Kaempferol Reverses Acute Kidney Injury in Septic Model by Inhibiting NF-<i>κ</i>B/AKT Signaling Pathway

Chen, Dagui; Ma, Senlin; Ye, Wangzheng; Wang, Wenwen; Sun, Da; Shang, Fusheng; Lin, Lili

doi:https://doi.org/10.1155/2023/1353449

Journal of Food Biochemistry

On this page

Abstract Introduction Materials and Methods Results Discussion Data Availability Conflicts of Interest Authors’ Contributions Acknowledgments References Copyright Related Articles

Research Article | Open Access

Volume 2023 | Article ID 1353449 | https://doi.org/10.1155/2023/1353449

Kaempferol Reverses Acute Kidney Injury in Septic Model by Inhibiting NF-κB/AKT Signaling Pathway

Dagui Chen,¹Senlin Ma,²Wangzheng Ye,³Wenwen Wang,⁴Da Sun,⁴Fusheng Shang,¹and Lili Lin⁴

Academic Editor: Jae Young Je

Received12 Oct 2022

Revised15 Feb 2023

Accepted21 Feb 2023

Published06 Mar 2023

Abstract

Sepsis is the main cause of acute kidney injury (AKI), mainly due to systemic immune dysregulation. Kaempferol (KAE) is a natural flavonoid compound with multiple biological activities including anti-inflammatory, antioxidant, and antiapoptotic properties. In this study, we constructed a sepsis-induced AKI mouse model and an LPS-induced glomerular mesangial cell (HK-2) in vitro sepsis AKI model. We found that KAE ameliorated sepsis-induced renal pathological damage, reversed renal function damage, and inhibited p-p65 and p-AKT protein expression. In addition, KAE reversed LPS-induced proliferation and inhibited apoptosis in HK-2 cells. These studies suggest that KAE reverses sepsis by inhibiting activation of the NF-κB/AKT pathway to reverse acute kidney injury.

1. Introduction

Acute kidney injury (AKI) is a clinical syndrome of rapidly declining kidney function and kidney injury caused by multiple factors, and infection is one of the most common causes of AKI [1]. Acute kidney injury currently affects 13 million people worldwide each year and is one of the most common complications in hospitalized patients [2, 3]; its adverse consequences include kidney failure, cardiovascular events, and increased mortality [4, 5]. In China, 29 million patients are hospitalized due to AKI; approximately 40% of them die of AKI, and most of them cannot fully recover [6].

Sepsis is a systemic immune response triggered by infection and is the main killer of patients in the ICU with AKI [7, 8]. Therefore, it is a challenge to prevent and control the occurrence of AKI and reduce the morbidity and mortality of septic patients. Pathophysiological mechanisms of AKI in sepsis are complex and multifactorial, posing significant obstacles to its treatment. Among the known mechanisms of AKI in sepsis, oxidative stress responses are associated with inflammatory responses [9, 10]. Huang et al. showed that ultrasmall TWNDs have a very strong ability to eliminate a variety of ROS, which allows them to restore renal function in AKI at very low doses [11]. Ren et al. showed that fesarone prevented AKI in sepsis by reducing renal inflammation and apoptosis through inhibition of Src-mediated NF-κB p65 and MAPK signaling pathways, thereby preventing AKI in sepsis [12].

Kaempferol (3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one, KAE) is a natural flavonoid compound that is present in a variety of edible plants (e.g., legumes, leeks, tea) and commonly used drugs in traditional Chinese medicines (e.g., kaempferol, cat eye grass, white hair grass) [13]. Kaempferol and its derivatives have been largely demonstrated to have anti-inflammatory, antioxidant, antibacterial, and antitumor effects [14]. Molitorisova et al. reported that kaempferol modulated allergic airway inflammation and associated asthma characteristics [15]. Similarly, Liu et al. demonstrated that kaempferol was able to reduce oxidative stress and inflammatory responses through the downregulation of ROS-dependent MAPK/NF-κB and pyroptosis signaling pathways [16]. However, kaempferol has not been reported to treat sepsis-induced AKI. It is a product of natural origin and has fewer toxic side effects and interactions with chemical agents and biological agents. Therefore, in this study, we established in vitro and in vivo AKI models of sepsis and investigated the effect of kaempferol on sepsis-induced AKI and its mechanism.

2. Materials and Methods

2.1. Construction and Grouping of Sepsis Mouse Model

Eight-week-old male C57BL/6 mice (22–26 g, SFP grade) were purchased from Kevens Animal Laboratory Co., Ltd., Changzhou, China. Mice were maintained at room temperature (25 ± 2°C, 55 ± 5% humidity) for 3 days with free access to food and water. All animal study procedures were performed following the Guide for the Care and Use of Laboratory Animals published by the National Academy of Sciences and the National Institutes of Health (NIH Publication No. 86-23, Revised 1996). The animal protocol was approved by the Ethics Committee of Shanghai University. Sepsis models were established using cecal ligation and puncture (CLP) surgery [17]. Forty mice were randomly divided into the following 5 groups (n = 8/group): control group, AKI group, KAE 25 mg/kg group, KAE 50 mg/kg group, and KAE 100 mg/kg group. All treatment reagents were injected through the tail vein, and treatment was continuously administered to the treatment groups for 3 weeks. At the end of the study, tissues were collected from euthanized mice after weighing and anaesthetization with ether (Sigma‒Aldrich).

2.2. H&E Staining

After harvesting the kidney tissues, the right kidney was washed with normal saline, fixed in 4% paraformaldehyde fixative for 48 hrs, stripped step-by-step, processed transparently, embedded in paraffin wax, cut into 5-μm-thick sections, deparaffinized, hydrated, stained with hematoxylin & eosin method, rinsed, dehydrated and cleared, mounted, and observed and photographed under a microscope (NIKON E100, Japan).

2.3. ELISA Experiments

Tissue and cell samples were processed according to TNF-α and IL-1β ELISA kit instructions (MULTISCIENCES, Hangzhou, China), and the absorbance at 450 nm was measured using a microplate reader to draw a standard curve and calculate the concentration.

2.4. RT‒PCR

Total RNA was extracted using TRIzol according to the manufacturer’s protocol, and recovered RNA was purified in strict accordance with the RNA recovery kit’s instructions. cDNA from a reverse transcription reaction was used, and we performed real-time PCR in triplicate using Power SYBR Green polymerase chain reaction (PCR) master mix and an ABI 7500 real-time PCR system. All procedures were performed according to the manufacturer’s recommendations. All primers were synthesized by Sangon Biotech Co., Ltd. (Shanghai, China), and the primer sequences used are shown in Table 1, with GAPDH used as an internal control. The relative expression of target genes was calculated based on the 2-Ct value.

2.5. Western Blot

Samples from each group were added to protein lysis buffer and PMSF, placed on ice for 40 min, and centrifuged at 12,000 r/min for 40 min at 4°C, and then the supernatant was taken. Protein quantification in the supernatant was performed by a Bradford assay using BSA as a standard. Twenty microgram protein samples were separated by 10% SDS‒PAGE. The antibodies used were NF-κB p65 (AF5006, Affinity), p-NF-κB p65 (AF3387, Affinity), Akt (AF6261, Affinity), and p-Akt (AF0016, Affinity), and HRP-labeled goat anti-mouse IgG (H + L) (SA00001-1; Proteintech) was used as a secondary antibody. Band intensities were quantified using ImageJ software, and all samples were compared to GAPDH (60004-1-Ig, Proteintech) as a reference protein.

2.6. Cell Culture

The human tubular epithelial cell line HK-2 (FH0228, FuHeng Biology) was cultured in high glucose DMEM containing 10% fetal bovine serum at 37°C and 5% CO₂. HK-2 cells were treated with 10 µg/ml lipopolysaccharide (Sigma‒Aldrich) for 24 h to induce a cellular model of sepsis acute kidney injury in vitro according to Sun et al. [18].

2.7. Cell Proliferation

Cells from the experimental and control groups in the logarithmic growth phase were inoculated into 96-well plates at 1 × 10⁴ cells/well, and culture medium was added to a final volume of 100 µl in each well; the cells were cultured in 5% CO₂ at 37°C, and 6 replicate wells and 2 control wells were included. CCK-8 reagent was added, and the absorbance at 450 nm was measured using a microplate reader. Cell growth curves were plotted with control zeroing, with time as the abscissa and absorbance as the ordinate.

2.8. Flow Apoptosis

Apoptosis was detected by flow cytometry using an Annexin V-FITC Apoptosis Assay Kit (Beyotime, Shanghai, China). After removing the intervention culture medium from each group, trypsin was added to digest the cells, and DMEM complete culture medium was used to adjust the cell suspension concentration to 10⁶/mL. Then, 75% ethanol was added up to 2 mL to fix the cells, and the cells were gently mixed after standing for 5 min and then placed in a low-temperature centrifuge for centrifugation at 12,000 rpg for 10 min. After the end of centrifugation, the supernatant was removed, and PBS solution was added to the cell pellet to gently wash the cells three times for 5 min each time. Annexin V-FITC/PI double staining and flow cytometer onboard detection were performed according to the manufacturer’s instructions.

2.9. Statistical Analysis

Experimental data are presented as the means ± SD, and one-way analysis of variance (ANOVA) and correlation analysis were performed using GraphPad Prism statistical software 7.0. Differences between the two groups were compared using Bonferroni post hoc comparisons. was considered statistically significant.

3. Results

3.1. KAE Improves Sepsis-Induced AKI

KAE treatment of septic mice significantly increased body weight (Figure 1(a)), significantly decreased the renal index (kidney weight/body weight) (Figure 1(b)), and significantly increased serum creatinine and blood urea nitrogen (Figures 1(c) and 1(d)). Taken together, the results suggest that KAE ameliorates sepsis-induced acute kidney injury in mice.

(a)

(b)

(c)

(d)

3.2. KAE Ameliorates Pathological Changes in Mice with Sepsis-Induced AKI

We performed HE staining to observe morphological changes in the kidney. As shown in Figure 2, septic mice showed marked changes in the renal tissue, such as glomerular necrosis and hypertrophy, which were significantly improved by KAE treatment.

3.3. Anti-inflammatory Response to KAE in Sepsis-Induced AKI Mice

Inflammation is well known to contribute to the pathogenesis of AKI [19]. In this study, we detected increased IL-1β and TNF-α protein levels in renal tissue during AKI and significantly decreased expression after administration of different doses of KAE (Figures 3(a) and 3(b)). We then detected IL-1β and TNF-α expression levels in kidney tissues from each group and found consistent changes in protein expression detected by ELISA (Figures 3(c) and 3(d)).

(a)

(b)

(c)

(d)

These results suggest that KAE plays an anti-inflammatory role in AKI therapy.

3.4. Mechanism of KAE in Sepsis-Induced AKI in Mice

To further investigate the potential mechanism of KAE in sepsis-induced AKI in mice, we examined changes in NF-κB/AKT pathway expression levels within renal tissue (Figure 4(a)). We found that KAE did not affect NF-κB p65 and AKT expression, whereas levels of NF-κB p65 and AKT phosphorylation were dose-dependently decreased (Figure 4(b)). Overall, our findings suggest that KAE reverses sepsis-induced AKI by inhibiting NF-κB/AKT pathway phosphorylation.

(a)

(b)

3.5. KAE Inhibits LPS-Induced Proliferation of Glomerular Mesangial Cells

To assess the toxicity of KAE to glomerular mesangial cells, we performed viability tests with different KAE concentrations. As KAE showed no significant inhibition of cell viability at concentrations below 25 µM (Figure 5(a)), we chose KAE doses of 5, 10, and 20 µM for in vitro experiments. In addition, LPS was found to inhibit glomerular mesangial cell proliferation, which was reversed by KAE (Figure 5(b)). In conclusion, KAE can promote mesangial cell proliferation in a dose-dependent manner.

(a)

(b)

3.6. KAE Suppresses the Secretion of Inflammatory Cytokines

Administration of KAE to LPS-treatedHK-2 cells significantly decreased the secretion of the inflammatory cytokines TNF-α and IL-1β, as measured by ELISA, and the secretion of inflammatory cytokines was significantly increased in LPS-treated cells (Figure 6(a)). Subsequently, we measured the mRNA expression levels of IL-1β and TNF-α in the cells of each group (Figure 6(b)), and the results were consistent with the ELISA results. These data suggest that KAE can reverse AKI injury by inhibiting the secretion of inflammatory cytokines.

(a)

(b)

(c)

(d)

3.7. KAE Inhibits HK-2 Cell Apoptosis

LPS promoted apoptosis in HK-2 cells, and KAE treatment significantly decreased the LPS-induced increase in apoptosis (Figure 7). These results suggest that KAE reverses AKI injury by inhibiting the apoptosis of HK-2 cells.

3.8. KAE Inhibits the NF-κB/AKT Pathway

LPS activated the NF-κB/AKT pathway, causing cell damage in HK-2 cells, while KAE reversed LPS-induced NF-κB/AKT pathway activation (Figures 8(a) and 8(b)). This result suggests that KAE reverses AKI injury by inhibiting NF-κB/AKT pathway activation.

(a)

(b)

4. Discussion

AKI is an acute disease that seriously threatens human life and health, and the mortality rate of AKI caused by sepsis is significantly higher than that of AKI patients without sepsis [20]. Studies have shown that AKI caused by sepsis is mostly manifested as injury caused by an inflammatory response and accompanied by apoptosis [21]. In our study, we first demonstrated through small mouse experiments that KAE can improve renal index and renal histological damage in sepsis-induced AKI, i.e., decrease BUN and SCr concentrations and TNF-α and IL-1β expression. In vitro, we constructed a LPS-induced sepsis injury model in HK-2 cells. The effects of KAE on cell proliferation, inflammation, and apoptosis were examined to further investigate the cytoprotective effect of KAE on septic kidney injury. The experimental results showed that KAE could reduce the expression of proinflammatory cytokines and increase the expression of anti-inflammatory cytokines in mice with suppurative AKI, thereby reversing AKI kidney injury. In addition, we demonstrated that KAE could modulate proliferation, apoptosis, and inflammation responses in LPS-treatedHK-2 cells.

BUN and SCr are important indicators for judging the severity of the renal injury and are commonly used to evaluate renal function. Alshehri et al. found that kaempferol decreased concentrations of BUN and SCr in a rat model of CdCl 2-induced kidney injury [22]. In this study, we found that kaempferol significantly improved the degree of kidney injury and decreased levels of injury parameters such as BUN and SCr in a mouse model of septic kidney injury. This study is the first to validate the protective effect of kaempferol in the AKI model. In addition, we also investigated the expression of TNF-α and IL-1β, representative regulators of inflammation, which were similar to the results for BUN and SCr. These results suggest that kaempferol can further explain its protective effect by inhibiting the inflammatory response caused by renal injury in sepsis.

In cellular experiments, Zhang et al. found that LPS can increase TNF-α and IL-1β expression in HK-2 cells [23]. In this study, HK-2 cells were treated with 10 µg/ml LPS, and TNF-α and IL-1β expression was increased, confirming that LPS can induce inflammatory damage in HK-2 cells. Subsequently, treatment with kaempferol at different concentrations was found to be effective in reducing inflammatory cell levels, and in addition, we found that kaempferol treatment significantly reduced LPS-induced apoptosis of HK-2 cells by flow cytometry, suggesting that kaempferol could attenuate LPS-induced inflammatory injury by inhibiting proinflammatory cytokine expression and inhibiting apoptosis.

NF-κB/AKT is an important regulator of cellular homeostasis [24]. NF-κB is a transcription factor that has been implicated in inflammation, tumors, apoptosis, and various autoimmune diseases, and it is recognized that NF-κB activation is caused by various external stimuli and is essential for the induction of various proinflammatory cytokines (e.g., IL-1β, TNF-α) [25, 26]. Inhibition of NF-κB signaling has been shown to attenuate acute kidney injury [27, 28]. AKT is a downstream target gene of NF-κB and an important functional protein in maintaining cell survival [29]. It has been demonstrated that AKT inhibition improves inflammatory responses to reverse AKI kidney injury [30]. In this study, we clarified that KAE reversed AKI kidney injury by inhibiting the NF-κB/AKT signaling pathway.

In our study, we first demonstrated that KAE lowers the expression of proinflammatory cytokines and increases the expression of anti-inflammatory cytokines in septic AKI mice, thereby reversing AKI kidney injury. Akhter N et al. reported that calcium dobesilate could reverse AKI injury in severely burned mice by inhibiting NF-κB/AKT expression [31], which is consistent with our study. Park et al. found that kaempferol was able to reduce LPS-induced inflammatory mediators by downregulating NF-κB and AKT [32]. The above information provides an effective research strategy from our study to reverse acute kidney injury caused by sepsis. In this study, we demonstrate that kaempferol reverses sepsis-induced acute kidney injury by inhibiting the NF-κB/AKT signaling pathway.

Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Authors’ Contributions

Fusheng Shang and Lili Lin conceived and designed the experiments; Dagui Chen, Senlin Ma, Wangzheng Ye, Wenwen Wang, and Da Sun performed the experiments; Dagui Chen, Senlin Ma, and Wangzheng Ye analyzed the data; Fusheng Shang and Lili Lin wrote the manuscript. All authors read and approved the final manuscript. Dagui Chen, Senlin Ma, and Wangzheng Ye contributed equally to this work.

Acknowledgments

The authors thank all students and technicians in the laboratory for their cooperation.

References

R. L. Mehta, J. A. Kellum, S. V. Shah et al., “Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury,” Critical Care, vol. 11, no. 2, p. R31, 2007.
View at: Publisher Site | Google Scholar
R. L. Mehta, J. Cerdá, E. A. Burdmann et al., “International Society of Nephrology's 0by25 initiative for acute kidney injury (zero preventable deaths by 2025): a human rights case for nephrology,” The Lancet, vol. 385, no. 9987, pp. 2616–2643, 2015.
View at: Publisher Site | Google Scholar
H. Wang, E. Lambourg, B. Guthrie, D. R. Morales, P. T. Donnan, and S. Bell, “Patient outcomes following AKI and AKD: a population-based cohort study,” BMC Medicine, vol. 20, no. 1, p. 229, 2022.
View at: Publisher Site | Google Scholar
J. A. Kellum, P. Romagnani, G. Ashuntantang, C. Ronco, A. Zarbock, and H. J. Anders, “Acute kidney injury,” Nature Reviews Disease Primers, vol. 7, no. 1, p. 52, 2021.
View at: Publisher Site | Google Scholar
C. Ronco, R. Bellomo, and J. A. Kellum, “Acute kidney injury,” The Lancet, vol. 394, no. 10212, pp. 1949–1964, 2019.
View at: Publisher Site | Google Scholar
L. Yang, G. Xing, L. Wang et al., “Acute kidney injury in China: a cross-sectional survey,” The Lancet, vol. 386, no. 10002, pp. 1465–1471, 2015.
View at: Publisher Site | Google Scholar
K. Y. d A. Santana, A. P. A. Santos, F. B. Magalhães, J. C. Oliveira, F. G. d M. S. Pinheiro, and E. S. Santos, “Prevalence and factors associated with acute kidney injury in patients in intensive care units,” Revista Brasileira de Enfermagem, vol. 74, no. 2, Article ID e20200790, 2021.
View at: Publisher Site | Google Scholar
J. Xu, X. Yang, L. Yang et al., “Clinical course and predictors of 60-day mortality in 239 critically ill patients with COVID-19: a multicenter retrospective study from Wuhan, China,” Critical Care, vol. 24, no. 1, p. 394, 2020.
View at: Publisher Site | Google Scholar
Q. Chen, Y. Nan, Y. Yang et al., “Nanodrugs alleviate acute kidney injury: manipulate RONS at kidney,” Bioactive Materials, vol. 22, pp. 141–167, 2023.
View at: Publisher Site | Google Scholar
C. L. Manrique-Caballero, G. Del Rio-Pertuz, and H. Gomez, “Sepsis-associated acute kidney injury,” Critical Care Clinics, vol. 37, no. 2, pp. 279–301, 2021.
View at: Publisher Site | Google Scholar
Q. Huang, Y. Yang, T. Zhao et al., “Passively-targeted mitochondrial tungsten-based nanodots for efficient acute kidney injury treatment,” Bioactive Materials, vol. 21, pp. 381–393, 2023.
View at: Publisher Site | Google Scholar
Q. Ren, F. Guo, S. Tao, R. Huang, L. Ma, and P. Fu, “Flavonoid fisetin alleviates kidney inflammation and apoptosis via inhibiting Src-mediated NF-κB p65 and MAPK signaling pathways in septic AKI mice,” Biomedicine & Pharmacotherapy, vol. 122, Article ID 109772, 2020.
View at: Publisher Site | Google Scholar
M. Imran, B. Salehi, J. Sharifi-Rad et al., “Kaempferol: a key emphasis to its anticancer potential,” Molecules, vol. 24, no. 12, p. 2277, 2019.
View at: Publisher Site | Google Scholar
W. Alam, H. Khan, M. A. Shah, O. Cauli, and L. Saso, “Kaempferol as a dietary anti-inflammatory agent: current therapeutic standing,” Molecules, vol. 25, no. 18, p. 4073, 2020.
View at: Publisher Site | Google Scholar
M. Molitorisova, M. Sutovska, I. Kazimierova et al., “The anti-asthmatic potential of flavonol kaempferol in an experimental model of allergic airway inflammation,” European Journal of Pharmacology, vol. 891, Article ID 173698, 2021.
View at: Publisher Site | Google Scholar
Z. Liu, X. Yao, B. Sun et al., “Pretreatment with kaempferol attenuates microglia-mediate neuroinflammation by inhibiting MAPKs-NF-κB signaling pathway and pyroptosis after secondary spinal cord injury,” Free Radical Biology and Medicine, vol. 168, pp. 142–154, 2021.
View at: Publisher Site | Google Scholar
L. Dejager, I. Pinheiro, E. Dejonckheere, and C. Libert, “Cecal ligation and puncture: the gold standard model for polymicrobial sepsis?” Trends in Microbiology, vol. 19, no. 4, pp. 198–208, 2011.
View at: Publisher Site | Google Scholar
C. Yu, D. Qi, J. F. Sun, P. Li, and H. Y. Fan, “Rhein prevents endotoxin-induced acute kidney injury by inhibiting NF-κB activities,” Scientific Reports, vol. 5, no. 1, Article ID 11822, 2015.
View at: Publisher Site | Google Scholar
H. Rabb, M. D. Griffin, D. B. McKay et al., “Inflammation in AKI: current understanding, key questions, and knowledge gaps,” Journal of the American Society of Nephrology, vol. 27, no. 2, pp. 371–379, 2016.
View at: Publisher Site | Google Scholar
C. Zheng, Y. Zhou, Y. Huang et al., “Effect of ATM on inflammatory response and autophagy in renal tubular epithelial cells in LPS-induced septic AKI,” Experimental and Therapeutic Medicine, vol. 18, no. 6, pp. 4707–4717, 2019.
View at: Publisher Site | Google Scholar
S. Peerapornratana, C. L. Manrique-Caballero, H. Gómez, and J. A. Kellum, “Acute kidney injury from sepsis: current concepts, epidemiology, pathophysiology, prevention and treatment,” Kidney International, vol. 96, no. 5, pp. 1083–1099, 2019.
View at: Publisher Site | Google Scholar
A. S. Alshehri, A. F. El-Kott, A. E. El-Kenawy et al., “The ameliorative effect of kaempferol against CdCl2- mediated renal damage entails activation of Nrf2 and inhibition of NF-kB,” Environmental Science and Pollution Research, vol. 29, no. 38, pp. 57591–57602, 2022.
View at: Publisher Site | Google Scholar
Y. Zhang, Y. Zhang, A. Yang, and F. Xia, “Downregulation of IRF2 alleviates sepsis-related acute kidney injury in vitro and in vivo,” Drug Design, Development and Therapy, vol. 15, pp. 5123–5132, 2021.
View at: Publisher Site | Google Scholar
A. K. V. Iyer, N. Azad, S. Talbot et al., “Antioxidant c-FLIP inhibits f ligand-induced NF-κB activation in a phosphatidylinositol 3-kinase/a-dependent manner,” The Journal of Immunology, vol. 187, no. 6, pp. 3256–3266, 2011.
View at: Publisher Site | Google Scholar
L. Barnabei, E. Laplantine, W. Mbongo, F. Rieux-Laucat, and R. Weil, “NF-κB: at the borders of autoimmunity and inflammation,” Frontiers in Immunology, vol. 12, Article ID 716469, 2021.
View at: Publisher Site | Google Scholar
H. Yu, L. Lin, Z. Zhang, H. Zhang, and H. Hu, “Targeting NF-κB pathway for the therapy of diseases: mechanism and clinical study,” Signal Transduction and Targeted Therapy, vol. 5, no. 1, p. 209, 2020.
View at: Publisher Site | Google Scholar
H. M. Niu, L. Q. Guo, Y. H. Qiao, and H. Y. Jiao, “MiR-429 prohibited NF-κB signalling to alleviate contrast-induced acute kidney injury via targeting PDCD4,” Autoimmunity, vol. 54, no. 5, pp. 243–253, 2021.
View at: Publisher Site | Google Scholar
J. Li, Z. Zhang, L. Wang et al., “Maresin 1 attenuates lipopolysaccharide-induced acute kidney injury via inhibiting NOX4/ROS/NF-κB pathway,” Frontiers in Pharmacology, vol. 12, Article ID 782660, 2021.
View at: Publisher Site | Google Scholar
J. G. Kiang, J. T. Smith, G. Cannon et al., “Ghrelin, a novel therapy, corrects cytokine and NF-κB-AKT-MAPK network and mitigates intestinal injury induced by combined radiation and skin-wound trauma,” Cell & Bioscience, vol. 10, no. 1, p. 63, 2020.
View at: Publisher Site | Google Scholar
Y. Yan, R. Z. Tan, P. Liu et al., “Oridonin alleviates IRI-induced kidney injury by inhibiting inflammatory response of macrophages via AKT-related pathways,” Medical Science Monitor, vol. 26, Article ID e921114, 2020.
View at: Publisher Site | Google Scholar
N. Akhter, H. Sun, J. O. Machuki, and H. Q. Ren, “Protective effect of calcium dobesilate on induced AKI in severely burned mice,” Nephron, vol. 145, no. 5, pp. 553–567, 2021.
View at: Publisher Site | Google Scholar
S. E. Park, K. Sapkota, S. Kim, H. Kim, and S. J. Kim, “Kaempferol acts through mitogen-activated protein kinases and protein kinase B/AKT to elicit protection in a model of neuroinflammation in BV2 microglial cells,” British Journal of Pharmacology, vol. 164, no. 3, pp. 1008–1025, 2011.
View at: Publisher Site | Google Scholar

Copyright

Copyright © 2023 Dagui Chen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation

Download other formats

Order printed copies