title: Full toxicity assessment of Genkwa Flos and the underlying mechanism in nematode Caenorhabditis elegans.
abstract: 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.
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, China; Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Medical School of Southeast University, Nanjing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Qiao
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Medical School of Southeast University, Nanjing, China.
authors.forename: Yunli
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Medical School of Southeast University, Nanjing, China.
authors.forename: Qiuli
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Medical School of Southeast University, Nanjing, China.
authors.forename: Lingmei
authors.initials: L
authors.lastname: Sun
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Qinli
authors.initials: Q
authors.lastname: Ruan
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Jinao
authors.initials: J
authors.lastname: Duan
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Medical School of Southeast University, Nanjing, China.
authors.forename: Dayong
authors.initials: D
authors.lastname: Wang
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000502:physiology; D032364:Daphne / Q000737:chemistry; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000737:chemistry; D008124:Locomotion / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species; D012098:Reproduction / Q000187:drug effects*
chemical_list: D004365:Drugs, Chinese Herbal; D017382:Reactive Oxygen Species