1. Inhibition of the Akt/NF-κB pathway is involved in the anti-gastritis effects of an ethanolic extract of the rhizome of Atractylodes macrocephala.
- Author
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Amin, Aftab, Hossen, Muhammad Jahangir, Fu, Xiu-Qiong, Chou, Ji-Yao, Wu, Jia-Ying, Wang, Xiao-Qi, Chen, Ying-Jie, Wu, Ying, Yin, Cheng-Le, Dou, Xiao-Bing, Liang, Chun, Chou, Gui-Xin, and Yu, Zhi-Ling
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LIPOPOLYSACCHARIDES , *BIOLOGICAL models , *IN vitro studies , *PROSTAGLANDINS E , *MEDICINAL plants , *NITRIC-oxide synthases , *ANTI-inflammatory agents , *ANIMAL experimentation , *GASTRITIS , *MACROPHAGES , *CELLULAR signal transduction , *PLANT roots , *RATS , *CELL survival , *GENE expression , *IMMUNOBLOTTING , *TRANSFERASES , *MESSENGER RNA , *ENZYME-linked immunosorbent assay , *DESCRIPTIVE statistics , *GASTROINTESTINAL agents , *PLANT extracts , *ETHANOL , *NITRIC oxide , *POLYMERASE chain reaction , *DATA analysis software , *GENETIC techniques , *OXIDOREDUCTASES , *PHOSPHORYLATION , *PHARMACODYNAMICS - Abstract
Gastritis can lead to ulcers and the development of gastric cancer. The rhizome of Atractylodes macrocephala Koidz. (Asteraceae), a traditional Chinese medicinal herb, is prescribed for the treatment of gastric disorders, hepatitis and rheumatism. Its bio-active compounds are considered to be particularly effective in this regard. However, the molecular processes of the herb's anti-inflammatory activity remain obscure. This study elucidates a mechanism upon which an ethanolic extract of this herb (Am-EE) exerts anti-inflammation effects in RAW264.7 macrophage cells (RAW cells) stimulated by lipopolysaccharide (LPS) treatment and HCl Ethanol-stimulated gastritis rats. To investigate the anti-gastritis activities of Am-EE and explore the mode of action. Ethanol (95%) was used to prepare Am-EE. The quality of the extract was monitored by HPLC analysis. The in vivo effects of this extract were examined in an HCl Ethanol-stimulated gastritis rat model, while LPS-stimulated RAW cells were used for in vitro assays. Cell viability and nitric oxide (NO) production were observed by MTT and Griess assays. Real-time PCR was used to examine mRNA expression. The PGE 2 ELISA kit was employed to detect prostaglandin E 2 (PGE 2). Enzyme activities and protein contents were examined by immunoblotting. Luciferase reporter gene assays (LRA) were employed to observe nuclear transcription factor (NF)-κB activity. The SPSS (SPSS Inc., Chicago, Illinois, United States) application was used for statistical examination. HPLC analysis indicates that Am-EE contains atractylenolide-1 (AT-1, 1.33%, w/w) and atractylenolide-2 (AT-2, 1.25%, w/w) (Additional Figure. A1). Gastric tissue damage (induced by HCl Ethanol) was significantly decreased in SD rats following intra-gastric application of 35 mg/kg Am-EE. Indistinguishable to the anti-inflammation effects of 35 mg/kg ranitidine (gastric medication). Am-EE treatment also reduced LPS-mediated nitric oxide (NO) and prostaglandin E 2 (PGE 2) production. The mRNA and protein synthesis of inducible cyclooxygenase (COX)-2 and NO synthase (iNOS) was down-regulated following treatment in RAW cells. Am-EE decreased NF-κB (p50) nuclear protein levels and inhibited NF-κB-stimulated LRA activity in RAW cells. Lastly, Am-EE decreased the up-regulated levels of phosphorylated IκBα and Akt proteins in rat stomach lysates and in LPS challenged RAW cell samples. Our study illustrates that Am-EE suppresses the Akt/IκBα/NF-κB pathway and exerts an anti-inflammatory effect. These novel conclusions provide a pharmacological basis for the clinical use of the A. macrocephala rhizome in the treatment and prevention of gastritis and gastric cancer. [Display omitted] [ABSTRACT FROM AUTHOR]
- Published
- 2022
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