ABSTRACT
This study aimed to investigate the protective effect of water extracts of Orychophragmus violaceus seeds on liver injury induced by thioacetamide(TAA) in mice. ICR male mice were randomly divided into seven groups: normal group, model group, bicyclol positive control group(200 mg·kg~(-1)), Kuihua Hugan Tablets group(350 mg·kg~(-1)), O. violaceus seeds low-dose water extract group(125 mg·kg~(-1)), middle-dose water extract group(250 mg·kg~(-1)), and high-dose water extract group(500 mg·kg~(-1)). Intragastric administration was given in all groups at 0.02 mL·g~(-1) body weight, 1 time a day for continuous 4 days. One h after the administration on the 4 th day, the liver injury model was induced by intraperitoneal injection of TAA(100 mg·kg~(-1)). The mice were put to death 24 hours later. Blood and tissues were taken and organ indexes were calculated. The activities of ALT, AST and TBiL in serum were detected. The content of MDA, GSH and the activity of SOD, GSH-Px in liver homogenate were examined by colorimetry method. HE staining was used to observe the pathological changes of liver tissues in mice. The protein expression levels of NF-κB p65, Keap-1, Nrf2, p-p38, p-JNK, p-ERK, Bax, Bcl-2, caspase-3, cleaved caspase-3 and caspase-8 were detected by Western blot. The results showed that as compared with the model group, various O. violaceus seeds groups could significantly improve the pathological conditions of liver and reduce ALT, AST, TBiL activities in serum of mice with liver injury. In the high-dose group, the activities of SOD, GSH-Px and the content of GSH were significantly increased, while MDA content was sharply declined. Meanwhile, O. violaceus seeds extract down-regulated the expressions of Bax, Keap-1, p-p38, p-JNK, p-ERK, NF-κB p65, cleaved caspase-3 and up-regulated the expressions of Nrf2, Bcl-2, caspase-3 and caspase-8. In conclusion, O. violaceus seeds extract exhibited potent protective effect on liver injury induced by TAA in mice, and its mechanism may be related to down-regulating levels of Keap-1, up-regulating the expressions of Nrf2, inhibiting the expressions of p-p38, p-ERK and NF-κB p65 signaling pathway, and inhibiting hepatocyte apoptosis by down-regulating the expressions of p-JNK and Bax and up-regulating the expressions of Bcl-2.
Subject(s)
Animals , Male , Mice , Apoptosis , Brassicaceae/chemistry , Chemical and Drug Induced Liver Injury/drug therapy , Liver/drug effects , Mice, Inbred ICR , Oxidative Stress , Plant Extracts/pharmacology , Seeds/chemistry , Signal Transduction , ThioacetamideABSTRACT
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.
ABSTRACT
OBJECTIVE: To study water-soluble constituents from the seeds Orychophragmus violaceus. METHODS: The constituents were isolated and purified by silica gel chromatography repeatedly, and the structures were identified by spectral analysis and chemical methods. RESULTS: Fifteen water-soluble compounds were isolated from the seeds Orychophragmus violaceus and their structures were identified as blumenol A(1), 3', 5', 5, 7-tetrahydroxylflavanone(2), (+)-catechin(3), quercetin(4), adenosine(5), salicylic acid(6), 2'-deoxy adenosine(7), p-coumaric acid(8), vanillic acid(9), protocatechuic acid(10), caffeic acid(11), syringic acid(12), daucosterol(13), succinic acid(14) and azelaic acid(15). CONCLUSION: All compounds are isolated from Orychophragmus violaceus for the first time. This study can establish the foundation for the classification chemical composition this plant.