Research progress on the toxicity of toxic Traditional Herbals from Thymelaeaceae.

ETHNOPHARMACOLOGICAL RELEVANCE: Plants from the Thymelaeaceae family are widely distributed in tropical and temperate regions, with approximately 113 species used as Traditional Herbals. There are numerous applications for them, such as treating leukemia, AIDS, and liver cancer. It should be noted that around 20% of these plants have shown harmful side effects when used in clinical applications, including solid irritations to the skin and mucous membranes, carcinogenic effects, organ damage, vomiting, and diarrhea. AIM OF THE STUDY: This paper aims to review the toxic side effects, toxic compounds, toxic mechanisms, and detoxification methods of Traditional Herbals in Thymelaeaceae, guiding their safe clinical uses. MATERIALS AND METHODS: This review employed the keywords "Thymelaeaceae," 48 different "genus," 966 "species," and the combination of "toxicity" to identify the medicinal value and toxicity of plants from Thymelaeaceae in scientific databases (Pubmed, SciFinder Scholar, Elsevier, Web of Science, and CNKI). Information relevant to the toxicity of Traditional Herbals from Thymelaeaceae up to June 2023 has been summarized. The plant names have been checked with "World Flora Online" (www.worldfloraonline.org). RESULTS: 28 toxic Traditional Herbals from 13 genera within the Thymelaeaceae family were categorized. Toxicities were summarized at the cellular, animal, and clinical levels. The toxic substances are primarily concentrated in the Daphne L. and Wikstroemia Endl. genera, with terpenes being the main toxic components. The toxicity mechanism is primarily associated with the mitochondrial pathways. Detoxification and enhanced efficacy can be achieved through processing methods such as vinegar-processing and sweat-soaking. CONCLUSIONS: Medicinal plants in the Thymelaeaceae exhibit significant pharmacological activities, such as anti-HIV and anti-tumor effects, indicating a broad potential for application. However, their clinical uses are hindered by their inherent toxicity. Researching the toxic components and mechanisms of these Traditional Herbals and exploring more effective detoxification methods can contribute to unveiling the latent value of these medicinal plants from Thymelaeaceae.

Cultivo e uso racional de plantas medicinais e fitoterápicos / Cultivation and rational use of medicinal and herbal plants / Cultivo y uso racional de plantas medicinales y herbáceas

A utilização de plantas medicinais como alternativa terapêutica vem atingindo um público cada vez maior. Assim, os fitoterápicos podem atuar como forma opcional de terapêutica levando em consideração o menor custo, e cujos benefícios se somam aos da terapia convencional. Com isso, o objetivo deste trabalho foi enfatizar a importância do cultivo e do uso racional de medicamentos fitoterápicos e plantas medicinais. Para tanto, foram incluídos artigos em português e inglês inseridos no banco de dados: Scielo, Google acadêmico, além de revistas eletrônicas, livros com embasamento científico de referência e base de dados do Ministério da Saúde entre os anos de 2018 a 2022. As plantas medicinais e os medicamentos fitoterápicos podem provocar efeitos adversos, interferir no efeito de medicamentos utilizados concomitantemente, além da possibilidade de causar intoxicações pela presença de contaminantes em produtos de baixa qualidade. Para a produção de bioativos, em níveis quali e quantitativamente adequados, o cultivo das plantas medicinais deve ser cuidadosamente realizado, através de técnicas adequadas para preservação do solo e plantio são essenciais, como a utilização de adubos verdes e a cobertura vegetal, que além de protegerem o solo da radiação solar, prevenir a evaporação excessiva da água e melhorar as características físicas, químicas e biológicas do sol. Esses critérios influenciam a qualidade do fitoterápico, portanto a fim de garantir a eficácia terapêutica, as plantas devem ser corretamente cultivadas, coletadas, identificadas e conservadas. Sendo assim, conclui-se que a utilização de plantas medicinais para tratamentos tem sido cada vez mais indicada pelos profissionais da saúde, ressaltando a importância do uso seguro e racional, com alerta para as suas consequências.

The use of medicinal plants as a therapeutic alternative has been reaching a growing public. Thus, herbal medicines can act as an optional form of therapy taking into account the lowest cost, and whose benefits are added to those of conventional therapy. Thus, the objective of this work was to emphasize the importance of the cultivation and rational use of herbal medicines and medicinal plants. To this end, articles in Portuguese and English inserted in the database: Scielo, Google academic, in addition to electronic journals, books with scientific reference base and database of the Ministry of Health between the years 2018 to 2022 were included. herbal medicines can cause adverse effects, interfere with the effect of medicines used concomitantly, in addition to the possibility of causing poisoning due to the presence of contaminants in low-quality products. For the production of bioactives, at qualitatively and quantitatively appropriate levels, the cultivation of medicinal plants must be carefully carried out, through techniques cultivated for soil preservation and planting are essential, such as the use of green manures and vegetation cover, which in addition to protect the soil from solar radiation, prevent excessive water evaporation and improve the physical, chemical and biological characteristics of the sun. These criteria influence the quality of the herbal medicine, therefore, in order to guarantee therapeutic efficacy, as the plants must be correctly cultivated, collected, identified and conserved. Therefore, it is concluded that the use of medicinal plants for treatments has been increasingly indicated by health professionals, emphasizing the importance of safe and rational use, with an alert to its consequences.

El uso de plantas medicinales como alternativa terapéutica ha ido alcanzando un público cada vez más amplio. Así, las plantas medicinales pueden actuar como una forma opcional de terapia teniendo en cuenta el menor coste, y cuyos beneficios se suman a los de la terapia convencional. Así, el objetivo de este trabajo fue destacar la importancia del cultivo y uso racional de las hierbas medicinales y plantas medicinales. Para ello, los artículos en portugués e Inglés insertados en la base de datos: Scielo, Google académico, además de revistas electrónicas, libros con base de referencia científica y base de datos del Ministerio de Salud entre los años 2018 a 2022 fueron incluidos. medicamentos a base de hierbas pueden causar efectos adversos, interferir con el efecto de los medicamentos utilizados concomitantemente, además de la posibilidad de causar intoxicación debido a la presencia de contaminantes en productos de baja calidad. Para la producción de bioactivos, en niveles cualitativa y cuantitativamente adecuados, el cultivo de plantas medicinales debe ser realizado cuidadosamente, siendo esenciales técnicas de preservación del suelo y de plantación, como el uso de abonos verdes y cobertura vegetal, que además de proteger el suelo de la radiación solar, evitan la evaporación excesiva del agua y mejoran las características físicas, químicas y biológicas del sol. Estos criterios influyen en la calidad de la fitoterapia, por lo que, para garantizar la eficacia terapéutica, las plantas deben cultivarse, recolectarse, identificarse y conservarse correctamente. Por lo tanto, se concluye que el uso de plantas medicinales para tratamientos ha sido cada vez más indicado por los profesionales de la salud, enfatizando la importancia del uso seguro y racional, con alerta a sus consecuencias.

The protein adduction derived from reactive metabolites of multiple furanoids in cortex Dictamni-treated mice.

The association of herb medicine Cortex Dictamni (CD) with severe even fatal hepatotoxicity has been widely reported. Recently, we demonstrated that the metabolic activation of at least ten furanoids in CD was responsible for the liver injury caused by the ethanol extract of CD (ECD) in mice. Protein adduction by reactive metabolites is considered to initiate the process of liver injury. Unlike single chemicals, the mode of and the details of protein modification by multiple components in an herb is unclear. This study aimed to characterize protein adductions derived from the reactive metabolite of furanoids in ECD-treated mice and define the association of protein adduction with liver injury. The hepatic cysteine- and lysine-based protein adducts derived from epoxide or cis-enedione of at least six furanoids were identified in mice. The furanoids with an earlier serum content Tmax were mainly to bind with hepatic glutathione and no protein adducts were formed except for dictamnine. The hepatic proteins were modified by the later absorbed furanoids. The levels of hepatic protein adduct were correlated with the degree of liver injury. In addition, the reactive metabolites of different furanoids can simultaneously bind to the model peptide by the identical reactive moiety, indicating the additive effects of the individual furanoids in the modification of hepatic proteins. In conclusion, hepatic protein adduction by multiple furanoids may play a role in ECD-induced liver injury. The earlier absorbed furanoids were mainly to bind with glutathione whereas the hepatic proteins were modified by the later furanoids.

Investigation into the biological properties, secondary metabolites composition, and toxicity of aerial and root parts of Capparis spinosa L.: An important medicinal food plant.

Capparis spinose L. also known as Caper is of great significance as a traditional medicinal food plant. The present work was targeted on the determination of chemical composition, pharmacological properties, and in-vitro toxicity of methanol and dichloromethane (DCM) extracts of different parts of C. spinosa. Chemical composition was established by determining total bioactive contents and via UHPLC-MS secondary metabolites profiling. For determination of biological activities, antioxidant capacity was determined through DPPH, ABTS, CUPRAC, FRAP, phosphomolybdenum, and metal chelating assays while enzyme inhibition against cholinesterase, tyrosinase, α-amylase and α-glucosidase were also tested. All the extracts were also tested for toxicity against two breast cell lines. The methanolic extracts were found to contain highest total phenolic and flavonoids which is correlated with their significant radical scavenging, cholinesterase, tyrosinase and glucosidase inhibition potential. Whereas DCM extracts showed significant activity for reducing power, phosphomolybdenum, metal chelation, tyrosinase, and α-amylase inhibition activities. The secondary metabolites profiling of both methanolic extracts exposed the presence of 21 different secondary metabolites belonging to glucosinolate, alkaloid, flavonoid, phenol, triterpene, and alkaloid derivatives. The present results tend to validate folklore uses of C. spinose and indicate this plant to be used as a potent source of designing novel bioactive compounds.

Phytochemical properties, biological activities and medicinal use of Centaurium erythraea Rafn.

ETHNOPHARMACOLOGICAL RELEVANCE: Centaurium erythraea is an important medicinal plant in many countries, e.g. Morocco, Algeria, Italy, Spain, Portugal, and countries of Balkan Peninsula. It is used in folk medicine to treat various illnesses. It is also used as an antiapoplectic, anticoagulant, anticholagogue, antipneumonic, hematocathartic, and as a hypotensive agent. AIM OF THE REVIEW: In this review, previous reports on the taxonomy, botanical description, geographic distribution, ethnomedicinal applications, phytochemistry, pharmacological properties, and toxicity of Centaurium erythraea were critically summarized. MATERIALS AND METHODS: Scientific search engines including PubMed, ScienceDirect, SpringerLink, Web of Science, Scopus, Wiley Online, SciFinder, and Google Scholar were consulted to collect data on C. erythraea. The data presented in this work summarized the main reports on C. erythraea phytochemical compounds, ethnomedicinal uses, and pharmacological activities. RESULTS: C. erythraea is used in traditional medicine to treat various diseases such as diabetes, fever, rhinitis, stomach ailments, urinary tract infections, dyspeptic complaints, loss of appetite, and hemorrhoids, and as diuretic. The essential oils and extracts of C. erythraea exhibited numerous biological properties such as antibacterial, antioxidant, antifungal, antileishmanial, anticancer, antidiabetic, anti-inflammatory, insecticidal, diuretic, gastroprotective, hepatoprotective, dermatoprotective, neuroprotective, and inhibitory agent for larval development. Phytochemical characterization of C. erythraea revealed the presence of several classes of secondary metabolites such as xanthonoids, terpenoids, flavonoids, phenolic acids, and fatty acids. CONCLUSIONS: Ethnomedicinal studies demonstrated the use of C. erythraea for the treatment of various disorders. Pharmacological reports showed that C. erythraea especially its aerial parts and roots exhibited potent, and beneficial activities. These findings confirmed the link between the traditional medicinal use and the results of the scientific biological experiments. Considering these results, further investigation using diverse in vivo pharmacological assays are strongly recommended to validate the results of its traditional use. Toxicological tests and pharmacokinetic studies are also required to validate the safety and efficacy of C. erythraea and its bioactive contents.

A comprehensive review on phytochemistry, bioactivities, toxicity studies, and clinical studies on Ficus carica Linn. leaves.

The leaves of Ficus carica Linn. (FC) have been widely used for medicine purposes since ancient times, and its decoction is consumed as tea. Many scientific papers have been published in the literature and the researchers across the world are still exploring the health benefits of FC leaves. In this review, we have collected the literature published since 2010 in the databases: Pubmed, Scopus, Web of Science, SciFinder, Google Scholar, Baidu Scholar and local classic herbal literature. The summary of the chemical constituents in FC leaves, biological activities, toxicity studies, and clinical studies carried out on FC leaves is provided in this review. In addition, the molecular mechanisms of the active constituents in FC leaves are also comprehended. FC leaves are reported to 126 constituents out of which the polyphenolic compounds are predominant. Many scientific studies have proven the antidiabetic, antioxidant, anti-inflammatory, anticancer, anticholinesterase, antimicrobial, hepatoprotective, and renoprotective activities. Many studies have carried out to provide the insights on molecular pathways involved in the biological activities of FC leaves. The toxicity studies have suggested that FC leaves exhibit toxicity only at very high doses. We believe this review serve as a comprehensive resource for those who are interested to understand the scientific evidence that support the medicinal values of FC leaves and also the research gaps to further improve the commercial value and health benefits of FC leaves.

Evaluation of ethnopharmacologically selected Vitex negundo L. for In vitro antimalarial activity and secondary metabolite profiling.

ETHANOPHARMACOLOGICAL RELEVANCE: Limited drugs, rise in drug resistance against frontline anti-malarial drugs, non-availability of efficacious vaccines and high cost of drug development hinders malaria intervention programs. Search for safe, effective and affordable plant based anti-malarial agents, thus becomes crucial and vital in the current scenario. The Vitex negundo L. is medicinal plant possessing a variety of pharmaceutically important compounds. The plant is used traditionally worldwide for the treatment of malaria including India and Malaysia by the indigenous tribes. In vitro studies have reported the anti-malarial use of the plant in traditional medicinal systems. AIM OF THE STUDY: The aim of the current study is to evaluate the traditionally used medicinal plants for in vitro anti-malarial activity against human malaria parasite Plasmodium falciparum and profiling secondary metabolite using spectroscopic and chromatographic methods. Chemical profiling of active secondary metabolites in the extracts was undertaken using LC-MS. MATERIALS AND METHODS: Based on the ethno-botanical data V. negundo L. was selected for in vitro anti-malarial activity against P. falciparum chloroquine-sensitive (3D7) and multidrug resistant (K1) strains using SYBR Green-I based fluorescence assay. Cytotoxicity of extracts was evaluated in VERO cell line using the MTT assay. Haemolysis assay was performed using human red blood cells. Secondary metabolites profiling was undertaken using chromatographic and spectroscopic analysis. Liquid chromatography analysis was performed using a C18, 150 X 2.1, 2.6 µm column with gradient mobile phase Solvent A: 95% (H2O: ACN), Solvent B: Acetonitrile, Solvent C: Methanol, Solvent D: 5 mM NH4 in 95:5 (H2O: ACN) at a constant flow rate of 0.250 ml/min. The LC-MS spectra were acquired in both positive and negative ion modes with electrospray ionization (ESI) source. RESULTS: The anti-malarial active extract of V. negundo L. leaf exhibited potent anti-malarial activity with IC50 values of 7.21 µg/ml and 7.43 µg/ml against 3D7 and K1 strains, respectively with no evidence of significant cytotoxicity against mammalian cell line (VERO) and no toxicity as observed in haemolysis assay. The HPLC-LC-MS analysis of the extract led to identification of 73 compounds. We report for the first time the presence of Sabinene hydrate acetate, 5-Hydroxyoxindole, 2(3,4-dimethoxyphenyl)-6, 7-dimethoxychromen-4-one, Cyclotetracosa-1, 13-diene and 5, 7-Dimethoxyflavanone in the anti-malarial active extract of V. negundo L. leaf. Agnuside, Behenic acid and Globulol are some of the novel compounds with no reports of anti-malarial activity so far and require further evaluation in pure form for the development of potent anti-malarial compounds. CONCLUSIONS: The result report and scientifically validate the traditional use of V. negundo L. for the treatment of malaria providing new avenues for anti-malarial drug development. Several novel and unknown compounds were identified that need to be further characterized for anti-malarial potential.

A review on traditional usages, chemical constituents and pharmacological activities of periploca forrestii schltr.

ETHNOPHARMACOLOGICAL RELEVANCE: Periploca forrestii Schltr. was listed as a classical medicinal plant in "Miao medicine", which is a branch of traditional Chinese medicine (TCM). According to the theory of TCM, P. forrestii has the efficacy of relaxing tendons and activating collaterals, and dispelling wind and eliminating dampness. Hence, it was often used for the therapy of rheumatoid arthritis and traumatic injury in clinical practice. AIMS OF THE REVIEW: This review aims to present comprehensive information for the research progress of P. forrestii. The researches on botany, traditional uses, phytochemistry, pharmacology and toxicology of the plant are summarized. We mainly focus on the phytochemical and pharmacological investigations. As a representative class of phytochemicals in P. forrestii, more attention is paid to cardiac glycosides. The insights into potential action of mechanisms and possible future studies on P. forrestii are also discussed. MATERIALS AND METHODS: Relevant literature was acquired from scientific databases including Google Scholar, Web of Science, Scifinder, Baidu Scholar, PubMed and Chinese national knowledge infrastructure. Monographs and Chinese pharmacopoeia were also utilized as references. RESULTS: To date, all kinds of phytochemical constituents have been isolated and identified from this plant including cardiac glycosides, steroids, terpenoids, flavonoids, phenylpropanoids, quinones, organic phenolic acids and others. Among these, cardiac glycosides were considered as the major ingredients and bioactive materials. Modern pharmacological studies demonstrated that the plant possessed extensive bioactivity, such as anti-inflammatory and analgesic effects, immunosuppressive action, wound healing activity, antioxidant, anti-tumor and, cardiotonic properties. CONCLUSIONS: As an important medicinal plant, lots of studies have proved that P. forrestii has significant therapeutical effects, especially on rheumatoid arthritis and traumatic injury. These results provide modern scientific evidence for traditional use and contribute to the development of novel remedies for chronic diseases. However, the exact mechanism of action remains to be elucidated. Furthermore, the long-term in vivo toxicity and clinical efficacy also require in-depth exploration in the future.

Cissampelos pareira L.: A review of its traditional uses, phytochemistry, and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Cissampelos pareira, a well-known medicinal climber-plant of the Menispermaceae family, has been extensively used in the traditional medicinal system since the ancient time for the treatment of numerous diseases such as ulcer, wound, rheumatism, fever, asthma, cholera, diarrhoea, inflammation, snakebite, malaria, rabies, and also recommended for blood purification. AIM OF THE REVIEW: The main purpose of this review is to provide updated information on ethnopharmacology, phytochemistry, chromatographic and spectroscopic analysis, pharmacology, and toxicology of C. pareira along with the possible future research. This information will help to provide a foundation for plant-based drug discovery in the near future. MATERIAL AND METHODS: The online databases such as Scifinder, Web of Science, PubMed, and Google Scholar were used to collect electronically available literature data on C. pareira. Ayurveda text is searched for the traditional uses of this plant in India. The published books are also searched for the information on this plant. Our search was based on traditional uses, botany, phytochemistry, and pharmacological potential by using "Cissampelos pareira" as the keyword. RESULTS: To date, approximately 54 phytomolecules have been isolated and characterized from C. pareira including mainly isoquinoline alkaloids along with few flavonoids, flavonoid glycosides, and fatty acids. The crude extracts of C. pareira have shown various pharmacological activities such as antipyretic, anti-inflammatory, antiarthritic, antiulcer, antidiabetic, anticancer, antifertility, antimicrobial, antioxidant, antivenom, antimalarial, and immunomodulatory, etc. The chemical fingerprinting of C. pareira carried out using HPTLC, HPLC, UPLC, LC-MS, and GC-MS, revealed the presence of alkaloids (isoquinoline alkaloids), fatty acids, and flavonoid glycosides. Moreover, the toxicological assessment of C. pareira has been moderately investigated, which requires further comprehensive studies. CONCLUSION: Comprehensive literature survey reveals that till date, remarkable growth has been made on phytochemistry and pharmacology of C. pareira reflecting the great medicinal potential of this plant. Although some of the traditional uses have been well clarified and documented by modern pharmacological analysis, the correlation between its pharmacological activities and particular phytoconstituents still needs to be validated. Furthermore, there is partial data available on most of the pharmacological studies, along with incomplete toxicological screening. Future research needs to pay more attention to pharmacological studies of C. pareira via pre-clinical and clinical trials. Additionally, scientific validation of traditional knowledge of C. pareira is vital for ensuring safety, efficacy, and mechanism of action before clinical uses.

In vivo and in vitro prospection of the anti-ophidic properties exercised by the extracts of Jacaranda decurrens L

The research and development of alternative treatments for snakebites (e.g., medicinal plants) is necessary due to the high costs of the existing ones. The effects of the aqueous extracts from Jacaranda decurrens leaves, roots, and xylopodium were analyzed upon the venom-induced (Bothrops spp. and Crotalus spp.) systemic and local toxicity. The extracts were able to partially inhibit the phospholipase activity of the venoms from Bothrops jararacussu and Crotalus durissus terrificus. The myotoxic, edema-inducing, coagulant, and hemorrhagic activities were also inhibited. The SDS-PAGE showed that the venom proteins were intact after their incubation with the extracts. This suggests that the possible mechanism of inhibition is not related to the degradation of the protein but rather to their binding to specific sites of the enzymes. The extracts significantly prolonged the survival time of animals in the lethality assay performed with Crotalus durissus terrificus venom and its toxin (crotoxin). The anti-ophidic activity of medicinal plants may aid in the management of snakebites in distant locations by reducing the victim’s local effects and time to heal.

Evaluation of Acute Toxicity and Semi-chronic Toxicity of Extract from Celastrus hindsii Benth.

BACKGROUND AND OBJECTIVE: Celastrus hindsii Benth. has been used for generations in Northern Vietnam, for the treatment of disease relating to ulcers, tumors and inflammation without safety evidence. This study's goal is to evaluate the safety of the aqueous extract of leaves of C. hindsii through an acute and semi-chronic toxicity oral administration. MATERIALS AND METHODS: In the acute study, a single oral dose (1000, 3000, 5000 and 15000 mg kg-1) of the aqueous of C. hindsii extract were administered to mice and observed for seven days. In the semi-chronic study, rabbits were administered daily with 1000 and 3000 mg kg-1 of the extract for 35 days. Hematological and biochemical analyzes were carried out on blood and serum samples collected. RESULTS: A single oral administration of 15000 mg kg-1 per day for white mice did not determine the LD50 dose. At doses of 1000 and 3000 mg kg-1 for 35 days, the extract from C. hindsii induced neither clinical symptoms of rabbits nor significant changes in hematological parameters such as; total blood cells, hemoglobin concentration, white blood cells and platelets. The quantity of aspartate transaminase (AST or GOT), alanine transaminase (ALT or GPT) of rabbits in the experimental and control group did not differ (p> 0.05). Liver and kidney organizations were also not affected adversely. CONCLUSION: The results indicate that the oral administration of C. hindsii extract did not produce any significant toxicity in mice, therefore, it is recommended to be used safely for traditional medical practices and modern pharmaceutical applications.

Consumption of Raw Herbal Medicines Is Associated with Major Public Health Risks amongst Ugandans.

Background: Community consumption of herbal plants in developing countries is a common practice, however, scarcity of information on their physiochemical composition is a major public health concern. In Uganda, Vernonia amygdalina is of interest in rural communities due to its therapeutical action on both bacterial and protozoal parasites, however no studies have been conducted to assess the heavy metal concentrations in traditional plants used in alternative medicine. The aim of the study was to establish concentrations of heavy metals in Vernonia amygdalina, model the estimated daily intake (EDI), and assess both the non-cancer-related health risk using the target hazard quotient (THQ), and the risk related to cancer through the incremental lifetime cancer risk (ILCR) for the Ugandan population. Methods: Leaves of Vernonia amygdalina were collected from 20 georeferenced villages and processed into powder in the laboratory using standard methods. These were then analyzed in the laboratory using an atomic absorption spectrometer for lead (Pb), chromium (Cr), copper (Cu), zinc (Zn), cobalt (Co), iron (Fe), cadmium (Cd), and nickel (Ni). Concentrations were compared against the World Health Organization (WHO) limits. The EDI, THQ, and ILCR were modelled and significance was measured at 95% confidence. Results: The study showed that mean ± SEM concentrations of heavy metals were highest in the order of Cr, 121.8 ± 4.291 ppm > Ni, 84.09 ± 2.725 ppm > Zn, 53.87 ± 2.277 ppm > Pb, 40.61 ± 3.891 ppm > Cu, 28.75 ± 2.202 ppm > Fe, 14.15 ± 0.7271 ppm > Co, 7.923 ± 0.7674 ppm > Cd, 0.1163 ± 0.005714 ppm. Concentrations of Pb, Cr, Zn, Co, and Ni were significantly higher than the WHO limits. The EDI was significantly higher in children than in adults, demonstrating an increased risk of toxicity in children. The THQ and ILCR were over 1000 times higher in all Ugandans, demonstrating the undesirable health risks following oral consumption of Vernonia amygdalina due to very high Cr and Ni toxicities, respectively. Conclusion: Consumption of raw Vernonia amygdalina was associated with a high carcinogenic risk, demonstrating a need to enact policies to promote physiochemical screening of herbal medicines used in developing countries against toxic compounds.

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.

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.

Caucasian endemic medicinal and nutraceutical plants: in-vitro antioxidant and cytotoxic activities and bioactive compounds.

OBJECTIVES: In order to assess traditional claims about the therapeutic potential of Caucasian endemic medicinal plants and to select plants for phytochemical research, nine plant species were selected and assessed for their in-vitro antioxidant and cytotoxic activities. The metabolite profiles of some priority plants were analysed. METHODS: Antioxidant effects were assessed using the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) system, lipid peroxidation and Folin-Ciocalteu methods. Cytotoxic activities were examined against human liver cancer cells (HepG2) using the Alamar Blue assay. Terpenoids of selected species were analysed by GC and GC-MS. Polyphenols were separated by HPLC. KEY FINDINGS: Thymus transcaucasicus, Heracleum transcaucasicum, Ribes armenum, Crataegus armena showed most promising antioxidant activity in ABTS model system. Moreover, Rubus takhtadjanii, C. armena, T. transcaucasicus showed a high level of antioxidant activity by inhibiting lipid peroxidation. C. armena and T. transcaucasicus expressed high-to-moderate cytotoxicity against HepG2 cells. The main terpenoids and polyphenols of Centaurea hajastana, C. armena and T. transcaucasicus were quantified. CONCLUSIONS: This study provides in-vitro data relevant for assessing the use of Caucasian endemic medicinal plants, most importantly C. armena and T. transcaucasicus as traditional antioxidant supplements and potential anticancer remedies. Metabolite profiles of some lead plants showed the nature of bioactive compounds of medical interest.

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.

Pharmaceutical ethnobotany in the Mahabad (West Azerbaijan) biosphere reserve: ethno-pharmaceutical formulations, nutraceutical uses and quantitative aspects

This study endeavors to overcome the limits of an orally transmitted pharmacopoeia, and tries to utilize the large ethnobotany patrimony of the area to investigate the biological diversity. Thirty-five traditional practitioners from dissimilar ethnic groups including traditional health practitioners (THPs) and indigenous people were interviewed. A total of 35 species of plants, belonging to 20 families were recognized for the treatment of more than 26 types of ailments. Informant consensus factor (FIC) values of this study reflected the high agreement in the use of plants in the treatment of gastro-intestinal complaints, infectious, parasitic diseases and constipation among the informants. Constipation had the highest use-reports and 8 species of plants had the highest fidelity level (FL) of 100%. In addition one of the species showed the highest relative importance (RI) value of 2.00. Priority should be given to phytochemical investigation of plants that scored the highest FL, FIC, RI values; as such values could be considered as a good indicator of potential plants for discovering new drugs. In addition, traditional knowledge of THPs should be taken into consideration in order to smooth continuation and extension of the nutraceutical aspects and biological diversity of the region.

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.

Metabolomics assisted fingerprint of Hypericum perforatum chemotypes and assessment of their cytotoxic activity.

Hypericum perforatum is known as an important medicinal plant, used for the treatment of several diseases, while its pharmacological properties are attributed to the presence of a wide range of secondary metabolites. Due to the great chemotypic variability of Hypericum species in the nature, and the demand for standardized herbal products, a detailed phytochemical investigation was carried out on different parts (herba, leaf, flowers) from wild collected and cultivated populations, using advanced chromatographic tools. Liquid Chromatographic analysis (LC-MS/MS MRM) revealed significant variability in the secondary metabolites content of the examined methanolic extracts. The most common derivatives belong to 9 groups i.e. benzoic acids, phenylpropanoids, coumarins, flavones, flavonols, flavan-3-ols, anthocyanins, phloroglucinols and naphtodianthrones. The main polyphenolic compounds were catechin, epicatechin, quercetin, quercetin 3-O-rhamnoside, quercetin 3-O-glucoside, neochlorogenic acid, proanthocyanidins (A and B series) and cyanidin-3-O-glucoside. In addition, the content of the characteristic compounds hypericin and hyperforin in herba crude extracts ranged between 0.5 and 1.7 mg/g and 0.6-3.3 mg/g respectively. The cytotoxic activity of the crude extracts was assessed at concentrations ranged between 0.01 and 100 µg/mL, on Caco-2 intestinal cancer cell cultures, and a cytotoxic behavior was shown only at the highest concentration of 100 µg/mL.

Metabolic state can define the ovarian response to environmental contaminants and medicinal plants.

Environmental contaminants and medicinal plants can affect reproductive processes. The aim of this study was to investigate the effect of maternal metabolic status on the response of mouse ovaries to the environmental contaminants benzene and xylene, as well as to extracts of the medicinal plant yucca. Ovaries isolated from normal-lean and slightly obese mice were cultured with or without 0.1% benzene or xylene for 24 h. Similarly, ovaries isolated from normal-lean, slightly obese, and significantly obese mice were cultured for 24 h with or without an extract of Yucca shidigera (YS, 10 µ g/mL). We found that the metabolic status did not influence the release of basal progesterone (P4), testosterone (T), or insulin-like growth factor I (IGF-I), but obesity influenced the effects of the environmental contaminants and YS. Benzene reduced P4 output in ovaries from obese but not normal-lean mice; it also reduced IGF-I (but not T) release from ovaries irrespective of the metabolic status. Xylene dramatically increased P4 and T (but not IGF-I) release by ovaries from normal-lean mice, but there were no changes in P4 and only small increases in T output in obese mice. YS increased P4 (but not T or IGF-I) release in normal-lean and slightly obese animal ovaries, whilst significant obesity was associated with a lack of P4 response to YS. Obesity might affect the basal ovarian release of T or IGF-I and increases the sensitivity of ovaries to the action of benzene but decreases their responsiveness to xylene and YS.