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This study aimed to investigate the effects of nanoparticles PLGA-NPs and mesoporous silicon nanoparticles(MSNs) of different stiffness before and after combination with menthol or curcumol on the mechanical properties of bEnd.3 cells. The particle size distributions of PLGA-NPs and MSNs were measured by Malvern particle size analyzer, and the stiffness of the two nanoparticles was quantified by atomic force microscopy(AFM). The bEnd.3 cells were cultured in vitro, and the cell surface morphology, roughness, and Young's modulus were examined to characterize the roughness and stiffness of the cell surface. The changes in the mechanical properties of the cells were observed by AFM, and the structure and expression of cytoskeletal F-actin were observed by a laser-scanning confocal microscope. The results showed that both nanoparticles had good dispersion. The particle size of PLGA-NPs was(98.77±2.04) nm, the PDI was(0.140±0.030), and Young's modulus value was(104.717±8.475) MPa. The particle size of MSNs was(97.47±3.92) nm, the PDI was(0.380±0.016), and Young's modulus value was(306.019±8.822) MPa. The stiffness of PLGA-NPs was significantly lower than that of MSNs. After bEnd.3 cells were treated by PLGA-NPs and MSNs separately, the cells showed fine pores on the cell surface, increased roughness, decreased Young's modulus, blurred and broken F-actin bands, and reduced mean gray value. Compared with PLGA-NPs alone, PLGA-NPs combined with menthol or curcumol could allow deepened and densely distributed surface pores of bEnd.3 cells, increase roughness, reduce Young's modulus, aggravate F-actin band breakage, and diminish mean gray value. Compared with MSNs alone, MSNs combined with menthol could allow deepened and densely distributed surface pores of bEnd.3 cells, increase roughness, reduce Young's modulus, aggravate F-actin band breakage, and diminish mean gray value, while no significant difference was observed in combination with curcumol. Therefore, it is inferred that the aromatic components can increase the intracellular uptake and transport of nanoparticles by altering the biomechanical properties of bEnd.3 cells.
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Animals , Mice , Menthol/pharmacology , Actins/metabolism , Endothelial Cells/metabolism , Nanoparticles/chemistryABSTRACT
AIM: To study the role and mechanism of curcumol in neovascularization induced by vascular endothelial growth factor(VEGF).METHODS: Human umbilical vein endothelial cells were cultured in vitro and treated with 50ng/mL VEGF and curcumol at different concentrations. Cell proliferation was detected by CCK-8 and EdU assay, the migration ability of cells was analyzed by Transwell assay, the angiogenesis ability of endothelial cells was analyzed by tube formation assay, and the change of Akt/mTORC1 signal pathway was detected by Western blot.RESULTS: CCK-8 results showed that the OD450 value of cells in 400 and 800 μmol/L curcumol+VEGF group was significantly lower than that in VEGF group(all P<0.01). EdU results showed that the rate of cell proliferation in 400 μmol/L curcumol+VEGF group was significantly lower than that in VEGF group(P<0.001). Transwell assay and the formation assay results showed that the number of migratory cells in 400 μmol/L curcumol+VEGF group was decreased, and the number and length of tube branches were also reduced compared with VEGF group(all P<0.001). Western blot results showed that curcumol significantly inhibited the expression of p-Akt and p-S6, which were downstream targets of Akt/mTORC1 pathway in cells.CONCLUSION: Curcumol can inhibit VEGF-induced cell proliferation, migration and tube formation of vein endothelial cells, and has a strong inhibitory effect on angiogenesis, which can be further studied in the treatment of ocular fundus neovascularization.
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OBJECTIVE To study the mechanism of curcumol inhibiting the pro liferation of breast cancer cells T 47D. METHODS MTT assay was used to detect the inhibitory effects of different doses of curcumol （0，6.25，12.5，25，50，100 μg/mL）on the proliferation of T 47D cells. After treated with curcumol （12.5，25，50，100 μg/mL），the morphology of T 47D cells was observed by inverted phase contrast microscope. The cell cycle and the levels of reactive oxygen species （ROS）were detected by flow cytometry. Quantitative real-time PCR （qRT-PCR）was used to detect the expressions of proliferating cell nuclear antigen （PCNA），cell cycle regular p 21 and cyclin-dependent kinase 2（CDK2）mRNA. Western blot assay was used to detect the protein expression of CDK 2，CDK6，Cyclin D ，PCNA，nucler transcription factor E 2-related factor （Nrf2）and Kelch-like ECH associated protein 1（Keap1）. Breast cancer cells T 47D were divided into 2 groups，one group was given different doses of curcumol ，and another group was given curcumol 33 μg/mL for 6，12，24，48 h. After the optimal oxidation time and administration concentration were determined according to the results of the above two groups ，the blank control group ，N-acetylcysteine（NAC）group（ROS antioxidant NAC alone ），curcumol group （curcumol alone ），curcumol combined with NAC group （pretreatment with ROS antioxidant NAC ，and then adding into curcumol ）. Cell cycle and fluorescence intensity of ROS were detected. RESULTS Curcumol could significantly increase the inhibitory rate of the proliferation of T 47D cells （P＜0.05 or P＜0.01），and showed a certain dose and time dependent trend. Curcumol blocked the ， cycle in the G 1 phase and significantly increased the level of ROS （P＜0.05 or P＜0.01）；ROS antioxidant NAC could significantly reverse above inductive effect of curcumol （P＜ 0.01）. qRT-PCR showed that curcumol down-regulated the com expression of PCNA and CDK 2 mRNA and up-regulated the expression of p 21 mRNA（P＜0.05 or P＜0.01）. Western blot assay showed that curcumol significantly down-regulated the edu.cn protein expression of Keap 1，Nrf2，CDK2，CDK6 and Cyclin D（P＜0.05，P＜0.01）；ROS antioxidant NAC could reverse the down-regulation effects of curcumol on the expression of these proteins（P＜0.05 or P＜0.01）. CONCLUSIONS Curcumol may induce oxidative stress and cell arrest in G 1 phase to inhibit the proliferation of T 47D cells.
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The present study clarified the molecular mechanism of curcumol against liver fibrosis based on its effects on the autopha-gy and apoptosis of hepatic stellate cells. The hepatic stellate cells were divided into a blank control group, a transforming growth factor-β1(TGF-β1)(10 ng·mL~(-1)) group, and low-(12.5 mg·L~(-1)), medium-(25 mg·L~(-1)), and high-dose(50 mg·L~(-1)) curcumol groups. The effect of curcumol on the viability of hepatic stellate cells induced by TGF-β1 was detected by the MTT assay kit. The apo-ptosis in each group was determined by flow cytometry. Real-time fluorescence-based quantitative PCR(RT-PCR) was employed for the detection of mRNA expression of α-smooth muscle actin(α-SMA), type Ⅰ collagen(collagen Ⅰ), and type Ⅲ collagen(collagen Ⅲ). Western blot was used to detect the protein expression of p62, microtubule-associated protein 1 light chain 3(LC3), beclin1, B cell lymphoma 2(Bcl-2), and Bcl-2-associated X protein(Bax). Transmission electron microscopy(TEM) was used to observe cell morphology and autophagosome formation in each group. The autophagic flux was observed after cell infection with adenovirus under double fluorescence labeling. The cell viability assay revealed that compared with the TGF-β1 group, the curcumol groups showed significantly decreased cell viability. The apoptosis assay showed that the apoptosis rates of the curcumol groups were significantly higher than that of the TGF-β1 group. RT-PCR indicated that the mRNA expression of α-SMA, collagenⅠ, and collagen Ⅲ in the curcumol groups was significantly lower than that of the TGF-β1 group. Western blot showed that the expression of p62, LC3, beclin1, Bcl-2, and Bax in the curcumol groups was significantly different from that in the TGF-β1 group. As demonstrated by TEM, compared with the TGF-β1 group, the curcumol groups showed significantly increased autophagosomes. The detection of autophagic flow by the adenovirus under double fluorescence labeling showed that autolysosomes in the curcumol groups were significantly increased compared with those in the TGF-β1 group. Curcumol can induce the autophagy and apoptosis of hepatic stellate cells, which may be one of its anti-liver fibrosis mechanisms.
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Humans , Actins/metabolism , Apoptosis , Autophagy , Hepatic Stellate Cells , Liver/metabolism , Liver Cirrhosis/metabolism , Sesquiterpenes , Transforming Growth Factor beta1/metabolismABSTRACT
Objective:To explore the effects and mechanism of zedoary turmeric oil and its active components on the vascular endothelial growth factor A （VEGFA）， signal transducer and activator of transcription 3 （STAT3）， and mechanistic target of rapamycin （mTOR） in the ovarian cancer （OC）. Method:Network pharmacology technology was employed to analyze the mechanism of Curcumae Rhizoma on OC. Bioinformatics was used to analyze the expression of VEGFA， STAT3， and mTOR in OC and the effect on the prognosis of OC to explore the feasibility of zedoary turmeric oil in regulating VEGFA， STAT3， and mTOR in OC.The xenograft tumor model of nude mice was established， and the effects of zedoary turmeric oil and its active components on VEGFA， STAT3， and mTOR in OC were observed by hematoxylin-eosin （HE） staining， real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR）， Western blot， and immunohistochemistry （IHC）. Result:Bioinformatics analysis and literature research showed that VEGFA， STAT3， and mTOR played a special regulatory role in the occurrence and development of OC， and were potential key targets for the proliferation of OC. Network pharmacology analysis revealed that Curcumae Rhizoma could regulate multiple disease targets of OC， and mediate VEGFA， STAT3， and mTOR in OC through these multiple targets. As demonstrated by HE staining， the tumor cells in the model group were densely arranged， with no erosion on the edge and no vesicles inside. Compared with the model group， the cell density in other treatment groups was reduced， and strip-shaped erosion on the edge and small empty vesicles were observed in the tumor tissue， especially in the zedoary turmeric oil group. According to the results of Real-time PCR and IHC， zedoary turmeric oil and its active components could inhibit the mRNA and protein expression of VEGFA， STAT3， and mTOR in the OC tissue （<italic>P</italic><0.05）. Conclusion:Zedoary turmeric oil and its active components could reduce the expression of VEGFA， STAT3， and mTOR in tumor tissue of nude mice， and inhibited the proliferation of OC through VEGFA， STAT3， and mTOR.
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Curcumol, as an important component of Curcuma Rhizoma, has anti-virus, anti-inflammatory, anti-tumor and other pharmacological activities, which has attracted more and more attentions in anti-tumor research area. The progress on the natural source, anti-tumor mechanism, structural modification, and anti-tumor evaluation of curcumol are reviewed in this paper, which will provide a novel strategy for its further structural optimization.
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ObjectiveTo investigate the molecular mechanism of the anti-liver fibrosis effect of curcumol by observing the effect of curcumol on the TLR4/NF-κB signaling pathway in liver sinusoidal endothelial cells. MethodsA total of 50 mice were randomly divided into blank group, model group, and curcumol group, and cells were divided into blank control group, LPS positive control group, curcumol intervention group, and PDTC group. HE staining and Masson staining were used to observe the change in liver structure; Western blot and quantitative real-time PCR (RT-PCR) were used to measure the protein and mRNA expression of the key molecules TLR4 and NF-κB in the TLR4/NF-κB signaling pathway; immunofluorescence assay was used to observe the expression and nuclear import of NF-κB in cells. A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsRT-PCR showed that compared with the positive control group, the curcumol intervention group had significant reductions in the mRNA expression of TLR4 and NF-κB (both P＜0.05). Western blot showed that compared with the positive control group, the curcumol intervention group had significant reductions in the expression of TLR4 and NF-κB (both P＜005). Immunofluorescence assay showed that compared with the positive control group, the curcumol intervention group had significant improvement in NF-κB nuclear import. ConclusionCurcumol can exert an anti-liver fibrosis effect possibly by inhibiting the activity of the TLR4/NF-κB signaling pathway.
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A demonstration research on Chinese herbal decoction pieces of Curcumae Rhizoma was performed based on the concept of quality markers (Q-markers), standard establishment, and research modes. The chemical constituents of both steamed processed pieces of Curcumae Rhizoma and vinegar-processed pieces of Curcumae Rhizoma decoction pieces were identified by ultra- performance liquid chromatography/quadrupole-time of flight mass spectrometry (UPLC-Q/TOF-MS). The major effective components were analyzed through pharmacodynamics, drug property, pharmacokinetics studies, and correlation analysis of chemical constituents. The Q-markers were determined by all the results. At last, five compounds including curdione, curcumol, germacrone, furanodiene and β-elemene were selected as Q-markers. The quality control methods of multi-component assaying and fingerprint were also established. Overall, this study provides a demonstration for the study of quality markers of Chinese herbal decoction pieces.
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Aim To investigate the effects of curcumol on the contractile activity of isolated jejunum and ileum smooth muscles in rats and explore its underlying mechanism. Methods Jejunum and ileum specimens were randomly divided into five groups (n = 12) : curcumol group, atropine plus curcumol group, isoprena- line plus curcumol group, norepinephrine plus curcumol group, Ca2t and curcumol group. The contractile amplitude and tension of jejunum and ileum were recorded by constant temperature perfusion. Results Curcumol promoted the contraction of normal intestinal smooth muscles and antagonize the effects of atropine, norepinephrine, isoprenaline and verapamil on relaxation of intestinal smooth muscles. Conclusions Curcumol can significantly promote the contraction of isolated jejunum and ileum smooth muscles, which may be achieved through M receptor, a receptor, p receptor and promoting extracellular calcium influx.
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OBJECTIVE: To investigate the effect of curcumol on the apoptosis inhibition of TRAF2 and XBP1 controled by IRE1 in rats with obstructive nephropathy. METHODS: Rats were randomly divided into sham control group, model control group and enalapril group as well as high, medium and low formononetin groups. Animal model of RIF was established by unilateral ureteral obstruction (UUO). The rats were sacrificed at 14 d after UUO, and blood samples were collected. Levels of serum creatinine (Scr) and blood urea nitrogen (BUN) were examined. Renal tubular damage index was determined by H&E staining. The area of RIF was determined by Masson staining. Expressions of GRP78,IRE1,p-IRE1,TRAF2 and XBP1 in kidney were determined by Western blotting analysis. Apoptosis of tubular epithelial cells was detected by TUNEL assay. RESULTS: Levels of Scr and BUN, tubulointerstitial injury index, RIF and apoptotic index as well as expressions of GRP78,IRE1,p-IRE1,TRAF2 and XBP1 were different between the model control and treatment groups (P<0.05, P<0.01). Compared with the enalapril group, tubulointerstitial injury index and RIF as well as the levels of Scr and BUN were decreased (P < 0.05) in the high curcumol group. CONCLUSION: The curcumol can block the apoptosis of renal tubular epithelial cells through interfering IRE1-XBP1 signaling pathway by inhibiting TRAF2 protein expression mediated by IRE1 phosphorylation. Ultimately, development of RIF was postponed.
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Aim To investigate the effects of curcumol on the contractile activity of isolated duodenal smooth muscle in rats and explore its underlying mechanisms. Methods The isolated duodenum specimens of rats were made. The effects of different concentrations of curcumol on the contraction of isolated duodenal smooth muscle were observed using BL-420F biological and functional experimental system with constant tem-perature perfusion method. A certain concentration of curcumol was combined with atropine,isoproterenol, norepinephrine,calcium-free Krebs solution,verapam-il respectively to observe its effect on smooth muscle contraction. Results Curcumol could stimulate duo-denal smooth muscle in vitro,and increase its contrac-tile amplitude and tension significantly. It could be an-tagonized partly by atropine,isoprenaline,norepineph-rine,verapamil. Conclusion Curcumol can promote the contraction of isolated duodenal smooth muscle in rats,which may be achieved by stimulating M recep-tor,inhibiting α and β receptors,and promoting the extracellular calcium influx.
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Curcumae Rhizoma comes from Curcuma genus,functional breaking blood stasis,detumescence and acesodyne for treatment of Zhengjia accumulation,amenorrhea,traumatic injury and bruising pain.Modem pharmacological studies have shown that the main monomer composition of zedoary turmeric has a good anti-inflammatory and anti-tumor effects.The main monomer composition of zedoary turmeric copies of curcumol,beta etemene,curcumin anti-inflammatory anti-tumor mechanism of review,provide the basis for the further research progress and clinical application of zedoary turmeric.
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Aim To explore the concentration range of organic solvent which can both effectively increase solubility of the difficult soluble medicine monomer, and have low toxicity to cells, and to clarify the influence of different concentration of ethanol on curcumol efficacy.Methods Different DMSO and ethanol concentrations were diluted in culture medium and incubated with cells A549, NCI-H460, NCI-H1299, NCI-1650, LTEP-a2 and SPC-A1 for 12 h, 24 h, or 48 h, cell viability was tested by a colorimetric assay with 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide(MTT), and different concentrations of ethanol with/without different concentrations of curcumol were also prepared with culture medium, then incubate with A549 and NCI-H460 cells for 24 h, and cell viability was tested by MTT as well.Results Within 48 h the solution with 0.008(V/V) DMSO or less had no significant effect on the cell A549 compared with control group, for NCI-H1650 the concentration was 0.004(V/V) or less, for NCI-H460 the result turned to be 0.002(V/V) or less, and the solution with DMSO below 0.001(V/V) had significant effect on the three other cells, NCI-H1299, LTEP-a2 and SPC-A1.While within 48 h, the liquor with 0.004(V/V) ethanol or less did not exhibit significant cytotoxic effect on the cell A549, for NCI-H460 and NCI-H1650 the result of ethanol concentration became 0.002(V/V) or less, for NCI-H1299 the data was 0.001(V/V) or less, and the liquor with ethanol below 0.001(V/V) showed significant cytotoxic effect on LTEP-a2and SPC-A1.When the proportion of ethanol in solution was below 0.01, it has no cytotoxic on cell A549 and NCI-H460, and the curcumol solution prepared with this kind of ethanol solution only represented the efficacy of curcumol on the cells.Since the solution with 0.01(V/V) ethanol dissolved the curcumol better, the cell viability changed from about 100% to about 35%.Conclusions Different organic solvent expressed different toxicity to the same cell, and the sensitivity of different cells to one organic solvent is dissimilar.and DMSO could be the optimum solvent for A549 and NCI-H1650, while the optimum solvent of NCI-H1299 is ethanol, for NCI-H460 it could be both and DMSO and ethanol, and DMSO and ethanol is not suitable for LETP-a2, SPC-A1 to be solvent.
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Objective Curcumol solid dispersions (Cur-SDs) were explored and the optimal formulation was selected for improving the in vitro dissolution of curcumol. Methods In this study, Cur-SDs were prepared by solvent method, fusion method and solvent-fusion method using F68, PVP K30, PEG4000, and PEG6000 as matrix, and in vitro dissolution rate was evaluated. Fourier transform infrared spectroscopy (IR), differential scanning calorimetry (DSC), and X-ray diffractometry (XRD) were employed to characterize the molecular arrangement of curcumol in SDs. And a brief investigation of its stability in the long-term storage process was also performed. Results The Cur-SD prepared with F68 as matrix and by solvent-fusion method was better in improving the in vitro dissolution than those with other matrix or those prepared by other methods. Furthermore, the optimal drug-matrix ratio was 1:5. DSC, IR and XRD indicated that the drug could be dispersed molecularly or amorphously in matrix, and no chemical reaction occurred. There was no decrease in its dissolution, and no significant change in molecular arrangement in a six-month stability study under room temperature. Conclusion The preparation of insoluble drug curcumol into solid dispersion can significantly improve its dissolution rate in vitro. Moreover, the preparation method is simple and feasible, and has good stability.
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Objective To develop a method of quantitative analysis of multi-components by single marker (QAMS) for simultaneously determining five compounds in Curcumae Aromaticae Radix.Methods An HPLC method was developed as QAMS to determine curcuma diol,ocathydro-1,4-dihydroxy-1,4-dimethyl-7-(propan-2-ylidene)azulen-5(1H)-one,original curcumol and curcumin in Curcumae Aromaticae Radix,using curdione as intermal reference substance,and the relative correction factor (RCF) of the four components was determined by HPLC with good reproducibility.Their contents in 10 batches of samples,collected from different areas,were determined by both external standard method and QAMS.Result No significant differences were found in the quantitative results of four compounds in 10 batches of Curcumae Aromaticae Radix determined by external standard method and QAMS.Conclusion It is feasible and suitable to evaluate the quality of Curcumae Aromaticae Radix by QAMS.
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Objective To observe the effect of the active ingredient present study curcumol impact on human glioma cell line U251 proliferation and apoptosis,its effect on the detection of apoptosis-related gene expression in glioma,and explore the possible mechanism of its anti-glioma,Chinese herbal medicine for the treatment of glioma accumulation of experimental data.Methods In cultured human glioma cell line U251 as a model to medium dilution Curcumol different concentrations,observation and detection following:MTT assay at different times,different concentrations curcumol on U251 cell proliferation;microscope Effect of different concentrations of curcumol U251 cell morphology;affected by flow cytometry curcumol different concentrations on apoptosis in U251;RT-PCR method to detect different concentrations curcumol on U251 cell apoptosis-related gene bcl-2 and COX-2 expression levels of influence.Results Curcumol U251 human glioma cell proliferation inhibition effect and showed concentration-dependent and time-dependent manner (P ＜ 0.05).Conclusions Curcumol U251 human glioma cell proliferation clear.Induce apoptosis and inhibit proliferation of glioma should be an important mechanism of inhibition of proliferation effect of curcumol.Curcumol down on U251 cells bcl-2 gene expression levels and COX-2should be its induction of apoptosis,an important mechanism of inhibition of proliferation.
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Objective: To investigate the chemical constituents in the roots and rhizomes of Curacuma aromtica. Methods: The chemical constituents were separated and purified by silica gel, Sephadex LH-20 column chromatography, preparative HPLC, and so on. Their structures were determined by physicochemical constants and spectral analyses. Results: Seventeen compounds were obtained and identified as curdione (1), β-sitosterol (2), stigmasterol (3), triaconatanoic acid (4), gweicurculactone (5), curcumenol (6), procurcumenol (7), eudesmane-3, 6-dione (8), lupeol (9), curcumin (10), demethoxycurcumin (11), aerugidiol (12), zedoarondiol (13), voleneol (14), uracil (15), curcumol (16), and curcumenone (17). Conclusion: Compounds 4, 5, 8, 9, 14, and 15 are isolated from the plant for the first time.
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AIM:To develop a new method of gas chromatography for simultaneously determining curcumol contentin and β-elemene in Zedoary Turmeric Oil.METHODS:Separation and quantification were achieved on a quartz capillary column(30 m×0.32 mm)of PEG with a column temperature gradient from 80℃(holding for 7 min)to 140℃ at a rate of 20℃/min,holding for 15 min,taking N2 as loader.The temperature for gasification was 210℃;the temperature for detection was 200℃;the compressive stress of column was 0.27 MPa.RESULTS:Under the optimal chromatographic conditions,the linear range of curcumol contentin was within 0.230 5-3.23 mg/mL and the linear range of the β-elemene was within 0.237 5-3.33 mg/mL.The average recovery of curcumol contentin was 100.4% with a relative standard deviation(RSD)of 1.1% and β-elemene was 100.2% with a RSD of 2.2%.CONCLUSION:The results show that it is a simple,rapid,accurate and sensitive method which is suitable for analysis of complex component(curcumol contentin and β-elemene)in Zedoary Turmeric Oil at the same time.
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[Objective] To study the effects of different growth periods on the contents of volatile oil and the curcumol in Curcuma aromatica Salisb. samples,which provided theoretical bases to control the quality of the crude drug of Curcuma aromatica Salisb.[Method]The contents of volatile oil in Curcuma aromatica Salisb. samples were determined by the method of Pharmacopeia,and HPLC method for determination of curcumol in different samples was established. [Result]The contents of volatile oil in different samples lied in the range of 0.820%～0.471%(g/g),and the contents of curcumol in different volatile oil samples were between 0.862%(g/g) and 1.380%(g/g). [Conclusion]Compared with the Curcuma aromatica Salisb. of a shorter growing period,the contents of longer growth period were higher.Different growing time had effects on the accumulating of volatile oil and the curcumol in Curcuma aromatica Salisb.
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OBJECTIVE:To observe the stabilities of zedoary turmeric oil and glucose injection mixing with 5 kinds of antibiotics METHODS:The contents of curcamol in mixed fluid were detected with UV spectrophotometry,and the external appearance and value of pH were observed RESULTS:After mixing zedoare turmeric oil and glucose injection with 5 kinds of antibiotics,no gas and sediment were found Values of pH were different in the 5 simples,and did not change markedly over 3 hours The concentration of curcumol was markedly reduced and the sample turned to brown in mixing with cefoperazone sodium;the concentration was declined in mixing with ceftriaxone sodium and decreased 6% with cefradine and was not markedly reduced in mixing with clindamycin and netilmicin CONCLUSION:This preparation is compatible with netilmicin and clindamycin,however,it is incompatible with cefoperazone and ceftriaxone