Dictamnine

Anticholinesterase activity evaluation of alkaloids and coumarin from stems of Conchocarpus fontanesianus[Reference: WebLink]

Rev. Bras. Farmacogn., 2012, 22(2):374-80.

METHODS AND RESULTS:
Conchocarpus fontanesianus (A. St.-Hill.) Kallunki & Pirani, Rutaceae, popularly known as pitaguará, is a native and endemic tree from São Paulo and Rio de Janeiro States, Brazil. Based in the information that anticholinesterasic derivatives could act as new prototypes to treatment of Alzheimer disease, this work describes the fractionation guided by evaluation of the anticholinesterase activity of the ethanolic stems extract from C. fontanesianus.
CONCLUSIONS:
This procedure afforded the alkaloids Dictamnine (1), γ-fagarine (2), skimianine (3), and 2-phenyl-1-methyl-4-quinolone (4), as well as the coumarin marmesin (5).

Global gene expression profile of Saccharomyces cerevisiae induced by dictamnine.[Pubmed: 18727144]

Yeast. 2008 Sep;25(9):631-41.

Dictamnine, a natural plant product, has been reported to have antimicrobial activity against bacteria and fungi; however, the Dictamnine response mechanisms of microorganisms are still poorly understood.
METHODS AND RESULTS:
We have shown that Dictamnine has antimicrobial activities against the model fungus Saccharomyces cerevisiae, with a minimum inhibitory concentration (MIC) value of 64 microg/ml. Commercial oligonucleotide microarrays were used to determine the global transcriptional response of S. cerevisiae triggered by treatment with Dictamnine. We interpreted our microarray data using the hierarchical clustering tool, T-profiler. Several major transcriptional responses were induced by Dictamnine. The first was the induced environmental stress response, mainly under the control of the Msn2p and Msn4p transcription factors, and the repressed environmental stress response in genes containing the PAC (RNA polymerase A and C box) and rRPE (ribosomal RNA processing element) motifs. The second was the Upc2p-mediated response involved in lipid biosynthesis. The third comprised the PDR3- and RPN4-mediated responses involved in multidrug resistance (MDR). Finally, the TBP-mediated response was induced with Dictamnine treatment.
CONCLUSIONS:
TBP is an essential general transcription factor involved in directing the transcription of genes. Quantitative real-time RT-PCR was performed on selected genes to verify the microarray results. Furthermore, morphological transitions during Dictamnine exposure to S. cerevisiae L1190 (MATa/alpha) were examined, using confocal laser microscopy.

Study on in Vitro Antifungal Activity of Dictamnine against Candida albicans.[Reference: WebLink]

Chinese Agricultural Science Bulletin, 2009, 25(16): 21-4.

Candida albicans (C. albicans) and other fungi important human and veterinary pathogens.
METHODS AND RESULTS:
The minimal inhibitory concentration (MIC) of Dictamnine alone and in combination with fluconazole (FLC) against clinical 22 clinical Candida albicans were tested, and checkerboard assay was used to analyze the ractional inhibitory concentration index (FICI) of the combination of Dictamnine and FLC.
CONCLUSIONS:
The result showed that Dictamnine had good antifungal activity alone and in combination with FLC against Candida albicans.

Isolation and Anti-inflammatory Effect of Dictamnine Extracted from Dictamni Cortex.[Reference: WebLink]

Chinese Journal of Experimental Traditional Medical Formulae, 2012, 18(14):128-31.

To detect the anti-inflammatory effects of ethanol extracts and Dictamnine extracted and isolated from Dictamni Cortex.
METHODS AND RESULTS:
High performance centrifugal partition chromatography method was used for separation of the essential Dictamnine,and anti-inflammatory effects of ethanol extracts and Dictamnine were investigated by xylene-induced aruical swelling in mice and the abdominal capillary permeability in mice.Separation was performed with a two-phase solvent system composed of hexane ethylacetate-ethanol-water(1∶1∶1∶1).The purity of Dictamnine obtained was 98% determined by high performance liquid chromatograph.The results showed that each dosage of ethanol extracts could significantly(P0.05) suppress the mouse auricle which caused by the xylene swelling(being 44.26%,52.46%,44.26%,respectively),as compared with the control group.The medium-dosage group of Dictamnine could obviously(P0.01) suppress the mouse auricle but the dosage was not increased significantly in abdominal capillary permeability in mice compared with control group.
CONCLUSIONS:
HPCPC is a recommendable method to prepare and purify the dictamnie with good separation and the method is simple,accurate and easy to operate.The results showed that ethanol extracts and Dictamnine showed different anti-inflammatory effect in variety of animal models of anti-inflammatory.

Cytotoxic effect of dictamnine on HepG2 cells and its possible mechanism[Reference: WebLink]

Chinese Journal of Pharmacology & Toxicology, 2013, 27(1):95-100.

To study the Dictamnine-induced hepatotoxicity in vitro and to explore its mechanism.
METHODS AND RESULTS:
HepG2 cells were exposed to Dictamnine 2.5-800 μmol·L-1 for 24 h,and cell viability was examined by MTT assay.Cell membrane injury was examined by detecting the release rate of lactate dehydrogenase(LDH),and the morphological changes were observed under a contrast microscope.The activities of alanine transaminase(ALT),aspartate aminotransferase(AST),glutathione S-transferase(GST) and glutamyltranspeptidase(GGT) in HepG2 cell cultures were measured using enzyme-labeled instrument,respectively.The mitochondrial membrane potential was measured by laser scanning confocal fluorescence microscope.RESULTS HepG2 cell viability was significantly reduced following exposure to Dictamnine 25-800 μmol·L-1 for 24 h in a concentration-dependent manner(r=0.965,P0.05),and IC50 value was(283±27)μmol·L-1.The LDH release rate of HepG2 cells was significantly increased after exposure to Dictamnine 12.5-50 μmol·L-1 for 24 h(P0.01).The morphology of HepG2 cells after 24 h exposure to Dictamnine 100 and 200 μmol·L-1 was changed greatly.The cells wrinkled up and dropped.Compared with control group,ALT and AST activities in HepG2 cell culture were significantly increased(P0.05) in a concentration-dependent manner(r=0.995,P0.05 and r=0.996,P0.05) following exposure to Dictamnine 100 and 200 μmol·L-1 for 24 h,and the mitochondrial membrane potential markedly declined(r=0.978,P0.05).After exposure to Dictamnine 100 and 200 μmol·L-1 for 4 h,GST activity in HepG2 cell culture was significantly increased(P0.05);and for 24 h,GST activity in Dictamnine 50,100 and 200 μmol·L-1 groups was also increased in a concentration-dependent manner(r=0.987,P0.05).After exposure to Dictamnine 200 μmol·L-1 for 48 h,GGT activity in HepG2 cell culture was increased(P0.05).
CONCLUSIONS:
Dictamnine at higher concentrations(≥100 μmol·L-1)has potential hepatotoxicity.The cell membrane damage and mitochondrial membrane damage may be involved in the Dictamnine-induced hepatotoxity mechanism.

Mutat Res. 1985 Dec;144(4):221-5.

Mutagenic activities of dictamnine and gamma-fagarine from dictamni radicis cortex (Rutaceae).[Pubmed: 4069140]

A methanol extract of Dictamni Radicis Cortex exhibited a mutagenic effect on Salmonella typhimurium TA100 and TA98 with S9 mix.
METHODS AND RESULTS:
Two mutagenic compounds in Dictamni Radicis Cortex were isolated on a Sephadex LH 20 column and silica gel column chromatography and by preparative TLC. These were identified as Dictamnine and gamma-fagarine by UV, EI-Mass, 1H-NMR. Dictamnine and gamma-fagarine were mutagenic in strain TA100 and TA98 with S9 mix. The dose-response curves were linear in the range 10-40 micrograms.
CONCLUSIONS:
Dictamnine and gamma-fagarine had specific activities (His+/microgram) of about 50-70 revertant colonies in strain TA100, while in strain TA98 there were about 30-50 revertant colonies.