Screening of Isoquinoline Alkaloids for Potent Lipid Metabolism Modulation with<i>Caenorhabditis elegans</i>

Chow, Yit-Lai; Sato, Fumihiko

doi:10.1271/bbb.130523

Cited by 10 publications

(19 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…More abundant molecules are alkaloids from isoquinoline class as 2 (17.17%) in leaves and (14.79%) in barks, 1 (31.07%) in leaves and (17.13%) in barks, 3 (9.63%) and 4 (8.61%). As reported in literature [30] isoquinoline alkaloids exhibit strong pharmacologic activity: berberine, sanguinarine, magnoflorine, tetrandine and aromoline alkaloids from this class showed lipid-reducing activity in Caenorabditis elegans. Compound 2 is an alkaloid characterized in species like Sinomenii caulis [31].…”

Section: Chemical Composition and Antioxidant Capacitysupporting

confidence: 57%

Identification of Alkaloid’s Profile in Ficus benjamina L. Extracts with Higher Antioxidant Power

Novelli¹,

Canuti²,

Canini³

2014

AJPS

View full text Add to dashboard Cite

Different classes of known alkaloid compounds were identified for the first time in leaves and barks of Ficus benjamina L. from Moraceae family. The identification of 28 alkaloids in F. benjamina leaves and 14 alkaloids in its barks was identified using chromatographic analysis as Gas Chromatography associated to Mass Spectrometry (GC-MS). This characterization analysis allows to verifying the presence of different alkaloids type-classes in both leaves and barks, such as isoquinoline class, indole class and quinolizidine class. The quantification results are deduced by analysis with spectrophotometric assay, using a calibration curve of boldine as standard alkaloid that reveals the presence of 26 ± 0.1 μg of alkaloids boldine equivalent in 1 gram of F. benjamina leaves and 3.8 ± 0.1 μg alkaloids boldine equivalent in 1 gram of its barks. A significant correlation was observed between the total alkaloid content of crude extracts and 2,2-diphenyl-1-picrylhydrazyl assay (DPPH), suggesting that the level of antioxidant activity in this species is strongly correlated to the alkaloid content. These findings should provide useful information for future on the pharmaceutical properties of these alkaloids from F. benjamina.

show abstract

Section: Chemical Composition and Antioxidant Capacitysupporting

confidence: 57%

Identification of Alkaloid’s Profile in Ficus benjamina L. Extracts with Higher Antioxidant Power

Novelli¹,

Canuti²,

Canini³

2014

AJPS

View full text Add to dashboard Cite

show abstract

“…5) However, this worm has extensive physical (such as a thick cuticle) and molecular (detoxification enzymes) defense mechanisms against xenobiotics. In many studies, the effective doses of test compounds in the worm were often several orders of magnitude higher than those in a mammalian cell culture.…”

Section: Discussionmentioning

confidence: 99%

“…22) Whereas we could not confirm the high content of sanguinarine in worm, sanguinarine could have higher bioavailability and thus is effective at a lower concentration (25 μM) than berberine (500 μM), as found in our previous experiment. 5) Many pharmaceutical drugs are isolated directly from plants or are semi-synthetic derivatives of natural products. However, the pipeline of drug discovery faces technical challenges in isolating new compounds with diverse structures and complex chemistries in sufficient quantities for screening.…”

Section: Discussionmentioning

confidence: 99%

“…12, -2013 through Oil Red O staining at 500 μM for berberine and 25 μM for sanguinarine, but lower concentrations, such as 50 μM berberine and 10 μM sanguinarine, were less effective. 5) In an attempt to enhance the sensitivity of the worm screening system and to minimize the effective concentration of test compounds needed for bioactivity assays, the detoxification response in C. elegans was impeded by knocking down nhr-8 and treating nhr-8 RNAi worms with lower alkaloid concentrations to check if this could increase the alkaloid bioavailability in these worms. Next, we investigated if the increased sensitivity to alkaloid treatment could be due to higher bioavailability in the worms by analyzing the accumulation of alkaloids in the worms.…”

Section: )mentioning

confidence: 99%

“…5) Since the detoxification process might reduce the effectiveness of alkaloids, we knocked-down nhr-8, a nuclear hormone receptor gene that is involved in the xenobiotic resistance response, with RNAi and examined the worm's susceptibility to alkaloid treatment (Supplemental Fig. 1).…”

Section: Rnai Knockdown Of Nhr-8 Enhanced the Lipidreducing Activity mentioning

confidence: 99%

See 2 more Smart Citations

Knockdown of the NHR-8 nuclear receptor enhanced sensitivity to the lipid-reducing activity of alkaloids in Caenorhabditis elegans

Chow

Kawasaki

Sato

2014

Bioscience, Biotechnology, and Biochemistry

Self Cite

View full text Add to dashboard Cite

Caenorhabditis elegans is a versatile, whole-organism model for bioactivity screening. However, this worm has extensive defensive mechanisms against xenobiotics which limit its use for screening of pharmacologically active compounds. In this study, we report that knockdown of nhr-8, a gene involved in the xenobiotic response, increased the worm’s sensitivity to the lipid-reducing effects of some isoquinoline alkaloids, especially berberine. On the other hand, crude extract of rhizome and cultured cells showed enhanced biological activity compared to the pure alkaloids in wild type worm, but this enhanced activity was not detected in nhr-8 RNAi worm, suggesting that some components in cell extracts might interfere with the defense response in this worm. The possibility of using C. elegans as a model for screening bioactive chemicals is discussed.

show abstract

Drug discovery: Insights from the invertebrate Caenorhabditis elegans

Giunti

Andersen

Rayes

et al. 2021

Pharmacology Res & Perspec

View full text Add to dashboard Cite

Since its introduction into research by Sydney Brenner in the early 60s, the nematode Caenorhabditis elegans has played a pivotal role in different areas of biomedical investigation. 1-9 Studies on C. elegans have contributed to fundamental breakthroughs in life science, such as the discovery of genetic regulators of programmed cell death, the use of the green fluorescent protein (GFP) as a protein marker, and the discovery of RNA interference (RNAi). 10-12

show abstract

Screening of Isoquinoline Alkaloids for Potent Lipid Metabolism Modulation withCaenorhabditis elegans

Cited by 10 publications

References 28 publications

Identification of Alkaloid’s Profile in Ficus benjamina L. Extracts with Higher Antioxidant Power

Identification of Alkaloid’s Profile in Ficus benjamina L. Extracts with Higher Antioxidant Power

Knockdown of the NHR-8 nuclear receptor enhanced sensitivity to the lipid-reducing activity of alkaloids in Caenorhabditis elegans

Drug discovery: Insights from the invertebrate Caenorhabditis elegans

Contact Info

Product

Resources

About