Protective Effect and Mechanism of Theanine on Lipopolysaccharide-Induced Inflammation and Acute Liver Injury in Mice.

Abstract

Theanine, a unique bioactive constituent from tea ( Camellia sinensis) leaves, is widely used as a functional ingredient and dietary supplement. To evaluate the anti-inflammatory and hepatoprotective effects of theanine and its molecular mechanism, the lipopolysaccharide (LPS)-induced inflammation mouse model was employed in this study. The survival rate of mice in the theanine-treated group increased significantly compared with that of LPS-only group mice. Furthermore, ICR male mice were randomly divided into three or four groups: control, LPS (LPS treatment only), LPS + theanine (20 mg/kg/day), and theanine (theanine treatment only). The results showed that compared with the LPS group, the liver damage and oxidative stress of the theanine-treated group decreased significantly, based on plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations, hepatic total superoxide dismutase (T-SOD), and malondialdehyde (MDA) levels, and histological scores and apoptosis [terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) staining and caspase-3 activity] in the liver tissues. Furthermore, compared with no treatment, pretreatment with theanine significantly decreased the release of interleukin (IL)-1β and tumor necrosis factor (TNF)-α, inhibited the expression of several inflammatory factors (including IL-1β, TNF-α, and IL-6), and increased the IL-10/interferon (IFN)-γ ratio in the hepatic tissues. In the LPS-induced inflammation model, theanine inhibited the expression of proinflammatory mediators involved in the nuclear factor-kappa B (NF-κB) pathway, such as inducible nitric oxide synthase (iNOS) and matrix metalloproteinase-3 (MMP-3), and attenuated the phosphorylation of NF-κB in the hepatic tissues. Moreover, theanine suppressed the acute-phase response (elevated nitric oxide and C-reactive protein levels). Furthermore, theanine suppressed the LPS-induced inflammatory state by normalizing hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. Taken together, the results suggest that theanine potentially ameliorates LPS-induced inflammation and acute liver injury; molecular mechanism of action may involve normalization of HPA axis hyperactivity and inactivation of the NF-κB signaling pathway.

• Authors: Dongxu Wang, Qiang Gao, Guangshan Zhao, Zhipeng Kan, Xiaoxiao Wang, Haisong Wang, Jinbao Huang, Taotao Wang, Frank Qian, Chi-Tang Ho, Yijun Wang
• Journal: Journal of agricultural and food chemistry (J Agric Food Chem) Vol. 66 Issue 29 Pg. 7674-7683 (Jul 25 2018) ISSN: 1520-5118 [Electronic] United States
• PMID: 29969892 (Publication Type: Journal Article)

Chemical References

• Glutamates
• Lipopolysaccharides
• NF-kappa B
• Malondialdehyde
• theanine
• Aspartate Aminotransferases
• Alanine Transaminase

Topics

• Acute Disease (therapy)
• Alanine Transaminase (blood)
• Animals
• Aspartate Aminotransferases (blood)
• Glutamates (administration & dosage)
• Humans
• Hypothalamo-Hypophyseal System (drug effects, metabolism)
• Lipopolysaccharides (adverse effects)
• Liver (drug effects, immunology)
• Liver Diseases (blood, etiology, immunology, prevention & control)
• Male
• Malondialdehyde (immunology)
• Mice
• Mice, Inbred ICR
• NF-kappa B (genetics, immunology)