Apigetrin attenuates high fat diet-induced intestinal inflammation and nonalcoholic fatty liver disease (NAFLD) process

// Zhi Liu 1 , Dan-Dan Li 1 , Yi Liu 1 and Li-Li Zhu 1 1 Department of Traditional Chinese Medicine, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an 223300, China Correspondence to: Zhi Liu, email: liuzhi_tcm000@qq.com Keywords: NAFLD; intestinal; apigetrin; oxidative stress; inflammation Received: August 23, 2017 Accepted: November 17, 2017 Published: December 21, 2017 ABSTRACT Obesity and non-alcoholic fatty liver disease (NAFLD) are characterized by abnormal gut inflammation, and microbiota. Apigetrin (AGT), a flavonoid isolated from various herbal medicines such as Matricaria chamomilla and Scutellaria baicalensis Georgi , has a number of beneficial health effects, including anti-inflammatory and anti-oxidative bioactivities. In the present study, we attempted to explore the metabolic impact of AGT on high fat diet (HFD)-induced NAFLD and to investigate the consequent anti-diabetic effects associated with gut microbiota. C57BL/6J mice were fed with normal diet (ND) or HFD. And the mice with HFD were gavaged daily with or without AGT for 56 days. The gut microbiota composition was measured using 16s rRNA gene sequences. The results indicated that AGT reduced the weight gain, visceral and subcutaneous fat of HFD-feeding mice. AGT administration increased insulin sensitivity as evidenced by the improved insulin tolerance. AGT treatment also reduced liver weight and triglyceride (TG) accumulation, associated with the blunted hepatic oxidative stress and inflammation. Further, AGT administration could lower serum lipopolysaccharide (LPS) levels, intestinal glucose uptake, TG content, as well as prevent intestinal inflammation and oxidative stress. AGT decreased the secretion of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1β, by inactivating nuclear factor-κB (NF-κB) pathway; and increased the levels of anti-oxidants, such as superoxide dismutase (SOD), heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf-2). Of note, AGT reduced the intestinal bacterial overgrowth. Further more, the anti-oxidant and anti-inflammatory effects of AGT were confirmed in LPS- and fructose-stimulated cells in vitro . The results above indicated that AGT showed beneficial metabolic effects to attenuate HFD-induced NAFLD and intestinal injury.