ReferenceID 4856
Cardamonin inhibits LPS-induced inflammatory responses and prevents acute lung injury by targeting myeloid differentiation factor 2
Phytomedicine
BACKGROUND: Acute lung injury (ALI) is a systemic inflammatory process, which has no pharmacological therapy in clinic. Accumulating evidence has demonstrated that natural compounds from herbs have potent anti-inflammato
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- Reference Id
- 4856
- Evidence Id
- 21446
- Core Evidence Id
- 21446
- Source Reference Id
- 2961
- Herb2 Reference Id
- HBREF003758
- Subject Paper Key
- HBIN019722_34638032
- Pubmed Id
- 34638032
- Doi
- 10.1016/j.phymed.2021.153785
- Paper Title
- Cardamonin inhibits LPS-induced inflammatory responses and prevents acute lung injury by targeting myeloid differentiation factor 2
- Paper Abstract
- BACKGROUND: Acute lung injury (ALI) is a systemic inflammatory process, which has no pharmacological therapy in clinic. Accumulating evidence has demonstrated that natural compounds from herbs have potent anti-inflammatory efficacy in several disease models, which could be the potential candidates for the treatment of ALI. HYPOTHESIS/PURPOSE: Anti-inflammatory screening from natural product bank may provide new anti-inflammatory compounds for therapeutic target discovery and ALI treatment. METHODS: 165 natural compounds were screened for their anti-inflammatory activity in LPS-stimulated macrophages. PCR array, SPR and ELISA were used to determine the potential target of the most active compound, Cardamonin (CAR). The pharmacological effect of CAR was further evaluated in both LPS-stimulated macrophages and ALI mice model. RESULTS: Out of the screened 165 compounds, CAR significantly inhibited LPS-induced inflammatory cytokine secretion in macrophages. We further showed that CAR significantly inhibited NF-kappaB and JNK signaling activation, and thereby inflammatory cytokine production via directly interacting with MD2 in vitro. In vivo, our data show that CAR treatment inhibited LPS-induced lung damage, systemic inflammatory cytokine production, and reduced macrophage infiltration in the lungs, accompanied with reduced TLR4/MD2 complex in lung tissues, Treatment with CAR also dose-dependently increased survival in the septic mice induced by DH5alpha bacterial infection. CONCLUSION: We demonstrate that a natural product, CAR, attenuates LPS-induced lung injury and sepsis by inhibiting inflammation via interacting with MD2, leading to the inactivation of the TLR4/MD2-MyD88-MAPK/NF-kappaB pathway.
- Journal
- Phytomedicine
- Publish Year
- 2021
- Experiment Subject
- mouse; lps-stimulated macrophages
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Acute Lung Injury; Sepsis; Septic; Lung Injury
- Paper Title Cn
- Paper Title En
- Cardamonin inhibits LPS-induced inflammatory responses and prevents acute lung injury by targeting myeloid differentiation factor 2
- Bilingual Status
- semi_complete