PMID- 29969892 OWN - NLM STAT- MEDLINE DCOM- 20180814 LR - 20180814 IS - 1520-5118 (Electronic) IS - 0021-8561 (Linking) VI - 66 IP - 29 DP - 2018 Jul 25 TI - Protective Effect and Mechanism of Theanine on Lipopolysaccharide-Induced Inflammation and Acute Liver Injury in Mice. PG - 7674-7683 LID - 10.1021/acs.jafc.8b02293 [doi] AB - 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)-1beta and tumor necrosis factor (TNF)-alpha, inhibited the expression of several inflammatory factors (including IL-1beta, TNF-alpha, and IL-6), and increased the IL-10/interferon (IFN)-gamma 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-kappaB) pathway, such as inducible nitric oxide synthase (iNOS) and matrix metalloproteinase-3 (MMP-3), and attenuated the phosphorylation of NF-kappaB 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-kappaB signaling pathway. FAU - Wang, Dongxu AU - Wang D AUID- ORCID: 0000-0001-7377-6190 AD - State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science & Technology , Anhui Agricultural University , Hefei , Anhui 230036 , China. AD - International Joint Laboratory on Tea Chemistry and Health Effects , Anhui Agricultural University , Hefei , Anhui 230036 , China. FAU - Gao, Qiang AU - Gao Q AD - State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science & Technology , Anhui Agricultural University , Hefei , Anhui 230036 , China. FAU - Zhao, Guangshan AU - Zhao G AD - State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science & Technology , Anhui Agricultural University , Hefei , Anhui 230036 , China. FAU - Kan, Zhipeng AU - Kan Z AD - State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science & Technology , Anhui Agricultural University , Hefei , Anhui 230036 , China. FAU - Wang, Xiaoxiao AU - Wang X AD - State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science & Technology , Anhui Agricultural University , Hefei , Anhui 230036 , China. FAU - Wang, Haisong AU - Wang H AD - State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science & Technology , Anhui Agricultural University , Hefei , Anhui 230036 , China. AD - International Joint Laboratory on Tea Chemistry and Health Effects , Anhui Agricultural University , Hefei , Anhui 230036 , China. FAU - Huang, Jinbao AU - Huang J AD - State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science & Technology , Anhui Agricultural University , Hefei , Anhui 230036 , China. AD - International Joint Laboratory on Tea Chemistry and Health Effects , Anhui Agricultural University , Hefei , Anhui 230036 , China. FAU - Wang, Taotao AU - Wang T AD - Department of Clinical Nutrition , Affiliated Hospital of Jiangsu University , Zhenjiang , Jiangsu 212000 , China. FAU - Qian, Frank AU - Qian F AD - Pritzker School of Medicine , University of Chicago , Chicago , Illinois 60637 , United States. FAU - Ho, Chi-Tang AU - Ho CT AD - International Joint Laboratory on Tea Chemistry and Health Effects , Anhui Agricultural University , Hefei , Anhui 230036 , China. AD - Department of Food Science , Rutgers University , New Brunswick , New Jersey 08901 , United States. FAU - Wang, Yijun AU - Wang Y AD - State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science & Technology , Anhui Agricultural University , Hefei , Anhui 230036 , China. AD - International Joint Laboratory on Tea Chemistry and Health Effects , Anhui Agricultural University , Hefei , Anhui 230036 , China. LA - eng PT - Journal Article DEP - 20180712 PL - United States TA - J Agric Food Chem JT - Journal of agricultural and food chemistry JID - 0374755 RN - 0 (Glutamates) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 4Y8F71G49Q (Malondialdehyde) RN - 8021PR16QO (theanine) RN - EC 2.6.1.1 (Aspartate Aminotransferases) RN - EC 2.6.1.2 (Alanine Transaminase) SB - IM MH - Acute Disease/therapy MH - Alanine Transaminase/blood MH - Animals MH - Aspartate Aminotransferases/blood MH - Glutamates/*administration & dosage MH - Humans MH - Hypothalamo-Hypophyseal System/drug effects/metabolism MH - Lipopolysaccharides/*adverse effects MH - Liver/drug effects/immunology MH - Liver Diseases/blood/etiology/*immunology/*prevention & control MH - Male MH - Malondialdehyde/immunology MH - Mice MH - Mice, Inbred ICR MH - NF-kappa B/genetics/immunology OTO - NOTNLM OT - hypothalamic-pituitary-adrenal axis OT - inflammation OT - lipopolysaccharide OT - liver injury OT - theanine EDAT- 2018/07/05 06:00 MHDA- 2018/08/15 06:00 CRDT- 2018/07/05 06:00 PHST- 2018/07/05 06:00 [pubmed] PHST- 2018/08/15 06:00 [medline] PHST- 2018/07/05 06:00 [entrez] AID - 10.1021/acs.jafc.8b02293 [doi] PST - ppublish SO - J Agric Food Chem. 2018 Jul 25;66(29):7674-7683. doi: 10.1021/acs.jafc.8b02293. Epub 2018 Jul 12.