Drug discovery from nature has a long, ethnopharmacologically-based background. Today, natural resources are undeniably vital reservoirs of active molecules or drug leads. Advances in (bio)informatics and computational biology emphasized the role of herbal medicines in the drug discovery pipeline.

This review summarizes bioinformatic approaches applied in recent drug discovery from nature.

It examines advancements in molecular networking, pathway analysis, network pharmacology within a systems biology framework and AI for assessing the therapeutic potential of herbal preparations.

A comprehensive literature search was conducted using Pubmed, SciFinder, and Google Database. Obtained data was analyzed and organized in subsections: AI, systems biology integrative approach, network pharmacology, pathway analysis, molecular networking, structure-based virtual screening.

Bioinformatic approaches is now essential for high-throughput data analysis in drug target identification, mechanism-based drug discovery, drug repurposing and side-effects prediction. Large datasets obtained from "omics" approaches require bioinformatic calculations to unveil interactions, and patterns in disease-relevant conditions. These tools enable databases annotations, pattern-matching, connections discovery, molecular relationship exploration, and data visualisation.

Despite the complexity of plant metabolites, bioinformatic approaches assist in characterization of herbal preparations and selection of bioactive molecule. It is perceived as powerful tool for uncovering multi-target effects and potential molecular mechanisms of compounds. By integrating multiple networks that connect gene-disease, drug-target and gene-drug-target, drug discovery from natural sources is experiencing a remarkable comeback.

For thousands of years, Vachellia nilotica has been widely used as an herbal medicine to treat some diseases and symptoms, including respiratory, gastrointestinal and urogenital ailments. The present study was adapted to document and assemble existing information about V. nilotica and its evidence-based ethnopharmacological activities, with brief reviews on the description, geographical distribution, ecology, medical uses and phytochemistry. A literature review and information up to 2024 was performed in various scientific databases, including PubMed, Science Direct and Google Scholar. The keywords were "Acacia nilotica", "Botany", "ecology", "Traditional uses", "Phytochemistry", "Polyphenols", "Molecular docking", "Ethnopharmacological activities" and "toxicity", among others. V. nilotica has a wide range of uses, with low toxicity, reported in different countries. It can be infused into oils or tea or incorporated into paste, poultice and biscuits, used as an emollient, antidiarrheal, astringent and as an antidote for bite poisons. Glucose and lipid-lowering, anti-inflammatory, analgesic, antipyretic, antioxidant, antihypertensive, antibacterial, antifungal, antiviral and anthelmintic activities are the most prominent. Over 150 chemical components have been identified from V. nilotica that could be associated with its potential actions. Quercetin, rutin, kaempferol, naringenin, catechin, epicatechin, gallic acid, ellagic acid, lupeol and niloticane are its main active constituents. From the research data, and despite the fact that human clinical trials and detailed methodological studies are scarce, V. nilotica has shown wide-ranging activities, though the most robust evidence is related to the treatment of microbial infections, diarrhea, wound and ulcer healing and for topical application. More pharmacological and toxicological studies are required to further elucidate the mechanisms of action, potential side effects, and optimal dosages for these treatments. Additionally, more clinical trials are needed to validate these traditional uses in human populations and to ensure the safety and efficacy of V. nilotica for these applications. This article offers an overview of therapeutic applications by utilizing traditional uses and recent findings on phytochemical studies, and clinical and pharmacological research.

Trifloxystrobin (TFS) is a widely used strobilurin class fungicide. Ginkgo biloba L. has gained popularity due to its recognized medicinal and antioxidant properties. The aim of this study was to determine whether Ginkgo biloba L. extract (Gbex) has a protective role against TFS-induced phytotoxicity, genotoxicity and oxidative damage in A. cepa. Different groups were formed from Allium cepa L. bulbs subjected to tap water (control), 200 mg/L Gbex (Gbex1), 400 mg/L Gbex (Gbex2), 0.8 g/L TFS solution (TFS), 200 mg/L Gbex + 0.8 g/L TFS (TFS + Gbex1) and 400 mg/L Gbex + 0.8 g/L TFS (TFS + Gbex2), respectively. The phenolic composition of Gbex and alterations in the morphological, physiological, biochemical, genotoxicity and anatomical parameters were evaluated. Rutin, protocatechuic acid, catechin, gallic acid, taxifolin, p-coumaric acid, caffeic acid, epicatechin, syringic acid and quercetin were the most prevalent phenolic substances in Gbex. Rooting percentage, root elongation, weight gain, chlorophyll a and chlorophyll b decreased by approximately 50%, 85%, 77%, 55% and 70%, respectively, as a result of TFS treatment compared to the control. In the TFS group, the mitotic index fell by 28% compared to the control group, but chromosomal abnormalities, micronuclei frequency and tail DNA percentage increased. Fragment, vagrant chromosome, sticky chromosome, uneven chromatin distribution, bridge, vacuole-containing nucleus, reverse polarization and irregular mitosis were the chromosomal abnormalities observed in the TFS group. The levels of proline (2.17-fold) and malondialdehyde (2.71-fold), as well as the activities of catalase (2.75-fold) and superoxide dismutase (2.03-fold) were increased by TFS in comparison to the control. TFS-provoked meristematic disorders were damaged epidermis and cortex cells, flattened cell nucleus and thickened cortex cell wall. Gbex combined with TFS relieved all these TFS-induced stress signs in a dose-dependent manner. This investigation showed that Gbex can play protective role in A. cepa against the phytotoxicity, genotoxicity and oxidative damage caused by TFS. The results demonstrated that Gbex had this antioxidant and antigenotoxic potential owing to its high phenolic content.

Flavonoids are a diversified group of natural substances which were discovered to provide a variety of health benefits in human beings. Vegetables, fruits, wine and tea are the primary flavonoid dietary sources for humans and as the flavonoids are so closely connected to human dietary items and health, it is vital to explore the structural-activity connection. The arrangement, replacement of functional groups, and total number of hydroxyl groups around flavonoid's nucleus structure affect their biological activity, metabolism, and bioavailability. Various flavonoids have been proven to have hepatoprotective properties, that help in the prevention of coronary heart disease. Similarly, these flavonoids also possess anticancer, and anti-inflammatory activities. Flavonoids have been found to have a functional and structural link with their enzyme inhibitory action, that appears to have antiviral effect through acting as antioxidants, damaging cell membranes, blocking enzymes, activating mechanisms of host self-defense, and limiting virus penetration and attaching to cells. Identification, characterization, isolation, and biological role of flavonoids, as well as their uses on health advantages, are all major topics in research and development currently. This review represents a summary of various sources of flavonoids, class, subclass, their chemical structures, biological activities, the pharmacokinetics of flavonoids and various analytical, bioanalytical and electrochemical methods for determination of flavonoids from different matrices.

Aporosa cardiosperma is a plant species majorly found in the Indian Western Ghats that belongs to the phyllanthaceae family with ethnobotanical importance. Using a Fourier Transform-Infrared Spectrometer (FT-IR) and Gas Chromatography-Mass Spectrometry (GC-MS) for evaluating leaf extracts of A. cardiosperma, significant functional groups and metabolite constituents were determined, and its total flavonoid, phenol, and tannin content were quantified. Further, its antibacterial efficacy was investigated against microorganisms that cause fish and human disease and are resistant to common antibiotics, including Staphylococcus aureus, Bacillus subtilis, Mycobacterium tuberculosis, Klebsiella pneumoniae, Aeromonas hydrophila, and Pseudomonas aeruginosa. Regarding the outcomes of GC-MS analysis, the primary metabolites in the A. cardiosperma leaf extracts were heneicosane (57.06%), silane (13.60%), 1-heptadecene (10.09%), 3-hexadecene (9.99%), and pentadecane (9.54%). In comparison to other solvents, methanolic extract of A. cardiosperma leaves had increased phenolic, flavonoid, and tannin content; these findings are consistent with in vitro antioxidant potential and obtained that the methanolic extract (100 µg/mL) exhibited the higher percentage of inhibition in DPPH (82.35%), FRAP (86.20%), metal chelating (72.32%), and ABTS (86.06%) antioxidant assays respectively. Similar findings were found regarding the antibacterial efficacy against pathogenic bacteria. Comparatively, to other extracts, methanolic extracts showed more significant antibacterial activity at a lower minimum inhibitory concentration (MIC) value (250 µg/mL), whilst ethyl acetate and hexane solvent extracts of A. cardiosperma leaves had higher MIC values 500 µg/mL and 1000 µg/mL respectively. The antimicrobial potential was validated by investigating bacterial growth through the extracts acquired MICs and sub-MICs range. Bacterial growth was completely inhibited at the determined MIC range. In conclusion, A. cardiosperma leaf extract's phytochemical fingerprint has been determined, and its potent antibacterial and antioxidant activities were discovered. These findings of the current study will pave the way for developing herbal treatments from A. cardiosperma for various fish and human diseases.

Bovine mastitis (BM) is the most common bacterial mediated inflammatory disease in the dairy cattle that causes huge economic loss to the dairy industry due to decreased milk quality and quantity. Milk is the essential food in the human diet, and rich in crucial nutrients that helps in lowering the risk of diseases like hypertension, cardiovascular diseases and type 2 diabetes. The main causative agents of the disease include various gram negative, and positive bacteria, along with other risk factors such as udder shape, age, genetic, and environmental factors also contributes much for the disease. Currently, antibiotics, immunotherapy, probiotics, dry cow, and lactation therapy are commonly recommended for BM. However, these treatments can only decrease the rise of new cases but can't eliminate the causative agents, and they also exhibit several limitations. Hence, there is an urgent need of a potential source that can generate a typical and ideal treatment to overcome the limitations and eliminate the pathogens. Among the various sources, medicinal plants and its derived products always play a significant role in drug discovery against several diseases. In addition, they are also known for its low toxicity and minimum resistance features. Therefore, plants and its compounds that possess anti-inflammatory and anti-bacterial properties can serve better in bovine mastitis. In addition, the plants that are serving as a food source and possessing pharmacological properties can act even better in bovine mastitis. Hence, in this evidence-based study, we particularly review the dietary medicinal plants and derived products that are proven for anti-inflammatory and anti-bacterial effects. Moreover, the role of each dietary plant and its compounds along with possible role in the management of bovine mastitis are delineated. In this way, this article serves as a standalone source for the researchers working in this area to help in the management of BM.

Hypertension is a major global public health issue, affecting quarter of adults worldwide. Numerous synthetic drugs are available for treating hypertension; however, they often come with a higher risk of side effects and long-term therapy. Modern formulations with active phytoconstituents are gaining popularity, addressing some of these issues. This study aims to discover novel antihypertensive compounds in Cassia fistula, Senna alexandrina, and Cassia occidentalis from family Fabaceae and understand their interaction mechanism with hypertension targeted genes, using network pharmacology and molecular docking. Total 414 compounds were identified; initial screening was conducted based on their pharmacokinetic and ADMET properties, with a particular emphasis on adherence to Lipinski's rules. 6 compounds, namely Germichrysone, Benzeneacetic acid, Flavan-3-ol, 5,7,3',4'-Tetrahydroxy-6, 8-dimethoxyflavon, Dihydrokaempferol, and Epiafzelechin, were identified as effective agents. Most of the compounds found non-toxic against various indicators with greater bioactivity score. 161 common targets were obtained against these compounds and hypertension followed by compound-target network construction and protein-protein interaction, which showed their role in diverse biological system. Top hub genes identified were TLR4, MMP9, MAPK14, AKT1, VEGFA and HSP90AA1 with their respective associates. Higher binding affinities was found with three compounds Dihydrokaempferol, Flavan-3-ol and Germichrysone, -7.1, -9.0 and -8.0 kcal/mol, respectively. The MD simulation results validate the structural flexibility of two complexes Flavan-MMP9 and Germich-TLR4 based on no. of hydrogen bonds, root mean square deviations and interaction energies. This study concluded that C. fistula (Dihydrokaempferol, Flavan-3-ol) and C. occidentalis (Germichrysone) have potential therapeutic active constituents to treat hypertension and in future novel drug formulation.

Our current study reports the successful synthesis of thiolated chitosan-based nanoparticles for targeted drug delivery of 5-Fluorouracil. This process was achieved through the ionic gelation technique, aiming to improve the efficacy of the chemotherapeutic moiety by modifying the surface of the nanoparticles (NPs) with a ligand. We coated these NPs with hyaluronic acid (HA) to actively target the CD44 receptor, which is frequently overexpressed in various solid malignancies, including breast cancer. XRD, FTIR, SEM, and TEM were used for the physicochemical analysis of the NPs. These 5-Fluorouracil (5-FU) loaded NPs were evaluated on MDA-MB-231 (a triple-negative breast cell line) and MCF-10A (normal epithelial breast cells) to determine their in vitro efficacy. The developed 5-FU-loaded NPs exhibited a particle size within a favorable range (< 300 nm). The positive zeta potential of these nanoparticles facilitated their uptake by negatively charged cancer cells. Moreover, they demonstrated robust stability and achieved high encapsulation efficiency. These nanoparticles exhibited significant cytotoxicity compared to the crude drug (p < 0.05) and displayed a promising release pattern consistent with the basic diffusion model. These traits improve the pharmacokinetic profile, efficacy, and ability to precisely target these nanoparticles, offering a potentially successful anticancer treatment for breast cancer. However, additional in vivo assessments of these formulations are obligatory to confirm these findings.

In this study, the effect of formaldehyde on phytochemical content and antioxidant activity of Agaricus bisporus was investigated. Synthetic compost based on wheat straw was prepared by fermentation and disinfection. After steam pasteurization, 5 g of A. bisporus mycelia were inoculated into 1 kg of compost. To determine the effects of formaldehyde, 2, 4, and 6% concentrations were added to the composts, while compost without formaldehyde was used for the control group. The harvesting period was set at 10 weeks. Total phenolic and flavonoid content, macro- and microelement profile, and phenolic content were analyzed in the harvested A. bisporus samples. Macro- and microelement content was determined by ICP-OES, and phenolic compound profile was determined by LC-MS/MS analysis. Formaldehyde levels in A. bisporus samples were determined by the acetylacetone spectrophotometry method. The antioxidant capacity of A. bisporus samples was determined by DPPH scavenging activity; antimutagenic effects of samples were determined by Allium test. Application of 2, 4, and 6% formaldehyde resulted in a 1.12-, 1.19-, and 2.07-fold reduction in total phenolic content, respectively. The total phenolic content was reduced between 34.4% and 71.8%. These changes were confirmed by LC-MS/MS analysis. Compounds such as protocatechuic acid, salicylic acid, ferulic acid, and 4-OH benzoic acid, which were detected in the control group, could not be detected in the samples treated with 6% formaldehyde, and it was found that the application of formaldehyde reduced the phenolic content. Similar changes were also observed in macro- and microelements, and significant changes in elemental contents were observed after formaldehyde application. While the presence of formaldehyde at a low level, which may be due to natural production, was detected in the control group, a residue of 11.41 ± 0.93 mg/kg was determined in the 6% FMD applied group. All these changes resulted in a decrease in the antioxidant activity of A. bisporus. The DPPH scavenging activity, which was determined in the range of 21.6-73.3% in the control samples, decreased to 12.3-56.7% in the samples treated with formaldehyde. These results indicate that the application of formaldehyde at different stages of A. bisporus cultivation leads to significant changes in the nutritional value and biological activity of A. bisporus.

The plants that we consume in our daily diet and use as a risk preventer against many diseases have many biological and pharmacological activities. In this study, the phytochemical fingerprint and biological activities of Beta vulgaris L. leaf extract, which are widely consumed in the Black Sea region, were investigated. The leaf parts of the plant were dried in an oven at 35 °C and then ground into powder. The main constituents in B. vulgaris were identified by LC-MS/MS and GC-MS analyses. Phenolic content, betaxanthin and betacyanin levels were investigated in the extracts obtained using three different solvents. The biological activity of the extract was investigated by anti-microbial, anti-mutagenic, anti-proliferative and anti-diabetic activity tests. Anti-diabetic activity was investigated by in vitro enzyme inhibition and in-silico molecular docking was performed to confirm this activity. In the LC-MS analysis of B. vulgaris extract, a major proportion of p_coumaric acid, vannilin, protecatechuic aldehyde and sesamol were detected, while the major essential oils determined by GC-MS analysis were hexahydrofarnesyl acetone and phytol. Among the solvents used, the highest extraction efficiency of 2.4% was obtained in methanol extraction, and 36.2 mg of GAE/g phenolic substance, 5.1 mg/L betacyanin and 4.05 mg/L betaxanthin were determined in the methanol extract. Beta vulgaris, which exhibited broad-spectrum anti-microbial activity by forming a zone of inhibition against all tested bacteria, exhibited anti-mutagenic activity in the range of 35.9-61.8% against various chromosomal abnormalities. Beta vulgaris extract, which did not exhibit mutagenic, sub-lethal or lethal effects, exhibited anti-proliferative activity by reducing proliferation in Allium root tip cells by 21.7%. 50 mg/mL B. vulgaris extract caused 58.9% and 55.9% inhibition of α-amylase and α-glucosidase activity, respectively. The interactions of coumaric acid, vanniline, hexahydrofarnesyl acetone and phytol, which are major compounds in phytochemical content, with α-amylase and α-glucosidase were investigated by in silico molecular docking and interactions between molecules via various amino acids were determined. Binding energies between the tested compounds and α-amylase were obtained in the range of - 4.3 kcal/mol and - 6.1 kcal/mol, while for α-glucosidase it was obtained in the range of - 3.7 kcal/mol and - 5.7 kcal/mol. The biological activities of B. vulgaris are closely related to the active compounds it contains, and therefore studies investigating the phytochemical contents of plants are very important. Safe and non-toxic plant extracts can help reduce the risk of various diseases, such as diabetes, and serve as an alternative or complement to current pharmaceutical practices.

Researchers are investigating the medicinal properties of herbal plants throughout the world, which often leads to the discovery of novel plants and their chemicals for prophylactic needs of humans. Natural phytochemicals continue to be sought as alternative treatments for various diseases because of their non-toxic and therapeutic properties. In recent years, computational phytochemistry has enabled large-scale screening of phytochemicals, enabling researchers to pursue a wide range of therapeutic research alternatives to traditional ethnopharmacology. We propose to identify an anti-diabetic plant by computational screening on Indian herbal plants in conjunction with experimental characterization and biological validation. The methodology involves the creation of an in-house Indian herbal plant database. Molecular docking is used to screen against alpha amylase for anti-diabetic prophylaxis. Cassia angustifolia was chosen because its phytochemicals are able to bind to alpha amylase. Plants were experimentally extracted, botanically studied and their biological activity was evaluated. Further, the use of molecular dynamics was then applied to pinpoint the phytochemicals responsible for the affinity of alpha amylase. Results in the phytochemical analysis of the extracts revealed strong presence of alkaloids, flavonoids and cardiac glycosides. Moreover, alpha amylase biological activity with C. angustifolia extracts of chloroform, hexane and ethyl acetate demonstrated activity of 3.26, 8.01 and 30.33 µg/ml validating computational predictions. In conclusion, this study developed, validated computational predictions of identifying potential anti-diabetic plants 'Cassia angustifolia' from house herbal databases. Hope this study shall inspire explore plant therapeutic repurposing using computational methods of drug discovery.Communicated by Ramaswamy H. Sarma.

The rising cases of resistance to existing antibiotic therapies in Salmonella typhimurium has made it necessary to search for novel drug candidates. The present study employed the molecular docking technique to screen a set of antibacterial cephalosporin analogues against penicillin-binding protein 1a (PBP1a) of the bacterium. This is the first study to screen cephalosporin analogues against PBP1a, a protein central to peptidoglycan synthesis in S. typhimurium.

Some cephalosporin analogues were retrieved from a drug repository. The structures of the molecules were optimized using the semi-empirical method of Spartan 14 software and were subsequently docked against the active sites of PBP1a using AutoDock vina software. The most potent ligands were chosen as the most promising leads and subsequently subjected to absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling using the SwissADME online server and DataWarrior chemoinformatics program. The CABSflex 2.0 server was used to carry out molecular dynamics (MD) simulation on the most stable ligand-protein complex.

Compounds 3, 23, and 28 with binding affinity (ΔG) values of -9.2, -8.7, and -8.9 kcal/mol, respectively, were selected as the most promising leads. The ligands bound to the active sites of PBP1a via hydrophobic bonds, hydrogen bonds, and electrostatic interactions. Furthermore, ADMET analyses of the ligands revealed that they exhibited sound pharmacokinetic and toxicity profiles. In addition, an MD study revealed that the most active ligand bound favorably and dynamically to the target protein.

The findings of this research could provide an excellent platform for the discovery and rational design of novel antibiotics against S. typhimurium. Additional in vitro and in vivo studies should be carried out on the drug candidates to validate the findings of this study.

Hypertension has become a global threat and is one of the greatest risk factors for chronic kidney disease. Fenchyl acetate is a monoterpene that has been assessed for its various pharmacological activities in the past, but no study has evaluated its diuretic potential and the mechanism involved in the diuretic activity after prolonged administration in rats. Therefore, this study aimed to measure the safety and diuretic profile of fenchyl acetate in rats. For evaluating the acute toxicity, a single dose of 2000 mg/kg was administered as per the OECD guideline no. 425, and the rats were observed for 14 days. After 14 days, blood samples were assessed for biochemical, hematological, and oxidative stress parameters. For the acute diuretic study, fenchyl acetate was given in doses of 100, 200, and 400 mg/kg, and urine samples after 8 h were assessed for sodium, potassium, creatinine, uric acid excretion, and urinary output. A single dose of fenchyl acetate (F.A) was selected for prolonged diuretic activity, and furosemide was taken as the standard drug in a repeated dose administration for 7 days. Rats' urine was assessed for pH, sodium, potassium, creatinine, and uric acid excretion along with urinary volume excretion. Furthermore, blood was withdrawn by cardiac puncture, and selected organs like the heart, liver, kidney, and spleen were analyzed for oxidative stress biomarkers. Using pharmacological antagonists or inhibitors, the involvement of L-NAME, acetylcholine, or prostaglandin in F.A.-induced diuresis was determined. Mitochondrial respiratory chain enzyme complexes were also assessed in the kidney homogenates. The acute toxicity results showed F.A to be safe as its LD50 was greater than 2000 mg/kg and there were no signs of mortality or toxicity. The acute diuretic study showed that F.A resulted in a significant and dose-dependent increase in sodium, potassium, creatinine, and uric acid excretion along with urinary output, and these results were comparable to the standard drug furosemide. Prolonged administration with F.A (400 mg/kg) resulted in a comparable excretion of sodium, potassium, creatinine, uric acid, and urine output with furosemide (15 mg/kg). The oxidative stress parameters revealed that F.A (400 mg/kg) resulted in reducing the formation of free radicals. The results from the mechanism-based studies showed the involvement of NO in inducing diuresis. Furthermore, F.A (400 mg/kg) significantly increased the mitochondrial complexes I, II, III, IV, I + III, and II + III in the kidney homogenates, thus restoring the mitochondrial enzymes and improving the renal function. The current study suggests that F.A is safe with a significant diuretic potential with the involvement of NO in its mechanism of action.

This study was designed to assess the recovery effect of pomegranate seed extract (PSEx) against nickel (Ni)-induced damage in Allium cepa. Except for the control group treated with tap water, five experimental groups were exposed to 265 mg L-1 PSEx, 530 mg L-1 PSEx, 1 mg L-1 NiCI2, 265 mg L-1 PSEx + 1 mg L-1 NiCI2, and 530 mg L-1 PSEx + 1 mg L-1 NiCI2, respectively. The toxicity of Ni was examined through the analysis of physiological (germination percentage, weight gain, and root length), cytotoxicity (mitotic index), genotoxicity (micronucleus, chromosomal anomalies, and Comet test), and biochemical (malondialdehyde, proline, chlorophyll a and chlorophyll b contents, the activities of superoxide dismutase and catalase) parameters. Meristematic cell defects were also investigated. The NiCl2-DNA interaction was evaluated through spectral shift analysis. Values of all physiological parameters, mitotic index scores, and chlorophyll contents decreased while micronucleus frequency, DNA tail percentage, chromosomal anomalies, proline, MDA, and enzyme activities increased following Ni administration. According to the tail DNA percentage scale, Ni application caused "high damage" to DNA. Ni-induced chromosomal anomalies were fragment, sticky chromosome, vagrant chromosome, bridge, unbalanced chromatin distribution, reverse polarization, and nucleus with bud. NiCl2-DNA interaction caused a hyperchromic shift in the UV/Vis spectrum of DNA by spectral profile analysis. Ni exposure impaired root meristems as evidenced by the formation of epidermis cell damage, flattened cell nucleus, thickened cortex cell wall, and blurry vascular tissue. Substantial recovery was seen in all parameters with the co-administration of PSEx and Ni. Recovery effects in the parameters were 18-51% and 41-84% in the 265 mg L-1 PSEx + 1 mg L-1 NiCI2 and 530 mg L-1 PSEx + 1 mg L-1 NiCI2 groups, respectively. The Comet scale showed that PSEx applied with Ni reduced DNA damage from "high" to "moderate." Ni-induced thickened cortex cell wall and blurry vascular tissue damage disappeared completely when 530 mg L-1 PSEx was mixed with Ni. PSEx successfully reduced the negative effects of Ni, which can be attributed to its content of antioxidants and bioactive ingredients.

In this study, the toxicity induced by the alkylating agent methyl methanesulfonate (MMS) in Allium cepa L. was investigated. For this aim, bulbs were divided into 4 groups as control and application (100, 500 and 4000 µM MMS) and germinated for 72 h at 22-24 °C. At the end of the germination period root tips were collected and made ready for analysis by applying traditional preparation methods. Germination, root elongation, weight, mitotic index (MI) values, micronucleus (MN) and chromosomal abnormality (CAs) numbers, malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase (CAT) activities and anatomical structures of bulbs were used as indicators to determine toxicity. Moreover the extent of DNA fragmentation induced by MMS was determined by comet assay. To confirm the DNA fragmentation induced by MMS, the DNA-MMS interaction was examined with molecular docking. Correlation and principal component analyses (PCA) were performed to examine the relationship between all parameters and understand the underlying structure and relationships among these parameters. In the present study, a deep neural network (DNN) with two hidden layers implemented in Matlab has been developed for the comparison of the estimated data with the real data. The effect of MDA levels, SOD and CAT activities at 4 different endpoints resulting from administration of various concentrations of MMS, including MN, MI, CAs and DNA damage, was attempted to be estimated by DNN model. It is assumed that the predicted results are in close agreement with the actual data. The effectiveness of the model was evaluated using 4 different metrics, MAE, MAPE, RMSE and R2, which together show that the model performs commendably. As a result, the highest germination, root elongation, weight gain and MI were measured in the control group. MMS application caused a decrease in all physiological parameters and an increase in cytogenetic (except MI) and biochemical parameters. MMS application caused an increase in antioxidant enzyme levels (SOD and CAT) up to a concentration of 500 µM and a decrease at 4000 µM. MMS application induced different types of CAs and anatomical damages in root meristem cells. The results of the comet assay showed that the severity of DNA fragmentation increased with increasing MMS concentration. Molecular docking analysis showed a strong DNA-MMS interaction. The results of correlation and PCA revealed significant positive and negative interactions between the studied parameters and confirmed the interactions of these parameters with MMS. It has been shown that the DNN model developed in this study is a valuable resource for predicting genotoxicity due to oxidative stress and lipid peroxidation. In addition, this model has the potential to help evaluate the genotoxicity status of various chemical compounds. At the end of the study, it was concluded that MMS strongly supports a versatile toxicity in plant cells and the selected parameters are suitable indicators for determining this toxicity.

The plants that we use as food in our daily diet and as risk preventers against many diseases have many biological and pharmacological activities. The heat treatments applied during the cooking of the plants cause changes in the phytochemical content and bioactivity. In this study, the phytochemical fingerprint and biological activities of raw and heat-treated extracts of Ornithogalum umbellatum L., which is widely consumed in the Black Sea region, were investigated. The bulb and leaf parts of the plant consumed as food were dried in an oven at 35 °C and then ground into powder. For heat treatment, the plant was boiled at 100 °C for 20 min. Differences in phytochemical contents of raw and heat-treated extracts were determined by ICP-MS, LC-MS/MS, and FTIR analysis. Biological activity was investigated with antiradical, antimicrobial, antimutagenic and antiproliferative activity tests. In this way, the effect of heat treatment on both the phytochemical content and biological activity of the O. umbellatum extract was determined. Gallic acid, procateuic acid and caffeic acid were found as the main compounds in the O. umbellatum extract, while the presence of procateuic aldehyde, vanillin and kaempferol in minor proportions was determined. There was a significant decrease in phenolic compound levels after heat treatment and gallic acid content decreased by 92.6%, procateuic acid content by 90% and caffeic acid content by 84.8%. Significant differences were detected in macro and micro element levels after heat treatment in ICP-MS results. While Cd, Ba and Zn levels of the raw extract increased; Na, Mg, K, Fe, U, Co levels decreased significantly. In FTIR spectrum, shifts and disappearances were observed in some of the vibrations and the emergence of new vibrations was also determined after heat treatment. Raw extract exhibited strong scavenging activity against H2O2 and DPPH and had a broad spectrum antimicrobial property. As a result of heat application, regressions were detected in antiradicalic, antibacterial and antifungal activities. Antimutagenic and antiproliferative activities were determined by the Allium test and a significant decrease in both activities and loss of activity against some chromosomal abnormalities were determined after heat treatment. While the antiproliferative activity of the raw extract was 20%, the activity of the heat-treated extract decreased to 7.6%. The raw extract showed the strongest antimutagenic effect with 69.8% against the unequal distribution of chromatin. Similarly, the antimutagenic activity of the extract, which reduced the bridges by 56.1%, decreased to 0.74% after heat treatment and almost lost its antimutagenic activity. The biological activities of raw O. umbellatum are closely related to the major compounds it contains, and the decrease in the levels of these compounds with the effect of heat was reflected in the activity. Studies investigating the phytochemical contents of plants are very important and the studies investigating biological activities related to phytochemical content are more remarkable. In this study, the phytochemical fingerprint of O. umbellatum was determined, its biological activities were related to the compounds it contained, and the biological activity was found to be heat sensitive.

In this study, heavy metal pollution in Batlama stream flowing into the Black Sea from Giresun (Turkiye) province and the toxicity induced by this pollution were investigated by Allium test. Heavy metal concentrations in stream water were analyzed by using ICP-MS. Germination percentage, weight gain, root length, micronucleus (MN), mitotic index (MI), chromosomal abnormalities (CAs), proline, chlorophyll, malondialdehyde (MDA), antioxidant enzyme activities were used as indicators of physiological, cytogenetic and biochemical toxicity. In addition, Comet assay was performed for detecting DNA fragmentation. Anatomical changes caused by heavy metals in the root meristem cells were observed under the microscope. A. cepa bulbs are divided into two groups as control and treatment. The bulbs in the control group were germinated with tap water and the bulbs in the treatment group were germinated with stream water. As a result, heavy metals such as Al, Ti and Co and radioactive heavy metals such as Rb, Sr, Sb and Ba were detected in the stream water above the acceptable parametric values. Heavy metals in the water caused a decrease in germination, root elongation, weight gain, MI and chlorophyll values, and an increase in MDA, proline, SOD, CAT, MN and CAs values. Comet assays indicated the presence of severe DNA damage. In addition, heavy metals in stream water caused different types of CAs and anatomical damage in root meristem cells. As a result, it was determined that there is intense heavy metal pollution in the stream water and this pollution promotes multi-dimensional toxicity in A. cepa, which is an indicator organism. For this reason, the first priority should be to prevent pollution of water resources in order to prevent heavy metal-induced toxicity in water.

The dried root of Saposhnikovia divaricata (Turcz.) Schischk. is popular as a good medicinal material, however the abundant aerial part is often discarded, which caused the waste of resources. In order to exploit resources, the essential oils of the plant aerial part and root were extracted, separately called as VOA and VOR, their chemicals were identified. The tumor necrosis factor-α, interleukin-6, nitric oxide and interleukin-1β were detected to evaluate the oils anti-inflammatory activities. Then, the oils free radical scavenging rates were measured with DPPH, ABTS and hydroxyl free radical. The oils antitumor activities were evaluated with HeLa and HCT-8 cancer cell lines. The results showed the concentrations of VOA and VOR were separately 0.261% and 0.475%. Seventeen components of VOA were identified, accounting for 80.48% of VOA, including phytol, spathulenol, phytone, 4(15),5,10(14)-Germacratrien-1-ol, neophytadiene, etc. Seven components of VOR were determined, representing 90.73% of VOR, consisted of panaxynol, β-bisabolene, etc. VOA and VOR significantly inhibited the secretion of nitric oxide, interleukin-1β, interleukin-6 and tumor necrosis factor-α, effectively scavenged the DPPH, ABTS and hydroxyl free radicals, and showed significant antiproliferative activity against HeLa and HCT-8. The two oils presented important biological activity, which provided a hopeful utilized basis, and helped to reduce the waste of the aerial non-medicinal resources of S. divaricata.

In pursuit of novel antibiotics that could curb the growing trend of multidrug resistance by Salmonella typhimurium, a data set of some cephalosporin analogues were subjected to Molecular Docking based virtual screening against a penicillin-binding protein (PBP 1b) of the bacterium to ascertain the binding affinity values of the bioactive ligands against the active sites of the PBP 1b protein target using the AutoDock Vina Software. Three compounds with binding affinity values ranging from -7.8 kcal/mol to -8.2 kcal/mol were selected as the most promising leads. The selected compounds also displayed better potencies against the bacterium when compared with Cefuroxime (binding affinity = -6.4 kcal/mol), a standard β-lactam antibiotic used herein for quality control and assurance. Furthermore, evaluation of the drug-likeness and ADMET properties of the three most promising leads revealed that they possess good oral bioavailability and excellent pharmacokinetic profiles. It is hoped that the findings of this study will provide an excellent template for developing more potent β-lactam antibiotics against Salmonella typhimurium.

In this study, the phytochemical content of Nasturtium officinale R. Br. (watercress) leaf extract (Noex) and its protective effects against paraben toxicity were investigated. GC-MS and HPLC analyses were performed to determine the phytochemical content. Paraben toxicity and protective properties of Noex were investigated with the Allium test, and 6 different groups were formed for this purpose. Toxicity in each group was investigated by using physiological, cytogenetic, biochemical, and anatomical parameters. DNA-paraben interaction was investigated with spectroscopic analysis for the genotoxicity mechanism. As a result of the study, paraben (500 mM) caused a regression in the physiological parameters related to germination in Allium cepa L. bulbs. Paraben caused a 43.3% reduction in mitotic index (MI) rates compared to control, which is likely the reason for the decrease in germination-related parameters. With the application of paraben in root tip cells, the frequency of micronucleus (MN) and chromosomal aberrations (CAs) increased and a high genotoxic effect was observed. Paraben promoted CAs such as fragment, sticky chromosome, bridge, unequal distribution of chromatin, and irregular mitosis. It also caused anatomical damage in the form of epidermis cell damage, flattened cell nucleus, cortex cell damage, cortex cell walls thickening, and unclear vascular tissue in root tip meristem cells. Paraben-DNA interaction was caused by bathochromic and hypochromic shifts in the UV spectrum of DNA, indicating the intercalation mode of interaction. Paraben also caused an increase in malondialdehyde (MDA) levels, a decrease in glutathione (GSH) levels, and abnormalities in antioxidant enzyme levels (superoxide dismutase = SOD and catalase = CAT), thereby disrupting the antioxidant/oxidant dynamics in the cell. The basis of physiological, cytological, and genetic abnormalities was attributed to the oxidative stress in the cell. Administration of Noex produced a dose-dependent incremental improvement in paraben-induced abnormalities. The increase in GSH levels and the decrease in MDA levels observed as a result of the Noex application contributed to the restoration of antioxidant/oxidant balance, and this improvement was also reflected in other parameters. Application of 200 mg/L Noex provided a 24.2% improvement in the MI rate reduced by paraben, and accordingly, an increase in germination parameters was observed. Similarly, the frequencies of MN and CAs, which are signs of genotoxicity, decreased with the Noex application. As a result of the phytochemical analysis of Noex with HPLC and GC-MS, the presence of strong antioxidant and antimutagenic substances such as rutin, coumaric acid, ferrulic acid, L-serine, L-proline, and phytol were determined in Noex structure. The curative effects of Noex against paraben toxicity can be attributed to these active ingredients.

In this study, phytochemical analysis and toxicity profile of leaf and flower extracts of Nerium oleander L. species collected from Giresun province (Turkey) were investigated. In phytochemical analyzes, the cardiac glycoside, alkaloid, saponin and tannin contents of the extracts were analyzed qualitatively and quantitatively. The physiological effects of extracts were determined by examining root elongation, weight gain and germination rates. Biochemical effects were determined by measuring the levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT), which are indicators of oxidative stress. Cytotoxic and genotoxic effects were investigated by mitotic index (MI), micronucleus (MN) and chromosomal abnormality (CA) tests. N. oleander leaf and flower extract applications caused significant decreases in the physiological parameters of Allium bulbs. SOD and CAT activity in root tip cells increased significantly after the application of leaf extract compared to the control group. Similar changes were observed in the application of flower extract, but these increases were found to be at a lower level compared to the increases induced by the leaf extract. An increase in MDA levels and a decrease in GSH levels were observed in groups treated with leaf and flower extracts. These changes show that the extracts cause deterioration in antioxidant/oxidant balance. It was determined that the extracts, which caused a decrease in MI rates and an increase in MN and CAs frequencies, showed the most prominent cytotoxic and genotoxic effects at 250 μg/mL doses. These toxic effects were associated with the phytochemical content of the extracts, and it was thought that cardiac glycosides and alkaloids, whose presence were detected in qualitative and quantitative analyzes, may play an important role in toxicity. Studies investigating the therapeutic properties of plants as well as their toxic effects are insufficient, which leads to the fact that plants exhibiting potential toxicity are not well known. Therefore, this study will lead many studies on the toxicity profile of the phytochemical contents of plants. Therefore, this study will draw attention to the investigation of the toxicity profile and phytochemical contents of plants and will lead to similar studies.