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A newly designed curcumin analog Y20 mitigates cardiac injury via anti-inflammatory and anti-oxidant actions in obese rats.

Qian Y, Zhong P, Liang D, Xu Z, Skibba M, Zeng C, Li X, Wei T, Wu L, Liang G - PLoS ONE (2015)

Bottom Line: In high fat diet-fed rats, oral administration of Y20 at 20 mg/kg or curcumin at 50 mg/kg significantly decreased the cardiac inflammation and oxidative stress and eventually improved the cardiac remodeling by mitigating cardiac disorganization, hypertrophy, fibrosis and apoptosis.Y20 at 20 mg/kg showed comparable and even stronger bioactivities than curcumin at 50 mg/kg.The beneficial actions of Y20 are closely associated with its ability to increase Nrf2 expression and inhibit NF-κB activation.

View Article: PubMed Central - PubMed

Affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.

ABSTRACT
Obesity is strongly associated with the cause of structural and functional changes of the heart in both human and animal models. Oxidative stress and inflammation play a critical role in the development of obesity-induced cardiac disorders. Curcumin is a natural product from Curcuma Longa with multiple bioactivities. In our previous study, in order to reach better anti-inflammatory and anti-oxidant dual activities, we designed a new mono-carbonyl curcumin analog, Y20, via the structural modification with both trifluoromethyl and bromine. This study was designed to investigate the protective effects of Y20 on obesity-induced cardiac injury and its underlying mechanisms. In high fat diet-fed rats, oral administration of Y20 at 20 mg/kg or curcumin at 50 mg/kg significantly decreased the cardiac inflammation and oxidative stress and eventually improved the cardiac remodeling by mitigating cardiac disorganization, hypertrophy, fibrosis and apoptosis. Y20 at 20 mg/kg showed comparable and even stronger bioactivities than curcumin at 50 mg/kg. The beneficial actions of Y20 are closely associated with its ability to increase Nrf2 expression and inhibit NF-κB activation. Taken together, these results suggest that Y20 may have a great therapeutic potential in the treatment of obesity-induced cardiac injury using Nrf2 and NF-κB as the therapeutic targets for treating obesity-related disorders.

No MeSH data available.


Related in: MedlinePlus

Y20 attenuates cardiac inflammation in the hearts of HFD-fed rats.(A) Representative images for immunohistochemical staining and immunofluorescent staining of TNF-α accumulation using the formalin-fixed myocardial tissues as described in Methods (400×magnification). The statistic data of the relative intensity was determined by imageJ software (NIH, Bethesda, MD), and data are presented as mean±SDs, n = 4; (B) Representative images for immunohistochemical staining of CD68 expression using the formalin-fixed myocardial tissues as described in Methods (400×magnification). The statistic data of the relative intensity was determined by imageJ software (NIH, Bethesda, MD), and data are presented as mean±SDs, n = 4; (C) Western blot analysis for the protein expression of IκB-α and VCAM-1 in the myocardial tissues was performed. (D-I) The mRNA expression of TNF-α, IL-6, IL-1β, VCAM-1, ICAM-1 and COX-2 in myocardial tissues was detected by real-time qPCR. Four rats in each group were used for above analysis. * P<0.05, ** P<0.01 v.s. HFD group; # P<0.05 v.s. vehicle control (Ctrl).
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pone.0120215.g003: Y20 attenuates cardiac inflammation in the hearts of HFD-fed rats.(A) Representative images for immunohistochemical staining and immunofluorescent staining of TNF-α accumulation using the formalin-fixed myocardial tissues as described in Methods (400×magnification). The statistic data of the relative intensity was determined by imageJ software (NIH, Bethesda, MD), and data are presented as mean±SDs, n = 4; (B) Representative images for immunohistochemical staining of CD68 expression using the formalin-fixed myocardial tissues as described in Methods (400×magnification). The statistic data of the relative intensity was determined by imageJ software (NIH, Bethesda, MD), and data are presented as mean±SDs, n = 4; (C) Western blot analysis for the protein expression of IκB-α and VCAM-1 in the myocardial tissues was performed. (D-I) The mRNA expression of TNF-α, IL-6, IL-1β, VCAM-1, ICAM-1 and COX-2 in myocardial tissues was detected by real-time qPCR. Four rats in each group were used for above analysis. * P<0.05, ** P<0.01 v.s. HFD group; # P<0.05 v.s. vehicle control (Ctrl).

Mentions: We then detected the inflammatory markers in cardiac tissues. TNF-α immunohistochemistry (IHC) staining and immunofluorescent (IF) staining showed that there was a significant increase in TNF-α protein accumulation (TNF-α were stained in brown for IHC, and in green for IF) in the hearts of HFD-fed rats (Fig. 3A). There was also an increased expression of CD68, a specific marker for macrophages, in the hearts of the HFD group, suggesting inflammatory cell infiltration in the obese hearts (CD68 positive cells were stained in brown, Fig. 3B). VCAM-1, a critical cell adhesion molecule for inflammatory cell infiltration, was then found to be increased in the hearts of the HFD group as evidenced by western blot analysis (Fig. 3C). In addition, IκB degradation was observed in the hearts of the HFD-fed rats, indicating nuclear factor κB (NF-κB), a transcript factor controlling the expression of a variety of pro-inflammatory cytokines, was activated via hyperlipidemia (Fig. 3C). We then determined the mRNA expression of several inflammatory genes by real-time qPCR. The results in Fig. 3D-3I showed that the expression of pro-inflammatory cytokines such as TNF-α, IL-6, IL-1β and COX-2 and cell adhesion molecules such as VCAM-1 and ICAM-1 were all up-regulated in myocardial tissues of obese rats. However, all of the above increases in cardiac inflammation were significantly attenuated by 4-week treatment with either curcumin or Y20; and generally, Y20 at 20 mg/kg exhibited a slightly stronger anti-inflammatory activity than curcumin at 50 mg/kg (Fig. 3A-3I).


A newly designed curcumin analog Y20 mitigates cardiac injury via anti-inflammatory and anti-oxidant actions in obese rats.

Qian Y, Zhong P, Liang D, Xu Z, Skibba M, Zeng C, Li X, Wei T, Wu L, Liang G - PLoS ONE (2015)

Y20 attenuates cardiac inflammation in the hearts of HFD-fed rats.(A) Representative images for immunohistochemical staining and immunofluorescent staining of TNF-α accumulation using the formalin-fixed myocardial tissues as described in Methods (400×magnification). The statistic data of the relative intensity was determined by imageJ software (NIH, Bethesda, MD), and data are presented as mean±SDs, n = 4; (B) Representative images for immunohistochemical staining of CD68 expression using the formalin-fixed myocardial tissues as described in Methods (400×magnification). The statistic data of the relative intensity was determined by imageJ software (NIH, Bethesda, MD), and data are presented as mean±SDs, n = 4; (C) Western blot analysis for the protein expression of IκB-α and VCAM-1 in the myocardial tissues was performed. (D-I) The mRNA expression of TNF-α, IL-6, IL-1β, VCAM-1, ICAM-1 and COX-2 in myocardial tissues was detected by real-time qPCR. Four rats in each group were used for above analysis. * P<0.05, ** P<0.01 v.s. HFD group; # P<0.05 v.s. vehicle control (Ctrl).
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Related In: Results  -  Collection

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pone.0120215.g003: Y20 attenuates cardiac inflammation in the hearts of HFD-fed rats.(A) Representative images for immunohistochemical staining and immunofluorescent staining of TNF-α accumulation using the formalin-fixed myocardial tissues as described in Methods (400×magnification). The statistic data of the relative intensity was determined by imageJ software (NIH, Bethesda, MD), and data are presented as mean±SDs, n = 4; (B) Representative images for immunohistochemical staining of CD68 expression using the formalin-fixed myocardial tissues as described in Methods (400×magnification). The statistic data of the relative intensity was determined by imageJ software (NIH, Bethesda, MD), and data are presented as mean±SDs, n = 4; (C) Western blot analysis for the protein expression of IκB-α and VCAM-1 in the myocardial tissues was performed. (D-I) The mRNA expression of TNF-α, IL-6, IL-1β, VCAM-1, ICAM-1 and COX-2 in myocardial tissues was detected by real-time qPCR. Four rats in each group were used for above analysis. * P<0.05, ** P<0.01 v.s. HFD group; # P<0.05 v.s. vehicle control (Ctrl).
Mentions: We then detected the inflammatory markers in cardiac tissues. TNF-α immunohistochemistry (IHC) staining and immunofluorescent (IF) staining showed that there was a significant increase in TNF-α protein accumulation (TNF-α were stained in brown for IHC, and in green for IF) in the hearts of HFD-fed rats (Fig. 3A). There was also an increased expression of CD68, a specific marker for macrophages, in the hearts of the HFD group, suggesting inflammatory cell infiltration in the obese hearts (CD68 positive cells were stained in brown, Fig. 3B). VCAM-1, a critical cell adhesion molecule for inflammatory cell infiltration, was then found to be increased in the hearts of the HFD group as evidenced by western blot analysis (Fig. 3C). In addition, IκB degradation was observed in the hearts of the HFD-fed rats, indicating nuclear factor κB (NF-κB), a transcript factor controlling the expression of a variety of pro-inflammatory cytokines, was activated via hyperlipidemia (Fig. 3C). We then determined the mRNA expression of several inflammatory genes by real-time qPCR. The results in Fig. 3D-3I showed that the expression of pro-inflammatory cytokines such as TNF-α, IL-6, IL-1β and COX-2 and cell adhesion molecules such as VCAM-1 and ICAM-1 were all up-regulated in myocardial tissues of obese rats. However, all of the above increases in cardiac inflammation were significantly attenuated by 4-week treatment with either curcumin or Y20; and generally, Y20 at 20 mg/kg exhibited a slightly stronger anti-inflammatory activity than curcumin at 50 mg/kg (Fig. 3A-3I).

Bottom Line: In high fat diet-fed rats, oral administration of Y20 at 20 mg/kg or curcumin at 50 mg/kg significantly decreased the cardiac inflammation and oxidative stress and eventually improved the cardiac remodeling by mitigating cardiac disorganization, hypertrophy, fibrosis and apoptosis.Y20 at 20 mg/kg showed comparable and even stronger bioactivities than curcumin at 50 mg/kg.The beneficial actions of Y20 are closely associated with its ability to increase Nrf2 expression and inhibit NF-κB activation.

View Article: PubMed Central - PubMed

Affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.

ABSTRACT
Obesity is strongly associated with the cause of structural and functional changes of the heart in both human and animal models. Oxidative stress and inflammation play a critical role in the development of obesity-induced cardiac disorders. Curcumin is a natural product from Curcuma Longa with multiple bioactivities. In our previous study, in order to reach better anti-inflammatory and anti-oxidant dual activities, we designed a new mono-carbonyl curcumin analog, Y20, via the structural modification with both trifluoromethyl and bromine. This study was designed to investigate the protective effects of Y20 on obesity-induced cardiac injury and its underlying mechanisms. In high fat diet-fed rats, oral administration of Y20 at 20 mg/kg or curcumin at 50 mg/kg significantly decreased the cardiac inflammation and oxidative stress and eventually improved the cardiac remodeling by mitigating cardiac disorganization, hypertrophy, fibrosis and apoptosis. Y20 at 20 mg/kg showed comparable and even stronger bioactivities than curcumin at 50 mg/kg. The beneficial actions of Y20 are closely associated with its ability to increase Nrf2 expression and inhibit NF-κB activation. Taken together, these results suggest that Y20 may have a great therapeutic potential in the treatment of obesity-induced cardiac injury using Nrf2 and NF-κB as the therapeutic targets for treating obesity-related disorders.

No MeSH data available.


Related in: MedlinePlus