Search Results (70)

Momordica charantia L. (Cucurbitaceae) has been widely recognized for its pharmacological potential, although studies on its leaves remain scarce. In this study, the hydroethanolic leaf extract (MCHLE) was chemically characterized by LC–MS/MS, revealing the presence of octopamine, ferulate, vitexin-2-O-rhamnoside, and other bioactive phenolics. Toxicological evaluation in Wistar rats demonstrated that both acute (2000 mg/kg) and repeated oral administration (up to 400 mg/kg for 28 days) caused no clinical or behavioral signs of toxicity. Notably, treatment significantly reduced glucose and cholesterol levels, in addition to attenuating lipid peroxidation and enhancing antioxidant defenses. In vivo, MCHLE inhibited leukocyte and neutrophil infiltration in the LPS-induced peritonitis model, with efficacy comparable to dexamethasone. It also reduced TNF-α secretion and nitric oxide generation in peritoneal fluids. In vitro assays with LPS-stimulated RAW 264.7 macrophages confirmed these effects, showing dose-dependent inhibition of TNF-α, IL-1β, and NO production. Gene expression analysis further demonstrated downregulation of TNF-α and MAPK, with marked suppression of NF-κB transcripts. Collectively, these results suggest that MCHLE exerts anti-inflammatory activity by targeting both mediator release and upstream signaling pathways, while maintaining a favorable safety profile, supporting its potential for further investigation as a promising source of bioactive compounds. Full article

Background: Some lactobacilli strains have been documented to cause bacteremia and sepsis in immunocompromised or critically ill hospitalized patients, challenging the universally presumed safety of lactobacilli. Therefore, strain-specific risk assessments are required for the use of Lactobacillus as a probiotic. Lactobacillus xujianguonis, a novel Lactobacillus species isolated from Marmota himalayana, has probiotic potential but lacks safety data. Objective: To evaluate the preclinical safety of L. xujianguonis for food-grade use. Methods: Systematic safety assessment includes in vitro studies and oral toxicity studies. In vitro studies encompassed gastrointestinal tolerance, auto-aggregation and pathogen inhibition, antibiotic susceptibility, and hemolysis/gelatinase activity assays. Oral toxicity studies contained acute single-dose and repeated-dose 28-day oral toxicity studies in mice based on the OECD toxicity study guidelines. Results: L. xujianguonis strains HT111-2 and 06-2 demonstrated certain probiotic traits, including high acid/bile tolerance, strong auto-aggregation, and antimicrobial activity against common human gastrointestinal pathogens. In vitro safety assessments showed susceptibility to nine antibiotics and absence of hemolytic/gelatinase activity. Acute oral exposure (1 × 10¹¹ CFU/kg) induced no mortality, clinical abnormalities, or organ toxicity. Subchronic 28-day administration (multiple doses) showed absence of adverse clinical signs with body weight stability and no hematological, biochemical, or histopathological deviations in C57BL/6 mice. Inflammatory and immunological markers remained unaffected. Histological staining results and transcriptional level validation revealed no evidence of intestinal tissue damage. Conclusions: This study provides preliminary evidence of the safety of L. xujianguonis, supporting its advancement to functional research. Full article

House flies (Musca domestica L.) are major vectors of numerous pathogens affecting both humans and animals. The global distribution of house flies has been steadily increasing the expansion of human settlements, increased waste production, and the growth of livestock farms established to meet the demand for animal-derived products. Frequent exposure to intensive pesticide applications in agricultural and livestock areas has accelerated the development of insecticide resistance, posing a serious challenge to sustainable control efforts. The widespread and repeated use of conventional chemical insecticides has contributed to rapid resistance evolution in many populations worldwide. In this study, the acute toxic effects of two insect growth regulators (IGRs)—cyromazine and methoprene—commonly used in the larval stages of house flies were evaluated against adult flies. Treatments were applied (3 replicates) orally via 40% sugar-water solutions containing 1%, 5%, and 10% concentrations, and bioassays were conducted on eight distinct house fly populations. The results showed that cyromazine caused average adult mortalities of 76.35%, 81.00%, and 84.50% within 48 h, while methoprene produced 70.62%, 99.37%, and 100% mortality at the same concentrations. At 10%, methoprene achieved 100% mortality across all populations, whereas cyromazine induced mortality ranging from 44.28% to 100%. These findings suggest that IGRs can be effective alternatives to conventional insecticides and can be integrated into IPM/IVM programs to reduce chemical use and delay resistance. Full article

Background: Slow-transit constipation (STC) lacks durable and safe prokinetics. Deglycosylated-azithromycin (Deg-AZM), a novel small-molecule transgelin agonist that restores colonic motility in STC, has been approved for clinical trials in 2024. Objectives: This study aimed to assess the genetic toxicity and embryo–fetal development (EFD) toxicity of Deg-AZM through a series of standardized non-clinical safety studies. Methods: We conducted Ames, in vivo micronucleus, and chromosomal aberration tests to evaluate genotoxicity. Acute and 28-day repeated-dose oral toxicity studies were performed in Sprague-Dawley rats. EFD toxicity was assessed in pregnant rats administered Deg-AZM from gestation day (GD) 6 to 15. Toxicokinetic analyses were integrated into repeated-dose and EFD studies. Results: Deg-AZM demonstrated no mutagenic potential in the bacterial reverse-mutation assay at concentrations up to 2500 µg/plate (with metabolic activation) or 150 µg/plate (without metabolic activation). No clastogenic effects were observed in micronucleus or chromosomal aberration assays. The median lethal dose (LD₅₀) exceeded 1600 mg/kg in acute oral toxicity. In the 28-day study, no adverse effects were observed at doses up to 600 mg/kg, though mild hematological and hepatic changes were noted at high doses, all of which were reversible. In the EFD study, Deg-AZM did not induce maternal toxicity, teratogenicity, or adverse fetal outcomes at doses up to 600 mg/kg. Conclusions: Deg-AZM demonstrates a favorable safety profile with no evidence of genetic toxicity or developmental harm at pharmacologically relevant doses, supporting its further development as a therapeutic agent for STC. Full article

This study evaluated the acute toxicity of the hydroethanolic extract and the butanolic fraction of Piper marginatum Jacq., following the OECD Guideline 423. Oral and intraperitoneal exposure of CD-1 mice was used in single-dose and repeated-dose schedules. No mortality or significant behavioral alterations were observed. Body weight remained stable during treatment, and histopathological analysis revealed only mild to moderate alterations, mainly in the liver, kidneys, and lungs. These results indicate the absence of acute systemic toxicity under the conditions evaluated. Preliminary phytochemical analysis and metabolomic profile analysis by LC-QTOF/MS revealed a diverse composition of secondary metabolites, including alkaloids, flavonoids, phenylpropanoids, and sphingolipids. Compounds with known biological activity and some with potential toxicity were identified. The findings support the safe use of Piper marginatum extracts in short-term applications and suggest further subchronic toxicity studies and mechanistic evaluation. This research provides fundamental data for preclinical characterization and standardization of extracts of plant origin. Full article

Hyaluronidase is a hydrolytic enzyme that cleaves β-1,4-glycosidic linkages in high-molecular-weight hyaluronic acid, generating low-molecular-weight oligosaccharides with enhanced biological functions. These products exhibit immunomodulatory, antioxidant, and tissue-regenerative properties, making them valuable in pharmaceutical, cosmetic, and functional food applications. However, most commercial hyaluronidases originate from pathogenic bacteria or recombinant hosts, raising concerns over their biosafety and regulatory acceptance, particularly in food-grade applications. In this study, we report the isolation and characterization of a novel non-pathogenic soil bacterium, Paenibacillus residui BSSK58, which produces an extracellular hyaluronidase. Whole-genome sequencing revealed the absence of known virulence factors and antibiotic resistance genes. Phenotypic safety evaluations confirmed that there was no hemolytic activity, biogenic amine production, or cytotoxicity against human intestinal epithelial cell lines (Caco-2 and HT-29). The purified BSSK58 hyaluronidase exhibited a molecular weight of approximately 170 kDa, with optimal activity at pH 8.0–9.0 and 50 °C. The enzyme showed broad substrate specificity toward hyaluronic acid, chondroitin sulfate, and alginate, and its depolymerizing activity was confirmed using gel permeation chromatography. Furthermore, a 13-week oral repeated-dose toxicity study under Good Laboratory Practice conditions demonstrated no adverse effects. These findings support the use of BSSK58 hyaluronidase as a safe, non-recombinant biocatalyst suitable for industrial applications under regulatory-compliant frameworks. Full article

Compound 221s (2,9) is a novel antihypertensive drug candidate synthesized utilizing danshensu, borneol, and proline by using the strategy of combinatorial molecular chemistry. This study aimed to systematically identify the safety of danshensu-derived compound 221s (2,9) by conducting an acute toxicity test and long-term toxicity study and to elucidate the in vivo metabolic pathways of 221s (2,9) in order to provide critical insights into the observed toxicity. In the acute toxicity study, a single oral dose of 221s (2,9) at 3000 mg/kg in mice produced no clinical signs of toxicity or mortality, indicating an MTD of 3000 mg/kg. In a subsequent 12-week repeated-dose toxicity study in rats, doses of 20, 40, and 80 mg/kg were well tolerated, with no adverse clinical observations or deaths. Notably, organ coefficient analysis revealed transient lung injury, which resolved following a 4-week recovery period. The metabolite identification study indicated that metabolism in rats is predominated by Phase II metabolites, potentially contributing to the low toxicity of 221s (2,9). Further investigation into the impact of the drug metabolic enzyme–transporter interplay on the in vivo disposition of 221s (2,9) is warranted. Full article

Environmental risk assessment (ERA) for pesticide approval in the context of predatory insects remains inadequate as it often overlooks the influence of agricultural practices. An increasing number of studies have shown that prolonged and synergistic pesticide exposure can elevate insect mortality. However, such effects remain largely unstudied in non-target predatory carabid beetles. The carabid beetle Platynus assimilis was subjected to repeated oral and continuous contact exposure to low doses of prothioconazole (20 g·ha⁻¹), lambda-cyhalothrin (0.4 g·ha⁻¹), or their combination over a 64-day period. The food consumption rate, body mass, locomotor activity, and mortality were monitored throughout the experiment. All pesticide-treated groups showed significantly increased final mortality, with median lethal times (LT₅₀) of 51.6 days for prothioconazole, 60.3 days for lambda-cyhalothrin, and 12.2 days for their combination. A significant synergistic effect on mortality was observed in the combined treatment group, with the highest synergistic ratio detected 20 days after the first exposure. Pesticide-treated beetles exhibited significant abnormalities in locomotor activity and body mass compared to the untreated group. These findings demonstrate that both time-cumulative mortality and potential synergistic interactions, reflecting field-realistic conditions, must be considered in ERA. Failure to do so may lead to an underestimation of pesticide toxicity to predatory carabids. Full article

Background/Objectives: 7-Methylxanthine (7-MX) is a naturally occurring metabolite of caffeine and theobromine that can inhibit the crystallization of monosodium urate (MSU) and may be useful for the prevention or treatment of gout. However, the pharmacokinetics and ex vivo activity of 7-MX remain poorly characterized. Methods: The present study assessed the pharmacokinetics of 7-MX in Sprague Dawley rats following a single oral dose (30 mg/kg), and the ex vivo inhibition of MSU crystallization by 7-MX in rat plasma after the repeated administration of oral 7-MX. Results: The pharmacokinetic analysis showed that 7-MX reached peak plasma concentration (C_max ≈ 30 µM) at 30 min after administration (t_max), the terminal half-life was approximately 1.4 h, and there was no evidence of accumulation after repeated daily dosing. After repeated administration, the relationship between dose (30 or 60 mg/kg) and plasma concentration was proportional. In vitro and ex vivo crystallization assays demonstrated that 7-MX inhibited MSU crystallization in a concentration-dependent manner. The in vitro studies showed that 100 µM 7-MX inhibited up to 74% of MSU crystallization under supersaturated conditions (400 mg/L urate). The ex vivo experiments indicated that plasma from rats that received 30 or 60 mg/kg of 7-MX had 41.4% and 52.6% inhibition of crystallization, consistent with the measured plasma concentrations. Conclusions: These findings confirm that oral administration of 7-MX to rats led to a plasma level that was sufficient to decrease MSU crystallization in plasma, and there were no observable toxicities. These results support the potential of 7-MX as a safe oral treatment for gout, especially in combination with urate-lowering therapies, such as allopurinol. Further clinical investigations are warranted to confirm the therapeutic potential of 7-MX in humans. Full article

Probiotics, as defined by the World Health Organization, are live microorganisms that, when consumed in sufficient quantities, provide health benefits to the host. Although some countries have approved specific probiotic species for use in food, safety concerns may still arise with individual strains. Lacticaseibacillus paracasei subsp. paracasei NTU 101 (NTU 101), isolated from the gut of healthy infants, has demonstrated various probiotic effects and shown safety in a prior 28-day animal feeding study. To further verify its safety and mitigate potential risks, we performed a comprehensive genotypic and phenotypic safety evaluation in accordance with the European Food Safety Authority guidelines for safety assessment through whole genome sequencing and related literature. In this research, minimum inhibitory concentration testing identified NTU 101’s resistance to chloramphenicol; however, subsequent gene analysis confirmed no associated risk of resistance. Assessments of safety, including biogenic amine content, hemolytic activity, mucin degradation, and D-lactic acid production, indicated a low level of risk. Additionally, a repeated-dose 90-day oral toxicity study in Sprague-Dawley rats revealed no toxicity at a dose of 2000 mg/kg body weight, further supporting the strain’s safety for consumption. Based on these comprehensive analyses, NTU 101 is considered safe for regular consumption as a health supplement. Full article

Semen persicae is the dried mature seeds of Prunus persica (L.) Batsch and P. davidiana (Carr.) Franch and is commonly used in traditional Chinese medicine (TCM) formulations because of its variety of biological effects. The present study aimed to evaluate the antioxidant activity and toxicity profiles of semen persicae extract (SPE) after determining the amygdalin content (4.95%) using HPLC. Regarding the in vitro antioxidant activity, SPE with 2 mg/mL concentration scavenged 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl, and ABTS free radicals with rates of 51.78%, 55.47%, and 57.16%, respectively. The same concentration of SPE chelated 30.76% Fe²⁺. The in vitro cytotoxicity study revealed that SPE induced 92.45% cell viabilities of HEPG2 even at 2000 μg/mL. In the acute toxicity study, oral administration of SPE did not provoke mortality or any toxic signs at doses up to 2000 mg/kg bw. Repeated oral administration for 28 days at doses of 100, 300, and 600 mg/kg per day in rats did not show any toxicity signs or gross pathological abnormalities. The results of the present research provide basic reference data for SPE with a moderate effect on antioxidant activity and low toxicity for future screening of biological and pharmacological properties. Full article

Globally, the edible insect industry is emerging due to its potential contributions to food security and environmental sustainability. Edible insects are rapidly being integrated into the development of alternative foods and new pharmaceuticals. Silkworms, known for their high protein content, are not only a potential new source of human food and animal feed but have also been traditionally used for medicinal purposes. However, conventional silkworms are difficult to ingest. To address this, we have developed a steamed and freeze-dried mature silkworm larva powder (SMSP), and it is essential to investigate its potential toxicity and food safety for further studies and applications. Therefore, this study aimed to evaluate the toxicity of SMSP. A toxicity assessment of SMSP was conducted according to OECD guidelines. An oral repeat-administration study was performed on male and female SD rats at doses of 625, 1250, and 2500 mg/kg/day for 4 and 13 weeks. No toxicological changes were observed in clinical signs, body weight, water and food intake, urine tests, hematology, clinical biochemistry, gross findings, or histopathological examination. In conclusion, the no observed adverse effect level (NOAEL) of SMSP was 2500 mg/kg/day, with no target organs identified in either sex of the rats. These results suggest that SMSP is safe, is without side effects and has potential for use as an edible ingredient and in health functional food applications. Full article

The impact of oral administration of mechanically fibrillated cellulose nanofibers (fib-CNF), a commonly used nanofiber, on toxicity and health remains unclear, despite reports of the safety and beneficial effects of chitin-based nanofibers. Thus, evaluating the oral toxicity of fib-CNF in accordance with OECD Test Guideline 407 (TG407) is essential. This study aimed to assess the safety of orally administered fib-CNF through an acute toxicity study in rats, following the OECD TG407 guidelines for 4 weeks. CNF “BiNFi-s” FMa-10005, derived from mechanically fibrillated pulp cellulose, was administered via gavage to male and female Crl:CD(SD) rats at doses of 50, 150, 500, and 1000 mg/kg/day for 28 days, with a control group receiving water for injection. The study evaluated the toxic effects of repeated administration, and the rats were monitored for an additional 14 days post-administration to assess recovery from any toxic effects. The results showed no mortality in either sex during the administration period, and no toxicological effects related to the test substance were observed in various assessments, including general condition and behavioral function observations, urinalysis, hematological examination, blood biochemical examination, necropsy findings, organ weights, and histopathological examination. Notably, only female rats treated with 1000 mg/kg/day of CNF exhibited a consistent reduction in body weight during the 14-day recovery period after the end of treatment. They also showed a slight decrease in pituitary and liver weights. However, hematological and blood biochemical tests did not reveal significant differences, suggesting a potential weight-suppressive effect of CNF ingestion. Full article

Background: (-)-Fenchone is a naturally occurring monoterpene found in the essential oils of Foeniculum vulgare Mill., Thuja occidentalis L., and Peumus boldus Molina. Pharmacological studies have reported its antinociceptive, antimicrobial, anti-inflammatory, antidiarrheal, and antioxidant activities. Methods: The preventive antiulcer effects of (-)-Fenchone were assessed through oral pretreatment in cysteamine-induced duodenal lesion models. Gastric healing, the underlying mechanisms, and toxicity after repeated doses were evaluated using the acetic acid-induced gastric ulcer rat model with oral treatment administered for 14 days. Results: In the cysteamine-induced duodenal ulcer model, fenchone (37.5–300 mg/kg) significantly decreased the ulcer area and prevented lesion formation. In the acetic acid-induced ulcer model, fenchone (150 mg/kg) reduced (p < 0.001) ulcerative injury. These effects were associated with increased levels of reduced glutathione (GSH), superoxide dismutase (SOD), interleukin (IL)-10, and transforming growth factor-beta (TGF-β). Furthermore, treatment with (-)-Fenchone (150 mg/kg) significantly reduced (p < 0.001) malondialdehyde (MDA), myeloperoxidase (MPO), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and nuclear transcription factor kappa B (NF-κB). A 14-day oral toxicity investigation revealed no alterations in heart, liver, spleen, or kidney weight, nor in the biochemical and hematological parameters assessed. (-)-Fenchone protected animals from body weight loss while maintaining feed and water intake. Conclusion: (-)-Fenchone exhibits low toxicity, prevents duodenal ulcers, and enhances gastric healing activities. Antioxidant and immunomodulatory properties appear to be involved in its therapeutic effects. Full article

The present study involves the precise identification and safety evaluation of Enterococcus casseliflavus KB1733, previously identified using 16S rRNA analysis, through whole-genome sequencing, phenotypic analysis, and preclinical toxicity studies. Analyses based on the genome sequencing data confirm the identity of KB1733 as E. casseliflavus and show that the genes related to vancomycin resistance are only present on the chromosome, while no virulence factor genes are present on the chromosome or plasmid. Phenotypic analyses of antibiotic resistance and hemolytic activity also indicated no safety concerns. A bacterial reverse mutation test showed there was no increase in revertant colonies of heat-killed KB1733. An acute toxicity test employing heat-killed KB1733 at a dose of 2000 mg/kg body weight in rats resulted in no deaths and no weight gain or other abnormalities in the general condition of the animals, with renal depression foci and renal cysts only occurring at the same frequency as in the control. Taking the background data into consideration, the effects on the kidneys observed in the current study were not caused by KB1733. Our findings suggest that KB1733 is non-pathogenic to humans/animals, although further studies involving repeated oral toxicity tests and/or clinical tests are required. Full article