No abstract

Magnolol (MG) is the main active compound of Magnolia officinalis and exerts a wide range of biological activities. In this study, we investigated the effects of MG using tyloxapol (Tylo)-induced (200 mg/kg, i.p.) hyperlipidemia in rats and palmitic acid (PA)-stimulated (0.3 mM) HepG2 cells. Our results showed that Tylo injection significantly increased plasma levels of triglyceride and cholesterol as well as superoxide anion in the livers, whereas MG pretreatment reversed these changes. MG reduced hepatic lipogenesis by attenuating sterol regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase (FAS) proteins and Srebp-1, Fas, Acc, and Cd36 mRNA expression as well as upregulated the lipolysis-associated genes Hsl, Mgl, and Atgl. Furthermore, MG reduced plasma interleukin-1β (IL-1β) and protein expression of NLR family pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), and caspase 1 as well as upregulated nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and induction of heme oxygenase-1 (HO-1) in hepatocytes of Tylo-treated rats. Enhanced autophagic flux by elevation of autophagy related protein 5-12 (ATG5-12), ATG7, Beclin1, and microtubule-associated protein light chain 3 B II (LC3BII)/LC3BI ratio, and reduction of sequestosome-1 (SQSTM1/p62) and phosphorylation of mTOR was observed by MG administration. However, autophagy inhibition with 3-methyladenine (3-MA) in HepG2 cells drastically abrogated the MG-mediated suppression of inflammation and lipid metabolism. In conclusion, MG inhibited hepatic steatosis-induced NLRP3 inflammasome activation through the restoration of autophagy to promote HO-1 signaling capable of ameliorating oxidative stress and inflammatory responses.

Long-term treatment with raloxifene reduces the severity of sepsis in OVX rats, attributed from up-regulation of HSP70 and HO-1 to exert the antioxidant and anti-inflammatory capacities. These findings provide new insights into bacterial infection during menopause and the molecular mechanism of raloxifene.

BackgroundBilateral ovariectomy is an experimental model used to analyze the conditions of menopause and develop strategies for alleviation of the deleterious effects during estrogen deficiency. Brown and beige adipocytes exert thermogenesis capacities and are promising therapeutic strategy for obesity. This study aims to investigate the adipose tissue browning potentials of antioxidant α-lipoic acid (ALA) and underlying mechanisms involved in ovariectomized (Ovx) rats.Methods:Eight weeks old female Wistar rats were randomly divided into Sham or Ovx groups. The Ovx rats were subjected to bilateral ovariectomy and administered with ALA 200 or ALA 300 mg/kg/day (gavage) for 8 weeks. Results:Ovx group significantly increased boy weight (BW) and fat pad mass as compared to Sham group, while ALA supplementation reversed these changes. Lipid profiles including serum triglycerides (TG), total (TC) and low-density lipoprotein cholesterol (LDL-C) levels were significantly elevated in the Ovx group, whereas the ALA treatment showed a significant decrease in these levels. Furthermore, high density lipoprotein cholesterol (HDL-C) and myokine irisin secretion were increased by ALA as well. Morphology results showed ALA treatment reduced Ovx-induced adipocyte hypertrophy and enhanced UCP1 expression by immunohistochemical staining in inguinal WAT. Protein expression of brown fat-specific markers UCP1, PRDM16 and CIDEA was markedly reduced in Ovx rats, whereas ALA treatment reversed these changes. ALA significantly increased liver kinase B1 (LKB1) and phosphorylation of AMP-activated protein kinase (AMPK) and the downstream acetyl-CoA carboxylase (ACC) that were decreased by Ovx, suggesting the browning effects were mediated by AMPK signaling. Conclusions:ALA ameliorates obesity caused by hormone deprivation in menopause via conversion of white to beige adipocytes concomitant with the activation of AMPK signaling.