Berberine Protects Against Palmitate-Induced Apoptosis in Tubular Epithelial Cells by Promoting Fatty Acid Oxidation

Sun, Jiye; Liu, Ting; Jiang, Xu-shun; Wu, Yue; Yang, Shan; Hua, Wei; Li, Zhengdong; Huang, Huizhe; Ruan, Xiongzhong; Du, Xuqin

doi:10.12659/msm.908927

Cited by 26 publications

(14 citation statements)

References 36 publications

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“…In the present study, BBR supplementation in the HL diet up-regulated the hepatic expressions of lpl, cpt1a and hsl, indicating that BBR could improve lipolysis and fatty acid β-oxidation in liver. Consistent with the present study, enhanced fatty acid oxidation by BBR supplementation was also reported in blunt snout bream (15,49,55) , obese rats (42) and in vitro (16,56) .…”

Section: Discussionsupporting

confidence: 92%

Dietary berberine regulates lipid metabolism in muscle and liver of black sea bream (Acanthopagrus schlegelii) fed normal or high-lipid diets

Wang

Sagada

et al. 2020

Br J Nutr

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This study investigated the influence of berberine (BBR) supplementation in normal and high lipid diets on lipid metabolism and accumulation in black sea bream (Acanthopagrus schlegelii). Berberine was supplemented at 50 mg/kg to control (Con, 11.1% crude lipid) and high lipid (HL, 20.2% crude lipid) diets and named as ConB and HLB, respectively. After the 8-week feeding trial, fish body length and specific growth rate were significantly reduced by high lipid diets (P < 0.05). Muscle and whole-body crude lipid contents were significantly influenced by both BBR supplementation and dietary lipid level. Fish fed HLB diet had significantly lower serum triglyceride, low-density lipoprotein cholesterol contents, and alanine aminotransferase activity compared with the HL group. The HL group presented vast lipid accumulation in the liver, and hypertrophied hepatocytes along with large lipid droplets, and translocation of nuclear to the cell periphery. These abnormalities in black sea bream were alleviated in the HLB group. Berberine supplementation in high lipid diet significantly downregulated the hepatic expression levels of accα, srebp-1, 6pgd, g6pd and pparγ, whereas the lpl, hsl, and cpt1a expression levels were significantly upregulated. However, the expression levels of these genes showed opposite trends in muscle (except for pparγ). In conclusion, dietary BBR supplementation in high lipid diet reduced hepatic lipid accumulation by downregulating lipogenesis gene expression and upregulating lipolysis gene expression, and it increased muscle lipid contents with opposite trends of the mechanism observed in the liver.

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Section: Discussionsupporting

confidence: 92%

Dietary berberine regulates lipid metabolism in muscle and liver of black sea bream (Acanthopagrus schlegelii) fed normal or high-lipid diets

Wang

Sagada

et al. 2020

Br J Nutr

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“…Studies have been conducted to explore the role of FAO in apoptosis and its related mechanisms. It has been reported that berberine treatment reversed palmitate‐induced apoptosis in renal tubular epithelial cells by promoting FAO 38 . Yao et al found that LC supplementation in endothelial cells accelerated FAO and attenuated apoptosis caused by hyperoxia.…”

Section: Discussionmentioning

confidence: 99%

l‐Carnitine protects against 1,4‐benzoquinone‐induced apoptosis and DNA damage by suppressing oxidative stress and promoting fatty acid oxidation in K562 cells

Sun

Man

et al. 2020

Environmental Toxicology

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Widespread occupational and environmental exposure to benzene is unavoidable and poses a public health threat. Studies of potential interventions to prevent or relieve benzene toxicity are, thus, essential. Research has shown l‐carnitine (LC) has beneficial effects against various pathological processes and diseases. LC possesses antioxidant activities and participates in fatty acid oxidation (FAO). In this study, we investigated whether 1,4‐benzoquinone (1,4‐BQ) affects LC levels and the FAO pathway, as well as analyzed the influence of LC on the cytotoxic effects of 1,4‐BQ. We found that 1,4‐BQ significantly decreased LC levels and downregulated Cpt1a, Cpt2, Crat, Hadha, Acaa2, and Acadvl mRNA expression in K562 cells. Subsequent assays confirmed that 1,4‐BQ decreased cell viability and increased apoptosis and caspase‐3, ‐8, and ‐9 activities. It also induced obvious oxidative stress and DNA damage, including an increase in the levels of reactive oxygen species and malondialdehyde, tail DNA%, and olive tail moment. Additionally, the mitochondrial membrane potential was significantly reduced. Cotreatment with LC (500 μmol/L) relieved these alterations by reducing oxidative stress and increasing the protein expression levels of Cpt1a and Hadha, particularly in the 20 μmol/L 1,4‐BQ group. Thus, our results demonstrate that 1,4‐BQ causes cytotoxicity, reduces LC levels, and downregulates the FAO genes. In contrast, LC exhibits protective effects against 1,4‐BQ‐induced apoptosis and DNA damage by decreasing oxidative stress and promoting the FAO pathway.

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“…It has previously been shown that berberine exerts its neuroprotective effect by upregulating PPARα protein levels in cells [22]. Yu et al [23] reported that berberine is a potential activator of PPARα.…”

Section: Discussionmentioning

confidence: 99%

Berberine Induces <b><i>CYP2J2</i></b> Expression in Human U251 Glioma Cells via Regulation of Peroxisome Proliferator-Activated Receptor Alpha

Wang

et al. 2019

Pharmacology

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Background: Berberine is a promising natural drug that has a potential therapeutic effect on neurodegenerative diseases. Objectives: Using U251 cells in vitro, we investigated whether berberine exerts its neuroprotective effect via regulation of CYP2J2. Method: After pretreatment with increasing concentrations (1, 3, and 10 μmol/L) of berberine for 0.5 h, U251 cells were stimulated with 1 μg/mL of lipopolysaccharide (LPS). Cell viability was measured 24 h later using a CCK8 kit. mRNA and protein levels of CYP2J2 and peroxisome proliferator-activated receptor alpha (PPARα) were measured by quantitative real-time-polymerase chain reaction and western blotting, respectively, after 24 h of exposure to 1, 3, or 10 μmol/L berberine. Fluorescence immunocytochemistry was also used to evaluate PPARα protein expression after treatment of U251 cells with 10-μmol/L berberine for 24 h. Transient transfection (cotransfection with the plasmid of PPARα-and RXRα-containing) followed by luciferase and chromatin immunoprecipitation assays was used to elucidate the molecular mechanism underlying the observed effects. Results: Compared to the control, LPS-induced U251 cell death was attenuated by berberine in a dose-dependent manner. After 24 h, cell viability was found to be 52.3% (p < 0.05), 66.2% (p < 0.01), and 70.9% (p < 0.001) using 1, 3, and 10 μmol/L berberine treatment, respectively. At these concentrations, berberine increased the CYP2J2 mRNA levels by 1.31-fold (p < 0.05), 1.48-fold (p < 0.01), and 1.88-fold (p < 0.01), respectively, and increased the PPARα mRNA levels 1.17-fold (p < 0.05), 1.29-fold (p < 0.05), and 1.53-fold (p < 0.01), respectively, compared with the respective control groups. In addition, the CYP2J2 and PPARα protein level was also significantly upregulated in U251 cells by berberine (concentrations in 1, 3, and 10 μmol/L) in a dose-dependent manner, compared with the respective control groups. Further investigation indicated that berberine enhances the heterodimerization of PPARα and RXRα, which together bind to the CYP2J2 promoter to induce the expression of CYP2J2 in U251 cells. Conclusion: Upon exposure of U251 cells to berberine, CYP2J2 expression is induced as a result of PPARα stimulation, resulting in a neuroprotective effect.

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Berberine Protects Against Palmitate-Induced Apoptosis in Tubular Epithelial Cells by Promoting Fatty Acid Oxidation

Cited by 26 publications

References 36 publications

Dietary berberine regulates lipid metabolism in muscle and liver of black sea bream (Acanthopagrus schlegelii) fed normal or high-lipid diets

Dietary berberine regulates lipid metabolism in muscle and liver of black sea bream (Acanthopagrus schlegelii) fed normal or high-lipid diets

l‐Carnitine protects against 1,4‐benzoquinone‐induced apoptosis and DNA damage by suppressing oxidative stress and promoting fatty acid oxidation in K562 cells

Berberine Induces <b><i>CYP2J2</i></b> Expression in Human U251 Glioma Cells via Regulation of Peroxisome Proliferator-Activated Receptor Alpha

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