Protective Effect of Isoorientin on Oleic Acid-Induced Oxidative Damage and Steatosis in Rat Liver Cells

Luo, Tongwang; Jiang, Sheng; Zhou, Bin; Song, Quanjiang; Du, Jing; Liu, Ping; Wang, Xiaodu; Song, Houhui; Shao, Chen

doi:10.3389/fphar.2022.818159

Cited by 6 publications

(3 citation statements)

References 40 publications

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“…Furthermore, therapeutic oral ISO signi cantly reduced plasma and colon MDA production, while promoting the synthesis of antioxidant enzymes, such as T-SOD and CAT. A previous study had demonstrated similar antioxidative effects [36][37][38] . Overall ISO relieved DSS-induced colitis in a dosedependent manner.…”

Section: Discussionmentioning

confidence: 67%

Isoorientin alleviates DSS-treated acute colitis in mice by regulating intestinal epithelial P-glycoprotein (P-gp) expression.

wang,

Yang,

Feng

et al. 2023

Preprint

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Background Isoorientin (ISO) is a naturally-occurring flavonoid with diverse functional properties that mitigate the risk of diseases stemming from oxidation, inflammation and cancer cell proliferation. P-glycoprotein (P-GP) is a vital component of the intestinal epithelium, and alterations in P-gp expression and functionality may play a role in the onset of intestinal inflammatory conditions, such as inflammatory bowel disease (IBD). Recent studies have suggested that short-chain fatty acids (SCFAs) and secondary bile acids produced by the gut microbiota, stimulate the increase in operational P-gp expression, alleviating excessive inflammation, and thereby aid the preservation of intestinal homeostasis. ISO has been shown to improve colon health and modulate gut microbiota. However, whether ISO can modulate the microbes and their metabolites to influence P-gp expression to alleviate IBD is unknown. Results First, the impact of ISO on dextran sulfate sodium (DSS)-treated colitis was investigated in mice. The present study indicated that ISO mitigated the symptoms and pathological damage associated with DSS-treated colitis in mice with ulcerative colitis. Western blot analysis revealed that ISO upregulated P-gp in colon tissues (P < 0.05), suggesting the critical role of P-gp protein in intestinal epithelial cells. It was speculated that ISO may maintain intestinal homeostasis by upregulating functional P-gp expression in the intestinal epithelium. 16S microbial diversity sequencing revealed that ISO restored the richness and variety of intestinal microorganisms in colitis-bearing mice and enriched short-chain fatty acid-producing bacteria, such as Lachnospiraceae_NK4A136_group. The experiments also revealed that the ISO fecal microbial transplantation (FMT) inoculation of DSS-treated mice had similarly beneficial results. FMT mice showed a reduction in colitis symptoms, which was being more pronounced in ISO-FMT than in CON-FMT mice. Meanwhile, ISO-FMT expanded the abundance of beneficial microorganisms such as the Lachnospiraceae_NK4A136_group, increased the expression of metabolites, such as SCFAs and total serum bile acids (SBAs), and significantly upregulated the expression level of P-gp protein. In addition, Spearman’s correlation analysis of metabolites demonstrated a positive correlation between the production of SCFAs and SBAs and the expression of P-gp. Conclusion The present study identified that ISO affects the heightened expression of P-gp in the intestinal epithelium by regulating intestinal microorganisms and their metabolites, which maintains colonic homeostasis, improves the integrity of the colonic epithelium, and alleviates colitis.

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Section: Discussionmentioning

confidence: 67%

Isoorientin alleviates DSS-treated acute colitis in mice by regulating intestinal epithelial P-glycoprotein (P-gp) expression.

wang,

Yang,

Feng

et al. 2023

Preprint

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show abstract

“…For example, when compared with Cont group, the contents of oleic acid uridine in serum of rats were considerably upregulated (fold change, FC >3.0) while a-tocotrienol was significantly downregulated (FC <0.5) in HFF group. In fact, oleic acid can induce oxidative damage and steatosis in hepatocytes both in vitro and in vivo (34). Uridine is one metabolite positively associated with obesity, and is also a potential biomarker of insulin resistance (35,36).…”

Section: Mhp Efficacy Is Associated With Ppar Signaling Pathway As Re...mentioning

confidence: 99%

Mulberry and Hippophae-based solid beverage promotes weight loss in rats by antagonizing white adipose tissue PPARγ and FGFR1 signaling

Zhou,

Zhu,

et al. 2024

Front. Endocrinol.

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Obesity, a multifactorial disease with many complications, has become a global epidemic. Weight management, including dietary supplementation, has been confirmed to provide relevant health benefits. However, experimental evidence and mechanistic elucidation of dietary supplements in this regard are limited. Here, the weight loss efficacy of MHP, a commercial solid beverage consisting of mulberry leaf aqueous extract and Hippophae protein peptides, was evaluated in a high-fat high-fructose (HFF) diet-induced rat model of obesity. Body component analysis and histopathologic examination confirmed that MHP was effective to facilitate weight loss and adiposity decrease. Pathway enrichment analysis with differential metabolites generated by serum metabolomic profiling suggests that PPAR signal pathway was significantly altered when the rats were challenged by HFF diet but it was rectified after MHP intervention. RNA-Seq based transcriptome data also indicates that MHP intervention rectified the alterations of white adipose tissue mRNA expressions in HFF-induced obese rats. Integrated omics reveals that the efficacy of MHP against obesogenic adipogenesis was potentially associated with its regulation of PPARγ and FGFR1 signaling pathway. Collectively, our findings suggest that MHP could improve obesity, providing an insight into the use of MHP in body weight management.

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“…In the construction of cellular steatosis models, fatty acids are usually used as inducers. At present, oleic acid (OA) [ 3 , 4 ], palmitic acid (PA) [ 5 , 6 ], and OA/PA [ 7 , 8 ] are mainly used to induce hepatocyte steatosis. These models were also widely used to study the mechanism of cellular steatosis.…”

Section: Introductionmentioning

confidence: 99%

The Different Mechanisms of Lipid Accumulation in Hepatocytes Induced by Oleic Acid/Palmitic Acid and High-Fat Diet

Zhang,

Bai,

et al. 2023

Molecules

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Non-alcoholic fatty liver disease (NAFLD) is the primary chronic liver disease worldwide, mainly manifested by hepatic steatosis. Hepatic lipids may be derived from dietary intake, plasma free fatty acid (FFA) uptake, or hepatic de novo lipogenesis (DNL). Currently, cellular and animal models of hepatocellular steatosis are widely used to study the pathogenesis of NAFLD and to investigate therapeutic agents. However, whether there are differences between the in vivo and in vitro models of the mechanisms that cause lipid accumulation has not been reported. We used OA/PA-induced NCTC 1469 cells and high-fat-diet-fed C57BL/6J mice to simulate a hepatocyte steatosis model of NAFLD and to detect indicators related to FFA uptake and DNL. In addition, when serological indicators were analysed in the mouse model, it was found that serum FASN levels decreased. The results revealed that, in the cellular model, indicators related to DNL were decreased, FASN enzyme activity was unchanged, and indicators related to FFA uptake were increased, including the high expression of CD36; while, in the animal model, indicators related to both FFA uptake and de novo synthesis were increased, including the high expression of CD36 and the increased protein levels of FASN with enhanced enzyme activity. In addition, after an analysis of the serological indicators in the mouse model, it was found that the serum levels of FASN were reduced. In conclusion, the OA/PA-induced cellular model can be used to study the mechanism of FFA uptake, whereas the high-fat-diet-induced mouse model can be used to study the mechanism of FFA uptake and DNL. Combined treatment with CD36 and FASN may be more effective against NAFLD. FASN in the serum can be used as one of the indicators for the clinical diagnosis of NAFLD.

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Protective Effect of Isoorientin on Oleic Acid-Induced Oxidative Damage and Steatosis in Rat Liver Cells

Cited by 6 publications

References 40 publications

Isoorientin alleviates DSS-treated acute colitis in mice by regulating intestinal epithelial P-glycoprotein (P-gp) expression.

Isoorientin alleviates DSS-treated acute colitis in mice by regulating intestinal epithelial P-glycoprotein (P-gp) expression.

Mulberry and Hippophae-based solid beverage promotes weight loss in rats by antagonizing white adipose tissue PPARγ and FGFR1 signaling

The Different Mechanisms of Lipid Accumulation in Hepatocytes Induced by Oleic Acid/Palmitic Acid and High-Fat Diet

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