OBJECTIVETo investigate the anti-inflammatory efficacy accompanied by side effects of water extract and alcohol extract of Sophorae Tonkinensis Radix et Rhizome (STRR), their molecular mechanism, and interpret the relationship of "toxicity-effect" of toxic medicine.

METHODThe ear swelling by croton oil and granuloma by agar test models were used, water extract and alcohol extract of STRR of different dosages were administrated ig to mice to observe the assident toxicity, at the same time the activities of ALT, AST and the content of SOD, MDA,PEG2, NO, NOS, Cr, BUN, GSH, TG and Gn in serum were tested.

RESULTBoth water extract and alcohol extract of STRR have a strong inhibitory effect on ear swelling by croton oil and granuloma by agar. The activities of ALT, AST in serum were higher than that of normal group. SOD, MDA, PEG2, NO, NOS, GSH, TG and Gn had obvious changes.

CONCLUSIONBoth water extract and alcohol extract of STRR had an anti-inflammatory effect on acute and chronic inflammation. At the same time, side effects and liver toxicity. The anti-inflammatory effect of STRR in probable relation to the reduced inflammatory mediators release. Oxidative damnification might be one of the liver injury mechanism.

Alanine Transaminase ; blood ; metabolism ; Animals ; Anti-Inflammatory Agents ; administration & dosage ; adverse effects ; isolation & purification ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; isolation & purification ; Female ; Humans ; Inflammation ; drug therapy ; Kidney ; drug effects ; metabolism ; Liver ; drug effects ; enzymology ; metabolism ; Male ; Mice ; Rhizome ; chemistry ; Sophora ; chemistry

OBJECTIVETo study on the time-toxicity and dose-toxicity relationships caused by multiple dose water extraction components of Evodia Fructus to mice.

METHODMice were grouped according to different time or dose points, to observe the death condition and toxicity of mice. The changes of the activity of ALT, AST and liver, kidney index were detected, and the morphological changes of liver tissue were observed under light microscope.

RESULTOn the first day after administration the hepatotoxicity which displayed with obvious increase of ALT, AST activity in serum and liver tissue and hepatic injury appeared. On the third day the hepatotoxicity kept a higher level that the active units in serum ALT, AST were significantly higher than the normal group. On the 7th day after administration ALT, AST level in serum are restored near normality. Compared with the normal group, within 7 days after the administration, water extracted components in 0.63-5.0 g x kg(-1) dose scope could cause significant damage to liver, the activity of ALT, AST, AKP, TBI elevated, while ALB reduced, and liver ratio increased, and under light microscope, the different doses' liver tissue of mice all had different degree's edema, fatty degeneration in liver cells and interstitial congestion. There were certain time-toxicity and dose-toxicity relationships. The above-mentioned change gradually aggravated with dose increasing, and it was the obvious discrepancy compared with distilled water control group.

CONCLUSIONMultiple intragastric administrations of water extracted components of Evodia Fructus with certain dosage may induce acute hepatotoxical injury in mice and show certain "dosage-time-toxicity" relationship.

Alanine Transaminase ; blood ; metabolism ; Animals ; Aspartate Aminotransferases ; blood ; metabolism ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; metabolism ; toxicity ; Evodia ; chemistry ; Female ; Fruit ; chemistry ; Kidney ; drug effects ; enzymology ; metabolism ; Liver ; drug effects ; enzymology ; metabolism ; pathology ; Male ; Mice

Hepatic ischemia‒reperfusion injury (HIRI) is a common and inevitable complication of hepatic trauma, liver resection, or liver transplantation. It contributes to postoperative organ failure or tissue rejection, eventually affecting patient prognosis and overall survival. The pathological mechanism of HIRI is highly complex and has not yet been fully elucidated. The proposed underlying mechanisms include mitochondrial damage, oxidative stress imbalance, abnormal cell death, immune cell hyperactivation, intracellular inflammatory disorders and other complex events. In addition to serious clinical limitations, available antagonistic drugs and specific treatment regimens are still lacking. Therefore, there is an urgent need to not only clarify the exact etiology of HIRI but also reveal the possible reactions and bottlenecks of existing drugs, helping to reduce morbidity and shorten hospitalizations. We analyzed the possible underlying mechanism of HIRI, discussed various outcomes among different animal models and explored neglected potential therapeutic strategies for HIRI treatment. By thoroughly reviewing and analyzing the literature on HIRI, we gained a comprehensive understanding of the current research status in related fields and identified valuable references for future clinical and scientific investigations.

Hepatic ischemia‒reperfusion injury (HIRI) is a common and inevitable complication of hepatic trauma, liver resection, or liver transplantation. It contributes to postoperative organ failure or tissue rejection, eventually affecting patient prognosis and overall survival. The pathological mechanism of HIRI is highly complex and has not yet been fully elucidated. The proposed underlying mechanisms include mitochondrial damage, oxidative stress imbalance, abnormal cell death, immune cell hyperactivation, intracellular inflammatory disorders and other complex events. In addition to serious clinical limitations, available antagonistic drugs and specific treatment regimens are still lacking. Therefore, there is an urgent need to not only clarify the exact etiology of HIRI but also reveal the possible reactions and bottlenecks of existing drugs, helping to reduce morbidity and shorten hospitalizations. We analyzed the possible underlying mechanism of HIRI, discussed various outcomes among different animal models and explored neglected potential therapeutic strategies for HIRI treatment. By thoroughly reviewing and analyzing the literature on HIRI, we gained a comprehensive understanding of the current research status in related fields and identified valuable references for future clinical and scientific investigations.

Hepatic ischemia‒reperfusion injury (HIRI) is a common and inevitable complication of hepatic trauma, liver resection, or liver transplantation. It contributes to postoperative organ failure or tissue rejection, eventually affecting patient prognosis and overall survival. The pathological mechanism of HIRI is highly complex and has not yet been fully elucidated. The proposed underlying mechanisms include mitochondrial damage, oxidative stress imbalance, abnormal cell death, immune cell hyperactivation, intracellular inflammatory disorders and other complex events. In addition to serious clinical limitations, available antagonistic drugs and specific treatment regimens are still lacking. Therefore, there is an urgent need to not only clarify the exact etiology of HIRI but also reveal the possible reactions and bottlenecks of existing drugs, helping to reduce morbidity and shorten hospitalizations. We analyzed the possible underlying mechanism of HIRI, discussed various outcomes among different animal models and explored neglected potential therapeutic strategies for HIRI treatment. By thoroughly reviewing and analyzing the literature on HIRI, we gained a comprehensive understanding of the current research status in related fields and identified valuable references for future clinical and scientific investigations.

Hepatic ischemia‒reperfusion injury (HIRI) is a common and inevitable complication of hepatic trauma, liver resection, or liver transplantation. It contributes to postoperative organ failure or tissue rejection, eventually affecting patient prognosis and overall survival. The pathological mechanism of HIRI is highly complex and has not yet been fully elucidated. The proposed underlying mechanisms include mitochondrial damage, oxidative stress imbalance, abnormal cell death, immune cell hyperactivation, intracellular inflammatory disorders and other complex events. In addition to serious clinical limitations, available antagonistic drugs and specific treatment regimens are still lacking. Therefore, there is an urgent need to not only clarify the exact etiology of HIRI but also reveal the possible reactions and bottlenecks of existing drugs, helping to reduce morbidity and shorten hospitalizations. We analyzed the possible underlying mechanism of HIRI, discussed various outcomes among different animal models and explored neglected potential therapeutic strategies for HIRI treatment. By thoroughly reviewing and analyzing the literature on HIRI, we gained a comprehensive understanding of the current research status in related fields and identified valuable references for future clinical and scientific investigations.