Protective effect of hydroxysafflor yellow A against acute kidney injury via the TLR4/NF-κB signaling pathway

Bai, Juan; Zhao, Jing; Cui, Dai; Fan, Wei; Song, Ying; Cheng, Lianghua; Gao, Kai; Wang, Jin; Li, Long; Li, Shujun; Jia, Yi‐Xia; Wen, Aidong

doi:10.1038/s41598-018-27217-3

Cited by 52 publications

(46 citation statements)

References 40 publications

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“…TLR‐4 leads to phosphorylation of the transcription factor NF‐κB, which induces proinflammatory cytokine production as TNF‐ α that leads further liver damage (Mahmoud et al, ). In contrast, the anti‐inflammatory factor IL‐10 was suppressed (Gendy et al, ; Bai et al, ). This well explains our findings where IR resulted in increased gene expression of both NF‐κB‐p65 and TLR‐4 consequently increased TNF‐ α and INF‐γ.…”

Section: Discussionmentioning

confidence: 99%

Perindopril Ameliorates Hepatic Ischemia Reperfusion Injury Via Regulation of NF‐κB‐p65/TLR‐4, JAK1/STAT‐3, Nrf‐2, and PI3K/Akt/mTOR Signaling Pathways

Kamel

Hassanein

Ahmed

et al. 2019

The Anatomical Record

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Hepatic ischemia reperfusion (IR) is an inevitable clinical problem for surgical procedures such as liver transplantation and liver resection. This study was designed to evaluate the protective effect of perindopril (PER) against hepatic IR injury. Thirty‐two rats were used and randomly allocated into four groups. Sham control group was subjected to sham operation and received saline only, IR group was subjected to IR and received vehicle, PER group was pretreated with PER (one milligram per kilogram per day i.p. for 10 consecutive days), and IR+PER group was pretreated with PER then subjected to IR. Liver function biomarkers (aspartate aminotransferase and alanine aminotransferase), oxidative stress (glutathione, malondialdehyde, myeloperoxidase, and superoxide dismutase) and inflammation markers (tumor necrosis factor‐alpha, interferon‐gamma, and inteleukin‐10 [IL‐10]), mRNA expression of NF‐κB‐p65 and TLR‐4, as well as protein expression of JAK1, STAT‐3, PI3K, mTOR, Akt, and Nrf‐2 were investigated concomitantly with histopathological examination. The results indicated that, hepatic IR induced a significant alteration in liver function biomarkers and structure, oxidative stress, and inflammation. At the molecular level, up‐regulation of NF‐κB‐p65, TLR‐4, JAK1, and STAT‐3 concomitantly with down‐regulation of Nrf‐2, IL‐10, PI3K, Akt, and mTOR were observed. These disturbances were alleviated by pretreatment of IR rats with PER in concomitant with hepatic structural improvement. Conclusively, the protective effect of PER presumably may be relevant to its ability to reduce oxidative stress, ameliorate the inflammatory processes, and modify the related signaling pathways. Anat Rec, 2019. © 2019 American Association for Anatomy Anat Rec, 303:1935–1949, 2020. © 2019 American Association for Anatomy

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Section: Discussionmentioning

confidence: 99%

Perindopril Ameliorates Hepatic Ischemia Reperfusion Injury Via Regulation of NF‐κB‐p65/TLR‐4, JAK1/STAT‐3, Nrf‐2, and PI3K/Akt/mTOR Signaling Pathways

Kamel

Hassanein

Ahmed

et al. 2019

The Anatomical Record

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“…They found HSYA prevented I/R induced apoptosis in kidney epithelial cells in vivo and in vitro. HSYA may attenuate TLR4 signaling to prevent apoptosis in kidney epithelial cells (Bai et al, 2018). Increasing the stability of HSYA in XBJ may further enhance the protection to the kidney (Pu et al, 2017).…”

Section: C0127 Prevents C Albicans-induced Kidney Failurementioning

confidence: 99%

Xuebijing Injection Maintains GRP78 Expression to Prevent Candida albicans–Induced Epithelial Death in the Kidney

Shang

Ren

et al. 2020

Front. Pharmacol.

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Sepsis and septic shock threaten the survival of millions of patients in the intensive care unit. Secondary fungal infections significantly increased the risk of mortality in sepsis patients. Chinese medicine Xuebijing injection (XBJ) has been routinely used as an add-on treatment to sepsis and septic shock in China. Our network pharmacology analysis predicted that XBJ also influences fungal infection, consisting with results of pioneer clinical studies. We conducted in vivo and in vitro experiments to verify this prediction. To our surprise, XBJ rescued mice from lethal Candida sepsis in a disseminated Candida albicans infection model and abolished the colonization of C. albicans in kidneys. Although XBJ did not inhibit the growth and the virulence of C. albicans in vitro, it enhanced the viability of 293T cells upon C. albicans insults. Further RNA-seq analysis revealed that XBJ activated the endoplasmic reticulum (ER) stress pathway upon C. albicans infection. Western blot confirmed that XBJ maintained the expression of GRP78 in the presence of C. albicans. Interestingly, key active ingredients in XBJ (C0127) mirrored the effects of XBJ. C0127 not only rescued mice from lethal Candida sepsis and prevented the colonization of C. albicans in kidneys, but also sustained the survival of kidney epithelial cells partially by maintaining the expression of GRP78. These results suggested that XBJ may prevent fungal infection in sepsis patients. Pre-activation of ER stress pathway is a novel strategy to control C. albicans infection. Network pharmacology may accelerate drug development in the field of infectious diseases.

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“…It is also reported that hydroxysafflor yellow A protected against acute kidney ischemia/reperfusion injury via the TLR4/NF-κB signaling pathway. 52 However, the role of TLR4/NF-κB signaling pathway in flap IR injury has not been reported yet. The results showed that the expression levels of TLR4 and galectin-3 were significantly increased after IR, and such outcomes were partially reversed by rhGH treatment.…”

Section: Tlr4 and P65 Participated In The Development Of Ir Flapmentioning

confidence: 99%

Recombinant human growth hormone treatment of mice suppresses inflammation and apoptosis caused by skin flap ischemia–reperfusion injury

Liu

Wang

et al. 2019

J of Cellular Biochemistry

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Background This study was to investigate the effects of recombinant human growth hormone (rhGh) on ischemia‐reperfusion (I/R) injury of mouse flaps. Methods Healthy mice were randomly divided into four groups as follows: sham group, the IR group, the sham+rhGH group and the IR+rhGH group, with 12 mice in each group. Skin pathology was tested by hematoxylin and eosin staining. The flap survival of each group was measured after 7 days. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were determined using corresponding kit. The levels of interleukin (IL)‐6 and tumor necrosis factor (TNF)‐α in serum and flap were respectively measured by performing enzyme‐linked immunosorbent assay and quantitative real‐time (qRT)‐PCR. The expressions of cleaved caspase‐3, B cell lymphoma/leukemia‐2 (Bcl‐2), Bcl‐2‐associated X protein (Bax), vascular endothelial growth factor (VEGF), MnSOD, toll‐like receptor 4 (TLR4), and galectin‐3 and (p)‐p65 were analyzed by RT‐PCR or/and Western blot. Results Prophylactic systemic application of recombinant human GH reduced the pathological damage of skin IR and significantly improved the flap survival of IR in mice, accompanied by elevation of VEGF. After administration of recombinant human GH, the activity of SOD/MnSOD in the flap was significantly increased, while the content of MDA was decreased. Cleaved caspase‐3 and Bax were downregulated and Bcl‐2 was upregulated in IR+rhGH group, compared to IR group. The levels of TLR4, Galectin‐3 and p‐p65 were decreased by rhGH. Conclusion rhGH had protective effects on flap IR injury, and can be used as a drug intervention target for the treatment of skin flap IR injury.

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Protective effect of hydroxysafflor yellow A against acute kidney injury via the TLR4/NF-κB signaling pathway

Cited by 52 publications

References 40 publications

Perindopril Ameliorates Hepatic Ischemia Reperfusion Injury Via Regulation of NF‐κB‐p65/TLR‐4, JAK1/STAT‐3, Nrf‐2, and PI3K/Akt/mTOR Signaling Pathways

Perindopril Ameliorates Hepatic Ischemia Reperfusion Injury Via Regulation of NF‐κB‐p65/TLR‐4, JAK1/STAT‐3, Nrf‐2, and PI3K/Akt/mTOR Signaling Pathways

Xuebijing Injection Maintains GRP78 Expression to Prevent Candida albicans–Induced Epithelial Death in the Kidney

Recombinant human growth hormone treatment of mice suppresses inflammation and apoptosis caused by skin flap ischemia–reperfusion injury

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