Heavy metal accumulation efficiency and subsequent of cytogenotoxicity evaluation in the medicinal plant Equisetum hyemale.

Heavy metals in soils represent a threat to the environment, food safety, as well as human and animal health. The bioaccumulation of these elements in plants might enhance medium- and long-term adverse health risk promoting genetic alterations that lead to dermal, gastrointestinal, circulatory, renal, and brain disorders. The present study aimed to determine the bioaccumulation potential and cytogenotoxic effect of Equisetum hyemale extracts. E. hyemale seedlings were divided into two groups: exposed group (plants cultivated in soil with heavy metals solution) and control (plants cultivated in soil with distilled water). Heavy metals were quantified in the cultivation soils (control and exposed) and extracts (ethanolic and infusion) of vegetative parts from E. hyemale cultivated in both soils. Root length and cytogenotoxic effect were determined utilizing Allium cepa bioassay. Data demonstrated that Equisetum hyemale present the ability to absorb and bioaccumulate different heavy metals including lead, copper, cobalt manganese, zinc, iron and chromium. Given this property E. hyemale may be considered a reliable bioindicator to assess cytogenotoxicity of certain substances that exert adverse risks to environment and human and animal health.

Licania rigida leaf extract: Protective effect on oxidative stress, associated with cytotoxic, mutagenic and preclinical aspects.

Brazilian plant biodiversity is a rich alternative source of bioactive compounds since plant-derived extracts and/or their secondary metabolites exhibit potential properties to treat several diseases. In this context, Licania rigida Benth (Chrysobalanaceae Family), a large evergreen tree distributed in Brazilian semi-arid regions, deserves attention for its widespread use in popular medicine, although its biological properties are still poorly studied. The aim of this study was to examine (1) acute and sub-chronic oral toxicity at 2000 mg/kg dose; (2) in vitro cytotoxicity at 0.1; 1; 10; 100 or 1000 µg/ml; (3) in vivo mutagenicity at 5, 10 or 20 mg/ml, and (4) potential antioxidant protective effect of L. rigida aqueous leaf extract of (AELr). No marked apparent toxic and genotoxic effects were observed using in vitro and in vivo assays after in vitro treatment of Chinese hamster ovary cell line (CHO-K1) with AELr or in vivo exposure of Wistar rats and Drosophila melanogaster to different extract concentrations. Concerning the antioxidant effect, the extract exhibited a protective effect by decreasing lipid peroxidation as determined by malondialdehyde levels. No significant changes were observed for glutathione (GSH) levels and activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Data demonstrate the beneficial potential of AELr to be employed for therapeutic purposes. However, further studies are required to validate the pharmacological application of this plant extract to develop as a phytotherapeutic formulation.

The Botanical Safety Consortium: A public-private partnership to enhance the botanical safety toolkit.

Botanical dietary supplement use is widespread and growing, therefore, ensuring the safety of botanical products is a public health priority. This commentary describes the mission and objectives of the Botanical Safety Consortium (BSC) - a public-private partnership aimed at enhancing the toolkit for conducting the safety evaluation of botanicals. This partnership is the result of a Memorandum of Understanding between the US FDA, the National Institute of Environmental Health Sciences, and the Health and Environmental Sciences Institute. The BSC serves as a global forum for scientists from government, academia, consumer health groups, industry, and non-profit organizations to work collaboratively on adapting and integrating new approach methodologies (NAMs) into routine botanical safety assessments. The objectives of the BSC are to: 1) engage with a group of global stakeholders to leverage scientific safety approaches; 2) establish appropriate levels of chemical characterization for botanicals as complex mixtures; 3) identify pragmatic, fit-for-purpose NAMs to evaluate botanical safety; 4) evaluate the application of these tools via comparison to the currently available safety information on selected botanicals; 5) and integrate these tools into a framework that can facilitate the evaluation of botanicals. Initially, the BSC is focused on oral exposure from dietary supplements, but this scope could be expanded in future phases of work. This commentary provides an overview of the structure, goals, and strategies of this initiative and insights regarding our first objectives, namely the selection and prioritization of botanicals based on putative toxicological properties.

Assessment of black cumin (Nigella sativa L.) as a food ingredient and putative therapeutic agent.

The whole or ground seeds of the food ingredient Nigella sativa L., known in Western culture as "black cumin" or "black caraway", has a three-millennial history of use in Middle- and Far-Eastern cultures as a food ingredient. The seed and its extracts have also been increasingly reported as a successful therapeutic agent with efficacy often attributed to the presence of the powerful antioxidant, thymoquinone. However, quantitative analysis of the seed (especially the volatile fraction) yields widely variable results, which may be due to one or a combination of different crop origins or possible varietal differences, contamination/adulteration, method of extraction, stage of maturation of the extracted seed and other factors. Nonetheless, despite the reported wide variability in bioactive constituents, many publications cite quantifiable outcomes in in vitro and in vivo toxicity testing and in clinical trials. There are a few reports describing allergic reactions in humans when N. sativa extracts are applied to the skin. Notwithstanding the foregoing, N. sativa seeds, used as a food ingredient at historical levels of consumption and as traditionally practiced are safe and Generally Recognized As Safe.

Aconitine disrupts serotonin neurotransmission via 5-hydroxytryptamine receptor in zebrafish embryo.

Medicinal plants of the genus Aconitum are one of the most commonly used herbs in traditional medicine in East Asia to treat conditions related to the heart, pain, or inflammation. However, these herbs are also dangerous as accidental poisoning due to misuse is a recurring issue. These plants contain a number of diester-diterpenoid alkaloid compounds and aconitine is the most abundant and active one. This study investigated neurotoxicity of aconitine to zebrafish embryos in early development in relation to serotonin regulation. Experimental results showed that aconitine exposure (1, 10, and 100 µM) increased frequency of coiling behavior in zebrafish embryos in a dose-dependent manner and this effect can be triggered by either exposure to 5-hydroxytryptamine 1A (5-HT1A) receptor agonist (±)-8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT) or overexpression of serotonin receptor 5-htr1ab. At the same time, coiling behavior caused by aconitine exposure could be rescued by co-exposure to 5-HT1A receptor antagonist WAY-100635 Maleate (WAY100635) and knockdown of 5-htr1ab using morpholino. Exposure to aconitine also significantly increased serotonin receptor 5-htr1ab and 5-htr1bd gene expression at 24 h post fertilization (hpf), but decreased their expression and protein expression of the serotonin receptor at 96 hpf with the high dose. These results suggest that neurotoxicity caused by aconitine is mediated through the 5-HT receptor.

Plant species used in Brazil and Asia regions with toxic properties.

Many efforts are being made to find biomolecules extracted from plants to be useful therapeutic agents to replace the drugs traditionally used in clinical medicine with known side effects and high financial investment, thus offering greater safety and less risk to the population. However, the presence of toxic substances such as alkaloids, amino acids, amides, glycosides, saponins, and tannins are the main reasons for the poisonous activity of some medicinal plants. In this sense, understanding plants constituents and lethal doses can be important source in managing several diseases in human life. This review aimed to present extracts, fractions, and/or compounds of plants of Brazil and Asia regions that have reported toxicity to in vitro and in vivo models. The results presented here contribute to warning the population about the toxicological characterization of some plants, however, further high-quality studies are needed to firmly establish the clinical efficacy of the plants (or compounds).

Nephrotoxicity of Herbal Products in Europe-A Review of an Underestimated Problem.

Currently in Europe, despite the many advances in production technology of synthetic drugs, the interest in natural herbal medicines continues to increase. One of the reasons for their popular use is the assumption that natural equals safe. However, herbal medicines contain pharmacologically active ingredients, some of which have been associated with adverse effects. Kidneys are particularly susceptible to injury induced by toxins, including poisonous constituents from medicinal plants. The most recognized herb-induced kidney injury is aristolochic acid nephropathy connected with misuse of certain Traditional Chinese herbal medicines. Data concerning nephrotoxicity of plant species of European origin are scarce. Here, we critically review significant data of the nephrotoxicity of several plants used in European phytotherapy, including Artemisia herba-alba, Glycyrrhiza glabra, Euphorbia paralias, and Aloe). Causative mechanisms and factors predisposing to intoxications from the use of herbs are discussed. The basic intention of this review is to improve pharmacovigilance of herbal medicine, especially in patients with chronic kidney diseases.

Assessment of acute, sub-acute, chronic and genotoxicity of polyherbal formulation DCD-684 in mice.

Digas colic drops (DCD-684) a polyherbal formulation containing Carum carvi, Foeniculum vulgare, Mentha arvensis, Mentha piperita and Zingiber officinale is widely used in Pakistan against gastrointestinal ailments including infantile colic. The DCD-684 (0.03-3ml/kg.bw) administered orally in acute (7-days) and sub-acute toxicity (14-days) tests, displayed neither mortality nor toxicological changes in physical, behavioral, biochemical and histopathological parameters. In chronic study (90-days), DCD-684 (0.3-12ml/kg.bw) also revealed no changes. However, at 18 and 36 ml/kg.bw, liver demonstrated mild inflammation correlating with raised aspartate transaminase (AST), alkaline phosphatase (ALP) and alpha fetoprotein (AFP) levels. Increased levels of urea and inflamed renal parenchyma indicated mild nephro-toxicity with high alanine aminotransferase (ALT) at 36ml/kg.bw. The LD50 of DCD-684 in mice was 27.5 ml/kg.bw. In hepatocytes at 36ml/kg.bw, elevated mRNA expression of pro-inflammatory chemokines and cytokines were evident. DCD-684 neither damaged DNA nor induced cytotoxicity in micronucleus assay. In conclusion, polyherbal DCD-684 caused neither hepatic, renal, genotoxicity nor any undesirable effect in mice. Higher doses administered for 90 days showed mild toxic effects with no sign of necrosis, fibrosis or genotoxicity. Thus, in mice DCD-684 demonstrated a wide margin of safety to be used for the relief of infantile colic.

Toxicological, chemopreventive, and cytotoxic potentialities of rare vegetal species and supporting findings for the Brazilian Unified Health System (SUS).

Caatinga flora which are found in a poor Brazilian region contain a substantial number of endemic taxa with biomedical and social importance for regional communities. This study examined the antioxidant and cytotoxic potential of 35 samples (extracts/fractions) from 12 Caatinga species and determined the antiproliferative and genotoxic action of dichloromethane fraction from Mimosa caesalpiniifolia stem bark (DC-Mca) on human and vegetal cells. Samples were assessed for chemopreventive ability, toxic effects on Artemia salina shrimp as well as cytotoxicity on tumor cell lines and erythrocytes. DC-Mca was also tested with respect to antiproliferative and genotoxic effects upon normal leukocytes and meristematic cells from A. cepa roots. Some extracts reduced free radical levels >95% and 7 samples exhibited a lethal concentration (LC) 50 < 100 µg/ml upon Artemia salina larvae. Eight samples displayed in vitro antitumor effects and three produced hemolysis. Data also demonstrated the pharmacological significance of bioactive extracts from Brazilian semi-arid region. There was no significant relationship between antioxidant, toxic, and antiproliferative activities, and that these properties were dependent upon the extractant. DC-Mca contained betulinic acid as main compound (approximately 70%), which showed higher (1) cytotoxic activity on cancer cell lines and dividing leukocytes, (2) reduced mitotic index of Allium cepa roots, and (3) induced cell cycle arrest and chromosomal bridges, thereby providing native promising sources for phytotherapy development. ABBREVIATIONS: ABTS: 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid); AcOH: ethyl acetate; ANOVA: analysis of variance; SUS: Brazilian Unified Health System; DC-Mca: dichloromethane fraction from Mimosa caesalpiniifolia stem bark; DMSO: dimethylsulfoxide; DPPH: 1,1-diphenyl-2-picrylhydrazyl; EC50: effective concentration 50%; EtOAc: ethyl acetate; FDA: Food and Drug Administration; GC-Qms: gas chromatograph quadrupole mass spectrometer; GI: genotoxic index; HCT-116: colon carcinoma line; HL-60: promyelocytic leukemia line; HPLC: high-performance liquid chromatography; HRAPCIMS: high resolution atmospheric pressure chemical ionization mass spectrum; IC50: inhibitory concentration 50%; LC50: lethal concentration 50%; MeOH = methyl alcohol; MI: mitotic index; MTT: 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide; MutI: mutagenic index; OVCAR-8 = ovarian carcinoma line; PBMC: peripheral blood mononuclear cells; RPMI-1640: Roswell Park Memorial Institute medium; SF-295: glioblastoma line; TEAC: trolox equivalent antioxidant capacity; TLC: thin-layer chromatography; Trolox: 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid.

An evaluation of the genotoxicity and subchronic toxicity of the peel extract of Ponkan cultivar 'Ohta ponkan' (Citrus reticulata Blanco) that is rich in nobiletin and tangeretin with anti-dementia activity.

Nobiletin and tangeretin are major components of polymethoxylated flavones in the peels of citrus fruits such as Citrus reticulata. Because nobiletin and tangeretin have attracted attention due to their beneficial health properties, citrus peel extracts, in which they are concentrated, have the potential to serve as a functional food ingredient to prevent diseases. In this study, a series of toxicological studies on the peel extract of Ponkan cultivar 'Ohta ponkan' (Citrus reticulata Blanco), was conducted. No mutagenic activity was observed in a bacterial reverse mutation test, whereas chromosomal aberrations were induced in an in vitro mammalian chromosomal aberration test. No genotoxicity was observed in an in vivo mammalian micronucleus test. In a 90-day study at daily doses of 54, 180, or 540 mg/kg body weight (bw)/day, hyaline droplet nephropathy, which specifically occurs in adult male rats, was observed in males of 540 mg/kg bw/day group. No other adverse effects were observed in the 90-day study. The no adverse effect level in the 90-day study was considered to be 540 mg/kg bw/day for female rats and less than 540 mg/kg bw/day for male rats.

Assessment of the 4-week repeated-dose oral toxicity and genotoxicity of GHX02.

Herbal medicines are widely utilized for disease prevention and health promotion. GHX02 consists of mixtures including Gwaruin (Trichosanthes kirilowii), Haengin (Prunus armeniaca), Hwangryeon (Coptis japonica) and Hwangkeum (Scutellaria baicalensis). It has been purported to have therapeutic effectiveness in cases of severe bronchitis. Non-clinical safety testing comprised a single-dose oral toxicity study and a 28-day repeated-dose oral toxicity study with a 14-day recovery period, and genotoxicity was assessed by a bacterial reverse mutation test, in vitro chromosomal aberration test, in vivo mouse bone marrow micronucleus test and single cell gel electrophoresis assay (comet assay). In the single-dose oral toxicity study, the approximate lethal dosage is estimated to be higher than 5000 mg/kg in rats. Thus, the dosage levels were set at 0, 1250, 2500 and 5000 mg/kg/day in the 28-day repeated-dose oral toxicity study, and 10 male rats and 10 female rats/dose were administered GHX02. No clinical signs of toxicological significance were recorded in any animal during the dosing and the observation period in the single-dose study. The no-observed-adverse-effect level of GHX02 was 5000 mg/kg/day when administered orally for 28 days to male and female Sprague-Dawley rats. Despite increases in the frequencies of cells with numerical chromosomal aberration in the in vitro test, the increases were not considered relevant to the in vivo genetic risk. Except for the increase of in vitro numerical chromosomal aberration, clear negative results were obtained from other genetic toxicity studies.

Toxicological safety evaluation of a novel highly bioavailable turmeric extract formulation.

Turmeric (Curcuma longa L.) extracts have a long history of use worldwide, but a major limitation of these extracts is their extremely low oral bioavailability, caused by low absorption, rapid metabolism and rapid excretion following ingestion. Thus, a new highly bioavailable turmeric extract formulation (comprising turmeric extract, acacia gum, sunflower oil and quillaia extract) has been developed and is intended for use as a food ingredient. Safety of this novel extract was evaluated using the standard Tier 1 battery of in vitro genotoxicity tests (bacterial reverse mutation test and an in vitro mammalian cell micronucleus test) followed by repeated-dose 28- and 90-day oral toxicity studies in rats. In the 90-day study, male and female Sprague-Dawley rats were dosed once daily, by oral gavage, either with the vehicle or the test item at 500, 1500 or 3000 mg/kg body weight/day. Clinical examinations were conducted regularly, and body weights and food consumption were recorded weekly throughout the study. At the end of the study, blood samples were analyzed for clinical pathology parameters, before a macroscopic necropsy was conducted and a full list of tissues were examined histopathologically. There was no evidence of genotoxicity in vitro. No test item-related adverse effects were observed in the 28- or 90-day studies; therefore, 3000 mg/kg body weight/day (the maximum feasible dose and highest dose tested in rats) was established as the no-observed-adverse-effect level.

Andiroba oil (Carapa guianensis Aubl) shows cytotoxicity but no mutagenicity in the ACPP02 gastric cancer cell line.

Andiroba (Carapa guianensis Aubl) is an Amazonian plant whose oil has been widely used in traditional medicine for various purposes, including anti-inflammation. Research reports indicate that the oil can confer antitumor activity due to the presence of fatty acids, which can directly influence cell death mechanisms. Thus, andiroba oil (AO) has gained interest for its potential to be used in antineoplastic therapies. Here, we report an in vitro analysis of the cytotoxic and mutagenic potential of AO in the gastric cancer cell line, ACP02. Cell survival was assessed by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, differential staining with ethidium bromide and acridine orange assessed apoptosis-necrosis, and mutagenesis was assessed by the micronucleus test. The apolar oil was first diluted in 0.1% dimethyl sulfoxide (DMSO) and then further diluted to six concentrations (0.01, 0.1, 1, 10 and 100 µg/mL and 1 mg/mL) in RPMI medium. Controls included RPMI alone (negative control) and 0.1% DMSO diluted in medium (vehicle control). The MTT test showed that AO significantly reduced cell viability (P < .05) only when the highest tested concentration was applied for 48 hours. The apoptosis/necrosis test showed that the highest concentration of AO induced cell death by apoptosis at 24 and 48 hours. There was no statistically significant increase in the frequency of micronuclei. The ability of the AO to decrease the viability of ACP02 cells via apoptosis, without exerting mutagenic effects, suggests that the oil could be useful as an alternative therapeutic agent for primary tumors of stomach cancer.

Potential Hepatotoxins Found in Herbal Medicinal Products: A Systematic Review.

The risk of liver injury associated with the use of herbal medicinal products (HMPs) is well known among physicians caring for patients under a HMP therapy, as documented in case reports or case series and evidenced by using the Roussel Uclaf Causality Assessment Method (RUCAM) to verify a causal relationship. In many cases, however, the quality of HMPs has rarely been considered regarding potential culprits such as contaminants and toxins possibly incriminated as causes for the liver injury. This review aims to comprehensively assemble details of tentative hepatotoxic contaminants and toxins found in HMPs. Based on the origin, harmful agents may be divided according two main sources, namely the phyto-hepatotoxin and the nonphyto-hepatotoxin groups. More specifically, phyto-hepatotoxins are phytochemicals or their metabolites naturally produced by plants or internally in response to plant stress conditions. In contrast, nonphyto-hepatotoxic elements may include contaminants or adulterants occurring during collection, processing and production, are the result of accumulation of toxic heavy metals by the plant itself due to soil pollutions, or represent mycotoxins, herbicidal and pesticidal residues. The phyto-hepatotoxins detected in HMPs are classified into eight major groups consisting of volatile compounds, phytotoxic proteins, glycosides, terpenoid lactones, terpenoids, alkaloids, anthraquinones, and phenolic acids. Nonphyto-hepatotoxins including metals, mycotoxins, and pesticidal and herbicidal residues and tentative mechanisms of toxicity are discussed. In conclusion, although a variety of potential toxic substances may enter the human body through HMP use, the ability of these toxins to trigger human liver injury remains largely unclear.

Evaluation of cytotoxic potential, oral toxicity, genotoxicity, and mutagenicity of organic extracts of Pityrocarpa moniliformis.

The objective of this study was to determine the cytotoxicity of organic extracts of P. moniliformis in vitro and identify the acute toxicity and genotoxicity in vivo. The leaves were extracted using three organic solvents (cyclohexane [EP1], ethyl acetate [EP2], and methanol [EP3]). Phytochemical qualitative analysis was performed by thin layer chromatography (TLC). Cytotoxicity tests were performed on human embryonic kidney (HEK) cells and J774 murine macrophages. Acute toxicity in mice was measured after intraperitoneal (ip) administration of 2000 mg/kg, while evaluation of genotoxicity and mutagenicity were assessed using the comet assay and the micronucleus (MN) test, respectively. The TLC analysis of the extracts revealed the presence of flavonoids, triterpenes, steroids, and saponins. In the cytotoxicity assay, extracts EP1 and EP3 altered proliferation of HEK cells, and all organic extracts increased the viability of J774 cells. In the toxicity tests, no deaths or behavioral alterations were observed in mice exposed to the acute dose of the extracts. Although some extracts led to changes in hematological and histological parameters, these results did not indicate physiological changes. In relation to the MN test and comet assay, no significant changes were detected in the DNA of the animals tested with the extracts EP1, EP2, and EP3. Thus, extracts of P. moniliformis were not considered to be toxic and did not induce formation of MN or damage to cellular DNA in the genotoxicity tests.

Cell line cytotoxicity, antiadipogenic and glucose uptake activity of Sarcostemma brevistigma Wight. & Arn.

Nature has gifted us with abundant plants possessing medicinal virtues which can cure several illnesses. Currently, diabetes mellitus is a severe threat to human well-being across the world due to the rapidly increasing incidence of diabetes. New effective bioactive drugs are in need, as plants do harbour and are proven to have potential antidiabetic activity than the present hypoglycemic medicines used in clinical therapy. In this study, in vitro cytotoxicity, glucose uptake, and anti-adipogenic activities of the plant extract (methanolic extract) of S. brevistigma were examined using 3T3L1 cell lines. The studies interpreted by MTT cytotoxicity assay and glucose uptake assay by using 3T3-L1 cell lines, it was found that a very low dosage (1 ng/mL) of plant extract showed lesser cytotoxicity effect (1.42%) and considerably higher glucose uptake activity of 38.04% which is equivalent to the glucose uptake shown by 100 nm insulin (40.10%). Though plant extract has antidiabetic activity, it is important to study whether it has any other related side effects when used at higher concentrations. Therefore, in this study, the appropriate non-toxic concentration was optimized.

Comparative cardio and developmental toxicity induced by the popular medicinal extract of Sutherlandia frutescens (L.) R.Br. detected using a zebrafish Tuebingen embryo model.

BACKGROUND: Sutherlandia frutescens is one of the most promising commercialized, indigenous and medicinal plants of South Africa that is used as an immune-booster, and a traditional treatment for cancer. However, few studies report on its toxicology and dosage in vivo. There is still room to better understand its cytotoxicity effects in animal systems. METHODS: We prepared two extracts, one with 80% (v/v) ethanol, and the other, with water. Both were studied to determine the maximum tolerable concentration when extracts were applied at 0 to 200 µg/ml to a Tuebingen zebrafish embryo line. The development of zebrafish embryos after 24 h post fertilization (hpf) was studied. A concentration range of 5 µg/ml to 50 µg/ml was then chosen to monitor the ontological development of cultured embryos. A liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method was used to study the differences of the two experimental extracts. Chemical variation between the extracts was illustrated using chemometrics. RESULTS: Both extracts led to bleeding and pericardial cyst formation when applied at high concentrations to the zebrafish embryo culture. Chronic teratogenic toxicities, leading to pericardial edema, yolk sac swelling, and other abnormal developmental characteristics, were detected. The aqueous extracts of S. frutescens were less toxic to the larvae than the ethanol extracts, validating preference for aqueous preparations when used in traditional medicine. Chemical differences between the water extracts and alcoholic extracts were analysed using LC-MS/MS. A supervised metabolomics approach, targeting the sutherlandiosides and sutherlandins using orthogonal partial least squares-discriminant analysis (OPLS-DA), illustrated that sutherlandiosides were the main chemical features that can be used to distinguish between the two extracts, despite the extracts being highly similar in their chemical constituents. CONCLUSION: The water extract caused less cytotoxic and abnormal developmental effects compared to the ethanolic extract, and, this is likely due to differences in concentrations of extracted chemicals rather than the chemical profile per se. This study provides more evidence of cytotoxicity effects linked to S. frutescens using the zebrafish embryo bioassay as a study tool.

[Chronic hepatotoxicity evaluation of Chinese medicinal herb Zishen Yutai pill prepared from Polygoni Multiflori Radix preparata in dogs].

To study the chronic hepatotoxicity of Chinese medicine Zishen Yutai pill (ZYP) prepared from Polygonum multiflorum with the recommended dosage in normal Beagle dogs. Low, middle and high doses of ZYP (1.5, 3.0, 6.0 g·kg⁻¹; i.e. 3×, 6× and 12× equivalent doses) were given orally to dogs for 39 consecutive weeks. At the same time, the same volume of deionized water was used as the solvent control group, one time a day. The general condition of the animals was observed every day during the period of administration, and the blood was collected before and 13, 26, 39, 43 weeks after administration to detect the biomarkers related to the hepatotoxicity of the dog serum. 2/7, 3/7 and 2/7 animals were dissected after 13, 39, and 43 weeks of administration to observe the pathological changes of the animal organs, weigh the mass of main organs and conduct pathological examination of the liver. As compared to the solvent control group, 11 liver hepatotoxicity traditional biomarkers such as ALT, AST were found no ZYP-related changes at month 3, 6, 9 of the administration and month 1 in recovery period; There was no significant difference in liver viscera index and liver pathology. Therefore, no obvious hepatotoxicity was shown by ZYP administered up to 6.0 g·kg⁻¹ for 9 months in normal dogs at doses of 1.5, 3.0, and 6.0 g·kg⁻¹.

Mycotoxins in spices and herbs-An update.

Spices and herbs have been used since ancient times as flavor and aroma enhancers, colorants, preservatives, and traditional medicines. There are more than 30 spices and herbs of global economic and culinary importance. Among the spices, black pepper, capsicums, cumin, cinnamon, nutmeg, ginger, turmeric, saffron, coriander, cloves, dill, mint, thyme, sesame seed, mustard seed, and curry powder are the most popular spices worldwide. In addition to their culinary uses, a number of functional properties of aromatic herbs and spices are also well described in the scientific literature. However, spices and herbs cultivated mainly in tropic and subtropic areas can be exposed to contamination with toxigenic fungi and subsequently mycotoxins. This review provides an overview on the mycotoxin risk in widely consumed spices and aromatic herbs.

Toxicological Effects of Glycyrrhiza glabra (Licorice): A Review.

Licorice (Glycyrrhiza glabra) has been considered as an herbal drug since ancient time. Nowadays, it is a well-known spice that possesses worth pharmacological effects. However, some relevant articles have revealed negative impacts of licorice in health. By considering the great wishes in using herbal medicine, it is important to show adverse effects of herbal medicine in health. At present, there are misunderstandings toward the safety of herbal medicines. Herein, we gathered scientific research projects on the toxicity effects of licorice and glycyrrhizin to highlight their safety. In this regards, we categorized our findings about the toxicity effects of licorice and glycyrrhizin in acute, sub-acute, sub-chronic, and chronic states. Besides, we discussed on the cytotoxicity, genotoxicity, mutagenicity, and carcinogenicity of licorice and glycyrrhizin as well as their developmental toxicity. This review disclosed that G. glabra and glycyrrhizin salts are moderately toxic. They need to be used with caution during pregnancy. G. glabra and glycyrrhizin possess selective cytotoxic effects on cancerous cells. The most important side effects of licorice and glycyrrhizin are hypertension and hypokalemic-induced secondary disorders. Licorice side effects are increased by hypokalemia, prolonged gastrointestinal transient time, decreased type 2 11-beta-hydroxysteroid dehydrogenase activities, hypertension, anorexia nervosa, old age, and female sex. Copyright © 2017 John Wiley & Sons, Ltd.