Dieckol Reduces Muscle Atrophy by Modulating Angiotensin Type II Type 1 Receptor and NADPH Oxidase in Spontaneously Hypertensive Rats

The renin-angiotensin system is involved in the development of hypertension and sarcopenia. Increased levels of angiotensin II (Ang II) lead to upregulation of Ang II type 1 receptor (AT1R), which results in increasing reactive oxygen species (ROS) by NAD(P)H oxidase (Nox). Increased ROS led to increased helper T17 (Th17) and decreased regulatory T (Treg) cells through HIF-1 alpha. Increased Th17 secretes more IL-17, leading to increased NF-kappa B and muscle atrophy. We evaluated the effect of Ecklonia cava extracts (ECE) and dieckol (DK) on attenuating muscle atrophy by decreasing AT1R and NOX activity in spontaneous hypertensive rats (SHRs). The serum levels of Ang II and expression of AT1R in the muscle were higher in SHRs than in normotensive animals of Wistar-Kyoto rats (2.4 and 1.8 times higher than WKY, respectively). The expression of AT1R decreased by ECE or DK (0.62 and 0.84 times lower than SHR, respectively). In SHRs, the expression of Nox 1, 2, and 4 were increased (1.2-1.15 times higher than WKY) but were decreased by the administration of ECE (0.8-0.9 times lower than SHR) or DK (0.7-0.9 times lower than SHR). The Nox activity was increased in SHRs (2.3 times more than WKY) and it was decreased by ECE (0.9 times lower than SHRs) and DK (0.9 times lower than SHRs). The expression of HIF-1 alpha, a marker of Th17 (ROR gamma t), and cytokine secreted by Th17 (IL-17) was increased in SHRs and was decreased by ECE or DK. The marker of Treg (Foxp3) and cytokine secreted from Treg cells (IL-10) was decreased in SHRs and was increased by ECE or DK. The expression of NF-kappa B/IL-1 beta/TNF-alpha and MuRF-1/MAFbx/atrogin-1 was increased in SHRs and these were decreased by ECE or DK. The cross-sectional area of muscle fiber was decreased in SHRs (0.7 times lower than WKY) and was increased by ECE (1.3 times greater than SHR) or DK (1.5 times greater than SHR). In conclusion, ECE or DK leads to a decreased expression of AT1R and Nox activity which modulates Th17/Treg balance and consequently, decreased muscle atrophy.

Automated summary

The study showed that Ecklonia cava extracts and dieckol can attenuate muscle atrophy in spontaneous hypertensive rats by decreasing the expression of AT1R and NOX activity, thus modulating the Th17/Treg balance.