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

Abstract

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-1α. Increased Th17 secretes more IL-17, leading to increased NF-κB 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-1α, a marker of Th17 (RORγt), 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-κB/IL-1β/TNF-α 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.

A Study on the Safety and Effects of Amorpha fruticosa Fruit Extract on Spontaneously Hypertensive Rats with Induced Type 2 Diabetes

“…The activated renin–angiotensin–aldosterone system in hypertension also induces oxidative stress. Elevated levels of angiotensin II (Ang II) (a pro-inflammatory adipokine) lead to the upregulation of NAD(P)H oxidase through the Ang II type 1 receptor, increase the production of ROS, and are involved, together with endothelial dysfunction, in the pathogenesis of insulin resistance [ 31 , 32 ].…”

“…In the present work, the antioxidant effect of A. fruticosa was confirmed in control and diabetic SHRs, where 35 days of oral administration of EAF decreased the MDA quantity and increased the GSH level. It should be noted that one of the main characteristics of spontaneously hypertensive rats is the increase in oxidative stress described by many research teams [ 31 , 32 ]. For this reason, the extract that we used reduces the content of MDA and increases the level of GHA, both in the control group of hypertensive animals and in the group with induced diabetes.…”

Role of Treg cell subsets in cardiovascular disease pathogenesis and potential therapeutic targets

“…Tregs, by secreting anti-inflammatory cytokines like IL-10 and TGF-b, can inhibit the activity of other inflammatory cells, thereby conserving endothelial function (185). Additionally, studies report that TREG cells might release IL-10 to optimize microvascular endothelial function in hypertensive patients (173).IL-10 itself can reduce NADPH oxidase activity, thereby enhancing endothelial relaxation function (186). Upon transferring normal mice TREG cells into angiotensin II-treated IL-10 deficient mice, restoration of endothelial function and a decrease in SBP were observed (187).…”

Role of inflammation, immunity, and oxidative stress in hypertension: New insights and potential therapeutic targets

“…IL-17A is generally considered to act synergistically with other cytokines (e.g., TNF) during inflammatory response. IL-17A and TNF-α have been demonstrated to synergistically enhance lung inflammation and expression of C-C motif chemokine ligand 2 (CCL2) in an NADPH oxidase-dependent manner ( 70 ), which affects vascular functions by influencing gene expression ( 71 ). Moreover, IL-17A is reported to be involved in multiple inflammatory diseases, such as asthma, psoriasis, and systemic lupus erythematosus ( 84 ).…”