Dataset Information

Zerumbone ameliorates the inflammatory response and organ damage in severe acute pancreatitis via the ROS/NF-κB pathway.

ABSTRACT:

Objective

The aim of the current study was to determine the mechanism by which Zerumbone (ZER) ameliorates inflammation and organ damage in a rat model of severe acute pancreatitis (SAP).

Methods

Different concentrations of ZER (10, 20 and 40 mg/kg) were administered by femoral vein puncture 30 min prior to establishment of the SAP model. Hematoxylin and eosin (H&E) staining was used to assess pathological changes in the pancreatic tissue of SAP-induced rats. The lung wet/dry (W/D) ratio was assessed and serum levels of amylase (AMY), alanine aminotransferase (ALT), creatinine (Cr), aspartate aminotransferase (AST) and phospholipase A₂ (PLA₂) were measured. Western blot analysis was used to examine changes in the expression of ROS/NF-κB pathway-associated proteins.

Results

SAP was confirmed by significant histopathological damage to the pancreas. ZER (10, 20 and 40 mg/kg) was found to alleviate pancreatitis and decrease ascites volume, lung W/D ratio, pancreatic pathology score, oxidative stress and inflammatory damage. High concentrations (20 and 40 mg/kg) of ZER were shown to increase levels of hepatorenal toxicity. In contrast, 10 mg/kg ZER was found to attenuate liver enzyme levels, reduce pathological damage to the liver, and protect against extrapancreatic organ damage to the liver in SAP-induced rats. Moreover, ZER showed no significant side effects in normal rats. Finally, we demonstrated that ZER mediated its anti-inflammatory effects on SAP through the ROS/NF-κB signaling pathway.

Conclusion

ZER alleviated SAP-induced oxidative stress and inflammatory injury via the ROS/NF-κB pathway, and had a protective effect on lung injury and liver damage.

SUBMITTER: Zhang F

PROVIDER: S-EPMC10538248 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Zerumbone ameliorates the inflammatory response and organ damage in severe acute pancreatitis via the ROS/NF-κB pathway.

Zhang Fengmei F Xu Dongjia D

BMC gastroenterology 20230927 1

<h4>Objective</h4>The aim of the current study was to determine the mechanism by which Zerumbone (ZER) ameliorates inflammation and organ damage in a rat model of severe acute pancreatitis (SAP).<h4>Methods</h4>Different concentrations of ZER (10, 20 and 40 mg/kg) were administered by femoral vein puncture 30 min prior to establishment of the SAP model. Hematoxylin and eosin (H&E) staining was used to assess pathological changes in the pancreatic tissue of SAP-induced rats. The lung wet/dry (W/D ...[more]

PMID: 37759163

Similar Datasets

Project description:BackgroundNormal tissue and immune organ protection are critical parts of the tumor radiation therapy process. Radiation-induced immune organ damage (RIOD) causes several side reactions by increasing oxidative stress and inflammatory responses, resulting in unsatisfactory curability in tumor radiation therapy. The aim of this study was to develop a novel and efficient anti irradiation nanoparticle and explore its mechanism of protecting splenic tissue from radiation in mice.MethodsNanoparticles of triphenylphosphine cation NIT radicals (NPs-TPP-NIT) were prepared and used to protect the spleens of mice irradiated with X-rays. Splenic tissue histopathology and hematological parameters were investigated to evaluate the protective effect of NPs-TPP-NIT against X-ray radiation. Proteomics was used to identify differentially expressed proteins related to inflammatory factor regulation. In addition, in vitro and in vivo experiments were performed to assess the impact of NPs-TPP-NIT on radiation therapy.ResultsNPs-TPP-NIT increased superoxide dismutase, catalase, and glutathione peroxidase activity and decreased malondialdehyde levels and reactive oxygen species generation in the spleens of mice after exposure to 6.0 Gy X-ray radiation. Moreover, NPs-TPP-NIT inhibited cell apoptosis, blocked the activation of cleaved cysteine aspartic acid-specific protease/proteinase, upregulated the expression of Bcl-2, and downregulated that of Bax. We confirmed that NPs-TPP-NIT prevented the IKK/IκB/NF-κB activation induced by ionizing radiation, thereby alleviating radiation-induced splenic inflammatory damage. In addition, when used during radiotherapy for tumors in mice, NPs-TPP-NIT exhibited no significant toxicity and conferred no significant tumor protective effects.ConclusionsNPs-TPP-NIT prevented activation of IKK/IκB/NF-κB signaling, reduced secretion of pro-inflammatory factors, and promoted production of anti-inflammatory factors in the spleen, which exhibited radiation-induced damage repair capability without diminishing the therapeutic effect of radiation therapy. It suggests that NPs-TPP-NIT serve as a potential radioprotective drug to shelter immune organs from radiation-induced damage.

Project description:Kaempferol (KA), an natural antioxidant of traditional Chinese medicine (TCM), is extensively used as the primary treatment for inflammatory digestive diseases with impaired redox homeostasis. Severe acute pancreatitis (SAP) was exacerbated by mitochondrial dysfunction and abundant ROS, which highlights the role of antioxidants in targeting mitochondrial function. However, low bioavailability and high dosage of KA leading to unavoidable side effects limits clinical transformation. The mechanisms of KA with poor bioavailability largely unexplored, hindering development of the efficient strategies to maximizing the medicinal effects of KA. Here, we engineered a novel thioketals (TK)-modified based on DSPE-PEG2000 liposomal codelivery system for improving bioavailability and avoiding side effects (denotes as DSPE-TK-PEG2000-KA, DTM@KA NPs). We demonstrated that the liposome exerts profound impacts on damaging intracellular redox homeostasis by reducing GSH depletion and activating Nrf2, which synergizes with KA to reinforce the inhibition of inadequate fission, excessive mitochondrial fusion and impaired mitophagy resulting in inflammation and apoptosis; and then, the restored mitochondrial homeostasis strengthens ATP supply for PAC renovation and homeostasis. Interestingly, TK bond was proved as the main functional structure to improve the above efficacy of KA compared with the absence of TK bond. Most importantly, DTM@KA NPs obviously suppresses PAC death with negligible side effects in vitro and vivo. Mechanismly, DTM@KA NPs facilitated STAT6-regulated mitochondrial precursor proteins transport via interacting with TOM20 to further promote Drp1-dependent fission and Pink1/Parkin-regulated mitophagy with enhanced lysosomal degradation for removing damaged mitochondria in PAC and then reduce inflammation and apoptosis. Generally, DTM@KA NPs synergistically improved mitochondrial homeostasis, redox homeostasis, energy metabolism and inflammation response via regulating TOM20-STAT6-Drp1 signaling and promoting mitophagy in SAP. Consequently, such a TCM's active ingredients-based nanomedicine strategy is be expected to be an innovative approach for SAP therapy.

Dataset Information

Zerumbone ameliorates the inflammatory response and organ damage in severe acute pancreatitis via the ROS/NF-κB pathway.

Objective

Methods

Results

Conclusion

Publications

Zerumbone ameliorates the inflammatory response and organ damage in severe acute pancreatitis via the ROS/NF-κB pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets