Protective role of crocin against sepsis-induced injury in the liver, kidney and lungs via inhibition of p38 MAPK/NF-κB and Bax/Bcl-2 signalling pathways

Abstract

Context Crocin has been reported to have multiple bioactivities. However, the effect of crocin administration on caecal ligation and puncture (CLP)-induced sepsis remains unknown. Objective We investigated the effects of crocin on CLP-induced sepsis in mice and the underlying mechanism of action. Materials and methods Five experimental groups ( n = 10) of BALB/c mice were used: control, CLP (normal saline) and CLP + crocin (50, 100 and 250 mg/kg, 30 min prior to CLP). Mice were sacrificed 24 h after CLP. Liver, kidney and lung histopathology, indicator levels, apoptotic status, pro-inflammatory cytokines and relative protein levels were evaluated. Results Compared to the CLP group, crocin treatment significantly increased the survival rate (70%, 80%, 90% vs. 30%). Crocin groups exhibited protection against liver, kidney and lung damage with mild-to-moderate morphological changes and lower indicator levels: liver (2.80 ± 0.45, 2.60 ± 0.55, 1.60 ± 0.55 vs. 5.60 ± 0.55), kidney (3.00 ± 0.71, 2.60 ± 0.55, 1.40 ± 0.55 vs. 6.20 ± 0.84) and lungs (8.00 ± 1.59, 6.80 ± 1.64, 2.80 ± 0.84 vs. 14.80 ± 1.79). The proinflammatory cytokines (IL-1β, TNF-α, IL-6 and IL-10 levels in the crocin groups) were distinctly lower and the apoptotic index showed a significant decrease. Crocin administration significantly suppressed p38 MAPK phosphorylation and inhibited NF-κB/IκBα and Bcl-2/Bax activation. Discussion and conclusions Pre-treatment with crocin confers protective effects against CLP-induced liver, kidney and lung injury, implying it to be a potential therapeutic agent.

Gene signature for the prediction of the trajectories of sepsis-induced acute kidney injury

“…This gene has been found to mediate activation of MAPK8 and MAP kinase p38 [ 27 , 28 ]. Consistent with our findings, p38 MAPK is involved in the development of sepsis-related multiple organ failure, including AKI [ 29 – 31 ]. It would be reasonable to hypothesize that inhibition of this pathway may protect against AKI.…”

Aldehyde Dehydrogenase 2 Ameliorates LPS-Induced Acute Kidney Injury through Detoxification of 4-HNE and Suppression of the MAPK Pathway

“…The MAPK pathway is one of the most important signal transduction pathways in cell proliferation, inflammation, differentiation, and apoptosis [42]. Recent studies have emphasized that activation of the MAPK pathway is involved in regulating inflammatory responses in sepsis-induced organ dysfunction [43,44]. In addition, ROS generation and 4-HNE accumulation are both efficient mediators of MAPK pathway activation [45][46][47].…”

LncRNA 152 attenuates lipopolysaccharide‐induced acute kidney injury in rats by regulating the FGF23/Klotho/MAPK axis

“…Then, large number of proinflammatory cytokines, such as IL-1 and IL-6, and chemokines are produced, which induces inflammatory response and aggravates kidney injury. 36 A study has stated that the binding of FGF23 to FGFR and Klotho initiates the MAPK signalling pathway, thereby regulating phosphate metabolism in the kidney. 37 In this paper, the increased p-p38/p38 ratio in AKI rats indicated the MAPK signalling pathway activation.…”

“…Activation of the MAPK signalling pathway promotes macrophage survival and accumulation. Then, large number of pro‐inflammatory cytokines, such as IL‐1 and IL‐6, and chemokines are produced, which induces inflammatory response and aggravates kidney injury 36 . A study has stated that the binding of FGF23 to FGFR and Klotho initiates the MAPK signalling pathway, thereby regulating phosphate metabolism in the kidney 37 .…”