ABSTRACT
Using the idiosyncratic lipopolysaccharide (LPS)-mediated hepatotoxicity model as a positive control, liver injury induced by Cortex Dictamni aqueous extract (AE) or Cortex Dictamni ethanol extracts (EE) was evaluated. Idiosyncratic hepatotoxicity model was established in rats [Institutional Animal Care and Use Committee (IACUC)-2018-008] by injecting LPS at a dosage of 2.8 mg·kg-1. Rats were randomly divided into 10 groups. The plasma levels of liver function biomarkers such as alanine transaminase (ALT), aspartate aminotransferase (AST) were measured. Histological changes (HE staining), hepatocellular apoptosis and the content of cytokines of liver were measured. Network pharmacology was used to analyze the relationship between chemical components and immunity in Cortex Dictamni. Compared with the control group, the doses (25, 50 g·kg-1) of AE or EE had no significant changes in ALT, AST and liver pathology (P>0.05). The doses of 4.2 g·kg-1 of AE or EE+LPS groups exhibited an elevation in ALT, AST and serum cytokines (P<0.01). Disorder of liver lobular arrangement and irregular island-like or massive necrosis of liver cells were observed in these groups. Network pharmacology shows that Cortex Dictamni may directly or indirectly participate in the process of immunomodulation. We found that Cortex Dictamni regulated 15 core targets and affected 19 pathways, including apoptosis, TNF-α, NF-kappa B signaling pathways. These results suggest that Cortex Dictamni can induce idiosyncratic hepatotoxicity and the water extract can induce more serious liver injury then ethanol extract of Cortex Dictamni. These findings provide a reference for elucidating the idiosyncratic hepatotoxicity induced by Cortex Dictamni.
ABSTRACT
OBJECTIVE To study the protective effect of Orychophragmus violaceus(OV)seed against acute hepatotoxicity induced by the traditional Chinese Medicine Cortex Dictamni in mice. METHODS Twenty-five mice were randomly divided into 5 groups:control group,Cortex Dictamni group(70 g · kg-1)and OV seed groups(36,54 and 72 g · kg-1). OV Seed groups were orally adminis?tered with the aqueous extract of OV seed for 4 consecutive days while the other groups were ig given water. On the 4th day,Cortex Dictamni group and OV seed groups were ig given the aqueous extract of Cortex Dictamni,and normal control group was ig given water. Twenty-four hours later,all the mice had their blood and liver samples taken after anesthesia. The serum chemical parameters were measured, including glutamic oxaloacetic transaminase (GOT),glutamate pyruvate transaminase (GPT) and lactate dehydrogenase(LDH),as well as malondialdehyde(MDA),glutathione(GSH)and oxidized glutathione(GSSG)levels in the liver. GSH/GSSG ratio was calculated. Histopathologic changes in the liver were observed and the area was calculated after HE staining. RESULTS Compared with normal control group,Cortex Dictamni(70 g · kg-1)increased the serum GOT,GPT and LDH levels by 500, 140 and 40 fold(P<0.01). OV seed reduced serum GOT,GPT and LDH levels increased by Cortex Dictamni(P<0.05,P<0.01),by as much as 62%,75% and 99% for GPT,70%,82% and 98% for GOT,and 55%,75%and 96%for LDH,respectively. The level of MDA and the ratio of GSH/GSSG in Cortex Dictamni group were 1.39 ± 0.58 and(3.53 ± 1.27)μmol · g-1,a 10-fold increase and 40%decline compared with normal control group(P<0.01). OV seed of 72 g·kg-1 lowered the level of MDA by 22%(P<0.05),and OV seed(36,54 and 72 g · kg-1)increased the GSH/GSSG ratio by 47%,42%and 54%(P<0.05). Histopathologic results showed that OV seed alleviated the liver damage induced by Cortex Dictamni from(64.1±8.5)%to(37.5±7.1)%and (20.0±0.8)%(P<0.01). CONCLUSION OV seed can effectively protect mice from the acute hepatotoxicity induced by Cortex Dictamni.