Attenuation and synergism of Hugan buzure recipe combined with oxaliplatin on hepatocellular carcinoma tumor bearing nude mice and its mechanism / 中国药房

OBJECTIVE To investigate the attenuation and synergism of Hugan buzure recipe （HBR） combined with oxaliplatin on hepatocellular carcinoma tumor bearing nude mice and its mechanism. METHODS Eight nude mice were selected from 40 nude mice as the blank group （normal saline）， and the remaining nude mice were inoculated with hepatoma cells Huh7 to establish the tumor-bearing model. The 32 modeled nude mice were randomly allocated to four groups： model group （normal saline， ig）， HBR group （0.69 g/kg， ig）， oxaliplatin group （10 mg/kg， ip）， and combination group （intraperitoneal injection of 0.69 g/kg HBR+intragastric administration of 10 mg/kg oxaliplatin）， with 8 mice in each group. Administer drug/normal saline once a day for 32 consecutive days； administer subcutaneous injection once every 7 days for a total of 5 times. During the experiment， the general condition of nude mice in each group was observed， and the tumor volume was measured every 4 days. On the 30th day of administration， the thermal stimulation paw withdrawal latency of nude mice in each group were detected. The tumor inhibition rate， spleen coefficient， the number of red blood cells， white blood cells and platelets in the whole blood of nude mice in each group， and the content of aspartate aminotransferase （AST） and creatinine in serum were detected after the end of administration. HE staining was used to observe the pathological changes in tumor tissues in nude mice in each group. The expression of microtubule-associated protein 1 light chain 3 （LC3），selective autophagy adaptor protein p62， B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， and Caspase-3 protein in tumor tissues. RESULT Compared with the model group， the tumor volume， tumor weight， white blood cells，red blood cells in the whole blood and spleen coefficients of nude mice in the oxaliplatin group were significantly decreased （P＜0.01）； the thermal stimulation paw withdrawal latency， AST and creatinine in serum were significantly increased （P＜0.05 or P＜0.01）. Compared with the oxaliplatin group， the tumor volume and tumor weight of nude mice in the combination group were significantly decreased （P＜0.01）； the white blood cells， red blood cells and platelets in the whole blood and spleen coefficients of nude mice were significantly increased （P＜0.05 or P＜0.01）； the thermal stimulation paw withdrawal latency， AST and creatinine in serum were significantly decreased （P＜0.01）； the expression levels of LC3， Bax and Caspase-3 proteins in tumor tissues of nude mice were significantly increased （P＜0.01）， and the expression levels of p62 and Bcl-2 proteins were significantly decreased （P＜0.01）. CONCLUSIONS HBR enhances the tumor inhibition rate of oxaliplatin by inducing apoptosis and autophagy， and can alleviate the peripheral neurotoxicity， hematological toxicity， hepatorenal toxicity， and immune organ toxicity caused by oxaliplatin in nude mice.

Effects of Different Processed Methods on Anti-gouty Arthritis and Cardiotoxicity of Aconiti Radix / 中国实验方剂学杂志

Objective:To study the effects of different processing methods on the anti-gouty arthritis and cardiotoxicity of Aconiti Radix， and to explore the possible attenuation and synergism mechanism of these different processing methods. Method:The swelling degree of knee joint， levels of inflammatory factors ［interleukin （IL） -1<italic>β</italic>， IL-18， tumor necrosis factor （TNF）-<italic>α</italic>］ and the activities of liver energy metabolism-related enzymes ［Ca²⁺-Mg²⁺-adenosine triphosphatase （ATPase）， Na⁺-K⁺-ATPase， succinate dehydrogenase （SDH）］ in rats with gouty arthritis were used as indicators to evaluate the effects of pharmacopoeia steaming Aconiti Radix， pharmacopoeia boiling Aconiti Radix， Jianchang faction processed Aconiti Radix， Zhang faction processed Aconiti Radix and raw Aconiti Radix. The activity of creatine kinase （CK）， lactate dehydrogenase （LDH） and the content of B-type natriuretic peptide （BNP） were used as indexes to evaluate the cardiotoxicity of Aconiti Radix and its different processed products. Result:In the anti-gouty arthritis test， compared with the blank group， the knee joint of the model group was significantly swollen （<italic>P</italic><0.01）， the levels of IL-1<italic>β</italic>， IL-18， and TNF-<italic>α</italic> in serum were significantly increased （<italic>P</italic><0.01）， and the Ca²⁺-Mg²⁺-ATPase activity was significantly decreased （<italic>P</italic><0.01）. Compared with the model group， raw Aconiti Radix and the four processed products could reduce knee joint swelling and decrease IL-1<italic>β</italic>， IL-18， and TNF-<italic>α</italic> levels in serum of rats. The activity of Ca²⁺-Mg²⁺-ATPase in the liver of rats from the pharmacopoeia steaming Aconiti Radix group was significantly higher than that in the model group （<italic>P</italic><0.01）， and there was no statistical difference in other groups. In the cardiotoxicity test， compared with the blank group， the activities of CK and LDH were significantly increased and the level of BNP was significantly increased in the raw Aconiti Radix group and the pharmacopoeia steaming/boiling Aconiti Radix groups （<italic>P</italic><0.01）. In terms of LDH activity and BNP content， the Zhang faction and Jianchang faction processed Aconiti Radix groups were significantly lower than those in the raw Aconiti Radix group （<italic>P</italic><0.01）. In the CK activity， the Zhang faction processed Aconiti Radix group was significantly lower than that in the raw Aconiti Radix group （<italic>P</italic><0.01）. Conclusion:Raw Aconiti Radix and the four processed products have certain anti-inflammatory effects， but there are some differences among different indicators. There are significant differences in cardiotoxicity between the raw products and processed products of Aconiti Radix， and the cardiotoxicity of Jianchang faction and Zhang faction processed products was the weakest.

Experimental Studies on Attenuating and Synergic effects of Modified Yigong Powder / 中药新药与临床药理

Objective To observe the effects of modified Yigong Powder (MYP) combined with chemotherapy on transplanted hepatocarcinoma of mice and to study its mechanisms. Methods Hepatocarcinoma 22 mouse model was established and then was used to observe the attenuating and synergic effects of MYP when applied together with 5-fluorouracil (5-FU). After 8 days of treatment,the tumor-inhibiting rate,activity of natural killer (NK)cells and interleukin-2 (IL-2) and small intestinal malondialdehyde (MDA) content were examined. Results MYP combined with 5-FU could increased the tumor-inhibiting rate to some extent and improve the immune function by increasing immune organ weight and increasing the activity of NK cells and IL-2. MYP combined with 5-FU could also reduce the 5-FU-induced intestinal injuries by relieving the damage of free radicals and inhibiting the lipid peroxidation and a good prognosis was expected in tumor-bearing animals treated with chemotherapy. Conclusion MYP exerts an attenuating and synergic effect when used together with 5-FU in treating tumor-bearing mice and its mechamism may be related to the improvement of immune function and reduction of intestinal injuries.