Benzo(a)pyrene (B(a)P) and pyrene, the most prominent subtypes of polycyclic aromatic hydrocarbons (PAHs), contaminate environments as organic pollutants. They adversely affect body systems, including degeneration of the central nervous system. This study investigated the in vitro toxic effects of B(a)P and pyrene on proliferation, endoplasmic reticulum (ER) stress induction, and autophagy in human astrocytes using U-87 MG human astrocytoma cells as a model. Both B(a)P and pyrene were toxic to U-87 MG cells in a concentration-dependent manner. Astrocytic proliferation was interfered with, enhancing S-phase cell cycle arrest. B(a)P promoted the presence of autophagic vesicles and the expression of autophagic markers LC3, beclin-1, and p62, suggesting activated autophagy. B(a)P enhanced the expression of ER stress markers BiP, PERK, and IRE1. ER stress appeared to be correlated with autophagy induction, as demonstrated by experiments using chloroquine, an autophagy inhibitor. Pyrene enhanced the expression of autophagic markers and ER stress primarily via PERK activation, although autophagic vesicles were not observed. The study demonstrates that B(a)P enhances ER stress-mediated autophagy more evidently than pyrene and affected toxicity to astrocytes. These results provide a basis for understanding the toxic effects of the main PAH substances affecting astrocytes.

Seaweed has attracted attention as a bioactive source for preventing different chronic diseases, including liver injury and non-alcoholic fatty liver disease, the leading cause of liver-related mortality. Caulerpa lentillifera is characterized as tropical edible seaweed, currently being investigated for health benefits of its extracts and bioactive substances. This study examined the effects of C. lentillifera extract in ethyl acetate fraction (CLEA) on controlling lipid accumulation and lipid metabolism in HepG2 cells induced with oleic acid through the in vitro hepatic steatosis model. Gas chromatography-mass spectrometry (GC-MS) analysis indicated that CLEA contained diverse organic compounds, including hydrocarbons, amino acids, and carboxylic acids. Docked conformation of dl-2-phenyltryptophane and benzoic acid, two major bioactive CLEA components, showed high affinity binding to SIRT1 and AMPK as target molecules of lipid metabolism. CLEA reduced lipid accumulation and intracellular triglyceride levels in HepG2 cells stimulated with oleic acid. The effect of CLEA on regulating expression of lipid metabolism-related molecules was investigated by qPCR and immunoblotting. CLEA promoted expression of the SIRT1 gene in oleic acid-treated HepG2 cells. CLEA also reduced expression levels of SREBF1, FAS, and ACC genes, which might be related to activation of AMPK signaling in lipid-accumulated HepG2 cells. These findings suggest that CLEA contains bioactive compounds potentially reducing triglyceride accumulation in lipid-accumulated HepG2 hepatocytes by controlling lipid metabolism molecules.

Tanapan Siangcham, Parisa Prathaphan, Jittiporn Ruangtong, Nattaya Thongsepee, Pongsakorn Martviset, Pathanin Chantree, Phornphan Sornchuer, and Kant Sangpairoj. Prev Nutr Food Sci 2022;27:376-83. https://doi.org/10.3746/pnf.2022.27.4.376

Parkinson’s disease (PD) is a neurodegenerative disorder caused by the death of dopaminergic neurons in the substantia nigra pars compacta (SNc). Lipid metabolism, especially phospholipids, has been reported to be altered in PD. The purpose of this study is to investigate the temporal expression and spatial distribution of phospholipids in the motor cortex and striatum at different time points of PD using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian mouse model. Mice were injected with saline (NSS) or MPTP at two different time points to create acute and subacute models. Motor analysis was performed at 0, 3, 7, 14, and 21 days post-injection. Tyrosine hydroxylase (TH) staining revealed progressive damage of neurons in the substantia nigra compacta (SNc) and reduced striatal fibers in MPTP-treated animals. By using MALDI-MSI, we identified changes in phosphatidylcholine (PC) profiles in the brains of MPTP-treated animals. Polyunsaturated PCs, including PC 36:4 (16:0/20:4), PC 38:6 (16:0/22:6), and PC 40:8 (18:2/22:6), were decreased in the MPTP-treated groups. These reductions were time-dependent and were more pronounced in the subacute MPTP-treated group. The loss of dopamine neurons caused by MPTP may be associated with the selective loss of polyunsaturated PCs in brain membranes, indicating that lipid metabolism and membrane structural alterations may contribute to the pathology of PD.

The application of natural bioactive compounds in cosmeceutical products, particularly as skin-lightening agents, has received increasing interest. Caulerpa racemosa, a green macroalga of the Chlorophyta division, contains beneficial nutrients that are applicable as food and cosmeceutical ingredients. This study investigated the in vitro effect of the ethanolic extract of C. racemosa (CR) on regulation of melanogenic-related signaling and gene expression in SK-MEL-5 human melanoma-derived cells. Identification of bioactive components revealed that catechin, rutin, and quercetin as flavonoid contents were found in CR extract, analyzed using HPLC. The expressions of microphthalmia-associated transcription factor (MITF), extracellular signal-regulated kinase (ERK) signaling molecules, and melanogenic-related molecules were analyzed via Western blotting and qPCR. The CR extract treatment applied to SK-MEL-5 cells decreased the MITF protein expression level, which correlated with increased pERK expression, and no cytotoxic effect was observed. The subsequent treatment reduced the expression of melanogenesis-related genes (TYR, TYRP1, MC1R, and DCT) that were downstream targets of MITF. This study provides preliminary evidence that CR extract may modulate melanogenesis-related signaling. However, the specific bioactive compounds responsible for the observed effects remain to be identified, as the extract contains a complex mixture of phytochemicals. Further fractionation studies are needed to pinpoint the active constituents. The variability of extract composition due to seasonal and geographical factors should be considered for future standardization.

Human exposure to benzo(a)pyrene [B(a)P] from contaminated environmental pollutants may induce cellular senescence. Mesenchymal stem cells (MSCs) are responsible for maintaining bone homeostasis, mineralization and integrity. Senescent MSCs may result from exogenous chemical exposure, leading to diminished osteogenic potential and increased bone loss. This study elucidated the toxicological effects of B(a)P exposure in human bone marrow-derived MSCs (BM-hMSCs) under induced osteogenic and adipogenic differentiation by in vitro testing and transcriptomic analyses. Cell viability assays following 1–20 µM of B(a)P showed no toxic effects after 24 to 72 h of exposure. Non-cytotoxic concentrations of B(a)P (1–20 µM) suppressed the differentiation of BM-hMSCs into osteogenic and adipogenic lineages over 7 to 21 days, as indicated by reduced phenotypic parameters and molecular expression of differentiation markers compared with differentiation-induced cells. B(a)P decreased osteoblastic proliferation of signaling Wnt/β-catenin, with increased AhR/AhRR expression, which is related to osteogenic damage. Furthermore, B(a)P increased the expression of senescence markers, includingintracellular β-galactosidase, p21 and the secretory markers IL-1β and IL-6, in osteogenic-differentiated BM-hMSCs. The transcriptomic profile of osteogenic-differentiated BM-hMSCs exposed to 10 µM of B(a)P for 21 days revealed upregulation of stress and inflammatory responses, along with downregulation of cell cycle regulation and genes associated with cellular integrity. RNA-seq profiles also revealed upregulation of senescence-associated markers. Collectively, B(a)P may impair their differentiation capacity and is associated with senescence induction, partly through AhR activation. This study highlights the implications for skeletal health risk of chronic exposure to environmental pollutants by detection of senescent-associated markers.