Abstract
The fruit of Ziziphus jujuba, commonly called jujube, has long been consumed for its health benefits. The aim of this study was to examine the protective effect of dietary supplementation of enzymatically hydrolyzed jujube against lung inflammation in mice. The macerated flesh of jujube was extracted with aqueous ethanol before and after Viscozyme treatment. The extract of enzyme-treated jujube, called herein hydrolyzed jujube extract (HJE), contained higher levels of quercetin, total phenolics, and flavonoids, and exhibited more effective radical-scavenging abilities in comparison to non-hydrolyzed jujube extract (NHJE). HJE treatment decreased production of inflammation-associated molecules, including nitric oxide and pro-inflammatory cytokines from activated Raw 264.7 or differentiated THP-1 cells. HJE treatment also reduced expression of nuclear factor-κB and its downstream proteins in A549 human lung epithelial cells. Moreover, oral supplementation of 1.5 g of HJE per kg of body weight (BW) attenuated histological lung damage, decreased plasma cytokines, and inhibited expression of inflammatory proteins and oxidative stress mediators in the lungs of mice exposed to benzo(a)pyrene at 50 mg/kg BW. Expression levels of antioxidant and cytoprotective factors, such as nuclear factor erythroid-derived 2-related factor 2 and heme oxygenase-1, were increased in lung and liver tissues from mice treated with HJE, compared to mice fed NHJE. These findings indicate that dietary HJE can reduce benzo(a)pyrene-induced lung inflammation by inhibiting cytokine release from macrophages and promoting antioxidant defenses in vivo.
Highlights
Lung inflammation can be triggered by pathogens, toxins, and pollutants [1,2,3]
A research group has shown that jujuboside B, a saponin found in jujube ethanolic extract, lowered the number of immune cells in bronchoalveolar lavage fluid, and decreased levels of allergic phenotype-regulating cytokines in lung homogenate from an ovalbumin-induced allergic asthma mouse model [26]. These findings suggest that jujube ethanolic extract contains a variety of bioactive substances and may relieve lung disease caused by exogenous inflammatory stimuli
For hydrolysis of jujube fruit, Viscozyme was chosen among multiple food industrial enzymes as the highest total phenolic content was acquired in a 50%
Summary
In response to exogenous inflammatory factors, the innate immune defense system is acutely activated to rehabilitate affected tissue and minimize systemic inflammation [4]. Inflammation in the lungs is regulated by a variety of molecular mediators, including proand anti-inflammatory chemokines and cytokines, which are produced by damaged pulmonary epithelial cells, as well as various types of activated leukocytes [6,7]. Mediators related to lung inflammation include tumor necrosis factor α (TNFα), interleukin-6 (IL-6), and interleukin-1β (IL-1β), Foods 2020, 9, 1033; doi:10.3390/foods9081033 www.mdpi.com/journal/foods. Foods 2020, 9, 1033 which regulate maturation of dendritic cells and induce recruitment of neutrophils at inflammatory sites [7,8]. COX-2 is expressed in most cells in an inducible manner at the local inflammation site, whereas COX-1 is constitutively expressed
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