To evaluate whether Shenfu injection （SFI） protects against cardiac myocyte injury induced by Fupian injection （FPI） in vitro. METHODS： H9c2 cells were separately treated with FPI, Renshen injection （RSI） and S...To evaluate whether Shenfu injection （SFI） protects against cardiac myocyte injury induced by Fupian injection （FPI） in vitro. METHODS： H9c2 cells were separately treated with FPI, Renshen injection （RSI） and SFI. Cell viability, lactate dehydrogenase （LDH） release, spontaneous beating rate of primative cardical cells, caspase-3/7 activity, cell apoptosis, and cytochrome P450 2J3 （CYP2J3） mRNA expression were analyzed. RESULTS： The viability of H9c2 cells treated with SFI （37 and 75 mg/mL） was significantly higher than that of H9c2 cells treated with FPI （25 and 50 mg/mL） （P〈0.05, P〈0.01, respectively）. LDH activity of H9c2 cells treated with SFI （75 mg/mL） was significantly decreased （P〈0.01） compared with that of H9c2 cells treated with FPI （50 mg/mL）. SFI （150 mg/mL） significantly attenuated FPI （100 mg/mL）-induced spontaneous beating rate decrease in primary myocardial cells after 4-hour treatment. Compared with FPI （12 and 25 mg/mL）, SFI （18 and 37 mg/mL） treatment could effectively reverse the change of caspase-3/7 activity （P〈0.01 and P〈0.01, respectively）. Compared with FPI （6 and 25 mg/mL）, apoptotic cells decreased significantly （P〈0.05, P〈0.01, respectively） when H9c2 cells were incubated with SFI （9 and 37 mg/mL）. The expression of CYP2J3 mRNA was down-regulated by FPI, while RSI and SFI could up-regulate the expression of CYP2J3 （P〈0.01）, which suggested the potential mechanism of protection of RSI against cardiac myocyte damage induced by FPI treatment. CONCLUSION： These observations indicate that SFI has the potential to exert cardioprotective effects against FPI toxicity. The effect was possibly correlated with the activation of CYP2J3.展开更多
Objective：Realgar–Indigo Naturalis formula（RIF）is a well-known arsenic-containing preparation that is used to treat acute promyelocytic leukemia（APL）in China.In recent multicenter clinical trials,complete remiss...Objective：Realgar–Indigo Naturalis formula（RIF）is a well-known arsenic-containing preparation that is used to treat acute promyelocytic leukemia（APL）in China.In recent multicenter clinical trials,complete remission rates in APL patients have ranged from 96.08%to 100%.RIF has a satisfactory therapeutic effect,but its safety is a widespread concern,since the preparation contains arsenic,a wide-ranging and naturally occurring toxicant.In this study,in order to determine the toxic potential of RIF,acute toxicity and sub chronic toxicity assays were performed to evaluate the toxic potential of Realgar and the adjuvant components of RIF in addition to Realgar’s synergy with these adjuvant components.Methods：KM mice and Wistar rats were selected for these experiments.To evaluate acute toxicity,the toxic effects of a single dose of a gradient of concentrations of Realgar were firstly determined.Then,the toxic effects of combinations of gradient doses of Realgar and fixed doses of Indigo naturalis and Salvia miltiorrhiza were evaluated.Results：The results showed that when Realgar was used alone,the2756.73 mg/kg（equivalent to 23.6 mg/kg）.However,theto 936.90 mg/kg when Realgar was used with I.naturalis.By contrast,theto 7538.86 mg/kg when Realgar was used with S.miltiorrhiza.Hence,I.naturalis strengthened the toxicity of Realgar,whereas S.miltiorrhiza displayed the opposite effect.The sub chronic toxicity assessment results revealed a trend that was consistent with acute toxicity.Changes in the levels of different valence states of arsenic were also taken into account.The test results of the effects of in vitro combinations of Realgar and adjuvant components on soluble arsenic dissolution showed that I.naturalis increased the level of soluble arsenic in Realgar extracts and I.naturalis suspensions when the Realgar/I.naturalis ratio was 2,1.5,and 1.0.However,S.miltiorrhiza did not affect it.Conclusion：Based on the collective experimental results presented here,it can be concluded that the toxicity of RIF is the result of the soluble arsenic in Realgar and that the I.naturalis and S.miltiorrhiza in the RIF exert completely opposite effects on the toxicity of Realgar.This maybe an intelligent explanation for the compatibility of this formula,and this RIF study may therefore be viewed as a classic case of traditional Chinese medicine research on compatibility.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.81274127,No.81073149)the National Basic Research Program("973 Program")of China(No.2012CB518402,No.2011CB505304)
文摘To evaluate whether Shenfu injection （SFI） protects against cardiac myocyte injury induced by Fupian injection （FPI） in vitro. METHODS： H9c2 cells were separately treated with FPI, Renshen injection （RSI） and SFI. Cell viability, lactate dehydrogenase （LDH） release, spontaneous beating rate of primative cardical cells, caspase-3/7 activity, cell apoptosis, and cytochrome P450 2J3 （CYP2J3） mRNA expression were analyzed. RESULTS： The viability of H9c2 cells treated with SFI （37 and 75 mg/mL） was significantly higher than that of H9c2 cells treated with FPI （25 and 50 mg/mL） （P〈0.05, P〈0.01, respectively）. LDH activity of H9c2 cells treated with SFI （75 mg/mL） was significantly decreased （P〈0.01） compared with that of H9c2 cells treated with FPI （50 mg/mL）. SFI （150 mg/mL） significantly attenuated FPI （100 mg/mL）-induced spontaneous beating rate decrease in primary myocardial cells after 4-hour treatment. Compared with FPI （12 and 25 mg/mL）, SFI （18 and 37 mg/mL） treatment could effectively reverse the change of caspase-3/7 activity （P〈0.01 and P〈0.01, respectively）. Compared with FPI （6 and 25 mg/mL）, apoptotic cells decreased significantly （P〈0.05, P〈0.01, respectively） when H9c2 cells were incubated with SFI （9 and 37 mg/mL）. The expression of CYP2J3 mRNA was down-regulated by FPI, while RSI and SFI could up-regulate the expression of CYP2J3 （P〈0.01）, which suggested the potential mechanism of protection of RSI against cardiac myocyte damage induced by FPI treatment. CONCLUSION： These observations indicate that SFI has the potential to exert cardioprotective effects against FPI toxicity. The effect was possibly correlated with the activation of CYP2J3.
基金supported by the Major Program of the National Natural Science Foundation of China (grant nos.82192910 and 82192911)the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine (grant nos.ZYYCXTD-D-202207 and ZYYCXTD-C-202009)。
基金financially supported by a Grant from the National Ministry of Science and Technology(no.2015ZX09501004)
文摘Objective：Realgar–Indigo Naturalis formula（RIF）is a well-known arsenic-containing preparation that is used to treat acute promyelocytic leukemia（APL）in China.In recent multicenter clinical trials,complete remission rates in APL patients have ranged from 96.08%to 100%.RIF has a satisfactory therapeutic effect,but its safety is a widespread concern,since the preparation contains arsenic,a wide-ranging and naturally occurring toxicant.In this study,in order to determine the toxic potential of RIF,acute toxicity and sub chronic toxicity assays were performed to evaluate the toxic potential of Realgar and the adjuvant components of RIF in addition to Realgar’s synergy with these adjuvant components.Methods：KM mice and Wistar rats were selected for these experiments.To evaluate acute toxicity,the toxic effects of a single dose of a gradient of concentrations of Realgar were firstly determined.Then,the toxic effects of combinations of gradient doses of Realgar and fixed doses of Indigo naturalis and Salvia miltiorrhiza were evaluated.Results：The results showed that when Realgar was used alone,the2756.73 mg/kg（equivalent to 23.6 mg/kg）.However,theto 936.90 mg/kg when Realgar was used with I.naturalis.By contrast,theto 7538.86 mg/kg when Realgar was used with S.miltiorrhiza.Hence,I.naturalis strengthened the toxicity of Realgar,whereas S.miltiorrhiza displayed the opposite effect.The sub chronic toxicity assessment results revealed a trend that was consistent with acute toxicity.Changes in the levels of different valence states of arsenic were also taken into account.The test results of the effects of in vitro combinations of Realgar and adjuvant components on soluble arsenic dissolution showed that I.naturalis increased the level of soluble arsenic in Realgar extracts and I.naturalis suspensions when the Realgar/I.naturalis ratio was 2,1.5,and 1.0.However,S.miltiorrhiza did not affect it.Conclusion：Based on the collective experimental results presented here,it can be concluded that the toxicity of RIF is the result of the soluble arsenic in Realgar and that the I.naturalis and S.miltiorrhiza in the RIF exert completely opposite effects on the toxicity of Realgar.This maybe an intelligent explanation for the compatibility of this formula,and this RIF study may therefore be viewed as a classic case of traditional Chinese medicine research on compatibility.
