LD50 Values Research Articles

A Minor Groove Binder with Significant Cytotoxicity on Human Lung Cancer Cells: The Potential of Hesperetin Functionalised Silver Nanoparticles.

Natural drug functionalised silver (Ag) nanoparticles (NPs) have gained significant interest in pharmacology related applications due to their therapeutic efficiency. We have synthesised silver nanoparticle using hesperetin as a reducing and capping agent. This work aims to discuss the relevance of the hesperetin functionalised silver nanoparticles (H-AgNPs) in the field of nano-medicine. The article primarily investigates the anticancer activity of H-AgNPs and then their interactions with calf thymus DNA (ctDNA) through spectroscopic and thermodynamic techniques. The green synthesised H-AgNPs are stable, spherical in shape and size of 10 ± 3nm average diameter. The complex formation of H-AgNPs with ctDNA was established by UV-Visible absorption, fluorescent dye displacement assay, isothermal calorimetry and viscosity measurements. The binding constants obtained from these experiments were consistently in the order of 104 Mol-1. The melting temperature analysis and FTIR measurements confirmed that the structural alterations of ctDNA by the presence of H-AgNPs are minimal. All the thermodynamic variables and the endothermic binding nature were acquired from ITC experiments. All these experimental outcomes reveal the formation of H-AgNPs-ctDNA complex, and the results consistently verify the minor groove binding mode of H-AgNPs. The binding constant and limit of detection of 1.8μM found from the interaction studies imply the DNA detection efficiency of H-AgNPs. The cytotoxicity of H-AgNPs against A549 and L929 cell lines were determined by in vitro MTT cell viability assay and lactate dehydrogenase (LDH) assay. The cell viability and LDH enzyme release are confirmed that the H-AgNPs has high anticancer activity. Moreover, the calculated LD50 value for H-AgNPs against lung cancer cells is 118.49µl/ml, which is a low value comparing with the value for fibroblast cells (269.35µl/ml). In short, the results of in vitro cytotoxicity assays revealed that the synthesised nanoparticles can be considered in applications related to cancer treatments. Also, we have found that, H-AgNPs is a minor groove binder, and having high DNA detection efficiency.

In silico, in vitro, and in vivo acute and sub-acute toxicity profiling of whole plant methanol extract of Equisetum diffusum D. Don from the sub-Himalayan West Bengal, India, having ethnobotanical uses

BackgroundEquisetum diffusum D. Don commonly known as ‘Himalayan horsetail’, has been traditionally used in the treatment of back pain, bone fracture and dislocation, and arthritis by various tribal communities of India. Our previous study confirmed the anti-inflammatory efficacy of the plant through in silico, in vitro, and in vivo model studies. Therefore, the current research is focused on safety dose evaluation for the first-time of the whole-plant methanol extract (EDME) of E. diffusum through appropriate in silico, in vitro, and in vivo approaches.MethodThe whole plant, along with its rhizomes, was collected, and the methanol extract was prepared. The in silico ADMET study was performed to predict the pharmacokinetics profile and toxicity of all the identified phyto-compounds of EDME previously screened by GC–MS study. In vitro cytotoxicity study of EDME was performed using two cell lines: kidney (HEK293) and liver (Huh7) cell lines. The in vivo toxicity study of EDME was validated by the acute toxicity (OECD 423, 2002) and sub-acute toxicity assays (OECD 407, 2008) in the Wistar Albino rat model.ResultsThe in silico ADMET study of all 47 bioactives predicted good pharmacokinetic and low toxicity profiles. In vitro cytotoxicity showed higher IC50 values of EDME viz., 672 ± 15.7 μg/mL and 1698 ± 6.54 μg/mL for both kidney (HEK293) and liver (Huh7) cell lines, respectively, which were considered as low-toxic. Based on acute oral toxicity, the LD50 value of the extract was considered “non-toxic” up to a feeding range of 2000 mg/kg of body weight. The regular consumption of the extract for an extended period (28 days) was also qualified as safe based on the body and organ weight, hematological, biochemical, and histoarchitecture results in the sub-acute toxicity assay.ConclusionThe detailed in silico, in vitro, in vivo (acute and sub-acute oral toxicity) studies gave us a new insight to the safety dose evaluation of Equisetum diffusum, which may serve as a reliable documentation for undertaking the experimental validation of the ethnobotanical uses of the plant which would help in the field of drug development for the treatment of inflammation related complications.

Toxicity and Repellent Effect of Three Plant Based Essential Oils against the Red Flour Beetle <i>Tribolium castaneum</i> (Herbst)

In this study jasmine (Jasminum officinale), lemon grass (Cymbopogon citratus), and sandalwood (Santalum album) essential oils were investigated for their efficacy against the red flour beetle Tribolium castaneum. Sandalwood oil consistently showed the highest contact toxicity, with LD50 values decreasing over time. Jasmine and lemon grass oils ranked lower but still exhibited toxicity. The order of contact toxicity was sandalwood > jasmine > lemon grass at each exposure period. Fumigation treatments revealed sandalwood’s initial superiority, though jasmine surpassed it at 48 hr. The order of fumigation toxicity shifted to jasmine > sandalwood > lemon grass at this extended exposure time. Repellency tests showed dose and time-dependent responses for both larval and adult stages, with occasional fluctuations. Sandalwood’s significance differed for adult beetles between time intervals, and jasmine exhibited insignificance in its efficacy for larvae at certain intervals. This study provides insights into the potential of these essential oils as alternatives for pest control.

Evaluation of Saffron Quality Using Rapid Quantitative Inspection Technology with Near-Infrared Spectroscopy.

A predictive model utilizing near-infrared spectroscopy was developed to estimate the loss on drying, total contents of crocin I and crocin II, and picrocrocin content of saffron. Initially, the LD values were determined using a moisture-ash analyzer, while HPLC was employed for measuring the total contents of crocin I, crocin II, and picrocrocin. The near-infrared spectra of 928 saffron samples were collected and preprocessed using first derivative, standard normal variable transformation, detrended correction, multivariate scattering correction, Savitzky-Golay smoothing, and mean centering methods. Leveraging the partial least squares method, regression models were constructed, with parameters optimized through a selective combination of the above six preprocessing methods. Subsequently, prediction models for loss on drying, total contents of crocin I and crocin II, and picrocrocin content were established, and the prediction accuracy of the models was verified. The correlation coefficients and root mean square error of loss on drying, total contents of crocin I and crocin II, and picrocrocin content demonstrated high accuracy, with R2 values of 0.8627, 0.8851, and 0.8592 and root mean square error values of 0.0260, 0.0682, and 0.0465. This near-infrared prediction model established in the present study offers a precise and efficient means of assessing loss on drying, total contents of crocin I and crocin II, and picrocrocin content in saffron and is useful for the development of a rapid quality evaluation system.

Antimicrobial characteristics of endophytic Aspergillus terreus and acute oral toxicity analysis

BackgroundEndophytic fungi produce biologically robust metabolites suitable for diverse applications, which support the increasing exploration of these fungi. The study aimed to investigate the in vitro antimicrobial properties of the metabolites of endophytic fungus Aspergillus terreus which isolated from the leaves of Psidium guajava plants while the acute oral toxicity was assessed in vivo. ResultsA. terreus (OR125572) was successfully isolated for the first time from P. guajava. The ethyl acetate extract of A. terreus exhibited antibactericidal effects against Enterobacter aerogenes with a minimum inhibitory concentration of 18.75 mg/ml in contrast to 75.00 ± 0.0, 37.50, and 37.50 mg/ml, respectively against Staphylococcus aureus, Escherichia coli, and Bacillus sphaericus were 75.00 ± 0.0, 37.50, and 37.50 mg/ml, respectively. Analysis of the crude extract obtained from A. terreus by GC-MS revealed a total of 32 distinct compounds. The major components included 1,2-benzenedicarboxylic acid, di-iso-octyl ester; hexyl oxecan-2-one and phenol. The acute oral toxicity study found no symptoms of toxicity and no mortality until the 14th d, suggesting that the LD50 value of A. terreus extract might exceed 1 ml/kg. The group receiving 0.5 ml/kg of A. terreus extract experienced a 42.9% increase in body weight, while administration of varying dosages resulted in a significant reduction in MCV levels. There was also a significant increase in the proportion of monocytes across all treated groups. ConclusionsThe study demonstrated the potential of A. terreus as a source of antimicrobial and other bioactive compounds, with relatively low acute toxicity.How to cite: Shehabeldine AM, Abdelaziz AM, Abdel-Maksoud MA, et al. Antimicrobial characteristics of endophytic Aspergillus terreus and acute oral toxicity analysis. Electron J Biotechnol 2024;72. https://doi.org/10.1016/j.ejbt.2024.07.003.

Anti-Inflammatory Activity and Acute Toxicity Of Pereskia aculeata, In Zophobas morio Larvae.

Pereskia aculeata has been widely investigated due to its anti-inflammatory potential. Among the metabolites found in this species are the phytosterols beta-sitosterol (β-SIT) and stigmasterol (STIG). The objective of the study was to evaluate the anti-inflammatory and toxicity activities of the hexane partition of P. aculeata (PHEX), as well as β-SIT and STIG. PHEX was prepared and the phytosterols were quantified. In terms of toxicity against L929 fibroblast cells, PHEX showed toxicity up to 200 μg/mL; STIG and β-SIT showed toxicity up to 25 μg/mL. PHEX inhibited 66 % of nitric oxide radicals, while STIG and β-SIT inhibited 33.73 % and 34.94 %, respectively. In an anti-inflammatory test against Zophobas morio larvae, all samples significantly reduced hemocyte levels. Additionally, the LD50 values were calculated: 229.6 mg/kg for PHEX, 101.5 mg/kg for STIG, and 103.8 mg/kg for β-SIT. In conclusion, the study indicates that the phytosterols present in PHEX may contribute to its anti-inflammatory activity.

Antiplasmodial evidence, host mitochondrial biology and possible mechanisms of action of a composite extract of Azadiractha indica and Curcuma longa in Plasmodium berghei-infected mice.

Azadirachta indica A. Juss (Meliaceae) (AI) and Curcuma longa L. (Zingiberaceae) (CL) are used for malaria treatment but their anti-glycolytic and host mitochondrial effects have not been studied. The AI stem-bark and CL rhizomes were extracted with methanol. Methanol extract of CL (Turmeric) was partitioned to yield methanol fraction (MF). Swiss mice infected with Plasmodium berghei (NK 65 strain) were treated with 200 and 400mg/kg of AI and turmeric for seven days. Turmeric and MF (200 and 400mg/kg) were combined with 400mg/kg AI to treat mice infected with Plasmodium berghei (ANKA strain) for four days. Drug and infected controls mice were treated with artemether lumefantrine (10mg/kg) and distilled water (10mL/kg), respectively. Serum lactate dehydrogenase (LDH) and aldolase activities were determined. Liver mitochondria were obtained for mitochondrial permeability transition (mPT) pore opening and FoF1 ATPase assays. The curcumin content of turmeric was determined using HPLC while LD50 of Turmeric and AI was also determined. The AI, and its combination with turmeric decreased parasite load and increased chemosuppression in both sensitive and resistant studies while MF and its combinations with AI induced mPT pore opening. In the resistant experiment, AI + Turmeric 400mg/kg decreased FoF1 ATPase, LDH and aldolase activities against the infected control. The LD50 values of both extracts were above 2000mg/kg while the MF had the highest curcumin content. Antiplasmodial mechanisms of action of AI, CL and their combinations involve anti-glycolytic effects. Their composite formulations are more potent in malaria treatment.

Virtual expedition into nature’s pharmacy: Unveiling promising anticancer compounds from Dendrophthoe falcata through in-silico exploration

Cancer is a leading threatful disease worldwide. Research focused on natural compounds for anticancer drugs has facilitated the identification of numerous medications presently employed in cancer treatment. There is an ongoing need to create novel, potent, and cost-effective anticancer medications. In the present study, we have virtually investigated the potential anticancer activity of compounds namely nonadecan-1-ol, stigmast-4-en-3-one, 3β-hydroxylup-20(29)-en-28-oic acid, 7-hydroxy-4′,5,6-trimethoxyflavone, and 2,3-dihydro-4-hydroxy-3,6,9-trimethylnaphtho[1,8-bc]pyran-7,8-dione extracted from the natural source Dendrophthoe falcata against cancer-causing target proteins (cdk-2, p53, and caspase-9) using various in silico techniques, including molecular docking and simulation. Furthermore, drug-likeness, ADMET prediction, toxicity prediction, and DFT were performed to explore the toxicity and efficacy of therapeutic molecules. The present study is the first report of compounds known for their enormous biological applications from D. falcata, highlighting its novelty. The results revealed the highest negative binding affinity of 7-hydroxy-4′,5,6-trimethoxyflavone and 2,3-dihydro-4-hydroxy-3,6,9-trimethylnaphtho[1,8-bc]pyran-7,8-dione with all three target proteins. Additionally, cytotoxicity revealed the highest LD50 value, suggesting the lowest toxicity for the selected compounds. ADME analysis showed good responses in terms of solubility and absorption, supporting the drug-likeness of the proposed molecules. MD simulation and DFT results indicated the stability of the complex at a temperature of 298 K. The results concluded that the proposed molecules extracted from D. falcata have drug-like properties with tight and stable binding with the targeted proteins and might behave as potential anticancer agents.

Toxicological profiling of methanolic seed extract of Abutilon indicum (L.) Sweet: in-vitro and in-vivo analysis

Ethnopharmacological relevanceAbutilon indicum, a shrub of the Malvaceae family, is found abundantly in tropical countries like India. A. indicum is widely used for its high medicinal properties. Traditionally, A. indicum seed powder is consumed to treat piles, constipation, chronic cystitis, gonorrhea, gleet, and pregnancy-related problems. Despite having numerous medicinal properties and widespread traditional use of A. indicum seeds, scientific validation, and toxicity studies have yet to be documented. Aims of the studyThe primary objective of this study is to conduct a comprehensive study on phytochemical profiling, in-vitro cytotoxicity, mutagenicity, and in-vivo acute and sub-acute toxicity, and genotoxicity on animal models of methanolic extract of A. indicum seed (MAS). Materials and methodsThe qualitative analysis of MAS was explored through FTIR and HR LC-MS. For in-vitro cytotoxicity, the HEK-293 cell line was used, and the TA100 (Staphylococcus typhimurium) bacterial strain was used for the Ames mutagenicity test. A single oral dose of 250, 500, 1000, or 2000 mg/kg body weight of MAS was given to each male and female rat for acute toxicity study and observed for 14 days for any toxicity signs. In the sub-acute toxicity study, 250, 500, or 1000 mg/kg body weight of MAS was administered orally to each rat for 28 days. The experimental animals were weighed weekly, and general behavior was monitored regularly. After 28 days of the experiment, the rats were sacrificed, and different serum biochemical, hematological, and histological analyses were performed. The blood samples of different doses of MAS were used for genotoxicity study through comet assay. ResultsFTIR analysis found different functional groups, which indicated the presence of phenolics, flavonoids, and alkaloids. HR LC-MS analysis depicts several components with different biological functions. The cell cytotoxicity and Ames mutagenicity results showed minimal toxicity and mutagenicity up to a certain dose. The acute toxicity study conducted in Wistar albino rats demonstrated zero mortality among the animals, and the LD50 value for seed extract was determined to be 2000 mg/kg body weight. Sub-acute toxicity assessments indicated that the administration of seed extract resulted in no adverse effects at dosages of 250 and 500 mg/kg body weight. However, at higher doses, specifically 1000 mg/kg body weight, the liver of the experimental rats exhibited some toxic effects. In the genotoxicity study, minimal DNA damage was found in 250 and 500 mg/kg doses, respectively, but slightly greater DNA damage was found in 1000 mg/kg doses in both male and female rats. ConclusionsThe consumption of A. indicum seed powder is deemed safe; however, doses exceeding 500 mg/kg body weight may raise concerns regarding use. These findings pave the path for the creation of innovative medicines with improved efficacy and safety profiles.

Assessment of Lambda-Cyhalothrin and Spinetoram Toxicity and Their Effects on the Activities of Antioxidant Enzymes and Acetylcholinesterase in Honey Bee (Apis mellifera) Larvae.

Honeybees play a crucial role as agricultural pollinators and are frequently exposed to various pollutants, including pesticides. In this study, we aimed to evaluate the toxicity of lambda-cyhalothrin (LCY) and spinetoram (SPI) in honey bee larvae reared in vitro through single (acute) and repeated (chronic) exposure. The acute LD50 values for LCY and SPI were 0.058 (0.051-0.066) and 0.026 (0.01-0.045) μg a.i./larva, respectively. In chronic exposure, the LD50 values of LCY and SPI were 0.040 (0.033-0.046) and 0.017 (0.014-0.019) μg a.i./larva, respectively. The chronic no-observed-effect dose of LCY and SPI was 0.0125 μg a.i./larva. Adult deformation rates exceeded 30% in all LCY treatment groups, showing statistically significant differences compared to the solvent control group (SCG). Similarly, SPI-treated bees exhibited significantly more deformities than SCG. Furthermore, we examined the activities of several enzymes, namely, acetylcholinesterase (AChE), glutathione-S-transferase (GST), catalase (CAT), and superoxide dismutase (SOD), in larvae, pupae, and newly emerged bees after chronic exposure at the larval stage (honey bee larval chronic LD50, LD50/10 (1/10th of LD50), and LD50/20 (1/20th of LD50)). LCY and SPI induced significant changes in detoxification (GST), antioxidative (SOD and CAT), and signaling enzymes (AChE) during the developmental stages (larvae, pupae, and adults) of honey bees at sublethal and residue levels. Our results indicate that LCY and SPI may affect the development of honey bees and alter the activity of enzymes associated with oxidative stress, detoxification, and neurotransmission. These results highlight the potential risks that LCY and SPI may pose to the health and normal development of honey bees.

Biodegradable Schiff bases: a novel approach for the management of pathogenic fungi (Sclerotium rolfsii and Rhizoctonia bataticola) and stored grain insect (Callosobruchus maculatus) in green gram (Vigna radiata).

Twenty-two eco-friendly, novel Schiff bases were synthesized from 2,4,5-trichloro aniline and characterized by using FT-IR, 1H NMR, and 13C NMR techniques. Fungicidal activity against pathogenic fungi Sclerotium rolfsii and Rhizoctonia bataticola and insecticidal activity against the stored grain insect pest Callosobruchus maculatus of the test compounds were evaluated under control condition. All of the investigated compounds, according to the study, exhibited moderate to good antifungal and insecticidal activities. The best antifungal activity against both pathogenic fungi was demonstrated by C15 and C16 whose ED50 values were recorded 11.4 and 10.4μg/mL against R. bataticola and 10.6 and 11.9μg/mL against S. rolfsii, respectively. They were further screened in for disease suppression against both pathogenic fungi under pot condition through different methods of applications in green gram (Vigna radiata L.) crop. The compounds C10 and C18 had the highest insecticidal activity, with LD50 values of 0.024 and 0.042 percentages, respectively. Stepwise regression analysis using root mean square error (RMSE) and correlation coefficient (R) method used to validate the quantitative structure activity relationship (QSAR) of synthesized compounds in addition to their fungicidal and insecticidal actions. To the best of our knowledge, this investigation on the 22 new Schiff bases as possible agrochemicals is the first one that has been fully reported.

Activity of antioxidant defense system in fenoxycarb treated mango leaf webber Orthaga exvinacea Hampson (Lepidoptera: Pyralidae)

The toxicity of the synthetic insecticide fenoxycarb, an insect growth inhibitor, was assayed against the sixth instar larvae of Orthaga exvinacea. This lepidopteran pest is considered as major annoyance of mango cultivation throughout India which could significantly reduce the crop yield. The lethality of this insecticide with different concentrations against the organism was examined. The effect of this insecticide on the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), peroxidase (POD) and glutathione reductase (GR) was estimated. The results revealed that the insecticide exerted excellent larvicidal activity against the target organism with an LD50 value of 30.339 ppm. The observations revealed that there was a consistent cutback in the activity of all of the antioxidant defense enzymes in response to the sublethal doses of the insecticide. The fenoxycarb treatment also resulted in lipid peroxidation (LPO) in the larvae. With reference to O. exvinacea, this study may provide information about the biological and physiological effects of fenoxycarb on pest species.

Layered double hydroxide/conductive polymer nanocomposites: Toward multifunctional biocompatible nanoadsorbents for wastewater treatment applications

ABSTRACT Layered double hydroxide (LDH)/conductive polymer nanocomposites combine the promising adsorption capabilities of 2D layered nanomaterials and the electric properties of conductive polymers, resulting in multifunctional adsorbents for wastewater treatment. In this work, a simple in situ polymerization of aniline was conducted in the presence of Zn-Fe LDH to synthesize a Zn-Fe LDH/PANI nanocomposite, which was characterized by XRD, FTIR, SEM, and BET. The composite showed a particle-like morphology with a size of 30–60 nm and a BET surface area of 23.27 m2/g and was used as an adsorbent for carbamazepine (CBZ). Zn-Fe LDH/PANI removed 98% of CBZ at pH 7, 0.2 g/L, and 40 mg/L CBZ. For biocompatibility, acute toxicity was assessed in vivo for ten days using male albino rats, and probit analysis (after 2, 6, and 24 hours) was used to determine the LD0, LD20, LD50, LD90, and LD100 values, which were calculated to be 890, 1051, 3188, 6371, and 11,300, respectively. During this time, the rats were weighed, and other observations were made, including mortality, behavior, injuries, and any symptoms of toxicity or side effects. Histopathological examination of organs such as the liver, kidney, brain, skin, intestine, and cecum for any pathological alterations was performed. Two green metrics were applied, the Analytical Eco-scale and the Analytical GREEness Calculator (AGREE).

Antiplasmodial potential of isolated xanthones from Mesua ferrea Linn. roots: an in vitro and in silico molecular docking and pharmacokinetics study

BackgroundMalaria is a major global health concern, particularly in tropical and subtropical countries. With growing resistance to first-line treatment with artemisinin, there is an urgent need to discover novel antimalarial drugs. Mesua ferrea Linn., a plant used in traditional medicine for various purposes, has previously been investigated by our research group for its cytotoxic properties. The objective of this study was to explore the compounds isolated from M. ferrea with regards to their potential antiplasmodial activity, their interaction with Plasmodium falciparum lactate dehydrogenase (PfLDH), a crucial enzyme for parasite survival, and their pharmacokinetic and toxicity profiles.MethodsThe isolated compounds were assessed for in vitro antiplasmodial activity against a multidrug-resistant strain of P. falciparum K1 using a parasite lactate dehydrogenase (pLDH) assay. In vitro cytotoxicity against Vero cells was determined using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The interactions between the isolated compounds and the target enzyme PfLDH were investigated using molecular docking. Additionally, pharmacokinetic and toxicity properties were estimated using online web tools SwissADME and ProTox-II, respectively.ResultsAmong the seven compounds isolated from M. ferrea roots, rheediachromenoxanthone (5), which belongs to the pyranoxanthone class, demonstrated good in vitro antiplasmodial activity, with the IC50 being 19.93 µM. Additionally, there was no toxicity towards Vero cells (CC50 = 112.34 µM) and a selectivity index (SI) of 5.64. Molecular docking analysis revealed that compound (5) exhibited a strong binding affinity of − 8.6 kcal/mol towards PfLDH and was stabilized by forming hydrogen bonds with key amino acid residues, including ASP53, TYR85, and GLU122. Pharmacokinetic predictions indicated that compound (5) possessed favorable drug-like properties and desired pharmacokinetic characteristics. These include high absorption in the gastrointestinal tract, classification as a non-substrate of permeability glycoprotein (P-gp), non-inhibition of CYP2C19, ease of synthesis, a high predicted LD50 value of 4,000 mg/kg, and importantly, non-hepatotoxic, non-carcinogenic, and non-cytotoxic effects.ConclusionsThis study demonstrated that compounds isolated from M. ferrea exhibit activity against P. falciparum. Rheediachromenoxanthone has significant potential as a scaffold for the development of potent antimalarial drugs.

Genotoxicity, acute and sub-acute toxicity profiles of methanolic Cordyceps militaris (L.) Fr. extract in Swiss Albino Mice

Ethnopharmacological relevanceCordyceps militaris, a traditional medicinal fungus, parasitizes the intestines of lepidopteron pupae or larvae, predominantly during the winter, and undergoes fruiting in the summer or autumn. Compounds extracted from C. militaris have demonstrated a broad spectrum of pharmacological effects, including antioxidant, anti-tumor, anti-metastatic, anti-inflammatory, antiviral, anti-diabetic, and various others. Aim of the studyHerein, our study aimed at elucidating the acute, sub-acute toxicity, and genotoxicity profiles of C. militaris methanolic extract following oral administration in Swiss albino mice, representing the inaugural comprehensive exploration of the toxicological and safety profiles of C. militaris. Materials and methodsPrior studies have predominantly focused on its biological activities rather than its toxicity. Acute oral toxicity study was conducted at 500, 1000, and 2000 mg/Kg B.W. doses of C. militaris over a 14-day period. For sub-acute toxicity study, three groups of mice were administered 100, 300, and 600 mg/Kg B.W. of C. militaris extract for 28 consecutive days; one group served as a control. Mice were monitored for their body weight and behavioural changes once daily. Hematological, serum biochemical, histopathological, histomorphometric, seminal parameters, and mutagenic investigations were performed post-treatment period. ResultsAcute oral toxicity study at 2000 mg/Kg revealed no signs of toxicity, with an LD50 value surpassing 2000 mg/Kg. No occurrences of mortality observed, and no significant changes were noted in body weight, organ weight, or behaviour. Hematological analysis illustrated a marked upsurge in RBC, Hb, HCT, PLT, MPV, and PCT, alongside minor variations in differential leucocyte count post 28-day treatment. Liver enzyme tests indicated slight elevation in ALP, while renal enzyme tests showed alterations in CRE and BUN levels. Genotoxicity profile and histopathological assessments of the liver, spleen, testis, and ovary manifested no remarkable irregularities, except for mild renal toxicity. Seminal parameters including sperm concentration, motility and testosterone levels demonstrated a noteworthy increase. ConclusionsThe study sheds light on the potential risks and safety considerations associated with C. militaris-based medicinal products. These findings establish a foundation for further investigations and the refinement of dosage optimization in the application of C. militaris, with the aim of mitigating any potential adverse effects.

Ornamental plants as vectors of pesticide exposure and potential threat to biodiversity and human health

The production of conventional ornamental plants is pesticide-intensive. We investigated whether pesticide active ingredients (AIs) are still present in ornamentals at the time of purchase and assessed their potential ecotoxicity to non-target organisms. We purchased 1000 pot plants and 237 cut flowers of different species from garden centers in Austria and Germany between 2011 and 2021 and analyzed them for up to 646 AIs. Ecotoxicological risks of AIs were assessed by calculating toxic loads for honeybees (Apis mellifera), earthworms (Eisenia fetida), birds (Passer domesticus), and mammals (Rattus norvegicus) based on the LD50 values of the detected AIs. Human health risks of AIs were assessed on the basis of the hazard statements of the Globally Harmonized System. Over the years, a total of 202 AIs were detected in pot plants and 128 AIs in cut flowers. Pesticide residues were found in 94% of pot plants and 97% of cut flowers, with cut flowers containing about twice as many AIs (11.0 ± 6.2 AIs) as pot plants (5.8 ± 4.0 AIs). Fungicides and insecticides were found most frequently. The ecotoxicity assessment showed that 47% of the AIs in pot plants and 63% of the AIs in cut flowers were moderately toxic to the considered non-target organisms. AIs found were mainly toxic to honeybees; their toxicity to earthworms, birds, and mammals was about 105 times lower. Remarkably, 39% of the plants labeled as “bee-friendly” contained AIs that were toxic to bees. More than 40% of pot plants and 72% of cut flowers contained AIs classified as harmful to human health. These results suggest that ornamental plants are vectors for potential pesticide exposure of consumers and non-target organisms in home gardens.

A standardized chamuangone enriched extract from Garcinia cowa Roxb. leaves shows acute and sub-acute safety

Ethnopharmacological relevanceThe safety assessment of herbal products is critical for their appropriate pharmacological applications. Garcinia cowa Roxb., commonly known as Cha-muang in Thai, has ethnopharmacological relevance for inflammation, infectious diseases, and diabetes. The leaf extracts of G. cowa have been extensively reported for their anticancer, anti-inflammatory, antimicrobial, and antioxidant effects. Notably, chamuangone is their major active constituent that contributes to various pharmacological properties. Aim of the studyThe current study aims to establish a standardized chamuangone enriched extract (CEE) and assess its acute and sub-acute toxicities in animal models. MethodologyCEE was established from G. cowa leaves using a microwave-assisted extraction (MAE), followed by fractionation and enrichment through silica gel vacuum and column chromatography. The concentration of chamuangone in the extract was quantified using a validated quantitative high-performance liquid chromatography (HPLC) method. The safety profiles of CEE were thoroughly evaluated in rodents according to the Organization for Economic Cooperation and Development (OECD) 425 and 407 guidelines. The effects on oxidative stress markers such as superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), and malondialdehyde (MDA) levels were also evaluated in various organs. ResultsBased on the quantitative HPLC analysis, the CEE contained 73.0 ± 2.0% w/w of chamuangone. In the acute toxicity study, following up and down procedure the female rats were dosed with CEE at 1750 and 550 mg/kg body weight (b.w.), with CEE 1750 mg/kg b.w. was toxic, causing mortality, while CEE 550 mg/kg b.w. was deemed safe. An LD50 value was calculated according to the standard protocols, resulting in 970 mg/kg b.w. In histopathological examination, 550 mg/kg b.w. of CEE was safe in all the selected organs, while the 1750 mg/kg b.w. CEE treated rats exhibited toxic effects in histological tissues sections in the form of necrosis in the brain, cardiac muscle hypertrophy, liver inflammation, mild untoward effect in the spleen, fibrosis in the lungs, pancreatitis, pyelonephritis, and ovarian cyst. Administration of CEE at doses of 550 mg/kg b.w. (single dose) in the acute and 100 mg/kg b.w. (regularly 28-days) in the sub-acute toxicity studies significantly (p < 0.05) decreased levels of uric acid, triglycerides, and cholesterol. Importantly, the CEE (550 and 100 mg/kg b.w.) also significantly increased the levels of antioxidant enzymes (SOD, GSH, and CAT) and decreased MDA levels. Normal histopathology was observed in the sub-acute toxicity study in all treated groups. ConclusionThis study successfully concludes that CEE at a dose of 100 mg/kg b.w. is safe for therapeutic application or use as a chemopreventive functional food utilizing green extraction methods. However, chronic toxicity studies are further recommended to validate safety concerns over an extended period.

Multifunctional CoCe/silica and CoMnCe/silica spinel ferrite nanocomposite: in vitro and in vivo evaluation for cancer therapy

Multifunctional magnetic spinel ferrite based on CoCe and CoMnCe/silica nanocomposites (NCs) were developed for targeted cancer therapeutics. The formation of spinel ferrite and co-existence of spinel ferrite/silica/chemo-drug, surface/pore size distribution, morphological features and magnetic properties were investigated using different characterization techniques. XRD pattern confirmed the pure phase of CoCe and CoMnCe spinel ferrite with estimated crystal size of 27.9 nm. After silica coating and pegylation, the crystal size of CoCe and CoMnCe increases to 36.3 nm and 76.2 nm. Nitrogen adsorption isotherm confirm an effective embedment of both spinel ferrites into silica with large surface area (653 m2/g and 718 m2/g) and uniform pore size distributions (6.1 nm and 6.9 nm). FT-IR spectra confirm the magnetic spinel ferrite/silica interactions (977, 1705 and 3410 cm−1), cisplatin functionalization (1645 cm−1) and PEG (1275–2900 cm−1). Coating SFNPswith Si and/or Cp and/or PEG, tunes the magnetic characteristics of the NCs system. For both CoCe and CoMnCe SFNPs, saturation magnetization (Ms) of 14.96 and 10.91 emu/g, residual magnetization (Mr) of 4.40 and 2.42 emu/g, Hc (coercivity) of 1072.1 and 719.3 Oe gradually diminish upon Si, respectively. The chemical state of CoMnCe SFNPs, CoCe SFNPs, their silica and active cisplatin NCs (Pt0 and Pt2+) were investigated using X-ray Photoelectron Spectroscopy (XPS). The anti-cancer efficacy of pegylated nanoformulations were tested in in vitro cells (HeLa, HCT-116 and HEK-293) and Hemolysis assay. The toxicity of different nanoformulations administered in different concentrations (20–2000 mg/kg) in in vivo was estimated based on LD50 value.

In vitro acute gamma radiation on tissue of pink and white lotus (Nelumbo nucifera Gaertn.) in Thailand

This research aimed to investigatethe age of embryos of pink and white lotus for in vitropropagation and examine the sensitivity of young lotus plants derived from tissue culture to acute gamma radiation. The seeds of both lotus varieties were 4-week, 6-week and 8-week-old embryos cultivated on solid MS medium. They were then transferred to solid MS medium supplemented with 3 mg/L BA. After culturing, the 6-week-old pink lotus embryos had an average maximum petiole length of 16.78 ± 1.01 cm and an average of 11.84 ± 0.44 roots/explant, while the 6-week-old white lotus embryos had an average maximum petiole length of 15.48 ± 0.68 cm and an average of 11.76 ± 0.70 roots/explant. Each young lotus plant produced one shoot. After treating the young lotus plants with liquid MS medium supplemented with 3 mg/L BA, both lotus varieties showed increased shoot numbers at 3.54 ± 0.13 and 3.40 ± 0.91 shoots/explant. Young lotus plants of both varieties were exposed to gamma radiation levels of 0, 20, 30 and 40 Gy. The LD50 value for pink lotus was 26.138 Gy, while the LD50 value for the white lotus was 32.031 Gy.The LD50 value will offer vital information for determining the optimal dosage of gamma radiation for both pink and white lotus in vitro.

Insecticidal Properties and Chemical Characterization of Laurus nobilis L. Essential Oils from Two Regions of Morocco against Callosobruchus maculatus (Coleoptera: Bruchinae)

Morocco is a significant botanical reservoir that boasts a wealth of raw materials with promising applications across various industrial sectors, notably in pharmaceuticals and food. The objective of this study was to assess the effectiveness of essential oils (EOs) derived from Laurus nobilis L. leaves originating from the Tanger (EOT) and Meknes (EOM) regions in combating Callosobruchus maculatus infection. The chemical compositions of these oils were examined using Fourier transform infrared (FTIR) spectroscopy and gas chromatography–mass spectrometry (GC-MS). The biological activity of the EOs was evaluated via repulsion and fumigation tests against C. maculatus at varying concentrations. FTIR analysis revealed distinct vibrational bands indicative of various chemical compounds. GC-MS analysis was used to delineate the major chemical constituents of the EOs. The three predominant compounds in the EOT were 1,8-cineole (37.64%), linalool (16.40%), and adamantane (12.00%), whereas 1,8-cineole (47.84%), toluene (17.60%), and α-phellandrene (8.44%) were the most abundant in the EOM. Notably, the EOs exhibited significant repellent activity against C. maculatus, with repulsion percentages ranging from 51.11 to 90.00% in Tanger and 67.78 to 93.33% in Meknes. Mortality rates varied from 0 to 100% depending on the treatment. However, the mean concentrations showed mortality rates ranging from 29.44 to 65.56% for the EOT and from 21.11 to 67.78% for the EOM, with LD50 values of 11.96 μL/L and 5.22 μL/L. Docking studies revealed that 1,8-cineole had the highest binding affinity for the active site of acetylcholinesterase, thus confirming its toxic activity against C. maculatus. The findings of this study highlight the ability of EOs extracted from L. nobilis in the Moroccan regions of Tanger and Meknes to act as effective insecticides and repellents against C. maculatus, thereby highlighting avenues for further exploration of pest management and agricultural practices.