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The Zingiberaceae family comprises 50 genera and 1300 species in South and Southeast Asia. Indonesia is one of the countries that have the greatest diversity of plant species from the Zingiberaceae family. This research aims to do phytochemical screening and bioassay of extracts of nine ginger species (Z. officinale var. Rubrum, Z. officinale Roscoe., Z. purpureum, C. longa, C. heyneana, C. purpurascens, C. aeruginosa, C. xanthorrhiza, and B. rotunda) from Indonesia. The dried powder rhizome of each species was extracted by maceration using methanol. The dry methanol extract obtained was tested for phytochemical screening and bioactivities. Phytochemical screening and activity assay were done using established methods. All extracts contained phenolics and flavonoids, with TPC values range 10-11 mg GAE/g. C. longa extract has the highest total flavonoid content (TFC = 1.720 QE/g). Z. officinale Roscoe exhibited the highest antioxidant activity against DPPH (IC50= 233.0 ± 7.9 µg/mL) and ABTS (IC50= 320.2 ± 27.4 µg/mL) radicals. C. xanthorrhiza extract showed the best anti-inflammatory activity with an IC50 value of 1.7 ± 0.0 µg/mL. Meanwhile, Z. officinale var. Rubrum, Z. officinale Roscoe, and B. rotunda exhibited the best cytotoxic activity against HeLa cells with respective IC50 values: 7.3 ± 0.3; 11.9 ± 1.3, 11.1 ± 1.4, and 13.7 ± 0.8 µg/mL. C. longa extract, also exhibited the most potent anti-dengue viral activity (IC50 value of 13.1 ± 0.2 µg/mL). This study's findings unravel the potential of the Zingiberaceae family as a source of antioxidant, anti-inflammatory, anticancer, and anti-dengue agents. [ABSTRACT FROM AUTHOR]

Bacteria are well known producers of bioactive secondary metabolites, including some of the most effective antibiotics in use today. While the caves of Oceania are still largely under-explored, they form oligotrophic and extreme environments that are a promising source for identifying novel species of bacteria with biologically active compounds. By using selective media that mimicked a cave environment, and pretreatments that suppressed the growth of fast-growing bacteria, we have cultured genetically diverse bacteria from a limestone cave in Fiji. Partial 16S rRNA gene sequences from isolates were determined and compared with 16S rRNA gene sequences in EzBioCloud and SILVA data bases. Fifty-five isolates purified from culture had Actinomycetelike morphologies and these were investigated for antibacterial activity. Initial screening using a cross streak test with pathogenic bacteria indicated that 34 of the isolates had antibacterial properties. The best matches for the isolates are bacteria with potential uses in the manufacture of antibiotics and pesticides, in bioremediation of toxic waste, in biomining, in producing bioplastics, and in plant growth promotion. Nineteen bacteria were confirmed as Actinomycetes. Thirteen were from the genus Streptomyces and six from genera considered to be rare Actinomycetes from Pseudonocardia, Kocuria, Micromonospora, Nonomuraea. Ten isolates were Firmicutes from the genera Bacillus, Lysinbacillus, Psychrobacillus and Fontibacillus. Two were Proteobacteria from the genera Mesorhizobium and Cupriavidus. Our findings identify a potentially rich source of microbes for applications in biotechnologies. [ABSTRACT FROM AUTHOR]

Bacteria are well known producers of bioactive secondary metabolites, including some of the most effective antibiotics in use today. While the caves of Oceania are still largely under-explored, they form oligotrophic and extreme environments that are a promising source for identifying novel species of bacteria with biologically active compounds. By using selective media that mimicked a cave environment, and pretreatments that suppressed the growth of fast-growing bacteria, we have cultured genetically diverse bacteria from a limestone cave in Fiji. Partial 16S rRNA gene sequences from isolates were determined and compared with 16S rRNA gene sequences in EzBioCloud and SILVA data bases. Fifty-five isolates purified from culture had Actinomycete-like morphologies and these were investigated for antibacterial activity. Initial screening using a cross streak test with pathogenic bacteria indicated that 34 of the isolates had antibacterial properties. The best matches for the isolates are bacteria with potential uses in the manufacture of antibiotics and pesticides, in bioremediation of toxic waste, in biomining, in producing bioplastics, and in plant growth promotion. Nineteen bacteria were confirmed as Actinomycetes. Thirteen were from the genus Streptomyces and six from genera considered to be rare Actinomycetes from Pseudonocardia, Kocuria, Micromonospora, Nonomuraea. Ten isolates were Firmicutes from the genera Bacillus, Lysinbacillus, Psychrobacillus and Fontibacillus. Two were Proteobacteria from the genera Mesorhizobium and Cupriavidus. Our findings identify a potentially rich source of microbes for applications in biotechnologies.

Two new ircinianin-type sesterterpenoids, ircinianin lactone B and ircinianin lactone C (7 and 8), together with five known entities from the ircinianin compound family (1, 3–6) were isolated from the marine sponge Ircinia wistarii. Ircinianin lactones B and C (7 and 8) represent new ircinianin terpenoids with a modified oxidation pattern. Despite their labile nature, the structures could be established using a combination of spectroscopic data, including HRESIMS and 1D/2D NMR techniques, as well as computational chemistry and quantum-mechanical calculations. In a broad screening approach for biological activity, the class-defining compound ircinianin (1) showed moderate antiprotozoal activity against Plasmodium falciparum (IC50 25.4 μM) and Leishmania donovani (IC50 16.6 μM). [ABSTRACT FROM AUTHOR]

Two novel natural products, the polyketide cuniculene and the peptide antibiotic aquimarin, were recently discovered from the marine bacterial genus Aquimarina. However, the diversity of the secondary metabolite biosynthetic gene clusters (SM-BGCs) in Aquimarina genomes indicates a far greater biosynthetic potential. In this study, nine representative Aquimarina strains were tested for antimicrobial activity against diverse human-pathogenic and marine microorganisms and subjected to metabolomic and genomic profiling. We found an inhibitory activity of most Aquimarina strains against Candida glabrata and marine Vibrio and Alphaproteobacteria species. Aquimarina sp. Aq135 and Aquimarina muelleri crude extracts showed particularly promising antimicrobial activities, amongst others against methicillin-resistant Staphylococcus aureus. The metabolomic and functional genomic profiles of Aquimarina spp. followed similar patterns and were shaped by phylogeny. SM-BGC and metabolomics networks suggest the presence of novel polyketides and peptides, including cyclic depsipeptide-related compounds. Moreover, exploration of the 'Sponge Microbiome Project' dataset revealed that Aquimarina spp. possess low-abundance distributions worldwide across multiple marine biotopes. Our study emphasizes the relevance of this member of the microbial rare biosphere as a promising source of novel natural products. We predict that future metabologenomics studies of Aquimarina species will expand the spectrum of known secondary metabolites and bioactivities from marine ecosystems. [ABSTRACT FROM AUTHOR]

Design, synthesis, and bioactivity evaluation of novel mannich bases (2a‐2j) and triazole‐chalcone derivatives (7a‐7k) of Eugenol 1 were reported. Among all the derivatives tested for antiproliferative activity, di‐amine manich derivative 2b (32.92 μM), and 4‐methoxy chalcone triazole derivative 7d (33.05 μM) significantly inhibited HepG2 cell lines when compared to the standard doxorubicin (37.29 μM). Whereas most of the compounds such as diethylamine 2a (17.75 μM), (aminomethyl) methane diamine 2b (17.02 μM), and bis (chloromethyl) amine 2c (20.12 μM) showed moderate to better inhibition towards MCF‐7 cell lines. The synthesized analogues were also tested for antidiabetic and antiobesity potentials. Compounds 2f (55.50%), 2c (54.34%), 7g (55.5%), and 2a (55.5%) have shown moderate inhibitory potentials toward intestinal α‐glucosidase enzyme when compared to the standard Acarbose (72.86%). Likewise, compounds 7d (82.95%), 7f (76.19%), 7g (74.81%), 7e (74.81%), and 2g (72.50%) have shown significant to moderate inhibitory potentials toward Pancreatic lipase enzyme when compared to the standard orlistat (91.10%). ROS induces life‐threatening diseases like diabetes, cancer, etc., and antioxidants play a major role in controlling their production. Compounds 2c (99.81%), 2i (99.80%), 2d (99.26%), 2g (98.79%), and 2f (98.42%) have shown significant antioxidant profiles in ABTS assay when compared to the standard Trolox (99.07%). Further, In silico Molecular docking and pharmacokinetic screening of the eugenol derivatives complemented the in vitro results indicating the drug likeness of the obtained active compounds. [ABSTRACT FROM AUTHOR]

The solid-phase peptide synthesis (SPPS) strategy, as the main procedure of peptide manufacturing, has a profound impact on the research of peptides. The rapid development of nanotechnology is expected to promote the evolution of the solid phase to miniaturization, convenience and multi-function. In this work, silica-coated magnetic ferriferous oxide (Fe3O4) nanoparticles (MNP/SiO2) were used as new generation of solid phase for SPPS in Fmoc chemistry. The superparamagnetic solid phase facilitated a multi-step synthesis reaction due to its magnetic maneuverability, which could efficiently separate reaction intermediates, and were then redispersed in the next-step synthetic solution for peptide elongation. In addition, this strategy further allowed the simultaneous acquisition of magnetic nanoparticle–peptide conjugates as available bioprobes to examine the biological function of synthesized peptides. The feasibility of this novel magnetic nanoparticle-based solid phase peptide synthesis (MNP-SPPS) strategy was confirmed by the synthesis of arginine-glycine-aspartic acid-glycine-glycine (RGDGG) as a model pentapeptide. The simultaneously acquired magnetic nanoparticle–peptide conjugates (RGDGG-MNP/SiO2), possessing excellent biological functions, could be recognized and further internalized by tumor cells through receptor-mediated endocytosis, thereby achieving the extraction and removal of malignant cells in vitro under an external magnetic field. The RGDGG-MNP/SiO2 could further be used as a contrasting agent for tumor-targeting T2 magnetic resonance imaging in vivo. This study developed a novel MNP-SPPS strategy that could realize the simple synthesis of peptides, and the synchronously obtained nanoprobes could quickly detect the biological activity of the target synthetic sequence. This strategy may have broad application prospects in combinatorial chemistry and the construction of peptide libraries in the future.

The chemical and biologically active characterization of jujube samples (fruits, cores, and leaves) were carried out by the integrated nontargeted metabolomics and bioassay. Firstly, collision cross-section values of active compounds in jujubes were determined by ultrahigh-performance liquid chromatography coupled with ion mobility quadrupole time-of-flight mass spectrometry. Then, a multidimensional statistical analysis that contained principal component analysis, partial least squares-discriminant analysis and hierarchical clustering analysis was employed to effectively cluster different tissues and types of jujubes, making identification more scientific. Furthermore, angiotensin-converting enzyme (ACE) and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) were used to evaluate the quality of jujubes from a double activity dimension. The analytical results obtained by using ACE and DPPH to evaluate the quality of jujube were different from multivariate statistics, providing a reference for the application of jujube. Therefore, integrating chemical and biological perspectives to evaluate the quality of jujube provided a more comprehensive evaluation and effective reference for clinical needs. [Display omitted] • A novel bioassay assisted nontargeted metabolomics was developed. • Secondary metabolites were identified by UHPLC-IM-Q-TOF/MS. • ACE and DPPH were employed to evaluate the quality of jujubes. • Chemometrics contained PCA, PLS-DA, and HCA were employed. [ABSTRACT FROM AUTHOR]

Two new ircinianin-type sesterterpenoids, ircinianin lactone B and ircinianin lactone C (7 and 8), together with five known entities from the ircinianin compound family (1, 3–6) were isolated from the marine sponge Ircinia wistarii. Ircinianin lactones B and C (7 and 8) represent new ircinianin terpenoids with a modified oxidation pattern. Despite their labile nature, the structures could be established using a combination of spectroscopic data, including HRESIMS and 1D/2D NMR techniques, as well as computational chemistry and quantum-mechanical calculations. In a broad screening approach for biological activity, the class-defining compound ircinianin (1) showed moderate antiprotozoal activity against Plasmodium falciparum (IC50 25.4 μM) and Leishmania donovani (IC50 16.6 μM).

Two novel natural products, the polyketide cuniculene and the peptide antibiotic aquimarin, were recently discovered from the marine bacterial genus Aquimarina. However, the diversity of the secondary metabolite biosynthetic gene clusters (SM-BGCs) in Aquimarina genomes indicates a far greater biosynthetic potential. In this study, nine representative Aquimarina strains were tested for antimicrobial activity against diverse human-pathogenic and marine microorganisms and subjected to metabolomic and genomic profiling. We found an inhibitory activity of most Aquimarina strains against Candida glabrata and marine Vibrio and Alphaproteobacteria species. Aquimarina sp. Aq135 and Aquimarina muelleri crude extracts showed particularly promising antimicrobial activities, amongst others against methicillin-resistant Staphylococcus aureus. The metabolomic and functional genomic profiles of Aquimarina spp. followed similar patterns and were shaped by phylogeny. SM-BGC and metabolomics networks suggest the presence of novel polyketides and peptides, including cyclic depsipeptide-related compounds. Moreover, exploration of the ‘Sponge Microbiome Project’ dataset revealed that Aquimarina spp. possess low-abundance distributions worldwide across multiple marine biotopes. Our study emphasizes the relevance of this member of the microbial rare biosphere as a promising source of novel natural products. We predict that future metabologenomics studies of Aquimarina species will expand the spectrum of known secondary metabolites and bioactivities from marine ecosystems.

Obesity is a complex disease resulting in several metabolic co-morbidities and is increasing at epidemic rates. The marine environment is an interesting resource of novel compounds and in particular cyanobacteria are well known for their capacity to produce novel secondary metabolites. In this work, we explored the potential of cyanobacteria for the production of compounds with relevant activities towards metabolic diseases using a blend of target-based, phenotypic and zebrafish assays as whole small animal models. A total of 46 cyanobacterial strains were grown and biomass fractionated, yielding in total 263 fractions. Bioactivities related to metabolic function were tested in different in vitro and in vivo models. Studying adipogenic and thermogenic gene expression in brown adipocytes, lipid metabolism and glucose uptake in hepatocytes, as well as lipid metabolism in zebrafish larvae, we identified 66 (25%) active fractions. This together with metabolite profiling and the evaluation of toxicity allowed the identification of 18 (7%) fractions with promising bioactivity towards different aspects of metabolic disease. Among those, we identified several known compounds, such as eryloside T, leptosin F, pheophorbide A, phaeophytin A, chlorophyll A, present as minor peaks. Those compounds were previously not described to have bioactivities in metabolic regulation, and both known or unknown compounds could be responsible for such effects. In summary, we find that cyanobacteria hold a huge repertoire of molecules with specific bioactivities towards metabolic diseases, which needs to be explored in the future.

Natural products represent an important source of potential novel antimicrobial drug leads. Low production by microorganisms in cell culture often delays the structural elucidation or even prevents a timely discovery. Starting from the anti-Gram-negative antibacterial compound albicidin produced by Xanthomonas albilineans, we describe a bioactivity-guided approach combined with non-targeted tandem mass spectrometry and spectral (molecular) networking for the discovery of novel antimicrobial compounds. We report eight new natural albicidin derivatives, four of which bear a β-methoxy cyanoalanine or β-methoxy asparagine as the central α-amino acid. We present the total synthesis of these albicidins, which facilitated the unambiguous determination of the (2 S,3 R)-stereoconfiguration which is complemented by the assessment of the stereochemistry on antibacterial activity. [ABSTRACT FROM AUTHOR]

Previous descriptions of quercetin, a widely studied flavonoid, as a frequently reported nonspecific screening hit due to aggregating behavior has raised questions about the reliability of in vitro bioactivity reports of phenolic compounds. Here a systematic study on 117 phenolic compounds is presented, concerning their aggregating tendency and the relevance of this phenomenon to obtaining false bioassay results. Fourteen compounds formed aggregates detectable by dynamic light scattering (DLS) when assayed at 10 µM in Tris-HCl pH 7.5. Flavonoids were more prone to aggregation than other phenolic compounds, and the aggregate formation was highly dependent on the vehicle, ionic strength and pH. The compounds were also assayed against three unrelated enzymes in the presence and absence of Triton X-100, and their bioactivity ratios were collected from PubChem database. By comparing these datasets, quercetin and rhamnetin were confirmed as promiscuous inhibitors. In general, flavonoids exhibited also higher bioactivity ratios in the PubChem database than coumarins or organic acids. To conclude, aggregate formation can be controlled with Triton X-100 and this phenomenon needs to be considered when bioassay data is interpreted, but our data indicates that it does not always lead to unspecific inhibition of biological targets.

This contribution reports on the first characterization of the venom proteome and the bioactivity screening of Vipera anatolica , the Anatolian Meadow Viper. The crude venom as well as an isolated dimeric disintegrin showed remarkable cytotoxic activity against glioblastoma cells. Due to the rare occurrence and the small size of this species only little amount of venom was available, which was profiled by means of a combination of bottom-up and top-down mass spectrometry. From this analysis we identified snake venom metalloproteases, cysteine-rich secretory protein isoforms, a metalloprotease inhibitor, several type A2 phospholipases, disintegrins, a snake venom serine protease, a C-type lectin and a Kunitz-type protease inhibitor. Furthermore, we detected several isoforms of above mentioned proteins as well as previously unknown proteins, indicating an extensive complexity of the venom which would have remained undetected with conventional venomic approaches. [ABSTRACT FROM AUTHOR]

The article presents a study on the involvement of Nhr-8 gene in the worm Caenorhabditis elegans' sensitivity to the lipid-reducing effects of isoquinoline alkaloids such as berberine.Topics discussed include involvement of Nhr-8 in the xenobiotic response, enhanced biological activity in crude extract of rhizome and cultured cells as compared to the pure alkaloids in wild type worms and possibility of using the worm as a model for screening bioactive chemicals.

Previous descriptions of quercetin, a widely studied flavonoid, as a frequently reported nonspecific screening hit due to aggregating behavior has raised questions about the reliability of in vitro bioactivity reports of phenolic compounds. Here a systematic study on 117 phenolic compounds is presented, concerning their aggregating tendency and the relevance of this phenomenon to obtaining false bioassay results. Fourteen compounds formed aggregates detectable by dynamic light scattering (DLS) when assayed at 10 μM in Tris-HCl pH 7.5. Flavonoids were more prone to aggregation than other phenolic compounds, and the aggregate formation was highly dependent on the vehicle, ionic strength and pH. The compounds were also assayed against three unrelated enzymes in the presence and absence of Triton X-100, and their bioactivity ratios were collected from PubChem database. By comparing these datasets, quercetin and rhamnetin were confirmed as promiscuous inhibitors. In general, flavonoids exhibited also higher bioactivity ratios in the PubChem database than coumarins or organic acids. To conclude, aggregate formation can be controlled with Triton X-100 and this phenomenon needs to be considered when bioassay data is interpreted, but our data indicates that it does not always lead to unspecific inhibition of biological targets. [ABSTRACT FROM AUTHOR]

The bioactivity screening of fractions from two inter-tidal sponges collected from the north of China Yellow Sea and one sponge collected from the South Chinese Sea was reported in this study. In sponge Hymeniacidon perleve there were 9 fractions out of 15 from CHCl3 extract with anti Staphylococcus aureus activity, 9 fractions out of 19 from BuOH extract with anti Escherichia coli activity, and three fractions from CHCl3 extract which had moderate to strong activity in inhibiting Bacillus subtilis, Candida albicans, and Aspergilus niger. The fractions of Reniochalina sp. showed bioactivity against bacteria and fungi. The fractions of Acanthella acuta Schmidt showed bioactivity against S. aureus and fungi. One compound from H. perleve obtained by the bioactively directing isolation was tested for bioactivity against the human hepatoma cell line Qgy7701 (IC50 10.1 μg/ml), Burkitt''s lymphoma cell line Raji (IC50 9.76 μg/ml) and chronic myelogenous leukemia K562 (IC50 1.90 μg/ml). [Copyright &y& Elsevier]

The development of simple, but highly sensitive and accurate in vitro methods for assessing the bioactivity of biomaterials is a key requirement for assuring their successful clinical application. Moreover, screening techniques that will allow various materials to be recommended, or otherwise, for further testing, have the potential to make appreciable savings in the time and expense associated with product development.This paper gives details of a novel whole blood chemiluminescence method, based on the photoprotein Pholasin®, which emits light in the presence of the free radical superoxide, other reactive oxygen species and the enzyme myeloperoxidase. This whole blood assay may have the potential as a screening method for assessing calcium phosphate (Ca-P) bioceramic powders according to their relative bioactivity. The method employed involves exposure of samples of anti-coagulated (heparinised) blood to the various Ca-P materials and stimulating the contacted leukocytes in the blood with phorbol-12-myristate-13-acetate (PMA). PMA stimulates protein kinase C directly and sets in motion a cascade of events in the leukocytes leading to the activation of the superoxide generating NADPH oxidase system. PMA also promotes degranulation, which is the fusion of the granule membrane with the plasma membrane and the extracellular release of granule enzymes.Changes in the free radical and degranulation activity of the cells, as measured by the luminescent response of Pholasin® to cells stimulated with PMA, after exposure to the Ca-P powders, are presented as percentage differences from the response to (control) blood samples not exposed to the powders. The resultant data clearly indicate significant differences in the light detected via Pholasin® from the blood exposed to the bioceramic materials compared to that from the relevant controls. These differences correlate well with the ascribed bioactivity of the Ca-P powders, as assigned from the measured chemical and structural properties. Furthermore, the method can also be applied to samples of blood, which have been diluted in the ratio 1:100 in standard blood dilution buffer. The light output response in the diluted blood experiments is exactly the same as that observed with undiluted whole blood but occurs immediately as compared to the many minutes required to give response in the latter case. Thermally processed (800°C) Ca-P materials have also been studied. A relationship between the heat-induced properties of the powders and the chemiluminescence responses recorded from blood cells stimulated with PMA has been established. [Copyright &y& Elsevier]

Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Rhizoma paridis saponins (RPS), the main bioactive ingredients of Paris polyphylla Smith var. yunnanensis (PPY), have been proved to have remarkable effects on NSCLC cell lines. However, the multi-component synergistic effects and mechanisms of RPS on NSCLC have not been elucidated., Objective: To decipher the multi-RPS synergistic effects and mechanisms against NSCLC based on network pharmacology combined with segmented solid-phase extraction (SPE) and bioactivity screening method., Methods: Firstly, segmented SPE and cytotoxicity assays were performed to screen the RPS-enrichment fraction of PPY, and the steroidal saponins in it were identified by LC-MS/MS. Then, a network pharmacology analysis was performed to predict the potential therapeutic targets of RPS on NSCLC. Finally, viable cell counting tests and RT-qPCR were utilized to verify the synergistic effects and mechanisms of RPS., Results: 48 potentially active compounds were identified from the 30% MeOH/EtOAc fraction of PPY (30% M/E PPY). The results of the network pharmacology analysis indicated that RPS exerted joint effects by regulating six key targets in the PI3K-AKT signaling pathway. In vitro experiments showed that due to the synergistic effects, 30% M/E PPY at 13.90 μg/mL could exert a stronger inhibitory activity on A549 cells by reducing the overexpression of six hub genes compared with the parallel control groups., Conclusion: This research elaborates on the multi-RPS synergy mechanisms against NSCLC and provides a way to develop new combination medicines for NSCLC., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Obesity is a complex disease resulting in several metabolic co-morbidities and is increasing at epidemic rates. The marine environment is an interesting resource of novel compounds and in particular cyanobacteria are well known for their capacity to produce novel secondary metabolites. In this work, we explored the potential of cyanobacteria for the production of compounds with relevant activities towards metabolic diseases using a blend of target-based, phenotypic and zebrafish assays as whole small animal models. A total of 46 cyanobacterial strains were grown and biomass fractionated, yielding in total 263 fractions. Bioactivities related to metabolic function were tested in different in vitro and in vivo models. Studying adipogenic and thermogenic gene expression in brown adipocytes, lipid metabolism and glucose uptake in hepatocytes, as well as lipid metabolism in zebrafish larvae, we identified 66 (25%) active fractions. This together with metabolite profiling and the evaluation of toxicity allowed the identification of 18 (7%) fractions with promising bioactivity towards different aspects of metabolic disease. Among those, we identified several known compounds, such as eryloside T, leptosin F, pheophorbide A, phaeophytin A, chlorophyll A, present as minor peaks. Those compounds were previously not described to have bioactivities in metabolic regulation, and both known or unknown compounds could be responsible for such effects. In summary, we find that cyanobacteria hold a huge repertoire of molecules with specific bioactivities towards metabolic diseases, which needs to be explored in the future. [ABSTRACT FROM AUTHOR]

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.