Rabbit anti-Mouse c-Jun polyclonal antibody

Background: Non-alcoholic fatty liver (NAFLD) is a chronic disease worldwide, which poses a huge threat to human health. Xiaochaihu decoction is a well-known traditional Chinese medicine prescription. It has been proven effective in treating NAFLD but its mechanism is still unclear. Objective: Multiple mechanisms of Xiaochaihu decoction are explored by identifying and connecting potential targets and active ingredients in the treatment of NAFLD. Methods Active ingredients and related targets of seven herbs were collected from TCMSP database. The related targets of NAFLD were obtained from Genes cards database, TDD and OMIM database. The intersected targets of disease targets and drug targets were input into STRING database to construct protein-protein interaction network. DAVID database was used for GO enrichment analysis and KEGG enrichment analysis. Results: After screening and removal of duplicates, a total of 145 active ingredients and 105 potential targets were obtained. PPI network manifested that AKT1, IL6, JUN MAPK8 and STAT3 were the key target proteins. The results of GO enrichment analysis mainly involved cytokine receptor binding, cytokine activity, and heme binding. The results of KEGG analysis suggested that the mechanism mainly involved in AGE-RAGE signaling pathway in diabetic complications, Hepatitis C, fluid shear stress and atherosclerosis. The signaling pathways were further integrated as network manner, including AGE-RAGE signaling pathway in diabetic complications, Fluid shear stress and atherosclerosis, Insulin resistance, HIF-1 signaling pathway, Th17 cell differentiation and IL-17 signaling pathway. The network contained immunity regulation, metabolism regulation and oxidative stress regulation. Conclusion: Xiaochaihu decoction plays a key role in the treatment of NAFLD with multiple targets and pathways. Immunity regulation, metabolism regulation and oxidative stress regulation consist of the crucial regulation cores in mechanism.

Background: Gambogenic acid (GNA), an active component of Garcinia hanburyi Hook.f. (Clusiaceae) (common name gamboge), exerts anti-inflammatory and antitumor properties. However, the underlying mechanism of GNA in colorectal cancer (CRC) is still not well understood. Purpose: This study aimed to investigate the antitumor effects and mechanisms of GNA on CRC in vitro and in vivo. Methods: Cell viability, colony formation and cell apoptosis assays were performed to determine the antitumor effects of GNA. qRT-PCR and Western blotting were performed to evaluate the expression of genes or proteins affected by GNA in vitro and in vivo. HCT116 colon cancer xenografts and the APC(min/+) mice model were used to confirm the antitumor effects of GNA on CRC in vivo. Results: GNA induced Noxa-mediated apoptosis by inducing reactive oxygen species (ROS) generation and c-Jun N-terminal kinase (JNK) activation. Moreover, GNA triggered endoplasmic reticulum (ER) stress, which subsequently activated inositol-requiring enzyme-1 alpha (IRE1 alpha) leading to JNK phosphorylation. ROS scavenger attenuated GNA-induced IRE1 alpha activation and JNK phosphorylation. Knockdown of IRE1 alpha also prevented GNA-induced JNK phosphorylation. In vivo, GNA suppressed tumor growth and progression in HCT116 colon cancer xenografts and the APC(min/+ )mices model. Conclusion: These findings revealed that GNA induced Noxa-mediated apoptosis by activating the ROS/IRE1 alpha/JNK signaling pathway in CRC both in vitro and in vivo. GNA is therefore a promising antitumor agent for CRC treatment.