Objective: To explore the effect of process factors on the safety of traditional Chinese medicine(TCM) preparation by comparing the effect of water extract and ethanol extract of Zhixue capsule on hepatotoxicity. Method: The 80 Wistar rats (40 male and 40 female) were randomly divided into blank control group

Zhixue capsule water extract group

Zhixue capsule 60% ethanol extract group

and 85% ethanol extract group. The rats in normal group received distilled water by gavage

and the rats in other groups received 4.1 g·kg-1 extraction by gavage for 30 days. Intraperitoneal injection of 10% chloral hydrate was used to anesthetize the rats after the last drug administration

then blood was taken from abdominal aorta and serum was taken by centrifugation. Aspartate aminotransferase (AST)

alkaline phosphatase (ALP)

alanine aminotransferase (ALT)

and total bilirubin (TBIL) in serum were detected to indicate the liver injury. Their livers were taken for weighing and calculating the viscera index

the liver tissues in the same place of the largest liver lobe were taken and fixed by 10% neutral formalin for 48 h

then dehydration

paraffin embedding

and slicing were conducted. After hematorylin-eosin(HE) staining

pathological examination was done under the microscope. Result: Zhixue capsule ethanol extract had clear hepatotoxicity

histopathologically demonstrated as small bubble type fatty degeneration surrounding hepatic lobule

and its hepatotoxicity was positively correlated with the ethanol concentration. In addition

water extract group had significantly better anti-inflammatory effect than ethanol extract group according to the liver focal necrosis and inflammatory cells infiltration scores

indicating that the effect of Zhixue capsule ethanol extract was lower than that of water extract. Conclusion: Processing factors have important effects on the safety of TCM compound preparations

indicating that the impact of modern technology on safety shall be concerned in new drug research and development

serious safety risks shall be emphasized in composition enrichment

and toxicity-effect thinking shall be adopted in technology screening.