Ecklonia cava Attenuates PM2.5-Induced Cognitive Decline through Mitochondrial Activation and Anti-Inflammatory Effect

Abstract

To evaluate the effects of Ecklonia cava (E. cava) on ambient-pollution-induced neurotoxicity, we used a mouse model exposed to particulate matter smaller than 2.5 µm in aerodynamic diameter (PM2.5). The intake of water extract from E. cava (WEE) effectively prevented the learning and memory decline. After a behavioral test, the toll-like receptor (TLR)-4-initiated inflammatory response was confirmed by PM2.5 exposure in the lung and brain tissues, and the WEE was regulated through the inhibition of nuclear factor-kappa B (NF-κB)/inflammasome formation signaling pathway and pro-inflammatory cytokines (IL-6 and IFN-γ). The WEE also effectively improved the PM2.5-induced oxidative damage of the lungs and brain through the inhibition of malondialdehyde (MDA) production and the activation of mitochondrial activity (mitochondrial ROS content, mitochondria membrane potential (MMP), adenosine triphosphate (ATP) content, and mitochondria-mediated apoptotic molecules). In particular, the WEE regulated the cognition-related proteins (a decreased amyloid precursor protein (APP) and p-Tau, and an increased brain-derived neurotrophic factor (BDNF)) associated with PM2.5-induced cognitive dysfunction. Additionally, the WEE prevented the inactivation of acetylcholine (ACh) synthesis and release as a neurotransmitter by regulating the acetylcholinesterase (AChE) activity, choline acetyltransferase (ChAT), and ACh receptor (AChR)-α3 in the brain tissue. The bioactive compounds of the WEE were detected as the polysaccharide (average Mw; 160.13 kDa) and phenolic compounds including 2′-phloroeckol.

Porphyra tenera Protects against PM2.5-Induced Cognitive Dysfunction with the Regulation of Gut Function

“…In our previous study, we confirmed that PM 2.5 -induced inflammation was initiated in TLR-4 in the brain and lungs [ 19 ]. TLRs are an innate immune receptor in the brain and recognize multiple endogenous ligands that are released as cellular damage signals [ 20 ].…”

“…The water extract and 80% ethanolic extract were dissolved using drinking water, and the mixture was mixed with water extract and 80% ethanolic extract at a ratio of 8:2. The dissolved WP and mixture were administrated with a feeding needle once a day before PM 2.5 exposure (500 μg/m 3 concentration in whole-body exposure, 5 h/day, 5 days/week for 12 weeks) [ 19 ].…”

“…SCFAs were then extracted from the mixtures using n -hexane, and the n -hexane fraction was analyzed using a GC-MS-TQ 8030 triple quadrupole mass spectrometer (Shimadzu, Kyoto, Japan) and GC/MS-QP 2010 Plus (Shimadzu, Kyoto, Japan). The SCFAs were separated using a DB-5MS column (30 m × 0.25 mm, thickness 0.25 μm) with a flow rate of 1.0 mL/min, and the following GC analysis conditions: the initial temperature was 40 °C, which was maintained for 5 min, and was then allowed to reach 310 °C at a rate of 10 °C /min (split ratio 60:1, injection temp 200 °C, and column oven temp 60 °C) [ 19 ].…”

PM2.5 exposure inducing ATP alteration links with NLRP3 inflammasome activation

“…Previous studies have shown that PM 2.5 can lead to intracellular mitochondrial dysfunction and subsequently weaken mitochondrial respiration and reduce ATP production (Ku et al 2016 ; Miao et al 2019 ; Park et al 2021 ). For example, exposure to haze, the dose of PM 2.5 can reduce ATP production in the lungs of rats, decrease the activity of malate dehydrogenase and citrate synthase [critical enzymes in the tricarboxylic acid (TCA) cycle], and attenuate the expression of mitochondrial respiration chain genes such as UQCRI1 and NDUFS2 (Jin et al 2019a ).…”

Water Extract of Ecklonia cava Protects against Fine Dust (PM2.5)-Induced Health Damage by Regulating Gut Health

“…, antioxidant, anti-inflammation, anti-diabetic, cognitive improvement, and anti-obesity effects) have been reported recently [ 15 , 16 ] . In our previous study, it was found that the water extract from Ecklonia cava (WEE) effectively prevented PM 2.5 -induced cognitive decline, and the major bioactive compounds of the WEE were fucoidan and phlorotannins [ 17 ]. However, it has been reported that fucoidan and most phlorotannins do not directly affect brain function as they cannot pass through the blood-brain-barrier (B-B-B) [ 18 - 20 ].…”