Study On Pharmacodynamics And Pharmacokinetics Of Brucine In Liver Cancerous Pain

ObjecticeStrychnos nux-vomical as traditional Chinese medicine has a long history.Now it is preferably used for the treatment of traumatic injury,ulcer,nervous system disease and rheumatoid disease in clinic.Brucine,the main alkaloid monomer of nux vomica,is not only active but also toxic ingredient,and its therapeutic dose and toxic dose is very close.Modern pharmacological studies showed that brucine has good anti-tumor activity.The mechanisms of the anti-tumor may be associated with its effect on inducing tumor cells apoptosis,anti-angiogenesis,reversing cancer multidrug resistance and regulating the expression of a variety of cytokines.In this paper,the distribution of drug in mice,pharmacokinetics and the effect on cancer pain is studied to evaluate the anti-tumor effect of brucine.Methods1.H₂₂hepatocarcinoma mice model was established,and drug concentration of brucine in head,heart,liver,spleen,lung,kidney and tumor tissue of mice after oral administration was determined by HPLC,to study distribution of brucine in mice and evaluate targeting property by researching the pharmacokinetic parameters.2.To determine brucine in rat plasma at different points in time by HPLC after oral administration?po?,intramuscular injection?im?,subcutaneous injection?ih?,intravenous injection?iv?of brucine liposome respectively.Compare the pharmacokinetic differences of brucine in rats after different administration methods of brucine liposome.3.Cancerouspainwasinducedwithdiethylnitrosamine,carbon tetrachloride?CCl₄?and olive oil in mice.The pain thresholds of the two sides of each group were measured by hot plate method,to observe the effect of brucine on the pain of cancer.Results1.The result of the anti-hepatoma targeting of brucine research shows that the content of brucine in heart,liver and spleen tissue with rich blood were higher than other tissues,and the content gradually reduced after 60min.Comparison with the content of brucine in the tumor tissue at different time points,the concentration ratio of brucine was 16.22,18.73,21.27,24.23and 25.67%at 10,30,60,90,120 min,respectively.The target parameters of tumor tissue reached 21.45%,which were higher than other tissues except liver?27.90%?and cardiac?23.73%?.2.Compared with other groups,AUC_0-tof ih were higher,Cmax were lower and MRT_0-twere significantly improved.3.The result of the effect of brucine on cancer pain shows that,compared with the blank control groups,model control groups could prolong the time of pain licking significantly?P<0.01?;compared with the model control groups,tramadol groups and brucine high dose groups could prolong the time of pain licking significantly?P<0.01?,the next was brucine middle dose groups;The pain threshold value in positive control groups and brucine high dose groups increased more than 35%,and brucine middle dose groups increased 16.8%.ConclusionBrucine has a wide distribution in mice and the content of brucine was high in heart,liver and spleen tissues.Brucine can penetrate the blood brain barrier into the brain tissue,and has a targeted migration on tumor tissues;The pharmacokinetics parameters and absolute bioavailability of brucine shows that bioavailability in rats after different administration methods of brucine liposome is ih?iv>im>po;Brucine can reduce pain threshold of mice induced by DEN-CCl₄-Olive Oil,so that plays the role of reducing the cancer pain.The results can provide theoretical basis for the further studies on the antitumor activity of brucine and Nux vomica preparations in clinical application.