| Abstract |
This study investigated the efects of nobiletin on cardiorenal changes and the underlying mechanisms
involved in two-kidney, one-clip (2K-1C) hypertension. 2K-1C rats were treated with nobiletin (15 or
30 mg/kg/day) or losartan (10 mg/kg/day) for 4 weeks (n= 8/group). Nobiletin (30 mg/kg) reduced high
levels of blood pressure and circulating angiotensin II and angiotensin-converting enzyme activity
in 2K-1C rats. Left ventricular (LV) dysfunction and remodelling in 2K-1C rats were alleviated in the
nobiletin-treated group (P< 0.05). Nobiletin reduced the upregulation of Ang II type I receptor (AT1R)/
JAK (Janus kinase)/STAT (signal transducer and activator of transcription) protein expression in cardiac
tissue of 2K-1C rats (P< 0.05). The reduction in kidney function, and accumulation of renal fbrosis in
2K-1C rats were alleviated by nobiletin (P< 0.05). Overexpression of AT1R and NADPH oxidase 4 (Nox4)
protein in nonclipped kidney tissue was suppressed in the nobiletin-treated group (P< 0.05). The
elevations in oxidative stress parameters and the reductions in antioxidant enzymes were attenuated
in 2K-1C rats treated with nobiletin (P< 0.05). In summary, nobiletin had renin-angiotensin system
inhibitory and antioxidant efects and attenuated LV dysfunction and remodelling via restoration of
the AT1R/JAK/STAT pathway. Nobiletin also resolved renal damage that was related to modulation of
the AT1R/Nox4 cascade in 2K-1C hypertension. |
Publication
Journal Publication
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