Evaluation of the toxicological effects of Neltuma alpataco (Prosopis alpataco) pod alkaloid extract.

The pods of Neltuma spp. have shown potential as a source of protein and energy in livestock. However, prolonged consumption of some of these species can lead to neurological symptoms in ruminants. This study aimed to determine the alkaloid content, as well as the in vitro and in vivo effects of an alkaloid-enriched extract (AEE) from N. alpataco pods. High performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS) identified juliprosine and juliprosopine as primary alkaloids, with juliprosine being most abundant. AEE from N. alpataco demonstrated dose-dependent cytotoxicity on glioma cells after 48 h, with a 50% cytotoxic concentration (CC50) of 24.69 µg/mL. However, the release of LDH was observed only at the highest tested concentration, indicating cellular damage. Further examination through phase-contrast microscopy and dual acridine orange/ethidium bromide fluorescence staining revealed morphological changes consistent with an apoptotic mechanism of cell death, ultimately leading to secondary necrosis. Finally, the LD50 after intraperitoneal injection in mice was determined to be 12.98 mg/kg. Taken together, these findings demonstrated for the first time the in vivo and in vitro toxicity of the AEE from N. alpataco pods.

Acute and subacute toxicological evaluation of the ethanol leaf extract of Morus mesozygia stapf. (Moraceae) in rodents.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditionally, the Morus mesozygia tree leaf has been used to manage maladies such as peptic ulcer, hyperglycemia, dermatitis, rheumatism, stomach-ache, arthritis, cough, malignancies, and malaria in parts of Africa. AIM OF THE STUDY: The study aimed to evaluate the potential of ethanol leaf extract of Morus mesozygia (EEMm) to induce toxicity by employing both acute and sub-acute oral toxicity experimental models. MATERIAL AND METHODS: The extract's cytotoxicity was studied using brine shrimps (Artemia salina) lethality assay (BSLA), while in the acute toxicity test, male and female mice were administered a single oral dose of EEMm (2000 mg/kg). Male and female Wistar rats received repeated doses of 100 or 500 mg/kg EEMm orally for 28 days in the sub-acute toxicity experiment. The phytochemical analysis of EEMm was done using the HPLC. RESULTS: The BSLA revealed a moderate cytotoxic potential of the extract, with an LC50 of 567.13 ± 0.27 µg/mL. All the animals survived the acute toxicity test, with no significant changes in the relative organ weights, suggesting that LD50 is greater than 2000 mg/kg. The animal weights did not vary significantly in the sub-acute toxicity test neither were the alterations in biochemical and hematological tests pronounced, although the histoarchitectures of the kidney, liver and spleen indicated slight anomalies in the evaluated animals. The HPLC analysis revealed the presence of quercetin, ferulic acid, rutin, caffeic acid, morin and gallic acid. CONCLUSIONS: Ethanol leaf extract of Morus mesozygia demonstrated a safe toxicity profile in rodents, supporting its broad folkloric use in African ethnomedicine.

Venom extraction method influences venom composition and potency in the giant house spider Eratigena atrica (C. L. Koch, 1843).

Extraction is the first step when investigating venom composition and function. In small invertebrates, widely used extraction methods include electrostimulation and venom gland extraction, however, the influence of these methods on composition and toxicology is poorly understood. Using the Giant House Spider Eratigena atrica as a model, we show that electrostimulation and venom gland removal extraction methods produce different protein profiles as assessed by Coomassie-stained SDS-PAGE and significantly different potencies in the cricket Acheta domesticus.

Acute and sub-acute toxicity study reveals no dentrimental effect of formononetin in mice upon repeated i.p. dosing.

AIM: Formononetin is a phytoestrogen which possess different pharmacological activities. The intraperitoneal route permits the identification of target organs involved in toxicity without compromising the molecule's bioavailability. The current study investigated the safety profile of intraperitoneal formononetin in Swiss albino mice. MATERIAL AND METHODS: For acute toxicity study, formononetin administered intraperitoneally to mice at the doses of 5, 50, 100, 150, 200, and 300 mg/kg for 14 days. For the subacute toxicity study, mice were intraperitoneally administered with formononetin (12.5, 25, and 50 mg/kg) daily for 28 days. RESULTS: During the acute study, no deteriorating effect was observed on body weight, food and water intake, no behavioral changes were observed in animals. The lethal dose 50% (LD50) of formononetin was determined to be 103.6 mg/kg of BW, with a no observed adverse effect level (NOAEL) of 50 mg/kg of BW. Mortality was observed in the 300 mg/kg dose group and histopathological changes such as a mild degree of diffuse granular degeneration in the liver but for rest all doses did not have any adverse effect. In subacute study, no signs of adverse effects, mortality, no changes in body weight, food and water intake, and hematological and biochemical parameters were observed. Histopathology of subacute study indicates, formononetin did not have any noxious effect on organs. CONCLUSION: Formononetin shows mortality at acute dose 300 mg/kg and LD50 at 103.6 mg/kg of BW, with a NOAEL of 50 mg/kg of BW, rest all doses for acute and sub-acute are safe when given intraperitoneally.

Multi-ligand molecular docking, simulation, free energy calculations and wavelet analysis of the synergistic effects between natural compounds baicalein and cubebin for the inhibition of the main protease of SARS-CoV-2.

Combination drugs have been used for several diseases for many years since they produce better therapeutic effects. However, it is still a challenge to discover candidates to form a combination drug. This study aimed to investigate whether using a comprehensive in silico approach to identify novel combination drugs from a Chinese herbal formula is an appropriate and creative strategy. We, therefore, used Toujie Quwen Granules for the main protease (Mpro) of SARS-CoV-2 as an example. We first used molecular docking to identify molecular components of the formula which may inhibit Mpro. Baicalein (HQA004) is the most favorable inhibitory ligand. We also identified a ligand from the other component, cubebin (CHA008), which may act to support the proposed HQA004 inhibitor. Molecular dynamics simulations were then performed to further elucidate the possible mechanism of inhibition by HQA004 and synergistic bioactivity conferred by CHA008. HQA004 bound strongly at the active site and that CHA008 enhanced the contacts between HQA004 and Mpro. However, CHA008 also dynamically interacted at multiple sites, and continued to enhance the stability of HQA004 despite diffusion to a distant site. We proposed that HQA004 acted as a possible inhibitor, and CHA008 served to enhance its effects via allosteric effects at two sites. Additionally, our novel wavelet analysis showed that as a result of CHA008 binding, the dynamics and structure of Mpro were observed to have more subtle changes, demonstrating that the inter-residue contacts within Mpro were disrupted by the synergistic ligand. This work highlighted the molecular mechanism of synergistic effects between different herbs as a result of allosteric crosstalk between two ligands at a protein target, as well as revealed that using the multi-ligand molecular docking, simulation, free energy calculations and wavelet analysis to discover novel combination drugs from a Chinese herbal remedy is an innovative pathway.

Chemical Composition and Bioinsecticidal Effects of Thymus zygis L., Salvia officinalis L. and Mentha suaveolens Ehrh. Essential Oils on Medfly Ceratitis capitata and Tomato Leaf Miner Tuta absoluta.

The present work was aimed to study the toxicity of the essential oils of three aromatic and medicinal plants on the tomato leaf miner Tuta absoluta and the Medfly Ceratitis capitata as an alternative to conventional pesticides. We carried out a phytochemical and insecticide study of T. zygis L., S. officinalis L. and M. suaveolens Ehrh. essential oils (EOs) through the study of their chemical composition and their toxicity on C. capitata adults and T. absoluta larvae. The extraction of the EOs by hydrodistillation showed yields of 3.87 ± 0.03, 4.09 ± 0.23 and 4.35 ± 0.11 for T. zygis, S. officinalis L. and M. suaveolens Ehrh., respectively. The identification of the chemical composition of the EOs by GC/MS showed that oxygenated monoterpenes constituted the most abundant group for all the extracted EOs. The major compounds were rather diversified depending on plant species. In fact, the S. officinalis L. EO mainly contained trans-thujone (21.80 %), the M. suaveolens Ehrh. EO mainly contained piperitenone oxide (71.19%), and carvacrol (61.60%) was the main component of the T. zygis L. EO. An insecticidal effect was observed for the three studied EOs on C. capitata adults and T. absoluta larvae. The observed LD50 values were 0.80 µL/mL and 11.04 µL/mL for M. suaveolens and S. officinalis, respectively, on T. absoluta larvae. For C. capitata adults, the obtained LD50 values were 0.9 µL/mL and 11.78 µL/mL for M. suaveolens and T. zygis, respectively. The presented findings could contribute to the development of biopesticides for plants as a component of integrated pest management strategies in citrus and tomato crops.

Phytochemical and toxicological evaluation of Zephyranthes citrina.

Drugs obtained from medicinal plants have always played a pivotal role in the field of medicine and to identify novel compounds. Safety profiling of plant extracts is of utmost importance during the discovery of new biologically active compounds and the determination of their efficacy. It is imperative to conduct toxicity studies before exploring the pharmacological properties and perspectives of any plant. The present work aims to provide a detailed insight into the phytochemical and toxicological profiling of methanolic extract of Zephyranthes citrina (MEZ). Guidelines to perform subacute toxicity study (407) and acute toxicity study (425) provided by the organization of economic cooperation and development (OECD) were followed. A single orally administered dose of 2000 mg/kg to albino mice was used for acute oral toxicity testing. In the subacute toxicity study, MEZ in doses of 100, 200, and 400 mg/kg was administered orally, consecutive for 28 days. Results of each parameter were compared to the control group. In both studies, the weight of animals and their selected organs showed consistency with that of the control group. No major toxicity or organ damage was recorded except for some minor alterations in a few parameters such as in the acute study, leukocyte count was increased and decreased platelet count, while in the subacute study platelet count increased in all doses. In the acute toxicity profile liver enzymes Alanine aminotransferase (ALT), as well as, aspartate aminotransferase (AST) were found to be slightly raised while alkaline phosphatase (ALP) was decreased. In subacute toxicity profiling, AST and ALT were not affected by any dose while ALP was decreased only at doses of 200 and 400 mg/kg. Uric acid was raised at a dose of 100 mg/kg. In acute toxicity, at 2000 mg/kg, creatinine and uric acid increased while urea levels decreased. Therefore, it is concluded that the LD50 of MEZ is more than 2000 mg/kg and the toxicity profile of MEZ was generally found to be safe.

Effects of the Oral Administration of Aqueous and Methanolic Leaf Extracts of Chenopodium ambrosioides L. (Amaranthaceae) on Blood Glucose Levels in Wistar Rats.

Background: Diabetes mellitus is a metabolic disorder that poses a major global health threat. The current diabetes mellitus uses insulin and oral hypoglycemic agents, which have limitations, including adverse effects and secondary failures. Herbal medicine is being evaluated for its role in the pharmacotherapy of diabetes. This study was aimed to assess the anti-diabetic potential and short-term toxicity level of Chenopodium ambrosioides collected from Bukavu in Democratic Republic of Congo. Methods: Leaves of C. ambrosioides were extracted by infusion and maceration with distilled water and 95% methanol, respectively. Hypoglycemic and antihyperglycemic potentials of the aqueous and methanolic were investigated in normoglycemic and intraperitoneal glucose-loaded rats at 100, 200, and 400 mg/kg body weight. An oral acute toxicity test was carried out on healthy female Wistar rats. Results: Acute toxicity test showed the mean lethal dose (LD50) for both aqueous and methanol extracts of C. ambrosioides to be more than 2000 mg/kg. The group treated with glibenclamide (5 mg/kg b.w) and aqueous extract of the plant (200 mg/kg b.w) showed a significant reduction (p< 0.0001 and p< 0.05) of fasting blood glucose by 46.91% and 16.72%, respectively, compared to control and all other treatment groups. In acute conditions, a single oral administration of the aqueous and methanolic extracts lowered fasting blood glucose in rats. Any manifestation and signs of toxicity and mortality have been recorded for 14 days of observation. Conclusion: Leaf aqueous and methanolic extracts of C. ambrosioides appeared safe at 2000 mg/kg. The plant demonstrated some anti-diabetic potential in rats, explaining its use as an anti-diabetic remedy locally.

Systematic investigation on the distribution of four hidden toxic Aconitum alkaloids in commonly used Aconitum herbs and their acute toxicity.

Yunaconitine (YAC), crassicauline A (CCA), 8-deacetylyunaconitine (DYA), and 8-deacetylcrassicauline A (DCA), as hidden toxic Aconitum alkaloids, are detected in some products of processed Aconitum carmichaelii lateral root and poisoning cases. The distribution and toxicity of these four components in Aconitum herbs should be further systematically studied for medication safety. This study developed a new UHPLC-QQQ-MS/MS method to determine ten Aconitum alkaloids, including aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine, benzoylhypaconine, YAC, CCA, DYA, and DCA, for Aconitum herbs simultaneously. YAC and CCA were founded in some samples of unprocessed A. carmichaelii lateral root (7.04%), A. carmichaelii root (9.43%), A. brachypodum root (6.00%), and A. ouvrardianum root (100%). Four hidden toxic Aconitum alkaloids were detected in processed A. carmichaelii lateral root (2.56%) and A. vilmorinianum root (100%). Four hidden toxic Aconitum alkaloids played significant roles in the classification of Aconitum herbs by OPLS-DA analysis. The acute toxicity test was performed by up-and-down procedure (UDP). The oral administration of the half lethal dose (LD50) of YAC, CCA, DYA, and DCA to female ICR mice was 2.37 mg/kg, 5.60 mg/kg, 60.0 mg/kg, and 753 mg/kg, respectively. The LD50 by intravenous injection was 0.200 mg/kg, 0.980 mg/kg, 7.60 mg/kg, and 34.0 mg/kg, respectively. The LD50 of unprocessed A. carmichaelii lateral root, A. vilmorinianum root, and A. brachypodum root to mice orally was 1.89 g/kg, 0.950 g/kg, and 0.380 g/kg, respectively. Symptoms of Aconitum alkaloid poisoning in mice were decreased activity, fur erect, palpebral edema, vomiting, polypnea, and convulsions. The main change of organs was flatulence. No poisoning or death occurred in mice at the maximum dosage (27.0 g/kg) of A. ouvrardianum root orally. To better control the quality and safety of Aconitum herbs, this study provides favorable support for improving the existing standards to strengthen the supervision of the four hidden toxic Aconitum alkaloids.

Acute and subacute (28 days) oral toxicity studies of tucum almond oil (Bactris Setosa Mart.) in mice.

Oils extracted from almonds are often used with particular interest due to their prospective health effects and benefits. Tucum is a Pantanal fruit widely consumed by local population and no in vivo toxicity studies regarding its safety are available in the literature to date. This study investigated the acute and subacute toxicity of tucum almond oil (TAO) in mice by evaluating its safety profile. For the acute (2000 mg/kg) and subacute (250, 500 and 1000 mg/kg) toxicity studies, TAO was administered orally to mice according to 425 and 407 Organization for Economic Cooperation and Development Guidelines, respectively. Food intake, body, and organ weight of animals were recorded. Signs of toxicity were assessed, and hematological, biochemical and histopathological analyses were performed. In the acute toxicity study, no mortality or behavioral changes were observed in mice treated with 2000 mg/kg, indicating that LD50 is higher than this dose. In the subacute toxicity test, the doses evaluated did not produce relevant changes in hematological, biochemical or histopathological parameters in the exposed animals. The data obtained suggest that TAO did not induce toxicity after exposure to a single or repeated doses and LD50 value may be considered to be more than 2000 mg/kg body weight.

In vivo anti-inflammatory and hepatoprotective activities of Orobanche crenata (Forssk.) aerial parts in relation to its phytomolecules.

A total methanolic extract and its sub-extracts of Orobanche crenata (Forssk.) aerial parts were subjected to acute toxicity, anti-inflammatory, and hepatoprotective investigations. The methanolic extract was safe upto 3 g/kg on mice. The EtOAc fraction reduced the carrageenan-induced rat paw edema better than indomethacin. It also demonstrated a drop in the elevated ALT, AST, and TB at 300 mg/kg, better than silymarin. Histopathological examination of liver cells of rats given the EtOAc fraction showed a complete absence of the CCl4-induced cloudy swelling. A phytochemical investigation of the n-hexane and EtOAc fractions yielded 11 compounds [indole-3-carboxylic acid (1), n-butyl palmitate (2), tyrosol (3), L-rhamnonic acid-1,4-lactone (4), ß-sitosterol/stigmasterol mixture (5/5'), ß-sitosterol/stigmasterol glycosides mixture (6/6'), chrysoeriol (7), luteolin (8), apigenin (9), crenatoside (10), and verbascoside (11)] as identified by UV, 1D & 2D NMR and ESIMS techniques. Their reported biological actions were in relation to and supported our herein detected pharmacological findings.

Lipophilic and hydrophilic leaf extracts of Portulaca oleracea (Purslane) disrupts female sex hormones in albino rats (Rattus norvegicus).

BACKGROUND AND AIM: Decoctions and infusions from the aerial parts of Portulaca oleracea Linn., especially the leaves and stems, are used by traditional medicine practitioners in Nigeria to enhance fertility in humans. The scarcity of literature on the use of this plant for the said purpose as well as its efficacy prompted this research. Study investigated effect of lipophilic and hydrophilic leaf extracts of Portulaca oleracea on oestrous cycle, female sex hormones at various phases of oestrous cycle and ovarian and uterine histomorphology in albino rats. EXPERIMENTAL PROCEDURE: Experimental animals were randomly divided into 7 groups of 5 rats each. Group A (control) received 0.5 ml 20% Tween 80 (vehicle), groups B, C & D received 125, 250 & 500 mg/kg of the lipophilic extract respectively and E, F & G received 125, 250 & 500 mg/kg of the hydrophilic extract respectively for 21 days. Oestrous cycle was assessed daily. At the end, blood samples (for hormones) and ovarian &uterine sections (histoarchitecture) were collected. RESULTS AND CONCLUSION: Both extracts had no significant (p > 0.05) effect on oestrous cycle, ovarian & uterine histoarchitecture and female sex hormones except at proestrus phase where significant (p < 0.05) decrease in LH and FSH was recorded. P.oleracea as used in this study may have deleterious effect on female reproductive system as shown by the disruption of the hormones at proestrus phase. This can form a basis to refute the use of P.oleracea leaf extracts in enhancing fertility as it has been shown to affect the gonadotropins involved in folliculogenesis.

Insights into forsythia honeysuckle (Lianhuaqingwen) capsules: A Chinese herbal medicine repurposed for COVID-19 pandemic.

Background: In December 2019, a novel coronavirus, SARS-CoV-2 caused a series of acute atypical respiratory diseases worldwide. However, there is still a lack of drugs with clear curative effects, and the clinical trial research of vaccines has not been completely finished. Purpose: LH capsules are approved TCM patent medicine that are widely used for the treatment of respiratory tract infectious diseases caused by colds and flu. On April 12, 2020, LH capsules and granules were officially repurposed by the China Food and Drug Administration (CFDA) for patients with mild COVID-19 based on their safety and efficacy demonstrated through multicentre, randomized, controlled clinical trials. We hope to conduct a comprehensive review of it through modern pharmacy methods, and try to explain its possible mechanism. Methods: Using the full names of LH capsules Lianhuaqingwen, Lianhua Qingwen andSARS-COV-2, COVID-19 as the keywords of the search terms, systemically search for existing related papers in various databases such as Web of Science and PubMed. And completed the collection of clinical data in ClinicalTrials.gov and Chinese Clinical Trial Registry. Last but not least, we have sorted out the anti-inflammatory and antiviral mechanisms of LH capsules through literature and Selleck. Results: This review systematically sorted out the active ingredients in LH capsules. Furthermore, the related pharmacological and clinical trials of LH capsule on SARS-CoV-2, IAV and IBV were discussed in detail. Moreover, the present review provides the first summary of the potential molecular mechanism of specific substances in LH capsules involved in resistance to SARS-COV-2 infection and the inhibition of cytokine storm syndrome (CSS) caused by IL-6. Conclusion: This review summarizes the available reports and evidence that support the use of LH capsules as potential drug candidates for the prevention and treatment of COVID-19. However, TCM exerts its effects through multiple targets and multiple pathways, and LH capsules are not an exception. Therefore, the relevant mechanisms need to be further improved and experimentally verified.

Computational screening of phytochemicals from three medicinal plants as inhibitors of transmembrane protease serine 2 implicated in SARS-CoV-2 infection.

Background: SARS-CoV-2 infection or COVID-19 is a major global public health issue that requires urgent attention in terms of drug development. Transmembrane Protease Serine 2 (TMPRSS2) is a good drug target against SARS-CoV-2 because of the role it plays during the viral entry into the cell. Virtual screening of phytochemicals as potential inhibitors of TMPRSS2 can lead to the discovery of drug candidates for the treatment of COVID-19. Purpose: The study was designed to screen 132 phytochemicals from three medicinal plants traditionally used as antivirals; Zingiber officinalis Roscoe (Zingiberaceae), Artemisia annua L. (Asteraceae), and Moringa oleifera Lam. (Moringaceae), as potential inhibitors of TMPRSS2 for the purpose of finding therapeutic options to treat COVID-19. Methods: Homology model of TMPRSS2 was built using the ProMod3 3.1.1 program of the SWISS-MODEL. Binding affinities and interaction between compounds and TMPRSS2 model was examined using molecular docking and molecular dynamics simulation. The drug-likeness and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of potential inhibitors of TMPRSS2 were also assessed using admetSAR web tool. Results: Three compounds, namely, niazirin, quercetin, and moringyne from M. oleifera demonstrated better molecular interactions with binding affinities ranging from -7.1 to -8.0 kcal/mol compared to -7.0 kcal/mol obtained for camostat mesylate (a known TMPRSS2 inhibitor), which served as a control. All the three compounds exhibited good drug-like properties by not violating the Lipinski rule of 5. Niazirin and moringyne possessed good ADMET properties and were stable in their interactions with the TMPRSS2 based on the molecular dynamics simulation. However, the ADMET tool predicted the potential hepatotoxic and mutagenic effects of quercetin. Conclusion: This study demonstrated the potentials of niazirin, quercetin, and moringyne from M. oleifera, to inhibit the activities of human TMPRSS2, thus probably being good candidates for further development as new drugs for the treatment or management of COVID-19.

Toxicological evaluation of a flavonoid, chrysin: morphological, behavioral, biochemical and histopathological assessments in rats.

Nowadays, medicines from plant sources play a vital role in healthcare management. Chrysin, a plant flavonoid, possesses a wide range of pharmacological activities. The aim of present investigation was to evaluate the safety of chrysin by determining toxicity after acute and sub-chronic oral administration in rats. Acute oral toxicity (AOT) and sub-chronic oral toxicity studies of chrysin were carried out according to OECD 425 and OCED 408 in Sprague Dawley rats. In AOT, oral administration of chrysin (5000 mg/kg) showed 40% mortality. In the sub-chronic toxicity study, daily oral administration of chrysin (1000 mg/kg) showed significantly decreased body weight whereas liver weight was increased significantly in male rats. A significant alteration in the hematology (RBC, MCH, MCHC, TLC, lymphocytes, and neutrophil) and blood chemistry (albumin, bilirubin, ALT, AST, creatinine, and GGT) were found in chrysin (1000 mg/kg) treated rats which were either limited to one sex or lacked dose-response or were within the normal laboratory ranges. There was a significant increase in hepatic and renal oxido-nitrosative stress in chrysin (1000 mg/kg) treated rats. There was no significant change in electrocardiographic (except heart rate), hemodynamic, the left ventricular function, and lung function test. Renal and hepatic histological aberrations were induced in chrysin (1000 mg/kg) treated rats. In conclusion results of the present investigation determined the LD50 value of chrysin to be 4350 mg/kg whereas NOAEL and LOAEL of chrysin was found to be 500 and 1000 mg/kg, respectively for both the sexes.

Toxicological study of aqueous-methanol solvent fraction of methanol extract of Dacryodes edulis leaves.

Dacryodes edulis (G. Don) H.J. Lam) is the most popular species under the genus Dacryodes. It is well known for its nutritional and ethno-medicinal uses in South-eastern and South-western Nigeria. This study was aimed to evaluate the toxicity of the aqueous-methanol fraction of crude methanol extract of Dacryodes edulis leaves (AMDE). The test rats were randomized to groups of single oral treatment of AMDE (10-5000 mg/kgbw) for the acute toxicity study. They were monitored for obvious signs of behavioural change and mortality. For the subacute toxicity study, the rats were randomized to three daily treatment groups (of 200, 400 and 600 mg/kgbw of AMDE) for 28 days. The fourth group (control) received 2.5 %v/v DMSO. At the end of the experiment, blood samples were collected for hematology and clinical chemistry evaluation. The histopathology of the livers and kidneys were assessed using the excised organs. The cytotoxicity and genotoxicity of AMDE were also evaluated using Allium cepa model. The result showed that acute administration of AMDE, up to a dose of 5000 mg/kgbw did not result in mortality of the test rats. The observed median lethal dose (LD50) was greater than 5000 mg/kgbw. The subacute oral administration of AMDE for 28 days showed no significant (p > 0.05) effect on liver function, kidney function indices, organ - body weight ratio, but significantly (p < 0.05) decreased erythrocytic indices: red blood cells, haematocrit, and haemoglobin at 600 mg/kgbw. The Allium cepa assay revealed a non-significant reduction in mitotic index and low chromosomal aberrations of the treated groups. In conclusion, the aqueous-methanol solvent fraction of methanol extract of Dacryodes edulis leaves, AMDE is relatively safe. However, there are strong indications that it may contain compounds that are cytotoxic and reduces erythrocytic indices including red blood cells at high doses. Thus, adequate care should be taken in dosing and administering the extract to avert anaemic condition.

Antagonistic effects of nano-selenium on broilers hepatic injury induced by Cr(VI) poisoning in AMPK pathway.

Cr (chromium, with common valence states of III and VI) is one of the common broiler feed additives. Liver injury and metabolic disorders could be caused by Cr(VI) (hexavalent chromium) poisoning in broilers. Oxidative damage and metabolic disorders of organisms caused by heavy metals could be antagonized by nano-Se (nano-selenium). Nano-Se was chosen to study the antagonism of Cr(VI) poisoning in broilers. AMPK (Adenosine 5,-monophosphate-activated protein kinase) is known as a "cell energy regulator" and plays a key regulatory role in carbohydrate and lipid metabolism. AMPK pathway and ACACA/CPT1A two genes were selected to study the prevention and treatment of nano-Se on Cr(VI) poisoning in broilers and its molecular mechanism. For this purpose, 180 1-day-old AA (Arbor Acres) broilers were selected and randomly divided into 6 groups (n = 30) for further testing. After feeding as planned for 35 days, the livers of such broilers were taken for further examination including histopathological examination, differential gene expression analysis, and further validation on both mRNA and protein levels using related techniques like RT-qPCR, western blot, and immunohistochemistry (IHC). The histopathological examination suggested that the liver cells of the Cr(VI) poisoning group were more severely injured than the nano-Se addition group. RT-qPCR results showed that the relative expression of ACACA gene in the Cr(VI) poisoning group was significantly increased (P < 0.05), while the CPT1A gene's expression was significantly decreased (P < 0.01). Those results were reversed in the nano-Se addition group. Western blot results were consistent with RT-qPCR and both suggested antagonism of nano-Se on Cr(VI). Through morphological and histopathological observation, as well as the measurement of the mRNA and protein expression levels of ACACA and CPT1A genes in AMPK pathway, it was confirmed that nano-Se has certain preventive and protective effects on Cr(VI) poisoning in broiler chickens. Furthermore, the adverse effects of Cr(VI) on carbohydrate and lipid metabolism in broilers can be antagonized by nano-Se through AMPK pathway. A new method and experimental basis were provided to the future study of Cr(VI) poisoning in broilers.

Acute and Subchronic Oral Toxicity of Oil Palm Puree in Sprague-Dawley Rats.

Palm puree is rich in antioxidants and is produced via blending various proportions of mesocarp fibre and crude palm oil. The aim of this study was to assess the acute and subchronic toxicity of palm puree in male and female Sprague-Dawley rats. For the acute toxicity study, animals administered single palm-puree doses (2000 mg kg-1) by gavage were observed daily for 14 d. For the subchronic toxicity study, the rats were administered 500, 1000, or 2000 mg kg-1 palm puree daily for 28 d. We evaluated body and organ weights; performed haematological, biochemical, and histopathological analyses of blood and organ samples during and after treatment; and calculated the oral no-observed-adverse-effect level (NOAEL). The toxicity studies showed no signs of toxicity or mortality. The haematological, biochemical, and histopathological analyses and body and organ weights indicated no evidence of substantial toxicity at any dose of palm puree. The oral lethal dose and NOAEL for the palm puree were greater than 2000 mg kg-1 d-1 over 28 d. To the best of our knowledge, the present study is the first to confirm the safety of palm puree as a novel functional food. These encouraging results warrant further studies to elucidate its potential for pharmaceutical formulations.

Acute oral toxicity and antioxidant studies of an amine-based diselenide.

BACKGROUND: Organochalcogen compounds have attracted the interest of a multitude of studies for their promising Pharmacological and biological activities. The antioxidant activity and acute toxicity of an organoselenium compound, 1-(2-(2-(2-(1-aminoethyl)phenyl)diselanyl)phenyl)ethanamine (APDP) was determined in mice. METHODS: Mice were randomly divided into four groups, with each group comprising of seven animals. Canola oil (1ml/kg of body weight) was administered to 1st group, while 2nd, 3rd & 4th groups were administered with 10 mg/kg, 30 mg/kg & 350 mg/kg of APDP respectively. APDP was administered by Intragastric gavage as a single oral dose. RESULTS: The APDP oral administration was found to be safe up to 350 mg/kg of body weight and no deaths of animals were recorded. The lethal dose 50 (LD50) for APDP was determined at 72 h and was estimated to be > 350 mg/kg. After acute treatment, all mice were sacrificed by decapitation to determine the antioxidant enzymes and lipid peroxidation values for the treated mice liver. No fluctuation in lipid peroxidation, vitamin C and non protein thiol (NPSH) levels was observed due to the administration of APDP. hepatic α-ALA-D activity, catalase (CAT), superoxide dismutase (SOD) and the biochemical parameters were evaluated. Experimental observation demonstrated that APDP protected Fe(II) induced thiobarbituric acid reactive substances (TBARS) production in liver homogenate significantly (p < 0.05). The administration of APDP (an amine-based diselenide) both in vitro and in vivo clearly demonstrated that this potential compound has no acute toxicity towards mice among all the tested parameter. CONCLUSION: On the basis of experimental results, it is concluded that APDP is a potential candidate as an antioxidant compound for studying pharmacological properties.