Aucubin inhibited lipid accumulation and oxidative stress via Nrf2/HO‐1 and AMPK signalling pathways

Abstract

Aucubin ( AU ) is the main active ingredient of Aucuba japonica which has showed many positive effects such as anti‐inflammation and liver protection. Non‐alcoholic fatty liver disease ( NAFLD ) is the most common cause of chronic liver disease. In this research, we explored the effects of AU on the tyloxapol‐induced NAFLD in mice and apolipoprotein C‐ III (apoC‐ III ) induced‐3T3L1 cells. Tyloxapol (300 mg/kg) was injected to C57 BL /6 mice with aucubin. The differentiated 3T3‐L1 cells were treated with or without aucubin after stimulation of apoC‐ III (100 μg/mL). In results, aucubin inhibited hyperlipidaemia, oxidative stress and inflammation by influencing the content of total cholesterol ( TC ), triglyceride ( TG ), low density lipoprotein ( LDL ), very low density lipoprotein ( VLDL ), myeloperoxidase ( MPO ), superoxide dismutase ( SOD ), tumour necrosis factor receptor‐α ( TNF ‐α), interleukin‐1β ( IL ‐1β), and IL ‐6 in blood. AU activated NF ‐E2‐related factor 2 (Nrf2), peroxisome proliferator‐activated receptor α ( PPAR α), PPAR γ and hemeoxygenase‐1 ( HO ‐1) and promoted the phosphorylation of adenosine 5′‐monophosphate‐activated protein kinase ( AMPK α), AMPK β, acetyl‐CoA carboxylase ( ACC ) and protein kinase B ( AKT ). In conclusion, AU performed the function of hypolipidaemic by its obvious anti‐inflammation and antioxidant activity, which may become a kind of new drug targeting at NAFLD .

Aucubin alleviates oxidative stress and inflammation via Nrf2-mediated signaling activity in experimental traumatic brain injury

“…However, under conditions of injury, Nrf2 dissociates from Keap1 and translocates into the nucleus, where it activates the Nrf2-ARE pathway. Au has been demonstrated to have the property to promote Nrf2 into nuclear, which triggers Nrf2-induced antioxidative signaling pathway [31,32]. In both in vitro and in vivo studies, we did nd that Au enhanced nuclear accumulation of Nrf2 and increased cytoplasmic expression of HO-1 and NQO1 in neurons.…”

“…There are several potential limitations deserving attention in our experiments. First, although studies have shown that Au plays a protective role by phosphorylating AMPK to regulate Nrf2 translocation into the nucleus [31,32], we did not explore the speci c molecular mechanism in TBI mice. Second, we only used Nrf2 shRNA to explore the mechanism, which might not have had an e cient inhibitor effect.…”

“…Nevertheless, its molecular mechanisms are not well understood. Recent reports have found that Au both exerts antioxidant and anti-in ammation properties by activating the Nrf2 signaling pathway in noncentral nervous system diseases [31,32]. However, to date, it remains unknown as to whether Au has the same protective effects on TBI.…”

Aucubin alleviates oxidative stress and inflammation via Nrf2-mediated signaling activity in experimental traumatic brain injury

“…Au has been demonstrated to have the property to promote Nrf2 into nuclear, which triggers Nrf2induced antioxidative signaling pathway [31,32]. In both in vitro and vivo studies, we did find that Au enhanced nuclear accumulation of Nrf2 and increased cytoplasmic expression of HO-1 and NQO1 in neurons.…”

Aucubin alleviates oxidative stress and inflammation via Nrf2-mediated signaling activity in experimental traumatic brain injury

“…Substantial evidence suggests that oxidative stress participates in secondary brain injury [4,10,11,17]. Recently, studies have demonstrated that Au has potent antioxidant effects and reduces excessive production of ROS in non-alcoholic fatty liver disease [31] and acute lung injury [32]. Until now, few experiments investigated the potential antioxidative in CNS diseases, except that Xue and colleagues reported the antioxidant bioactivities of Au in P12 cells (a neuronal cell line) [38,39] and in a rat model of diabetic encephalopathy [27][28][29].…”