OBJECTIVETo compare the influence on the dissolution of tanshinone IIA (TS IIA) solid dispersions in complex carriers and single, which used in preparation of TS IIA solid dispersions, and further enhance the dissolution of TS IIA.

METHODThe TS IIA solid dispersions were prepared by solvent technique with polyvinylpyrrolidone K30 (PVPK30), poloxamer188 (F68) and combination of PVPK30 and F68 as carriers, respectively. The physical characteristics of TS IIA solid dispersions was studied using differential scanning calorimetry (DSC). Dissolution rates were studied using small cup method (CHP XC III). The solubility of TS IIA with the solid dispersions and pure drug form were determined by HPLC method.

RESULTThe DSC analysis suggested that TS IIA was dispersed as an amorphous form in the combination of PVPK30 and F68. Dissolution profile of the prepared solid dispersions could be described by Weibull equation (R>0.99). For tested three carries, Td value (calculated time to 63.2% of total drug release according to Weibull equation) were (90.40 +/- 2.82) min, (204.5 +/- 8.20) min and (25.83 +/- 0.13) min, respectively. The PVPK30/F68-TS IIA solid dispersion resulted in a significant increase of TS IIA solubility compared with prepared PVPK30-TS IIA and F68-TS IIA solid dispersions (P<0.01).

CONCLUSIONAs compared to single use of PVPK30 or F68, the combination of PVPK30 and F68 improve the dissolution rate and solubility of TS IIA significantly in the prepared solid dispersions (P<0.01). The application of complex carriers in solid dispersion technology should be paid more attention to improvement of poorly soluble drugs dissolution in the future.

OBJECTIVETo analyze the content of tanshinone IIA in Radix Salviae Miltiorrhizae from different habitats are regularly altered and find out the deviation between the studies.

METHODThe data of the content of tanshinone IIA in samples of Radix Salviae Miltiorrhizae from different areas and related information since 1997 was collected and statistically analyzed.

RESULT AND CONCLUSIONThe content of tanshinone IIA in wild Salvia was generally higher than that in the cultivated Salvia, and the content in nearly half cultivated Salvia was less than 0.2%. There existed a big difference between the used statistical model, and the data related the content in samples from Sichuan was the most divisive. The coefficient of variation of wild Salvia was below the cultivated Salvia, and the cultivated Salvia from different areas showed different coefficients of variation. The content of tanshinone IIA was lower when samples were extracted using the heating reflux method.

Triptolide has wide clinical applications due to its anti-inflammatory, anti-tumor and immunosuppressive activities. In this study, we investigated the effect of blocking isopentenyl pyrophosphate (IPP) translocation on the biosynthesis of triptolide by exogenously adding D,L-glyceraldehyde (DLG) to the suspension cells of Ttripterygium wilfordii at different stages (7 d, 14 d). Subsequently, the cell viability, biomass accumulation, triptolide contents, as well as the profiles of the key enzyme genes involved in the upstream pathway of triptolide biosynthesis, were analyzed. The results showed that IPP translocation is involved in the biosynthesis of triptolide. IPP is mainly translocated from the plastid (containing the MEP pathway) to the cytoplasm (containing the MVA pathway) in the early stage of the culture, but reversed in the late stage. Blocking the translocation of IPP affected the expression of key enzyme genes involved in the upstream pathway of triptolide, which in turn affected the accumulation of triptolide. Understanding the characteristics and mechanism of IPP translocation provides a theoretical basis for further promoting triptolide biosynthesis through synthetic biology.
Diterpenes ; Epoxy Compounds ; Hemiterpenes ; Organophosphorus Compounds ; Phenanthrenes

The fibrous roots are the residues of production of cut crude drug of Danshen (Salvia miltiorrhiza). Enzymatic pretreatment and ultrasonic extraction are beneficial to extract effective constituents from fibrous roots more effectively. The present research was to optimize the enzymatic parameters by the central composite design and response surface method. Under the best conditions, the yields of total tanshinones and total salvianolic acids in the extracts of enzymatic pretreatment increased by 113.92% and 30.64%, comparing with the non-enzymatic extraction, respectively. TLC analysis also showed that the types of effective constituents in the two samples were not affected by enzymatic hydrolysis. Meanwhile, the complex correlation coefficients of the mathematical models were high, which provided a good prediction.
Diterpenes, Abietane ; Drugs, Chinese Herbal ; chemistry ; Phenanthrenes ; chemistry ; Plant Roots ; chemistry ; Salvia miltiorrhiza ; chemistry

OBJECTIVETo establish a method to determine the dissolution of Tanshinone IIA in xianling gubao capsules, and compare the dissolution of Xianling Gubao capsules prepared by different processes.

METHODThe small cup method was used at a rotary speed of 100 r x min(-1), the dissolubility was inspected in the following 6 mediums: (1) water; (2) 0.1 mol x L(-1) hydrochloric acid solution; (3) pH 6.8 phosphate buffer; (4) pH 6.8 phosphate buffer solution + 0.5% cholic acid; (5) pH 6.8 phosphate buffer solution + 1.0% cholic acid; (6) pH 7.6 phosphate buffer solution + 4. 0% cholic acid. A HPLC method was used to determine the dissolution samples of tanshione IIA in different dissolution mediums. The accumulative dissolution percentages were calculated, and the resemblance of release curves were compared by similarity factors (f2).

RESULTThe accumulative dissolution percentage was the highest while pH 7.6 phosphate buffer solution + 4.0% cholic acid was used as medium. The similarity factor values (f2) of tanshinone IIA dissolution curves of different preparation processes of Xianling Gubao capsules were all less than 50.

CONCLUSIONThere is significant difference in tanshinone IIA dissolution between Xianling Gubao capsules of different preparation processes. The accumulative dissolution percentages of the tanshinone IIA in new Xianling Gubao capsules is higher than that in the capsules prepared by other preparation processes.

OBJECTIVETo isolate and elucidate the constituents from rhizome of Arundina graminifolia.

METHODTheconstituents were extracted with 95% alcohol and isolated by chromatography on silica gel, Sephedax LH-20. The structures were determined by UV, IR, NMR and MS spectral analysis.

RESULTFive phenanthrene constituents were identified as 7-hydroxy-2, 4-dimethoxy-9, 10-dihydrophenanthrene( I ), 4, 7-dihydroxy-2-methoxy-9, 10-dihydrophenanthrene ( II ), 2, 7-dihydroxy-4-methoxy-9, 10-dihydrophenanthrene ( III ), 7-hydroxy-2-methoxyphenanthrene-1,4-dione ( IV ), 7-hydroxy-2-methoxy-9, 10-dihydrophenanthrene-1,4-dione (V), respectively.

CONCLUSIONAll compounds were isolated from rhizome of A. graminifolia for the first time.

BACKGROUND AND OBJECTIVES: Cisplatin (CP) is a widely used agent for chemotherapy of head and neck squamous cell carcinoma but some tumor cell shows resistance to CP. Accordingly, it is necessary to seek a method to increase the sensitivity of tumor cell to CP. This study was conducted to investigate whether Triptolide (TP) is effective in the inhibition of proliferating head and neck cancer cell and sensitizes cancer cells to CP. MATERIALS AND METHOD: To assess how the combination of TP and CP influence apoptosis of head and neck cancer cell, AMC-HN4 cells were treated with different concentrations of TP and/or CP. Then, their growth was analyzed by XTT assay and the degree of apoptosis was analyzed by flow cytometry. RESULTS: The combination of TP and CP increased suppression of the growth of tumor cells more significantly and enhanced apoptosis more than that of TP or CP alone, and suppressed expression of anti-apoptotic protein. CONCLUSION: This study showed that TP alone had antitumor activity in AMC-HN4 cells, and the combination of TP or CP also might sensitize head and neck cancer cell to CP by suppressing the expression of antiapoptotic protein.
Apoptosis ; Carcinoma, Squamous Cell ; Cisplatin ; Diterpenes ; Epoxy Compounds ; Flow Cytometry ; Head ; Head and Neck Neoplasms ; Neck ; Phenanthrenes

Halofantrine is a newer antimalarial drug which has not been approved for clinical use in Papua New Guinea. We assessed 21 Central Province isolates of Plasmodium falciparum for their in vitro susceptibility to halofantrine. The concentration required to inhibit 50% of parasite growth (IC50) ranged from 0.05 to 7.0 nM with a mean of 1.90 nM and a median of 1.50 nM. The minimum inhibitory concentration (MIC) values ranged from 2.5 to 50 nM with a median of 5.0 nM. All but one isolate had an MIC of 10 nM or less. These results indicate that halofantrine would be a suitable alternative for the treatment of P. falciparum malaria in the region in the future, if and when the need arises, provided that its use was carefully monitored. PIP: Halofantrine is a newer antimalarial drug which has not been approved for clinical use in Papua New Guinea. The authors assessed 21 Central Province isolates of Plasmodium falciparum for their in vitro susceptibility to halofantrine. The concentration required to inhibit 50% of parasite growth (IC50) ranged from 0.05 to 7.0 nmol with a mean of 1.90 nmol and a median of 1.50 nmol. The minimum inhibitory concentration (MIC) values ranged from 2.5 to 50 nmol with a median of 5.0 nmol. All but one isolate had an MIC of 10 nmol or less. These results indicate that halofantrine would be a suitable alternative for the treatment of P. falciparum malaria in the region in the future, if and when the need arises, provided that its use was carefully monitored.
Antimalarials - pharmacology ; In Vitro Techniques ; Microbial Sensitivity Tests ; Papua New Guinea ; Phenanthrenes - pharmacology

Polycyclic aromatic hydrocarbons (PAHs) are a class of common environmental pollutants that pose threats to human health. In this study, a mesophilic bacterial strain CFP312 (grown at 15-37 °C, optimal at 30 °C) was isolated from PAHs-contaminated soil samples. It was identified as Moraxella sp. by morphological observation, physiological and biochemical test, and 16S rRNA gene phylogeny analysis. This is the first reported PAHs degrading strains in Moraxella. Degradation analysis showed that 84% and 90% of the loaded phenanthrene (400 mg/L) were degraded within 48 h and 60 h, and the degradation rates reached 1.21 and 1.29 mg/(L·h), respectively. During the degradation of phenanthrene, phenanthrene-3,4-dihydrodiol was detected as an intermediate. Based on this, it was proposed that double oxygenation at the positions 3 and 4 of phenanthrene was the first step of biodegradation. Adaptability of strain CFP312 to different enhanced phenanthrene-degradation systems was tested in aqueous-organic system, micellar aqueous system, and cloud point system. Strain CFP312 showed good adaptability to different systems. In addition, the bacterium can rapidly degrade the phenanthrene in contaminated soil in slurry-aqueous system, indicating great potential in environmental remediation.
Biodegradation, Environmental ; Humans ; Phenanthrenes ; Polycyclic Aromatic Hydrocarbons ; RNA, Ribosomal, 16S/genetics* ; Soil Microbiology ; Soil Pollutants

Triptolide(TP), the main active and toxic component of Tripterygium wilfordii, has the limitations of low bioavailability, poor absorption, low concentration in plasma, and small lethal dose. Microneedle(MN), the hybrid of hypodermic needle and transdermal patch, is a physical penetration-enhancing system. Dissolving microneedles(DMNs) can be tailored to specific needs of degradation rate. In this study, the TP-loaded DMNs(DMNs-TP) were prepared with the two-step centrifugation method. The optimal ratio of PVA to PVP K30, water content in matrix solution, demoulding method, and plasticizer for preparing DMNs were investigated with the indexes of formability and mechanical strength. The drug loading capacity was determined by HPLC and morphological characteristics were observed under an optical microscope. The mechanical properties were investigated by H&E staining and Franz diffusion cell was used to detect the in vitro skin permeation characteristics. Through the experiment, we confirmed that the optimal backing material should be PVA and PVP K30(3∶1) and the optimal ratio of matrix material to water should be 3∶4. The prepared DMNs-TP were pyramidal with smooth surface and length of approximately 550 μm. Each patch(2.75 cm~2) had the drug loading capacity of(153.41±2.29) μg, and TP was located in the upper part of the needle. The results of in vitro skin permeation assay demonstrated that the cumulative penetration of TP in DMNs-TP reached 80% in 24 h, while little TP solution penetrated the skin, which proved that DMNs promoted the transdermal delivery of TP.
Administration, Cutaneous ; Diterpenes ; Drug Delivery Systems ; Epoxy Compounds ; Needles ; Phenanthrenes ; Skin