The Hepatoprotective Effect of Leonurine Hydrochloride Against Alcoholic Liver Disease Based on Transcriptomic and Metabolomic Analysis.

Excessive alcohol consumption can eventually progress to alcoholic liver disease (ALD). The underlying mechanism of ALD toxicity is primarily associated with oxidative damage. Many alkaloids have been reported to possess potential antioxidative efficacy, while the mechanism of their hepatoprotective activity against ALD is still not clear. In this study, eight alkaloids were selected from a monomer library of Traditional Chinese Medicine and evaluated for their antioxidant activity against ALD by the evaluation of Glutathione (GSH) and Malondialdehyde (MDA). The result suggested that Leonurine hydrochloride (LH) was a potent antioxidant that could reduce alcoholic liver damage. To further investigate the underlying mechanism of LH against ALD, the molecular pathway induced by LH was identified by RNA-seq analyses. Transcriptome data revealed the principal mechanism for the protective effect of LH against ALD might be attributed to the differentially expressed genes (DEGs) of PI3K-AKT, AMPK, and HIF-1 signaling pathways involved in the lipid metabolism. Given the hepatoprotective mechanism of LH is involved in lipid metabolism, the lipid metabolism induced by LH was further analyzed by UHPLC-MS/MS. Metabolome analysis indicated that LH significantly regulated glycerophospholipid metabolism including phosphatidylcholine, 1-acyl-sn-glycero-3-phosphocholine, phosphatidylethanolamine and 1-acyl-sn-glycero-3-phosphoethanolamine in the liver. Overall, this study revealed that the hepatoprotective mechanism of LH against alcoholic liver damage might be associated with the genes involved in glycerophospholipid metabolism.

Targeted Lipidomics Reveal the Effect of Perchlorate on Lipid Profiles in Liver of High-Fat Diet Mice.

Perchlorate, commonly available in drinking water and food, acts on the iodine uptake by the thyroid affecting lipid metabolism. High-fat diets leading to various health problems continually raise public concern. In the present study, liver lipid metabolism profiles and metabolic pathways were investigated in C57BL/6J mice chronically exposed to perchlorate using targeted metabolomics. Mice were fed a high-fat diet and treated orally with perchlorate at 0.1 mg/kg bw (body weight), 1 mg/kg bw and 10 mg/kg bw daily for 12 weeks. Perchlorate induced disorders of lipid metabolism in vivo and hepatic lipid accumulation confirmed by serum biochemical parameters and histopathological examination. There were 34 kinds of lipid in liver detected by UHPLC-MS/MS and key metabolites were identified by multivariate statistical analysis evaluated with VIP > 1, p-value < 0.05, fold change > 1.2 or < 0.8. Perchlorate low, medium and high dose groups were identified with 11, 7 and 8 significantly altered lipid metabolites compared to the control group, respectively. The results of the metabolic pathway analysis revealed that the differential metabolites classified into different experimental groups contribute to the glycerophospholipid metabolic pathway. These findings provide insights into the effects of perchlorate on lipid metabolism during long-term exposure to high-fat diets and contribute to the evaluation of perchlorate liver toxic mechanisms and health effects.

Geographical discrimination and adulteration analysis for edible oils using two-dimensional correlation spectroscopy and convolutional neural networks (CNNs).

Geographical discrimination and adulteration analysis play significant roles in edible oil analysis. A novel method for discrimination and adulteration analysis of edible oils were proposed in this study. The two-dimensional correlation spectra of edible oils were obtained by solvents perturbation and the convolutional neural networks (CNNs) were constructed to analyze the synchronous and asynchronous correlation spectra of the edible oils. The differences for geographical origins of oils or oil types could be amplificated through the networks. For different networks, the layer sequences and the filter number of convolutional layers may affect the analysis results. A group of sesame oils from different geographical origins and a group of olive oils adulterated by other vegetable oils were adopted to evaluate the proposed method. The results show that the proposed method may provide an alternative method for edible oil discrimination and adulteration analysis in practical applications. For the two datasets, the prediction accuracy could be 97.3% and 88.5%, respectively.

Simultaneous and rapid determination of sesamin and sesamolin in sesame oils using excitation-emission matrix fluorescence coupled with self-weighted alternating trilinear decomposition.

BACKGROUND: Sesamin and sesamolin are two typical and important lignans isolated from sesame oil. Various studies have shown the bioactivity, physiological activity, and potential health benefits of the two components. In this study, a rapid method for the simultaneous determination of sesamin and sesamolin in sesame oils was proposed. The excitation-emission fluorescence spectra of the oils were obtained after a simple pretreatment, then self-weighted alternating trilinear decomposition was used to extract the quantitative information from the very overlapping spectra. RESULTS: It was found that reasonable quantification results could be obtained with the limits of detection for the two lignans. These limits were 0.05 mg/g and 0.24 mg/g, and the limits of quantitation were 0.14 mg/g and 0.74 mg/g, respectively. The average recoveries for sesamin and sesamolin were 99.05% and 94.97%. CONCLUSION: The results indicate that, with simple sample pretreatment, the application for combining excitation-emission fluorescence spectra and self-weighted alternating trilinear decomposition can be a useful and sensitive tool for the determination of lignans in sesame oil. © 2020 Society of Chemical Industry.

Rapid determination of phytosterols by NIRS and chemometric methods.

Phytosterols have been extensively studied because it plays essential roles in the physiology of plants and can be used as nutritional supplement to promote human health. We use a rapid method by coupling near-infrared spectroscopy (NIRS) and chemometric techniques to quickly and efficiently determine three essential phytosterols (ß-sitosterol, campesterol and stigmasterol) in vegetable oils. Continuous wavelet transform (CWT) method was adopted to remove the baseline shift in the spectra. The quantitative analysis models were constructed by partial least squares (PLS) regression and randomization test (RT) method was used to further improve the models. The optimized models were used to calculate the phytosterol contents in prediction set in order to evaluate their predictability. We have found that the phytosterol contents obtained by the optimized models and Gas Chromatography/Mass Spectrometry (GC/MS) analysis are almost consistent. The root mean square error of prediction (RMSEP) and ratio of prediction to deviation (RPD) for the three phytosterols are 525.7590, 212.2245, 65.1611 and 4.0060, 4.7195 and 3.5441, respectively. The results have proved the feasibility of the proposed method for rapid and non-destructive analysis of phytosterols in edible oils.

Dietary DHA/EPA Ratio Changes Fatty Acid Composition and Attenuates Diet-Induced Accumulation of Lipid in the Liver of ApoE-/- Mice.

Diets containing various docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) ratios protect against liver damage in mice fed with a high-fat diet (HFD). However, it is unclear whether these beneficial roles of DHA and EPA are associated with alterations of fatty acid (FA) composition in the liver. This study evaluated the positive impacts of n-6/n-3 polyunsaturated fatty acids (PUFAs) containing different DHA/EPA ratios on HFD-induced liver disease and alterations of the hepatic FA composition. ApoE-/- mice were fed with HFDs with various ratios of DHA/EPA (2 : 1, 1 : 1, and 1 : 2) and an n-6/n-3 ratio of 4 : 1 for 12 weeks. After treatment, the serum and hepatic FA compositions, serum biochemical parameters, liver injury, and hepatic lipid metabolism-related gene expression were determined. Our results demonstrated that dietary DHA/EPA changed serum and hepatic FA composition by increasing contents of n-6 and n-3 PUFAs and decreasing amounts of monounsaturated fatty acids (MUFAs) and the n-6/n-3 ratio. Among the three DHA/EPA groups, the DHA/EPA 2 : 1 group tended to raise n-3 PUFAs concentration and lower the n-6/n-3 ratio in the liver, whereas DHA/EPA 1 : 2 tended to raise n-6 PUFAs concentration and improve the n-6/n-3 ratio. DHA/EPA supplementation reduced the hepatic impairment of lipid homeostasis, oxidative stress, and the inflammatory responses in HFD-fed mice. The DHA/EPA 2 : 1 group had lower serum levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol and higher levels of adiponectin than HFD group. The DHA/EPA 1 : 2 group had elevated serum levels of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, without significant change the expression of genes for inflammation or hepatic lipid metabolism among the three DHA/EPA groups. The results suggest that DHA/EPA-enriched diet with an n-6/n-3 ratio of 4 : 1 may reverse HFD-induced nonalcoholic fatty liver disease to some extent by increasing n-6 and n-3 PUFAs and decreasing the amount of MUFAs and the n-6/n-3 ratio.

Protective effects of various ratios of DHA/EPA supplementation on high-fat diet-induced liver damage in mice.

BACKGROUND: A sedentary lifestyle and poor diet are risk factors for the progression of non-alcoholic fatty liver disease. However, the pathogenesis of hepatic lipid accumulation is not completely understood. Therefore, the present study explored the effects of dietary supplementation of various ratios of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on a high-fat diet-induced lipid metabolism disorder and the concurrent liver damage. METHODS: Using high-fat diet-fed C57BL/6 J mice as the animal model, diets of various ratios of DHA/EPA (2:1, 1:1, and 1:2) with an n-6/n-3 ratio of 4:1 were prepared using fish and algae oils enriched in DHA and/or EPA and sunflower seed oils to a small extent instead of the high-fat diet. RESULTS: Significantly decreased hepatic lipid deposition, body weight, serum lipid profile, inflammatory reactions, lipid peroxidation, and expression of adipogenesis-related proteins and inflammatory factors were observed for mice that were on a diet supplemented with DHA/EPA compared to those in the high-fat control group. The DHA/EPA 1:2 group showed lower serum triglycerides (TG), total cholesterol (TC), and low-density lipoprotein-cholesterol levels, lower SREBP-1C, FAS, and ACC-1 relative mRNA expression, and higher Fra1 mRNA expression, with higher relative mRNA expression of enzymes such as AMPK, PPARα, and HSL observed in the DHA/EPA 1:1 group. Lower liver TC and TG levels and higher superoxide dismutase levels were found in the DHA/EPA 2:1 group. Nonetheless, no other notable effects were observed on the biomarkers mentioned above in the groups treated with DHA/EPA compared with the DHA group. CONCLUSIONS: The results showed that supplementation with a lower DHA/EPA ratio seems to be more effective at alleviating high-fat diet-induced liver damage in mice, and a DHA/EPA ratio of 1:2 mitigated inflammatory risk factors. These effects of n-3 polyunsaturated fatty acids (PUFA) on lipid metabolism may be linked to the upregulation of Fra1 and attenuated activity of c-Jun and c-Fos, thus ultimately reducing the severity of the lipid metabolism disorder and liver damage to some extent.

Protective role of n6/n3 PUFA supplementation with varying DHA/EPA ratios against atherosclerosis in mice.

The effects of n3 polyunsaturated fatty acids (PUFA) on cardiovascular disease are controversial. We currently explored the effects of various ratios of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on high-fat-induced atherosclerosis. In model apoE(-/-) mice, high-fat diets (HFD) were partially replaced with fish and algal oils (DHA/EPA 2:1, 1:1 and 1:2) and/or plant oils enriched in linoleic and alpha-linolenic acids with an n6/n3 ratio of 4:1. PUFA supplementation significantly reduced the atherosclerotic plaque area, serum lipid profile, inflammatory response, aortic ROS production, proinflammatory factors and scavenger receptor expression as compared to those in the HFD group. However, plant oils did not have a significant effect on the following: serum HDL-C level; aortic ABCA1, ABCG1 and LAL mRNA expression; and CD36 and LOX-1 protein expression. Compared to the plant-oil-treated group, the DHA/EPA 1:1 group had a smaller atherosclerotic plaque area, higher serum HDL-C levels and lesser CD36 and MSR-1 mRNA expression; the DHA/EPA 2:1 group had lower serum TC, LDL-C and TNF-α levels and lower aortic ROS levels. Our study suggested that n3 PUFA from animals had more potent atheroprotective effects than that from plants. Supplementation involving higher DHA/EPA ratios and an n6/n3 ratio of 4:1 was beneficial for reducing serum "bad cholesterol" and a 1:1 DHA/EPA ratio with an n6/n3 ratio of 4:1 was beneficial for improving serum "good cholesterol" and inhibiting ox-LDL uptake. Our results suggest that achieving an n6/n3 ratio of 4:1 in the diet is also important in addition to having an optimal DHA/EPA ratio.

Folic Acid Supplementation Reduces the Mutagenicity and Genotoxicity Caused by Benzo(a)pyrene.

Folate is a vital vitamin for the human being and its deficiency can lead to a variety of clinical abnormalities ranging from neural tube defects to cancers. Benzo(a)pyrene (BaP), a strong mutagen and carcinogen, is considered one of the common contaminants in food. The aim of this study was to investigate the positive effect of folate on cancer prevention at a fundamental level. In the present study, we investigated the impact of folic acid on BaP-induced mutagenicity and genotoxicity by means of in vitro and in vivo experiments. The reformed Ames test was applied to study the antimutagenicity of folic acid against BaP. The protective effect of folic acid on cytotoxicity caused by BaP in human liver cell line L02 was evaluated by MTT assay. In addition, the effect of folic acid on the BaP-induced genotoxicity in vivo was assessed by mouse bone marrow micronucleus assay. The results indicated that folic acid significantly inhibited the reverse mutation of Salmonella typhimurium strains TA98 and TA100, and protected the viability of human liver cells against BaP (p<0.01). The micronucleus test showed that all doses of folic acid had a remarkable protective effect for the female mice (p<0.01). In conclusion, folic acid was found to reduce the mutagenicity and genotoxicity induced by BaP.

Antioxidant and antigenotoxic activity of bioactive extracts from corn tassel.

This study is designed to evaluate antioxidant and antigenotoxic activities of corn tassel extracts (CTTs). The major bioactive components of CTTs include flavonoid, saponin and polysaccharide. The antioxidant properties of the three bioactive components of CTTs were investigated by Ferric Reducing Antioxidant Property (FRAP) and 1, 1-diphenyl-2-picrylhydrazyl (DPPH) assays. The activities of the extracts were determined by assessing the inhibition of mutagenicity of the direct-acting mutagen fenaminosulf, sodium azide, and indirect-acting mutagen 2-aminofluorene using the Ames test (strains TA98 and TA100). The results showed that the extraction rates of flavonoid, saponin, and polysaccharide from the dried corn tassels were 1.67%, 2.41% and 4.76% respectively. DPPH and FRAP assay strongly demonstrated that CTTs had antioxidant properties. CTTs at doses of 625, 1250 and 2500 µg per plate reduced 2-aminofluorene mutagenicity by 12.52%, 28.76% and 36.49% in Salmonella typhimurium TA98 strain assay respectively and by 10.98%, 25.27% and 37.83%, at the same doses in Salmonella typhimurium TA100 assay system, respectively. 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay showed that the different concentrations of CTTs inhibited the proliferation of MGC80-3 cells in a dose-dependent manner (P<0.01). It is concluded that these integrated approaches to antioxidant and antigenotoxicity assessment may be useful to study corn tassel as a natural herbal material.