Novel anti-obesity effect of scutellarein and potential underlying mechanism of actions

Aims: Scutellarein (Sc), a natural compound and an active ingredient of Erigeron breviscapus (vant.), shows anti-inflammatory and antioxidant properties and has the potential for obesity treatment. However, no previous in vivo study has been conducted to assess the role of Sc in obesity. This study investigated the effects of Sc on obesity and associated hyperlipidemia and fatty liver and explores the underlying mechanisms of action in a mouse model. Methods: The study was conducted using a well-established mouse model of obesity induced by high-fat diet (HFD) feeding. Anti-obesity effects were assessed using body weight, abdominal circumference, white adipose tissue, adiposity index, and fatty liver index. Lipid lowering and liver protective effects were examined by blood sample analysis. Lipid dystopia deposition was confirmed by liver pathological sections. The signaling pathways of lipid metabolism and cytokine/inflammatory mediator were evaluated using Real-Time PCR and Western blot. Results: Central obesity, dyslipidemia, inflammation, and hepatic steatosis were developed in mice fed with HFD. Administration of Sc at a dose of 50 mg/kg for 16 weeks effectively attenuated all obesity indicators tested. Further studies revealed the antagonistic effect of Sc on hyperlipidemia was a result of the repression of the lipid synthesis pathway, de novo pathway, HMGCR, promoting fatty acid oxidation (PPAR alpha, CPT-1a) and increased cholesterol output (PPAR gamma-LXR alpha-ABCA1). The anti-inflammatory effect was attributed to blocking the expression of inflammatory genes, including TNF-alpha, IL-6, NF-kappa B. Conclusions: These results suggest that Sc possesses important novel anti-obesity effects accompanying lipid lowering and anti-inflammation-based liver protective effects. These favorable effects are causally associated with the suppression of gene expression of inflammatory cytokines and fine regulation of genes responsible for energy metabolism. Our results advance the understanding of the pharmacological actions of Sc, and provides a role for Sc in effective management of obesity.