC Complement Med Ther. 2021;21:207.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Ren N, Wang WF, Zou L, Zhao YL, Miao H, Zhao YY. The nuclear factor kappa B signaling pathway is a master regulator of renal fibrosis. Front Pharmacol. 2023;14:1335094.

    Article  CAS  PubMed  Google Scholar 

  60. Wang YN, Li XJ, Wang WF, Zou L, Miao H, Zhao YY. Geniposidic acid attenuates chronic tubulointerstitial nephropathy through regulation of the NF‐κB/Nrf2 pathway via aryl hydrocarbon receptor signaling. Phytother Res. 2024;38:5441–57.

    Article  CAS  PubMed  Google Scholar 

  61. Li XJ, Wang YN, Wang WF, Nie X, Miao H, Zhao YY. Barleriside A, an aryl hydrocarbon receptor antagonist, ameliorates podocyte injury through inhibiting oxidative stress and inflammation. Front Pharmacol. 2024;15:1386604.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Naim MJ. A review on mushrooms as a versatile therapeutic agent with emphasis on its bioactive constituents for anticancer and antioxidant potential. Explor Med. 2024;5:312–30.

    Article  CAS  Google Scholar 

  63. Li XJ, Suo P, Wang YN, Zou L, Nie XL, Zhao YY, et al. Arachidonic acid metabolism as a therapeutic target in AKI-to-CKD transition. Front Pharmacol. 2024;15:1365802.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Jiang YC, Lin X, Mao Y, Zhao JQ, Zhang GH, Yu JL, et al. Acteoside alleviates renal fibrosis by inhibiting β-catenin/CTGF signaling pathway in UUO rats. Nat Prod Commun. 2022;17:1934578X2211348.

    Google Scholar 

  65. Xie Y, Lin X, Yuan J, Dong R, Yu JL, Zha Y. Effects of acteoside on the expressions of MCP-1 and TGF-β1 in the diabetic nephropathy mice. Eur J Inflamm. 2022;20:1721727X221118348.

    Article  CAS  Google Scholar 

  66. Zhang X, He H, Liang D, Jiang Y, Liang W, Chi ZH, et al. Protective effects of berberine on renal injury in streptozotocin (STZ)-induced diabetic mice. Int J Mol Sci. 2016;17:1327.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Platten M, Nollen EAA, Röhrig UF, Fallarino F, Opitz CA. Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond. Nat Rev Drug Discov. 2019;18:379–401.

    Article  CAS  PubMed  Google Scholar 

  68. Vécsei L, Szalárdy L, Fülöp F, Toldi J. Kynurenines in the CNS: recent advances and new questions. Nat Rev Drug Discov. 2013;12:64–82.

    Article  PubMed  Google Scholar 

  69. Zhao H, Zhao T, Li P. Gut microbiota-derived metabolites: a new perspective of traditional Chinese medicine against diabetic kidney disease. Integr Med Nephrol Androl. 2024;11:e23–00024.

    Article  Google Scholar 

  70. Stone TW, Darlington LG. Endogenous kynurenines as targets for drug discovery and development. Nat Rev Drug Discov. 2002;1:609–20.

    Article  CAS  PubMed  Google Scholar 

  71. Li XJ, Shan QY, Wu X, Miao H, Zhao YY. Gut microbiota regulates oxidative stress and inflammation: a double-edged sword in renal fibrosis. Cell Mol Life Sci. 2024;81:480.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Cernaro V, Calabrese V, Loddo S, Corsaro R, Macaione V, Ferlazzo VT, et al. Indole-3-acetic acid correlates with monocyte-to-high-density lipoprotein (HDL) ratio (MHR) in chronic kidney disease patients. Int Urol Nephrol. 2022;54:2355–64.

    Article  CAS  PubMed  Google Scholar 

  73. Nayak S, Boopathi S, Chandrasekar M, Panda SP, Manikandan K, Chitra V, et al. Indole-3-acetic acid exposure leads to cardiovascular inflammation and fibrosis in chronic kidney disease rat model. Food Chem Toxicol. 2024;192:114917.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study is supported by the National Natural Science Foundation of China (82074002, 82274079, 82274192, 82474062), Shaanxi Key Science and Technology Plan Project (2023-ZDLSF-26) and Shaanxi Natural Science Basic Research Program (2025JC-YBQN-1210).

Author information

Author notes

  1. These authors contributed equally: Yan-ni Wang, Xin Wu, Qi-yan Shan.

Authors and Affiliations

  1. School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China

    Yan-ni Wang, Xin Wu, Qi-yan Shan, Qiao Yang, Hua Miao, Gang Cao & Ying-yong Zhao

  2. Department of Nephrology, Shaanxi Traditional Chinese Medicine Hospital, Xi’an, 710003, China

    Xiao-yong Yu

  3. Department of Pharmacy, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011, China

    Jian-hua Yang

  4. Xinjiang Key Laboratory of Clinical Drug Research, Department of Pharmacy, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011, China

    Jian-hua Yang

Authors
  1. Yan-ni Wang
    View author publications

    Search author on:PubMed Google Scholar

  2. Xin Wu
    View author publications

    Search author on:PubMed Google Scholar

  3. Qi-yan Shan
    View author publications

    Search author on:PubMed Google Scholar

  4. Qiao Yang
    View author publications

    Search author on:PubMed Google Scholar

  5. Xiao-yong Yu
    View author publications

    Search author on:PubMed Google Scholar

  6. Jian-hua Yang
    View author publications

    Search author on:PubMed Google Scholar

  7. Hua Miao
    View author publications

    Search author on:PubMed Google Scholar

  8. Gang Cao
    View author publications

    Search author on:PubMed Google Scholar

  9. Ying-yong Zhao
    View author publications

    Search author on:PubMed Google Scholar

Contributions

HM and YYZ conceived and designed the experiments. YNW, XW, QYS and QY conducted and analysed the experiments. HM and YYZ performed statistical analysis. YYZ wrote the initial draft of the manuscript. XYY, JHY and GC revised the manuscript. All authors have critically revised the manuscript and approved its final version.

Corresponding authors

Correspondence to Hua Miao, Gang Cao or Ying-yong Zhao.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, Yn., Wu, X., Shan, Qy. et al. Acteoside-containing caffeic acid is bioactive functional group of antifibrotic effect by suppressing inflammation via inhibiting AHR nuclear translocation in chronic kidney disease. Acta Pharmacol Sin (2025). https://doi.org/10.1038/s41401-025-01598-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41401-025-01598-4

Keywords

Search

Advanced search

Quick links