Acute and sub-acute oral toxicity of aqueous whole leaf and green rind extracts of Aloe vera in Wistar rats

Background Several local communities in Central, Western, Eastern, and Northern regions of Uganda have been using the whole leaf extracts of Aloe vera (L.) Burm. f. (Asphodelaceae) in the treatment of various ailments. Also, several commercial companies sell A. vera as soft drinks in Uganda. However, there are inadequate reports on the toxicities of such preparations. This paper reports the acute and sub-acute oral toxicity of aqueous extracts of whole leaf and green rind of A. vera in Wistar rats. Methods Acute oral toxicity test was carried out in female Wistar rats at doses of 175, 550, 1750, and 5000 mg/kg, p.o. The animals were observed for signs of toxicity for 14 days. Similarly, a sub-acute oral toxicity test was performed in both sexes of rats at doses of 200, 400, and 800 mg/kg, p.o. daily for 28 days. All the groups of animals were monitored for behavioral, morphological, biochemical, and physiological changes, including mortality and compared with respective controls. Body weights were measured weekly while the animals’ relative organ weights, hematological, biochemical, gross, and microscopic pathology were examined on day 29. Results There was no mortality or apparent behavioral changes at the doses tested in acute and sub-acute oral toxicity tests. Thus, the Median Lethal Dose (LD50) of green rind and whole leaf aqueous extracts was above 5000 mg/kg. Gross anatomy revealed that the rats’ relative spleen weight in green rind extract at 200 mg/kg significantly decreased compared to the control group. The creatinine levels in female rats that received green rind extract and the chloride ion levels in male rats administered whole leaf extract were significantly elevated. Conversely, Mean Corpuscular Hemoglobin Concentration (MCHC) levels significantly decreased at lower doses of the green rind extract compared to the control. Histopathology of the kidney revealed the renal interstitium’s inflammation at doses of 200 and 800 mg/kg of the whole leaf extract. Conclusion The findings demonstrated that A. vera green rind and whole leaf extracts are non-toxic at relatively high doses when used for a short duration. Prolonged use of the aqueous whole leaf extract might be associated with kidney toxicity.

Acute, subacute oral toxicity and Ames test of Py-mulin: an antibacterial drug candidate

Background Py-mulin is a new pleuromutilin derivative with potent antibacterial activities in vitro and in vivo, suggesting this compound may lead to a promising antibacterial drug after further development. The present study is aimed to evaluate the acute and subacute oral toxicity, and the genotoxicity with the standard Ames test according to standard protocols. Methods Acute oral toxicity of Py-mulin was determined using Kunming mice. The 28-day repeated dose oral toxicity study in SD rats was performed according to OECD guideline No. 407. The bacterial reverse mutation (Ames test) was carried out using four Salmonella typhimurium (S. typhimurium) strains TA97, TA98, TA100 and TA1535 with and without S9 metabolic activation. Results The LD50 values in acute oral toxicity were 2973 mg/kg (female mice) and 3891 mg/kg (male mice) calculated by the Bliss method. In subacute toxicity study, 50 mg/kg Py-mulin did not induce any abnormality in body weight, food consumption, clinical sign, hematology, clinical chemistry, organ weight, and histopathology in all of the treatment groups. However, high doses of Py-mulin (100 and 300 mg/kg) displayed slightly hepatotoxicity to female rats. Furthermore, Py-mulin did not significantly increase the number of revertant colonies of four standard S. typhimurium strains with the doses of 0.16–1000 μg/plate in the Ames study. Conclusions Based on our findings, our study provides some information for the safety profile of Py-mulin.

Evaluation of anxiolytic and anti-depressant activity of Neolamarckia cadamba in mice

Objective: Evaluation of anxiolytic and anti-depressant activity of Neolamarckia cadamba in mice. Material & Method: The aqueous and methanolic extract of “Neolamarckia cadamba” and chose low medium and high doses for therapy. The behavioral consequences of an oral acute or subacute (10 days) treatment. Neolamarckia cadamba (250 and 500 mg/kg, p.o) aqueous and methanolic stem bark extract assessed in male and female Swiss mice (EPM). Diazepam (1 mg/kg) will also be evaluated. Anti-anxiety drug testing in the lab. Results: Neolamarckia cadamba, acute oral toxicity was detected with different extracts (ENC & AQNC) having dose (5, 50, 300, 1000 mg/kg ) via the oral route, shows no change in behavioral responses and observation shows no acute oral toxicity. Hence depending upon it, Dose was selected 250 mg/kg & 500 mg/kg for our experimental work. Conclusion: Neolamarckia cadamba has both anxiolytic and antidepressant properties, which likely operate through BZD receptors, selective serotonin reuptake inhibitors. The antidepressant and anxiolytic properties of Neolamarckia cadamba ethanolic and aqueous extracts were investigated in Swiss albino mice at doses of 250 and 500 mg/kg, respectively. Both extracts (ANC & ENC) showed strong antidepressant and anxiolytic efficacy using TST and EPM parameters.

Evaluation of Toxicity, Bacteriostatic, Analgesic, Anti-Inflammatory, and Antipyretic Activities of Huangqin-Honghua-Pugongying-Jinyinhua Extract

The extensive use of antibiotics has caused the global spread of multidrug-resistant bacteria and genes, seriously reducing antibiotic efficacy and threatening animal and human health. As an alternative, traditional Chinese veterinary medicine (TCVM) was used in this study for its lack of drug resistance and low toxicity. Huangqin-honghua-pugongying-jinyinhua extract (HHPJE), a novel TCVM, consists of the extracts of Huangqin (Scutellaria baicalensis), Honghua (Carthami Flos), Pugongying (Taraxacum) and Jinyinhua (Lonicerae Japonicae Flos), and was developed to treat bovine mastitis. In this study, we evaluated the toxicity, bacteriostatic, analgesic, anti-inflammatory, and antipyretic activities of HHPJE. Our results show that HHPJE did not show any acute oral toxicity and can be considered safe for oral administration. Additionally, HHPJE possessed a dose-dependent antibacterial effect on Staphylococcus aureus, Escherichia coli, Streptococcus agalactiae and Streptococcus dysgalactiae. HHPJE (60, 30 and 15 g/kg) can reduce the abdominal pain by 44.83 ± 7.69%, 43.15 ± 9.50% and 26.14 ± 4.17%, respectively. The percentages of anti-inflammation inhibition (60, 30 and 15 g/kg) were 35.34 ± 2.17%, 22.29 ± 2.74% and 12.06 ± 3.61%, respectively. The inhibition rates (60, 30 and 15 g/kg) of antipyretic activity were 82.05%, 65.71% and 52.80%, respectively. The evaluation of pharmacodynamics and toxicity indicate that HHPJE possesses significant bacteriostatic, analgesic, anti-inflammatory and antipyretic potential, and also that it is safe for acute oral toxicity, which means it has potential value for treating bovine mastitis in future and alleviating clinical symptoms with no drug resistance or side effects.

Utilization of Gelling Polymer to Formulate Nanoparticles Loaded with Epalrestat-Cyclodextrin Inclusion Complex: Formulation, Characterization, In-Silico Modelling and In-Vivo Toxicity Evaluation

Epalrestat (EPL) is an aldose reductase inhibitor with poor aqueous solubility that affects its therapeutic efficacy. The research study was designed to prepare epalrestat-cyclodextrins (EPL-CDs) inclusion complexes to enhance the aqueous solubility by using beta-cyclodextrin (β-CD) and sulfobutyl ether₇ β-CD (SBE7 β-CD). Furthermore, polymeric nanoparticles (PNPs) of EPL-CDs were developed using chitosan (CS) and sodium tripolyphosphate (sTPP). The EPL-CDs complexed formulations were then loaded into chitosan nanoparticles (CS NPs) and further characterized for different physico-chemical properties, thermal stability, drug-excipient compatibility and acute oral toxicity studies. In-silico molecular docking of cross-linker with SBE7 β-CD was also carried out to determine the binding site of the CDs with the cross-linker. The sizes of the prepared NPs were laid in the range of 241.5–348.4 nm, with polydispersity index (PDI) ranging from 0.302–0.578. The surface morphology of the NPs was found to be non-porous, smooth, and spherical. The cumulative percentage of drug release from EPL-CDs loaded CS NPs was found to be higher (75–88%) than that of the pure drug (25%). Acute oral toxicity on animal models showed a biochemical, histological profile with no harmful impact at the cellular level. It is concluded that epalrestat-cyclodextrin chitosan nanoparticles (EPL-CDs-CS NPs) with improved solubility are safe for oral administration since no toxicity was reported on vital organs in rabbits.

Acute and subacute toxicity study of Aucklandia lappa Decne seed oil

Purpose: To investigate the acute and subacute toxicity of Aucklandia lappa Decne. seed oil (ALDO) in mice and rats.Methods: A single dose of 10 g ALDO/kg was administered to Kunming mice in an acute oral toxicity experiment. Their weight and feed consumption were recorded for 14 days to observe whether they had symptoms of poisoning and mortality. Sprague-Dawley (SD) rats were administered 0.89, 1.77 and 3.54 g/kg for 28 days, and symptoms of poisoning and mortality were monitored daily. Body weight, feedconsumption, hematology, serum biochemical parameters, relative organ weight, and histopathology of the experimental and control groups were compared.Results: The acute oral toxicity study revealed that there was no significant difference in the macroscopic results, including mortality, feed consumption and weight growth between the group dosed with 10 g ALDO/kg (p > 0.05) and the control group. In the subacute toxicity test, SD rats had a higher weight growth rate and feed utilization after doses of 0.89 g ALDO/kg (p < 0.01). However, compared with the control group (p > 0.05), there was also no significant difference in biochemical and hematological parameters, relative organ weight, or in macroscopic and histological features of both animal types. The electrolyte concentrations of Na and Cl increased at the doses of 1.77 and 3.54 g/kg (p < 0.01).Conclusion: These results suggest that ALDO is relatively safe when administered orally to rats and provide a theoretical basis for the development of new food resources.