Galgravin Isolated from Piper kadsura Ameliorates Lipopolysaccharide (LPS)-Induced Endotoxemia in Mice

Author:

Ou Shih-Ming12,Hsu Yin-Chieh3ORCID,Fu Shu-Ling3,Lin Lie-Chwen4ORCID,Lin Chao-Hsiung1ORCID

Affiliation:

1. Department of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan

2. Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11467, Taiwan

3. Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan

4. National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei 11221, Taiwan

Abstract

Sepsis results from uncontrolled inflammation, characterized by cytokine storm and immunoparalysis. To assess whether galgravin, a natural lignan isolated from Piper kadsura, can be used to treat sepsis, models of bacterial lipopolysaccharide (LPS)-activated macrophages and LPS-induced endotoxemia mice were used. Galgravin suppressed NF-κB activation in LPS-activated RAW 264.7 macrophages without causing significant cytotoxicity, in which proinflammatory molecules like TNF-α, IL-6, iNOS, and COX-2 were downregulated. In addition, the expression of TNF-α and IL-6 was also suppressed by galgravin in LPS-activated murine bone marrow-derived macrophages. Moreover, galgravin significantly downregulated the mRNA expression of TNF-α, IL-6, and iNOS in the lungs and decreased TNF-α and IL-6 in the serum and IL-6 in the bronchoalveolar lavage fluid of LPS-challenged mice. The COX-2 expression in tissues, including the lung, liver, and kidney, as well as the lung alveolar hemorrhage, was also reduced by galgravin. The present study reveals the anti-inflammatory effects of galgravin in mouse models and implies its potential application in inflammation diseases.

Funder

National Science and Technology Council of Taiwan

Interdisciplinary Research Center for Healthy Longevity of National Yang Ming Chiao Tung University

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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