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. 2017:2017:7038789.
doi: 10.1155/2017/7038789. Epub 2017 May 31.

Actinidia chinensis Planch. Improves the Indices of Antioxidant and Anti-Inflammation Status of Type 2 Diabetes Mellitus by Activating Keap1 and Nrf2 via the Upregulation of MicroRNA-424

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Actinidia chinensis Planch. Improves the Indices of Antioxidant and Anti-Inflammation Status of Type 2 Diabetes Mellitus by Activating Keap1 and Nrf2 via the Upregulation of MicroRNA-424

Longfeng Sun et al. Oxid Med Cell Longev. 2017.

Abstract

The fruit juice of Actinidia chinensis Planch. has antioxidant and anti-inflammation properties on patients with type 2 diabetes mellitus (T2DM), but the molecular mechanism was unclear. The patients took the juice and the serum level of antioxidant miR-424, Kelch-like ECH-associated protein 1 (Keap1), erythroid-derived 2-like 2 (Nrf2), and biochemical indices were measured. The juice increased the levels of serum microRNA-424, Keap1, and Nrf2 and reduced the levels of interleukin-1 (IL-1) beta and IL-6 in T2DM patients. The levels of SOD and GSH were higher while the levels of ALT and AST were lower in the patients consuming the juice when compared to the patients without taking the juice. The Spearman rank correlation analysis showed that the serum levels of miR-424 were positively related to Keap1 and Nrf2 levels while Keap1 and Nrf2 levels were positively related to the levels of SOD and GSH and negatively related to IL-1 beta and IL-6. Thus, FJACP improves the indices of antioxidant and anti-inflammation status by activating Keap1 and Nrf2 via the upregulation of miR-424 in the patients with T2DM. This trial is registered with ChiCTR-ONC-17011087 on 04/07/2017.

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Figures

Figure 1
Figure 1
The flowchart of the present study. FJACPG: FJACP group; CG: placebo group. The whole period of the follow-up was nine months.
Figure 2
Figure 2
Measurement of the concentrations of IL-1 beta and IL-6 by ELISA in blood samples. (a) The concentration of IL-1 beta. (b) The concentration of IL-6. FJACPG: FJACP group; CG: placebo group. All data were presented as mean values ± SD.
Figure 3
Figure 3
qRT-PCR analysis of relative mRNA levels. (a) Relative mRNA levels of serum miR-424. (b) Relative mRNA levels of Keap1. (c) Relative mRNA levels of Nrf2. FJACPG: FJACP group; CG: placebo group. All data were presented as mean values ± SD.
Figure 4
Figure 4
Western blot analysis of relative protein levels of Keap1 and Nrf2. (a) Relative protein levels of Keap1. (b) Relative protein levels of Nrf2. FJACPG: FJACP group; CG: placebo group. All data were presented as mean values ± SD.
Figure 5
Figure 5
The relationship between the level of miR-424 and the levels of proinflammatory cytokines. (a) The relationship between the level of miR-424 and the level of IL-1 beta. (b) The relationship between the level of miR-424 and the level of IL-6. Spearman's rank correlation test was performed to compare two variables. There is a strong negative association if the value of rho falls between −1 and −0.5.
Figure 6
Figure 6
The relationship between the level of miR-424 and the levels of biomarkers of antioxidant factors. (a) The relationship between the level of miR-424 and the level of SOD. (b) The relationship between the level of miR-424 and the level of GSH. (c) The relationship between the level of miR-424 and the level of ALT. (d) The relationship between the level of miR-424 and the level of AST. Spearman's rank correlation test was performed to compare two variables. There is a strong negative association if the value of rho falls between −1 and −0.5. There is a strong positive association if the value of rho falls between 0.5 and 1.
Figure 7
Figure 7
The relationship between the level of Nrf2 and the levels of proinflammatory cytokines. (a) The relationship between the level of Nrf2 and the level of IL-1 beta. (b) The relationship between the level of Nrf2 and the level of IL-6. Spearman's rank correlation test was performed to compare two variables. There is a strong negative association if the value of rho falls between −1 and −0.5.
Figure 8
Figure 8
The relationship between the level of Nrf2 and the levels of biomarkers of antioxidant factors. (a) The relationship between the level of Nrf2 and the level of SOD. (b) The relationship between the level of Nrf2 and the level of GSH. (c) The relationship between the level of Nrf2 and the level of ALT. (d) The relationship between the level of Nrf2 and the level of AST. Spearman's rank correlation test was performed to compare two variables. There is a strong negative association if the value of rho falls between −1 and −0.5. There is a strong positive association if the value of rho falls between 0.5 and 1.
Figure 9
Figure 9
The relationship between the level of miR-424 and the levels of Keap1 or Nrf2. (a) The relationship between the level of miR-424 and the level of Keap1. (b) The relationship between the level of miR-424 and the level of Nrf2. Spearman's rank correlation test was performed to compare two variables. There is a strong negative association if the value of rho falls between −1 and −0.5. There is a strong positive association if the value of rho falls between 0.5 and 1.
Figure 10
Figure 10
The multiple functions of FJACP on T2DM patients.

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