Solidago chilensis Meyen hydroalcoholic extract reduces JNK/IκB pathway activation and ameliorates insulin resistance in diet-induced obesity mice

Abstract

Hydroalcoholic extract of Solidago chilensis (Sc) is employed in popular medicine to treat inflammatory disease. The low-grade proinflammatory state and the activation of serine/threonine kinases in adipose tissue, like c-jun kinase (JNK) and IKK, and transcription factors, have an important role in obesity-associated insulin resistance. The aim of this study was to further investigate the effects of the Sc extract on glucose homeostasis in diet-induced obesity mice. Male Swiss mice were randomized to three groups: a control group (C) fed with standard laboratory chow; a group with an experimental high-fat diet (HFD); and a group fed with a high-fat (45% kcal from fat) diet + extract of Sc (via intraperitoneal, 3 mg/kg) (ScHFD). The dietary treatment lasted for eight weeks. Subsequently, the expression and phosphorylation of proteins of interest in the liver, hypothalamus and skeletal muscle were evaluated by Western blot analysis. Body weight, epididymal fat pad mass and liver triglycerides were higher in HFD than in control mice, but these parameters were reduced by intraperitoneal administration of the extracts (3 mg/kg) to the HFD group. AKT phosphorylation stimulated by insulin in the liver, hypothalamus and skeletal muscle was higher in ScHFD as compared with HFD mice. Additionally, liver expression of phosphoenolpyruvate carboxykinase (PEPCK) and fatty acid synthase were lower in ScHFD as compared with HFD mice. Nuclear factor κB, p-IκB and p-JNK levels were higher in HFD when compared with control mice, but they were lowered by treatment with extract (ScHFD). In addition, in db/db mice, Sc extract also improved liver AKT phosphorylation stimulated by insulin and reduced PEPCK expression. The data presented herein show that Sc improves AKT activation. This effect may be promoted by reduction of the proinflammatory pathway in the liver and hypothalamus. Therefore, systemic action of the Sc components may contribute to improve obesity-associated pathophysiology.

Celastrol, an NF-κB Inhibitor, Improves Insulin Resistance and Attenuates Renal Injury in db/db Mice

“…In addition, celastrol also markedly increased the adiponectin gene expression that is associated with increased plasma levels of adiponectin, all of which are related with improved insulin resistance. These results agree with those of a previous study that demonstrated that NF-κB levels were higher in mice treated with a high fat diet, and that inhibition of NF-κB restored the lipotoxicity of adipose tissue and decreased fat mass [39]. Furthermore, celastrol treatment significantly decreased the levels of SFAs, and increased the levels of MUFAs in hepatic and adipose tissue, that are more anti-inflammatory fatty acid composition.…”

Garlic-derived S-allylmercaptocysteine is a hepato-protective agent in non-alcoholic fatty liver disease in vivo animal model

“…To study the signaling pathway involved in the pathophysiological processes of NAFLD induced by the elevation of FFA and the effects of SAMC intervention, we measured the phosphorylation status and total expression of MAPK kinases signaling pathways including p38 MAPK, JNK and MEK/ERK, which play important roles in insulin and inflammatory responses [18, 19]. Interestingly, our result showed that an increase in the phosphorylation level of p38 MAPK and JNK/c-Jun, but a decrease in the phosphorylation of MEK/ERK1/2 was observed in NAFLD rat liver tissue.…”

Hypoglycemic and hypolipidemic effects of Solidago chilensis in rats

“…Its main chemical constituents are acetophenone, carotenes, diterpenoids with labdanic and clerodanic skeletons (Soares-Valverde et al, 2009), flavonoids, glycosides, 3-methoxybenzaldehyde, essential oils, and saponins (Silva et al, 2010), with quercetrin being the major constituent (Torres et al, 1987 Ethnopharmacological investigations have found this species to have antispasmodic, antihemorrhagic (Alonso, 1998), woundhealing (Facury-Neto et al, 2004, and anti-inflammatory effects (Tamura et al, 2009). Recently, there has been considerable progress in the investigation of S. chilensis and gastric protection (Bucciarelli et al, 2010) as well as a better understanding of the effect of S. chilensis on insulin resistance in obese mice (Melo et al, 2011). However, the hypoglycemic and hypolipidemic effects of S. chilensis on the glucose tolerance curve have not yet been studied.…”