Flavonoid fisetin alleviates kidney inflammation and apoptosis via inhibiting Src-mediated NF-κB p65 and MAPK signaling pathways in septic AKI mice

Ren, Qian; Guo, Fan; Tao, Sibei; Huang, Rongshuang; Fu, Ping

doi:10.1016/j.biopha.2019.109772

Cited by 278 publications

(180 citation statements)

References 29 publications

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“…Control animals were treated with an equivalent volume of vehicle (0.5% CMC-Na, 10 ml/kg) which was used to dissolve the test compound. Data were represented as mean ± SD (n = 10), ** p < 0.01 vs. control group COX-2 and the release of inflammatory cytokines (Yeung et al 2018;Ren et al 2019). In our study, we found that azadirone (1) inhibited the releases of inflammatory factors in LPS-induced macrophages.…”

Section: Discussionsupporting

confidence: 54%

“…The formalin test is a classic animal model for evaluating analgesic effects of candidate drugs. This model consists two different phases, the early phase is related to the formalin-induced pain directly, and the late phase is related to the inflammation-caused pain (Shamsi Meymandi et al 2019). Our present results indicated that 1 can only Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, the compound was further purified by HPLC column to yield 66.3 mg of compound 1 with a purity > 95%, instrumental conditions: YMC-Pack Pro C 18 column (20 × 250 mm, 10 μm); isocratic elution with MeOH-H 2 O (75:25); flow rate 10 ml/min; sample injection 500 μl (0.1 mg/μl). The isolated azadirone (1) was identified by 1 H-NMR and compared with reported data (Siddiqui et al 2000;Nanduri et al 2003).…”

Section: Purification Of Azadironementioning

confidence: 99%

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Azadirone from Toona sinensis possesses anti-inflammatory and analgesic activities via suppressing MAPK signal pathway

Zhang

2020

Rev. Bras. Farmacogn.

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This study was designed to investigate the anti-inflammatory, analgesic activity of azadirone from Toona sinensis (Juss.) M. Roem., Meliaceae, and explore its potential mechanisms. Anti-inflammatory activities of azadirone were evaluated using dimethylbenzene-induced ear edema, acetic acid-induced vascular permeability, and cotton ball granuloma in mice; in addition, its analgesic activities were investigated using acetic acid writhing, hot plate pain, and formalin pain tests. The results showed that azadirone had obvious anti-inflammatory and analgesic effects in animals. Further studies revealed that azadirone can reduce levels of TNF-α, IL-6, and IL-1 in lipopolysaccharide-stimulated RAW 264.7 cells. In addition, azadirone can downregulate COX-2 and substance P in spinal cord tissues of formalin-stimulated mice. Also, expressions of ERK, P38, and JNK in RAW 264.7 cells were suppressed by azadirone. Collectively, azadirone has promising anti-inflammatory and analgesic potentials, and its mechanism is closely related to the reduction of pro-inflammatory cytokines and the blocking of MAPK signal pathway.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Section: Purification Of Azadironementioning

confidence: 99%

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Azadirone from Toona sinensis possesses anti-inflammatory and analgesic activities via suppressing MAPK signal pathway

Zhang

2020

Rev. Bras. Farmacogn.

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“…In human multiple myeloma U266 cells, fisetin stimulated the production of free radical species that led to apoptosis signaling as well as showed AMP‐activated protein kinase signaling (Jang et al., 2012). Multiple studies also authenticated the anticancer role of fisetin through various signaling pathways such as blocking of mammalian target of rapamycin (PI3K/Akt/mTOR)/phosphatidylinositol‐3‐kinase/protein kinase B, mitogen‐activated protein kinases (MAPK)‐dependent nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB), and p38, respectively, whereas these cellular processes have significantly led to malignancy (Mukhtar, Adhami, Sechi, & Mukhtar, 2015; Ren et al., 2020).…”

Section: Introductionmentioning

confidence: 99%

Fisetin: An anticancer perspective

Imran

Saeed

Gilani

et al. 2020

Food Science & Nutrition

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“…LPS-induced AKI in mice recapitulates several of the clinical manifestations observed in human septic AKI. Therefore, it is one of the most commonly used animal models to investigate the pathogenesis and potential treatment of septic AKI [ 15 , 16 ]. The present study used this animal model to examine the effects of TOFA on septic AKI.…”

Section: Introductionmentioning

confidence: 99%

Tofacitinib Ameliorates Lipopolysaccharide-Induced Acute Kidney Injury by Blocking the JAK-STAT1/STAT3 Signaling Pathway

Yang

Chen

Wang

et al. 2021

BioMed Research International

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Septic acute kidney injury (AKI) is the most common AKI syndrome in the intensive care unit (ICU), and it accounts for approximately half of AKI cases. Tofacitinib (TOFA) is a pan-Janus kinase (JAK) inhibitor that exhibits potent anti-inflammatory activity in rheumatoid arthritis. However, no study has examined the functional role of TOFA in septic AKI. In the present study, we investigated the protective effects of TOFA on septic AKI and the underlying mechanisms. A lipopolysaccharide- (LPS-) induced AKI model was established in C57BL/6 mice via an intraperitoneal injection of LPS (10 mg/kg). One hour after LPS challenge, the mice were orally administered TOFA (5, 10, or 15 mg/kg) every 6 h until sacrifice at 24 h. We found that TOFA significantly ameliorated LPS-induced renal histopathological changes and dysfunction. TOFA also suppressed the expression levels of proinflammatory cytokines (TNF-α, IL-1β, IL-6, and IFN-γ) and the parameters of oxidative stress (MDA, GSH, SOD, and CAT) in kidney tissues. These results may be associated with the inhibitory effect of TOFA on the JAK-STAT1/STAT3 pathway, which was significantly activated by LPS challenge. TOFA treatment also inhibited LPS-induced activation of the TLR4/NF-κB pathway. In conclusion, we revealed that TOFA had a protective effect on LPS-induced AKI, and it may be a promising therapeutic agent for septic AKI.

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Flavonoid fisetin alleviates kidney inflammation and apoptosis via inhibiting Src-mediated NF-κB p65 and MAPK signaling pathways in septic AKI mice

Cited by 278 publications

References 29 publications

Azadirone from Toona sinensis possesses anti-inflammatory and analgesic activities via suppressing MAPK signal pathway

Azadirone from Toona sinensis possesses anti-inflammatory and analgesic activities via suppressing MAPK signal pathway

Fisetin: An anticancer perspective

Tofacitinib Ameliorates Lipopolysaccharide-Induced Acute Kidney Injury by Blocking the JAK-STAT1/STAT3 Signaling Pathway

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