Limits...
Inhibition of TGF-β by a novel PPAR-γ agonist, chrysin, salvages β-receptor stimulated myocardial injury in rats through MAPKs-dependent mechanism.

Rani N, Bharti S, Bhatia J, Tomar A, Nag TC, Ray R, Arya DS - Nutr Metab (Lond) (2015)

Bottom Line: This beneficial effect of chrysin was well supported with increased expression of PPAR-γ and decreased expression of TGF-β as evidenced by western blotting and immunohistochemistry analysis.Additionally, chrysin in a dose dependent fashion improved NO level, redox status of the myocardium (GSH and MDA levels and SOD, GSHPx and CAT activities), cardiac injury markers (CK-MB and LDH levels) and oxidative DNA damage marker (8-OHdG level) and displayed preservation of subcellular and ultrastructural components.We established that activation of PPAR-γ and inhibition of TGF-β via MAPKs dependent mechanism is critical for cardioprotective effect of chrysin.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, 110029 India.

ABSTRACT

Background: Pharmacological stimulation of peroxisome proliferator-activated receptor-gamma (PPAR-γ) has been recognized as a molecular switch in alleviating myocardial injury through modulating oxidative, inflammatory and apoptotic signaling pathways. This study was designed to elucidate the effect of chrysin, a novel PPAR-γ agonist and its functional interaction with TGF-β/MAPKs in isoproterenol-challenged myocardial injury in rats.

Methods: Male Wistar Albino rats were either subjected to vehicle (1.5 mL/kg, p.o.) or chrysin (15-60 mg/kg, p.o.) for 28 days. Isoproterenol (85 mg/kg, s.c.) was administered to rats on 27(th) and 28(th) day to induce myocardial injury.

Results: Chrysin dose dependently improved ventricular (±LVdP/dtmax and LVEDP) and hemodynamic (SAP, MAP and DAP) dysfunction in isoproterenol-insulted rats. This beneficial effect of chrysin was well supported with increased expression of PPAR-γ and decreased expression of TGF-β as evidenced by western blotting and immunohistochemistry analysis. Moreover, downstream signaling pathway of TGF-β viz. P-ERK½/ERK½ activation and P-JNK/JNK, P-p38/p38 and MMP-2 inhibition were also observed. Chrysin also attenuated NF-κBp65 and IKK-β expressions, TNF-α level and TUNEL positivity thereby validating its anti-inflammatory and anti-apoptotic properties. Additionally, chrysin in a dose dependent fashion improved NO level, redox status of the myocardium (GSH and MDA levels and SOD, GSHPx and CAT activities), cardiac injury markers (CK-MB and LDH levels) and oxidative DNA damage marker (8-OHdG level) and displayed preservation of subcellular and ultrastructural components.

Conclusion: We established that activation of PPAR-γ and inhibition of TGF-β via MAPKs dependent mechanism is critical for cardioprotective effect of chrysin.

No MeSH data available.


Related in: MedlinePlus

Effect of chrysin on a1-f1:Light microscopic changes(10X,Scale bar 100 μm),a2-f2:Electron microscopic changes(4000X,Scale bar 1 μm,N:nucleus;MC:mitochondria;F:myofibrils),a3-f3:PPAR-γ immunohistochemistry(10X,Scale bar 50 μm),a4-f4:TUNEL positivity(20X,Scale bar 100 μm)and a5-f5:TGF-β immunohistochemistry(10X,Scale bar 50 μm)in different experimental groups. Sham group (a1-a5); ISO (b1-b5); Chr15, 30, 60 + ISO mg/kg respectively (c1-c5, d1-d5 and e1-e5); and Chr60ps (f1-f5).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4359541&req=5

Fig5: Effect of chrysin on a1-f1:Light microscopic changes(10X,Scale bar 100 μm),a2-f2:Electron microscopic changes(4000X,Scale bar 1 μm,N:nucleus;MC:mitochondria;F:myofibrils),a3-f3:PPAR-γ immunohistochemistry(10X,Scale bar 50 μm),a4-f4:TUNEL positivity(20X,Scale bar 100 μm)and a5-f5:TGF-β immunohistochemistry(10X,Scale bar 50 μm)in different experimental groups. Sham group (a1-a5); ISO (b1-b5); Chr15, 30, 60 + ISO mg/kg respectively (c1-c5, d1-d5 and e1-e5); and Chr60ps (f1-f5).

Mentions: To further strengthen our western blotting findings, we performed immunohistochemistry analysis to check the distribution and localization of PPAR-γ and TGF-β within the myocardial cells. In consonance with western blotting results, we also found that chrysin significantly augmented PPAR-γ expression and mitigated TGF-β expression in recovered myocardium as compared to the failing myocardium (Figures 5a3-f3 and a5-f5).Figure 5


Inhibition of TGF-β by a novel PPAR-γ agonist, chrysin, salvages β-receptor stimulated myocardial injury in rats through MAPKs-dependent mechanism.

Rani N, Bharti S, Bhatia J, Tomar A, Nag TC, Ray R, Arya DS - Nutr Metab (Lond) (2015)

Effect of chrysin on a1-f1:Light microscopic changes(10X,Scale bar 100 μm),a2-f2:Electron microscopic changes(4000X,Scale bar 1 μm,N:nucleus;MC:mitochondria;F:myofibrils),a3-f3:PPAR-γ immunohistochemistry(10X,Scale bar 50 μm),a4-f4:TUNEL positivity(20X,Scale bar 100 μm)and a5-f5:TGF-β immunohistochemistry(10X,Scale bar 50 μm)in different experimental groups. Sham group (a1-a5); ISO (b1-b5); Chr15, 30, 60 + ISO mg/kg respectively (c1-c5, d1-d5 and e1-e5); and Chr60ps (f1-f5).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4359541&req=5

Fig5: Effect of chrysin on a1-f1:Light microscopic changes(10X,Scale bar 100 μm),a2-f2:Electron microscopic changes(4000X,Scale bar 1 μm,N:nucleus;MC:mitochondria;F:myofibrils),a3-f3:PPAR-γ immunohistochemistry(10X,Scale bar 50 μm),a4-f4:TUNEL positivity(20X,Scale bar 100 μm)and a5-f5:TGF-β immunohistochemistry(10X,Scale bar 50 μm)in different experimental groups. Sham group (a1-a5); ISO (b1-b5); Chr15, 30, 60 + ISO mg/kg respectively (c1-c5, d1-d5 and e1-e5); and Chr60ps (f1-f5).
Mentions: To further strengthen our western blotting findings, we performed immunohistochemistry analysis to check the distribution and localization of PPAR-γ and TGF-β within the myocardial cells. In consonance with western blotting results, we also found that chrysin significantly augmented PPAR-γ expression and mitigated TGF-β expression in recovered myocardium as compared to the failing myocardium (Figures 5a3-f3 and a5-f5).Figure 5

Bottom Line: This beneficial effect of chrysin was well supported with increased expression of PPAR-γ and decreased expression of TGF-β as evidenced by western blotting and immunohistochemistry analysis.Additionally, chrysin in a dose dependent fashion improved NO level, redox status of the myocardium (GSH and MDA levels and SOD, GSHPx and CAT activities), cardiac injury markers (CK-MB and LDH levels) and oxidative DNA damage marker (8-OHdG level) and displayed preservation of subcellular and ultrastructural components.We established that activation of PPAR-γ and inhibition of TGF-β via MAPKs dependent mechanism is critical for cardioprotective effect of chrysin.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, 110029 India.

ABSTRACT

Background: Pharmacological stimulation of peroxisome proliferator-activated receptor-gamma (PPAR-γ) has been recognized as a molecular switch in alleviating myocardial injury through modulating oxidative, inflammatory and apoptotic signaling pathways. This study was designed to elucidate the effect of chrysin, a novel PPAR-γ agonist and its functional interaction with TGF-β/MAPKs in isoproterenol-challenged myocardial injury in rats.

Methods: Male Wistar Albino rats were either subjected to vehicle (1.5 mL/kg, p.o.) or chrysin (15-60 mg/kg, p.o.) for 28 days. Isoproterenol (85 mg/kg, s.c.) was administered to rats on 27(th) and 28(th) day to induce myocardial injury.

Results: Chrysin dose dependently improved ventricular (±LVdP/dtmax and LVEDP) and hemodynamic (SAP, MAP and DAP) dysfunction in isoproterenol-insulted rats. This beneficial effect of chrysin was well supported with increased expression of PPAR-γ and decreased expression of TGF-β as evidenced by western blotting and immunohistochemistry analysis. Moreover, downstream signaling pathway of TGF-β viz. P-ERK½/ERK½ activation and P-JNK/JNK, P-p38/p38 and MMP-2 inhibition were also observed. Chrysin also attenuated NF-κBp65 and IKK-β expressions, TNF-α level and TUNEL positivity thereby validating its anti-inflammatory and anti-apoptotic properties. Additionally, chrysin in a dose dependent fashion improved NO level, redox status of the myocardium (GSH and MDA levels and SOD, GSHPx and CAT activities), cardiac injury markers (CK-MB and LDH levels) and oxidative DNA damage marker (8-OHdG level) and displayed preservation of subcellular and ultrastructural components.

Conclusion: We established that activation of PPAR-γ and inhibition of TGF-β via MAPKs dependent mechanism is critical for cardioprotective effect of chrysin.

No MeSH data available.


Related in: MedlinePlus