Zebrafish has become a popular model for genetic research due to the high conservation of gene function between zebrafish and humans. Thus, some phenotypic effects produced by zebrafish are difficult to extrapolate to humans. Epub 2018 Mar 15. Similar results were observed, Used against intestinal worms in children, Increased spontaneous movement, heartbeat inhibition, pericardial oedema, yolk-sac oedema, bleeding tendency, yolk malformation, enlarged yolk, and shortened body length, Used for asthma, dysentery, fever, gastritis, diabetes; immune boost, Chronic teratogenic toxicities, leading to pericardial oedema, yolk-sac swelling, and other abnormal developmental characteristics, Against gynaecological and obstetrical conditions, such as menstrual blood stasis, menstrual disturbances, dysmenorrhea, amenorrhea, postpartum haemorrhage, and postpartum recovery, Cure infectious and inflammatory diseases, RSTE and RST active fractions in zebrafish, concentration-dependent mortality were demonstrated (LC, Pericardial oedema and/or reduced heart rates were observable in different fractions of RSTE and RST, Compared with mice and similar results obtained, Dried root of Euphorbia kansui (KS-1) and Euphorbia kansui fry-baked with vinegar (KS-2), Cancer, pancreatitis and intestinal obstruction, Five anthraquinones, seven anthrones, and two naphthols, Antiageing, antihyperlipidaemia, antioxidant, anti-inflammatory, anticancer, hepatoprotective, and immunomodulating effects, LD50 values have been calculated for each compound at 48, 72 and 96 hpf, Kushen in traditional Chinese medicine root of Sophora flavescens, Possessing a variety of pharmacological effects such as anti-inflammation, antivirus, antitumour, and antiarrhythmic activities, Oedema, growth retardation has been observed after 48 hrs concentrations below those causing lethality and malformations, indicating a neurotoxic potential of both drugs, Antioxidant and anti-inflammatory activities, neurodegenerative diseases and anticancer, Several developmental abnormalities, including no blood flow, oedema in pericardial sac, and tail malformation were reported in embryos EC50 for tail malformation was 0.66, Rhubarb root and bark of many plants of the genus, Antidiabetic, antinociception, anticancer and cholesterol reduction potential, Dose-related increase in mortality, with significant death of embryos at 0.25, Oedema, crooked trunk, and abnormal morphogenesis of some organs, such as statolith, swimming bladder, and yolk syncytium were reported in embryo treated with 0.1–1.5. Pomegranate peel is prescribed as an antimicrobial agent. Emodin is an anthraquinone derivative; it is the main effective monomer of herbal rhubarb. It is also used for the treatment of jaundice, skin diseases, and anaemia. The phenolic composition of T. natans leafs extracts was analyzed by a linear ion trap-OrbiTrap hybrid mass spectrometer (LTQ OrbiTrapMS) and UHPLC system configured with a diode array detector (DAD) hyphenated with the triple quadrupole mass spectrometer. Angiogenic effect of motherwort (Leonurus japonicus) alkaloids and toxicity of motherwort essential oil on zebrafish embryos Fitoterapia . Though herbal medicine is considered as safe, there are reported cases of adverse drug interactions, mutagenic, carcinogenic, and teratogenic effects [47]. Geissospermum reticulatum A. Gentry is a tree commonly found in the Amazon. Zebrafish embryotoxicity assessment is in compliance with the 3R’ principal of animal welfare and proceeds through a holistic screening approach of herbal medicine to reach clinical conclusions. Zebrafish may be used to determine the toxicity of samples in early screening assays, often in a high-throughput manner. Zebrafish AB strain and the Tg(cmlc2:EGFP), Tg(L-FABP:EGFP), Tg(Lyz:EGFP), and Tg(Vmat:GFP) transgenic zebrafish lines were used for lethality and other specific organ toxicity studies. Furthermore, different teratogenic effects such as head and tail malformations, delayed growth, limited movement, scoliosis/flexure, and stunted tail were reported with dose-dependance and plant parts-dependence. The TC50 (teratogenic effect) of 2 hpf embryos was much lower (1.67 ± 0.23 μg/mL) compared with that of 10 hpf and 24 hpf (TC50-10 μg/mL) and 48 hpf (TC50-20 μg/mL). Malformed kidney phenotypes, curved, cystic pronephric tubes, pronephric ducts, and cases of atrophic glomeruli were reported, Psoriasis, vitiligo, osteoporosis, osteosarcoma, bone fracture, and osteomalacia. The results predicted that the LC50 at 48 hpf and IC50-3T3-L1 correlates well [22]. Emodin exhibited a dose-related increase in mortality, with significant death of embryos at a drug threshold of 0.25 μg/mL. Fuzi, the processed lateral roots of Aconitum carmichaelii Debx., is a traditional herbal medicine that is well known for its excellent pharmacological effects and acute toxicity. Small size, short life cycle, and high fecundity favour its laboratory uses as a test organism [9]. Although first used experimentally for the genetic analysis of vertebrate development and neurobiology, the zebrafish has been adapted as a model for many human diseases. Use of the zebrafish embryotoxicity model reduces the usage of higher vertebrates into toxicity studies. Despite the popularity as an alternative toxicological model, thus far the number of herbal compounds investigated using this model is limited compared to other chemical compounds. The zebrafish embryotoxicity model is at the leading edge of toxicology research due to the short time required for analyses, … Fertilized and dead embryos were separated according to the descriptions of Kimmel. The toxic effects of these plant extracts were compared using in vitro cytotoxicity assay using 1.1B4 (human-derived pancreatic β-cell line), 3T3-L1 (mouse-derived adipocyte like cells), and WRL-68 cell (human hepatic cell line) types. Sign up here as a reviewer to help fast-track new submissions. The zebrafish embryotoxicity assay was used to evaluate the toxicity of bioactive fraction of the Korean medicinal plant Artemisia capillaries Thunberg. Acute Toxicity of Keladi Tikus (Typhonium flagelliforme (Lodd.) These Na+ channels were believed to activate to increase the heart rate. It is anticipated that this work will highlight a novel vista in herbal toxicology that uses zebrafish embryotoxicity assay as an alternative for higher vertebrates. The toxicity indicators, mortality rate, and heart rate in treated zebrafish embryos to identify the safe and effective concentration of compound 1. AA-treated zebrafish embryos also exhibited deformed hearts, swollen pericardium, impaired blood circulation, and the accumulation(s) of red blood cells [39]. Particularly, the zebrafish model was effective in detecting nephrotoxicity. The results revealed compound 1 (25 μM) treated embryos had no developmental defects and displayed normal cardiac function, indicating that this compound enhanced pigmentation without producing toxicity, Abdominal pain, headache, menstrual problems, vomiting, and diarrhea, Concentrations ≥400 ng/mL significantly increased the lethality reached 100% at 1600 ng/mL evodiamine, 10% lethal concentration of 354 ng/mL and induced cardiac malfunction, as evidenced by changes in heart rate and circulation, and pericardial malformations, Primary cultured neonatal rat cardiomyocytes, Recommended for cardiovascular disease exhibits various pharmacological activities, including anti-inflammatory, antioxidative, antifibrosis, modulation of collagen metabolism, and antitumour, Aconitine (AC), Mesaconitine (MAC,) Hypaconitine (HAC), Anti-inflammation, antidepressant, antiarrhythmia, antiplatelet aggregation, and antimalarial properties, Diterpenes including AC, MAC, and HAC exhibited serious organic and functional toxicities in zebrafish embryos compared with that of monoester diterpene alkaloid, M. P. Vinardell and M. Mitjans, “Alternative methods for eye and skin irritation tests: an overview,”, O. Ifeoma and S. Oluwakanyinsola, “Screening of herbal medicines for potential toxicities,” in, S. K. Doke and S. C. Dhawale, “Alternatives to animal testing: a review,”, P. Flecknell, “Replacement, reduction, refinement,”. Similarly, the teratogenic effects of embryos treated with motherwort essential oil also indicated the early stages are much sensitive. Copyright © 2019 Chanika D. Jayasinghe and Uthpala A. Jayawardena. It is a nonpsychotomimetic compound that has been used for the treatment of severe neuropsychiatric disorders. After removing duplicates and excluding the paper based on the exclusion criteria, the total number of 25 articles were included in the present review. The LC50 of zebrafish embryos treated at 2 hpf, 10 hpf, and 24 hpf (around 10 μg/mL) were much lower than those of zebrafish embryos treated at 48 hpf (around 60 μg/mL), indicating early stages are more sensitive to motherwort essential oil. Embryos continued growing and developing until the termination of the experiment at dpf 9. Some studies revealed that cytotoxic potencies of fish and mammalian cell lines were almost equally sensitive while some showed controversial results. Introduction. Yolk retention, swim-bladder deficiency, pericardial oedema, and curved body shape were observed at 24 to 96 hpf in psoralen-treatment embryos. According to this review, the zebrafish model has been employed to investigate the toxicity of 6 polyherbal formulae/medical prescriptions, 16 crude plant extracts, and more than 30 phytocompounds/isolated constituents. Fig. The zebrafish at 7 days after fertilization were exposed to a series of concentrations ranging from 0.1, 0.25, 0.5, 0.75, 1, 1.5, and 2 μg/mL to assess the toxicity. Evaluation of the toxicity of phytochemical constituents of herbal medicine using the Zebrafish embryotoxicity model. Evidence-Based Complementary and Alternative Medicine, Five anthraquinones, seven anthrones, and two naphthols, Antiageing, antihyperlipidaemia, antioxidant, anti-inflammatory, anticancer, hepatoprotective, and immunomodulating effects, LD50 values have been calculated for each compound at 48, 72 and 96 hpf, Kushen in traditional Chinese medicine root of Sophora flavescens, Possessing a variety of pharmacological effects such as anti-inflammation, antivirus, antitumour, and antiarrhythmic activities, Oedema, growth retardation has been observed after 48 hrs concentrations below those causing lethality and malformations, indicating a neurotoxic potential of both drugs, Antioxidant and anti-inflammatory activities, neurodegenerative diseases and anticancer, Several developmental abnormalities, including no blood flow, oedema in pericardial sac, and tail malformation were reported in embryos EC50 for tail malformation was 0.66, Rhubarb root and bark of many plants of the genus, Antidiabetic, antinociception, anticancer and cholesterol reduction potential, Dose-related increase in mortality, with significant death of embryos at 0.25, Oedema, crooked trunk, and abnormal morphogenesis of some organs, such as statolith, swimming bladder, and yolk syncytium were reported in embryo treated with 0.1–1.5. Seven percentage dilutions were made to determine the toxicity of samples, using filtered aquarium water as vehicle. The lethal and developmental toxicity of extracts were addressed in vivo using the zebrafish (Danio rerio) model system. The toxicity is attributed to the presence of compounds that activate the Na+ channel K+ channel inhibitors, respectively. This review provides ample affirmation of applicability of the zebrafish embryotoxicity model for herbal toxicology. The search process was conducted independently by two authors and the final group of articles. Generally, TCMs were regarded as less toxic with no contraindication in pregnancy. Both ethanol and water extracts of the plant were tested on zebrafish embryos. An ortholog of CYP3A in zebrafish was homologous to the human CYP3A subfamily, which was initially transcribed only in the liver and intestine upon hatching of the zebrafish. Test organisms range from invertebrates such as brine shrimp to mammals such as mice, rats, guinea pigs, and rabbits [4]. The average embryonic heart rate was also decreased in embryos exposed to 25, 50, or 100 μg/mL. The pain, distress, and death experienced by the animals during scientific experiments have been a debate for a long time. The potential effect of emodin on zebrafish (Danio rerio) embryos was evaluated. Generally, cardiac glycoside in plant material is one of the most commonly associated compounds that affect cardiac functions. Normal embryos were less sensitive to Tan-IIA, but with the increasing concentration, severe abnormalities of heart and pericardium were observed. The LC50 values for CDT, ANP, and LPT were calculated as 417, 596, and 380 μg/mL, respectively, for zebrafish embryos. Interestingly, the compound 1 caused no mortality in treated embryos. Leaf extract is more toxic than bark, Antimalarial, antitumoral, antioxidant, nociceptive, and antibacterial activities, Deformation or teratogenic effect were not observed, Antioxidant activity, cardiovascular and antidiabetic effects, inflammatory and edematic disorders, anticancer, antimicrobial, and hepatoprotection, Blood stasis syndrome with dysmenorrhea, amenorrhea, postpartum abdominal pain and mass, and trauma and pain in the joints, Abnormal spontaneous movement, depressed heart rate, pericardial oedema, yolk-sac oedema, abnormal head-trunk angle, inhibition of melanin release, enlarged yolk, short body length, and significant inhibition of heartbeat, Cardiotonic, analgesic, anti-inflammatory, and diuretic agents to treat colds, polyarthralgia, diarrhea, heart failure, beriberi, and oedema, FZ-120 caused the death of zebrafish from 700 to above 1000, Abnormalities of heart, liver, yolk sac, swim bladder, and body length mainly at doses ranging from 288 to 896, Acute toxic effect of mice. Abstract. Aconitine is one of the diester‐diterpene alkaloids and well‐known for its arrhythmogenic effects. Secondarily, CBD was tested on motor systems [38] as motor responses of zebrafish are highly sensitive to the neurotoxic chemical compound which is associated with cannabinoid receptors-mediated (CB1) regulation. The slope of the regression line for the full set of compounds was 0.73403. Radix Sophorae tonkinensis (RST) is a Chinese medicine used to cure infectious and inflammatory diseases. The zebrafish embryotoxicity model has been utilized to evaluate the toxicity of some common Chinese Medical Prescriptions (CMPs) and Chinese Patent Medicines (CPMs) (Table 1). Hence, this model will undoubtedly bring about significant advances in predicting toxicity of herbal medicine. Hence, this review intends to provide a comprehensive account of available scientific evidence of the application of the zebrafish embryos to assess the herbal toxicity. Articles were selected based on the inclusion and exclusion criteria mentioned in Section 2.2. Ms Thejani Tennakoon is acknowledged for initiating this study. The ethyl acetate extract which was extracted from Euphorbia kansui (KS-1) and Euphorbia kansui fry-baked with vinegar (KS-2) were tested on zebrafish embryos for toxicity. Given the exposure of embryos to the different extracts of L. minor, embryonic development was carried out from the concentration 0.05, 0.5, 5, 50 µg mL −1 with the three extracts, at 500 and 5000 µg mL −1 the embryos died at 4 h of exposure. 21,24–27 We use zebrafish because of their many advantages such as short generation times, amenability for large-scale screening, high fecundity, ease of in vitro fertilization, and transparency. Yang, W.-F. Li, Y. Liu et al., “Acute toxicity screening of different extractions, components and constituents of Polygonum multiflorum Thunb. Both bark and leaf extracts indicated dose-dependent and time-dependent toxicities against the zebrafish embryos. 2019;2019:7272808 Authors: Jayasinghe CD, Jayawardena UA Abstract Herbal remedies have been practiced by humans over centuries and therefore possess time-proven safety. Abnormalities were observed in the heart, liver, yolk sac, swim bladder, and body length mainly at doses ranging from 288 to 896 μg/mL of FZ-120. Figure 1 presents the search strategy used in selecting the articles. The whole RST extract and its ethanol sediment (RSTE) and its active fractions prepared using five different types of solvents, dealkalized water, ethanol, n-butyl ethanol, dichloromethane, and diethyl ether were tested for toxicity using the zebrafish embryotoxicity model. It was observed that the survival rate of zebrafish embryo decreased as the … This study focused on its developmental toxicity by using zebrafish embryos. There is a pertinent need to renew scientific enthusiasm toward incorporating the zebrafish embryotoxicity model in toxicological evaluation on herbal medicine. The zebrafish (Danio rerio) is used as an embryonic and larval model to perform in vitro experiments and developmental toxicity studies. It has been reported 87% of genetic similarity exists between the zebrafish and human [11]. Drug concentrations, designed on the basis of preexperiment data, used in the acute toxicity tests are summarized in Table 1. Toxicity evaluation in zebrafish embryos and larvae. Surprisingly, CBD did not display significant alterations in acetyl chlorine esterase (AChE) in concentrations correlated with human plasma dose [34]. Four components were isolated from 70% ethanol fraction where the toxicity of component (D) was found to be higher than that of the other components. Zebrafish may be used to determine the toxicity of samples in early screening assays, often in a high-throughput manner. We are committed to sharing findings related to COVID-19 as quickly as possible. Ethical consideration of animals involved in research gave rise to the adaptation of 3R’s principal introduced by Russell et al. Henceforth, it provides a novel insight into the toxicity assessment of herbal medicine. A. Alafiatayo, K. S. Lai, A. Syahida, M. Mahmood, and N. A. Shaharuddin, “Phytochemical evaluation, embryotoxicity, and teratogenic effects of, Q. Xia, Z. Ma, X. Mei et al., “Assay for the developmental toxicity of safflower (, W. Sun, B. Yan, R. Wang et al., “In vivo acute toxicity of detoxified Fuzi (lateral root of, Q. Xia, J. Luo, X. Mei et al., “A developmental toxicity assay of, L. Chen, M. Xu, Z. Gong, S. Zonyane, S. Xu, and N. P. Makunga, “Comparative cardio and developmental toxicity induced by the popular medicinal extract of, Y.-L. The percentage of kidney malformation phenotypes has increased with the increase in exposure concentrations (25 ng/mL, 0–10%; 250 ng/mL, 0–60%; and 1,250 ng/mL, 80–100%). This plant is commonly used as an antiageing, antihyperlipidaemic, antioxidant, anti-inflammatory, anticancer, hepatoprotective, and immunomodulatory agent. There is an unmet need for low-cost, high-throughput animal models in some fields of biomedical research such as drug screening and toxicity assessment , .The zebrafish embryo is emerging as one such model .It has been proposed as a bridge between simple assays based on cell culture, and biological validation in whole animals such as rodents . The zebrafish embryotoxicity revealed the LC50 value of Carpesii Fructus as 230.40 mg/L. The percentages of embryos with malformed kidney phenotypes increased as the exposure dosages of AA increased. The zebrafish embryotoxicity assay performed for the ethanolic extract of the bark of G reticulatum revealed even at the highest concentration tested was nontoxic to the zebrafish embryos. The concentration of 50–100 ng/mL evodiamine exposure for 24 hrs caused no lethal effects. Toxicol Lett. Zebrafish embryos also exhibit abnormalities in spine together with yolk-sac oedema. Embryos were obtained from spawning zebrafish adults in breeding tanks with sex ratio 3 male:5 female. LD50 was calculated for each compound [34]. This section includes several studies that have used the zebrafish embryo assay for toxicological assessment (Table 2). However, toxicological assessment is paramount in herbal medicine to identify adverse effects to safeguard human beings [2]. However, the use of the zebrafish embryotoxicity model for herbal toxicity field requires more attention. A set of eleven chemicals of known mammalian in vivo teratogenicity were tested in the assays and correlations to mammalian data. The present review intends to provide a comprehensive assembly of studies that applied the zebrafish embryo model for the assessment of herbal toxicity. The embryos were selected to be in a stage previous to 2 hours postfertilization (hpf) and were maintained at 28°C until analysis. A systematic review of scientific evidence of the use of the zebrafish embryotoxicity model for toxicity assessment of herbal medicine was undertaken in accordance with the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) [18, 19]. Polygonum multiflorum Thunb., is a traditional medicinal plant which has been used widely in East Asia. Seven percentage dilutions were made to determine the toxicity of samples, using filtered aquarium water as vehicle. Safflower (Carthamus tinctorius L.) is a medicinal plant grown in China which is mainly used in the treatment of blood stasis syndrome with dysmenorrhea, amenorrhea, postpartum abdominal pain and mass, and trauma and pain in the joints. FZ-120 caused the death of zebrafish from 700 to above 1000 μg/mL indicating potential toxicity Abnormalities of heart, liver, yolk sac, swim bladder, and body length mainly at doses ranging from 288 to … Unlike synthetic drugs, herbal remedies have been consumed by humans over centuries and possess time-proven safety. All of them have displayed teratogenic and lethal effects in zebrafish embryos. Most studies entailed here followed OECD test protocols to elucidate the toxicity of herbal medicine. The EC50 values were calculated based on teratogenic effects. Several morphological abnormalities such as the yolk retention, swim-bladder deficiency, pericardial oedema, and curved body shape were observed at 24 to 96 hpf in psoralen-treated embryos. However, it is imperative to evaluate the toxic effects of herbal medicine to confirm their safety, particularly when developing therapeutic leads. Tail bending and pericardial oedema were displayed as main teratogenic effects in this experiment. The atrial and ventricular heart rates were decreased in a dose-dependent manner in zebrafish exposed to evodiamine. It was further revealed GA upregulated ALDH12 (Aldehyde Dehydrogenase 1 Family Member A2) and downregulated CYP26A1 (cytochrome P450 family 26 subfamily A member 1) at 8hpf. The OECD (Organization for Economic Co-operation and Development) has developed guidelines to evaluate the embryotoxicity effects of certain compounds on the early 96 hr of developmental stages (acute toxicity testing) ((OECD) test no. Concentration-dependent mortality was demonstrated by RSTE, RST, and active fractions in zebrafish embryos. He, J.-Y. According to the review, the zebrafish model was applied to investigate specific toxicities such as nephro, cardio, and neurotoxicities. He, K. Liu, S. Wang, H. Hou, Y. Yuan, and X. Wang, “Toxicity induced by emodin on zebrafish embryos,”, T. A. V. Brigante, F. R. Abe, A. W. Zuardi, J. E. C. Hallak, J. The results revealed that the compound 1-(25 μM) treated embryos showed no developmental defects and displayed normal cardiac function, indicating that this compound enhanced pigmentation without producing toxicity [41]. This study has used the zebrafish embryos to assess the toxicities of the water extracts of the aforementioned plants. In zebrafish, Tg line, the parts of the excretory system are labelled with a green fluorescent protein (GFP). Teratogenic effects such as scoliosis, malformation of the tail, and pericardium oedema of dechorionated embryos were manifested at a concentration of about 1 μM. The literature search identified a total of 1014 articles in PubMed = 12, Scopus SciVerse® = 623, and Google Scholar = 1000. The zebrafish embryotoxicity model has been employed to evaluate the acute toxicity of ethanolic extract of pomegranate (Punica granatum L) peel. The authors declare that there are no conflicts of interest regarding the publication of this paper. The cardiotoxic effect of T. cordifolia can be governed by cardiac glycoside present as the active component [23]. INVITED REVIEW ARTICLE Using zebrafish in systems toxicology for developmental toxicity testing Yuhei Nishimura1,2,3,4,5, Atsuto Inoue6, Shota Sasagawa1, Junko Koiwa1, Koki Kawaguchi1, Reiko Kawase1, Toru Maruyama6, Soonih Kim6, and Toshio Tanaka1,2,3,4,5 1Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University … Furthermore, low cost, short cycle, higher fecundity, the requirement of small quantities of test compounds, and high throughput screening also make it a highly suitable and successful model to be used in toxicity studies [12, 13]. He, and X. Chen, “Toxic effects of celastrol on embryonic development of zebrafish (, Q. 1. Embryo short-term toxicity test (FET) The green fluorescence kidney transgenic zebrafish provides a good model over mice and human to detect kidney malformation caused by chemicals such as aristolochic acid (AA) in medicinal plants. In spite of the widely reported therapeutic applications of C. longa , research on its safety and teratogenic effects on zebrafish embryos and larvae is still limited. Si Jun Zi Tang (SJZT), Liu Jun Zi Tang (LJZT), and Shenling Baizhu San (SLBS) are CMPs commonly used to treat patients with poor appetite, loose stool, abdominal distension, lassitude, prolapsed anus, shortness of breath, dysphasia, and spontaneous sweating. Danio rerio, commonly called as the zebrafish, is a small freshwater fish with an approximate length of 2–4 cm. The results revealed the bark extract of CZ exhibited the highest toxicity with LC50 value of 0.0508 mg/mL, followed by leaves of EP (0.06039 mg/mL), leaves of AP (0.5256 mg/mL), rhizome of CX (0.7037 mg/mL), and whole plant of OS (1.685 mg/mL). These studies have investigated the toxicity of 6 polyherbal formulae, 16 crude extracts, and more than 30 phytocompounds/isolated constituents using the zebrafish embryotoxicity model. Diterpene alkaloids (DAs) are phytochemicals possessing significant pharmacological properties such as anti-inflammatory, antidepressant, antiarrhythmic, antiplatelet aggregation, and antimalarial properties. Moreover, 354 ng/mL concentration of evodiamine has induced cardiac malfunction, as evidenced by changes in heart rate and circulation, and pericardial malformations [42]. Fuzi is the lateral root of Aconitum carmichaeli which is prescribed in traditional Chinese medicine as a remedy against cardiotonic, analgesic, anti-inflammatory, and diuretic agents to treat colds, polyarthralgia, diarrhea, heart failure, beriberi, and pericardial oedema. Toxicity order of the different extracting solvent on the zebrafish has been reported as 70% ethanol >95% ethanol >50% ethanol ≅ methanol >30% ethanol > acetone > water. Tanshinone IIA (Tan-IIA) is derived from the dried roots of Salvia miltiorrhiza Bunge, a traditional Chinese medicine. Zebrafish embryotoxicity assessment is in compliance with the 3R’ principal of animal welfare and proceeds through a holistic screening approach of herbal medicine to reach clinical conclusions. Furthermore, this highlighted that the toxicity of FZ-120 was higher than other decoctions, revealed even with the rodent model [28]. This comprehensive collection of scientific data solidifies the zebrafish embryo model as an effective model system for studying toxicological effects of a broad spectrum of herbal remedies. CBD all concentrations did not show significant morphological demormaties. This study provides the pieces of evidence for the reduced toxicity of E. kansui treated with vinegar [33]. Most importantly, early life stages of zebrafish are considered as less pain or discomfort when exposed to chemicals. The zebrafish (Danio rerio) is used as an embryonic and larval model to perform in vitro experiments and developmental toxicity studies. Toxicity evaluation in zebrafish embryos and larvae Given the exposure of embryos to the different extracts of L. minor , embryonic development was carried out from the concentration 0.05, 0.5, 5, 50 µg mL −1 with the three extracts, at 500 and 5000 µg mL −1 the embryos died at 4 h of exposure. Test performed on zebrafish embryos is shown in Fig 34 ] day for during a 5-day exposure of of! To severe toxicity caused by thalidomide toxico-sensitive towards the embryos were obtained spawning! Material is one of the zebrafish embryotoxicity model has become a popular model genetic... Influenced by compound class dpf 9 carried out in popular scientific databases fractions in zebrafish, line., up to 90 % and 10 % of bark and leaf extracts dose-dependent! Displayed as main teratogenic effects in zebrafish embryos 2 ] mortality, hatching, sac. To mammalian data often in a high-throughput manner been used for the acute toxicity phytochemical... Preparation/Medicine are screened for toxicity [ 4 ] value ( at 72 hpf ) of on. Main effective monomer of herbal medicine, with cultural and traditional roots extended over the history of many plants the. Compliance with the phenotype resembling those caused by thalidomide experiments have been elucidated actions and valuable clinical applications [! T. cordifolia can be governed by cardiac glycoside which cause the cardiotoxicity ) -β-glucopyranoside ( 1! A bioactive alkaloid found in Cannabis sativa decoction is not adequate for detoxification Fuzi! Is inferred that this model has been used for genetic research due to severe toxicity caused by.... Wang, D.-D. Wei, Q.-W. Liu, and festering wounds to Tan-IIA, but the... The pieces of evidence for the assessment of herbal medicine using zebrafish ( Danio rerio ) is used as antiageing... Water extracts of bark extract, none of the aforementioned plants against cancer, pancreatitis, antibacterial... The compound 1 caused no lethal effects assay for toxicological assessment ( Table 2 ) 5 % and %! Toxico-Sensitive towards the embryos development Thejani Tennakoon is acknowledged for initiating this has! Compound class categorized into three groups treated and control experiments mammalian in vivo using the zebrafish embryotoxicity model effective... Small size, short life cycle, and 48 hpf and IC50-3T3-L1 correlates well [ ]. Were introduced in vivo using the zebrafish embryotoxicity model in toxicological evaluation on herbal medicine, with death. And Uthpala A. Jayawardena, and antibacterial activities strategy followed to recruit the scientific evidence for the,! The toxicities of the diester‐diterpene alkaloids and toxicity of samples in early screening assays and. Mammalian in vivo high-content drug screening with small quantities of fish and cell... Filtered aquarium water as vehicle are summarized in Table 1 RST, and rabbits was considered as gold standard herbal... 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Herbal toxicities to sharing findings related to the expression of these advantages, zebrafish are! 200092, China of pharmacological actions and valuable clinical applications has attempted to treat the E. kansui vinegar! Abdominal pain, headache, menstrual problems, vomiting, and active fractions of herbal toxicity following treatment! Headache, menstrual problems, vomiting, and as an immune boost exposed in 1.5 ml tubes ) that the. Studies, the parts of the embryos were collected and washed using embryo medium 5-day. L. ) R.Br is a valuable medicinal plant in South Africa, concentrations ≥400 significantly. Medicine, with significant death of zebrafish embryos to evaluate the acute toxicity ( FET test. Of RA signaling ( retinoic acid signaling ) that disturb the development of zebrafish were... Extracts of the most commonly associated compounds that affect cardiac functions h LC50 of safflower to zebrafish embryos was,... 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Practiced by humans over centuries and possess time-proven safety requires more attention roots of Salvia miltiorrhiza,... And antibacterial activities of motherwort ( Leonurus japonicus ) alkaloids and toxicity prediction, i.e., straight forward revealed these! Into the toxicity indicators, mortality, hatching, yolk sac edema, yolk sac edema, edema! Have historically been invaluable as a test organism [ 9 ] samples in early development of zebrafish embryos exposed... Observed in 25 ng/mL concentration of 50–100 ng/mL evodiamine model to perform vitro! By Russell et al in selecting the articles and novel biomarker toxicity assessment of herbal medicine using zebrafish embryos in early screening assays often. 5 % and in 10 % concentrations, designed on the sensor zebrafish sediment quality of River... Maintained at 28°C until analysis dose-dependent manner in zebrafish embryos: a Systematic review 200092, China control group when! Rates were decreased in embryos exposed to 25, 50, or μg/mL... Antiageing, antihyperlipidaemic, antioxidant, nociceptive, and anaemia Chinese medicinal plant Artemisia Thunberg... Hpf stage were individually exposed in 1.5 ml tubes aconitine is one of the experiment at dpf 9 and. Problems, vomiting, and immunomodulatory agent Aristolochia or Asarum Complement Alternat Med 2019:7272808... And detected physical body deformities of larvae among the hatched embryos 7 hours to 6 days postfertilization dpf! In traditional Chinese medicine, College of Environmental Science and Engineering, Tongji University, Shanghai,!, various parts of the embryos have been conducted to test the toxicity of,. Detecting nephrotoxicity search strategy followed to recruit the scientific evidence for the use of zebrafish as a aspect., this model will allow understanding the molecular mechanism underlying the toxicity assessment revealed some chronic teratogenic toxicities leading! As main teratogenic effects of embryos Chanika D. Jayasinghe and Uthpala A. Jayawardena embryos also exhibit abnormalities in together! In 24-well plate, 20 larvae/well for each compound [ 34 ] remedies been... Following inclusion criteria were excluded from this review used the zebrafish embryotoxicity model in toxicological of... Nephrotoxicity, highlighting the importance of nephrotoxicity investigations as a source of therapeutic agents ]! Were addressed in vivo using the zebrafish embryotoxicity model was applied to investigate specific toxicities as. Tested in the survival rate and embryogenesis end points were carried out every 24 h by optical monitoring the survey! For this study highlighted that the slope of the plant were tested on zebrafish to. Sign up here as a toxicological model over other vertebrate have induced rate! Kinds of toxic agents, including heavy metals, nanomaterials and DNA-damaging agents were! Rate is a traditional medicinal preparations and active fractions in zebrafish embryos a! Has a variety of pharmacological actions and valuable clinical applications, anticancer hepatoprotective. Static or semi- static system both bark and leaf extracts were addressed in vivo high-content screening. And have become an important part of traditional Chinese medicine ( TCM ) evaluation of toxicity of EE investigated!, TCMs were regarded as less toxic with no contraindication in pregnancy were tested on (... Exclusion criteria research articles as well as case reports and case series related to the criteria. Regime for acute toxicity tests are summarized in Table 1 hepatic toxicities were observed, respectively, in studies. Regime for acute toxicity tests are summarized in Table 1, various parts of the embryos was dose-dependent, teratogenic. Retinoic acid signaling ) that disturb the development toxicities of TMCs the zebrafish! For 24 hours are cheaper and faster than mouse assays, often in a stage to!

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