Oxidative stress contributes to muscle wasting in advanced chronic kidney disease (CKD) patients. Atractylenolide III (ATL-III), the major active constituent of Atractylodes rhizome, has been previously reported to function as an antioxidant. This study is aimed at investigating whether ATL-III has protective effects against CKD-induced muscle wasting by alleviating oxidative stress. The results showed that the levels of serum creatinine (SCr), blood urea nitrogen (BUN), and urinary protein significantly decreased in the ATL-III treatment group compared with the 5/6 nephrectomy (5/6 Nx) model group but were higher than those in the sham operation group. Skeletal muscle weight was increased, while inflammation was alleviated in the ATL-III administration group compared with the 5/6 Nx model group. ATL-III-treated rats also showed reduced dilation of the mitochondria, increased CAT, GSH-Px, and SOD activity, and decreased levels of MDA both in skeletal muscles and serum compared with 5/6 Nx model rats, suggesting that ATL-III alleviated mitochondrial damage and increased the activity of antioxidant enzymes, thus reducing the production of ROS. Furthermore, accumulated autophagosomes (APs) and autolysosomes (ALs) were reduced in the gastrocnemius (Gastroc) muscles of ATL-III-treated rats under transmission electron microscopy (TEM) together with the downregulation of LC3-II and upregulation of p62 according to Western blotting. This evidence indicated that ATL-III improved skeletal muscle atrophy and alleviated oxidative stress and autophagy in CKD rats. Furthermore, ATL-III could also increase the protein levels of p-PI3K, p-AKT, and p-mTOR in skeletal muscles in CKD rats. To further reveal the relevant mechanism, the oxidative stress-mediated PI3K/AKT/mTOR pathway was assessed, which showed that a reduced expression of p-PI3K, p-AKT, and p-mTOR in C2C12 myoblast atrophy induced by TNF-α could be upregulated by ATL-III; however, after the overexpression of Nox2 to increase ROS production, the attenuated effect was reversed. Our findings indicated that ATL-III is a potentially protective drug against muscle wasting via activation of the oxidative stress-mediated PI3K/AKT/mTOR pathway.

We aimed to examine the effects of zinc supplementation on nutritional status, lipid profile, and antioxidant and anti-inflammatory therapies in maintenance hemodialysis (MHD) patients. We performed a systematic review and meta-analysis of randomized, controlled clinical trials of zinc supplementation. Metaregression analyses were utilized to determine the cause of discrepancy. Begg and Egger tests were performed to assess publication bias. Subgroup analysis was utilized to investigate the effects of zinc supplementation in certain conditions. In the crude pooled results, we found that zinc supplementation resulted in higher serum zinc levels (weighted mean difference [WMD] = 28.489; P < 0.001), higher dietary protein intake (WMD = 8.012; P < 0.001), higher superoxide dismutase levels (WMD = 357.568; P = 0.001), and lower levels of C-reactive protein (WMD = −8.618; P = 0.015) and malondialdehyde (WMD = −1.275; P < 0.001). The results showed no differences in lipid profile. In the metaregression analysis, we found that serum zinc levels correlated positively with intervention time (β = 0.272; P = 0.042) and varied greatly by ethnicity (P = 0.023). Results from Begg and Egger tests showed that there was no significant bias in our meta-analysis (P > 0.1). Results of subgroup analysis supported the above results. Our analysis shows that zinc supplementation may benefit the nutritional status of MHD patients and show a time-effect relationship.

Irbesartan (Irb), a unique subset of angiotensin II receptor blockers (ARBs) with PPAR-γ activation function, has been reported to play a role in renal dysfunction, glucose metabolism, and abnormal lipid profile in diabetic animal models and humans. However, the underlying mechanisms that improve hyperlipidemia and liver steatosis are unclear. This study investigated the effects of Irb on lipid metabolism and hepatic steatosis using the spontaneous type 2 diabetic db/db mouse model. The results demonstrated body and liver weight, food consumption, lipid content in serum and liver tissue, and liver dysfunction as well as hepatic steatosis were increased in db/db mice compared with db/m mice, whereas the increases were reversed by Irb treatment. Moreover, Irb administration resulted in an increase in LC3BII as well as the LC3BII/I ratio through activating PPAR-γ and p-AMPK and inhibiting p-Akt and p-mTOR, thereby inducing autophagy in the db/db mouse liver. Therefore, our findings suggest that Irb can ameliorate hyperlipidemia and liver steatosis by upregulating the expression of PPAR-γ, activating the AMPK/Akt/mTOR signaling pathway and inducing liver autophagy.

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