Humulene Inhibits Acute Gastric Mucosal Injury by Enhancing Mucosal Integrity.

Dahee Yeo,Ye-Seul Song,Hyo-Jong Lee,Su-Jung Hwang

doi:10.3390/antiox10050761

Dahee Yeo, Ye-Seul Song + Show 2 more

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https://doi.org/10.3390/antiox10050761

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Abstract

This study was designed to determine whether α-humulene, a major constituent in many plants used in fragrances, has a protective role against gastric injury in vivo and in vitro. A rat model of hydrochloric acid (HCl)/ethanol-induced gastritis and human mast cells (HMC-1) were used to investigate the mucosal protective effect of α-humulene. α-Humulene significantly inhibited gastric lesions in HCl/ethanol-induced acute gastritis and decreased gastric acid secretion pyloric ligation-induced gastric ulcers in vivo. In addition, α-humulene reduced the amount of reactive oxygen species and malondialdehyde through upregulation of prostaglandin E2 (PGE2) and superoxide dismutase (SOD). In HMC-1 cells, α-humulene decreased intracellular calcium and increased intracellular cyclic adenosine monophosphate (cAMP) levels, resulting in low histamine levels. α-Humulene also reduced the expression levels of cytokine genes such as interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF) by downregulating nuclear factor-κB (NF-κB) nuclear translocation. Finally, α-humulene upregulated the expression levels of mucin 5AC (Muc5ac), Muc6, trefoil factor 1 (Tff1), trefoil factor 2 (Tff2), and polymeric immunoglobulin receptor (pigr). α-Humulene may attenuate HCl/ethanol-induced gastritis by inhibiting histamine release and NF-κB activation and stimulating antioxidants and mucosal protective factors, particularly Muc5ac and Muc6. Therefore, these data suggest that α-humulene is a potential drug candidate for the treatment of stress-induced or alcoholic gastritis.

Highlights

Gastritis refers to the inflammation of the mucosal lining that protects the inner layers of the stomach
Bank (KCLB, Seoul, Korea) and cultured at 37 ◦ C and 5% CO2 in Iscove’s modified Dulbecco’s medium supplemented with 10% fetal bovine serum, penicillin (100 U/mL), and streptomycin (100 μg/mL; Gibco BRL, Gaithersburg, MD, USA). α-Humulene, ranitidine, dimethyl sulfoxide (DMSO), Alcian Blue 8GX, curcumin, histamine, compound 48/80, phorbol-12-myristate-13-acetate (PMA), and o-phthalaldehyde were purchased from Sigma
Considering the main role of intracellular calcium (Ca2+ ) signaling in mast cell degranulation, we investigated whether α-humulene affects compound 48/80-induced Ca2+ mobilization in human mast cell-1 (HMC-1) cells

Summary

Introduction

Gastritis refers to the inflammation of the mucosal lining that protects the inner layers of the stomach. It can be classified as gastritis with damage only at the mucosal surface and gastric ulcer, with damage deeper than the mucosal layer. It directly reaches the mucus layer of the stomach and stimulates excessive gastric juice secretion [5]. As gastric acid secretion increases, damage to the mucus layer increased. Alcohol induces inflammatory activity, while decreasing antioxidant activity and mucus protective factors. These multiple factors work together, eventually leading to gastritis. Since the consumption of alcohol is still rising worldwide, many researchers have focused on the treatment of alcoholic gastritis [8]

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