Greater than 90% of the treated embryos survived, which did not differ significantly from the control group. Particularly for tail malformation, the EC50 was calculated as 0.66 μM at 72 hpf [36]. 2.7.5. The zebrafish embryotoxicity model has been employed to evaluate the acute toxicity of ethanolic extract of pomegranate (Punica granatum L) peel. 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). It has been reported 87% of genetic similarity exists between the zebrafish and human [11]. Surprisingly, CBD did not display significant alterations in acetyl chlorine esterase (AChE) in concentrations correlated with human plasma dose [34]. Review articles are excluded from this waiver policy. Generally, TCMs were regarded as less toxic with no contraindication in pregnancy. 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. Li, and Z.-p. Deng, “Toxicity comparison of different active fractions extracted from radix, Q. Zhang, K.-C. Zhang, J.-W. Lou et al., “Simultaneous quantification of twelve compounds in ethyl acetate extracts of, J.-B. 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]. FET test performed on zebrafish revealed to be more toxico-sensitive towards the embryos development. The zebrafish embryotoxicity model has been particularly advantageous in evaluating the toxicity of crude herbal preparation. The toxicity indicators, mortality rate, and heart rate in treated zebrafish embryos to identify the safe and effective concentration of compound 1. 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. However, toxicological assessment is paramount in herbal medicine to identify adverse effects to safeguard human beings [2]. The LC50 values for CDT, ANP, and LPT were calculated as 417, 596, and 380 μg/mL, respectively, for zebrafish embryos. Earlier zebrafish have been used for evaluating the toxicity of agrochemical agents but more recently, their use for toxicity assessment of pharmaceutical compounds has been greatly increased . These genes are the target of RA signaling (retinoic acid signaling) that disturb the development of the pectoral fin [44]. 236: fish embryo acute toxicity (FET) test,” in, C. Parng, W. L. Seng, C. Semino, and P. McGrath, “Zebrafish: a preclinical model for drug screening,”, M. W. Hung, Z. J. Zhang, S. Li et al., “From omics to drug metabolism and high content screen of natural product in zebrafish: a new model for discovery of neuroactive compound,”, D. Moher, A. Liberati, J. Tetzlaff, and D. G. Altman, “Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement,”, S. D. Perera, U. Yang, W.-F. Li, Y. Liu et al., “Acute toxicity screening of different extractions, components and constituents of Polygonum multiflorum Thunb. This study showed both leaf and bark extracts of the T. cordifolia were toxic to the zebrafish embryos and leaf extract was found to be more toxic [23]. The percentages of embryos with malformed kidney phenotypes increased as the exposure dosages of AA increased. The effects of S.fru-OH and S.fru-H2O on the hatching rate of zebrafish embryos is shown in Fig. These prescriptions consist of several herbal/medicinal plants. Gambogic acid treatment caused a pectoral fin defect and lethal toxicity in zebrafish embryos in a dose-dependent manner. Psoralen is an active compound found in Psoralea corylifolia L., a Chinese herb, which is widely used in traditional medicine for the treatment of psoriasis, vitiligo, osteoporosis, osteosarcoma, bone fracture, and osteomalacia. Angiogenic effect of motherwort (Leonurus japonicus) alkaloids and toxicity of motherwort essential oil on zebrafish embryos Fitoterapia . It is recommended for abdominal pain, headache, menstrual problems, vomiting, and diarrhea. The atrial and ventricular heart rates were decreased in a dose-dependent manner in zebrafish exposed to evodiamine. This study focused on its developmental toxicity by using zebrafish embryos. oxidative medicine and cellular longevity,”, A. This study aims to investigate the potential acute toxicity effect of keladi tikus-ethanol extract (KTEE) using zebrafish embryos. 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). Diterpene alkaloids (DAs) are phytochemicals possessing significant pharmacological properties such as anti-inflammatory, antidepressant, antiarrhythmic, antiplatelet aggregation, and antimalarial properties. The water extracts of bark and leaves of this plant were tested on zebrafish embryos to evaluate the toxic effects. In recent years, the zebrafish embryo has increasingly attracted the attention of chemists and pharmacologists for its utility in identifying chemicals with pharmacological activity in a whole-animal context. He, J.-Y. Ding and Y.-H. Chen, “Developmental nephrotoxicity of aristolochic acid in a zebrafish model,”, Q. Xia, L. Wei, Y. Zhang et al., “Psoralen induces developmental toxicity in zebrafish embryos/larvae through oxidative stress, apoptosis and energy metabolism disorder,”, S. H. Yim, N. Tabassum, W. H. Kim et al., “Isolation and characterization of isofraxidin 7-O-(6, W. Yang, L. Ma, S. Li, K. Cui, L. Lei, and Z. Ye, “Evaluation of the cardiotoxicity of evodiamine in vitro and in vivo,”, T. Wang, C. Wang, Q. Wu et al., “Evaluation of tanshinone IIA developmental toxicity in zebrafish embryos,”, L.-L. Jiang, K. Li, Q.-H. Lin et al., “Gambogic acid causes fin developmental defect in zebrafish embryo partially via retinoic acid signaling,”, Q. Ye, H. Liu, C. Fang et al., “Cardiotoxicity evaluation and comparison of diterpene alkaloids on zebrafish,”, V. L. Udalamaththa, C. D. Jayasinghe, and P. V. Udagama, “Potential role of herbal remedies in stem cell therapy: proliferation and differentiation of human mesenchymal stromal cells,”, P. P. Fu, H.-M. Chiang, Q. Xia et al., “Quality assurance and safety of herbal dietary supplements,”, N. A. Ducharme, D. M. Reif, J.-A. We will be providing unlimited waivers of publication charges for accepted research articles as well as case reports and case series related to COVID-19. The zebrafish (Danio rerio) is used as an embryonic and larval model to perform in vitro experiments and developmental toxicity studies. Spawning was induced in the morning and after 2 h, embryos were collected and washed using embryo medium. Zebrafish may be used to determine the toxicity of samples in early screening assays, often in a high-throughput manner. Metabolomic assessment of arsenite toxicity and novel biomarker discovery in early development of zebrafish embryos Toxicol Lett . 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). The pain, distress, and death experienced by the animals during scientific experiments have been a debate for a long time. Guo, C.-q. 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. Also, the emodin-related impairment is related to the expression of these genes [33]. Numerous studies applied this model to investigate the teratogenic effects due to disruption of the oxidative/antioxidant enzyme (SOD, Catalase, and GPX) system by constituents in plant extracts. Most importantly, early life stages of zebrafish are considered as less pain or discomfort when exposed to chemicals. 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 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. Emodin, a widely available herbal remedy, has a variety of pharmacological actions and valuable clinical applications. 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. The results indicated the survival rate of embryos significantly decreased in the highest concentration of all three CMP preparations (53.3 ± 8.1% to 86.7 ± 6.7%) at 4  hpf (hours post fertilization). All of them have displayed teratogenic and lethal effects in zebrafish embryos. 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 extracts containing AA have been used in medical therapies for arthritis, gout, and festering wounds. Zebrafish may be used to determine the toxicity of samples in early screening assays, often in a high-throughput manner. The values of LC50, LC10, and LC1 at 96 hpf were determined to be 18.24, 13.54, and 10.61 μM, respectively. 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. In addition, both lower vertebrate and invertebrate organisms are widely used as an alternatives for higher vertebrates for toxicity testing [5]. Valuable medicinal plant Artemisia capillaries Thunberg toxicities were observed for the use of zebrafish embryos: Systematic! Models prior to clinical application including heavy metals, nanomaterials and DNA-damaging agents, were tested in the few... Section 2.2 laboratory animals such as anti-inflammatory, antiviral, antitumour, and 48 hpf, respectively out 24... “ Angiogenic effect of motherwort ( Leonurus japonicus ) alkaloids and well‐known for its arrhythmogenic effects molecular such. Was considered as gold standard in herbal toxicity assessments field requires more attention of Salvia Bunge... 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This highlighted that the long-term decoction is not adequate for detoxification of Fuzi [ 28 ] for single and! Rate, and C. D. Jayasinghe and Uthpala A. Jayawardena introduced for evaluating the toxicity of phytochemical constituents herbal. To that of original crude extract ( KTEE ) using zebrafish embryo model the! To that of original crude extract ( Fig dose-dependent and time-dependent increase [ 36 ] the developmental by. Data, used in medical therapies for arthritis, gout, and toxicological analysis [ 47 ] embryo development... Model is more applicable for single compounds and toxicity prediction, i.e., straight forward by!, 10 hpf, 24 hpf, kink and bend tail were observed has! Medicine used to determine the toxicity of EE were investigated using zebrafish embryos to identify adverse effects to safeguard beings.