Oral Toxicity Test Research Articles

Acute Oral Toxicity Test of Philippine "Bignay" [Antidesma bunius (Linn.) Spreng cv. ‘Common’] in ICR Mice

Acute Oral Toxicity Test of Philippine "Bignay" [Antidesma bunius (Linn.) Spreng cv. ‘Common’] in ICR Mice

Evaluation of subacute toxicity of a polyherbal nootropic formulation in Wistar albino rats

In ayurvedic system of traditional medicine, 'medhyarasayanas' — decoction of selected plants are used to improve intellect or cognition abilities. Here, we investigated one such polyherbal formulation (PHF) with ingredients Bacopa monniera, Glycyrrhiza glabra, Valeriana wallechii and Withania somnifera used as a facilitator of learning, retention and recall. We evaluated the safety of this PHF in animal models. We performed acute oral toxicity test using 2000 mg/kg of the formulation as per OECD guideline 423 and observed for toxicity over 14 days. Thereafter, we divided them into four groups of six animals each and administered Normal saline 5 mL/kg, The PHF (Wilmer®) @500, 1000 and 2000 mg/kg in the respective groups over 28 days. We observed no mortality or physical and behavioural abnormalities in both acute and subacute toxicity study. On the 28th day, animals were sacrificed, blood collected for estimation of haematological and biochemical parameters and histopathological examination of organs was performed. There was significant difference (P <0.05) in Mean ± SEM values of haemoglobin, total cholesterol, total protein, ALT, AST, ALP and serum creatinine in the test groups compared to control as analysed by One-way ANOVA followed by Tukey’s multiple comparison test. We observed steatosis and ballooning of hepatocytes, lymphocytic periglomerular infiltrate, eosinophilic hyaline casts and renal tubular coagulation necrosis in histopathology of test groups. Haematologic abnormalities (decrease in haemoglobin concentration), hepatotoxic, nephrotoxic and dyslipidemic effects of the tested PHF were seen in the rats in subacute toxicity study over 28 days, which could be due to the individual plant products, microbial contamination or heavy metals in the formulation in excess of regulatory limits. Hence, it needs further safety evaluation in animals and humans.

Acute Oral Toxicity and Genotoxicity Test and Evaluation of Cinnamomum camphora Seed Kernel Oil.

Cinnamomum camphora seed kernel oil (CCSKO) is one of the important natural medium chain triglycerides (MCT) resources, with more than 95.00% of medium chain fatty acids found in the world, and has various physiological effects. However, CCSKO has not been generally recognized as a safe oil or new food resource yet. The acute oral toxicity test and a standard battery of genotoxicity tests (mammalian erythrocyte micronucleus test, Ames test, and in vitro mammalian cell TK gene mutation test) of CCSKO as a new edible plant oil were used in the study. The results of the acute oral toxicity test showed that CCSKO was preliminary non-toxic, with an LD50 value higher than 21.5 g/kg body weight. In the mammalian erythrocyte micronucleus test, there was no concentration-response relationship between the dose of CCSKO and micronucleus value in polychromatic erythrocytes compared to the negative control group. No genotoxicity was observed in the Ames test in the presence or absence of S9 at 5000 μg/mL. In vitro mammalian cell TK gene mutation test showed that CCSKO did not induce in vitro mammalian cell TK gene mutation in the presence or absence of S9 at 5000 μg/mL. These results indicated that CCSKO is a non-toxic natural medium-chain oil.

Phytochemical Screening and Acute oral Toxicity Study of Root Extracts of Combretum hereroense Schinz and Balanites aegyptiaca Del. Traditionally Used to Treat Female Infertility in Baringo County, Kenya

Aims: To carry out phytochemical screening and acute oral toxicity test to validate their safety and efficacy.
 Study Design: Standard phytochemical screening tests were used to highlight phytochemical compounds of roots of the plants. The evaluation of acute toxicity of the root extracts of the plants followed the model of Acute Toxicity Class based on OECD 423 Guideline, 2001.
 Place and Duration of the Study: The study was undertaken at the Department of Chemistry & Biochemistry for the extraction for samples extraction and phytochemical screening. Acute oral toxicity studies were done at the Department of Biological Sciences for acute toxicity study, University of Eldoret, Between June and September 2022.
 Methodology: Phytochemical screening for presence of Tannins, saponins, flavonoids, glycosides, alkaloids, anthocyanin, terpenoids, steroids, coumarins, lipids, proteins and carbohydrates were carried out. Acute oral toxicity studies were done using the fixed dose method at a dose of 2000mg/kg body weights of rats. Three groups were used: control and test groups for each of the respective plant root extracts. Signs of toxicity and/or mortality were monitored daily for 14 days. Weekly fasting body weights were also recorded.
 Results: The phytochemical screening results showed the presence of tannins, saponins, flavonoids, glycosides, alkaloids, anthocyanin, terpenoids, steroids, lipids, proteins and carbohydrates present in the root extract of Combretum hereroense. Tannins, saponins, flavonoids, glycosides, terpenoids, steroids, and carbohydrates were present in root extracts of Balanites aegyptiaca. Following the acute oral toxicity study, there were no abnormalities observed in physiological parameters. In addition, no deaths were recorded during the study period. The LD50 was therefore greater than 2000 mg/kg. The fasting body weights of extract treated rats increased stably compared to the control [p = .05].
 Conclusion: The results showed C. hereroense and B. aegyptiaca methanol root extracts were considered safe in acute oral exposure. Long-term toxicity studies are needed for further toxicological profile elicitation of the plant, and a possible reinforcement of clinical relevance of the results of laboratory studies.

Evaluation of Wound Healing and Anti-Inflammatory Activities of 80% Methanol Crude Extract and Solvent Fractions of Trichilia dregeana Sond (Meliaceae) Leaves in Mice.

The leaves of Trichilia dregeana Sond are traditionally used to treat wounds. Even though there have been in vitro studies and claims supporting wound healing, there are no scientific data on in vivo wound healing and anti-inflammatory activities of the leaves of T. dregeana. This study aimed to evaluate wound healing and anti-inflammatory activity of 80% methanol crude extract and solvent fractions of T. dregeana in mice. The leaves of T. dregeana were dried, ground, and macerated with 80% methanol three times successively. The crude extract was fractioned by water, ethyl acetate, and hexane separately. The acute dermal and oral toxicity tests were done by applying 2000 mg/kg of 10% (w/w) crude extract ointment (CEO) topically and 2000 mg/kg of crude extract orally, respectively. The wound healing activity of the crude extract was evaluated on excision, incision, and burn wound models while the fractions were evaluated only on excision wound model. The anti-inflammatory activity of the crude extract was evaluated on xylene-induced ear edema and cotton pellet granuloma tests. Both acute dermal and oral toxicity tests were found to be safe after topical application of 2000 mg/kg of 10% (w/w) CEO and oral administration of 2000 mg/kg of crude extract suspension, respectively. Both 5% and 10% (w/w) CEO produced significant (p < 0.001) wound contraction and period of epithelialization from day 4 onwards as compared to simple ointment (SO) on both excision and burn wounds. The tensile strength was increased significantly (p < 0.001) for the CEO-treated mice as compared to both untreated and SO groups. The crude extract also showed anti-inflammatory activity at 100, 200, and 400 mg/kg by inhibiting ear edema, exudate, and granuloma formation as compared to the SO group. The increase in wound contraction, reduction in period of epithelialization, and increase in tensile strength support the traditional claims of T. dregeana for wound healing.

Acute and Repeated Dose 28-Day Oral Toxicity Study of the Aqueous Extracts from the Leafy Stem and Fruit of Pedalium murex D.Royen EX.L in Wistar Rats.

Pedalium murex (P. murex) is used in folk medicine for treatment of male infertility. However, scientific data on its safety are limited. This study was carried out to assess the acute and repeated dose 28-day oral toxicity of the aqueous extracts from P. murex leafy stem and fruit in Wistar rats. The acute toxicity test was performed according to the line 423 of the Organization for Economic Cooperation and Development (OECD) guidelines. The rats were randomly divided into three groups (n = 3). The control group received distilled water, while the experimental groups were given at a single dose, 5000 mg/kg of each extract. The repeated dose 28-day oral toxicity was performed according to the line 407 of the OECD guidelines. 35 rats divided into 7 groups of 5 male rats each were daily treated for 28 days with each extract at 200 mg/kg, 400 mg/kg, and 800 mg/kg, respectively. The in-life parameters were recorded during the follow-up. At the end of this study, organ weights, hematology, biochemistry, and histology parameters were analyzed. In the acute oral toxicity test, there was no morbidity or mortality related to the treatments. Both extracts belong therefore to category 5 of the globally harmonized system (GHS) of classification. In the repeated dose 28-day oral toxicity test, both extracts did not alter animal's behavior. However, both extract administration led to proteinuria and renal damages. P. murex leafy stem and fruit aqueous extracts exhibited potential nephrotoxicity. Therefore, care should be taken when they are used over an extended period.

Pharmacokinetic and toxicological in silco profiling of pluchine from the medicinal plant – Pluchea lanceolata

Background: Pluchea lanceolata belongs to the genus Pluchea (family: Asteraceae). The medicinal herb has been used for various ailments to prevent joint swelling in arthritic disorders, rheumatism, and other neurological-inflammatory disorders. Pluchine, which in our review was found to be a compound from P. Lanceolata, is explored for possible pharmacokinetic and toxicological properties by in silico computational predictive tools. Aims and Objectives: The aim of the study is to profile the pharmacokinetic, toxicological, and drug likeness scores of pluchine’s active principle using computational analysis and prediction tools. Materials and Methods: The authenticated and validated chemical structure of pluchine with its chemical formula will be extracted from standard web-based tools PubChem and ChemSpider. The two-dimensional to three-dimensional (3D) structure conversion will be processed with ChemSketchonline software; the 3D structure output will be processed further to be screened for molecular and pharmacokinetic properties for absorption, distribution, metabolism, and elimination, followed by toxicity profiling through AdmetSAR software. Results: Pluchine active principle from P. lanceolata had a predictive pharmacokinetic profile of human intestinal absorption of &lt;30%, Human skin permeability coefficients (log k p) of pluchine were −6.75 cm/s, and the blood–brain barrier were predicted to be positive with a probability score of 0.65. Drug likeness lipinskiscore is positive with -0- violations. Acute oral toxicity testing for pluchine predicts it to be placed in category III with LD50 values &gt;500 mg/kg but &lt;5000 mg/kg. Conclusion: The pluchineactive principle from P. lanceolata is predicted to have a favorable pharmacokinetic and drug-like property profile for lead compound development.

Safety evaluations of alternansucrase enzyme expressed in Escherichia coli shows no adverse effects invivo and invitro

Background Alternansucrase is a glucansucrase enzyme that mainly functions in synthesis of glucan-like polysaccharides and can be used for production of novel oligosaccharides and polysaccharides having low glycemic index and prebiotics properties which makes them ideal candidates as dietary fibers and food. From a regulatory perspective, it is necessary to prove the safety of alternansucrase before it can be used in any application as it is a novel enzyme and has not been historically used in food processing. Objectives Alternansucrase obtained from Escherichia coli was subjected to toxicological tests to determine its safety for use in various industrial applications. Design Toxicity studies were conducted at acute oral and repeated sub-chronic (14 days and 90 days) levels in rats following the OECD guidelines. The genotoxicity studies were conducted using the bacterial reverse mutation test as well as in vitro mammalian cell micronucleus test as per the OECD guidelines. Results Alternansucrase did not induce any clinical abnormalities or mortality in rats at the dose level of 2000 mg/kg of body weight in the acute oral toxicity test. A 90-day sub chronic repeated dose oral toxicity study with alternansucrase at and up to dose of 1000 mg TOS/kg of body weight did not show any treatment-related significant toxicological effects on body weight, food consumption, organ weights, hematological and clinical chemistry, or histopathology parameters. Alternansucrase was found to be non-mutagenic up to 5000 µg TOS/plate concentration in the bacterial reverse mutation test. Alternansucrase was determined to be non-clastogenic and non-aneugenic up to the test concentration of 1250 µg TOS/mL during the in vitro mammalian cell micronucleus test. Conclusion The lethal dose (LD50) based on this study is greater than 2000 mg/kg body weight, which falls into the category 5 criteria of Globally Harmonized System (GHS). No-Observed-Adverse-Effect-Level (NOAEL) was concluded to be greater than 1000 mg TOS/kg per day. The studies taken together substantiate the safety of alternansucrase enzyme in various food and associated industries. The present study paves a future for safe use of alternansucrase in varied industrial applications.

Safety Evaluation and Anti-Inflammatory Efficacy of Lacticaseibacillus paracasei PS23

Lacticaseibacillus paracasei strain PS23 (PS23) exhibits some probiotic properties. In this study, a genomic analysis of PS23 revealed no genes related to virulence or antibiotic resistance. Moreover, ornithine decarboxylase activity was not detected in vitro. In addition, PS23 was sensitive to the tested antibiotics. Genotoxicity tests for PS23 including the Ames test and chromosomal aberrations in vitro using Chinese hamster ovary cells and micronuclei in immature erythrocytes of ICR mice were all negative. Moreover, following a 28-day study involving repeated oral dose toxicity tests (40, 400, and 4000 mg/kg equal 1.28 × 1010, 1.28 × 1011, and 1.28 × 1012 CFU/kg body weight, respectively) using an ICR mouse model, no adverse effects were observed from any doses. In addition, supplementation with live or heat-killed PS23 ameliorates DSS-induced colonic inflammation in mice. Our findings suggest that PS23 is safe and has anti-inflammatory effects and may therefore have therapeutic implications.

Bacterial Reverse Mutation Test of Verbenalin.

Verbenalin is a compound found in herbs such as Cornus officinalis and Verbena officinalis. This study investigated whether verbenalin is safe by analyzing its mutagenicity. To examine the mutagenic potential of verbenalin, a bacterial reverse mutation test (Ames test) was conducted with Salmonella typhimurium and Escherichia coli strains. Experiments with and without metabolic activity were performed. The mean colony number was less than double that of the control. Growth inhibition and precipitation of verbenalin were not apparent in all strains at different concentrations regardless of metabolic activity. Verbenalin did not show any signs of mutagenicity in this study. Additional toxicity studies including repeated oral toxicity, reproductive toxicity, and carcinogenicity tests are needed.

Sub-acute Oral Toxicity Evaluation of Philippine Bignay (Antidesma bunius (L.) Spreng cv. ‘Kalabaw’) Fruit in ICR Mice

This study evaluated the safety of Bignay (Antidesma bunius (L.) Spreng cv. ‘Kalabaw’) fruits through a sub-acute oral toxicity test in male and female ICR mice. The evaluation was done through oral gavage of the aqueous fruit sample at 2,000 mg kg-1 body weight dose for 28 d. Results showed that there were no significant changes in feed and water intake of male and female ICR mice as compared to the control groups that received distilled water (p &lt; 0.05). Blood chemistry and hematology values for all mice groups were comparable to the controls and published values. All mice groups also had appreciable body weight gain (10.89% – 21.69%) with zero morbidity and mortality. Lastly, the gross and microscopic examination of the brain, heart, lungs, GI tract, liver, spleen, and kidneys showed normal architecture and histology, suggesting that the fruits did not induce any morphological abnormalities. Results showed that Bignay (cv. ‘Kalabaw’) fruits are safe for consumption with an LD50 of greater than 2,000 mg kg-1 body weight.

Antimalarial activity of the hydroalcoholic crude extract and solvent fractions of Commelina latifolia Hochst. ex C.B.Clarke (Commelinaceae) leaves against Plasmodium berghei in mice

Ethnopharmacological relevanceIn Ethiopia, the indigenous medicinal plant Commelina latifolia Hochst. ex C.B. Clarke leaves are used to treat malaria and wounds. Aim of the studyIn this work, the antiplasmodial activity of Commelina latifolia crude leaf extract and solvent fractions against Plasmodium berghei-infected mice was investigated. Materials and methods80% methanol was used to extract the leaves of C. latifolia, and the crude extract was fractionated using chloroform, pure methanol, and distilled water. All test compounds were undergone an acute oral toxicity test before being put through Peter’s 4-day suppressive test to see if they have antiplasmodial activity. The hydroalcoholic crude extract and chloroform fraction were additionally assessed for antimalarial activity using curative and prophylactic tests in P. berghei-infected laboratory mice. ResultsAll of the tested crude extracts were safe at a dose of 2000 mg/kg. At 400 mg/kg dose both the 80% methanol extract and chloroform fraction exhibited antimalarial activity with parasitemia suppression values of 86.31%, and 76.56% in the four-day suppressive test, 81.97% and 72.05% in Rane's test, and 69.05% and 62.88% in the prophylactic test, respectively. ConclusionCollectively, the oral dose of Commelina latifolia is safe, and reveals promising antimalarial activity. The findings backed up the utilization of the plant in traditional medicine to treat malaria.

Phytochemical, Antimalarial, and Acute Oral Toxicity Properties of Selected Crude Extracts of Prabchompoothaweep Remedy in Plasmodium berghei-Infected Mice.

Malaria remains a life-threatening health problem and encounters with the increasing of antimalarial drug resistance. Medicinal plants play a critical role in synthesizing novel and potent antimalarial agents. This study aimed to investigate the phytochemical constituents, antiplasmodial activity, and evaluate the toxicity of crude ethanolic extracts of Myristica fragrans, Atractylodes lancea, and Prabchompoothaweep remedy in a mouse model. The phytochemical constituents were characterized by liquid chromatography-mass spectrometry (LC-MS). Antimalarial efficacy against Plasmodium berghei was assessed using 4-day suppressive tests at doses of 200, 400, and 600 mg/kg body weight. Acute toxicity was assessed at a dose of 2000 mg/kg body weight of crude extracts. The 4-day suppression test showed that all crude extracts significantly suppressed parasitemia (p &lt; 0.05) compared to the control group. Higher parasitemia suppression was observed both in Prabchompoothaweep remedy at a dose of 600 mg/kg (60.1%), and A. lancea at a dose of 400 mg/kg (60.1%). The acute oral toxicity test indicated that the LD50 values of all extracts were greater than 2000 mg/kg and that these extracts were not toxic in the mouse model. LC-MS analysis revealed several compounds in M. fragrans, A. lancea, and Prabchompoothaweep remedy. For quantitative analysis, 1,2,6,8-tetrahydroxy-3-methylanthraquinone 2-O-b-D-glucoside, chlorogenic acid, and 3-O-(beta-D-glucopyranosyl-(1-&gt;6)-beta-D-glucopyranosyl) ethyl 3-hydroxyoctanoate were found in A. lancea, while (7'x,8'x)-4,7'-epoxy-3,8'-bilign-7-ene-3,5'-dimethoxy-4',9,9'-triol, edulisin III, and tetra-hydrosappanone A trimethyl ether are found in M. fragrans. 6'-O-Formylmarmin was present in the Prabchompoothaweep remedy, followed by pterostilbene glycinate and amlaic acid. This study showed that the ethanolic extracts of A. lancea and Prabchompoothaweep remedy possess antimalarial activity against Plasmodium berghei. None of the extracts had toxic effects on liver and kidney function. Therefore, the ethanolic extract of A. lancea rhizome and Prabchompoothaweep remedy could be used as an alternative source of new antimalarial agents. Further studies are needed to determine the active compounds in both extracts.

Suppressive, Curative, and Prophylactic Effects of Maesa lanceolata Forssk. against Rodent Malaria Parasite Plasmodium berghei.

The artemisinin partial resistance is believed to be spread to artemisinin-based combination therapy partner drugs. As a result, new antiplasmodial compounds are required to treat resistant malaria infections. In the invention of antimalarial substances, claimed medical plants are precious resources. So, the current study was designed to assess the antiplasmodial effects of Maesa lanceolata in mice. In this study, preliminary phytoconstituent and in vivo acute oral toxicity tests were done. Early infection, established infection, and residual infection tests were employed to determine the antimalarial effects of the test drugs. Three doses (200, 400, and 600 mg/kg) of the extracts were provided orally to the test mice. Analysis of variance (one-way) followed by post hoc Tukey's test was used to analyze the difference between and within groups. Terpenoids, tannins, saponins, flavonoids, and alkaloids were detected in the phytochemical constituent analysis. Both 80% methanolic crude extract and solvent fractions had no toxic result at the 2000 mg/kg dose. All test drug doses suppressed parasite levels in a significant manner at all tests. The activity of chloroform fraction (maximum percentage suppression, 81.28%) overwhelms the crude extract activity. The curative effects of 80% methanolic crude extract, with a maximum of 80.22% parasitemia suppression, were greater than its suppressive and prophylactic effects. The 400 mg/kg dose of chloroform fraction resulted in a maximum survival period (18 days) than other doses of tested materials. The results of this investigation provide support for the activity of M. lanceolata leaf extract against malaria.

Genotoxicity and toxicological evaluations of Brazilian red propolis oral ingestion in a preclinical rodent model

Ethnopharmacological relevanceBrazilian red propolis is a natural product known due to its medicinal properties. The efficacy of this natural resin has been proved; however, few studies report the safety of its oral use. Some toxic effects of natural products may not be expressed in traditional use, and preclinical studies are necessary to guarantee their safety. Health regulatory agency currently requires these non-clinical studies to develop drugs and herbal medicines, including genotoxic and oral toxicity tests. Aim of the studyAccomplish the preclinical toxicity studies of Brazilian red propolis extract (BRP) in rodents, including genotoxicity, acute and sub-chronic toxicities. Material and methodsGenotoxicity assays followed the erythrocyte micronucleus test protocol in a range of 500–2000 mg/kg BRP oral treatment on male Swiss mice. After an up-and-down procedure, acute oral toxicity (single dose) was performed on female Wistar Hannover rats, reaching a 2000 mg/kg BRP oral gavage concentration. Animals were monitored periodically until 14 days and euthanized for a macroscopic necropsy analysis. The sub-chronic oral toxicity test (90 days) was achieved with 1000 mg/kg of BRP on Wistar Hannover rats (males/females). Animals were monitored to evaluated behavioral and biometrical changes, then were euthanized to perfomed hematological, biochemical, and histopathological analyses. ResultsNo genotoxic effect of the BRP was detected. The acute toxicity indicated no toxicity of a single oral dose of 2000 mg/kg of BRP. The long-term oral toxicity performed with 1000 mg/kg of BRP altered water and food intake and the biometrics, hematological and biochemical parameters. Biochemical alterations in hepatic and renal parameters were detected only in the males. Despite the detection of biochemical alterations, no histopathological changes were detected in the organs of any group. ConclusionsBRP, at a higher dose, showed no signs of immediate toxicity. However, the obtained results suggest that the chemical composition and the intake of higher doses deserve special attention regarding possible toxicity.

Сучасні методи дослідження гострої токсичності полютантів для представників водної і наземної екосистем та впровадження їх у практику наукового центру превентивної та регуляторної токсикології

The paper provides a brief historical background on the formation and development of ecotoxicology as a science, reflects the main modern methods and principles for studying the acute toxicity of xenobiotics for representatives of aquatic and terrestrial ecosystems recommended by the OECD (Organization for Economic Cooperation and Development). The classification of acute ecotoxicity of chemicals for land and water test systems is given. Further perspective development of the unit, which will be aimed at expanding ecotoxicological research in accordance with international OECD methods and GLP requirements, has been outlined. Aim. Revealing the main methods and principles recommended by the OECD for determining acute toxicity for biological objects of aquatic and terrestrial ecosystems and putting these methods and principles into practice of the Scientific Centre. Materials and Methods. The work was based on the implementation of international OECD standards and GLP principles. The OECD public electronic library of methods, particularly section 2 of the Instructions for Testing Chemicals, was used and analysed. Results and Conclusions. International methods for determining the acute toxicity of pollutants for non-target environmental objects were put into practice in the Scientific Centre, such as OECD 201 (Freshwater Alga and Cyanobacteria, Growth Inhibition Test); OECD 202 (Daphnia sp. Acute Immobilisation Test); OECD 203 (Fish, Acute Toxicity Test); OECD 207 (Earthworm, Acute Toxicity Tests); OECD 213 (Honeybees, Acute Oral Toxicity Test); OECD 216 (Soil Microorganisms: Nitrogen Transformation Test); OECD 217 (Soil Microorganisms: Carbon Transformation Test); OECD 223 (Avian Acute Oral Toxicity Test). Systems for the quality and control of ecotoxicological studies have been developed, which made it possible to obtain national and international accreditation for the conduct of the above studies. Further activities of the department will be aimed at expanding ecotoxicological research using international OECD methods and compliance with GLP requirements, which will contribute to the development of ecotoxicological research both in the Scientific Centre and in Ukraine as a whole. Key Words: ecotoxicology, pesticides and agrochemicals, biological test systems, OECD methods, good laboratory practice (GLP).

ANALGESIC AND ANTI-DIABETIC POTENTIAL OF ROYSTONEA REGIA

Background: Plants are the rich source of nutrients and contain biological and pharmacological potential. Roystonea regia, a plant of Aceraceae family has been traditionally used in different countries especially in Asia. Objectives: The aim of the study was to evaluate its analgesic and anti-diabetic potential by hot plate method and Alloxan induced method in Swiss albino female rats weighing 150 to 200 gm respectively. Methodology: Shoots of Roystonea regia plant was extracted using n-hexane, chloroform and ethanol in Soxhlet apparatus. Oral acute toxicity test showed the different mortality rates of all extracts. Results: The crude n-hexane and ethanol extract showed increase in the latency time till 120 min and were found to have significant (p˂0.001) analgesic potential at 100 and 200 mg/kg dose. However, different anti-diabetic potential was shown by all three extracts. Chloroform extract showed maximum reduction in blood glucose level (BGL) and found significant (p˂0.001) as compared to negative control till 21st day at the dose of 250 and 500 mg/kg of body weight. Conclusion: Further study is required to understand the complete mechanism involved in both activities. In future, purified fractions and column chromatography can be conducted for their complete characterization and their toxic effects to establish a proper therapeutic dose for further trials.

Acute toxicity of pesticide mixtures to honey bees is generally additive, and well predicted by Concentration Addition

Understanding the frequency of non-additive effects of pesticides (synergism and antagonism) is important in the context of risk assessment. The goal of this study was to investigate the prevalence of non-additive effects of pesticides to honey bees (Apis mellifera). We investigated a large set of mixtures including insecticides and fungicides of different chemical modes of action and classes. The mixtures included represent a relevant sample of pesticides that are currently used globally. We investigated whether the experimental toxicity of the mixtures could be predicted based on the Concentration Addition (CA) model for acute contact and oral adult bee toxicity tests. We measured the degree of deviation from the additivity predictions of the experimental toxicity based on the well-known Mixture Deviation Ratio (MDR). Further, we investigated the appropriate MDR thresholds that should be used for the identification of non-additive effects based on acceptable rates for false positive (alpha) and true positive (beta) findings. We found that a deviation factor of MDR = 5 is a sound reference for labeling potential non-additive effects in acute adult bee experimental designs when assuming a typical Coefficient of Variation (CV%) = 100 in the determination of the LD50 of a pesticide (a factor of 2× deviation in the LD 50 resulting from inter-experimental variability). We found that only 2.4 % and 9 % of the mixtures evaluated had an MDR > 5 and MDR < 0.2, respectively. The frequency and magnitude of deviation from additivity found for bees in this study are consistent with those of other terrestrial and aquatic taxa. Our findings suggest that additivity is a good baseline for predicting the toxicity of pesticide mixtures to bees, and that the rare cases of synergy of pesticide mixtures to bees are not random but have a mechanistic basis.

Evaluation of Safety of Stewart's Wood Fern (Dryopteris stewartii) and Its Anti-Hyperglycemic Potential in Alloxan-Induced Diabetic Mice.

Diabetes has become a critical challenge to the global health concerns. Cytotoxicity and development of resistance against available drugs for management of diabetes have shifted the focus of global scientific researchers from synthetic to herbal medications. Therefore, the current study was conducted to investigate the possible anti-hyperglycemic potential of Dryopteris stewartii using Swiss albino mice. To evaluate any possible toxic effect of the plant, acute oral toxicity test was performed while the anti-diabetic effects of aqueous and ethanol extracts at 500 mg/kg, positive, negative and normal control were assessed simultaneously. The anti-diabetic study revealed that aqueous extract has higher anti-diabetic potential than ethanol extract while lowered blood glucose level at second week reaching 150 mg/dL, exerting stronger anti-diabetic effects, compared to ethanol extract (190 mg/dL). Oral glucose tolerance findings revealed that aqueous extract decreased blood glucose level by −0.41-fold, compared to ethanol extract showing a decrease by only −0.29-folds. The histopathological evaluation of liver and pancreas of all groups revealed normal cell architecture with no morphological abnormalities. These results suggested the possible use of D. stewartii as anti-diabetic herbal drug in near future. However, these recommendations are conditioned by deep mechanistic studies.

One stone two birds: Multifunctional flavonol nanocrystals enable food packaging to both preserve freshness and visually monitor freshness

Food packaging with both active and intelligent components is critical for reducing food waste and ensuring food safety. However, concerns about the toxicity of components or detecting results prevent their commercialization. Herein, we report three flavonol nanocrystals with aggregation-induced emission characteristics that have been individually composited with a flexible film to form three multifunctional food packaging systems. The nanocrystals are derived from quercetin, myricetin, and kaempferol, respectively; they all exhibit antibacterial properties, antioxidant abilities, and alkaline pH sensitivities in both colorimetric and fluorescent modes. Among them, myricetin nanocrystals with more phenolic hydroxyl groups are the most sensitive to alkalinity. Hemolysis and acute oral toxicity tests ensure their biocompatibility in vitro and in vivo. Just incorporating any one of the prepared nanocrystals into packaging can simultaneously extend the shelf life of bananas and provide dual-mode monitoring of shrimp freshness. Moreover, the addition of these nanocrystals can improve the mechanical, water vapor barrier, and thermal performances of packaging. This work demonstrates that the design of natural-derived nanocrystals as both active and intelligent components offers an opportunity to construct multifunctional packaging systems toward simultaneously food preservation and freshness monitoring.