Oral Toxicity Study Research Articles

Toxicity of a management bait for grass carp (Ctenopharyngodon idella) incorporated with Antimycin A.

No current technology can specifically target grass carp (Ctenopharyngodon idella) for control within aquatic ecosystems. Rotenone and Carbon Dioxide-Carp are currently the only available registered pesticides for grass carp; they are nonselective and typically applied throughout the water, equally exposing target and native species. A more selective control tool or pesticide application could be used by resource managers to support mitigation efforts. Development of delivery systems that exploit carp feeding strategies could increase selectivity of pesticides and minimize effects on native fishes. A pesticide with selective delivery could be less labor intensive and used within an integrative pest management strategy. The present study examined Antimycin A toxicity in juvenile and sub-adult grass carp and rainbow trout (Oncorhynchus mykiss) across two routes of exposure. Water-based toxicity studies were used to calculate the concentration to cause lethality in 50% of treated fish (LC50) at 24-h, while oral gavage toxicity studies were used to calculate the dose to cause lethality in 50% of treated grass carp and rainbow trout (LD50) 24- to 96-h. Although rainbow trout were more sensitive than grass carp to Antimycin A through water-based exposure, oral toxicity was similar between species, even with inherent gastrointestinal morphological differences. Successful delivery of a lethal dose of Antimycin A to grass carp was achieved through an oral route of exposure using the rapeseed bait and shows promise for registration as a control tool and eventual use in pest management plans. Although a lethal dose of Antimycin A could be incorporated into a single bait pellet, more bait was required to achieve desired mortality when fed to fish under laboratory conditions.

Evaluating the performance of multi-omics integration: a thyroid toxicity case study.

Multi-omics data integration has been repeatedly discussed as the way forward to more comprehensively cover the molecular responses of cells or organisms to chemical exposure in systems toxicology and regulatory risk assessment. In Canzler etal. (Arch Toxicol 94(2):371-388. https://doi.org/10.1007/s00204-020-02656-y ), we reviewed the state of the art in applying multi-omics approaches in toxicological research and chemical risk assessment. We developed best practices for the experimental design of multi-omics studies, omics data acquisition, and subsequent omics data integration. We found that multi-omics data sets for toxicological research questions were generally rare, with no datasets comprising more than two omics layers adhering to these best practices. Due to these limitations, we could not fully assess the benefits of different data integration approaches or quantitatively evaluate the contribution of various omics layers for toxicological research questions. Here, we report on a multi-omics study on thyroid toxicity that we conducted in compliance with these best practices. We induced direct and indirect thyroid toxicity through Propylthiouracil (PTU) and Phenytoin, respectively, in a 28-day plus 14-day recovery oral rat toxicity study. We collected clinical and histopathological data and six omics layers, including the long and short transcriptome, proteome, phosphoproteome, and metabolome from plasma, thyroid, and liver. We demonstrate that the multi-omics approach is superior to single-omics in detecting responses at the regulatory pathway level. We also show how combining omics data with clinical and histopathological parameters facilitates the interpretation of the data. Furthermore, we illustrate how multi-omics integration can hint at the involvement of non-coding RNAs in post-transcriptional regulation. Also, we show that multi-omics facilitates grouping, and we assess how much information individual and combinations of omics layers contribute to this approach.

Exploring the Potential Antidiabetic Effects of Alkannin (A Naphthoquinone Compound): In Vivo and In Silico Studies

Background It is estimated that the plant has been utilized in India’s traditional medical system for close to 2,500 years. Alkanin is a key active component in Boraginaceae medicinal plant roots. Many scientists are interested in this tiny molecule due to its biological potential. Purpose To examine the hypoglycemic effects of alkannin (a naphthoquinone pigment). Methods Initially, we determined the dosage of alkannin by conducting an acute oral toxicity study per Organisation for Economic Co-operation and Development guidelines. Subsequently, streptozocin was used to induce diabetes in mice, and we chose several parameters such as body weight, food and water intake, blood glucose level, and biochemical estimation for the in vivo evaluation. The enhanced pharmacokinetic features of alkannin, such as its better cytochromes P450 metabolism profiles and higher intestinal absorption as compared to glimepiride, were validated by in silico investigations utilizing Swiss ADME (Absorption, Distribution, Metabolism, and Excretion) and AutoDock Vina. Results In particular, blood glucose levels and body weight in the alkannin-treated group drastically decreased to 138 ± 1.45 mg/dL and 27.9±0.54 g, respectively, as compared with the diabetic-treated group. Moreover, alkaline phosphatase levels dropped to 57.26 ± 3.05 U/L in the alkannin group, suggesting enhanced liver and kidney functions. Creatinine levels also decreased from 1.44 ± 0.10 mg/dL to 0.92 ± 0.09 mg/dL, and serum glutamic oxaloacetic transaminase/aspartate aminotransferase levels decreased from 64.16 ± 3.14 U/L to 47.85 ± 2.01 U/L. Additionally, diabetic controls maintained cholesterol levels between 102.1 ± 11.46 mg/dL and 93.53 ± 2.61 mg/dL. With a considerable binding score of –9.2 kcal/mol for alkannin, molecular docking demonstrated a high degree of binding efficiency and robust interaction with biological targets. The docking results revealed that alkannin exhibits drug-like properties. In addition, it satisfies the lead likeness requirement and has a lower synthetic accessibility score compared to glimepiride. Conclusion The results revealed the promising characteristics and positive outcomes of alkannin, underscoring its potential as a viable candidate for further investigation and prospective advancement as a treatment drug for diabetes.

Subchronic Toxicity Evaluation of Dietary Administration of a Fungal Biomass From Rhizomucor pusillus.

Fungal-derived food products align with sustainable food supply principles and offer a sustainable and nutritious option for consumers. Rhizomucor pusillus strain CBS 143028 has emerged as a candidate food ingredient. Fermentation of R. pusillus CBS 143028 results in a mycelium biomass mainly comprising fungal proteins, cell wall components, and micronutrients. Although R. pusillus has a history of safe use in the production of food enzymes and in traditional fermented foods, the fungal biomass obtained after fermentation of R. pusillus CBS 143028 is considered a novel food and requires a thorough safety assessment. To this end, a 90-day oral toxicity study was conducted in which Wistar rats (10/sex/group) were provided diets containing 0, 100,000, 200,000, or 300,000 ppm of R. pusillus mycelium. Standard toxicity study parameters as given in OECD Test Guideline 408 were examined. The mean achieved dosages of R. pusillus mycelium were 6398, 12,738, or 19,668 mg/kg body weight/day for males and 7235, 14,949, or 22,461 mg/kg body weight/day for females in the low-, mid-, and high-dose groups, respectively. Although statistically significant differences were reported, these effects were not considered biologically relevant or test article-related due to atypical values in the control groups, the lack of a dose response relationship, or were attributed to normal biological variation. Thus, the no-observed-adverse-effect level (NOAEL) was established at 300,000 ppm (corresponding to 19,668 and 22,461 mg/kg body weight/day for males and females, respectively), the highest concentration tested.

EVALUATION OF ANTI-DIABETIC ACTIVITY OF METHANOLIC EXTRACT FROM THE FRUIT PEEL OF ATALANTIA MONOPHYLLA (LINN.) IN ALLOXAN INDUCED DIABETIC MICE

Objective: Atlantia monophylla is an indigenous medicinal plant, with a folk reputation as hypoglycemic agent throughout India. Considerable research has shown that plants rich in flavonoids content with anti-oxidant potential are known to be bioactive for the management of diabetes mellitus (DM). In the present investigation, hypoglycemic activity of aqueous fruit peel extract of A. monophylla was evaluated using alloxan-induced hyperglycemic mice. Methods: Aqueous extract of the fruit peel of A. monophylla (AEAM) was subjected to preliminary phytochemical screening and acute oral toxicity study as per Organization for Economic Cooperation and Development guidelines 425. AEAM was evaluated for hypoglycemic activity, Alloxan induced DM in mice, oral glucose tolerance test in fasted mice. In vitro α- amylase inhibitory in albino mice method was employed for evaluation of hypoglycemic activity. Results: All of the mice in each group had their blood glucose levels measured both before and after the treatments on fasting animals. The extract was given at doses of 200 mg/kg and 400 mg/kg body weight, or 100 mg/kg body weight of the conventional antidiabetic medication Metformin. A glucometer was used to measure the blood glucose level. After 1 h, 2 h, and 4 h, the extract-treated diabetic mice had a substantial (p≤0.05) drop in blood glucose levels. The hypoglycemic action was similar to that of the medication Metformin used as a benchmark. Conclusion: The results of this study indicate that AEAM has strong hypoglycemic properties. One such method might include the activation of insulin receptors and subsequent release of insulin once β cells are stimulated. The hypoglycemic effect of the plant could be achieved through increasing insulin release from the pancreas.

Non-clinical safety evaluation of Yongdamsagan-tang water extract: A 13-week subchronic oral toxicity study in Sprague Dawley rats.

Despite the continued clinical application of traditional herbal medicines, scientific evidence such as toxicological safety profile of Yongdamsagan-tang water extract (YSTW) has not yet been established. The purpose of this study was to investigate the potential toxicity profile of YSTW following a 13-week repeated oral administration at various concentrations to Sprague Dawley rats. YSTW was administered orally to rats once daily at doses of 0, 1000, 2000, and 5000 mg/kg bw/day for 13 weeks. During the experimental period, there were no significant toxicological changes related to YSTW treatment. These results indicate that the administration of YSTW for 13 weeks in the rat resulted in no signs of toxicity at up to 5000 mg/kg bw/day, which was considered the no-observed-adverse-effect level.

Chemical Characterization, Evaluation of Acute Oral Toxicity, and Anti-Diabetic Activity of Aloe sabaea Flowers Extract on Alloxan-Induced Diabetic Rats.

The study aimed to conduct chemical profiling, acute in-vivo toxicity evaluation, and the potential anti-diabetic effect of standardized Aloe sabaea flowers ethanolic extracts (ASFEE) on alloxan-induced diabetic rats. The chemical composition was analyzed using GC-MS and TLC techniques. The oral acute toxicity study was performed according to the WHO 2000 and the OECD 420 guidelines. Furthermore, anti-diabetic activity was investigated using two doses of ASFEE (0.2 and 0.5 g/kg/day BW, p.o.) compared with glibenclamide (5 mg/kg/day, p.o.). A molecular docking investigation of the identified components with the PTPN9 enzyme was performed to figure out the proposed anti-diabetic mechanism. GC-MS analysis displayed the existence of 18 compounds; mostof the compoundswere fatty acids and theiresters, and phytosterols. Total phenolic and flavonoid contents were 42.00±1.26 mg GAE/g DW and 22.21±1.55 mg QE/g DW, respectively. The results of the in-vivo toxicity study revealed the absence of noticeable signs of toxicity or mortality at various doses establishing the safety of the tested extract. The estimated LD50 value was higher than 10 g/kg. Antidiabetic action exhibited a noticeable decline in fasting blood glucose (FBG) levels comparable to glibenclamide with no inducing intense hypoglycemia and considerable excess weight.

Acute oral toxicity and genotoxicity assessment of the essential oil from Croton pulegiodorus Baill (Euphorbiaceae) leaves in mice

Essential oils obtained from Croton pulegiodorus leaf are renowned for their biological activities; however, data on their toxicity are limited. Therefore, this study aimed to evaluate the acute oral toxicity and genotoxicity of a C. pulegiodorus leaf essential oil (CPLEO). Chemical characterization of CPLEO was conducted by gas chromatography coupled to mass spectrometry (GC-MS). In vitro assay was performed to verify the hemolytic capacity of the oil in mice erythrocytes. Next, an acute oral toxicity study was conducted on female mice at CPLEO doses of 2000, 1000, 500, 250, 100, and 50 mg/kg. Hematological, biochemical, and histopathological markers were assessed in mice from groups were no death occurred. Relative consumption of water and food and the weight of animals and their organs were also recorded. Finally, a genotoxicity analysis was performed using the micronucleus and comet assays. The extraction yield of CPLEO was 1.149% and its major compounds were ascaridole (23.18%), eucalyptol (17.20%), camphor (14.20%), p-cymene (7.91%), α-terpineol (4.69%), and isobornyl acetate (4.57%). CPLEO showed a hemolytic effect only at high concentrations (185.5–1000 mg/mL). It showed acute oral toxicity in mice with a LD50 of 460.42 mg/kg. CPLEO (50–250 mg/kg) caused some significant changes in hematological and biochemical parameters. Histopathological evaluation indicated alterations in liver and kidneys but transaminases, urea and creatinine levels remained like the negative control. CPLEO administration impaired weight gain and reduced water and food consumption. Finally, it was not genotoxic by both comet and micronucleus tests. The results highlight the need for attention when choosing doses to evaluate the bioactivities of CPLEO.

Safety evaluation of the food enzyme endo-1,3(4)-β-glucanase from the non-genetically modified Talaromyces versatilis strain PF8.

The food enzyme endo-1,3(4)-β-glucanase (3-(1-3;1-4)-β-d-glucan 3(4)-glucanohydrolase; EC 3.2.1.6) is produced with the non-genetically modified Talaromyces versatilis strain PF8 by Erbslöh Geisenheim AG. The food enzyme was free from viable cells of the production organism. It is intended to be used in four food manufacturing processes. Dietary exposure to the food enzyme-total organic solids (TOS) was calculated to be up to 0.110 mg TOS/kg body weight (bw) per day in European populations. Genotoxicity tests did not indicate a safety concern. The systemic toxicity was assessed by means of a repeated dose 90-day oral toxicity study in rats. The Panel identified a no observed adverse effect level of 2229 mg TOS/kg bw per day, the highest dose tested, which when compared with the estimated dietary exposure resulted in a margin of exposure of at least 20,264. A search for homology of the amino acid sequence of the food enzyme to known allergens was made and four matches with respiratory or contact allergens were found. The Panel considered that the risk of allergic reactions upon dietary exposure cannot be excluded, but the likelihood is low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns, under the intended conditions of use.

Safety evaluation of the food enzyme endonuclease from the non-genetically modified Penicillium citrinum strain NP 11-15.

The food enzyme endonuclease (Aspergillus nuclease S1; EC 3.1.30.1) is produced with the non-genetically modified Penicillium citrinum strain NP 11-15 by Shin Nihon Chemical Co., Ltd. The food enzyme is free from viable cells of the production organism. It is intended to be used in the processing of yeast and yeast products. Dietary exposure to the food enzyme-total organic solids (TOS) was estimated to be up to 0.006 mg TOS/kg body weight (bw) per day in European populations. Genotoxicity tests did not indicate a safety concern. The systemic toxicity was assessed by means of a repeated dose 90-day oral toxicity study in rats. The Panel identified a no observed adverse effect level of 1010 mg TOS/kg bw per day, the highest dose tested, which when compared with the estimated dietary exposure, resulted in a margin of exposure of at least 168,333. A search for homology of the amino acid sequence of the food enzyme to known allergens was made and no match was found. The Panel considered that the risk of allergic reactions by dietary exposure cannot be excluded, especially for individuals allergic to Penicillium. However, the likelihood of such reactions will not exceed the likelihood of allergic reactions to Penicillium. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.

Safety evaluation of the food enzyme carboxypeptidase C from the genetically modified Aspergillus niger strain PEG.

The food enzyme carboxypeptidase C (EC 3.4.16.5) is produced with the genetically modified Aspergillus niger strain PEG by DSM Food Specialties B.V. The genetic modifications do not give rise to safety concerns. The food enzyme is free from viable cells of the production organism and its DNA. It is intended to be used in nine food manufacturing processes. Dietary exposure to the food enzyme-total organic solids (TOS) was estimated to be up to 2.053 mg TOS/kg body weight (bw) per day in European populations. The toxicity studies were carried out with a xylanase obtained from A. niger strain XEA. The Panel considered this food enzyme as a suitable substitute for the carboxypeptidase to be used in the toxicological studies, because both strains were derived from the same recipient strain, the location of the inserts was comparable, no partial inserts were present and the production methods were essentially the same. Genotoxicity tests did not raise a safety concern. The systemic toxicity was assessed by means of a repeated dose 90-day oral toxicity study in rats. The Panel identified a no observed adverse effect level of 1850 mg TOS/kg bw per day, the highest dose tested, which when compared with the estimated dietary exposure, resulted in a margin of exposure of at least 901. A homology search for the amino acid sequence of the food enzyme to known allergens was made and one match with a wheat allergen was found. The Panel considered that the risk of allergic reactions by dietary exposure cannot be excluded, especially in wheat-allergic individuals, but the likelihood is low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.

Re-evaluation of the reduced heart weights in male rats in a 28-day oral repeated-dose toxicity study of tetramethylammonium hydroxide

We recently conducted a detailed hazard assessment of tetramethylammonium hydroxide (TMAH), a priority chemical substance under the Japan Chemical Substances Control Law. During this assessment, there was debate regarding the reduced heart weight observed in the treated male groups in the 28-day rat oral repeated-dose toxicity study. This finding was not observed in females in this study and in both sexes of oral toxicity studies for tetramethylammonium chloride (TMAC) or tetramethylammonium hydrogen phthalate (TMAHP). Unpublished individual data from the oral TMAH developmental and reproductive toxicity (DART) screening study were also obtained; no effect on heart weight was observed. In addition, background data on rat heart weight from six 28-day oral toxicity studies conducted in the same facility, year, strain, age, and breeder as the TMAH study were obtained from the Japan Existing Chemical Substances Database (JECDB). These investigations suggest that the statistically significant lower heart weight in the treated males in the 28-day toxicity study is likely caused by an incidental skewing of individuals with heavier heart weights toward control male groups and is not due to TMAH treatment. Thus, it is worthwhile to include as much relevant data as possible to confirm or refute unexpected findings in toxicity studies.

Roflumilast-loaded nanostructured lipid carriers attenuate oxidative stress and neuroinflammation in Parkinson’s disease model

Parkinson’s disease (PD) is a progressive neurodegenerative disorder with limited symptomatic treatment options. Targeting phosphodiesterase 4 (PDE4) has shown a promising result in several preclinical studies. In our study, we aim to repurpose US FDA-approved PDE4 inhibitor for PD. Through in-silico study, we identified roflumilast (ROF) as the potential candidate targeting PDE4B2. In Drosophila PD expressing the A30P mutant α-synuclein model, ROF exhibited anti-PD effects as indicated by negative geotaxis and antioxidant activities. Given the low brain distribution of ROF (<50%) at clinical doses, incorporation into nanostructured lipid carriers (NLCs) was carried out to enhanced blood-brain barrier permeability. In vitro release studies indicated sustained ROF release from NLCs (≈75%) over 24 h. Single-dose oral toxicity studies reported no mortality or toxicity signs. ROF-loaded NLCs significantly alleviated behavioural deficits, increased antioxidant parameters (p < 0.05), and reduced TNF-α and IL-6 levels (p < 0.5) in the striatum compared to pure ROF. ROF-loaded NLCs demonstrated potential anti-PD effects with high efficacy than pure ROF. Our study suggests that nanostructured lipid carriers (NLCs) can be a promising drug delivery system to overcome limitations associated with poor brain bioavailability of lipophilic drugs like ROF for PD treatment. Further investigation related to brain occupancy and underlying mechanisms of our formulation is warranted to confirm and strengthen our current findings.

The effect of aging on the repeated-dose liver micronucleus assay using N-nitrosodipropylamine, quinoline, and carbendazim

The repeated dose liver micronucleus (RDLMN) assay has been sufficiently validated in terms of the numbers and types of chemicals studied. However, it remains unclear whether aging affects assay results. The OECD Test Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents) indicates that dosing should begin as soon as feasible after weaning and in any event before 9 weeks of age. Therefore, it is particularly important to determine whether there are age-related differences between 6 and 8 weeks of age at the start of dosing when considering the possibility of integrating this assay into a 4-week repeated dose general toxicity study. We evaluated the impact of the rats’ age on the RDLMN assay with three chemicals: N-nitrosodipropylamine, quinoline, and carbendazim. There were no significant age-related differences for the first two chemicals, whereas a markedly higher frequency of micronucleated hepatocytes (MNHEPs) was observed in younger rats for carbendazim. However, regardless of the age of animals, micronucleus induction was detected in all three chemicals. Combined with the previous reports on clofibrate and diethylnitrosamine, we concluded that animals of any age from 6 to 8 weeks could be used in the RDLMN assay.

PSIII-27 Blood biochemistry, histology, and metabolomic profiling of contaminated with mycotoxin: A repeated dose oral toxicity study in rats

Abstract Mycotoxins causes diseases and physiological responses in humans and livestock. This study was performed to estimate the effects of binary mixtures mycotoxin {e.g., deoxynivalenol (DON) and fumonisin (FB)] on blood biochemistry, histology, and metabolic profiles in rats fed with different toxin concentrations. Experimental animals were administered by oral gavage with 0.9% saline, DON (1, 5, and 10 mg/kg BW), FB (1, 5, and 10 mg/kg) at 8 wk of age. Histological changes, metabolomic profiling, and blood biochemical analysis were performed Masson’s trichrome stain kit, liquid chromatography mass spectrometry, and VetTest chemistry analyzer, respectively. The final BW of the rats contaminated with mixtures mycotoxin significantly decreased compared with the control group. Biochemistry results and fibrosis were also significantly differentially regulated according to mycotoxin concentrations. Additionally, we observed collagen fibers in the liver and kidney showed blue staining after toxin contamination. For metabolomic profiling, data were analyzed using MetaboAnalyst 4.0. Results were analyzed by multivariate analysis to elucidate the potential compounds. The toxin-treated groups observed discriminating metabolites in the liver and kidney tissue but no differences in ileum. The profiling revealed potential metabolites such as glycine, serine and threonine metabolism. Phosphatidylethanolamine and tryptophan were identified with high sensitivity as candidate biomarkers via variable importance in the projection plot in piglets fed with mycotoxin (FDR &amp;lt; 0.05; P &amp;lt; 0.05). The differently treated groups showed discriminating metabolites in different concentrations. In conclusion, these findings suggest that mycotoxin exposure disturbs histological changes and metabolites. Dietary toxins in rats may better understand the physiological effects consistent with metabolism, which are commonly reported in animals.

Bifidobacterium longum subsp. infantis YLGB-1496-Toxicological evaluation.

Bifidobacterium infantis YLGB-1496, originally isolated from breast milk from a Taiwanese mother, is under study for use as a probiotic. As part of safety assessment, an Ames, in vivo mouse micronucleus, and in vivo mouse spermatocyte chromosome aberration assay were conducted along with a 13-week oral rat toxicity study. B.infantis YLGB-1496 had no activity in any of the genotoxicity assays. Administration of the bacteria to Sprague-Dawley rats at doses ranging from 0 to 1.5 g/kg bw/day had no treatment-related effects on any of the endpoints measured. There appear to be no concerns for translocation or pathogenicity of B.infantis YLGB-1496 based on extensive experience with the species in general. The results of the current investigations support potential use of B.infantis YLGB-1496 as a probiotic in infant formula.

The subchronic toxicity of higher olefins in Han Wistar rats

Higher olefins (HO) are a category of unsaturated hydrocarbons widely used in industry applications to make products essential for daily human life. Establishing safe exposure limits requires a solid data matrix that facilitates understanding of their toxicological profile. This in turn allows for data to be read across to other members of the category, which are structurally similar and have predictable physico-chemical properties. Five independent subchronic oral toxicity studies were conducted in Wistar rats with Oct-1-ene, Nonene, branched, Octadec-1-ene, Octadecene and hydrocarbon C12-30, olefin-rich, ethylene polymn. by product, at doses ranging from 20 to 1000 mg/kg bw. These HO were selected considering gut absorption, carbon chain length, double-bond position and carbon backbone structural variations. Generally, limited and non-adverse toxicity effects were observed at the end of the treatment for short carbon chain HO. For instance, alpha 2u-globulin nephropathy in the male rats and liver hypertrophy. No clear trend in systemic toxicity was linked to the double-bond position. Key factors for hazard assessment include absorption, carbon chain length, and branching, with Nonene, branched, identified as the worst-case substance. Taken together, the no observed adverse effect level (NOAEL) of each HO in these subchronic studies was set at the highest dose tested.

Evaluation of Anti-Diabetic Activity of Galinosa parviflora in Diabetic Rats

Galinosa parviflora commonly known as Potato weed widely used in traditional system of medicine for the treatment of diabetes mellitus In the present study, Methanol extract of Galinosa parviflora (MEGP) leaves were subjected to phytochemical investigation and evaluated for antidiabetic activity in STZ induced diabetic rats. MEGP (100, 200 mg/kg) and Glibenclamide (5mg/kg) were administered orally in STZ (60mg/kg, i.p.) induced diabetic rats. In acute oral toxicity (OECD Guide line 423) study, administration of MEGP no mortality upto 1000 mg/kg was observed. OGTT, Fasting blood glucose level, body weight, plasma insulin, were evaluated in normal and diabetic rats. preliminary phytochemical investigation revealed the presence of alkaloids, flavonoids, glycosides, tannins as the major constituents in the methanol extract of Galinosa parviflora. These results suggest that MEGP (200mg/kg) showed antihyperglycemic activity in STZ induced diabetic rats.

Evaluations of the in vitro and in vivo antidiabetic activity of 70 % ethanolic fruit extracts of Rosa abyssinica

BackgroundDiabetes mellitus is becoming major health challenge with continually increasing burden. High costs of conventional medicines and numerous side effects associated with them, on the other hand, easy availability and accessibility of traditional herbal medicines calls upon experimental investigations to validate their effect on lowering blood glucose level. MethodsThe dried fruit of Rosa abyssinica was macerated with 70 % ethanol and the extract's in vitro antidiabetic activity was investigated using dinitrosalisylic acid method for alpha amylase inhibitory activity. Furthermore, the in vivo hypoglycemic and Antihyperglycemic effects of various doses of the extract (100, 200 and 400 mg/kg) was determined on normoglycemic, glucose loaded (1500 mg/kg) and Streptozotocine (180 mg/kg)-induced diabetic mice models. ResultsThe acute oral toxicity study revealed the plant showed no toxic effect on swiss albino mice at 2000 mg/kg. The in vitro alpha amylase inhibitory activity study showed that the extract has comparable IC50 value of 21.37 ± 4.252 μg/ml with the standard drug acarbose (IC50 value of 26.72 ± 3.59 μg/ml). On the other hand, in normal mice, none of the dose levels except at 400 mg/kg significantly reduces blood glucose level. This is in contrast to the oral glucose tolerance test, which the extract produced significant reduction at 60, 90 and 120 min following glucose challenge. The 70 % ethanolic fruit extracts of Rosa abyssinica also experienced profound antidiabetic activity in streptozotocin-induced diabetic model. In the single-dose study, both RAFE200 and RAFE400 demonstrated a significant (P˂0.05) reduction in blood glucose levels at 1, 2, 3, and 4 h. Similarly, in the repeated-dose study, RAFE200 and RAFE400 not only significantly reduced blood glucose levels but also produced a notable improvement in animal body weight. ConclusionThe 70 % ethanolic fruit extracts of Rosa abyssinica have shown significant in vitro alpha amylase inhibition effect and an in vivo blood glucose level lowering effects in diabetic mice.Therefore, this study supports the traditional use of Rosa abyssinica in the management of diabetes mellitus.

Airways Relaxant and Antiasthmatic Activity of Aconitum heterophyllum Wall ex Royle. Roots: A Mechanistic Insight.

Aconitum heterophyllum Wall ex Royle. (Ranunculaceae) is a traditional medicinal herb that has shown extensive pharmacological potential to treat cough, diarrhea, and infectious diseases but no scientific evidence is available to validate its antiasthmatic potential. In this study, we have investigated the tracheal relaxation and antiasthmatic activity of the selected bioactive fraction of A. heterophyllum. Chemical profiling of the most effective fraction obtained via bioassay-guided fractionation was done using LC-MS (Liquid chromatography-mass spectrometry, a technique utilized in the identification, separation, and quantification of known and unknown compounds). Molecular docking analysis of characterized constituents was performed to recognize the binding receptors, followed by an evaluation of the tracheal relaxation ability of active fraction. An acute oral toxicity study of the most effective fraction was done using OECD guidelines 423. Further, the therapeutic efficacy of the fraction was validated in asthma using a guinea pig model of ovalbumin (OVA) induced allergic asthma. The bio-guided activity revealed that hydro-methanolic extract of A. heterophyllum roots (F-1) was the most active fraction. LC-MS analysis of F-1 showed the presence of six major bioactive compounds in F-1. Molecular docking studies revealed strong binding affinities of identified constituents with histaminic receptor (H1) and muscarinic receptor (M3). The ex vivo study demonstrated smooth muscle relaxant activity of F-1 via dysregulating diverse signal transduction pathways viz. histaminic and muscarinic receptors antagonism (non-competitive), stimulation of β2-adrenergic receptor pathway, and soluble guanylyl cyclase activation. The findings of acute oral toxicity studies revealed that F-1 had no toxicity up to the dose of 2000 mg/Kg. The anti-asthmatic therapeutic efficacy of F-1 was further confirmed by the amelioration of respiratory hyperresponsiveness in asthmatic guinea pigs. This is the first evidence-based study showing the antiasthmatic therapeutic potential of the traditionally used herb A. heterophyllum through, computational and animal studies.