Abstract: Abstract: Objective To investigate the effect of Phyllanthus emblica freeze-dried powder (PEFP) on cadmium induced subacute liver injury in mice, and to analyze the possible regulatory mechanism by transcriptomics. Methods male KM mice were randomly divided into control group (control group), PEFP group (300 mg/kg PEFP), cadmium group (3 mg/kg CdCl2) and PEFP+CdCl2 group(300 mg/kgPEFP+3 mg/kg CdCl2). Six mice per group were gavaged with PEFP (once a day) and intraperitoneal injection of CdCl2 (once every other day) for 32 days. After dissection, the cadmium content, liver function (ALT, AST, ALP), oxidative stress and other indicators of liver tissue were detected, and the cell morphology of liver tissue was observed by HE staining, the apoptosis was determined by TUNEL method, the differentially expressed genes were determined by RNA sequencing technology, and the protein levels were detected by Western blot (WB). Results compared with the control group, the weight change rate (13.97±2.06%) of mice in the cadmium exposure group decreased significantly (p<0.05), the liver cadmium accumulation (3.49±0.09 μg/kg) increased (p<0.05), the serum ast, ALT and ALP concentrations (707.55±60.19 μ/l, 614.58±24.40 μ/l, 186.85±12.51 μ/l) increased (p<0.05), and the hepatocyte apoptosis rate (32.89±2.53%) increased (p<0.05). Cadmium combined with PEFP treatment could significantly reverse the above changes caused by cadmium.(p<0.05). RNA sequencing showed that 69 genes were significantly differentially expressed after PEFP intervention (14 up-regulated and 55 down regulated), and these differentially expressed genes were related to inflammation, oxidative damage and apoptosis. We selected 4 of 69 differential genes (anaxa2, S100A11, MCP1, galectin3) for WB detection, and the results were consistent with the results of RNA sequencing, suggesting that these genes are involved in the process of PEFP antagonizing cadmium. Conclusion PEFP has an antagonistic effect on cadmium induced subacute liver injury in mice, which may improve liver tissue injury by inhibiting inflammatory response, oxidative damage and apoptosis.

Key words: cadmium chloride, Phyllanthus emblica freeze dried powder, Liver injury, Oxidative stress, inflammation