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1.
J. venom. anim. toxins incl. trop. dis ; 27: e20200073, 2021. tab, graf, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1154769

ABSTRACT

he resistance against antimalarial drugs represents a global challenge in the fight and control of malaria. The Brazilian biodiversity can be an important tool for research and development of new medicinal products. In this context, toxinology is a multidisciplinary approach on the development of new drugs, including the isolation, purification, and evaluation of the pharmacological activities of natural toxins. The present study aimed to evaluate the cytotoxicity, as well as the antimalarial activity in silico and in vitro of four compounds isolated from Rhinella marina venom as potential oral drug prototypes. Methods: Four compounds were challenged against 35 target proteins from P. falciparum and screened to evaluate their physicochemical properties using docking assay in Brazilian Malaria Molecular Targets (BraMMT) software and in silico assay in OCTOPUS® software. The in vitro antimalarial activity of the compounds against the 3D7 Plasmodium falciparum clones were assessed using the SYBR Green I based assay (IC50). For the cytotoxic tests, the LD50 was determined in human pulmonary fibroblast cell line using the [3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay. Results: All compounds presented a ligand-receptor interaction with ten Plasmodium falciparum-related protein targets, as well as antimalarial activity against chloroquine resistant strain (IC50 = 3.44 µM to 19.11 µM). Three of them (dehydrobufotenine, marinobufagin, and bufalin) showed adequate conditions for oral drug prototypes, with satisfactory prediction of absorption, permeability, and absence of toxicity. In the cell viability assay, only dehydrobufotenin was selective for the parasite. Conclusions: Dehydrobufotenin revealed to be a potential oral drug prototype presenting adequate antimalarial activity and absence of cytotoxicity, therefore should be subjected to further studies.(AU)


Subject(s)
Bufanolides/administration & dosage , Bufonidae , Biodiversity , Malaria/immunology , Antimalarials , In Vitro Techniques , Computer Simulation
2.
Article in Chinese | WPRIM | ID: wpr-773157

ABSTRACT

As known,simultaneous determination of various chemical indicators is one of the future trends in quality control of traditional Chinese medicines because of the extremely complex chemical compositions. This project is to screen the quality markers that can accurately control the quality of the Bufonis Venenum by exploring the intrinsic correlation of components. In this study,venom of Bufo bufo gargarizans from 17 different sources were used as research samples,and the contents of 7 bufogenin were determined by HPLC-DAD. Then,the data obtained were analyzed by Spearman correlation analysis and principal component analysis( PCA). In addition,a stepwise regression analysis was used to establish a predictive model for the contents of the seven bufogenin components( independent variable) and the total contents of the bufogenin( dependent variable). The results indicated that there is a significant positive correlation between the contents of telocinobufagin and cinobufotalin,and there is a significant positive correlation between the contents of bufalin,cinobufagin and resibufogenin. In contrast,the contents of telocinobufagin and cinobufotalin are negatively correlated with the contents of bufalin,cinobufagin and resibufogenin. However,the correlation between gamabufotalin and bufotalin and other components are not obvious. Furthermore,further study found that there is a correlation between the sum of the contents of bufalin,cinobufagin and telocinobufagin and the total contents of the bufogenin. In fact,the application of bufalin,cinobufagin and telocinobufagin as the quality control indicators of the Bufonis Venenum can better reflect the quality characteristics of the Bufonis Venenum compared with the previous quality control indicators. The conclusions will provide a reference for the revision of the quality standards of the Bufonis Venenum.


Subject(s)
Amphibian Venoms , Chemistry , Animals , Bufanolides , Bufo bufo , Chromatography, High Pressure Liquid , Medicine, Chinese Traditional , Quality Control
3.
Article in English | LILACS, VETINDEX | ID: biblio-1002500

ABSTRACT

Studies on toad poison are relevant since they are considered a good source of toxins that act on different biological systems. Among the molecules found in the toad poison, it can be highlighted the cardiotonic heterosides, which have a known mechanism that inhibit Na+/K+-ATPase enzyme. However, these poisons have many other molecules that may have important biological actions. Therefore, this work evaluated the action of the low molecular weight components from Rhinella schneideri toad poison on Na+/K+-ATPase and their anticonvulsive and / or neurotoxic effects, in order to detect molecules with actions of biotechnological interest. Methods: Rhinella schneideri toad (male and female) poison was collected by pressuring their parotoid glands and immediately dried and stored at -20 °C. The poison was dialysed and the water containing the low molecular mass molecules (< 8 kDa) that permeate the dialysis membrane was collected, frozen and lyophilized, resulting in the sample used in the assays, named low molecular weight fraction (LMWF). Na+/K+ ATPase was isolated from rabbit kidneys and enzyme activity assays performed by the quantification of phosphate released due to enzyme activity in the presence of LMWF (1.0; 10; 50 and 100 µg/mL) from Rhinella schneideri poison. Evaluation of the L-Glutamate (L-Glu) excitatory amino acid uptake in brain-cortical synaptosomes of Wistar rats was performed using [3H]L-glutamate and different concentration of LMWF (10-5 to 10 µg/µL). Anticonvulsant assays were performed using pentylenetetrazole (PTZ) and N-methyl-D-aspartate (NMDA) to induce seizures in Wistar rats (n= 6), which were cannulated in the lateral ventricle and treated with different concentration of LMWF (0.25; 0.5; 1.0; 2.0; 3.0 and 4.0 µg/µL) 15 min prior to the injection of the seizure agent. Results: LMWF induced a concentration-dependent inhibition of Na+/K+-ATPase (IC50% = 107.5 μg/mL). The poison induces an increased uptake of the amino acid L-glutamate in brain-cortical synaptosomes of Wistar rats. This increase in the L-glutamate uptake was observed mainly at the lowest concentrations tested (10-5 to 10-2 µg/µL). In addition, this fraction showed a very relevant central neuroprotection on seizures induced by PTZ and NMDA. Conclusions: LMWF from Rhinella schneideri poison has low molecular weight compounds, which were able to inhibit Na+/K+-ATPase activity, increase the L-glutamate uptake and reduced seizures induced by PTZ and NMDA. These results showed that LMWF is a rich source of components with biological functions of high medical and scientific interest.(AU)


Subject(s)
Animals , Poisons , Synaptosomes , Bufo rana , Neuroprotection , Anticonvulsants , Glutamic Acid , Molecular Weight
4.
Article in Chinese | WPRIM | ID: wpr-851886

ABSTRACT

Bufonis Venenum, as a precious Chinese materia medica, has complex chemical constituents and has been widely used in clinical treatment with significant effects. The chemical constituents in Bufonis Venenum mainly included bufadienolides, indole alkaloids, and steroids, etc. Modern pharmacological research has demonstrated its antitumor, cardiac, anti-inflammatory, and narcotic analgesic, etc. This paper reviewed the chemical constituents, pharmacological activity, and artificial synthesis of Bufonis Venenum, providing theoretical reference for material basic research, pharmacodynamic mechanism interpretation, development, and utilization.

5.
Article in Chinese | WPRIM | ID: wpr-687373

ABSTRACT

Toad venom (Chansu) is prepared from the dried secretion of parotid gland and skin gland from Bufo bufo gargarizans or B. melanostictus. Up to now, much attention shall be paid to the poor quality of commercial toad venom because of the adulteration. So, it is urgent to establish a scientific and perfect quality control method to improve the quality of toad venom and guarantee its safety and effectiveness in clinical application. The different batches of toad venom samples were assayed by high performance liquid chromatography (HPLC) and the quantitative analysis of multi-components by single marker (QAMS) was used to detect the contents of five bufagenins. As a result, the reference characteristic chromatogram was established, displaying serotonin, gamabufotalin, arenobufagin, hellebrigenin, telocinobufagin, bufotalin, cinobufotalin, bufalin, cinobufagin and resibufogenin as characteristic peaks. Taking cinobufagin as an internal reference substance, QAMS was verified for the determination of five bufagenins (gamabufotalin, bufotalin, bufalin, cinobufagin, resibufogenin) in toad venom samples. The durability and applicability of the relative correction factor (RCF) were also studied systematically. RCFs of cinobufagin to gamabufotalin, bufotalin, bufalin and resibufogenin were determined as 1.05, 0.895, 1.09 and 0.913, respectively. The characteristic chromatogram and QAMS established in this study could effectively control the quality of toad venom and provide scientific evidence for the improvement of the quality standard of the toad venom to be described in Chinese Pharmacopoeia (2020 edition).

6.
Article in Chinese | WPRIM | ID: wpr-275448

ABSTRACT

Toad venom (Chansu) is prepared from the dried secretion of Bufo bufo gargarizans or B. melanostictus. It is not only one of the famous and expensive traditional Chinese medicines(TCMs) from animal origin, but also one of 28 kinds of toxic TCMs to be required for special management issued by the State Council of the People's Republic of China. Chansu contains the rich bufadienolides and indole alkaloids, and displays various bioactivity including cardiotonic, anti-tumor, analgesia, and local anesthesia. Based on the published references in the recent years, the advance on the identification of adulterants and quality evaluation as well as the influence factors on the quality of toad venom was summarized to improve the quality standards and promote the level of quality control of toad venom and its preparations.

7.
Article in Chinese | WPRIM | ID: wpr-852974

ABSTRACT

Objective: To establish an HPLC-MS method for determining nine bufadienolides (gamabufotalin, arenobufagin, telocinobufagin, desacetylcinobufotalin, bufotalin, cinobufotalin, bufalin, cinobufagin, and resibufogenin) in Bufonis Venenum and Liushen Pill. Methods: HPLC analysis was performed on ODS-2 column (250 mm×4.6 mm, 5 μm) with the mobile phase made up of acetonitrie and 0.15% phosphoric in water. Flow rate was set at 1 mL/min and column temperature was 40℃. The detection wavelength was 296 nm. Nine bufadienolides were determined by HPLC-ESI-TOF-MS with the mobile phase made up of acetonitrie and 0.2% formic acid in water. Eletrospray ionization source was applied and operated in the positive ion mode. Results: Nine bufadienolides were separated at baseline with good linearity (r≥0.9996). The recovery rates were 92%-105% (RSD<5%). Conclusion: The method established is rapaid, simple, and accurate, which is helpful to control the quality of Liushen Pill.

8.
Article in Chinese | WPRIM | ID: wpr-678758

ABSTRACT

The latest results from our research group in the biotransformation of triptolides and bufadienolides were reviewed. The trends in the development of biotransformation in the future were also briefly discussed.

9.
Article in Chinese | WPRIM | ID: wpr-521683

ABSTRACT

Objective To establish a method used for quantitative determination of bufadienolides in human liver tissues by HPLC. Methods using solid phase extraction of human liver with Oasis (HLB car-tridge coupled with reserved phase HPLC and diode array detection. Results Recoveries obtained from spiked liver for the bufadienolides were better than 70% . The linearity was studied up to 1200ng/g and the detection limits of the method was 0.4ng for cinobufotalin and bufalin, 0.5ng for cinobufagin and resibufo-genin. Conclusion This method is fast and accurate. It is useful for forensic medicine detection.

10.
Article in Chinese | WPRIM | ID: wpr-577640

ABSTRACT

AIM: To investigate the concentration of bufadienolides in Liushen Pill from two enterprises. METHODS: Four kinds of bufadienolides were simultaneously determined by using HPLC with DAD detector. RESULTS: Recoveries obtained from the four kinds of bufadienolides were higher than 96%,the linearity was in the range of 1 ?g/mL-100 ?g/mL.The concentration of bufadienolides in Liushen Pill was significantly higher than that in other related TCM compatibilities. CONCLUSION: The well-distributed compatibility in Liushen Pill has an influence on the solubilization of bufadienolides,may be in relation to eahancing to release.

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