Dysregulated lipid metabolism in liver is an important hallmark of non-alcoholic fatty liver disease (NAFLD), which may be modulated by dietary polyphenols or microRNAs (miRNAs). However, the underlying epigenetic regulatory mechanism of polyphenols remain unclear. The current study aimed to address how miRNA mediates hepatic lipid metabolic control of curcumin, a polyphenolic food supplement. The results showed that 24 h treatment with 5-20 mu M curcumin prevented free fatty acid -induced lipid accumulation by around 10-50% in HepG2 cells, which was attenuated by pre-transfection with 40 nM miR-22-3p mimic for 48 h. In consequence, transfection with 40 nM miR-22-3p inhibitor for 48 h significantly reduced lipid accumulation by around 10%. And, 48 h overexpression of miR-22-3p targeting cardiolipin synthase 1 (CRLS1) gene, which encodes a mitochondrial phospholipid synthase, showed a similar regulatory effect. Thus, miR-22-3p and CRLS1 showed opposite effects in modulating lipid metabolism, which probably involved mitochondrial control. In summary, this study demonstrated that curcumin improved hepatic lipid metabolism via targeting the miR-22-3p/CRLS1 pathway. Identification of the epigenetic regulatory mechanism underlying lipid metabolism may thereby facilitate alleviation of metabolic disorders by natural polyphenols.

Objective: Oxidative stress represents a characteristic of neurodegenerative diseases, which may be alleviated by the functional food component-curcumin. However, the underlying mechanism remains unclear. The current study aimed to address how curcumin protects variant differentiated pheochromocytoma (PC12) cells against hydrogen peroxide (H2O2)-induced cell stress, using low- and high-differentiated PC12 cells, and validated in old-aged mice. Methods: The MTT assay was first carried out to test the cell viability upon H2O2 and/or curcumin treatment and cellular lipid peroxidation was assessed as cellular damages by quantifying the amount of cellular malondialdehyde. Cellular oxidative stress was determined by measuring the cellular and mitochondrial ROS levels, and total cellular antioxidant capacities were determined as the ABTS free radical scavenging ability (ABTS) and Fe3+ reduction ability of cells. The activities and expression of major antioxidant enzymes, including glutathione peroxidase (GPx), superoxidase dismutase (SOD) and catalase (CAT), were also tested. Furthermore, oxidative phosphorylation of mitochondria was assessed by measuring the ATP level and the ADP/ATP ratio. Finally, the antioxidant activity of curcumin was determined in 6-month-old mice by measuring cellular antioxidant capacity and antioxidant enzyme activities. Results: H2O2 caused oxidative damage and decreased cell viability, which was reversed by curcumin with different dosed effects in variant differentiated PC12 cells. Moreover, curcumin's protective effect was attributed to an enhanced antioxidant enzyme system. In consistent, curcumin recovered H2O2-deteriorated oxidative phosphorylation. Further studies verified that curcumin significantly improved the antioxidant capacity of old-aged mice, which may have elevated oxidative stress. Conclusion: Taken together, curcumin improved the antioxidant capacity of variant differentiated PC12 cells and old-aged mice, which was closely associated with the modulation of mitochondrial function and antioxidant enzyme system. This study may shed light on the molecular mechanism underlying the alleviation of neurodegenerative diseases by natural polyphenols.

The antioxidant activity of curcumin has been extensively investigated for years. However, its molecular function mechanism remained unclear. Our preliminary study showed that curcumin downregulated miR-22-3p expression. This study aimed to address whether miR-22-3p mediated the antioxidant activity of curcumin and the possible action mechanism. The results showed that miR-22-3p repression increased the total cellular antioxidant capacity and enhanced the endogenous antioxidant enzyme system of LO2 cells. In addition, miR-22-3pdeteriorated cellular antioxidant capacity was prevented by curcumin pretreatment. Moreover, miR-22-3p inhibition significantly improved mitochondrial function and biogenesis. Further investigation demonstrated that a mitochondrial key regulator, the cardiolipin synthase gene (CRLS1), was targeted and downregulated by miR-223p. CRLS1 overexpression also significantly improved cellular antioxidant capacity and enhanced mitochondrial function and biogenesis in LO2 cells. Taken together, all these data suggested that miR-22-3p modulated the antioxidant effect of curcumin via targeting CRLS1, which may provide novel insights into miRNA-mediated antioxidant mechanism of curcumin.

As a natural polyphenolic food supplement and the principal curcuminoid in turmeric, curcumin shows antioxidant, anti-inflammatory, and antitumor activities. However, its specific functional mechanism remains unclear. Our preliminary study indicated that miR-125b-5p was downregulated by a curcumin extract. This study aimed to determine whether miR-125b-5p is involved in the antioxidant regulation of curcumin. The results showed that miR-125b-5p overexpression had a pro-oxidant effect by reducing the cellular antioxidant capacity, as well as decreasing the activities of catalase (CAT) and superoxide dismutase (SOD) in the normal liver cell line LO2. However, miR-125b-5p repression significantly increased the cellular antioxidant capacity and enhanced the activities of CAT and SOD. Further investigation demonstrated that the cellular antioxidant capacity induced by curcumin extract was inhibited by miR-125b-5p overexpression. Thus, curcumin may exhibit antioxidant effects by repressing miR-125b-5p expression, which provides new insights into the molecular antioxidant mechanism of curcumin and other functional food components.

Docosahexaenoic acid (DHA) is an essential omega-3 polyunsaturated fatty acid (PUFA) for human body, which is highly rich in deep sea fish oil and marine microalgae. Mitochondria are the energy factory of cells. Mitochondrial functions and biogenesis can be regulated by DHA which exhibits antioxidation, anti-inflammatory and anti-cancer activities. This article review the research progress of mitochondrial-mediated DHA antioxidation and the possible underlying mechanism. The effects of DHA in eliminating reactive oxygen species (reactive oxygen species, ROS) and regulating mitochondrial biogenesis and functions, as well as the microRNA-mediated DHA antioxidant epigenetic mechanism were addressed, which may provide evidence for better DHA product exploration and application.