Targeting Sirt1 in a rat model of high‑fat diet‑induced non‑alcoholic fatty liver disease: Comparison of Gegen Qinlian decoction and resveratrol

Abstract

The present study aimed to explore the mechanism of action of Gegen Qinlian decoction (GGQLD) in experimental non-alcoholic fatty liver disease (NAFLD). A total of 30 rats were randomly divided into five groups: The chow, model, high- and low-dose GGQLD (GGQLD-H and GGQLD-L, respectively) and resveratrol (Resl) groups, and were treated with saline, GGQLD and Resl when a model of high-fat diet (HFD)-induced NAFLD was established. Blood lipid and liver enzymes were detected following treatment for 8 weeks and liver tissue pathology was observed using Oil Red O and haematoxylin and eosin staining. Furthermore, the liver protein and mRNA expression of sirtuin (Sirt)1, peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) were measured using western blotting and reverse transcription-quantitative polymerase chain reaction. Compared with the chow group, the model group demonstrated significantly increased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (P<0.01). GGQLD doses and Resl attenuated the elevated serum ALT and AST levels. GGQLD-H and Resl significantly increased the serum high-density lipoprotein cholesterol level compared with that in the model group (P<0.01), while GGQLD-L and Resl significantly decreased serum low-density lipoprotein cholesterol levels (P<0.01). The GGQLDs and Resl groups revealed an evident improvement in Sirt1 protein and mRNA expression. Although GGQLD and Resl significantly decreased NF-κB gene expression compared with the model group (P<0.01), the effect on NF-κB protein expression was not significant. Furthermore, the PGC-1α gene and protein expression in the HFD rat group slightly decreased compared to the levels in the chow group, but the decrease was insignificant. However, an evident increase in PGC-1α mRNA expression was observed in the GGQLD-H group compared with the model group (P<0.01). Histological staining revealed that GGQLD and Resl decreased the lipid droplets in hepatocytes and normalized steatosis in rats fed with a HFD. The results indicated that GGQLD treatment may be a potent strategy for managing NAFLD by managing lipid metabolism and inflammatory and histological abnormalities by triggering the Sirt1 pathway.

Regulatory effect of a Chinese herbal medicine formula on non-alcoholic fatty liver disease

“…Chinese herbal medicine (CHM) has been traditionally used in China and other Asian countries for thousands of years. A specific and basic feature of Chinese medicine is the use of formulas containing several herbs (herbal cocktail) to ameliorate abnormal symptoms associated with a particular disease[8]. Dachaihu decoction (DCHD), a classical formula from the Treatise on Febrile Disease , is one of the well-known traditional Chinese medicines and consists of: Chinese thorowax root ( Bupleurum chinensis DC .…”

Mangiferin Improves Hepatic Lipid Metabolism Mainly Through Its Metabolite-Norathyriol by Modulating SIRT-1/AMPK/SREBP-1c Signaling

“…Liver is a central metabolic organ that regulates essential functions of lipid homeostasis. SIRT-1 plays an important role in TG metabolism in the liver, and increasing evidences suggest an inverse correlation between SIRT-1 levels and non-alcoholic fatty liver disease (NAFLD) ( Mariani et al, 2015 ; Guo et al, 2017 ). Liver specific deletion of SIRT-1 contributes to increased inflammation, endoplasmic reticulum stress and hepatic steatosis ( Purushotham et al, 2009 ).…”

Gegen Qinlian Decoction Attenuates High‐Fat Diet‐Induced Steatohepatitis in Rats via Gut Microbiota

“…A unique and basic feature of CHM is the use of multicomponent herbal formulas to ameliorate various abnormalities and diseases. For example, formulas like Linggui Zhugan [24], Yinchenhao [25], and Gegen Qinlian decoction (GGQLD) [26] have been used to treat NAFLD. GGQLD, a well-known traditional CHM from the Treatise on Febrile Diseases, consists of Kudzu root , Rhizoma coptidis, Scutellaria baicalensis Georgi, and Glycyrrhizae Radix and is widely used to clinically treat NASH.…”

“…Therefore, GGQLD, which is under conventional dose, has been regarded as a kind of safe and potential treatment in treating NASH until now. In our previous studies, we found that GGQLD has an anti-inflammatory effect [27, 28], which could regulate lipid metabolism disorders and improve liver histology of the rats during NAFLD pathogenesis [26, 29]. In addition, the active components of GGQLD, including baicalin, glabridin, and berberine, have been shown to alleviate inflammation and oxidative stress in vivo and in vitro [30, 31].…”