Acute Toxicity Study Research Articles

Ameliorated in vitro anti-cancer efficacy of methotrexate loaded zinc oxide nanoparticles in breast cancer cell lines MCF-7 & MDA-MB-231 and its acute toxicity study

Traditional therapies often struggle with specificity and resistance in case of cancer treatments. It is therefore important to investigate new approaches for cancer treatment based on nanotechnology. Zinc oxide nanoparticles (ZnONPs) are known to exhibit anti-cancer properties by inducing oxidative stress, apoptosis, and cell cycle arrest. Methotrexate (MTX) a known anti-folate shows specificity to folate receptors and interrupts healthy functioning of cells. This study proposes the use of previously characterized biocompatible Methotrexate loaded Zinc oxide nanoparticles (MTX-ZnONPs) as a dual action therapeutic strategy against breast cancer cell lines, MCF-7 (MTX-sensitive) and MDA-MB-231 (MTX-resistant). To elucidate the cytotoxicity mechanism of MTX-ZnONPs an in depth In vitro study was carried out. In vitro assays, including cell cycle analysis, apoptosis assay, and western blot analysis to study the protein expression were performed. Results of these assays, further supported the anti-cancer activity of MTX-ZnONPs showing apoptotic and necrotic activity in MCF-7 and MDA-MB-231 cell line respectively. In vivo acute oral toxicity study to identify the LD50 in animals revealed no signs of toxicity and mortality up to 550 mg kg−1 body weight of animal, significantly higher LD50 values than anticipated therapeutic levels and safety of the synthesized nanosystem. The study concludes that MTX-ZnONPs exhibit anti-cancer potential against breast cancer cells offering a promising strategy for overcoming resistance.

Bioproduction of yeast single cell oil with acute oral toxicity study intended for edible oil application.

Human nutrition and health rely on edible oils. Global demand for edible oils is expanding, necessitating the discovery of new natural oil sources subjected to adequate quality and safety evaluation. However, in contrast to other agricultural products, India's edible oil supply is surprisingly dependent on imports. The microbial oil is generated by fermentation of oleaginous yeast Rhodotorula mucilaginosa IIPL32 MTCC 25056 using biodiesel plant byproduct crude glycerol as a fermentable carbon source. Enriched with monounsaturated fatty acid, nutritional indices mapping based on the fatty acid composition of the yeast SCO, suggested its plausible use as an edible oil blend. In the present study, acute toxicity evaluation of the yeast SCO in C57BL/6 mice has been performed by randomly dividing the animals into 5 groups with 50, 300, 2000, and 5000mg/Kg yeast SCO dosage, respectively, and predicted the median lethal dose (LD50). Detailed blood biochemistry and kidney and liver histopathology analyses were also reported. The functions of the liver enzymes were also evaluated to check and confirm the anticipated toxicity. To determine cell viability and in vitro biocompatibility, the 3T3-L1 cell line and haemolysis tests were performed. The results suggested the plausible use of yeast SCO as an edible oil blend due to its non-toxic nature in mice models.

Acute and sub-chronic toxicity study of novel polyherbal formulation in non-alcoholic fatty liver using Wistar rats.

Aim: This study assessed the acute and sub-chronic toxicity of a novel polyherbal formulation tablet in Wistar rats Materials & methods: Acute toxicity and sub-chronic toxicity was assessed following OECD (Organisation for the Economic Co-operation and Development) guidelines based on 423 and 408. Results & conclusion: No mortality and toxicity showed in rats during acute toxicity. The LD50 of the extract was at 2000mg/kg. In sub-chronic study, both sex rats were orally administered at 250, 500,1000 and 2000mg/kg for 90days and revealed no significant difference (p<0.05) in hematological and other parameters compared with the control. Histopathology study did not reveal morphological alteration. The No observed adverse effect level of the tablet was observed until2000mg/kg.

Bioactive Components Analysis and Pharmacological Properties of Extracts and Metabolites of Lichen Umbilicaria crustulosa

Lichens, a diverse group of organisms, have a unique structure consisting of fungal filaments and photosynthetic partner cells. This research conducted a comprehensive chemical analysis and evaluation of the anti-inflammatory and antioxidant properties of methanolic and acetone extracts from Umbilicaria crustulosa lichen, along with its isolated metabolites. The process involved separating atranorin and chloratranorin fractions, physodic acid, and gyrophoric acid. Secondary metabolites were identified using chromatographic and spectroscopic data. The total polyphenols content was determined spectrophotometrically. This study examined the antioxidant activity of extracts of the lichen U. crustulosa and the isolated fractions using three methods: DPPH scavenging activity, ABTS scavenging activity, and reducing power. This study also evaluated the acute oral toxicity and the anti-inflammatory activity of the extracts in Wistar albino rats. A higher content of the total phenolic compounds was found in the acetone extract, but antioxidant and anti-inflammatory activities were more prominent in the methanolic extract. The isolated atranorin and chloratranorin fractions and compound physodic acid showed the highest antioxidant activity. No toxic effects were noted in the acute oral toxicity study. This study highlights the potential of the investigated lichen as a valuable source of novel biological agents.

Toxicity and speciation of inorganic arsenics and their adverse effects on in vivo endpoints and oxidative stress in the marine medaka Oryzias melastigma

Here, we investigate the effects of acute and chronic exposure to arsenate (AsV) and arsenite (AsIII) in the marine medaka Oryzias melastigma. In vivo effects, biotransformation, and oxidative stress were studied in marine medaka exposed to the two inorganic arsenics for 4 or 28 days. An investigation of embryonic development revealed no effect on in vivo parameters, but the hatching rate increased in the group exposed to AsIII. Exposure to AsIII also caused the greatest accumulation of arsenic in medaka. For acute exposure, the ratio of AsV to AsIII was higher than that of chronic exposure, indicating that bioaccumulation of inorganic arsenic can induce oxidative stress. The largest increase in oxidative stress was observed following acute exposure to AsIII, but no significant degree of oxidative stress was induced by chronic exposure. During acute exposure to AsV, the increase in the enzymatic activity of glutathione-S-transferase (GST) was twice as high compared with exposure to AsIII, suggesting that GST plays an important role in the initial detoxification process. In addition, an RNA-seq–based ingenuity pathway analysis revealed that acute exposure to AsIII may be related to cell-cycle progression. A network analysis using differentially expressed genes also revealed a potential link between the generation of inflammatory cytokines and oxidative stress due to arsenic exposure.

ACUTE AND SUB-ACUTE TOXICOLOGICAL STUDY OF VANGA BHASMA

Introduction: Vanga is a dhatu, that has been used externally since the Samhita period. During the rasa shastra era, vanga was utilized internally for Prameha, (urinary disorder ) Medoroga(diseases of medadhatu – fat tis-sue), Kapha Vikaras(diseases of kapha-bodily constitution ), and other purposes after Bhasmikara-na.(preaparation of Bhasma - medicine ) Objective: Evaluate Acute and Sub-acute toxicity of Vanga Bhasma. Materials &amp;Methods: The acute and sub-acute toxicity studies of Vanga Bhasma were carried out on Wistar Albino rats using 425 and 407 OECD guidelines, respectively. Acute oral toxicity study of the test drug was car-ried out at the limit dose of 2000 mg/kg orally in rats. In a sub-acute toxicity study, Vanga bhasma was adminis-tered to rats for 28 consecutive days at doses of 22.5(TED-therapeutic equivalent dose), 112.5(TEDX5), and 225 mg/kg(TEDX10). The effects of the drug were assessed on haematological, biochemical, histological, and pon-deral parameters. Results: Acute toxicity: the study showed the LD 50 value of Vanga Bhasma is greater than 2000mg/kg. Sub-acute toxicity: this study did not produce any signs or symptoms of toxicity at TED, TEDX5, and TEDX10. Conclusion: The single dose of 2000mg/kg body weight evaluated by acute toxicity study is proved to be non-toxic. Overall analysis reveals that test drug vanga bhasma is very well tolerated at rat human therapeutic equivalent dose and multiples of it. Therefore, Vanga bhasma, prepared and administered in accord-ance with customary protocols, is safe to consume at therapeutic dose levels.

Evaluation of Neuroprotective effect of Cassia occidentalis L. against Colchicine Induced Memory Impairment in Wistar Rats

Background: Alzheimer’s disease (AD) is a progressive neurological disorder that develops with aging. Objective: In this research, we have examined the anti - Alzheimer’s effect of ethanolic extract from roots of Cassia occidentalis L. on colchicine-induced Alzheimer’s in Wistar rats Methods: Ethanolic extract was obtained and spectroscopic, chromatography analysis was performed. Acute toxicity studies using Organization of Economic Co-operation and Development (OECD) Guidelines 423 were performed to examine and make sure that there were no signs of toxic effects. The induction of AD was done using colchicine which leads to symptoms like neurotoxicity, neuroinflammation, and neurodegeneration. In this experiment, a thorough analysis of body weight, behavioral parameters, locomotor activity, and biochemical evaluation was performed to estimate the medicinal properties of Cassia occidentalis L in treating Alzheimer’s disease. Results: Pharmacognostic analysis showed the presence of vascular bundles, starch grains, fibers, calcium oxalate crystals, elongated parenchyma, and collenchyma mucilage as shown in the supplementary files. Locomotor activity, Escape latency time, Conditioned avoidance response, and Transfer latency were improved with treatment. Interleukin- 6 (IL - 6) levels were reduced significantly in the Colchicine + 200 Cassia mg/kg group (739.2 ± 0.37 pg/ml) than in the Colchicine Group (850.6±0.40 pg/ml). Tumor necrosis factor (TNF-α) was decreased in the Colchicine + 200 Cassia mg/kg Group (1030.93±0.51 pg/ml) than in the Colchicine Group (1455.06±1.25 pg/ml). A significant decrease in total protein level was observed in the Colchicine Group (2.52±0.10 mg/ml), (3.33±0.90 mg/ml) as compared to Colchicine + 200 Cassia mg/kg Group (5.27±0.09 mg/ml, (5.01±0.10 mg/ml) respectively, in the Hippocampus and Entorhinal cortex. The levels of antioxidant enzymes such as Catalase (CAT), Serum superoxide dismutase (SOD), Reduced glutathione (GSH) and Malondialdehyde (MDA) were measured. When compared to the Colchicine Group (7.33±0.16 nM/ mg, the MDA level was lower in the Colchicine + 100 Cassia mg/kg Group (3.20±0.01 nM/ mg). The level of CAT in Colchicine + 200 Cassia mg/kg Group (7.01±0.03 μmoles of H2O2/mg of protein) was seen to be increased when compared to Colchicine Group (3.32 ± 0.17 μmoles of H2O2/mg of protein). The level of SOD in Colchicine + 200 Cassia mg/kg Group (7.43±0.02 U mg -1 of protein) was seen to be increased when compared with Colchicine Group (4.55±0.03 U mg -1 of protein). The level of GSH in Colchicine + 200 Cassia mg/kg Group (10.07±0.19 nM/mg -1 of protein) was increased when compared with the Colchicine Group (5.82±0.11nM/mg -1 of protein). Histopathology of the Hippocampus and Entorhinal cortex showed diminished amyloid plaques, and neurodegeneration in the treatment groups Conclusion: The present study showed that ethanolic extract from the roots of Cassia occidentalis L. At 100 and 200 mg/kg doses in Wistar rats improved memory damage, by reducing oxidative stress. Levels of the antioxidant enzymes as CAT, and SOD, GSH were increased and MDA was decreased. The cytokine levels in the serum of Wistar rats of IL-6 level and TNF-α level were reduced significantly. Estimation of total protein level was found to be increased. It restored neuronal degeneration in the Hippocampus, and Entorhinal cortex and reduced oxidative stress. This suggests that the ethanolic extract of Cassia occidentalis L. could be an effective therapeutic treatment for neurodegenerative diseases like AD.

Cell based and In vivo systematic evaluation of some Egyptian plant extracts targeting breast cancer

The prevalence of breast cancer as a significant public health concern necessitates continued exploration of natural resources for novel anti-cancer agents is crucial. Material and methodsAnticancer activity of plant extracts on monolayer breast cancer cell line (MCF7) with lower levels of toxicity towards normal (RPE1) underwent further assessment using a three-dimensional model (3D). The extract's effects were investigated through multiple assays including apoptosis induction using quantifying cleaved cytokeratin-18 (CK18) and DNA fragmentation. Additionally, the expression of Bcl-2 and Bax was quantitative using real-time PCR. The median lethal dose (LD50) was determined by the acute oral toxicity, while biomarkers associated with tumorigenesis, metastasis, and cell death were quantified by ELISA. ResultsLimoniastrum monopetalum and Bauhinia variegata exhibited the most potent antitumor efficacy among the investigated extracts. They demonstrated potent cytotoxicity against MCF7 with no significant effect on hTERT RPE-1, with an IC50 of 100 μM. The extract demonstrated effectiveness in killing cancer cells within 3D tumor-like structures, induced apoptosis through caspase-3 activation and cleavage of cytokeratin-18, up-regulated the tumor suppressor p53, down-regulated the anti-apoptotic Bcl-2 gene, and caused DNA fragmentation. Acute oral toxicity studies in mice indicated low toxicity, and in a syngeneic mouse tumor model, the extract significantly inhibited tumor growth, suggesting its potential for further development. ConclusionLimoniastrum monopetalum and Bauhinia variegata exhibited the most potent antitumor efficacy among the investigated extracts.

ASSESSING THE SAFETY PROFILE OF POLYMERS IN TRANSDERMAL MICRONEEDLE PATCH FABRICATION: INSIGHTS FROM AN ACUTE TOXICITY STUDY

The acute toxicity study is a crucial component of preclinical toxicology assessments conducted to evaluate the potential adverse effects of a substance or compound on albino rabbits. This study provides key findings and implications of an acute toxicity study of natural and synthetic polymers that are used in the preparation of transdermal microneedle patches (TMNPs) for sustained delivery of doxazocin mesylate. In this study, we divided the albino rabbits into three equal groups (n = 6). Group-I was labeled as a control group and group-II was treated with TMNPs-1 (HPMC, maltose) and group-III was treated with TMNPs-2 (PLGA, polyvinyl acetate). The results obtained from feed consumption, hematology profile, biochemical studies, vital organ weight, and histopathological changes in vital organs were compared with the control group, and proved the safety profile of the polymers involved in the fabrication of microneedle patches. Mechanical strength and dermal safety study established the facts about the safety of microneedle patches and potential risks to health as a carrier system for the delivery of drugs into the systemic circulation directly.

Pilot and Acute Toxicity Studies on Sodium Chloride Administered Orally in WistarRats

No Abstract

Study the hepatoprotective effect of the methanolic extract of Plumbago auriculata Lam. against CCl4-induced hepatocyte damage in mice

The liver is an important organ in the body; its diseases are considered the major causes of morbidity and mortality around the world. Hepatotoxic chemicals cause damage to liver cells. Medicinal plants have a powerful hepatoprotective effect. This study has been aimed to assess the potential hepatoprotective effect of the methanolic extract of Plumbago auriculata Lam. against carbon tetrachloride (CCl4)- induced hepatocyte damage in albino mice. The methanolic extract of the plant was subjected to preliminary phytochemical analysis to determine the presence of secondary metabolites according to standard protocols. The acute toxicity study was carried out to measure the LD50. Swiss albino mice were divided into 4 groups treated intraperitoneally (IP) once daily for 7 days; the first group was a negative control, while the second group, considered as a CCl4 model, received a single dose of carbon tetrachloride during the last day. The third group received 500 mg/kg of body weight of methanolic extract of P. auriculata, and the last group received 100 mg/kg of body weight of standard silymarin, after 2 h of treatment, on the last day, all animals (except negative control group) have received CCl4 at a dose of 1 mL/kg of body weight. Biochemical analysis of collected blood and histopathological examination were performed. Results revealed that the preliminary phytochemical screening of the methanolic extract of the plant confirmed the presence of many biologically active secondary metabolites like flavonoids, steroids, terpenoids, saponins, glycosides and phenols and LD50 of the extract was 2.5 g/kg. The CCl4- intoxicated mice showed an increase in biochemical enzyme levels (ALT and AST) compared with the negative control group. The extract of 500 mg/kg revealed a significant reduction (p ? 0.05) in enzyme activities. The histopathological analysis of plant extract and silymarin-treated groups revealed a decrease in the pathological features compared with the CCl4-intoxicated group. It was concluded that the extract of P. auriculata has a significant effect on hepatoprotection against CCl4-induced hepatocyte damage and this may be because of the combined effects of the bioactive compositions of plant extract.

TOXICOLOGICAL EVALUATION OF OLEANOLIC ACID (PENTACYCLIC TRITERPENOID) EXTRACTED FROM LANTANA CAMARA ROOTS FOLLOWING ORAL EXPOSURE IN WISTAR RATS

Objective: The aim of the present study was to perform an acute toxicity study to obtain information on the possible adverse effects from a single oral administration of Oleanolic acid in Wistar rats as the onset of toxicity, and to determine the range of exposure (to the LD50 cut-off criteria). Following a sub-chronic 90-days Repeated toxicity study by oral route to determine any potential indication of its dose response relationship and determine no observed effect level (NOEL)/ no-observed adverse effect level (NOAEL)/ low observed effect level (LOEL)/ low observed adverse effect level (LOAEL). Methods: A dose level of 2000mg/kg body weight was employed as step one for single acute study. Based on the survival pattern of the previously dosed animals after 48 hours, same dose 2000 mg/kg body weight) was repeated for Step 2 as a confirmatory test. For the 90-day toxicity study, the highest dose was determined as 1000mg/kg Body weight, and the middle and lower doses were 500 and 250mg/kg Body weight respectively. The rat group was held for a 14-day recovery period after the last dose administration, to observe for any persistence or reversal of toxic effects. Results: Results of the acute toxicity study showed no mortality on the dose level of 2000mg/kg body weight with no significant clinical and body weight changes. During the 90-day Repeated dose oral sub-chronic toxicity study, no rats died. There were no significant clinical changes related to the test item in terms of functional evaluation, body weight, food and water consumption, ophthalmological tests, urine analysis, necropsy findings, or organ weight, Hematology, and biochemistry at the highest dose level of 1000 mg/kg bwt. Conclusion: It is concluded that LD50 Cut-off Value of “Oleanolic acid” in from acute oral toxicity study in Wistar Rats is 2000 mg/kg b.wt. In addition, 90 days study have showed no significant changes with respect to any hematological or blood chemical analyses in 1000, 500 and 250 mg/kg bwt groups. Based on histopathological findings, clinical signs and other parameters, it may be concluded that upon repeated once oral administration for consecutive 90 days, the Oleanolic acid (Pentacyclic Triterpenoid) extracted from Lantana camara roots at the dose level of 1000 mg/kg body weight have caused no adverse effect in both sexes of Wistar Rats.

ACUTE ORAL TOXICITY OF TOFACITINIB CITRATE IN WISTAR RATS: IMPLICATIONS FOR NOVEL MOUTH DISSOLVING FORMULATIONS

Objective: Tofacitinib citrate is a commonly used therapeutic agent for various diseases. Mouth-dissolving formulations provide potential benefits for patient compliance. This study aims to evaluate the acute oral toxicity of tofacitinib citrate in these formulations to ensure their safety and efficacy. Methods: This study aimed to assess the acute oral toxicity of tofacitinib citrate in mouth-dissolving formulations and evaluate its effects on food and water consumption, hematological and biochemical parameters, and organ histopathology. Male and female Wistar rats were divided into four groups. The control group received distilled water, while the treated groups were orally administered tofacitinib citrate at 5 mg/kg, 100 mg/kg, and 300 mg/kg. Observations were made over 14 d, assessing general appearance, behavior, food and water consumption, and mortality. Hematological and biochemical analyses and histopathological examinations were conducted on vital organs. Results: In acute toxicity studies, Wistar rats showed no toxicity at up to 300 mg/kg tofacitinib citrate. Compared to controls, food/water intake and hematological, biochemical, and histopathological parameters of major organs remained unchanged, indicating no systemic effects and affirming the compound's safety in mouth-dissolving formulations. Conclusion: Tofacitinib citrate in mouth-dissolving formulations demonstrated a favorable safety profile with no acute oral toxicity. Normal consumption, unchanged parameters, and no organ abnormalities support its safety. Further investigation is required to assess chronic toxicity and long-term safety.

EVALUATION OF ACUTE AND SUB-ACUTE TOXICITY OF METHANOLIC LEAF EXTRACT OF BAMBUSA VULGARIS ON MALE WISTAR RATS

Objectives: The study aims to evaluate the potential toxicity of methanolic extract of leaves of Bambusa vulgaris in male Wistar rats. Methods: The methanolic extract was prepared for acute and sub-acute toxicity to determine the lethal dose. During the acute toxicity study, male rats were orally administered with leaf extracts at single doses of 100, 500,800, and 2000 mg/kg according to OECD Guidelines 425 for 14 days. Sub-acute toxicity dose at 200, 400, and 800 mg/kg was studied by daily dosing on male rats for 30 days. Results: The acute toxicity study revealed no lethal effects and behavioral signs of toxicity at the tested doses indicating that LD50 is &lt;2000 mg/kg. In a sub-acute study, non-significant changes in the body weight (p&lt;0.05), body weight gain percentage (p&lt;0.05) food intake (p&lt;0.05), and relative organ weight percentage (p&lt;0.05), and hematological parameters (p&lt;0.05) of the rats were observed. A significant (p&lt;0.05) increase in ALT level was observed dose at 800 mg/kg. Histopathological analysis showed mild cell distortion in the liver and kidney in male rats treated at 800 mg/kg of extract. Conclusion: Our study suggests that oral administration of methanolic leaf extract Bambusa vulgais is safe. However, a dose of 800 mg/kg may be toxic for the liver and kidney.

Bioassay-guided isolation of anti-inflammatory and antinociceptive metabolites among three Moroccan Juniperus leaves extract supported with in vitro enzyme inhibitory assays

Ethnopharmacological relevanceHerbs of the genus Juniperus (family Cupressaceae) have been commonly used in ancestral folk medicine known as “Al'Araar” for treatment of rheumatism, diabetes, inflammation, pain, and fever. Bioassay-guided isolation of bioactives from medicinal plants is recognized as a potential approach for the discovery of novel drug candidates. In particular, non-addictive painkillers are of special interest among herbal phytochemicals. Aim of the studyThe current study aimed to assess the safety of J. thurifera, J. phoenicea, and J. oxycedrus aqueous extracts in oral treatments; validating the traditionally reported anti-inflammatory and analgesic effects. Further phytochemical investigations, especially for the most bioactive species, may lead to isolation of bioactive metabolites responsible for such bioactivities supported with in vitro enzyme inhibition assays. Materials and methodsFirstly, the acute toxicity study was investigated following the OECD Guidelines. Then, the antinociceptive, and anti-inflammatory bioactivities were evaluated based on chemical and mechanical trauma assays and investigated their underlying mechanisms. The most active J. thurifera n-butanol fraction was subjected to chromatographic studies for isolating the major anti-inflammatory metabolites. Moreover, several enzymatic inhibition assays (e.g., 5-lipoxygenase, protease, elastase, collagenase, and tyrosinase) were assessed for the crude extracts and isolated compounds. ResultsThe results showed that acute oral administration of the extracts (300–500 mg/kg, p. o.) inhibited both mechanically and chemically triggered inflammatory edema in mice (up to 70% in case of J. thurifera) with a dose-dependent antinociceptive (tail flick) and anti-inflammatory pain (formalin assay) activities. This effect was partially mediated by naloxone inhibition of the opioid receptor (2 mg/kg, i. p.). In addition, 3-methoxy gallic acid (1), quercetin (2), kaempferol (3), and ellagic acid (4) were successfully identified being involved most likely in J. thurifera extract bioactivities. Nevertheless, quercetin was found to be the most potent against 5-LOX, tyrosinase, and protease with IC50 of 1.52 ± 0.01, 192.90 ± 6.20, and 399 ± 9.05 μM, respectively. ConclusionJ. thurifera extract with its major metabolites are prospective drug candidates for inflammatory pain supported with inhibition of inflammatory enzymes. Interestingly, antagonism of opioid and non-opioid receptors is potentially involved.

Technology of dry extract from the &lt;i&gt;Filipendula ulmaria&lt;/i&gt; (L.) Maxim. and preliminary assessment of its safety profile

Introduction. Medicines of natural origin have advantages over synthetic drugs and occupy a significant share in the assortment of pharmacies. Filipendula ulmaria (L.) Maxim., characterized by a chemical composition rich in phenolic compounds and various types of biological activity has the potential in terms of the development of new herbal medicines. In an in vivo experiment, F. ulmaria extract showed immunomodulatory, anti-inflammatory, osteogenic activity and effectively stimulated myelopoiesis in conditions of microbial damage of bone tissue.Aim. Development of an optimal technology for obtaining dry extract of F. ulmaria by remaceration and investigation of its аcute toxicity.Materials and methods. The technology of extract was developed in a laboratory reactor equipped with a water heater jacket and a stirrer. The content of flavonoids was determined by differential spectrometry. Flowability was determined on a flowability tester for powders and granules, bulk density was determined on a bulk density tester for powders and granules, moisture content was developed on a moisture content analyzer. Acute toxicity was determined on Wistar rats.Results and discussion. The dry extract of F. ulmaria, obtained using 70 % ethanol by remaceration, is effective in conditions of microbial damage of bone tissue and bone marrow, which determined the choice of extragent and the type of extract. The optimal parameters for obtaining the extract were determined (three-fold maceration at a water jacket temperature of 80 °C, the ratio of raw materials to extragent 1 : 14, time 30 min), its main technological characteristics were determined and a wet granulation method for improving them was proposed. In the study of acute toxicity of the extract, according to the results of toxicometry for 14 days after administration and necropsy data, the studied extract was classified as low-toxic substance.Conclusion. The dry extract of F. ulmaria, obtained by remaceration using 70 % ethanol, has specific activity in conditions of microbial damage to bone tissue. Optimal extraction parameters allow to increase the yield of target components, it is advisable to improve the technological parameters of the extract by wet granulation. The assessment of the safety profile of the dry extract from F. ulmaria, along with its high biological activity, provides a perspective for its further study and implementation into medical practice.

In-Vivo Anti-Malarial Activity of 80% Methanol Leaf Extract of Croton Dichogamus Pax and Ehretia Cymosa Thonn in Plasmodium Berghei Infected Mice.

Malaria is causing high mortality and morbidity due to Plasmodium's resistance to currently available anti-malarial drugs and mosquito's resistance to insecticides. Thus, there is a critical need to search for novel anti-malarial drugs from natural sources. Therefore, this study investigated in vivo antimalarial activities of two Ethiopian medicinal plants, Croton dichogamus Pax and Ehretia cymosa Thonn, in Plasmodium berghei infected Swiss albino mice. Soxhlet extraction method using 80% methanol as a solvent was used to prepare crude extracts of the two plants. Acute oral toxicity and 4-day suppressive in vivo antimalarial activity tests were performed on healthy female mice and P. berghei infected male mice, respectively. Antimalarial activity of the crude extracts at doses of 100, 200, and 400 mg/kg and the standard drug, chloroquine were used to assesse in Plasmodium berghei infected Swiss albino mice. Parasitemia level, packed cell volume, body weight, and rectal temperature of the mice were determined before infection (day 0) and after treatment (day 4). Survival time was determined by recording the date on which the mice died, considering the date of infection as day 0. The recorded data were analyzed using ANOVA and SPSS version 24. The result of the acute toxicity study revealed that the crude extracts were non-toxic at doses up to 2 g/kg. The extract of E. cymosa suppressed parasitemia level by 66.28, 63.44 and 63.14% at 400, 200, and 100mg/kg, levels while C. dichogamus extract suppressed parasitemia level by 45.29% at a dose of 400mg/kg. The remaining two dose levels of C.dichogamus extract suppressed parasitemia level by < 30%. C. dichogamus and E. cymosa showed anti-plasmodial activities. E. cymosa exhibited a more pronounced anti-plasmodial effect than C. dichogamus. The activities of both plants observed in this study support their traditional use as antimalarial drugs. Further studies on these plants using solvent fractions are required to identify their active ingredients.

STUDY OF KAJJALIKODAYA MALAHARA FOR EVALUATION OF WOUND HEALING ACTIVITY

Introduction: Kajjalikodaya malahara, mentioned in the Rasatarangini text, is indicated in different types of wounds like chronic wounds and fistula in ano, which did not respond to other treatment modalities. So, this formulation was selected for the present study. Material and methods: The Kajjalikodaya malahara prepared as per reference -anagni (without fire) and also modified version- agni siddha (with fire) method and subjected for antimicrobial, acute dermal toxicity studies and also screened for wound healing efficacy in excision and incision wound healing models. Results: The trial drug prepared by both methods was found safe in an antimicrobial study and did not reveal any acute dermal toxic conditions. In excision and incision wound healing model showed better therapeutic efficacy. Conclusion: Both formulations were efficient in the wound healing model’s study. Compared to a modified version of the agni siddha test drug, classically prepared anagni siddha was better in therapeutic efficacy.

Prospects for the use of medicinal plants extracts (Mallotus oppositifolius and Kalanchoe crenata) as antimicrobials against salmonellosis in poultry

This study is a contribution to the search for alternatives to combat antibiotic resistance in Salmonella strains in poultry farming. The objective of this work is to highlight the main phytochemical compounds of 2 Ivorian medicinal plants (Mallotus oppositifolius and Kalanchoe crenata) and to evaluate their acute oral toxicity with a view to their use in the poultry sector, to fight against certain avian pathologies, including Salmonellosis. The phytochemical compounds of the different extracts of the plants used in this study were highlighted by colouring and precipitation methods. Acute oral toxicity was adapted to broilers according to the guideline OECD 425, 2008. This experimental study, which is the very first adapted to broiler chickens, was carried out with the agreement of the National Ethics Committee for Life and Health Sciences. The phytochemical screening carried out showed that each of these three antibacterial extracts possesses at least the major phytochemical groups sought. At the end of the acute oral toxicity study, no mortality was observed and the biochemical analysis of the subjects' blood showed creatinine values ​​≤ 10 mg/L.; aspartate aminotransferase (ASAT) ≤ 275 IU/L; alanine aminotransferase (ALT) ≤ 50 IU/L, urea=0.01g/L, CRP≤6 mg/L; and blood sugar was between 2 and 5 g/L in subjects from different batches. Ultimately, the aqueous and ethanolic extracts of Mallotus oppositifolius and the ethanolic extract of Kalanchoe crenata can be used as an antibacterial in broiler farming.

Subacute toxicity of isoliquiritigenin-zein phosphatidylcholine nanoparticles on biochemical, hematological, and histopathological parameters in Sprague-Dawley rats

Aim: Isoliquiritigenin (ISL) is a natural flavonoid found in many natural plants, which exhibits numerous pharmacological properties including anti-inflammatory, antioxidant, antitumor, and antiviral activities. However, the low bioavailability and stability of ISL limit its application in clinical practice. To overcome these limitations, ISL-zein phosphatidylcholine hybrid nanoparticles (ISL@ZLH NPs) have been developed to improve the bioavailability and stability of ISL. The present study aimed to evaluate the acute and subacute toxicity of ISL@ZLH NPs in Sprague-Dawley (SD) rats. Methods: The ISL@ZLH NPs were prepared by the solvent evaporation method. The acute toxicity was evaluated by administering a single dose of 110 mg/kg and 160 mg/kg of ISL@ZLH NPs extracted in distilled water via oral gavage in rats and mice, respectively. The subacute toxicity was evaluated by administering doses of 27.5 mg/(kg∙day), 55 mg/(kg∙day), and 110 mg/(kg∙day) of ISL@ZLH NPs for 30 days and 90 days. The biochemical, hematological, and histopathological parameters were analyzed in both studies. Results: In the acute toxicity study, no mortality or significant changes in the biochemical and hematological parameters were observed in both Kunming (KM) mice and SD rats. In the subacute toxicity study, no toxic reactions were observed in both species at all doses tested. Moreover, no significant changes in the biochemical, hematological and histopathological parameters were observed in both species. Conclusions: The results of this study suggest that ISL@ZLH NPs are safe and non-toxic in both KM mice and SD rats. The nanoparticles (NPs) did not induce any adverse effects on the biochemical, hematological, and histopathological parameters in both acute and subacute toxicity studies. These results indicate that ISL@ZLH NPs are safe for prolonged consumption. Further studies are needed to evaluate the long-term toxicity and efficacy of these NPs in vivo.