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The anti-inflammatory effects of oridonin in resisting esophageal cancer
Mengfan Peng1,2,3, Xiaofang Zhang1, Lei Yang1
1Faculty of Medicine, Huanghuai University, Zhumadian, Henan, China.
Objectives:
Explore whether Oridonin (Ori) improves esophageal cancer by interfering in the TLR4/NF-κB/NLRP3 inflammasome.
Materials And Methods:
An esophageal mouse model was induced by 4-nitroquinoline N-oxide (4-NQO) for 16 weeks. Starting from the 17th week of modeling, the mice were randomly divided into three groups: the model group (M), the high dose group of Ori (Ori -H) and the low dose group of Ori (Ori -L). The weight, diet, and water intake of the mice were recorded at the end of the experiment. H&E staining was used for esophageal tissue to evaluate pathological status. The tumor markers, inflammatory factor, mRNA and protein expression of TLR4/NF-κB/NLRP3 inflammasome related indicators in serum and esophageal tissue was determined by ELISA, qPCR, and western blot (WB) respectively. The blood cell analyzer was used for measuring the proportion of various blood cells.
Results:
Ori can increase the weight, the intake amount of food and water of mice (P<0.05, P<0.01). In parallel, Ori can alleviate pathological changes of esophageal tissue, decrease the levels of inflammatory factor tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2), and interleukin-6 (IL-6) in serum (P<0.01), and down-regulate granulocyte (Gran), Gran-to- Lymphocyte (Lymph) ratio (NLR), monocyte (Mon)-to-lymph ratio (MLR), and platelets-to-Lymph ratio (PLR) in the peripheral blood, while increasing Lymph, red blood cell (RBC), hemoglobin (HGB) (P<0.05, P<0.01). Moreover, the protein expression of toll-like receptor 4 (TLR4), phosphorylated nuclear factor-κB (p-NF-κB), IL-1β, NOD-like receptor hot protein domain related protein 3 (NLRP3), aspartate specific cysteine protease-1 (Caspase-1), apoptosis-associated speck-like protein (ASC), N-cadherin, and p-GSK3β was significantly inhibited by Ori (P<0.05, P<0.01), and the mRNA expression of proliferating cell nuclear antigen (PCNA), Ki67, and B-cell lymphoma-2 (Bcl-2) was significantly inhibited, while Bax mRNA was increased by Ori (P<0.05, P<0.01).
Conclusion:
This study provides evidence indicating that Ori may inhibit inflammatory response by inhibiting TLR4/NF-κB/NLRP3 inflammasome activation, ultimately exert anti esophageal cancer effects.
Insights
Oridonin (Ori) shows promise in combating esophageal cancer by reducing inflammation. It achieves this by inhibiting the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB)/NLRP3 inflammasome pathway.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Esophageal cancer is a significant global health concern.
- The Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB)/NLRP3 inflammasome pathway plays a critical role in inflammation and cancer development.
- Oridonin (Ori) is a natural compound with potential anti-cancer properties.
Purpose of the Study:
- To investigate the therapeutic effects of Oridonin (Ori) on esophageal cancer.
- To determine if Ori modulates the TLR4/NF-κB/NLRP3 inflammasome pathway in esophageal cancer.
Main Methods:
- An experimental esophageal cancer mouse model was established using 4-nitroquinoline N-oxide (4-NQO).
- Mice were treated with varying doses of Oridonin (Ori).
- Evaluations included pathological analysis, inflammatory marker assessment, and molecular analysis of key pathway proteins and gene expression via H&E staining, ELISA, qPCR, and Western blot.
Main Results:
- Oridonin (Ori) treatment improved mouse weight and food/water intake.
- Ori alleviated esophageal tissue damage and reduced serum inflammatory factors (TNF-α, IL-1β, COX-2, IL-6).
- Ori significantly inhibited the protein and mRNA expression of key components of the TLR4/NF-κB/NLRP3 inflammasome pathway, including TLR4, p-NF-κB, IL-1β, NLRP3, Caspase-1, and ASC, while also affecting cancer proliferation and apoptosis markers.
Conclusions:
- Oridonin (Ori) demonstrates anti-esophageal cancer effects.
- Ori inhibits the inflammatory response by suppressing the TLR4/NF-κB/NLRP3 inflammasome pathway.
- These findings suggest Oridonin (Ori) as a potential therapeutic agent for esophageal cancer.
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