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Chansu has demonstrated adverse reactions in clinical settings, which is associated with its toxicity and limits its clinical applications. But there are methodological limitations for drug safety evaluation. In the current study, ultra-high performance liquid chromatography, lipidomic profiling, and molecular docking were used to systemically assess Chansu-induced acute inflammatory irritation and further identify the underlying drug targets. Compared with the EtOAc extract, Chansu water fraction containing indolealkylamines caused acute inflammatory irritation in rats, including acute pain (spontaneous raising foot reaction), and inflammation (paw edema). At the molecular level, lipids analysis revealed significantly higher levels of pro-inflammatory mediators of the COX and LOX pathways. However, anti-inflammatory mediators from the CYP 450, ALA, and DHA pathways markedly decreased after exposure to Chansu water fraction. Moreover, four indolealkylamines from Chansu showed a high theoretical affinity to a known irritation target, 5-HT
Subject(s)
Animals , Rats , Bufanolides , Edema/drug therapy , Inflammation , Lipidomics , Molecular Docking Simulation , WaterABSTRACT
Objective To evaluate the efficacy and safety of Chansu injection (CHS) combined with EOAP regimen in patients with advanced non-Hodgkin lymphoma (NHL).Methods 65 patients with advanced NHL were divided into two groups according to random number table.All were given EOAP regimen (VP16 60 mg/m2 on d 1-5;VCR 1.4 mg/m2 on d1;Ara-C 60 mg/m2,Q12 h,on d 1-5;Pred 60 mg/m2 on d 1-5),and the observation group received EOAP combined with CHS (20 ml/d,intravenous drip,on d 1-14).The regimen was repeated every 21 days.The efficacy and toxicity were evaluated after two cycles.Results The effective rate of the observation group was higher than that of the control group,but there was no significant difference between two groups [87.9 ％ (29/33) vs 81.3 ％ (26/32),P ＞ 0.05].The quality of life of the observation group was superior to that of the control group,and there was significant difference (P ＜ 0.05).Hematological toxicities and gastrointestinal tract reaction were the main side effects in both groups.The incidence of myelosuppression of the observation group was significantly lower than that of the control group (P ＜ 0.05).Conclusion Chansu injection combined with EOAP regimen can enhance the efficacy,reduce toxicity and improve the quality of life in the treatment of advanced NHL.
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AS a result of a better understanding,people pay increasing attention to the adverse effect of traditional Chinese medicine. Chansu as a rare Chinese traditional medicine has been widely used in clinical treatment and known to have cardiotoxicity. The mechanism and relationships with blood drug concentrations need to be elucidated urgently. Bufadienolides,whose chemical structure is similar to that of digoxigenin,are the major component of Chansu and also belong to cardiac glycosides. They show both excitation and inhibition effects on the heart. Myocardial cells can not only be excited to trigger tachycardia and rapid arrhythmias at a low dose,but inhibited to induce heart block and slow arrhythmias at a high dose. As the key regulator of intracellular energy and calcium ion concentration , Na+/K+ATPase can be inhibited by bufadienolides through a combination of alpha subunits of the enzyme , resulting in calcium overload and energy disorders in myocardial cells. This might be the main mechanism of cardiotoxicity. In this paper,the progress in experimental research of substances of cardiotoxicity,animal tests,enzyme and ion channel,lipid metabolism and ion homeostasis,correlations between pharma?cokinetics and cardiotoxicity are reviewed.
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Objective To study the changes of gene expression profiling in HL-60 cells treated by Chan'su, and the possible mechanisms of Chan'su-induced apoptosis in HL-60 cells. Methods Apoptosis was determined by morphology and agarose gel electrophoresis of DNA fragmentation. The changes of gene expression profiling were detected with DNA microarray. Results 1%(v/v) Chan'su could obviously induce HL-60 cells apoptosis. In the tested 1152 genes, mRNA expression levels of 9 genes changed prior to apoptosis in Chan'su-treated HL-60 cells. Of the 9 genes, 8 gene mRNA levels were up-regulated and 1 gene mRNA level was down-regulated. Conclusion Apoptosis in HL-60 cells treated by Chan'su was involved in many genes. Bcl-2 down-regulation and IL-8 up-regulation were closely correlated with the Chan'su-induced HL-60 cells apoptosis.
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AIM: To establish the method for quality control of Chansu Tongbi Ointment(Venenum Bufonis,Borneolum Syntheticum,Radix Stephanial Tetrandrae etc.) METHODS: Radix Stephaniae Tetrandrae in Chansu Tongbi Ointment was identified by TLC,and the content of cinobufagin and resibufogenin were determined by HPLC. RESULTS: Radix Stephaniae Tetrandrae could be identified by TLC.Cinobufagin showed a good linear relationship at the range of 1.15 ?g-5.75 ?g,r=0.999 7.The RSD of measurement precision test was 1.05%,The average recovery was 97.95%(RSD=1.63%,n=5).Resibufogenin showed a good linear relationship at the range of 1.05 ?g-5.25 ?g,r=0.999 6.The RSD of measurement precision test was 1.02%,The average recovery was 97.45%(RSD=0.61%,n=5. CONCLUSION: The method is accurate,reliable and available with a reproducibility and can be used to control the quality of this ointment effectively.
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AIM: To investigate the pbarmacokinetics of lyophilization of toad venom(Venenum Bufouis)-loaded solid lipid nanoparticles(Vs-SLN). METHODS: Cinobufagin and resibufogenin plasma concentration in rat was determined by RP-HPLC. RESULTS: Statistic test showed that there was significant difference between lyophilization of Vs-SLN and Vs-injection for C_(max)、 AUC_(extra)、 MRT. CONCLUSION: As the circulating time of the drug in blood was markedly prolonged,Vs-SLN can be developed to a novel preparation for controlled release of lipophilic drugs.