Berry Phenolic and Volatile Extracts Inhibit Pro-Inflammatory Cytokine Secretion in LPS-Stimulated RAW264.7 Cells through Suppression of NF-κB Signaling Pathway

Abstract

Berries are a rich source of phytochemicals, especially phenolics well known for protective activity against many chronic diseases. Berries also contain a complex mixture of volatile compounds that are responsible for the unique aromas of berries. However, there is very limited information on the composition and potential health benefits of berry volatiles. In this study, we isolated phenolic and volatile fractions from six common berries and characterized them by HPLC/HPLC-MS and GC/GC-MS, respectively. Berry phenolic and volatile fractions were evaluated for an anti-inflammatory effect using lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells by measuring levels of pro-inflammatory cytokines and the nuclear factor-kappa B (NF-κB) signaling pathway. Results showed that LPS-induced excessive production of nitric oxide (NO), prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), which were inhibited by berry phenolic and volatile extracts. Moreover, berry phenolic and volatile extracts reduced the nuclear translocation of NF-κB by blocking the phosphorylation of p65 and degradation of IκBα. These findings showed that berry volatiles from six berries had comparable anti-inflammatory effects to berry phenolics through the suppression of pro-inflammatory mediators and cytokines expression via NF-κB down-regulation, despite being present in the fruit at a lower concentration.

Analysis of the Chemical, Antioxidant, and Anti-Inflammatory Properties of Pink Pepper (Schinus molle L.)

“…PPE inhibited LPS-induced phosphorylation of p38, but not p65, JNK, or ERK (Figure 3E,F). Gu et al suggested that phenolic and volatile extracts of six berries suppressed LPS-mediated abnormal NO production by 48-94% [33]. In the present study, the inhibitory effect of PPB and PPS on LPS-induced NO production was 86.3% and 67.7%, respectively (Figure 3A).…”

“…In the present study, the inhibitory effect of PPB and PPS on LPS-induced NO production was 86.3% and 67.7%, respectively (Figure 3A). Therefore, it seems that pink pepper exhibits inhibitory activity similar to that of berries, which are well known for their inhibition of NO production [33]. Interestingly, although materials that have a suppressive effect on LPS-induced NO production mainly regulated phosphorylation of p65 [23,33,34], a catalytic subunit of NF-κB, PPB and PPS only affected the phosphorylation of p38 in MAPKs in RAW264.7 cells.…”

“…Therefore, it seems that pink pepper exhibits inhibitory activity similar to that of berries, which are well known for their inhibition of NO production [33]. Interestingly, although materials that have a suppressive effect on LPS-induced NO production mainly regulated phosphorylation of p65 [23,33,34], a catalytic subunit of NF-κB, PPB and PPS only affected the phosphorylation of p38 in MAPKs in RAW264.7 cells. Our previous study also reported that ultrasonicated seaweed extract only affected phosphorylation of MAPKs and activator protein (AP-1), and not NF-κB [7].…”

New Polyketides With Anti-Inflammatory Activity From the Fungus Aspergillus rugulosa

“…They can be stimulated by LPS, and then, they secrete multiple pro-inflammatory factors, such as NO, COX-2, IL6, IL1β, and TNF-α ( Duarte et al, 2014 ). Excessive NO can induce DNA damage, apoptosis, and oxidative stress, thereby amplifying the inflammatory response ( Gu et al, 2020 ). Accordingly, all of the isolates were evaluated for anti-inflammatory activity against the production of NO in RAW264.7 stimulated by LPS.…”

Anti-Inflammatory and Antioxidant Properties of Plant Extracts

“…In addition, berries also contain a complex mixture of volatile compounds that are responsible for its aroma. Gu et al [7] found that both berry phenols and volatile fractions show an anti-inflammatory effect on LPS-stimulated RAW264.7 cells through the suppression of the nuclear factor-kappa B (NF-kB) signaling pathway.…”