isoquercitrin receptor br Author contributions br Conflict o

Author contributions
Conflict of interests
Acknowledgments RPR, YS, GG and KM are funded by a grant from the ALS Association and gifts from Steps 4 Doug, Families Unite Against ALS, John and Patricia McDonald, Gerry Kaufman, Arnold Sarnoff, Susan Warso, and Marc and Barbara Posner. This work was also partly supported by grants to EF from NYSTEM CO29559. AS is currently supported by the People Programme (Marie Curie Actions) of the European Union 7th Framework Programme FP7 under REA grant agreement no. 629861. EF is an Investigator of the Howard Hughes Medical Institute.
Introduction Increasing investigations show that the earthworm extract has various beneficial pharmacological activities, including fibrinolytic [2] and anticoagulative activity [3], anti-inflammatory activity [4], anti-oxidative activity [5], [6], peripheral nerve regeneration [7], bone regeneration [8] and wound healing [9], [10]. Earthworms have many advantages, such as beneficial pharmacological activities, abundant resources and low-cost and so on. However, in-depth studies on the active ingredients of earthworms and their pharmacological action are limited. Thus, there is a great potential and prospect for development in this isoquercitrin receptor field. In the pre-animal experiments, we observed that the EWAs (earthworm active ingredients) can significantly reduce the levels of ALT (serum alanine aminotransferase) and AST (aspartate aminotransferase) in the acute liver injured mice. Such results suggest that the EWAs may have a protective effect on the liver. The main functions of the endoplasmic reticulum in eukaryotic cells include protein synthesis and protein folding to form the correct three-dimensional conformation [11]. Malfunctions of endoplasmic reticulum induced by various factors, such as ones that regulate protein folding, post-translational modification, lipid and steroid synthesis, gene expression, cellular metabolism and calcium signaling, can lead to UPR (unfolded proteins response), resulting in ERS [12]. As a result, the endoplasmic reticulum launches various coping mechanisms to alleviate the damage, allowing the cell to adapt to the environmental stress. On the other hand, if the recovery of cellular adaptation is not achieved prolonged ERS triggers apoptosis [13]. ERS-induced apoptosis took part in the pathogenesis and development of disease, such as heart disease [14], cerebral ischemia [15], diabetes [16], atherosclerosis [17] and cancer [18]. The hepatocyte contains abundant endoplasmic reticulum. ERS in the hepatocyte, especially ERS-mediated hepatocyte injury and apoptosis, might be an important contributor to hepatic diseases [19], [20].
Materials and methods
Results
Discussion Tunicamycin is a kind of nucleoside antibiotics, it can inhibit N-acetyl glucosamine transferases, prevent formation of N-linked glycoproteins, perturb ER homeostasis and then cause ERS [22]. In this study, tunicamycin was used as an inducer to establish ERS model in L02 cells. MTT assay indicated that the best condition of establishing ERS model was 60μg/mL tunicamycin treatment for 24h, which was used for the following experiments.