Talk:Abnormal Development - Herbal Drugs
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Cite this page: Hill, M.A. (2024, April 26) Embryology Abnormal Development - Herbal Drugs. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Abnormal_Development_-_Herbal_Drugs |
2020
Huang CH, Wang FT & Chan WH. (2020). Dose-dependent beneficial and harmful effects of berberine on mouse oocyte maturation and fertilization and fetal development. Toxicol Res (Camb) , 9, 431-443. PMID: 32905254 DOI.
Dose-dependent beneficial and harmful effects of berberine on mouse oocyte maturation and fertilization and fetal development
Previous studies have shown that berberine, an isoquinoline alkaloid isolated from several traditional Chinese herbal medicines, suppresses growth and induces apoptosis in some tumor cell lines. It has also been shown that berberine possesses anti-atherosclerosis and antioxidant activities in hyperlipidemic model rats. Our previous study in mice found that berberine causes harmful effects on preimplantation and postimplantation embryonic development, both in vitro and in vivo, by triggering reactive oxygen species (ROS)-mediated apoptotic cascades in mouse blastocysts. In the current investigation, we further showed that berberine treatment has distinct dose-dependent effects on oocyte maturation and subsequent development. Preincubation of oocytes with 2.5 μM berberine significantly enhanced maturation and in vitro fertilization (IVF) rates, with subsequent beneficial effects on embryonic development. In contrast, preincubation with 10 μM berberine negatively impacted mouse oocyte maturation, decreased IVF rates and impaired subsequent embryonic development. Similar dose-dependent effects were also demonstrated in vivo. Specifically, intravenous injection of berberine significantly enhanced mouse oocyte maturation, IVF rate and early-stage embryo development after fertilization at a dose of 1 mg/kg body weight but significantly impaired oocyte maturation and IVF rates and caused harmful effects on early embryonic development at a dose of 5 mg/kg. Mechanistically, we found that berberine enhanced intracellular ROS production and apoptosis of oocytes at a concentration of 10 μM but actually significantly decreased total intracellular ROS content and had no apoptotic effect at a concentration of 2.5 μM. Moreover, pretreatment of oocytes with Ac-DEVD-cho, a caspase-3-specific inhibitor, effectively blocked berberine-induced negative impacts on oocyte maturation, fertilization and subsequent development. Collectively, these findings establish the dose-dependent beneficial versus deleterious effects of berberine and suggest that the mechanism underlying the deleterious effects of berberine involves a caspase-3-dependent apoptotic process acting downstream of an increase in intracellular ROS levels.
2019
Li L, Yin Tang L, Liang B, Wang R, Sun Q, Bik San Lau C, Chung Leung P, Fritsche E, Liebsch M, Seiler Wulczyn AEM, Spielmann H & Wang CC. (2019). Evaluation of in vitro embryotoxicity tests for Chinese herbal medicines. Reprod. Toxicol. , 89, 45-53. PMID: 31228572 DOI.
Evaluation of in Vitro Embryotoxicity Tests for Chinese Herbal Medicines
Chinese herbal medicines (CHMs) have been widely used during pregnancy, but feto-embryo safety tests are lacking. Here we evaluated in vitro embryotoxicity tests (IVTs) as alternative methods in assessing developmental toxicity of CHMs. Ten CHMs were selected and classified as strongly, weakly and non-embryotoxic. Three well validated IVTs and prediction models (PMs), including embryonic stem cell test (EST), micromass (MM) and whole embryo culture (WEC), were compared. All strongly embryotoxic CHMs were predicted by MM and WEC PM2. While all weakly embryotoxic CHMs were predicted by MM and WEC PM1. All non-embryotoxic CHMs were classified by EST, MM, but over-classified as weakly embryotoxic by WEC PM1. Overall predictivity, precision and accuracy of WEC determined by PM2 were better than EST and MM tests. Compared with validated chemicals, performance of IVTs for CHMs was comparable. So IVTs are adequate to identify and exclude embryotoxic potential of CHMs in this training set.
Alafiatayo AA, Lai KS, Syahida A, Mahmood M & Shaharuddin NA. (2019). Phytochemical Evaluation, Embryotoxicity, and Teratogenic Effects of Curcuma longa Extract on Zebrafish (Danio rerio). Evid Based Complement Alternat Med , 2019, 3807207. PMID: 30949217 DOI.
Phytochemical Evaluation, Embryotoxicity, and Teratogenic Effects of Curcuma longa Extract on Zebrafish ( Danio rerio)
Curcuma longa L. is a rhizome plant often used as traditional medicinal preparations in Southeast Asia. The dried powder is commonly known as cure-all herbal medicine with a wider spectrum of pharmaceutical activities. 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. Hence, this research aimed to assess the toxicity of C. longa extract on zebrafish. Using a reflux flask, methanol extract of C. longa was extracted and the identification and quantification of total flavonoids were carried out with HPLC. Twelve fertilized embryos were selected to test the embryotoxicity and teratogenicity at different concentration points. The embryos were exposed to the extract in the E3M medium while the control was only exposed to E3M and different developmental endpoints were recorded with the therapeutic index calculated using the ratio of LC50/EC50. C. longa extract was detected to be highly rich in flavonoids with catechin, epicatechin, and naringenin as the 3 most abundant with concentrations of 3,531.34, 688.70, and 523.83μg/mL, respectively. The toxicity effects were discovered to be dose-dependent at dosage above 62.50μg/mL, while, at 125.0μg/mL, mortality of embryos was observed and physical body deformities of larvae were recorded among the hatched embryos at higher concentrations. Teratogenic effect of the extract was severe at higher concentrations producing physical body deformities such as kink tail, bend trunk, and enlarged yolk sac edema. Finally, the therapeutic index (TI) values calculated were approximately the same for different concentration points tested. Overall, the result revealed that plants having therapeutic potential could also pose threats when consumed at higher doses especially on the embryos. Therefore, detailed toxicity analysis should be carried out on medicinal plants to ascertain their safety on the embryos and its development.
Gotardo AT, Mattos MIDS, Hueza IM & Górniak SL. (2019). The effect of Cynara scolymus (artichoke) on maternal reproductive outcomes and fetal development in rats. Regul. Toxicol. Pharmacol. , 102, 74-78. PMID: 30611817 DOI.
The Effect of Cynara Scolymus (Artichoke) on Maternal Reproductive Outcomes and Fetal Development in Rats
Cynara scolymus (C.scolymus) is a plant employed worldwide as an herbal medicine. However, there is a paucity of data related to the evaluation of its toxicity in commercial preparations; thus, the aim of this study was to evaluate the possible teratogenic effect of the dry extract of C.scolymus leaves in Wistar rats. Females were treated, from gestation day (GD) 6 until GD19, with 0.0, 1.0, 2.0 or 4.0 g/kg body weight of C.scolymus extract. At GD20, a cesarean section was performed for evaluation of maternal and fetal parameters. C.scolymus did not induce changes in food consumption, preimplantation or postimplantation losses, placental weight or biochemical profile. An increase in water consumption was observed in pregnant females treated with the higher doses of C.scolymus. Experimental groups showed lower body weight gain during pregnancy and lower gravid uterus weight. Maternal body weight minus the gravid uterus weight did not result in significant differences. Reductions in fetal weight and length were observed in experimental groups. The number of live pups per litter was lower in the highest dose group. No fetal skeletal or visceral malformations were detected. The results showed that the consumption of artichoke during pregnancy clearly has a negative impact on fetuses.
2018
Maternal and developmental toxicity of the hallucinogenic plant-based beverage ayahuasca in rats
Reprod Toxicol. 2018 Mar 6. pii: S0890-6238(17)30703-7. doi: 10.1016/j.reprotox.2018.03.002. [Epub ahead of print]
da Motta LG1, de Morais JA2, Tavares ACAM1, Vianna LMS3, Mortari MR4, Amorim RFB3, Carvalho RR5, Paumgartten FJR5, Pic-Taylor A2, Caldas ED6.
Abstract
Rats were treated orally with ayahuasca (AYA) on gestation days (GD) 6-20 at doses corresponding to one-(1X) to eight-fold (8X) the average dose taken by a human adult in a religious ritual, and the pregnancy outcome evaluated on GD21. Rats treated with 4X and 8X doses died during the treatment period (44 and 52%), and those that survived showed kidney injury. Rats surviving the 8X dose showed neuronal loss in hippocampal regions and in the raphe nuclei, and those from the 2X dose neuronal loss in CA1. Delayed intrauterine growth, induced embryo deaths and increased occurrence of foetal anomalies were observed at the 8X dose. At non-lethal doses, AYA enhanced embryolethality and the incidence of foetal soft-tissue and skeleton anomalies. This study suggested that AYA is developmentally toxic and that its daily use by pregnant women may pose risks for the conceptus. KEYWORDS: Ayahuasca; Banisteriopsis caapi; Psychotria viridis; developmental toxicity; gestation losses; serotonin syndrome; teratogenicity PMID: 29522798 DOI: 10.1016/j.reprotox.2018.03.002
2016
Teratogenic Effect of Verbascoside, Main Constituent of Lippia citriodora Leaves, in Mice
Iran J Pharm Res. 2016 Spring;15(2):521-5.
Etemad L1, Zafari R2, Moallem SA3, Vahdati-Mashhadian N4, Skouei Shirvan Z3, Hosseinzadeh H5.
Abstract
Verbascoside (acteoside), a phenyl propanoid glycoside, comprises 0.5 to 3.5 % dry weight of Lippia citriodora leaves. A wide range of biological activities are attributed to verbascoside including anti-inflammatory, antioxidant, anti-bacterial, anti-tumor, anti-fungal, photoprotective as well as chelating effects. The objective of this study is to evaluate the effect of verbascoside on pregnancy outcome in mice. Timed-pregnant mice received doses of 1g/kg/day verbascoside or the vehicle control during organogenesis, intraperitoneally. Maternal body weights were measured throughout pregnancy. The litters were examined for external malformations and skeletal abnormalities. Then they were stained with Alizarin red S and Alcian blue. Maternal exposure to verbascoside throughout pregnancy did not influence the mean of maternal weight gain. Statistically significant difference was not found in mean number of implantation sites, live and resorbed fetuses between control and experiment groups. Our data demonstrate that the main component of L. citriodora, verbascoside using during organogenesis possesses no risk to fetuses. However, more research projects are needed to confirm these findings and determine the exact effects of verbascoside on human embryo development. KEYWORDS: Aloysia triphylla; Herbal medicine; Lippia citriodora; Teratogen; Verbascoside
PMID 27642323 PMCID: PMC5018280
