Lycopene Alleviates Endoplasmic Reticulum Stress in Steatohepatitis through Inhibition of the ASK1-JNK Signaling Pathway.

Lycopene has been proven to alleviate nonalcoholic steatohepatitis (NASH), but the precise mechanisms are inadequately elucidated. In this study, we found a previously unknown regulatory effect of lycopene on the apoptosis signal-regulating kinase 1 (ASK1) signaling pathway in both in vivo and in vitro models. Lycopene supplementation (3 and 6 mg/kg/day) exhibited a significant reduction in lipid accumulation, inflammation, and fibrosis of the liver in mice fed with a high-fat/high-cholesterol diet or a methionine-choline-deficient diet. RNA sequencing uncovered that the mitogen-activated protein kinases signaling pathway, which is closely associated with inflammation and endoplasmic reticulum (ER) stress, was significantly downregulated by lycopene. Furthermore, we found lycopene ameliorated ER swelling and decreased the expression levels of ER stress markers (i.e., immunoglobulin heavy chain binding protein, C/EBP homologous protein, and X-box binding protein 1s). Especially, the inositol-requiring enzyme 1α involved in the ASK1 phosphorylation was inhibited by lycopene, resulting in the decline of the subsequent c-Jun N-terminal kinase (JNK) signaling cascade. ASK1 inhibitor DQOP-1 eliminated the lycopene-induced inhibition of the ASK1-JNK pathway in oleic acid and palmitic acid-induced HepG2 cells. Molecular docking further indicated hydrophobic interactions between lycopene and ASK1. Collectively, our research indicates that lycopene can alleviate ER stress and attenuate inflammation cascades and lipid accumulation by inhibiting the ASK1-JNK pathway.

Colorimetric ELISA based on urease catalysis curcumin as a ratiometric indicator for the sensitive determination of aflatoxin B1 in grain products.

There is an urgent need to measure aflatoxin B1 (AFB1) in food to prevent contaminated food consumption. In this work, a novel colorimetric enzyme-linked immunosorbent assay (ELISA) was developed for the detection of AFB1 using curcumin as a colorimetric indicator. An indirect competitive enzyme-label immunoassay was developed using urease and rabbit anti-mouse immunoglobulin G labeled with gold nanoparticles as the signal-transduction tag. Urease catalyzed the hydrolysis of urea to produce ammonia, which increased the pH of the solution. The phenolic hydroxyl group of curcumin ionized into phenolic oxygen anions under alkaline conditions, which strengthened the synergistic effect of electron supply and absorption in curcumin. As a result, the color of curcumin changed from yellow to reddish-brown, producing a visible color change. Under optimal conditions, AFB1 could be qualitatively determined with the naked eye, and quantitatively assessed by measuring the ratio of absorbance at wavelengths of 550 and 428 nm. The change in the ratio of absorbance Δ550/Δ428 decreased linearly in a range of 0.01-5 ng mL-1, and the limit of detection was 67 pg mL-1. Therefore, the selectivity and reliability of this proposed method were well validated. This method was also successfully used for the quantitation of AFB1 in spiked rice flour and wheat flour samples. This approach may broaden the application field of colorimetric ELISA for aflatoxin, providing a promising platform for the rapid screening of aflatoxin in food.