Zedoary turmeric oil injection ameliorates lung inflammation via platelet factor 4 and regulates gut microbiota disorder in respiratory syncytial virus-infected young mice.

BACKGROUND: Respiratory syncytial virus (RSV)-induced lung inflammation is one of the main causes of hospitalization and easily causes disruption of intestinal homeostasis in infants, thereby resulting in a negative impact on their development. However, the current clinical drugs are not satisfactory. Zedoary turmeric oil injection (ZTOI), a patented traditional Chinese medicine (TCM), has been used for clinical management of inflammatory diseases. However, its in vivo efficacy against RSV-induced lung inflammation and the underlying mechanism remain unclear. PURPOSE: The present study was designed to confirm the in vivo efficacy of ZTOI against lung inflammation and intestinal disorders in RSV-infected young mice and to explore the potential mechanism. STUDY DESIGN AND METHODS: Lung inflammation was induced by RSV, and cytokine antibody arrays were used to clarify the effectiveness of ZTOI in RSV pneumonia. Subsequently, key therapeutic targets of ZTOI against RSV pneumonia were identified through multi-factor detection and further confirmed. The potential therapeutic material basis of ZTOI in target tissues was determined by non-target mass spectrometry. After confirming that the pharmacological substances of ZTOI can reach the intestine, we used 16S rRNA-sequencing technology to study the effect of ZTOI on the intestinal bacteria. RESULTS: In the RSV-induced mouse lung inflammation model, ZTOI significantly reduced the levels of serum myeloperoxidase, serum amyloid A, C-reactive protein, and thymic stromal lymphoprotein; inhibited the mRNA expression of IL-10 and IL-6; and decreased pathological changes in the lungs. Immunofluorescence and qPCR experiments showed that ZTOI reduced RSV load in the lungs. According to cytokine antibody arrays, platelet factor 4 (PF4), a weak chemotactic factor mainly synthesized by megakaryocytes, showed a concentration-dependent change in lung tissues affected by ZTOI, which could be the key target for ZTOI to exert anti-inflammatory effects. Additionally, sesquiterpenes were enriched in the lungs and intestines, thereby exerting anti-inflammatory and regulatory effects on gut microbiota. CONCLUSION: ZTOI can protect from lung inflammation via PF4 and regulate gut microbiota disorder in RSV-infected young mice by sesquiterpenes, which provides reference for its clinical application in RSV-induced lung diseases.

ß-Elemene in zedoary turmeric oil injection induces dyspnea by binding to hemoglobin and upregulating HIF-1α.

ETHNOPHARMACOLOGICAL RELEVANCE: Zedoary turmeric oil injection (ZTOI) extracted from the rhizome extract of Curcuma phaeocaulis Valeton, Curcuma wenyujin Y. H. Chen et C. Ling or Curcuma kwangsiensis S. G. Lee et C. F. Liang, is widely used for the treatment of virus-induced upper respiratory tract infections, peptic ulcers, viral pneumonia, etc. However, it has attracted widespread attention because it often causes adverse drug reactions (ADRs), including dyspnea. However, little is known about the mechanism underlying dyspnea caused by ZTOI, which limits its clinical application. AIM OF THE STUDY: To investigate the major pathophysiologic signatures and underlying mechanism of ZTOI-related dyspnea. METHODS: Respiratory function detection was used to explore the pathophysiologic signature of dyspnea induced by ZTOI. UV-vis absorption spectroscopy and isothermal titration calorimetry were applied to test the interaction between ZTOI and hemoglobin (Hb). GC‒MS was used to identify the main components in ZTOI. Molecular docking, surface plasmon resonance, and circular dichroism spectroscopy were employed to test the reaction between ß-elemene and Hb. Western blot was performed to investigate the effect of ß-elemene on the hypoxia signaling pathway. RESULTS: The results showed that ZTOI-induced dyspnea was related to a decreased oxygen carrying capacity of Hb. The molecular interaction between ZTOI and Hb was proven. Notably, ß-elemene in ZTOI exhibited high binding affinity to Hb and altered its secondary structure. Furthermore, it was found that ß-elemene downregulated the expression of prolyl hydroxylase-domain protein 2 and upregulated the expression of hypoxia-inducible factor-1α. CONCLUSIONS: Our study is valuable for better understanding the pathophysiological characteristics and underlying mechanism of ZTOI to ensure its safe clinical application. We also provided a strategy to elucidate the underlying mechanism based on inspiration from clinical ADR phenotypes for investigating other medical products with ADRs in the clinic.

Multiple anti-inflammatory mechanisms of Zedoary Turmeric Oil Injection against lipopolysaccharides-induced acute lung injury in rats elucidated by network pharmacology combined with transcriptomics.

BACKGROUND: Prospects for the drug treatment of acute lung injury (ALI) is unpromising. Managing inflammation can prevent ALI from progressing and minimize further deterioration. Zedoary turmeric oil injection (ZTOI), a patented traditional Chinese medicine (TCM) that has been used against ALI, has shown significant anti-inflammatory effects. However, the mechanisms underlying these effects remain unclear. PURPOSE: Elucidate the anti-inflammatory mechanism by which ZTOI acts against ALI in rats using an ingredients-targets-pathways (I-T-P) interaction network. STUDY DESIGN AND METHODS: The key ingredients of ZTOI were characterized using UPLC-MS/MS combined with literature mining. The target profiles of each ingredient were established using drug-target databases. The anti-inflammatory activity of ZTOI against lipopolysaccharides (LPS)-induced rat ALI was validated using histopathology and inflammatory factor assessments. The therapeutic targets of ZTOI were screened by integrating transcriptomic results of lung tissues with protein-protein interaction (PPI) expansion. Using KEGG pathway enrichment, an I-T-P network was established to determine the essential interactions among ingredients, targets, and pathways of ZTOI against lung inflammation in ALI. Molecular docking and immunofluorescence staining were utilized to confirm the accuracy of the I-T-P network. RESULTS: A total of 11 sesquiterpenes, whose target profiles may characterize the potential function of ZTOI, were identified as key ingredients. In the ALI rat model, ZTOI can alleviate lung inflammation by decreasing the levels of C-reactive protein, interleukin-6, interleukin-1ß, and tumor necrosis factor α both in serum and lung tissues. Based on our biological samples, transcriptomics, PPI network expansion, and KEGG pathway enrichment, 11 ingredients, 174 targets, and 8 signaling pathways were linked in the I-T-P networks. From these results, ZTOI could be inferred to exert multiple anti-inflammatory effects against ALI through Toll-like receptor, NF-kappa B, RIG-I-like receptor, TNF, NOD-like receptor, IL-17, MAPK, and the Toll and Imd signaling pathways. In addition, two significantly regulated targets in the transcriptome, Usp18 and Map3k7, could be the essential anti-inflammatory targets of ZTOI. CONCLUSION: By integrating network pharmacology with ingredient identification and transcriptomics, we show the multiple anti-inflammatory mechanisms by which ZTOI acts against ALI on an I-T-P level. This work also provides a methodological reference for related research into TCM.

Network pharmacology-based dissection of the underlying mechanisms of dyspnoea induced by zedoary turmeric oil.

Zedoary turmeric oil (ZTO) has been widely used in clinic. However, the unpleasant induced dyspnoea inevitably impedes its clinical application. Thus, it is urgent to elucidate the mechanism underlying the ZTO-induced dyspnoea. In this study, network pharmacology was firstly performed to search the clue of ZTO-induced dyspnoea. The key target genes of ZTO-induced dyspnoea were analysed using GO enrichment analysis and KEGG pathway analysis. GO analysis suggested that haem binding could be a key molecular function involved in ZTO-induced dyspnoea. Hence, the haemoglobin (Hb) was focused for its oxygen-carrying capacity with haem as its critical component binding to the oxygen. Ultraviolet-visible absorption spectrum indicated that the ZTO injection (ZTOI) perturbed the Soret band of Hb, suggesting an interaction between ZTO and Hb. GC-MS analysis revealed that ß-elemene, germacrone, curdione and furanodiene were main components of ZTOI. Molecular docking was used to illustrate the high affinity between representative sesquiterpenes and Hb, which was finally confirmed by surface plasmon resonance, suggesting their potential roles in dyspnoea by ZTO. Following a network pharmacology-driven strategy, our study revealed an intervened Hb-based mechanism underlying the ZTO-induced dyspnoea, providing a reference for elucidating mechanism underlying adverse drug reactions of herbal medicines in clinic.

Curcumae Rhizoma: A botanical drug against infectious diseases.

Curcumae Rhizoma is the dry rhizome coming from Curcuma longa L. which grow widely in tropical south and southwest Asia. It has been used to treat conditions such as dermatoses, infections, stress, and depression. Moreover, in China, Curcumae Rhizoma and its active constituents have been made into different pharmaceutical preparations. Growing evidence suggests that these preparations can exert antioxidant, anti-inflammatory, and anti-cancer effects, which may play crucial roles in the treatment of various diseases, including cancer, infectious-, autoimmune-, neurological-, and cardiovascular diseases, as well as diabetes. The anti-infective effect of Curcumae Rhizoma has become a popular field of research around the world, including for the treatment of COVID-19, influenza virus, hepatitis B virus, human immunodeficiency virus, and human papilloma virus, among others. In this paper, the basic characteristics of Curcumae Rhizoma and its active constituents are briefly introduced, and we also give an overview on their applications and mechanisms in infectious diseases.

Target separation and antitumor metastasis activity of sesquiterpene-based lysine-specific demethylase 1 inhibitors from zedoary turmeric oil.

Lysine-specific histone demethylase 1 (LSD1) was the first histone demethylase identified in epigenetics and has recently emerged as an attractive therapeutic target for treating tumors. To date, almost all reported LSD1 inhibitors have been chemosynthesized; however, natural products possess pharmacological and biological activity and can be sources for drug development. Here, we established a target separation countercurrent chromatography technique to isolate LSD1 inhibitors from zedoary turmeric oil. Four sesquiterpene-based LSD1 inhibitors were efficiently obtained with an inhibition ratio equal to or less than that of the positive control drug. Compound 2 showed the most potent inhibitory activity, with a half-maximal inhibitory concentration of 3.97 µM, and was further tested to determine its ability to inhibit LSD1 and its antitumor metastatic effects in MDA-MB-231 cells. These four compounds are the first sesquiterpene-based natural LSD1 inhibitors to be characterized. Our findings provide a new molecular framework for studying LSD1 inhibitors and offer a template for designing more sesquiterpene-based LSD1 inhibitors with potential antitumor activity.

Formulation and evaluation of a topical liposomal gel containing a combination of zedoary turmeric oil and tretinoin for psoriasis activity.

This study was to develop a combination of zedoary turmeric oil (ZTO) and tretinoin (TRE)-loaded liposomal gel as a topical drug delivery system. We used a combination of single-factor experiment and orthogonal experiment to systematically optimize encapsulation process of the compound liposomes. The optimized liposome vesicles were incorporated into Carbopol gel matrix and studied by continuous in vitro (skin penetration and retention) and in vivo (anti-psoriatic activity using mouse vaginal model and mouse tail model) experiments. The optimized liposomes had an entrapment efficiency (EE) of ZTO was (64.63 ± 1.00)%, EE of TRE was (90.33 ± 0.72)%, drug loading (DL) of ZTO was (9.09 ± 0.14)%, DL of TRE was (1.43 ± 0.02)%, particle size of 257.41 ± 7.58 nm, polydispersity index (PDI) of 0.10 ± 0.04 and zeta potential of -38.77 ± 0.81 mV. Transmission electron microscopy showed liposomes had a regular spherical surface. After 1-month storage at (4 ± 2)°C, the optimized liposome preparations maintained its stability. In vitro study indicated that liposome formulations could significantly prolong the penetration of drugs into the hair follicles of mice and keep more drugs in the skin compared with conventional gel formulations. In vivo study showed that liposomal gel was more effective than conventional gel in treating psoriasis and had a significant dose-dependent effect on psoriasis. In summary, liposomal gel is expected to be an ideal carrier for topical drug delivery systems of ZTO and TRE.

Regulatory Mechanism of Zedoary Turmeric Oil on VEGFA， STAT3 and mTOR in Ovarian Cancer / 中国实验方剂学杂志

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.

Chitosan mediated solid lipid nanoparticles for enhanced liver delivery of zedoary turmeric oil in vivo.

Zedoary turmeric oil (ZTO) has a strong antitumor activity. However, its volatility, insolubility, low bioavailability, and difficulty of medication owing to oily liquid limit its clinical applications. Solid lipid nanoparticles can provide hydrophobic environment to dissolve hydrophobic drug and solidify the oily active composition to decrease the volatility and facilitate the medication. Chitosan has been widely used in pharmaceutics in recent years and coating with chitosan further enhances the internalization of particles by cells due to charge attract. Here, Chitosan (CS)-coated solid lipid nanoparticles (SLN) loaded with ZTO was prepared and characterized using dynamic laser scanner (DLS) and transmission electron microscope (TEM). The uptake and distribution of drug were evaluated in vitro and in vivo. The average sizes of ZTO-SLN and CS-ZTO-SLN were 134.3 ± 3.42 nm and 210.7 ± 4.59 nm, respectively. CS coating inverted the surface charge of particles from -8.93 ± 1.92 mV to +9.12 ± 2.03 mV. The liver accumulation of CS-ZTO-SLN was higher than ZTO-SLN (chitosan-uncoated particles) by analysis of tissue homogenate using HPLC, and the bioavailability of ZTO was also obviously improved. The results suggested that SLN coated with CS improved the features of ZTO formulation and efficiently deliver drug to the liver.

Feasibility analysis of coronavirus disease 2019 co-treated by Zedoary Turmeric Oil Injection / 中草药

Because of no specific drug for the treatment of coronavirus disease 2019 (COVID-19), a number of treatment plans for COVID-19 had been released by national medical treatment authorities. The efficacy of zedoary turmeric oil and its preparation for antiviral and pulmonary fibrosis treatment had been confirmed by many basic studies and clinical applications. It was speculated that Zedoary Turmeric Oil Injection could be used in the clinical diagnose and treatment of COVID-19, especially in the treatment of pulmonary fibrosis caused by pulmonary interstitial changes, antidiarrheal and fever. In addition, the compatibility of Zedoary Turmeric Oil Injection with other antiviral and antibiotic drugs suggested that it could be used to reduce drug-induced liver injury in the treatment of COVID-19 patients, and improve the therapeutic effect, which provided a theoretical basis for the scientific use of zedoary turmeric oil and its injection in the treatment of COVID-19.

Antifungal activity of zedoary turmeric oil against Phytophthora capsici through damaging cell membrane.

Phytophthora capsici is a plant oomycete pathogen, which causes many devastating diseases on a broad range of hosts. Zedoary turmeric oil (ZTO) is a kind of natural plant essential oil that has been widely used in pharmaceutical applications. However, the antifungal activity of ZTO against phytopathogens remains unknown. In this study, we found ZTO could inhibit P. capsici growth and development in vitro and in detached cucumber and Nicotiana benthamiana leaves. Besides, ZTO treatment resulted in severe damage to the cell membrane of P. capsici, leading to the leakage of intracellular contents. ZTO also induced a significant increase in relative conductivity, malondialdehyde concentration and glycerol content. Furthermore, we identified 50 volatile organic compounds from ZTO, and uncovered Curcumol, ß-elemene, curdione and curcumenol with strong inhibitory activities against mycelial growth of P. capsici. Overall, our results not only shed new light on the antifungal mechanism of ZTO, but also imply a promising alternative for the control of phytophthora blight caused by P. capsici.

Inhibition effect of Zedoary turmeric oil on Listeria monocytogenes and Staphylococcus aureus growth and exotoxin proteins production.

PURPOSE: Zedoary turmeric oil (ZTO), the steam extract of Curcuma zedoaria Rosc was researched for its chemical composition, antibacterial activity, and mechanism for countering two major food-borne pathogenic species, Listeria monocytogenes and Staphylococcus aureus. METHODOLOGY: Gas chromatography-mass spectrometry (GC-MS) was used to analyse and characterize the chemical composition of ZTO. Its MICs for the two bacterial species and growth curves were measured. Western blot and real-time reverse-transcription (RT)-PCR assays were utilized to elaborate the mechanism of the antibacterial effect of ZTO by examining the expression levels of virulence-related extracellular proteins. ELISA was used to explore the biological relevance. RESULTS: GC-MS revealed high contents of curzerene, eucalyptol, germacrone and (-)-g-elemene representing 28.45, 10.94, 10.77 and 10.54  %, respectively, of the whole components. The MICs of ZTO that combatted L. monocytogenes and S. aureus were similar (1-2 mg ml-1 ). After adding ZTO at increasing concentrations, there was an evident reduction in the transcription of hly, iap, hla, sea, seb and agrA in a dose-dependent manner. Furthermore, TNF-α accumulation in RAW264.7 cells stimulated by L. monocytogenes and S. aureus supernatants was restricted by a 1/4 MIC of ZTO. CONCLUSION: Overall, L. monocytogenes and S. aureus were comparably susceptible to ZTO. These data demonstrated that ZTO's antimicrobial property was mediated by the repression of the production of virulence factors involved in L. monocytogenes and S. aureus pathogenesis, a finding that can potentially further progress in the development of new anti-virulence drugs.

Preparation and Quality Evaluation of Zedoary Turmeric Oil Compound Liposomes / 中国药房

OBJECTIVE: To prepare zedoary turmeric oil compound liposomes (ZTOC-LPS) and evaluate its quality.METHODS: The preparation method of liposome, the addition amount of soybean phosphatidylcholine (SPC), ratio of SPC to cholesterol (CH) in lipid, drug-lipid ratio of zedoary turmeric oil (ZTO), drug-lipid ratio of tretinoin in formulation, and water bath temperature were screened using encapsulation efficiency and drug-loading amount of ZTO (represented by germacrone) and tretinoin as investigation indexes. Quality evaluation and primary stability investigation were conducted for liposomes prepared by optimal preparation technology. RESULTS: The optimal preparation method was ethanol injection method; The optimal preparation technology were SPC 4 mg in 1 mL lipid, the mass ratio of SPC to CH 3:1, the ratio of ZTO to lipid 1:9, the ratio of tretinoin to lipid 1:70, water bath temperature of 55 ℃. Encapsulation efficiencies of ZTO and tretinoin were (64. 63 ± 1. 00)％ and (90. 33 土 0. 72)％ in 3 batches of ZTOC-LPS, respectively. Drug-loading amount of ZTO and tretinoin were (9. 09 ± 0. 14)％ and (1. 43 ± 0. 02)％, respectively. Particle size was (257. 41 ± 7. 58) nm, Zeta potential was (-38. 77 ± 0. 81) mV,PDI was 0. 10 ± 0. 04; the results of centrifugal acceleration test showed that the liposomes had good physical stability. No obvious change was found in each investigation index of ZTOC-LPS that stored at (4 ± 2) ℃ for 1 month. CONCLUSIONS: Established preparation technology is simple and feasible, the quality of the prepared ZTOC-LPS conforms to the requirements, and it can provide reference for the following research of ZTOC-LPS.

Preparation of zedoary turmeric oil microcapsule by spray drying method / 中草药

Objective: To establish the optimal prescription and technique for preparing zedoary turmeric oil (ZTO) microcapsule. Methods: Using the diameter of microcapsule, microcapsule form, and embedding rate as indexes, the ratio of capsule materials, ratio of core material and capsule material, content of dry matter, content of additive, speed of emulsifying, time of emulsifying, temperature of wind and the power of feed were studied. Results: The optimal conditions for preparation of spray drying of ZTO microcapsule were as follows: gum Arabic-gelatin (1.0∶1.0), core material-capsule material (0.30∶1.0), PEG6000 content of 2%, dry matter content of 20%; The optimal technique was as follows: The emulsion speed was 10 600 r/min, emulsifying time was 9 min, temperature of inlet air was 160 ℃, and feed power was 6%. According to the optimum experimental conditions, the microcapsule was round relatively, the surface density was well, the particle size of microcapsule appeared uniform distribution, most concentrates in 1.0—2.5 μm, and showed good normal distribution, the average particle size was 1.913 μm, the embedding rate could reach 75.4%. Conclusion: This experiment can increase the stability of ZTO, cover up its bad smell, and raise the utilization ratio of drugs, the repeatability is also good.

Effects of zedoary turmeric oil on cell proliferation and apoptosis and Caspase-3, Bax, Bcl-2 protein expression in rectal carcinoma cell line SW1463 / 药物评价研究

Objective To explore the effects of zedoary turmeric oil on proliferation and apoptosis of SW1463 cell line and the expression of Caspase-3,Bax and Bcl-2.Methods Volatile oil from Curcumae Rhizoma in Guizhou was extract by steam distillation,which was used to intervene SW1463 cells for 24,48 and 72 h at concentration of 40,80,120,160,200,240 and 280 mg/mL.MTT method was used to detect the inhibitory rate of zedoary turmeric oil on SW1463 cell proliferation.Effects of different concentrations of zedoary oil on apoptosis of SW1463 cells were observed by Giemsa staining.Western blotting was used to detect Capase-3,Bax and Bcl-2 protein expression.Results Zedoary turmeric oil inhibited the proliferation of SW1463 cells and showed a time dose correlation,and half maximal inhibitory concentration (IC50) of 24,48 and 72 h was 144.33,134.11 and 120.04 mg/L,respectively.Giemsa staining showed obvious morphological characteristics of apoptotic cells.Western blotting results showed that compared with control group,the expression of Caspase-3 and Bax in cells treated with zedoary turmeric oil for 24 h were significantly up-regulated (P ＜ 0.05),and the expression of Bcl-2 protein was significantly down-regulated (P ＜ 0.05).Conclusion Zedoary turmeric oil can obviously inhibit the proliferation of SW1463 cells and induce apoptosis,which may be related to the up-regulation of Caspase-3 and Bax protein expression and down-regulation of Bcl-2 protein expression.

Effects of zedoary turmeric oil on cell proliferation and apoptosis and Caspase-3, Bax, Bcl-2 protein expression in rectal carcinoma cell line SW1463 / 药物评价研究

Objective To explore the effects of zedoary turmeric oil on proliferation and apoptosis of SW1463 cell line and the expression of Caspase-3,Bax and Bcl-2.Methods Volatile oil from Curcumae Rhizoma in Guizhou was extract by steam distillation,which was used to intervene SW1463 cells for 24,48 and 72 h at concentration of 40,80,120,160,200,240 and 280 mg/mL.MTT method was used to detect the inhibitory rate of zedoary turmeric oil on SW1463 cell proliferation.Effects of different concentrations of zedoary oil on apoptosis of SW1463 cells were observed by Giemsa staining.Western blotting was used to detect Capase-3,Bax and Bcl-2 protein expression.Results Zedoary turmeric oil inhibited the proliferation of SW1463 cells and showed a time dose correlation,and half maximal inhibitory concentration (IC50) of 24,48 and 72 h was 144.33,134.11 and 120.04 mg/L,respectively.Giemsa staining showed obvious morphological characteristics of apoptotic cells.Western blotting results showed that compared with control group,the expression of Caspase-3 and Bax in cells treated with zedoary turmeric oil for 24 h were significantly up-regulated (P ＜ 0.05),and the expression of Bcl-2 protein was significantly down-regulated (P ＜ 0.05).Conclusion Zedoary turmeric oil can obviously inhibit the proliferation of SW1463 cells and induce apoptosis,which may be related to the up-regulation of Caspase-3 and Bax protein expression and down-regulation of Bcl-2 protein expression.

Study on the Distribution of Germacrone from Zedoary Turmeric Oil in Tissues of Mice / 中国药房

OBJECTIVE:To study the distribution characteristics of germacrone from zedoary turmeric oil (ZTO) in each tis-sue of mice,and to provide reference for further application of zedoary turmeric oil. METHODS:30 KM mice were given zedoary turmeric oil 0.5 mL;6 mice were randomly selected 1,2,4,8,12 h after medication,respectively. The contents of germacrone in heart,liver,spleen,lung and kidney tissues were determined by HPLC. 15 KM mice were selected,medication and sampling method were same as above;3 mice were collected at each time point respectively. The fluorescence intensity of germacrone in above sections were observed by fluorescence. The same number of mice were selected as control in 2 trials. RESULTS:The con-centration of germacrone in each tissue 1-4 h increased gradually as time and reached the peak value at 4 h. The contents of ger-macrone in liver and spleen were significantly higher than in heart and lung. The concentrations of germacrone in each tissue were ranked as liver>spleen>kidney>heart>lung. The results of fluorescence intensity observation was same as above results. CON-CLUSIONS:Results of 2 methods show same distribution characteristics of germacrone in mice tissues,and indicate that ger-macrone is distributed more in liver,spleen and kidney tissues and less in heart and lung.

Pharmacodynamics study of zedoary turmeric oil chitosan microspheres administered via arterial embolization.

Zedoary turmeric oil, a plant extract currently in clinical use, may provide potent pharmacological actions such as liver injury. In the previous study, to improve the in vivo absorption of ZTO and produce a high oral bioavailability, chitosan was employed to prepare sustained-release microspheres containing ZTO. In this study, a portability liver cancer model of rats was established successfully to compare the pharmacodynamic of ZTO microspheres and injection. In vitro results showed that microspheres had almost uniformly spherical shapes and were well dispersed by a relatively dynamic stable system. In vivo, compared with the control group, all ZTO microspheres groups resulted in growing inhibition of walker-256 cells transplanted solid tumor and the obvious controlled tumor size. At the same dose, ZTO microspheres suggested a better effect. The data showed that three doses of ZTO microspheres could prolong the average survival time considerably. None of the severe signs such as the pimelosis, fibrotic changes and fibrous septum were detected in the histopathology study.

Long-term Toxicity Study of Compound Zedoary Turmeric Oil Cream for External Use in Rats / 中国药房

OBJECTIVE:To investigate toxic reaction of Compound zedoary turmeric oil cream in experimental rats with long-term consecutive transdermal administration,and to provide reference for safe use of it in the clinic. METHODS:60 SD rats were randomly divided into blank control (cream matrix) group,Compound zedoary turmeric oil cream intact skin and damaged skin low-dose and high-dose(5%,10%)groups,with 12 rats in each group,half male and half female. All of them were given relevant medicine twice a day. 92 d consecutive medication later,general situation of rats were observed,and body weight,blood routine(WBC,RBC,HGB,LYMPH,etc.)and blood biochemical indicators(AST,ALT,PA,etc.)were all detected;systemati-cal observation of organs,organ coefficient calculation and histopathology examination were carried out. RESULTS:There was no statistical significance in those indicators between Compound zedoary turmeric oil cream groups and blank control group (P>0.05),except hemoglobin decreased in intact skin low-dose group,while hemoglobin decreased,LYMPH and PA increased in dam-aged skin high-dose group(P<0.05). Pathology results showed that Compound zedoary turmeric oil cream had no significant toxici-ty for the main organs. CONCLUSIONS:Compound zedoary turmeric oil cream has no long-term toxicity to experimental rats.

A validated LC-MS/MS assay for the quantitative determination of curdione in rabbit plasma and its application to a pharmacokinetic study after administration of zedoary turmeric oil and bioavailability of the oil.

A selective and sensitive liquid chromatography tandem mass spectrometry method was developed for the first time for the identification and quantification of curdione in rabbit plasma after vaginal drug administration and intravenous administration of zedoary turmeric oil (ZTO) solution (10 mg/kg). The analysis was performed on a triple-quadrupole tandem mass spectrometer with multiple reaction monitoring mode via electrospray ionization source in positive ionization mode. After mixing with internal standard diazepam, plasma samples were extracted with ethyl ether-acetic ether (1:1, v/v). Chromatographic separation was carried out on a C18 column with gradient elution using a mixture of water and acetonitrile (both containing 0.1% formic acid) as mobile phases. Linearity ranged over 1.06-106 and 10.6-530 ng/mL (r ≥ 0.995) with the lower limit of quantfication 1.06 ng/mL. The intra- and inter-day precision relative standard deviation values were <12% and the accuracy relative error was from -10.6 to -6.1% at all quality control sample levels. The method was applied to a study of the pharmacokinetics of curdione after vaginal drug administration and intravenous administration of ZTO.