Author Correction: Ophiopogonin D maintains Ca2+ homeostasis in rat cardiomyocytes in vitro by upregulating CYP2J3/ EETs and suppressing ER stress.

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Influences of Realgar-Indigo naturalis, A Traditional Chinese Medicine Formula, on the Main CYP450 Activities in Rats Using a Cocktail Method.

The purpose of this work was to study the influences of Realgar-Indigo naturalis (RIF) and its principal element realgar on 4 main cytochrome P450 enzymes activities in rats. A simple and efficient cocktail method was developed to detect the four probe drugs simultaneously. In this study, Wistar rats were administered intragastric RIF and realgar for 14 days; mixed probe drugs were injected into rats by caudal vein. Through analyzing the pharmacokinetic parameter of mixed probe drugs in rats, we can calculate the CYPs activities. The results showed that RIF could inhibit CYP1A2 enzyme activity and induce CYP2C11 enzyme activity significantly. Interestingly, in realgar high dosage group, CYP3A1/2 enzyme activity was inhibited significantly, and different dosage of realgar manifested a good dose-dependent manner. The RIF results indicated that drug coadministrated with RIF may need to be paid attention in relation to drug-drug interactions (DDIs). Realgar, a toxic traditional Chinese medicine (TCM), does have curative effect on acute promyelocytic leukemia (APL). Its toxicity studies should be focused on. We found that, in realgar high dosage group, CYP3A1/2 enzymes activity was inhibited. This phenomenon may explain its potential toxicity mechanism.

Antithrombotic activities of ferulic acid via intracellular cyclic nucleotide signaling.

Ferulic acid (FA) produces protective effects against cardiovascular dysfunctions. However, the mechanisms of FA is still not known. Here we examined the antithrombotic effects of FA and its potential mechanisms. Anticoagulation assays and platelet aggregation was evaluated in vitro and in vivo. Thromboxane B2 (TXB2), cyclic adenosine monophosphate(cAMP), and cyclic guanosine monophosphate (cGMP) was determined using enzyme immunoassay kits. Nitric oxide (NO) production was measured using the Griess reaction. Protein expression was detected by Western blotting analysis. Oral administration of FA prevented death caused by pulmonary thrombosis and prolonged the tail bleeding and clotting time in mice,while, it did not alter the coagulation parameters, including the activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). In addition, FA (50-200 µM) dose-dependently inhibited platelet aggregation induced by various platelet agonists, including adenosine diphosphate (ADP), thrombin, collagen, arachidonic acid (AA), and U46619. Further, FA attenuated intracellular Ca(2)(+) mobilization and TXB2 production induced by the platelet agonists. FA increased the levels of cAMP and cGMP and phosphorylated vasodilator-stimulated phosphoprotein (VASP) while decreased phospho-MAPK (mitogen-activated protein kinase) and phosphodiesterase (PDE) in washed rat platelets, VASP is a substrate of cyclic nucleotide and PDE is an enzyme family responsible for hydrolysis of cAMP/cGMP. These results suggest that antithrombotic activities of FA may be regulated by inhibition of platelet aggregation, rather than through inhibiting the release of thromboplastin or formation of thrombin. The mechanism of this action may involve activation of cAMP and cGMP signaling.

Ophiopogonin D maintains Ca2+ homeostasis in rat cardiomyocytes in vitro by upregulating CYP2J3/EETs and suppressing ER stress.

AIM: CYP2J3 in myocardium metabolizes arachidonic acid to 4 regioisomeric epoxyeicosatrienoic acids (EETs), which have diverse biological activities in rat heart. In this study we examined whether CYP2J3 was involved in cardioprotective effects of ophiopogonin D (OPD), a steroidal glycoside isolated from Chinese herb Radix ophiopogonis. METHODS: Rat cardiomyoblast cell line (H9c2 cells) was tested. Intracellular Ca(2+) concentrations ([Ca(2+)]i) were measured using Fluo-4/AM. The expression of calcium-regulating molecules and ER stress signaling molecules was measured with qRT-PCR and Western blot analyses. Cell apoptosis was quantified with Hoechst 33258 staining and TUNEL assay. The level of 14,15-DHET, a stable metabolite of 14,15-EET, was assessed with ELISA. RESULTS: Angiotensin II (10(-6) mol/L) significantly decreased the expression of calcium-regulating molecules (SERCA2a, PLB, RyR2 and FKBP12.6), and elevated [Ca(2+)]i in H9c2 cells. Furthermore, angiotensin II markedly increased the expression of ER stress signaling molecules (GRP78, CHOP, p-JNK and cleaved caspase-12) and ER stress-mediated apoptosis. OPD (100, 250 and 500 nmol/L) dose-dependently increased CYP2J3 expression and 14,15-DHET levels in normal H9c2 cells. Pretreatment of H9c2 cells with OPD suppressed angiotensin II-induced abnormalities in Ca(2+) homeostasis, ER stress responses and apoptosis. Overexpression of CYP2J3 or addition of exogenous 14,15-EET also prevented angiotensin II-induced abnormalities in Ca(2+) homeostasis, whereas transfection with CYP2J3 siRNA diminished the effects of OPD on Ca(2+) homeostasis. Furthermore, the intracellular Ca(2+) chelator BAPTA suppressed angiotensin II-induced ER stress responses and apoptosis in H9c2 cells. CONCLUSION: OPD is a novel CYP2J3 inducer that may offer a therapeutic benefit in treatment of cardiovascular diseases related to disturbance of Ca(2+) homeostasis and ER stress.

Ginkgolide B protects human umbilical vein endothelial cells against xenobiotic injuries via PXR activation.

AIM: Pregnane X receptor (PXR) is a nuclear receptor that regulates a number of genes encoding drug metabolism enzymes and transporters and plays a key role in xeno- and endobiotic detoxification. Ginkgolide B has shown to increase the activity of PXR. Here we examined whether ginkgolide B activated PXR and attenuated xenobiotic-induced injuries in endothelial cells. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with ginkgolide B. The expression of PXR, CYP3A4, MDR1, VCAM-1, E-selectin and caspase-3 were quantified with qRT-PCR and Western blot analysis. Cell apoptosis was analyzed with flow cytometry. Fluorescently labeled human acute monocytic leukemia cells (THP-1 cells) were used to examine cell adhesion. RESULTS: Ginkgolide B (30-300 µmol/L) did not change the mRNA and protein levels of PXR in the cells, but dose-dependently increased nuclear translocation of PXR protein. Ginkgolide B increased the expression of CYP3A4 and MDR1 in the cells, which was partially reversed by pretreatment with the selective PXR signaling antagonist sulforaphane, or transfection with PXR siRNA. Functionally, ginkgolide B dose-dependently attenuated doxorubicin- or staurosporine-induced apoptosis, which was reversed by transfection with PXR siRNA. Moreover, ginkgolide B suppressed TNF-α-induced THP-1 cell adhesion and TNF-α-induced expression of vascular adhesion molecule 1 (VCAM-1) and E-selectin in the cells, which was also reversed by transfection with PXR siRNA. CONCLUSION: Ginkgolide B exerts anti-apoptotic and anti-inflammatory effects on endothelial cells via PXR activation, suggesting that a PXR-mediated endothelial detoxification program may be important for protecting endothelial cells from xeno- and endobiotic-induced injuries.

[3D evaluation model for drug hepatotoxicity testing on HepG2 cells and its application in drug safety evaluation].

3D in vitro toxicity testing model was developed by magnetic levitation method for culture of the human hepatoma cell line HepG2 and applied to evaluate the drug hepatotoxicity. After formation of stable 3D structure for HepG2 cells, their glycogen storage capacity under 2D and 3D culture conditions were detected by immunohistochemistry technology, and the mRNA expression levels of phase Ⅰ and Ⅱ drug metabolism enzymes, drug transporters, nuclear receptors and liver-specific marker albumin(ALB) were compared between 2D and 3D culture conditions by using RT-PCR method. Immunohistochemistry results showed that HepG2 cells had abundant glycogen storage capacity under 3D culture conditions, which was similar to human liver tissues. The mRNA expression levels of major drug metabolism enzymes, drug transporters, nuclear receptors and ALB in HepG2 cells under 3D culture conditions were up-regulated as compared with 2D culture conditions. For drug hepatotoxicity evaluation, the typical hepatotoxic drug acetaminophen(APAP), and most reported drugs Polygonum multiflorum Thunb.(Chinese name He-shou-wu) and Psoraleae corylifolia L.(Chinese name Bu-gu-zhi) were selected for single dose and repeated dose(7 d) exposure. In the repeated dose exposure test, 3D HepG2 cells showed higher sensitivity. This established 3D HepG2 cells model with magnetic levitation 3D culture techniques was more close to the human liver tissues both in morphology and functions, so it was a better 3D hepatotoxicity evaluation model.

[Effects of aqueous extract of Cassiae Semen on activity hepatic microsomal CYP450 isozymes in rats].

To study the effect of aqueous extract of Cassiae Semen on the activity, mRNA and protein expressions of cytochrome P450(CYP450) system in rat liver microsomes, microsomes of rat liver were prepared after the oral administration with aqueous extract of Cassiae Semen for 14 days. The enzyme activity was quantified by Cocktail method. Meanwhile, the mRNA and protein expressions of CYP1A2, CYP2B1, CYP2C11, CYP2D2, CYP2E1 and CYP3A1 in the livers were detected by RT-PCR and Western blot. The result of this experiment was that aqueous extract of Cassiae Semen obviously induced the enzyme activities of CYP1A2, CYP2B1, CYP2C11, CYP2D2, CYP2E1 and CYP3A1. Low dose of aqueous extract of Cassiae Semen significantly reduced the activity of CYP2D2, but the activity of CYP2D2 was significantly induced by middle dose and high dose of aqueous extract of Cassiae Semen. These subtypes were increased in a dose-dependent manner except for CYP3A1. The mRNA levels of CYP1A2, CYP2C11, CYP2D2 and CYP2E1 were also induced in rats treated with aqueous extract of Cassiae Semen, but with no significant effect in CYP2B1 and CYP3A1 mRNA expressions. The protein levels of CYP2C11 and CYP2E1 were also induced in rats treated with aqueous extract of Cassiae Semen, but with no significant difference. Since the enzyme activity, mRNA and protein expressions of CYP450, particularly CYP2C11and2E1subtypes, were induced or inhibited by aqueous extract of Cassiae Semen to varing degrees, suggesting the potential drug-drug interactions should be concerned.

[Effects of Reduning injection on activity of hepatic microsomal CYP450 isozymes in rats].

To research the influence of Reduning injection on the activity and mRNA expression of cytochrome P450 (CYP450) system in rat liver microsomes. Rat liver microsomes were prepared after a seven-days continuous administration of Reduning injection. An HPLC-MS method was applied to determine the specific metabolites of CYP450 probe substrates in rat liver microsomal incubations. The activity of CYP450 isozymes were represented by the formation of metabolites. The Real-time quantitative polymerase chain reaction (Q-PCR) was applied to determine the mRNA expression levels of CYP450. Reduning injection significantly reduced the activity of CYP2B1, 2C12, 2C13 (P < 0.01), but did not affect CYPlA2; low dose and high dose of Reduning injection had an inhibition trend on the activity of CYP2D2, but did not statistically differ from control group; low dose of Reduning injection significantly induced the activity of CYP3A1 (P < 0.01), high dose of Reduning injection had an induce trend on the activity of CYP3A1, but did not statistically differ from control. At the mRNA level, low and high dose of Reduning injection had an induce trend on the expression of CYP1A2, 2C11, 2D1, 2E1, 3A1, but did not statistically differ from control. Reduning injection significantly induced the activity of CYP2B1. Reduning injection significantly induced the activity of CYP3A1 in mRNA expression and enzyme activity levels, which may result adverse drug reaction after being combined with macrolides antibiotics. Reduning injection significantly reduced the activity of CYP2B1, 2C12, 2C13, 2D2 in enzyme activity levels, when combined with other drugs, it should be fully taken into account of the possible drug-drug interaction in order to avoid adverse side effects.

[Cardiotoxicity study of Shenfu compatibility in rats based on metabonomics].

To research the effect of Ginseng Radix et Rhizoma and Aconiti Lateralis Radix Praeparata compatibility on cardiac toxicity in rats by UPLC-Q-TOF/MS, and explore the endogenous markers and molecule mechanism. Different compatibility of Shenfu decoction were given to male Wistar rats at dosage of 20 g · kg(-1) for 7 days, collected the serum, and analyze the endogenous metabolites effected by Shenfu formulation by principal component analysis and partial least-squares analysis. Results showed that content of glutathione, phosphatidylcholine and citric acid decreased in mixed-decoction group, while ascorbic acid, uric acid, D-galactose, tryptophan, L-phenylalanine increased. The results showed cardiac toxicity of Aconiti Lateralis Radix Praeparata in Shenfu mixed-decoction. Shenfu co-decoction group showed a similar or weaker trend compared with control group, but most of them do not have a statistically significant. The results indicated the scientific basis of Shenfu compatibility by comparison of co-decoction group with mixed-decoction group. Shenfu compatibility can reduce cardiac toxicity induced by Aconiti Lateralis Radix Praeparata, and citric acid, glutathione, phosphatidyl choline, uric acid might be regarded as potential markers of cardiotoxicity.

[Preliminary study on hepatotoxicity induced by dioscin and its possible mechanism].

Dioscin has a wide range of biological effects and broad application prospects. However the studies concerning the toxicology and mechanism of dioscin is small. This article is to study the hepatotoxicity of dioscin and the effect of dioscin treatment on expression of aryl hydrocarbon receptor (AhR) mRNA and CYP1A mRNA and protein in HepG2 cells in vitro. Dioscin 0.5-32 µmol · L(-1) exposed to HepG2 cells for 12 h, cell viability was examined by CCK-8 assay and the release rate of lactate dehydrogenase (LDH) was to evaluate cell membrane damage. HepG2 cells morphologic changes were quantified by inverted Microscope, and the effect on production of reactive oxygen species (ROS) was detected by flow cytometry. The mRNA expression of CYP1A and AhR was evaluated by RT-RCR. The protein expression of CYP1A1 was detected by western blot. The cell viability was significantly inhibited after HepG2 cells were exposed to dioscin 0.5-32 µmol · L(-1). Compared with the control, the LDH release rate and ROS were significantly increased. The expression of CYPlA and AhR mRNA was increased. The expression of CYP1Al protein was increased after dioscin treatment, and resveratrol, an AhR antagonist, could downregulate the expression of CYP1A1. It follows that large doses dioscin has potential hepatotoxicity. The possible mechanism may be dioscin can active aryl hydrocarbon receptor (AhR) and induce the expression of CYP1A.

Serum Pharmacochemistry Analysis Using UPLC-Q-TOF/MS after Oral Administration to Rats of Shenfu Decoction.

The purpose of this study was to study the serum pharmacochemistry of SFD as well as the material basis through analyzing the constituents absorbed in blood. The SFD was orally administrated to Wistar rats at 20 g·kg(-1), and Ultra Performance Liquid Chromatography (UPLC) fingerprints of SFD were created. Serum samples were collected for analysis, and further data processing used MarkerLynx XS software. 19 ginsenosides and 16 alkaloids were detected in SFD. The absorption of alkaloids (mainly monoester diterpenoid alkaloids) increased when Aconitum carmichaeli Debx. was combined with Panax ginseng, while the ginsenosides remained stable. Diester diterpenoid alkaloids were not present in the serum samples. A suitable serum pharmacochemistry method was successfully established to study pharmacological effects and potential improvements in formulation. This may also be useful for toxicity reduction. We suspect that the increased absorption of the monoester diterpenoid alkaloids from the mixture of Panax and Radix, compared to the Panax only extract, may be the reason for the combination of the two herbs in popular medicine formulas in China.

Panax ginseng inhibits intestinal absorption of toxic Aconitum carmichaeli alkaloids in Vitro.

OBJECTIVE: To evaluate the rationality and compatibility of Shenfu Formula (, SFF), a typical Chinese medicine (CM) comprised of Panax ginseng and Aconitum carmichaeli. METHODS: Caco-2 cells were used to study the permeability of Aconitum carmichaeli marker compounds when the CM preparation was combined with Panax ginseng. P-glycoprotein (P-gp) activity and protein as well as multidrug resistance 1 (MDR1) mRNA were analyzed with rhodamine123 efflflux, western blot and real time quantitative polymerase chain reaction. RESULTS: Aconitine (AC), mesaconitine (MA), hypaconitine (HA) and fifive other active alkaloids in Aconitum carmichaeli were selected as marker compounds. Panax ginseng inhibited intestinal absorption of highly toxic AC, MA and HA from Aconitum carmichaeli in Caco-2 cells. P-gp and breast cancer resistance protein (BCRP) were observed to be involved in AC, MA and HA efflflux. Panax ginseng induced P-gp activity in Caco-2 cells via increased MDR1/P-gp expression. Thus, Panax ginseng facilitated P-gp-mediated efflflux of toxic Aconitum carmichaeli alkaloids and restricted their intestinal absorption without inflfluencing other active components. CONCLUSION: Future studies to elucidate mechanism of reduced toxicity of Aconitum carmichaeli when combined with Panax ginseng will guide future formula optimization.

Ferulic acid alleviates Aß25-35- and lipopolysaccharide-induced PC12 cellular damage: a potential role in Alzheimer's disease by PDE inhibition.

OBJECTIVE: Phosphodiesterase (PDE) plays an important role in the pathogenesis of Alzheimer's disease (AD). Ferulic acid (FA) has a therapeutic benefit in the treatment of AD. We investigated whether this therapeutic effect is based on the modulation of the PDE/cyclic adenosine monophosphate (cAMP) pathway. In the present study, we investigated whether FA could abrogate Aß25-35- and lipopolysaccharide-induced cellular damage. MATERIALS AND METHODS: Cell viability, superoxide production, and the levels of inflammatory factors were investigated. We further investigated the intracellular levels of cAMP and Ca2+, both of which are associated with PDE activity. Furthermore, molecular docking was used to identify the binding mode between phosphodiesterase 4B2 (PDE4B2) and FA. RESULTS: Pretreatment with FA significantly maintained cell viability, increased the levels of superoxide dismutase, and inhibited production of TNF-α and IL-1ß induced by Aß25-35. Moreover, pretreatment with FA increased the intracellular levels of cAMP and decreased the intracellular levels of Ca2+. The docking results also showed that FA has the potential to inhibit PDE4B2 activity. CONCLUSIONS: Taken together, our results suggested that one of the therapeutic effects of FA on AD was potentially mediated by modulating the PDE/cAMP pathway.

[Effect of Siwu decoction on function and expression of P-glycoprotein in Caco-2 cells].

To study the effect of Siwu decoction on the function and expression of P-glycoprotein (P-gp) in Caco-2 cells. The Real-time quantitative poly-merase chain reaction (Q-PCR) was used to analyze the mRNA expression of MDR1 gene in Caco-2 cells. Flow cytometer was used to study the effect of Siwu decoction on the uptake of Rhodamine 123 in Caco-2 cells, in order to evaluate the efflux function of P-gp. Western blotting method was used to detect the effect of Siwu decoction on the P-gp protein expression of Caco-2 cells. Compared with the blank control group, after Caco-2 incubation with Siwu decoction at concentrations of 3.3, 5.0, 10.0 g x L(-1) for 24, 48, 72 h, the mRNA expression of MDR1 was up-regulated, suggesting the effect of Siwu decoction in inducing the expression of MDR1. After the administration with Siwu decoction in Caco-2 cells for 48 h, the uptake of Rhodamine 123 in Caco-2 cells decreased by respectively 16.6%, 22.1% (P < 0.05) and 45.4% (P < 0.01), indicating that the long-term administration of Siwu decoction can enhance the P-gp efflux function of Caco-2 cells. After the incubation of Caco-2 cells with Siwu decoction for 48 h, the P-gp protein expression on Caco-2 cell emebranes, demonstrating the effect of Siwu decoction in inducing the protein expression of P-gp.

[Pharmacology research on PXR as a potential target in screening bioactive components of Chinese material medica].

Pregnane X receptor (PXR) is key transcription factors which mainly regulate the expression of CYP3A genes. At the molecular level, PXR has been revealed the protection mechanism of the body against xenochemicals and a major mode of the drug-drug interactions. Besides playing an important role in drug metabolism and interactions, PXR and its target genes also play an important role in maintaining normal physiological function and homeostasis. Therefore, it is necessary to study the regulation of PXR and its related pharmacological effects of TCM and natural products, and to provide new clues for the new pharmacological pathway.

Tetramethylpyrazine protects lymphocytes from radiation-induced apoptosis through nuclear factor-κB.

AIM: Radiation induces an important apoptosis response in irradiated organs. The objective of this study was to investigate the radioprotective effect of tetramethylpyrazine (TMP) on irradiated lymphocytes and discover the possible mechanism of protection. METHOD: Lymphocytes were pretreated for 12 h with TMP (25-200 µmol·L(-1)) and then exposed to 4 Gy radiation. Cell apoptosis and the signaling pathway were analyzed. RESULTS: Irradiation increased cell death, DNA fragmentation, activated caspase activation and cytochrome c translocation, downregulated B-cell lymphoma 2 (Bcl-2) and up-regulated Bcl-2-associated X protein (Bax). Pretreated with TMP significantly reversed this tendency. Several anti-apoptotic characteristics of TMP, including the ability to increase cell viability, inhibit caspase-9 activation, and upregulate Bcl-2 and down-regulate Bax in 4Gy-irradiated lymphocytes were determined. Signal pathway analysis showed TMP could translate nuclear factor-κB (NF-κB) from cytosol into the nucleus. CONCLUSION: The results suggest that TMP had a radioprotective effect through the NF-κB pathway to inhibit apoptosis, and it may be an effective candidate for treating radiation diseases associated with cell apoptosis.

[Effect of Panax notoginseng saponins on liver drug metablic enzyme activity, mRNA and protein expressions in rats].

To study the effect of Panax notoginseng saponins (PNS) on liver drug metabolic enzyme activity, mRNA and protein expressions in rats. Male Wistar rats were randomly divided into nine groups. After administration of the test drugs, their liver microsomes, liver total RNA and total protein were extracted to detect the regulating effect of PNS on liver drug metabolic enzyme activity-related subtype enzymatic activity, mRNA and protein expression by substrate probe, quantitative PCR and Western Blot technology. The result of this experiment was that PNS could significantly induce CYP1A2 and CYP2E1 enzyme activity, mRNA expression, CYP2E1 protein expression level. PNS significantly induced CYP3A mRNA expression, but with no significant effect in CYP3A enzyme activity level. PNS had no significant effect CYP1A1 and CYP2B mRNA expressions and enzyme activity levels. PNS had selective regulations on different P450 subtypes, and the major subtypes were CYP1A2 and CYP2E1. In clinical practice, particularly in the combination with CYP1A2 and CYP2E1 metabolism-related drugs, full consideration shall be given to the possible drug interactions in order to avoid potential toxic and side effects. Meanwhile, whether the induction effect of CYP2E1 gets involved in ginsenoside's effect incavenging free radicals deserves further studies.

Cardioprotection of Shenfu preparata on cardiac myocytes through cytochrome P450 2J3.

OBJECTIVE: 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.

[Research on the incompatibility of Radix adenophora, Radix glehniae combined with Veratrum nigrum L. by uniform designed toxicity assay].

OBJECTIVE: To study the toxicity changes of different proportions of Radix Adenophora, Radix Glehniae combined with Veratrum nigrum L., thus providing acute toxicity data and investigating whether decoction factors were correlated with toxicity. METHODS: The uniform design method was used by two factors and seven levels to investigate the toxicity changes in different proportions of Radix Adenophora, Radix Glehniae combined with Veratrum nigrum L. The decoction factors were also investigated. RESULTS: The compatibility toxicity was affected mainly by Veratrum nigrum L. and the toxicity increased along with increased doses of Veratrum nigrum L. The toxicity of co-decoction was higher than mixed decoction in the same dosage of Radix Glehniae and Veratrum nigrum L. The promotion of the dissolution of the toxic component of Veratrum nigrum L. in co-decoction may be the cause of the higher toxicity. CONCLUSION: Radix Adenophora and Radix Glehniae combined with Veratrum nigrum L. resulted in higher toxicity, which indicated that the incompatibility between Radix Adenophora, Radix Glehniae, and Veratrum nigrum L. In clinic practice, a prescription contained these drugs should be avoided.

[Effect of shenfu injection on CYP450s of rat liver].

The paper is to report the study of the effect of Shenfu injection on the enzyme activity of liver CYP450 and its mRNA level of rat liver. Microsome of rat liver was prepared after intravenous administration of Shenfu injection for 7 days. The enzyme activity was quantified by Cocktail method. Meanwhile, the mRNA expression of CYP1A2, CYP2B1/2, CYP2C11 and CYP3A1 in the liver was detected by RT-PCR. Shenfu injection obviously induced the enzyme activities of CYP2B and CYP2C. Meantime Shenfu injection decreased the enzyme activities of CYP1A2 and CYP3A. The mRNA levels of CYP2B and CYP2C were also induced in rats treated with Shenfu injection. But it obviously inhibited the mRNA level of CYP1A2 and CYP3A. Since the enzyme activity and mRNA level were obviously changed after administration, the potential effect of drug-drug interaction should be concerned.