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1.
Environ Res ; 243: 117802, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38043891

RESUMO

This investigation was designed and performed to compare the phytochemical profiling, activities of antibacterial, thrombolytic, anti-inflammatory, and cytotoxicity of methanol extract (ME-E) and aqueous extract (AQ-E) of aerial parts of Achyranthes aspera through in-vitro approach. Also characterize the functional groups of bioactive compounds in the ME-E through Fourier-transform infrared (FTIR) spectroscopy analysis. Interestingly, qualitative phytochemical screening proved that the ME-E contain more number of vital phytochemicals such as phenolics. saponins, tannins, alkaloids, flavonoids, cardiac glycosides, steroids, and phlobatannins than AQ-E. Similarly, the ME-E showed notable antibacterial activity as dose dependent manner against Bacillus subtilis, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa at 1000 µg mL-1 concentration. ME-E also showed 75.2 ± 2% of clot lysis (thrombolytic activity) at 1000 µg mL-1 dosage and it followed by AQ-E 51.24 ± 3%. The ME-E showed moderate and AQ-E demonstrate poor anti-inflammatory activity evidenced by albumin denaturation inhibition and anti-lipoxygenase assays. Furthermore, the ME-E demonstrated a dose dependent cytotoxicity was noted against brine shrimp larvae. In support of this ME-E considerable activities, the Fourier transform infrared (FTIR) analysis confirmed that this extract contain more number peaks attributed to the stretch of various essential functional groups belongs to different bioactive compounds. Hence this ME-E of A. aspera can be considered for further in depth scientific investigations to validate their maximum biomedical potential.


Assuntos
Achyranthes , Extratos Vegetais , Extratos Vegetais/toxicidade , Antibacterianos/toxicidade , Antibacterianos/análise , Metanol/análise , Compostos Fitoquímicos/toxicidade , Compostos Fitoquímicos/análise , Componentes Aéreos da Planta/química
2.
J Toxicol Environ Health A ; 87(16): 662-673, 2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-38808737

RESUMO

Pseudobombax marginatum, popularly known as "embiratanha," is widely used by traditional communities as anti-inflammatory and analgesic agent. This study aimed to determine the phytochemical profile as well as cytotoxicity, acute oral toxicity, genotoxicity, and mutagenicity attributed to exposure to aqueous (AqEx) and ethanolic (EtEx) extracts of embiratanha bark. Phytochemical screening was conducted using thin-layer chromatography (TLC). Cell viability was analyzed using MTT assay with human mammary gland adenocarcinoma (MDA-MB-231) and macrophage (J774A.1) cell lines, exposed to concentrations of 12.5, 25, 50, or 100 µg/ml of either extract. For acute oral toxicity, comet assay and micronucleus (MN) tests, a single dose of 2,000 mg/kg of either extract was administered orally to Wistar rats. TLC analysis identified classes of metabolites in the extracts, including cinnamic acid derivatives, flavonoids, hydrolyzable tannins, condensed tannins, coumarins, and terpenes/steroids. In the cytotoxicity assay, the varying concentrations of extracts derived from embiratanha induced no significant alterations in the viability of MDA-MB-231 cells. The lowest concentration of EtEx significantly increased macrophage J774A.1 viability. However, the higher concentrations of AqEx markedly lowered macrophage J774A.1 viability. Animals exhibited no toxicity in the parameters analyzed in acute oral toxicity, comet assay, and MN tests. Further, EtEx promoted a significant reduction in DNA damage index and DNA damage frequency utilizing the comet assay, while the group treated with AqEx exhibited no marked differences. Thus, data demonstrated that AqEx or EtEx of embiratanha may be considered safe at a dose of 2,000 mg/kg orgally under our experimental conditions tested.


Assuntos
Extratos Vegetais , Ratos Wistar , Extratos Vegetais/toxicidade , Extratos Vegetais/química , Animais , Humanos , Ratos , Linhagem Celular Tumoral , Masculino , Ensaio Cometa , Testes para Micronúcleos , Feminino , Sobrevivência Celular/efeitos dos fármacos , Compostos Fitoquímicos/toxicidade , Compostos Fitoquímicos/análise , Camundongos , Casca de Planta/química , Mutagênicos/toxicidade , Testes de Mutagenicidade , Etanol/química
3.
ScientificWorldJournal ; 2024: 3607396, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39050386

RESUMO

Syzygium polyanthum is known for its capacity to regulate blood glucose levels in individuals with diabetes, while Muntingia calabura leaves have a traditional history as an alternative therapy due to their antidiabetic compounds. The combination of these two plants is expected to yield more optimized antidiabetic agents. This study aims to assess the antidiabetic activity of the combined ethanolic extract of S. polyanthum and M. calabura leaves by measuring the in vitro inhibition of the α-glucosidase enzyme and the blood glucose level in streptozotocin-induced rats and to determine the phytochemical contents of total phenolics, total flavonoids, and quercetine as marker compounds. Acute oral toxicity test was also evaluated. Both plants were extracted by maceration using 96% ethanol. Various combinations of S. polyanthum and M. calabura leaves extracts (1 : 1, 2 : 1, 3 : 1, 1 : 3, and 1 : 2) were prepared. The in vitro test, along with the total phenolic and total flavonoid content, were measured by using UV-Vis spectrophotometry, while quercetine levels were quantified through high-performance liquid chromatography (HPLC). The in vivo and acute toxicity tests were performed on rats as an animal model. The findings demonstrated that the 1 : 1 combination of S. polyanthum and M. calabura leaves ethanolic extract displayed the highest enzyme inhibitory activity with IC50 value of 36.43 µg/mL. Moreover, the combination index (CI) was found <1 that indicates the synergism effect. This combination also decreases the blood glucose level in rats after 28 days of treatments without significant difference with positive control glibenclamide (p > 0.005), and it had medium lethal doses (LD50) higher than 2000 mg/kg BW. Phytochemical analysis showed that the levels of total phenolics, total flavonoids, and quercetine were 30.81% w/w, 1.37% w/w, and 3.25 mg/g, respectively. These findings suggest the potential of combined ethanolic extracts of S. polyanthum and M. calabura leaves (1 : 1) as raw materials for herbal antidiabetic medication.


Assuntos
Diabetes Mellitus Experimental , Etanol , Hipoglicemiantes , Compostos Fitoquímicos , Extratos Vegetais , Folhas de Planta , Syzygium , Animais , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Hipoglicemiantes/toxicidade , Folhas de Planta/química , Ratos , Syzygium/química , Compostos Fitoquímicos/química , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/toxicidade , Etanol/química , Diabetes Mellitus Experimental/tratamento farmacológico , Masculino , Glicemia/efeitos dos fármacos , Flavonoides/análise , Testes de Toxicidade Aguda , Ratos Wistar
4.
Bioorg Chem ; 131: 106288, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36470194

RESUMO

The use of medicinal plants has gained renewed wide popularity in Africa, Asia, and most parts of the world because of the decreasing efficacy of synthetic drugs. Thus, natural products serve as a potent source of alternative remedy. Tetrapleura tetraptera is a medicinal plant with cultural and traditional significance in West Africa. In addition to the plant being commonly used as a spice in the preparation of traditional spicy food for postpartum care it is also widely used to constitute herbal concoctions and decoctions for treatment of diseases. This review aimed to provide an up-to-date information on the ethnomedicinal uses, pharmacological activities and phytoconstituents of T. tetraptera. Preclinical studies regarding the plant's toxicity profile were also reviewed. For this updated review, literature search was done on PubMed, Science Direct, Wiley, and Google Scholar databases using the relevant keywords. The review used a total of 106 papers that met the inclusion criteria from January 1989 - February 2022 and summarised the bioactivities that have been reported for the rich phytoconstituents of T. tetraptera studied using various chemical methods. Considering the huge report, the review focused on the antimicrobial and antiinflammatory activities of the plant extracts and isolated compounds. Aridan, aridanin and several bioactive compounds of T. tetraptera have shown pharmacological activities though their mechanisms of action are yet to be fully understood. This study also highlighted the influence of plant parts and extraction solvents on its biological activities. It also presented data on the toxicological profile of the plant extracts using different models. From cultural uses to modern pharmacological research the bioactive compounds of T. tetraptera have proved effective in infectious disease management. We hope that this paper provided a robust summary of the biological activities and toxicological profile of T. tetraptera, thus calling for more research into the pharmacological and pharmacokinetic activities of natural products to help combat the growing threat of drug resistance and provide guidelines for their ethnomedicinal uses.


Assuntos
Plantas Medicinais , Tetrapleura , Compostos Fitoquímicos/toxicidade , Extratos Vegetais/toxicidade
5.
J Toxicol Environ Health A ; 86(16): 557-574, 2023 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-37350297

RESUMO

This study aimed to characterize the phytochemical profile of bark and leaves aqueous extract Commiphora leptophloeos, and conduct in vivo and in vitro assays to determine the presence of any toxicological consequences due to exposure. The phytochemical analysis was carried out using high-performance liquid chromatography (HPLC). The antioxidant activity was estimated utilizing DPPH free radical scavenging and phosphomolybdenum assays. Cell viability was measured by the MTT method on J774 and human adenocarcinoma cells, which were treated with concentrations of 12,5, 25, 50, 100 or 200 µg/ml of both extracts. Acute oral toxicity, genotoxicity, and mutagenicity assays were determined using a single oral dose of 2000 g/kg in male Swiss albino mice (Mus musculus). Biochemical analysis of the blood and histological analyses of the kidneys, liver, spleen, pylorus, duodenum and jejunum were undertaken. Genotoxicity and mutagenicity were determined utilizing blood samples. Gallic acid, catechin, and epicatechin were identified in the bark and chlorogenic acid in leaves. Data demonstrated a high content of phenolic compounds and flavonoids associated with significant antioxidant potential. No significant signs in damage or symptoms of toxicity were detected. No marked reduction in cell viability was found at lower concentrations tested. On histomorphometry, only the gastrointestinal organs exhibited significant difference. Renal hepatic and blood parameters were within the normal range. No apparent signs of toxicity, genotoxicity, mutagenicity or cytotoxicity were found in vivo and in vitro experiments.


Assuntos
Antioxidantes , Catequina , Camundongos , Animais , Masculino , Humanos , Antioxidantes/química , Extratos Vegetais/toxicidade , Extratos Vegetais/química , Commiphora , Casca de Planta/química , Compostos Fitoquímicos/toxicidade , Folhas de Planta/química
6.
Drug Chem Toxicol ; 46(2): 330-342, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35114863

RESUMO

Fruit of Cycas pectinata Buch.-Ham has been used as medicine by the local community in some parts of the north eastern state of India. Despite its uses for different purposes, the safety assessment study has not been conducted. Therefore, we have evaluated the acute and the sub-acute toxicity of methanolic extract of C. pectinata fruit (CPFE) in a mice model via oral route of administration. Phytochemicals analysis was carried out by liquid chromatography-mass spectroscopy (LC-MS), nuclear magnetic resonance (NMR), and Fourier-transform infrared spectroscopy (FTIR). The acute toxicity study was performed at a single dose of 1000, 3000 and 5000 mg/kg and the sub-acute toxicity study at a dose of 100, 300 and 500 mg/kg was administered daily for 28 days. The calculated Lethal dose 50 (LD50) of CPFE was found to be 4000 mg/kg. Both acute and sub-acute studies showed that 5000 mg/kg and 500 mg/kg dose was toxic to the mice. The results of acute toxicity showed CPFE could have a mild toxic effect on the kidney at a dose of 3000 and 5000 mg/kg, as some deteriorated changes in the kidney along with increase creatinine levels were observed. Acute toxicity also showed an increase in white blood cells (WBC) at a dose of 3000 mg/kg.However, sub-acute toxicity studies do not show any detrimental effects on liver, kidney and hematological parameters. Thus, it can be suggested that CPFE at a dose of 100 and 300 mg/kg would be safe for consumption. The phytochemicals analysis by LC-MS, NMR and FTIR showed the presence of 32 major chemical compounds with certain biological activity like anti-neoplastic, antioxidant, and possible modulator of steroid metabolism (cholesterol antagonist and agonist of testosterone 17ß-dehydrogenase) as predicted by PASS analysis.


Assuntos
Cycas , Extratos Vegetais , Camundongos , Animais , Extratos Vegetais/toxicidade , Extratos Vegetais/química , Metanol , Sementes , Compostos Fitoquímicos/toxicidade , Testes de Toxicidade Aguda
7.
Semin Cancer Biol ; 68: 143-163, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-31883912

RESUMO

Drug repurposing (or repositioning) is an emerging concept to use old drugs for new treatment indications. Phytochemicals isolated from medicinal plants have been largely neglected in this context, although their pharmacological activities have been well investigated in the past, and they may have considerable potentials for repositioning. A grand number of plant alkaloids inhibit syngeneic or xenograft tumor growth in vivo. Molecular modes of action in cancer cells include induction of cell cycle arrest, intrinsic and extrinsic apoptosis, autophagy, inhibition of angiogenesis and glycolysis, stress and anti-inflammatory responses, regulation of immune functions, cellular differentiation, and inhibition of invasion and metastasis. Numerous underlying signaling processes are affected by plant alkaloids. Furthermore, plant alkaloids suppress carcinogenesis, indicating chemopreventive properties. Some plant alkaloids reveal toxicities such as hepato-, nephro- or genotoxicity, which disqualifies them for repositioning purposes. Others even protect from hepatotoxicity or cardiotoxicity of xenobiotics and established anticancer drugs. The present survey of the published literature clearly demonstrates that plant alkaloids have the potential for repositioning in cancer therapy. Exploitation of the chemical diversity of natural alkaloids may enrich the candidate pool of compounds for cancer chemotherapy and -prevention. Their further preclinical and clinical development should follow the same stringent rules as for any other synthetic drug as well. Prospective randomized, placebo-controlled clinical phase I and II trials should be initiated to unravel the full potential of plant alkaloids for drug repositioning.


Assuntos
Alcaloides/farmacologia , Antineoplásicos/farmacologia , Descoberta de Drogas , Reposicionamento de Medicamentos/métodos , Neoplasias/tratamento farmacológico , Compostos Fitoquímicos/farmacologia , Alcaloides/toxicidade , Animais , Humanos , Compostos Fitoquímicos/toxicidade , Testes de Toxicidade
8.
Regul Toxicol Pharmacol ; 133: 105221, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35792244

RESUMO

Richardia brasiliensis, known as poaia branca, is a medicinal species widely distributed throughout Brazil and used in folk medicine. However, studies on its toxicity are practically non-existent, and little is known about its biological activity. This study aimed to investigate its phytochemical compounds, assess its in vitro and in vivo toxicities, and determine its antiproliferative activity. UHPLC-ESI-HRFTMS performed the phytochemical characterization, and the antiproliferative activity was analyzed in different tumor cell lines. In vitro toxicity was evaluated in PBMC cells, and in vivo acute and repeated dose toxicity was evaluated according to OECD guidelines. It was identified alkaloids and terpenes as significant compounds. Regarding its antiproliferative activity, the human melanoma strain decreased its viability by about 95%. In vitro toxicity showed that the extracts maintained the viability of PBMCs; however, higher concentrations were able to increase the production of dsDNA quantity. In vivo tests showed no mortality nor signs of toxicity; the alterations found in hematological and biochemical parameters are within the standards for the species. The results indicate that R. brasiliensis has a good effect against the tumor cell line; still, more studies on its toxicity at higher concentrations are needed.


Assuntos
Alcaloides , Leucócitos Mononucleares , Linhagem Celular Tumoral , Humanos , Compostos Fitoquímicos/toxicidade , Extratos Vegetais/química , Extratos Vegetais/toxicidade
9.
Drug Chem Toxicol ; 45(1): 223-230, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31642336

RESUMO

The genus Tamarix includes several plant species well-known for their medicinal properties since ancient times. Tamarix stricta Boiss is a plant native to Iran which has not been previously investigated regarding its phytochemical and biological properties. This study assessed phytochemical and toxicological aspects of T. stricta. The plant was collected from Kerman province of Iran and after authentication by botanist, it was extracted with 70% ethanol. Total phenolic compounds, total flavonoids, and antioxidant properties were measured using spectrophometric methods. Quercetin content of the extract was measured after complete acid hydrolysis with high-performance liquid chromatography. The phytochemical profile of the extract was provided using liquid chromatography-mass spectrometry method. Acute toxicity study with a single intragastric dose of 5000 mg/kg of the extract and sub-chronic toxicity using 50, 100, and 250 mg/kg of the extract was assessed in Wistar rats. Phytochemical analysis showed that polyphenols constitute the major components of the extract. Also, the extract contained 1.552 ± 0.35 mg/g of quercetin. Biochemical, hematological, and histological evaluations showed no sign of toxicity in animals. Our experiment showed that T. stricta is a rich source of polyphenols and can be a safe medicinal plant. Further pharmacological evaluations are recommended to assess the therapeutic properties of this plant.


Assuntos
Tamaricaceae , Animais , Antioxidantes/toxicidade , Cromatografia Líquida de Alta Pressão , Flavonoides/análise , Compostos Fitoquímicos/toxicidade , Extratos Vegetais/toxicidade , Polifenóis/toxicidade , Ratos , Ratos Wistar
10.
Drug Chem Toxicol ; 45(2): 810-821, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32538198

RESUMO

Natural products are often used by the population to treat and/or prevent several disorders. Tucumã is an Amazonian fruit widely consumed by local population and no in vivo toxicity studies regarding its safety are available in the literature to date. Therefore, the phytochemical characterization, acute and repeated dose 28-day oral toxicities of crude extract of tucumã's pulp (CETP) in Wistar rats were evaluated. For the CETP preparation, tucumã pulp was crushed and placed into sealed amber glass jars containing absolute ethanol solution for extraction. CETP phytochemical analyses evidenced the presence of carotenoids, flavonoids, unsaturated and satured fatty acids, and triterpenes. In the acute toxicity, female rats from the test group were treated with CETP at single dose of 2000 mg/kg. For the repeated dose toxicity, CETP was administered to male and female rats at doses of 200, 400 and 600 mg/kg, for 28 days. Body weight was recorded during the experiment and blood, liver and kidney were collected for further analysis. No mortality or toxicity signs were observed during the studies. CETP was classified as safe (category 5, OECD guide), in acute toxicity. In repeated dose study was observed alterations in some biochemical parameters, as well as in oxidative damage and enzymatic activity. Histopathological findings showed renal damage in male rats at higher dose. The data obtained suggest that CETP did not induced toxicity after exposure to a single or repeated doses in female rats. However, in males may be considered safe when given repeatedly in low doses.


Assuntos
Arecaceae , Animais , Arecaceae/química , Carotenoides , Feminino , Frutas/química , Masculino , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/toxicidade , Extratos Vegetais/química , Ratos , Ratos Wistar , Testes de Toxicidade Aguda
11.
Molecules ; 27(3)2022 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-35164354

RESUMO

Plant-derived natural products are significant resources for drug discovery and development including appreciable potentials in preventing and managing oxidative stress, making them promising candidates in cancer and other disease therapeutics. Their effects have been linked to phytochemicals such as phenolic compounds and their antioxidant activities. The abundance and complexity of these bio-constituents highlight the need for well-defined in vitro characterization and quantification of the plant extracts/preparations that can translate to in vivo effects and hopefully to clinical use. This review article seeks to provide relevant information about the applicability of cell-based assays in assessing anti-cytotoxicity of phytochemicals considering several traditional and current methods.


Assuntos
Antioxidantes/toxicidade , Antioxidantes/uso terapêutico , Compostos Fitoquímicos/toxicidade , Compostos Fitoquímicos/uso terapêutico , Animais , Humanos , Estresse Oxidativo , Extratos Vegetais/uso terapêutico , Extratos Vegetais/toxicidade , Testes de Toxicidade
12.
J Toxicol Environ Health A ; 84(10): 399-417, 2021 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-33494643

RESUMO

Combretum leprosum Mart. (Combretaceae), a shrub popularly known as mofumbo, is used in folk medicine for treatment of uterine bleeding, pertussis, gastric pain, and as a sedative. The aim of this study was to (1) determine the phytochemical profile,(2) identify chemical constituents and (3) examine antioxidant and cytogenotoxic activity of ethanolic extracts and fractions of stem bark and leaves. The plant material (leaf and stem bark) was submitted to extraction with ethanol, followed by partition using hexane, chloroform, and ethyl acetate. It was possible to identify and quantify the epicatechin in the ethanolic stem bark extract (0.065 mg/g extract) and rutin in the leaf extract (3.33 mg/g extract). Based upon in vitro tests a significant relationship was noted between findings from antioxidant tests and levels of total phenolic and flavonoid. Comparing all samples (extracts and fractions), the ethyl acetate fractions of stem bark (411.40 ± 15.38 GAE/g) and leaves (225.49 ± 9.47 GAE/g) exhibited higher phenolic content, whereas hexanic fraction of stem bark (124.28 ± 56 mg/g sample) and ethyl acetate fraction of leaves (238.91 ± 1.73 mg/g sample) demonstrated a higher content of flavonoids. Among the antioxidant tests, the intermediate fraction of stem bark (28.5 ± 0.60 µg/ml) and ethyl acetate fraction of leaves (40 ± 0.56 µg/ml) displayed a higher % inhibition of free radical DPPH activity, whereas intermediate fraction of stem bark (27.5 ± 0.9 µg/ml) and hydromethanol fraction of leaves (81 ± 1.4 µg/ml) demonstrated inhibition of the free radical ABTS. In biological tests (Allium cepa and micronucleus in peripheral blood), data showed that none of the tested concentrations of ethanolic extracts of leaves and stem bark produced significant cytotoxicity, genotoxicity, and mutagenic activity.Abbreviations AA%: percentage of antioxidant activity; ABTS: 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid); CEUA: Ethics Committee in the Use of Animals; TLC: Thin Layer Chromatography; DNA: deoxyribonucleic acid; DPPH: 1,1-diphenyl-2-picrylhydrazyl; ROS: Reactive oxygen species; EEB: ethanol extract of the stem bark; HFB: Hexanic fraction of stem bark; IFB: Intermediate fraction of stem bark; CFB: Chloroform fraction of stem bark; EAFB: Ethyl acetate fraction of stem bark; HMFB: Hydromethanol fraction of the stem bark; EEL: Ethanol extract from leaves; HFL: Hexane fraction of leaves; CFL: Chloroform fraction of leaves; EAFL: Ethyl acetate fraction of leaves; HMFL: Hydromethanol fraction of leaves; GAE: Gallic Acid Equivalent; IC50: 50% inhibition concentration; HCOOH: Formic acid; HCl: hydrochloric acid; HPLC: High-performance liquid chromatography; MN: micronucleus; WHO: World Health Organization; UFLC: Ultra-Fast Liquid Chromatography; UESPI: State University of Piauí.


Assuntos
Antioxidantes , Combretum/química , Flavonoides , Fenóis , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Antioxidantes/farmacologia , Citotoxinas/toxicidade , Flavonoides/farmacologia , Flavonoides/toxicidade , Testes para Micronúcleos , Mutagênicos/toxicidade , Cebolas/efeitos dos fármacos , Fenóis/farmacologia , Fenóis/toxicidade , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/toxicidade , Casca de Planta/química , Extratos Vegetais/química , Folhas de Planta/química , Caules de Planta/química
13.
Regul Toxicol Pharmacol ; 123: 104960, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34022260

RESUMO

Cassia occidentalis Linn (CO) is an annual/perennial plant having traditional uses in the treatments of ringworm, gastrointestinal ailments and piles, bone fracture, and wound healing. Previously, we confirmed the medicinal use of the stem extract (ethanolic) of CO (henceforth CSE) in fracture healing at 250 mg/kg dose in rats and described an osteogenic mode of action of four phytochemicals present in CSE. Here we studied CSE's preclinical safety and toxicity. CSE prepared as per regulations of Current Good Manufacturing Practice for human pharmaceuticals/phytopharmaceuticals and all studies were performed in rodents in a GLP-accredited facility. In acute dose toxicity as per New Drug and Clinical Trial Rules, 2019 (prior name schedule Y), in rats and mice and ten-day dose range-finding study in rats, CSE showed no mortality and no gross abnormality at 2500 mg/kg dose. Safety Pharmacology showed no adverse effect on central nervous system, cardiovascular system, and respiratory system at 2500 mg/kg dose. CSE was not mutagenic in the Ames test and did not cause clastogenicity assessed by in vivo bone marrow genotoxicity assay. By a sub chronic (90 days) repeated dose (as per OECD, 408 guideline) study in rats, the no-observed-adverse-effect-level was found to be 2500 mg/kg assessed by clinico-biochemistry and all organs histopathology. We conclude that CSE is safe up to 10X the dose required for its osteogenic effect.


Assuntos
Compostos Fitoquímicos/toxicidade , Extratos Vegetais/toxicidade , Senna , Animais , Etanol , Camundongos , Nível de Efeito Adverso não Observado , Ratos , Roedores , Testes de Toxicidade
14.
Regul Toxicol Pharmacol ; 119: 104822, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33217502

RESUMO

Zaleya decandra is a prostrate, glabrous, succulent herb of the family Aizoaceae. In recent years the pharmacological efficacy of the plant such as the hepatoprotective, antimicrobial, antidiabetic, anti-inflammatory and anticancer activities has been reported. However, a long-term toxicity study of Z. decandra is yet to be carried out. In the present study, the acute dose of 2000 mg/kg b.w. of ethanolic extract of Z. decandra (EEZD) administered orally to Wistar rats gained gradual weight with time and appeared healthy without any record of mortality. In the sub-chronic toxicity study, the rats showed no remarkable increase or decrease in their weight even at the highest dose of 500 mg/kg b.w. The haematological, biochemistry and serum marker enzyme parameters did not show any dose dependent change in the values. Further, the histology micrographs confirmed that the tissue architecture of all the vital organs were not affected by EEZD treatment. Hence, the EEZD (500 mg/kg b.w.) is considered safe for a 90-day period. Therefore, the present study warrants extensive investigation of EEZD using higher pre-clinical model system to substantiate the findings. The GC-MS analysis revealed the presence of 39 phytoconstituents including octadecenoic acid, hexadecanoic and phytosterols such as campesterol, sitosterol and stigmasterol.


Assuntos
Aizoaceae , Extratos Vegetais/toxicidade , Administração Oral , Animais , Etanol/química , Feminino , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/toxicidade , Extratos Vegetais/química , Raízes de Plantas/química , Ratos Wistar , Solventes/química , Testes de Toxicidade Aguda , Testes de Toxicidade Subcrônica
15.
Ecotoxicol Environ Saf ; 210: 111877, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33412283

RESUMO

Fumigant toxicity of phytochemical volatiles has been widely reported against stored product insect pests. Such volatiles are considered as natural fumigants and bio-fumigants in post-harvest food protection research. In the present study, persistence and ingestion of diallyl disulfide, citral, eucalyptol, eugenol and menthol were investigated in Sitophilus oryzae adults in comparison with fumigant toxicity and microstructural impact in elytra. The fumigant toxicity bioassay was performed with increasing concentrations of phytochemical volatiles at 25, 125, 250 and 500 µL/L air against S. oryzae adults in 50 mL glass vials. The phytochemical residues were examined from the treated adults by Gas Chromatography coupled with Flame Ionization Detector (GC-FID) and their pathological impacts on the elytral surface was observed under Scanning Electron Microscopy (SEM). After 72 h of fumigation, diallyl disulfide and eucalyptol were identified as potential fumigants with 5.24 and 8.30 µL/L air LC50 values, respectively. GC-FID analyses showed that diallyl disulfide and eucalyptol molecules persistence (1.29 and 2.60 ppb persistence with 0.94 and 0.90 r2 values respectively at 72 h exposure) on the body surface of weevil was positively correlated with the fumigation exposure and toxicity. Whereas, phytochemical molecules ingestion into the body of weevils was not directly linked with the insect mortalities. The SEM observations indicated that diallyl disulfide and eucalyptol molecules caused severe microstructural impacts on the elytra of weevils compared to other molecules. As a result, the present study suggested that phytochemical fumigants are persisted on the body surface and caused insecticidal toxicities in S. oryzae adults. In addition, it was predicted that persisted molecules might be entered into the body of weevils via cuticular penetration.


Assuntos
Inseticidas/toxicidade , Compostos Fitoquímicos/toxicidade , Gorgulhos/efeitos dos fármacos , Monoterpenos Acíclicos/toxicidade , Compostos Alílicos/toxicidade , Animais , Dissulfetos/toxicidade , Ingestão de Alimentos , Eucaliptol/toxicidade , Eugenol/toxicidade , Fumigação/métodos , Mentol/toxicidade , Oryza
16.
Phytother Res ; 35(9): 4632-4659, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33987899

RESUMO

Prized medicinal spice true nutmeg is obtained from Myristica fragrans Houtt. Rest species of the family Myristicaceae are known as wild nutmegs. Nutmegs and wild nutmegs are a rich reservoir of bioactive molecules and used in traditional medicines of Europe, Asia, Africa, America against madness, convulsion, cancer, skin infection, malaria, diarrhea, rheumatism, asthma, cough, cold, as stimulant, tonics, and psychotomimetic agents. Nutmegs are cultivated around the tropics for high-value commercial spice, used in global cuisine. A thorough literature survey of peer-reviewed publications, scientific online databases, authentic webpages, and regulatory guidelines found major phytochemicals namely, terpenes, fatty acids, phenylpropanoids, alkanes, lignans, flavonoids, coumarins, and indole alkaloids. Scientific names, synonyms were verified with www.theplantlist.org. Pharmacological evaluation of extracts and isolated biomarkers showed cholinesterase inhibitory, anxiolytic, neuroprotective, anti-inflammatory, immunomodulatory, antinociceptive, anticancer, antimicrobial, antiprotozoal, antidiabetic, antidiarrhoeal activities, and toxicity through in-vitro, in-vivo studies. Human clinical trials were very few. Most of the pharmacological studies were not conducted as per current guidelines of natural products to ensure repeatability, safety, and translational use in human therapeutics. Rigorous pharmacological evaluation and randomized double-blind clinical trials are recommended to analyze the efficacy and therapeutic potential of nutmeg and wild nutmegs in anxiety, Alzheimer's disease, autism, schizophrenia, stroke, cancer, and others.


Assuntos
Myristica , Myristicaceae , Compostos Fitoquímicos , Extratos Vegetais , Etnofarmacologia , Humanos , Medicina Tradicional , Myristica/química , Myristica/toxicidade , Myristicaceae/química , Myristicaceae/toxicidade , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/toxicidade , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade
17.
Molecules ; 26(14)2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34299388

RESUMO

In a project designed to investigate the specific and infraspecific taxa of Matthiola endemic to Sicily (Italy) as new potential sources of bioactive compounds in this work, the infraspecific taxa of Matthiola fruticulosa were studied, namely, subsp. fruticulosa and subsp. coronopifolia. HPLC-PDA/ESI-MS and SPME-GC/MS analyses of hydroalcoholic extracts obtained from the aerial parts of the two subspecies led to the detection of 51 phenolics and 61 volatile components, highlighting a quite different qualitative-quantitative profile. The antioxidant properties of the extracts were explored through in vitro methods: 1,1-diphenyl-2-picrylhydrazyl (DPPH), reducing power and Fe2+ chelating activity assays. The results of the antioxidant tests showed that the extracts possess a different antioxidant ability: particularly, the extract of M. fruticulosa subsp. fruticulosa exhibited higher radical scavenging activity than that of subsp. coronopifolia (IC50 = 1.25 ± 0.02 mg/mL and 2.86 ± 0.05 mg/mL), which in turn displayed better chelating properties (IC50 = 1.49 ± 0.01 mg/mL and 0.63 ± 0.01 mg/mL). Lastly, Artemia salina lethality bioassay was performed for toxicity assessment. The results of the bioassay showed lack of toxicity against brine shrimp larvae for both extracts. The data presented indicate the infraspecific taxa of M. fruticulosa as new and safe sources of antioxidant compounds.


Assuntos
Antioxidantes/toxicidade , Brassicaceae/química , Larva/crescimento & desenvolvimento , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/toxicidade , Extratos Vegetais/toxicidade , Animais , Artemia , Larva/efeitos dos fármacos , Sicília , Testes de Toxicidade
18.
Molecules ; 26(8)2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33918091

RESUMO

The aim of the study was to investigate the micromorphology of Mentha pulegium leaves and flowers harvested in three different Sicilian (Italy) areas with peculiar pedo-climatic conditions, and to characterize the phytochemical profile, the phytotoxic activity, and the eco-compatibility of their essential oils (EOs) for potential use as safe bioherbicides. Light microscopy (LM) and scanning electron microscopy (SEM) highlighted that M. pulegium indumentum consists of non-glandular and glandular trichomes of different types. Peltate trichomes of plants from the different sites showed few significant differences in dimension and abundance, but they were characterized by a surprisingly high number of secretory cells both in leaves and flowers. Phytochemical analyses showed that oxygenated monoterpenes were the most abundant class in all the EOs investigated (92.2-97.7%), but two different chemotypes, pulegone/isomenthone and piperitone/isomenthone, were found. The complex of morphological and phytochemical data indicates that soil salinity strongly affects the expression of the toxic metabolite pulegone, rather than the EO yield. Phytotoxicity tests showed a moderate activity of EOs against the selected species as confirmed by α-amylase assay. Moreover, the low toxicity on brine shrimp provided a rationale for the possible use of investigated EOs as eco-friendly herbicides.


Assuntos
Economia , Mentha pulegium/química , Animais , Artemia , Flores/anatomia & histologia , Flores/ultraestrutura , Geografia , Itália , Mentha pulegium/anatomia & histologia , Mentha pulegium/ultraestrutura , Óleos Voláteis/análise , Óleos Voláteis/economia , Compostos Fitoquímicos/toxicidade , Folhas de Planta/anatomia & histologia , Folhas de Planta/ultraestrutura , Sus scrofa , Testes de Toxicidade , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/metabolismo
19.
Molecules ; 26(6)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33809398

RESUMO

Spondias mombin L. (Anacardiaceae) has a worldwide distribution and is present in all regions of Brazil. Its leaves, flowers and bark are used as teas in folk medicine to treat diseases of the digestive system. This study aimed to evaluate the acute non-clinical toxicity, gastroprotective activity, and the related mechanisms of action of nebulized extract and tablets based on dried Spondias mombin (SmNE). SmNE screening showed the presence of flavonoids (0.65%), polyphenols (25.50%), where the major compound is gallic acid. In the acute oral toxicity assay, a dose of 2000 mg/kg of SmNE administered orally in Swiss mice did not induce any behavioral changes. SmNE (250 or 500 mg/kg p.o) significantly reduced the ulcerative lesion area when compared to the control group in ethanol and non-steroidal anti-inflammatory drug (NSAIDs) models. Results showed that treatment with SmNE (250 mg/kg) reduced acid secretion and gastric content, accompanied with an increase in pH. Previous administration of indomethacin and glibenclamide reversed the protection provided by SmNE, confirming the participation of prostaglandins (PGs) and ATP-sensitive potassium channels (KATP) in its gastroprotective effect. The SmNE tablets met the pharmacopeial quality requirements with gastroprotective activity and similar protection in comparison to the isolated extract administrated. In conclusion, SmNe has a gastroprotective activity related to cytoprotective mechanisms, such as the participation of endogenous prostaglandins and KATP channels, having an anti-secretory effect with systemic action. The formulation obtained presented gastroprotective effects similar to the administration of the extract, the tablets showed favorable compression characteristics by the direct route and met the pharmacopeial quality requirements.


Assuntos
Anacardiaceae/química , Antiulcerosos/administração & dosagem , Fitoterapia , Úlcera Gástrica/prevenção & controle , Animais , Anti-Inflamatórios não Esteroides/toxicidade , Antiulcerosos/química , Antiulcerosos/toxicidade , Modelos Animais de Doenças , Composição de Medicamentos , Etanol/toxicidade , Feminino , Ácido Gástrico/metabolismo , Canais KATP/metabolismo , Masculino , Camundongos , Nebulizadores e Vaporizadores , Compostos Fitoquímicos/administração & dosagem , Compostos Fitoquímicos/química , Compostos Fitoquímicos/toxicidade , Piroxicam/toxicidade , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/toxicidade , Plantas Medicinais/química , Prostaglandinas/metabolismo , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Comprimidos
20.
Molecules ; 26(3)2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33499159

RESUMO

Allium sativum L. (garlic bulbs) and Allium fistulosum L. (Welsh onion leaves) showed quantitative differences of identified compounds: allicin and alliin (380 µg/mL and 1410 µg/mL in garlic; 20 µg/mL and 145 µg/mL in Welsh onion), and the phenolic compounds (chlorogenic acid, p-coumaric acid, ferulic acid, gentisic acid, 4-hydroxybenzoic acid, kaempferol, isoquercitrin, quercitrin, quercetin, and rutin). The chemical composition determined the inhibitory activity of Allium extracts in a dose-dependent manner, on human normal cells (BJ-IC50 0.8841% garlic/0.2433% Welsh onion and HaCaT-IC50 1.086% garlic/0.6197% Welsh onion) and tumor cells (DLD-1-IC50 5.482%/2.124%; MDA-MB-231-IC50 6.375%/2.464%; MCF-7-IC50 6.131%/3.353%; and SK-MES-1-IC50 4.651%/5.819%). At high concentrations, the cytotoxic activity of each extract, on normal cells, was confirmed by: the 50% of the growth inhibition concentration (IC50) value, the cell death induced by necrosis, and biochemical determination of LDH, catalase, and Caspase-3. The four tumor cell lines treated with high concentrations (10%, 5%, 2.5%, and 1.25%) of garlic extract showed different sensibility, appreciated on the base of IC50 value for the most sensitive cell line (SK-MES-1), and the less sensitive (MDA-MB-231) cell line. The high concentrations of Welsh onion extract (5%, 2.5%, and 1.25%) induced pH changes in the culture medium and SK-MES-1 being the less sensitive cell line.


Assuntos
Allium/química , Neoplasias/tratamento farmacológico , Fitoterapia , Caspase 3/metabolismo , Catalase/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Alho/química , Humanos , L-Lactato Desidrogenase/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Cebolas/química , Fenóis/farmacologia , Fenóis/toxicidade , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/toxicidade , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade
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