Urolithins Attenuate LPS-Induced Neuroinflammation in BV2Microglia via MAPK, Akt, and NF-κB Signaling Pathways

Abstract

Emerging data suggest that urolithins, gut microbiota metabolites of ellagitannins, contribute toward multiple health benefits attributed to ellagitannin-rich foods, including walnuts, red raspberry, strawberry, and pomegranate. However, there is limited data on whether the potential neuroprotective effects of these ellagitannin-rich foods are mediated by urolithins. Herein, we evaluated the potential mechanisms of antineuroinflammatory effects of urolithins (urolithins A, B, and C; 8-methyl-O-urolithin A; and 8,9-dimethyl-O-urolithin C) in BV2 murine microglia in vitro. Nitrite analysis and qRT-PCR suggested that urolithins A and B reduced NO levels and suppressed mRNA levels of pro-inflammatory genes of TNF-α, IL-6, IL-1β, iNOS, and COX-2 in LPS-treated microglia. Western blot revealed that urolithins A and B decreased phosphorylation levels of Erk1/2, p38 MAPK, and Akt, prevented IκB-α phosphorylation and degradation, and inhibited NF-κB p65 subunit phosphorylation and nuclear translocation in LPS-stimulated microglia. Our results indicated that urolithins A and B attenuated LPS-induced inflammation in BV2 microglia, which may be mediated by inhibiting NF-κB, MAPKs (p38 and Erk1/2), and Akt signaling pathway activation. The antineuroinflammatory activities of urolithins support their role in the potential neuroprotective effects reported for ellagitannin-rich foods warranting further in vivo studies on these ellagitannin gut microbial derived metabolites.

Urolithin a attenuates IL-1β-induced inflammatory responses and cartilage degradation via inhibiting the MAPK/NF-κB signaling pathways in rat articular chondrocytes

“…A recent study demonstrated that the Liraglutide (GLP-1 agonist) ameliorates cartilage degeneration in a rat model of knee osteoarthritis with anti-inflammatory activity [32]. Valproic acid and butyrate were widely reported as latent therapeutic agents for OA due to their ability to suppress IL-1β-induced inflammation and cartilage degradation [33,34]. During disease progression, IL-1β stimulates the expression of the matrix metalloproteinase (MMPs) that mediate the degradation of cartilage matrix components and suppress proteoglycan synthesis [35].…”

Polyphenols in Alzheimer’s Disease and in the Gut–Brain Axis

“…It was shown that the catabolites derived from the ellagitannin, such as urolithins and pyrogallol, are effective antiglycating as well as antioxidant agents [45]. Urolithins were also shown to attenuate the neuroinflammation in BV2 microglia by various other mechanisms, including the NF-κB, MAPK and Akt signaling pathways [60]. Urolithins, such as those derived from pomegranates, act as neuroprotectors and can potentially prevent the AD.…”

Elucidation of The Anti‐Inflammatory Effect of Vanillin In Lps‐Activated THP‐1 Cells

“…Vanillin (4‐hydroxy‐3‐methoxybenzaldehyde) (VA), a kind of phenolic compound, is a major component of Vanilla planifolia seed (Sinha, Sharma, & Sharma, ; Xu et al., ) and widely found in food and beverage (as shown in Supporting Information Table S1), such as biscuit (9.3 to 42.6 µg/g), candy (36.7 to 2860.0 µg/g), milk powder (132.9 to 1990.0 µg/g), and Baijiu (210 to 306 µg/L) (Deng, Xu, Zeng, & Ding, ; Ni, Zhang, & Kokot, ; Zhao et al., ; Ziyatdinova, Kozlova, Ziganshina, & Budnikov, ). In Gujinggong Baijiu (a well‐known brand of strong‐aroma type Baijiu), VA was identified as a contributor for the aroma profile due to its higher flavor dilution value (≥729) (Liu & Sun, ; Zhao et al., ).…”