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Genkwa Flos (GF), the dried flower bud from Daphne genkwa Sieb. et Zucc. (Thymelaeaceae), is a well-known and widely used traditional Chinese medicine. However, we know little about the in vivo mechanism of GF toxicity. Nematode Caenorhabditis elegans has been considered as a useful toxicity assay system by offering a system best suited for asking the in vivo questions. In the present study, we employed the prolonged exposure assay system of C. elegans to perform the full in vivo toxicity assessment of raw-processed GF. Our data show that GF exposure could induce the toxicity on lifespan, development, reproduction, and locomotion behavior. GF exposure not only decreased body length but also induced the formation of abnormal vulva. The decrease in brood size in GF exposed nematodes appeared mainly at day-1 during the development of adult nematodes. The decrease of locomotion behavior in GF exposed nematodes might be due to the damage on development of D-type GABAergic motor neurons. Moreover, we observed the induction of intestinal reactive oxygen species (ROS) production and alteration of expression patterns of genes required for development of apical domain, microvilli, and apical junction of intestine in GF exposed nematodes, implying the possible dysfunction of the primary targeted organ. In addition, GF exposure induced increase in defecation cycle length and deficits in development of AVL and DVB neurons controlling the defecation behavior. Therefore, our study implies the usefulness of C. elegans assay system for toxicity assessment from a certain Chinese medicine or plant extract. The observed toxicity of GF might be the combinational effects of oxidative stress, dysfunction of intestine, and altered defecation behavior in nematodes. [ABSTRACT FROM AUTHOR]

Genkwa Flos (GF), the dried flower bud from Daphne genkwa Sieb. et Zucc. (Thymelaeaceae), is a well-known and widely used traditional Chinese medicine. However, we know little about the in vivo mechanism of GF toxicity. Nematode Caenorhabditis elegans has been considered as a useful toxicity assay system by offering a system best suited for asking the in vivo questions. In the present study, we employed the prolonged exposure assay system of C. elegans to perform the full in vivo toxicity assessment of raw-processed GF. Our data show that GF exposure could induce the toxicity on lifespan, development, reproduction, and locomotion behavior. GF exposure not only decreased body length but also induced the formation of abnormal vulva. The decrease in brood size in GF exposed nematodes appeared mainly at day-1 during the development of adult nematodes. The decrease of locomotion behavior in GF exposed nematodes might be due to the damage on development of D-type GABAergic motor neurons. Moreover, we observed the induction of intestinal reactive oxygen species (ROS) production and alteration of expression patterns of genes required for development of apical domain, microvilli, and apical junction of intestine in GF exposed nematodes, implying the possible dysfunction of the primary targeted organ. In addition, GF exposure induced increase in defecation cycle length and deficits in development of AVL and DVB neurons controlling the defecation behavior. Therefore, our study implies the usefulness of C. elegans assay system for toxicity assessment from a certain Chinese medicine or plant extract. The observed toxicity of GF might be the combinational effects of oxidative stress, dysfunction of intestine, and altered defecation behavior in nematodes. [ABSTRACT FROM AUTHOR]

In the present study, we used Caenorhabditis elegans assay system to investigate in vivo toxicity from clentuberol and ractopamine and the possible underlying mechanism. Both acute and prolonged exposures to clentuberol or ractopamine decreased brood size and locomotion behavior, and induced intestinal autofluorescence and reactive oxygen species (ROS) production. Although acute exposure to the examined concentrations of clentuberol or ractopamine did not induce lethality, prolonged exposure to 10 µg/L of clentuberol and ractopamine reduced lifespan. At relatively high concentrations, ractopamine exhibited more severe toxicity than clentuberol on nematodes. Overexpression of sod-2 gene encoding a Mn-SOD to prevent induction of oxidative stress effectively inhibited toxicity from clentuberol or ractopamine. Besides oxidative stress, we found that clentuberol might reduce lifespan through influencing insulin/IGF signaling pathway; however, ractopamine might reduce lifespan through affecting both insulin/IGF signaling pathway and TOR signaling pathway. Ractopamine more severely decreased expression levels of daf-16, sgk-1, skn-1, and aak-2 genes than clentuberol, and increased expression levels of daf-2 and age-1 genes at the examined concentration. Therefore, the C. elegans assay system may be useful for assessing the possible toxicity from weight loss agents, and clentuberol and ractopamine may induce toxicity through different molecular mechanisms. [ABSTRACT FROM AUTHOR]

Caenorhabditis elegans is as an ideal model system for the study of mechanisms underlying learning and memory. In the present study, we employed C. elegans assay system of thermotaxis memory to investigate the possible role of serotonin neurotransmitter in memory control. Our data showed that both mutations of tph-1, bas-1, and cat-4 genes, required for serotonin synthesis, and mutations of mod-5 gene, encoding a serotonin reuptake transporter, resulted in deficits in thermotaxis memory behavior. Exogenous treatment with serotonin effectively recovered the deficits in thermotaxis memory of tph-1 and bas-1 mutants to the level of wild-type N2. Neuron-specific activity assay of TPH-1 suggests that serotonin might regulate the thermotaxis memory behavior by release from the ADF sensory neurons. Ablation of ADF sensory neurons by expressing a cell-death activator gene egl-1 decreased the thermotaxis memory, whereas activation of ADF neurons by expression of a constitutively active protein kinase C homologue (pkc-1(gf)) increased the thermotaxis memory and rescued the deficits in thermotaxis memory in tph-1 mutants. Moreover, serotonin released from the ADF sensory neurons might act through the G-protein-coupled serotonin receptors of SER-4 and SER-7 to regulate the thermotaxis memory behavior. Genetic analysis implies that serotonin might further target the insulin signaling pathway to regulate the thermotaxis memory behavior. Thus, our results suggest the possible crucial role of serotonin and ADF sensory neurons in thermotaxis memory control in C. elegans. [ABSTRACT FROM AUTHOR]

Caenorhabditis elegans is as an ideal model system for the study of mechanisms underlying learning and memory. In the present study, we employed C. elegans assay system of thermotaxis memory to investigate the possible role of serotonin neurotransmitter in memory control. Our data showed that both mutations of tph-1, bas-1, and cat-4 genes, required for serotonin synthesis, and mutations of mod-5 gene, encoding a serotonin reuptake transporter, resulted in deficits in thermotaxis memory behavior. Exogenous treatment with serotonin effectively recovered the deficits in thermotaxis memory of tph-1 and bas-1 mutants to the level of wild-type N2. Neuron-specific activity assay of TPH-1 suggests that serotonin might regulate the thermotaxis memory behavior by release from the ADF sensory neurons. Ablation of ADF sensory neurons by expressing a cell-death activator gene egl-1 decreased the thermotaxis memory, whereas activation of ADF neurons by expression of a constitutively active protein kinase C homologue (pkc-1(gf)) increased the thermotaxis memory and rescued the deficits in thermotaxis memory in tph-1 mutants. Moreover, serotonin released from the ADF sensory neurons might act through the G-protein-coupled serotonin receptors of SER-4 and SER-7 to regulate the thermotaxis memory behavior. Genetic analysis implies that serotonin might further target the insulin signaling pathway to regulate the thermotaxis memory behavior. Thus, our results suggest the possible crucial role of serotonin and ADF sensory neurons in thermotaxis memory control in C. elegans. [ABSTRACT FROM AUTHOR]