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Original Research

Open Access

Hispidulin protective impact on sepsis induced acute kidney injury is mediated by regulation of AKT and NF-κB pathway

  • Haihong Xu1
  • Xiaomei Chen1
  • Daoqin Liu1
  • Yanlang Yang1,*,

1Department of Nephrology, Wannan Medical College Affiliated Yijishan Hospital, 241000 Wuhu, Anhui, China

DOI: 10.22514/sv.2023.109 Vol.19,Issue 6,November 2023 pp.152-159

Submitted: 31 August 2023 Accepted: 16 October 2023

Published: 08 November 2023

*Corresponding Author(s): Yanlang Yang E-mail:


Sepsis-induced acute kidney injury is associated with inflammatory dysregulations within the kidney. This study aimed to explore the renal protective effect of hispidulin on suppressing the apoptosis rate, and inhibiting reactive oxygen species production and inflammatory response after cecal puncture (CLP) operation. In order to gain a deeper understanding of the relationship between sepsis and acute kidney injury, the CLP induced kidney injury animal model was established. The automated biochemical analyzer was used to measure the kidney function related biomarkers including serum cystatin C (ScysC), blood urea nitrogen (BUN), and serum creatinine (Scr). The pathological changes of damaged kidney tissues were detected by hematoxylin and eosin (H&E) staining. The expression of inflammatory cytokines including tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interleukin 6 (IL-6) were detected by their corresponding test kits and Real-Time Quantitative Reverse Transcription PCR (qRT-PCR). The level of reactive oxygen species production-related protein including myeloperoxidase (MPO), glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) in kidney tissue from each group were quantized using Enzyme-linked immunosorbent assay (ELISA). The protein expression was measured using western blot and the apoptotic rate of kidney tissue was measured by terminal deoxynucleotidyl transferase Deoxyuridine Triphosphate (dUTP) nick end labeling (TUNEL) assay. Our results revealed that hispidulin has the protective ability in sepsis-induced acute kidney injury. The potential mechanism of hispidulin on sepsis-induced cell apoptosis, oxidative stress and inflammatory response was also investigated. Finally, our results highlighted that hispidulin exerted a protective effects on CLP-induced acute kidney injury by suppressing the protein kinase B (AKT) and Nuclear factor kappa B (NF-κB) signaling pathways. In summary, the current study provided a piece of novel evidence, that hispidulin can be explored as a potential drug in CLP-induced acute kidney injury by examining its effects on suppressed the oxidative stress, inflammatory responses, and apoptosis in kidney tissue.


Sepsis; Acute kidney injury; Hispidulin; AKT; NF-κB

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Haihong Xu,Xiaomei Chen,Daoqin Liu,Yanlang Yang. Hispidulin protective impact on sepsis induced acute kidney injury is mediated by regulation of AKT and NF-κB pathway. Signa Vitae. 2023. 19(6);152-159.


[1] Watchorn J, Huang D, Bramham K, Hutchings S. Decreased renal cortical perfusion, independent of changes in renal blood flow and sublingual microcirculatory impairment, is associated with the severity of acute kidney injury in patients with septic shock. Critical Care. 2022; 26: 261.

[2] Yue S, Li S, Huang X, Liu J, Hou X, Zhao Y, et al. Machine learning for the prediction of acute kidney injury in patients with sepsis. Journal of Translational Medicine. 2022; 20: 215.

[3] Ren Q, Guo F, Tao S, Huang R, Ma L, Fu P. Flavonoid fisetin alleviates kidney inflammation and apoptosis via inhibiting Src-mediated NF-κB p65 and MAPK signaling pathways in septic AKI mice. Biomedicine & Pharmacotherapy. 2020; 122: 109772.

[4] Lin WH, Jiang WP, Chen CC, Lee LY, Tsai YS, Chien LH, et al. 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: 2877.

[5] Liu L, Shi Q, Wang K, Qian Y, Zhou L, Bellusci S, et al. Fibroblast growth factor 10 protects against particulate matter-induced lung injury by inhibiting oxidative stress-mediated pyroptosis via the PI3K/Akt/Nrf2 signaling pathway. International Immunopharmacology. 2022; 113: 109398.

[6] Wang Y, Wu Y, Peng S. Resveratrol inhibits the inflammatory response and oxidative stress induced by uterine ischemia reperfusion injury by activating PI3K-AKT pathway. PLOS ONE. 2022; 17: e0266961.

[7] Lee HW, Choi IW, Ha SK. Immunostimulatory activities of theobromine on macrophages via the activation of MAPK and NF-κB signaling pathways. Current Issues in Molecular Biology. 2022; 44: 4216–4228.

[8] Liu K, Zhao F, Yan J, Xia Z, Jiang D, Ma P. Hispidulin: a promising flavonoid with diverse anti-cancer properties. Life Sciences. 2020; 259: 118395.

[9] An P, Wu T, Yu H, Fang K, Ren Z, Tang M. Hispidulin protects against focal cerebral ischemia reperfusion injury in rats. Journal of Molecular Neuroscience. 2018; 65: 203–212.

[10] Ruiz S, Vardon-Bounes F, Merlet-Dupuy V, Conil J, Buléon M, Fourcade O, et al. Sepsis modeling in mice: ligation length is a major severity factor in cecal ligation and puncture. Intensive Care Medicine Experimental. 2016; 4: 22.

[11] Song C, Adili A, Kari A, Abuduhaer A. FSTL1 aggravates sepsis-induced acute kidney injury through regulating TLR4/MyD88/NF-κB pathway in newborn rats. Signa Vitae. 2021; 17:167–173.

[12] Djudjaj S, Boor P. Cellular and molecular mechanisms of kidney fibrosis. Molecular Aspects of Medicine. 2019; 65: 16–36.

[13] Abdelnaser M, Alaaeldin R, Attya ME, Fathy M. Modulating Nrf-2/HO-1, apoptosis and oxidative stress signaling pathways by gabapentin ameliorates sepsis-induced acute kidney injury. To be published in Naunyn-Schmiedeberg’s Archives of Pharmacology. 2023. [Preprint].

[14] Liu K, Zhao F, Yan J, Xia Z, Jiang D, Ma P. Hispidulin: a promising flavonoid with diverse anti-cancer properties. Life Sciences. 2020; 259: 118395.

[15] Wang X, Fan D, Cao X, Ye Q, Wang Q, Zhang M, et al. The role of reactive oxygen species in the rheumatoid arthritis-associated synovial microenvironment. Antioxidants. 2022; 11: 1153.

[16] Chen Y, Zhou X, Wu Y. The miR-26a-5p/IL-6 axis alleviates sepsis-induced acute kidney injury by inhibiting renal inflammation. Renal Failure. 2022; 44: 551–561.

[17] Zhang B, Zeng M, Li B, Kan Y, Wang S, Cao B, et al. Arbutin attenuates LPS-induced acute kidney injury by inhibiting inflammation and apoptosis via the PI3K/Akt/Nrf2 pathway. Phytomedicine. 2021; 82: 153466.

[18] Liu D, Zhong Z, Karin M. NF-κB: a double-edged sword controlling inflammation. Biomedicines. 2022; 10: 1250.

[19] Potočnjak I, Marinić J, Batičić L, Šimić L, Broznić D, Domitrović R. Aucubin administered by either oral or parenteral route protects against cisplatin-induced acute kidney injury in mice. Food and Chemical Toxicology. 2020; 142: 111472.

[20] Karimian A, Mir SM, Parsian H, Refieyan S, Mirza‐Aghazadeh‐Attari M, Yousefi B, et al. Crosstalk between phosphoinositide 3-kinase/Akt signaling pathway with DNA damage response and oxidative stress in cancer. Journal of Cellular Biochemistry. 2019; 120: 10248–10272.

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