Genipin Attenuates Sepsis by Inhibiting Toll-Like Receptor Signaling

Kim, Tae-Hoon; Yoon, Sungpil; Lee, Sun-Mee

doi:10.2119/molmed.2011.00308

Cited by 51 publications

(31 citation statements)

References 35 publications

(32 reference statements)

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“…Previous in vitro and in vivo studies have demonstrated that genipin has potent anti-oxidant and anti-inflammatory effects [13,14]. More importantly, it has been documented that genipin can suppress the activation of the MAPK and TLR signaling pathways [15,16]. Based on these findings, we hypothesized that genipin has therapeutic activities against hypertension and the related nephropathy.…”

Section: Introductionmentioning

confidence: 81%

Genipin ameliorates hypertension-induced renal damage via the angiotensin II-TLR/MyD88/MAPK pathway

Shi

Bao

et al. 2016

Fitoterapia

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Section: Introductionmentioning

confidence: 81%

Genipin ameliorates hypertension-induced renal damage via the angiotensin II-TLR/MyD88/MAPK pathway

Shi

Bao

et al. 2016

Fitoterapia

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“…The factors regulating the release of cytokines from macrophages are not fully understood although it has been hypothesized that this process is regulated, at least in part, by increases in cellular ROS which has led some to hypothesize that the use of antioxidants may be valuable for the treatment of sepsis [9–11]. Although promising in animals, the vast majority of interventional studies examining the effects of antioxidant therapies have been largely ineffective in clinical trials [12].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of MAP kinase/NF-kB mediated signaling and attenuation of lipopolysaccharide induced severe sepsis by cerium oxide nanoparticles

et al. 2015

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Sepsis is a life threatening disease that is associated with high mortality. Existing treatments have failed to improve survivability in septic patients. The purpose of this present study is to evaluate whether cerium oxide nanoparticles (CeO2NPs) can prevent lipopolysaccharide (LPS) induced severe sepsis mortality by preventing hepatic dysfunction in male Sprague Dawley rats. Administration of a single dose (0.5 mg/kg) of CeO2NPs intravenously to septic rats significantly improved survival rates and functioned to restore body temperature, respiratory rate and blood pressure towards baseline. Treatment-induced increases in animal survivability were associated with decreased hepatic damage along with reductions in serum cytokines/chemokines, and diminished inflammatory related signaling. Kupffer cells and macrophage cells exposed to CeO2NPs exhibited decreases in LPS-induced cytokine release (TNF-α, IL-1β, IL-6, HMGB1) which were associated with diminished cellular ROS, reduced levels of nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), and decreased nuclear factor-kappa light chain enhancer of activated B cells (NF-kB) transcriptional activity. The findings of this study indicate that CeO2NPs may be useful as a therapeutic agent for sepsis.

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“…The samples were then embedded in paraffin, sliced into 5-μm sections and stained with hematoxylin and eosin (H&E) for histological assessment by a pathologist blinded to their group allocation. Hepatocellular necrosis, hemorrhage/congestion, parenchyma inflammation, sinusoidal inflammation, and degenerative changes were evaluated objectively on a scale of 0–3, with 0 meaning “absent,” 1 meaning “mild,” 2 meaning “moderate,” and 3 meaning “severe.” The total injury score was expressed as the sum of the scores for all of these parameters 18 .…”

Section: Methodsmentioning

confidence: 99%

Novel pharmacologic treatment attenuates septic shock and improves long-term survival

Zhao

Liu

et al. 2013

Surgery

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Background We have previously demonstrated that suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, improves survival in a lipopolysaccharide (LPS)-induced lethal endotoxemia model. The goal of this study was to investigate the impact of SAHA on survival in a more clinically relevant cecal ligation and puncture (CLP)-induced septic shock model, and to elucidate changes in cytokine responses and organ injury. Methods C57BL/6J mice were subjected to CLP, and 1 hour later given either SAHA dissolved in dimethyl sulfoxide (DMSO) or DMSO only, intra-peritoneal. Survival was monitored for 10 days. In a second study, livers were harvested for evaluation of acute liver injury, and peritoneal fluid and blood samples were collected for cytokine assays. In addition, RAW264.7 and bone marrow-derived macrophages (BMMs) were utilized to assess effects of SAHA on cytokine responses. Results SAHA treated animals displayed a significant improvement in survival. In addition, SAHA also significantly attenuated cytokine levels in blood and peritoneal fluid compared to vehicle animals, as well as in culture supernatant of macrophages stimulated with bacterial components (LPS or Pam3CSK4). Moreover, SAHA treated animals showed a significant decrease in acute liver injury. Conclusions SAHA treatment improves survival, reduces “cytokine storm”, and prevents distant organ damage in a lethal septic model.

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Genipin Attenuates Sepsis by Inhibiting Toll-Like Receptor Signaling

Cited by 51 publications

References 35 publications

Genipin ameliorates hypertension-induced renal damage via the angiotensin II-TLR/MyD88/MAPK pathway

Genipin ameliorates hypertension-induced renal damage via the angiotensin II-TLR/MyD88/MAPK pathway

Inhibition of MAP kinase/NF-kB mediated signaling and attenuation of lipopolysaccharide induced severe sepsis by cerium oxide nanoparticles

Novel pharmacologic treatment attenuates septic shock and improves long-term survival

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