OBJECTIVEUnder various drought conditions and nitrogen application, the content of vindoline, catharanthine, vincristine and vinblastine in the leaf of Catharanthus roseus were illustrated to improve the content of alkaloid theoretically.

METHODSix groups were set in the experiment, which included: CK (natural control), CN (natural control + nitrogen), LK (low drought), LN (low drought + nitrogen), HK (high drought), HN (high drought + nitrogen) to discuss the change characteristics of total nitrogen, the activity of alkaline POD and TDC, the content of four alkaloids under the different conditions were measured.

RESULTUnder LK condition, the activity of POD, TDC were enhanced. In the early stage of stress (0-21 d), vindoline, catharanthine, vincristine and vinblastine accumulated, and reduced in the later stage (28-35 d). For all groups, adding exogenous nitrogen could improve the total content of nitrogen, vindoline and vinblastine, meanwhile the activity of POD and TDC were enhanced as well. The LN, HN treatments were beneficial to accumulating catharanthine and vinblastine.

CONCLUSIONDrought stress or additional nitrogen have an influence on both of the activities of POD and TDC, and the four alkaloids were affected as well. Thereinto, the LN condition was the most effective treatment for accumulating the four alkaloids (vindoline, catharanthine, vincristine and vinblastine), which were regulated by improve nitrogen content and enzymatic activity.

Catharanthus ; metabolism ; Nitrogen ; metabolism ; Peroxidase ; metabolism ; Stress, Physiological ; Vinblastine ; analogs & derivatives ; metabolism ; Vinca Alkaloids ; metabolism ; Vincristine ; metabolism ; Water ; metabolism

AIM: To identify the structure of the acid-catalyzed product of strictosamide and explore the reaction mechanism. METHODS: The acid-catalyzed reaction process of strictosamide was monitored by HPLC, and a macroporous resin was used to purify the reaction solution. The structure of the product was confirmed by MS, NMR, and ROESY spectra. RESULTS: The acid-catalyzed transformation yield from strictosamide to vincoside lactam was 52%. CONCLUSION The reaction mechanism of the transformation from strictosamide to vincoside lactam may be related to the stability of the three-dimensional configuration of the compound. These results offer a new way to obtain vincoside lactam from the widely distributed indole alkaloid strictosamide by acid-catalysis.
Acids ; chemistry ; Catalysis ; Lactams ; chemistry ; Molecular Structure ; Vinca Alkaloids ; chemistry

Catharanthine content and agronomic traits in major Catharanthus roseus varieties were analyzed. It was found that there existed great difference in catharanthine content and agronomic traits among the varieties. Catharanthine content was the highest in variety Pacifica Polka Dot (PPD), reaching 3.79 mg g(-1) dry leaf weight, and the lowest in variety Cooler Pink (CP) with only 0.9 mg g(-1) dry leaf weight. Correlation existed in certain extent between catharanthine content and agronomic traits in C. roseus. Path analysis showed that among all the agronomic traits analyzed, internodal distance positively affected catharanthine content at significant level (P<0.05), with the path coefficient being 1.473. This study provides useful information for high-catharanthine content C. roseus introduction and breeding.
Catharanthus ; anatomy & histology ; chemistry ; metabolism ; Plant Leaves ; anatomy & histology ; chemistry ; metabolism ; Vinca Alkaloids ; analysis ; metabolism

OBJECTIVEThe content of vindoline, catharanthine and vinblastine in the root, stem, leaf, flower and fruit of Catharanthus roseus at various developmental stages were determined, and the biomass allocation was also determined to find the best harvest time.

METHODThe content of vindoline, catharanthine and vinblastine in the root, stem, leaf, flower and fruit of C. roseus were determined by HPLC.

RESULTThe content of these alkaloids were influenced by season and it varied in the different tissues of the plant. The content of vindoline and catharanthine in the leaves were the highest, and there was no vindoline detected in the root, but the content of vinblastine in the flower was the highest; the content of vindoline and catharanthine reached the maximum between the August and September, and the content of vinblastine reached the highest after the September. The biomass was the highest in the initial stage of September.

CONCLUSIONThe best harvest time was in the initial stage of September.

Catharanthus ; chemistry ; growth & development ; metabolism ; China ; Chromatography, High Pressure Liquid ; Flowers ; chemistry ; growth & development ; metabolism ; Plant Extracts ; analysis ; metabolism ; Plant Leaves ; chemistry ; growth & development ; metabolism ; Plant Roots ; chemistry ; growth & development ; metabolism ; Seasons ; Vinblastine ; analogs & derivatives ; analysis ; metabolism ; Vinca Alkaloids ; analysis ; metabolism

BACKGROUND: Although combined chemotherapy has increased survival rates among children with cancer, such treatments can induce sensorineural hearing loss. Therefore, we aimed to identify risk factors for hearing impairments in patients with childhood cancer.METHODS: Audiograms were obtained from 115 patients with childhood cancer and survivors (age < 20 years). Pure tone audiometry (PTA) was performed at octave intervals within the range of 250-8000 Hz. We evaluated clinical risk factors associated with hearing impairments. Hearing loss was evaluated based on the maximal decibel (dB) loss in any frequency for each ear (RA(max) or LA(max)) and weighted mean dB loss for specific frequencies (RA(avg) or LA(avg)).RESULTS: Forty percent of patients (N=46) exhibited hearing loss >20 dB based on the weighted mean value in either ear. Severe hearing impairments were observed in 56% of patients with brain tumors. Although cisplatin or vinca alkaloids were significant risk factors for hearing impairment, the use of both cisplatin and vinca alkaloids exhibited the highest odds ratio for hearing impairment (P < 0.001, < 0.001 for R/LA(max); P=0.099, 0.039 for R/LA(avg)). Multivariate analysis revealed that the use of both cisplatin and vinca alkaloids was an independent risk factor for hearing impairment based on RA(max), LA(max), and LA(avg) (P < 0.001, < 0.001, 0.039, respectively).CONCLUSION: Our findings indicate that cisplatin and vinca alkaloids exert an additive effect on the risk of hearing impairment in survivors of childhood cancer. Further prospective studies are thus required to determine the most effective chemotherapeutic regimen for reducing ototoxicity.
Audiometry ; Brain Neoplasms ; Child ; Cisplatin ; Drug Therapy ; Ear ; Hearing Loss ; Hearing Loss, Sensorineural ; Hearing ; Humans ; Multivariate Analysis ; Odds Ratio ; Prospective Studies ; Risk Factors ; Survival Rate ; Survivors ; Vinca Alkaloids ; Vinca

To study chemical constituents of the leaves of Nauclea officinalis, eight alkaloids were isolated from 95% ethanol extract by various chromatographic methods. The structures were elucidated on the basis of spectroscopic data (IR, UV, ESI-MS, 1D and 2D NMR) and identified as naucleactonin C (1), strictosamide (2), vincosamide (3), pumiloside (4), angustoline (5), angustine (6), 18, 19-dihydroangustine (7) and naucleofficine D (8). Compound 1 is a new indole alkaloid. Compounds 6 and 7 were isolated from this plant for the first time.
Alkaloids ; chemistry ; isolation & purification ; Camptothecin ; analogs & derivatives ; chemistry ; isolation & purification ; Indole Alkaloids ; chemistry ; isolation & purification ; Indoles ; chemistry ; isolation & purification ; Molecular Structure ; Plant Leaves ; chemistry ; Plants, Medicinal ; chemistry ; Rubiaceae ; chemistry ; Vinca Alkaloids ; chemistry ; isolation & purification

OBJECTIVETo study on the purification of strictosamide from Nauclea officinalis by macroporous resin to provide reference for production.

METHODThe best macroporous resin was selected among 10 kinds of resins according to adsorption and desorption of the static adsorption experiments. The adsorption quantity, elution volume of water, concentration and elution volume of alcohol were determined according to the single factor experiment.

RESULTHPD400 was the best resin, and the best adsorption quantity was 20.23 mg x g(-1), the elution volume of water and 30% alcohol was 6 BV, and the elution volume of 70% alcohol was 4 BV.

CONCLUSIONThis technology is simple, feasible, and it can provide reference for the industrialized production.

Adsorption ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Ethanol ; chemistry ; Resins, Synthetic ; chemistry ; Rubiaceae ; chemistry ; Technology, Pharmaceutical ; methods ; Vinca Alkaloids ; chemistry ; isolation & purification

The objective of this study is to compare the differences between self-microemulsifying drug delivery system (SMEDDS) and solid dispersion (SD) technology used to improve the dissolution rate and bioavailability of vinpocetine (VIP). The formulation of VIP-SMEDDS was composed of Labrafac, oleic acid, Cremophor EL, Transcutol P, and gum acacia which was used as solid absorbent. VIP-SD was prepared using poloxamer F68 as the carrier. In the solubility test, the solubility of VIP in SMEDDS was 17.3 times as much as that in SD. In the dissolution test, SMEDDS had shown better enhancement and stability in dissolving VIP than SD. When compared to VIP crude powder, the bioavailability of VIP in SMEDDS (VIP-SMEDDS) was 1.89-fold higher, and was less affected by food intake. However, the bioavailability of VIP in SD (VIP-SD) was bioequivalent to that of VIP crude powder. The tissue uptake of VIP-SMEDDS in Peyer's patches, intestine and liver after administration for 2 hours was more favorable than that of VIP-SD, which was 3.7 times higher in Peyer's patches, 2.2 times higher in intestine and 1.5 times higher in liver. In Caco-2 tests, the apparent permeability (P(app)) of VIP-SMEDDS was 2.65 times of that of VIP-SD. The width of the cell tight junctions of Caco-2 cell monolayer treated with VIP-SMEDDS were 9.6-fold wider, but there was no significant change after treatment with VIP-SD, when compared to the blank control. In conclusion, SMEDDS was more efficient than the traditional SD technology in increasing solubility, dissolution, intestinal permeability, lymphatic absorption and bioavailability of the insoluble drugs such as VIP, which is less affected by food intake.
Animals ; Biological Availability ; Caco-2 Cells ; Dosage Forms ; Drug Delivery Systems ; Emulsions ; chemistry ; pharmacokinetics ; Humans ; Male ; Rats ; Rats, Sprague-Dawley ; Solubility ; Vinca Alkaloids ; chemistry ; pharmacokinetics

OBJECTIVE: A number of disease-modifying anti-rheumatic drugs (DMARDs) have been shown to be more effective than placebo in the management of rheumatoid arthritis (RA). However, most course of DMARDs, except methotrexate, are discontinued after 2 or 3 years, because of toxicity, lack of efficacy or escape from control. The multi-drug resistance (MDR) is a phenomenon in which cells develop cross-resistance to many agents such as anthracyclin, vinca alkaloids and colchicine. In our hypothesis, MDR phenomenon could be implicated in acquired resistance to DMARDs in RA. We have established a mdr1 cell line and tested whether DMARDs are substrate for P-glycoprotein (P-gp). METHODS: The mdr1-cDNA was cloned into retroviral vector, and the recombinant retroviral vector was transfected into PA317 cells. The target cells, NIH3T3, were infected with recombinant retroviruses. A colony most resistant to vinblastin was selected for the following experiments; expression of mdr1 gene in NIH3T3 cells was confirmed by RT-PCR, and biological function of mdr1 gene product, P-gp, was tested using Rhodamine-123 (Rh123) efflux assay. Resistance of the target cells expression P-gp which can survive against hydroxychloroquine (HCQ) and methotrxate (MTX) were measured by MTT assay. RESULTS: RT-PCR for mdr1 gene showed successful transfer of the gene into the NIH3T3 cells. Rh123 assay revealed expression of P-gp on the selected cells as follows; Rh123 efflux activity of uninfected NIH3T3 cells was 6%, that of PLXSN was 0.2%, and that of selected cells was 44%. The 50% proliferation inhibitory capacity of the selected cells were twice for HCQ but there was no difference of that for MTX. CONCLUSION: We established a mdr1 cell line and using the cell line, HCQ was a substrate of MDR, but MTX was not related to MDR.
Antirheumatic Agents* ; Arthritis, Rheumatoid ; Cell Line ; Clone Cells ; Colchicine ; Drug Resistance, Multiple ; Hydroxychloroquine ; Methotrexate ; P-Glycoprotein ; Retroviridae ; United Nations ; Vinca Alkaloids ; Zidovudine

In order to study the chemical constituents in the water extract of the stem of Nauclea officinalis, column chromatography over D101 macroporous resin and silica gel and an automatic purification system were used to isolate and purify the chemical constituents from the extract. Nine compounds were obtained. By analysis of the physicochemical properties and spectral data, their structures were identified as naucleamide G (1), 3, 4-dimethoxyphenol-beta-D-apiofuranosyl (1-->6)-beta-D-glucopyranoside (2), kelampayoside A (3), 3alpha, 5alpha-tetrahydrodeoxycordifoline lactam (4), naucleamide A-10-O-beta-D-glucopyranoside (5), pumiloside (6), 3-epi-pumiloside (7), strictosamide (8) and vincosamide (9), separately. Among them, compound 1 is a new compound, compound 2 was found in plants of the genus Nauclea for the first time, and compounds 3 and 4 were isolated from this plant for the first time.
Camptothecin ; analogs & derivatives ; chemistry ; isolation & purification ; Carbolines ; chemistry ; isolation & purification ; Glucosides ; chemistry ; isolation & purification ; Indole Alkaloids ; chemistry ; isolation & purification ; Molecular Structure ; Plant Stems ; chemistry ; Plants, Medicinal ; chemistry ; Rubiaceae ; chemistry ; Vinca Alkaloids ; chemistry ; isolation & purification