The aim is to investigate the effect of lotus (Nelumbo nucifera Gaertn.) seedpod extract (LSE) on acetaminophen (APAP)-induced hepatotoxicity. LSE is rich in polyphenols and has potent antioxidant capacity. APAP is a commonly used analgesic, while APAP overdose is the main reason for drug toxicity in the liver. Until now, there has been no in vitro test of LSE in drug-induced hepatotoxicity responses. LSEs were used to evaluate the effect on APAP-induced cytotoxicity, ROS level, apoptotic rate, and molecule mechanisms. The co-treatment of APAP and LSEs elevated the survival rate and decreased intracellular ROS levels on HepG2 cells. LSEs treatment could significantly reduce APAP-induced HepG2 apoptosis assessed by DAPI and Annexin V/PI. The further molecule mechanisms indicated that LSEs decreased Fas/FasL binding and reduced Bax and tBid to restore mitochondrial structure and subsequently suppress downstream apoptosis cascade activation. These declines in COX-2, NF-κB, and iNOS levels were observed in co-treatment APAP and LSEs, which indicated that LSEs could ameliorate APAP-induced inflammation. LSE protected APAP-induced apoptosis by preventing extrinsic, intrinsic, and JNK-mediated pathways. In addition, the restoration of mitochondria and inflammatory suppression in LSEs treatments indicated that LSEs could decrease oxidative stress induced by toxic APAP. Therefore, LSE could be a novel therapeutic option for an antidote against overdose of APAP.

Background Acetaminophen (APAP) is one of the most widely used analgesic agents while overdose APAP will lead to severe hepatotoxicity. Lotus seedpod, a traditional herbal, is rich in polyphenol and has been shown to possess antioxidant, radioprotective and anti-cancer activities. This study examined the hepatoprotective role of lotus seedpod extracts (LSE) in vitro and in vivo. Methods Firstly, LSE or its main compound epigallocatechin (EGC) dose-dependently improved the survival of human hepatocyte HepG2 cells from APAP-induced loss of viability. In vivo study, the BALB/c mice were supplemented with or without LSE (1% and 2%) during the 9-week treatment period in the presence or absence of APAP (i.p.; 400 mg/kg) twice per week. Results In vitro study revealed that LSE or EGC showed potential in reducing APAP-induced occurrence of apoptosis confirmed by morphological and biochemical features, including an increase in the distribution of hypodiploid phase, apoptotic bodies formation, and caspases activation. Molecular data showed that antiapoptotic effects of LSE or EGC mediated via intrinsic, extrinsic and ASK 1/JNK apoptotic signaling pathways. Further data showed that LSE inhibited the APAP-induced the protein expression of iNOS to decrease inflammation. In vivo study showed that LSE treatments significantly decreased the serum levels of the hepatic enzyme markers GOT and GPT induced by APAP. LSE also inhibited the serum levels of inflammatory cytokines (IL-6 and IL-1β) during APAP treatment. LSE at 1% significantly restored the decrease in glutathione (GSH) content and elevated the levels of antioxidant enzymes, including catalase and glutathione reductase (GRd), in the liver. Western blotting data demonstrated that LSE inhibited the expression of caspase − 3, -8, -9 in APAP-induced liver injury. Conclusions LSE protected APAP-induced hepatotoxicity which could be a novo strategy for treatment.