Sesame lignans upregulate glutathione S-transferase expression and downregulate microRNA-669c-3p

Abstract

Oxidative stress is associated with aging and pathologies such as cardiovascular diseases, Alzheimer's disease, and cancer. Glutathione S-transferase (GST), a family of detoxification enzymes, plays a crucial role in countering oxidative stress. Therefore, there is a need for the development of physiologically functional foods and agricultural products, which enhance GST activity. Sesamin and episesamin are major lignans in refined sesame oil that exhibit beneficial properties including antioxidative stress effects. A previous study showed that sesamin upregulated GST activity. This study aimed to elucidate the mechanism underlying the GST activity enhancement elicited by sesame lignans. C57BL/6J mice were orally administered 20 mg/kg body weight sesame lignans (sesamin:episesamin = 1:1) for 7 days. Oral administration of sesame lignans increased the GST activity in the mouse liver. Furthermore, the lignans upregulated GSTA1, GSTA4, and GSTM4 protein expression. Microarray analysis revealed that sesame lignans changed the expression of various microRNAs (miRNAs) (84 upregulated, 19 downregulated). We also found 16 miRNAs, including miR-669c-3p, that may negatively regulate GST expression among the 19 miRNAs with reduced expression caused by the sesame lignans. miR-669c is reportedly negatively correlated with GST. Additionally, we transfected NMuLi cells with an miR-669c-3p mimic and evaluated the effect of miR-669c-3p on GST mRNA and protein expressions. The results showed that the miR-669c-3p mimic suppressed the mRNA and protein levels of GSTA4 and GSTM4. In conclusion, sesame lignans increased GST protein expression and activity and downregulated miRNAs, including miR-669c-3p, which is a possible suppressor of GST.

Phytochemical Profiling and Anti-Fibrotic Activities of the Gemmotherapy Bud Extract of Corylus avellana in a Model of Liver Fibrosis on Diabetic Mice

“…Previous studies regarding Corylus avellana kernels revealed the presence of phenolic acids, flavonoids such as myricetin, catechins, quercetin, proantocyanidines and lignans, as well as diarylheptanoids such as curcumin [ 7 ]. But in DCA individuals, the GSH concentration decreased significantly versus the DF and DFR ones, probably due to catechins that increased the activities of glutathione peroxidases [ 22 ] and lignans that up-regulated glutathione-S-transferase [ 23 ] both enzymes having as a co-substrate GSH and being involved in the neutralization/excretion of lipid peroxides. On the other hand, it is probable that the antioxidant compounds of Corylus avellana could diminish the production of the end-products of lipid peroxidation and AOPPs by direct interaction with them and by reactive oxygen species.…”

(−)‑Epigallocatechin‑3‑O‑gallate upregulates the expression levels of miR‑6757‑3p, a suppressor of fibrosis‑related gene expression, in extracellular vesicles derived from human umbilical vein endothelial cells

“…The final concentration of the control or miR-6757-3p mimics was 20 nM. The concentration was determined according to a previous study (30). Subsequently, 5 h after transfection, HFL-1 cells were treated with 10% FBS/DMEM with or without TGF-β (the concentration of TGF-β was 5 ng/ml) for 48 h. Finally, HFL-1 cells were lysed using the TRI reagent ® (Sigma-Aldrich; Merck KGaA).…”