Ethanol extracts of Rhaponticum uniflorum (L.) DC inflorescence ameliorate LPS-mediated acute lung injury by alleviating inflammatory responses via the Nrf2/HO-1 signaling pathway.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

Rhaponticum uniflorum (L.) DC is a member of the Compositae family. Loulu flowers (LLF) is the inflorescence of this plant, which is a commonly used Mongolian medicine for the treatment of inflammatory diseases due to its heat-clearing and detoxifying properties. It is used caused by. However, its anti-inflammatory mechanisms are not clear.

AIM OF THIS STUDY:

We investigated whether ethanol extracts of LLF can alleviate LPS-induced acute lung injury and explored the mechanism involved.

MATERIAL AND METHODS:

BALB/C mice were intragastrically administered with sodium carboxymethyl cellulose (0.5%, 1 mL/100 g) or ethanol extracts of LLF at a dose of 100, 200, and 400 mg/kg, once daily, for 3 days. Subsequently, mice models of acute lung injury were established by LPS and used for the determination of anti-inflammatory effects of LLF. After 6 h of treatment, mice were sacrificed to collect lung tissues and bronchoalveolar lavage fluid (BALF). H&E staining assay was performed on the tissues for pathological analysis. The ELISA test was conducted to measure NO, IL-6, TNF-α, MPO, SOD, CAT, MDA and GSH-PX levels. The expression level of proteins associated with the Nrf2/HO-1 and MAPK/NF-κB signaling pathways were determined using Western blot analysis. Levels of F4/80 and Nrf2 in lungs were quantified using immunohistochemistry.

RESULTS:

Oral administration of LLF extracts alleviated LPS-induced pathological alterations, reduced lung W/D weight ratio, decreased levels of TP, pro-inflammatory factors (TNF-α and IL-6), and NO in BALF. Pretreatment with LLF extract downregulated F4/80 expression in lung tissue and suppressed LPS-induced elevations in BALF and lung tissue levels of MPO. Moreover, treatment with LLF extract reduced the expression level of proteins associated with the MAPK signaling pathway (p-p38, p-JNK, p-ERK) and TLR4/NF-κB signaling pathways (TLR4, Myd88, p-IκB, p-p65). Moreover, LLF extract upregulated Nrf2, HO-1 and NQO1 protein levels, downregulated Keap1 protein level. Immunohistochemical analysis revealed that LLF reduced the LPS-induced increase in Nfr2 expression in lung tissues.

CONCLUSION:

Ethanol extracts of LLF ameliorated LPS-induced acute lung injury by suppressing inflammatory response and enhancing antioxidation capacity, which correlated with the MAPK/NF-κB and Nfr2/HO-1 signaling pathways.

• Authors: Dong Zhen, Chunyan Liu, Tianpeng Huang, Danni Fu, Xue Bai, Qianqian Ma, Mingyang Jiang, Guohua Gong
• Journal: Journal of ethnopharmacology (J Ethnopharmacol) Vol. 296 Pg. 115497 (Oct 05 2022) ISSN: 1872-7573 [Electronic] Ireland
• PMID: 35738472 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Interleukin-6
• Kelch-Like ECH-Associated Protein 1
• Lipopolysaccharides
• Membrane Proteins
• NF-E2-Related Factor 2
• NF-kappa B
• Plant Extracts
• Toll-Like Receptor 4
• Tumor Necrosis Factor-alpha
• Ethanol
• Heme Oxygenase-1
• Hmox1 protein, mouse

Topics

• Acute Lung Injury (chemically induced, drug therapy, metabolism)
• Animals
• Anti-Inflammatory Agents
• Asteraceae (chemistry)
• Ethanol
• Heme Oxygenase-1 (metabolism)
• Inflammation (chemically induced, drug therapy, metabolism)
• Inflorescence
• Interleukin-6 (metabolism)
• Kelch-Like ECH-Associated Protein 1 (metabolism)
• Leuzea (chemistry)
• Lipopolysaccharides (toxicity)
• Membrane Proteins (metabolism)
• Mice
• Mice, Inbred BALB C
• NF-E2-Related Factor 2 (metabolism)
• NF-kappa B (metabolism)
• Plant Extracts (chemistry, pharmacology, therapeutic use)
• Signal Transduction
• Toll-Like Receptor 4 (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)