Artocarpus heterophyllus, a popular tropical fruit commonly known as the jackfruit tree, is normally planted in subtropical or tropical areas. Since a variety of phytochemicals isolated from A. heterophyllus have been found to possess potently anti-inflammatory, antiviral and antimalarial activities, researchers have devoted much interest to its potential pharmaceutical value. However, the exact mechanism underlying its anti-inflammatory activity is not well characterized. In this study, seven natural products isolated from A. heterophyllus, including 25-Hydroxycycloart-23-en-3-one (HY), Artocarpin (AR), Dadahol A (DA), Morachalcone A (MA), Artoheterophyllin B (AB), Cycloheterophyllin (CY) and Moracin C (MC) were collected. Lipopolysaccharide (LPS)-stimulated inflammatory response in RAW264.7 macrophages were used in this study. Among these compounds, MC significantly inhibited LPS-activated reactive oxygen species (ROS) and nitric oxide (NO) release without marked cytotoxicity. Furthermore, MC effectively reduced LPS stimulated up-regulation of mRNA and protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and serval pro-inflammatory cytokines (interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α)). Mechanistic studies revealed that the anti-inflammatory effect of MC was associated with the activation of the mitogen activated protein kinases (MAPKs) (including p38, ERK and JNK) and nuclear factor-κB (NF-κB) pathways, especially reducing the nuclear translocation of NF-κB p65 subunit as revealed by nuclear separation experiment and confocal microscopy.

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The gut microbiota is engaged in multiple interactions affecting host health. Bacteriocins showed the ability of impeding the growth of intestinal pathogenic bacteria and modulating gut microbiota in animals. Few studies have also discovered their regulation on human intestinal flora using an in vitro simulated system. However, little is known about their effect on gut microbiota of different enterotypes of human. This work evaluated the modification of the gut microbiota of two enterotypes (ET B and ET P) by the class IIb bacteriocin plantaricin NC8 (PLNC8) by using an in vitro fermentation model of the intestine. Gas chromatography results revealed that PLNC8 had no influence on the gut microbiota’s production of short-chain fatty acids in the subjects’ samples. PLNC8 lowered the Shannon index of ET B’ gut microbiota and the Simpson index of ET P’ gut microbiota, according to 16S rDNA sequencing. In ET B, PLNC8 enhanced the abundance of Bacteroides, Bifidobacterium, Megamonas, Escherichia-Shigella, Parabacteroides, and Lactobacillus while decreasing the abundance of Streptococcus. Prevotella_9, Bifidobacterium, Escherichia-Shigella, Mitsuokella, and Collinsella were found more abundant in ET P. The current study adds to our understanding of the impact of PLNC8 on the human gut microbiota and lays the groundwork for future research into PLNC8’s effects on human intestinal disease.