Peripheral and central pathophysiological changes in a new rat model of acid reflux combined with mental stress.

BACKGROUND: Mental stress is an important risk factor for gastroesophageal reflux disease (GERD), which interacts with acid reflux and affects the efficacy of single acid suppression treatment. However, the specific mechanism remains elusive, and there is a lack of available models for further support. METHODS: This study established a new compound model combining acid reflux and chronic unpredictable mild stress (CUMS) to observe potential peripheral and central pathophysiological changes. KEY RESULTS: Rats in the compound model suffered from significant weight loss and manifested depression-like behaviours. In addition, the acid reflux was not aggravated despite the presence of mental stress, along with dilated intercellular space (DIS), increased expression of desmoglein-1 (DSG1) mRNA, and injury of the lower oesophageal mucosa. The balance between pro-inflammatory and anti-inflammatory factors was disrupted. In the hypothalamus of rats in the compound model, the expression of corticosterone-releasing factor (CRF) and its receptors, protein kinase A (PKA), and γ-aminobutyric acid (GABA) receptors were decreased. This might be related to the "escape" of stress, which weakened the suppressive effect on excitatory transmission to cope with the damage of pressure to the body. CONCLUSIONS & INFERENCES: Mental stress and acid reflux affect GERD through peripheral and central aspects, which can result in the poor efficacy of acid inhibitors. This may provide a new direction for the treatment of GERD.

Anti-inflammatory sesquiterpene dimers and diterpenes from the aerial part of Inula japonica.

Phytochemical investigation on the 95% alcohol extract of the aerial part of Inula japonica led to the isolation of three new compounds, inulanolides F-G (1-2) and 17α-carboxaldehyde-ent-kaur-18-oic acid (3), together with four known compounds (4-7). The structures of new compounds were elucidated by using spectroscopic data. Most of the isolated compounds showed significant anti-inflammatory activities.

Neolinulicin A and B from Inula japonica and their anti-inflammatory activities.

A phytochemical study performed on Inula japonica led to isolation of a new 1,10-seco-sesquiterpene dimer Neolinulicin A (1) and 1,10-seco-sesquiterpene Neolinulicin B (2), together with nine known sesquiterpenes (3-11). Among them, Neolinulicin A (1), which has a new carbon skeleton, was a Diels-Alder [4 + 2] adduct of two sesquiterpene moieties. Their structures were established by extensive spectroscopic analysis. All of the isolated compounds showed inhibition of NO production in RAW 264.7 macrophages. The findings might supply information for the future design of anti-inflammatory agents from I. japonica.