The zebrafish embryotoxicity revealed the LC50 value of Carpesii Fructus as 230.40 mg/L. 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. It is anticipated, in future, the zebrafish model may provide a novel vista in herbal toxicology as an alternative assay to higher vertebrates. Embryo short-term toxicity test (FET) Yang, W.-F. Li, Y. Liu et al., “Acute toxicity screening of different extractions, components and constituents of Polygonum multiflorum Thunb. We are committed to sharing findings related to COVID-19 as quickly as possible. The search process was conducted independently by two authors and the final group of articles. The zebrafish embryotoxicity model is more suitable for isolated compounds from herbal medicine as the test can be performed with small quantities. Carpesii Fructus, the dried fruit of Carpesium abrotanoides L, is a traditional Chinese remedy used to cure the intestinal worms in children. This study provides the pieces of evidence for the reduced toxicity of E. kansui treated with vinegar [33]. 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. Particularly for tail malformation, the EC50 was calculated as 0.66 μM at 72 hpf [36]. After screening, 25 articles were included in this review, and they were categorized into three groups in which the zebrafish embryotoxicity assay has been applied to investigate the toxicity of (1) polyherbal formulae/medical prescription (2 full texts), (2) crude extracts (12 full texts), and (3) phytocompounds/isolated constituents (11 full texts). 4c-d. No zebrafish embryos had hatched when the dose of the treatment was 300 μg/ml, irrespective of extraction method used to generate the herbal drug. 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]. Fraction 1 did not produce any noticeable toxicity including the cardiac toxicity in treated zebrafish embryos, however, fraction # 2 successfully replicated the cardiac toxicity phenotype in zebrafish embryos and also at much lower concentration i.e. Blume) Ethanol Extract on Zebrafish (Danio rerio) Embryo In Vivo Traditionally, various parts of this tree are known to possess antimalarial, antitumoral, antioxidant, nociceptive, and antibacterial activities. Matrine and sophocarpine are two alkaloids found in the root of Sophora flavescens commonly known as Kushen in traditional Chinese medicine (TCM). Medicinal plants have historically been invaluable as a source of therapeutic agents. 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. This study highlighted that the long-term decoction is not adequate for detoxification of Fuzi [28]. There was a significant difference in the survival rate of the embryos between the treated and control experiments. In depth investigation of the molecular mechanism revealed that there is an increase in mRNA accumulation of drug-metabolism genes (CYP3A) and a multiple drug-resistance gene (MDR1) in embryos. The EC50 values were calculated based on teratogenic effects. Different exposure routes including oral gavage, inhalation/mucosal, and dermal or by injection into the bloodstream, abdomen, or the muscles could be evaluated following the administration of a test product [4]. toxicity assessment of herbal medicine was undertaken in ... toxicity,” “Zebrafish embryo/larval toxicity medicinal plants,”wereincludedinthesearch.Articleswereselected 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). 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. Moreover, this study utilized the UPLC-MS assay (Ultra Performance Liquid Chromatography-Mass Spectrometry) to identify the toxic compounds in the FZ-120 and suggested an appropriate test system to unravel aconitine-related acute toxicity [28]. The zebrafish embryotoxicity model has been employed to evaluate the acute toxicity of ethanolic extract of pomegranate (Punica granatum L) peel. Among the two extracts, 5% and 10% of leaf extract recorded the highest mortality of 100%. 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. The zebrafish embryotoxicity assay has been employed to investigate the toxic effect of Curcuma longa. The 96 h LC50 of safflower to zebrafish embryos was reported as 345.6 mg/L. Toxicity screening is conducted with animal and nonanimal models prior to clinical application. This study focused on its developmental toxicity by using zebrafish embryos. (motherwort) is a Chinese medicine. Zebrafish larvae exposed to linuron displayed pericardial edema, yolk sac edema, and spinal curvature. 236, 2013) [15]. The LC50 values were calculated based on the lethality endpoint, coagulation, lack of somite formation, lack of heartbeat, and none detachment of tail end compliance with the OECD guidelines. Both ethanol and water extracts of the plant were tested on zebrafish embryos. There are several advantages for the use of zebrafish as a toxicological model over other vertebrate. The zebrafish embryo toxicity test is based on a 48 hours exposure of newly fertilized eggs in a static or semi- static system. Then, the increase in heart rate made the myocardium overloaded and finally resulted in functional and organic damage on the zebrafish heart [45]. Moreover, 354 ng/mL concentration of evodiamine has induced cardiac malfunction, as evidenced by changes in heart rate and circulation, and pericardial malformations [42]. 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. Furthermore, this model was instrumental in investigating the underlying molecular mechanisms. He, J.-Y. Zebrafish larvae exposed to linuron displayed pericardial edema, … Thus, the heart-specific green fluorescence zebrafish model was introduced for evaluating the cardiotoxicity. Zhu, J.-h. Chen, S.-y. These prescriptions consist of several herbal/medicinal plants. Similarly, the zebrafish model provides valuable information about cardiotoxicity. The zebrafish embryos exposed to CBD (all concentrations) did not show significant morphological malformations. However, the embryo stages are preferably used for toxicological assessments particularly due to the transparent nature of the egg which allows the direct observation of developmental stages and assessment of endpoint in toxicity. Zebrafish embryos are more easily subjected to molecular screening such as analysis of gene expression studies. Fig. These preparations are commercially available for the public and have become an important part of Traditional Chinese Medicine (TCMs). 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. According to the study, both genes were upregulated in zebrafish embryos following the treatment with emodin [37]. Abstract. Recently, the zebrafish embryotoxicity model has received considerable attention in toxicity assessment of natural products and herbal medicine. Zebrafish embryos also exhibit abnormalities in spine together with yolk-sac oedema. The present study has attempted to treat the E. kansui with vinegar to reduce the toxicity. Mortality rates in the treatment group exhibited a dose and time-dependent increase. The toxicity assessment revealed some chronic teratogenic toxicities, leading to pericardial oedema, yolk sac swelling, and other abnormal developmental characteristics. Furthermore, in some studies, the molecular mechanisms underlying the toxicity of herbal medicine have been elucidated. However, the studies entailed in this review revealed embryo and development toxicities of TMCs. Toxicity evaluation in zebrafish embryos and larvae. The zebrafish embryotoxicity model is at the leading edge of toxicology research due to the short time required for analyses, … Toxicity Assessment of Herbal Medicine Using Zebrafish Embryos: A Systematic Review . The LC50 value for 24, 48,72, 96, and 120 hrs was calculated as 92.41, 79.19, 68.31, 56.67, and 55.89 μg/mL, respectively [26]. These two matrine-type alkaloids exhibited a variety of pharmacological properties such as anti-inflammatory, antiviral, antitumour, and antiarrhythmic activities. Furthermore, there is no reliable method of dose translation from zebrafish to human. We are committed to sharing findings related to COVID-19 as quickly as possible. Assessment of sediment quality of Yangtze River estuary using zebrafish (Danio rerio) embryos Lingling Wu. Tail bending and pericardial oedema were displayed as main teratogenic effects in this experiment. Kong, “Developmental toxicity and neurotoxicity of two matrine-type alkaloids, matrine and sophocarpine, in zebrafish (, S. Wang, K. Liu, X. Wang, Q. Moreover, this model provides an effective detection of the activities of some specific genes such as drug-metabolism genes (CYP3A) and a multiple drug-resistance gene (MDR1) which can be altered by phytocompounds like emodin. Articles were selected based on the inclusion and exclusion criteria mentioned in Section 2.2. The aerial parts of this plant are prescribed against gynaecological and obstetrical conditions, such as menstrual blood stasis, menstrual disturbances, dysmenorrhea, amenorrhea, postpartum haemorrhage, and postpartum recovery. Toxicity Assessment of Herbal Medicine Using Zebrafish Embryos: A Systematic Review. Evid Based Complement Alternat Med. The information gathered in this review collectively indicates the zebrafish embryotoxicity model holds a great promise in herbal toxicity assessment and provides an ideal alternative to laboratory animals like rats, mice, or rabbits. The methanol extract of the C. longa dosage at 62.5 μg/mL exhibited teratogenic effect and higher concentrations caused physical body deformities such as kink tail, bend trunk, and enlarged yolk sac. FET test performed on zebrafish revealed to be more toxico-sensitive towards the embryos development. The heart rate has been decreased progressively with increasing concentrations [27]. 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. The zebrafish embryotoxicity assay was used to evaluate the toxicity of bioactive fraction of the Korean medicinal plant Artemisia capillaries Thunberg. Metabolomic assessment of arsenite toxicity and novel biomarker discovery in early development of zebrafish embryos. This section includes several studies that have used the zebrafish embryo assay for toxicological assessment (Table 2). It has a variety of pharmacological actions such as antidiabetic, antinociception, anticancer, and cholesterol reduction potential. Review articles are excluded from this waiver policy. Aconitine is one of the diester‐diterpene alkaloids and well‐known for its arrhythmogenic effects. The percentages of embryos with malformed kidney phenotypes increased as the exposure dosages of AA increased. Zebrafish embryos were incubated with 0.1–2 μg/mL of emodin from 7 hours to 6 days postfertilization (dpf). The results predicted that the LC50 at 48 hpf and IC50-3T3-L1 correlates well [22]. Most studies entailed here followed OECD test protocols to elucidate the toxicity of herbal medicine. On the other hand, BAC, BMAC, and BHAC decreased the heart rates in the dose range of 31.3–250 μM, while the highest dose (500 μM) of BAC and BMAC increased the heart rates. Angiogenic effect of motherwort (Leonurus japonicus) alkaloids and toxicity of motherwort essential oil on zebrafish embryos Fitoterapia . Acute Toxicity of Keladi Tikus (Typhonium flagelliforme (Lodd.) Chanika D. Jayasinghe, Uthpala A. Jayawardena, "Toxicity Assessment of Herbal Medicine Using Zebrafish Embryos: A Systematic Review", Evidence-Based Complementary and Alternative Medicine, vol. 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. Hence this study was designed to find out the developmental toxicity of M. charantia using zebrafish (Danio rerio)embryos. Diterpene alkaloids (DAs) are phytochemicals possessing significant pharmacological properties such as anti-inflammatory, antidepressant, antiarrhythmic, antiplatelet aggregation, and antimalarial properties. Concentration at 250 mg/L revealed significant inhibition of heartbeat at 48 hpf and 72 hpf. Metabolomic assessment of arsenite toxicity and novel biomarker discovery in early development of zebrafish embryos Toxicol Lett . Cannabidiol (CBD) is an active compound found in Cannabis sativa. Radix Sophorae tonkinensis (RST) is a Chinese medicine used to cure infectious and inflammatory diseases. Hence, it is inferred that this model is more applicable for single compounds and toxicity prediction, i.e., straight forward. Pomegranate peel is prescribed as an antimicrobial agent. After screening, 25 articles were included in this review, and they were categorized into three groups in which the zebrafish embryotoxicity assay has been applied to investigate the toxicity of (1) polyherbal formulae/medical prescription (2 full texts), (2) crude extracts (12 full texts), and (3) phytocompounds/isolated constituents (11 full texts). Egg coagulation, mortality, hatching, yolk sac edema, pericardial edema and teratogenicity were recorded each day for during a 5-day exposure. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Teratogenic effects were exerted by all three preparations with an EC50 value at 351, 793, and 220 μg/mL for CDT, ANP, and LPT, respectively. Studies which have used the zebrafish embryos or larval stages to assess the toxicity of (a) crude herbal/medicinal preparation (b) different chemical fractions derived from herbal medicine, (c) group of compounds derived from herbal medicine or medicinal plants, (d) single compound extracted from herbal plants/medicine, and (e) herbal products/traditional prescriptions were included in this study. 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. Shi, C. Peng et al., “Angiogenic effect of motherwort (, H.-c. Liu, X.-y. The zebrafish (Danio rerio) is used as an embryonic and larval model to perform in vitro experiments and developmental toxicity studies. Animal models are considered as gold standards in toxicology testing since the whole animal is typically closely correlated to human toxicity and more importantly incorporates pharmacokinetics, absorption, distribution, and metabolism [4]. The LC50 value for Euphorbia kansui (KS-1) and fry-baked with vinegar KS-2 was reported as 2.78 ± 0.86 μg/mL and 6.62 ± 1.24 μg/mL, respectively, indicating that the KS-2 was less toxic than KS-1. Epub 2018 Mar 15. Zebrafish embryos were incubated with 0.1–2 μg/mL of emodin from 7 hours to 6 days postfertilization (dpf). At 96 and 120 hpf, kink and bend tail were observed, respectively, in embryos treated with 62.5 μg/mL. Using zebrafish embryos, Langheinrich et al. It is a nonpsychotomimetic compound that has been used for the treatment of severe neuropsychiatric disorders. Toxicity Assessment of Herbal Medicine Using Zebrafish Embryos: A Systematic Review. Teratogenetic effects such as pericardial oedema, tail malformation, notochord malformation, scoliosis, yolk oedema, and growth retardation were observed after 48 hrs. Hence, this research aimed to assess the toxicity of C. longa extract on zebrafish. Drug concentrations, designed on the basis of preexperiment data, used in the acute toxicity tests are summarized in Table 1. [7]. The LD50 value (at 72 hpf) of emodin on 7 hpf embryos were approximately 0.20 μg/mL. 2018 Jun 15;290:116-122. doi: 10.1016/j.toxlet.2018.03.014. Zebrafish has become a popular model for genetic research due to the high conservation of gene function between zebrafish and humans. The average embryonic heart rate was also decreased in embryos exposed to 25, 50, or 100 μg/mL. 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Influenced by compound class be more toxico-sensitive towards the embryos were used to cure infectious and diseases!

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