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Fluoride is an environmental contaminant that is ubiquitously present in air, water, and soil. It is commonly added in minute quantity to drinking water, toothpaste, and mouth rinses to prevent tooth decay. Epidemiological findings have demonstrated that exposure to fluoride induced neurodevelopmental toxicity, developmental neurotoxicity, and motor disorders. The neuroprotective effect of clofibrate, a peroxisome proliferator‐activated receptor alpha agonist, was investigated in the present study. Forty male Wistar rats were used for this study and randomly grouped into 10 rats per group as control, sodium fluoride (NaF) alone (300 ppm), NaF plus clofibrate (250 mg/kg), and NaF plus lisinopril (10 mg/kg), respectively, for 7 days. NaF was administered in drinking water while clofibrate and lisinopril were administered by oral gavage. Markers of neuronal inflammation and oxidative stress, acetylcholinesterase activity, and neurobehavioral (hanging wire and open field) tests were performed. Immunohistochemistry was performed on brain tissues, and they were probed with glial fibrillary acidic protein, ionized calcium‐binding adaptor molecule 1, and cerebellar Ca2+‐binding protein calbindin‐D28k. The results showed that NaF significantly increased of oxidative stress and neuroinflammation and inhibited AChE activity. Immunostaining showed reactive astrocytes, microgliosis, loss of dendritic spines, and arborization in Purkinje cells in rats administered only NaF. Neurobehavioral results showed that cotreatment of NaF with clofibrate improved muscular strength and locomotion, reduced anxiety, and significantly reduced astrocytic count. Overall, cotreatment of NaF with either clofibrate or lisinopril showed neuroprotective effects by mitigating neuronal inflammation and oxidative and motor incoordination. Hence, clofibrate could be seen as a novel drug candidate against neurodegeneration and motor disorders. [ABSTRACT FROM AUTHOR]

In this study, we report on the inhibitory activity of synthesized aminonaphthoquinones against two bacterial and one fungal species to determine their antimicrobial properties. A minimum inhibitory concentration (MIC) of 7.8 μg/mL was obtained against the fungus, Candida albicans, which was better than that of Amphotericin B (MIC = 31.25 μg/mL). Escherichia coli (Gram ‐), was inhibited at a MIC of 23.4 μg/mL and Staphylococcus aureus (Gram +) at a MIC of 31.3 μg/mL. The aminonaphthoquinones were also screened against HCT116 colon, PC3 prostate and HepG2 liver cancer cell lines to evaluate their cytostatic effects. They had potent activity (GI50 = 5.87–9.90 μM) which was about three‐6‐fold better than that of parthenolide (GI50 = 25.97 μM) against the prostate cancer cell line. These compounds were generally more selective for cancer cells than for normal human lung fetal fibroblasts (WI‐38). [ABSTRACT FROM AUTHOR]

Background: Influenza infection is a major public health threat. The role of influenza A virus-induced inflammatory response in severe cases of this disease is widely recognized. Drug resistance and side effects of chemical treatments have been observed, resulting in increased interest in alternative use of herbal medications for prophylaxis against this infection. The South African medicinal plant, Rapanea melanophloeos (RM) (L.) Mez of the family Myrsinaceae was selected owing to its traditional use for the treatment of several diseases such as respiratory ailments and also previous preliminary studies of anti-influenza activity of its methanolic extract. The aim of this study was to investigate the immunomodulatory properties of a glycoside flavone isolated from RM against influenza A virus. Methods: The non-cytotoxic concentration of the quercetin-3-O-α-L-rhamnopyranoside (Q3R) was determined by MTT assay and tested for activity against influenza A virus (IAV) in simultaneous, pre-penetration and post-penetration combination treatments over 1 h incubation on MDCK cells. The virus titer and viral load targeting NP and M2 viral genes were determined using HA and qPCR, respectively. TNF-α and IL-27 as pro- and anti-inflammatory cytokines were measured at RNA and protein levels by qPCR and ELISA, respectively. Results: Quercetin-3-O-α-L-rhamnopyranoside at 150 μg/ml decreased the viral titer by 6 logs (p < 0.01) in the simultaneous procedure. The NP and M2 genes copy numbers as viral target genes, calculated based on the Ct values and standard formula, significantly decreased in simultaneous treatment (p < 0.01). The expression of cytokines was also considerably affected by the compound treatment. Conclusions: This is the first report of quercetin-3-O-α-L-rhamnopyranoside from RM and its immunomodulatory properties against influenza A virus. Further research will focus on detecting the specific mechanism of virus-host interactions. [ABSTRACT FROM AUTHOR]

Selenium (Se) plays an important role for many organisms as an essential trace element nutrient. Its biological effects comprise mainly incorporation into the structure of selenoproteins, which are involved in cell activation, proliferation and differentiation in innate and adaptive immunity. Additionally, Se demonstrates antioxidant and anticancer potential at optimal doses. Furthermore, sulfur (S)-containing compounds have considerable promise regarding antimicrobial and anticancer drug development, in addition to the area of green and ecofriendly pesticides. Nitric oxide (NO) is known as a pro-inflammatory mediator associated with various physiological processes and plays an important role in the immune response. Regarding primary metabolites, water-soluble sugars and organic acids affect the taste and other organoleptic properties of fruits and vegetables such as color, flavor and aroma. The aim of the present study was to investigate the influence of Se and S enrichment on antibacterial and cytotoxicity activities, NO inhibition and further changes in primary metabolism in multi-leaf green (V1) and red (V2) lettuce. The plants were treated with three levels of Se via foliar application in the presence of three S levels in the nutrient solution under greenhouse conditions. The authors tested the hypothesis that the 'crosstalk' between Se and S can affect antibacterial activity, cytotoxicity and NO inhibition in lettuce plants under Se and S enrichment. Additionally, Se and S have a unique effect on soluble sugars and organic acids biosynthesis. The results indicated that extracts of the treated green and red multi-leaf lettuce were not cytotoxic to Vero kidney cells at the highest concentration tested of 1 mg/mL. The acetone extract of red lettuce had antibacterial activity against Pseudomonas aeruginosa with minimum inhibitory concentration (MIC) of 0.156 and 0.625 µg/mL under S2/Se1 and S2/Se2 treatments, respectively. Extracts of both previous treatments were active against Staphylococcus aureus and Escherichia coli with MIC = 1.25 µg/mL. As with antibacterial activity, the acetone extract of green (V1) and red (V2) lettuce treated with higher S (S2) under Se-limiting condition produced the best NO inhibition with IC50 = 97 µg/mL. Moreover, the red cultivar (V3) exhibited NO inhibition with IC50 = 113 and 130 µg/mL in response to S1/Se2 and S2/Se2 treatments, respectively. Under higher S and Se-limiting condition in the green and red multi-leaf lettuce, the levels of glucose and fructose increased therein to 125.0±0.36 and 94.8±1.6 mg g-1 DM, respectively, whereas in the red lettuce subjected to higher S and low Se (Se1) fertilization, the glucose level significantly increased to 89.3±0.37 mg g-1 DM. Under higher S and Se conditions (Se2/S2) glucose level in green and red lettuce enhanced dramatically (80.8±0.25 and 75.4±1.4 mg g-1 DM, respectively) in comparison to Se0/S0, Se1/S1, Se2/S1 treatments, but did not show significant changes between both cultivars. The elevated Se and S treatments (Se2/S2) accumulated more fructose in red lettuce (66.1±0.6 mg g-1 DM) than the green one (53.9±1.5 mg g-1 DM). Apart from watersoluble sugars malic acid accumulated in red lettuce under Se and S treatments, however its concentration remained unaltered among all treatments. While in green lettuce a synergistic interaction between Se and S revealed a dramatic decline in malic acid level from (15.3 ±0.86 mg g-1 DM) under Se and S-limiting condition to 11.0±0.74 and 6.64±0.43 mg g-1 DM in response to Se1/S1 and Se2/S2 treatments, respectively. Collectively, the findings indicate that Se and S enrichment evoked antibacterial and NO inhibitory activities. Additionally, Se/S crosstalk showed both antagonistic and synergistic effects on the biosynthesis of soluble sugars and organic acids and have great effects on the final nutritional value and quality of lettuce plants. [ABSTRACT FROM AUTHOR]

One new triterpenoid, (3 β,11 α,19 β)-3-(butanoyloxy)-11-hydroxytaraxast-20(30)-ene-23,28-dioic acid (clerodendrumic acid; 1) was isolated from the hexane extract of the leaves of Clerodendrum glabrum var. glabrum along with heptadecanoic acid ( 2). The structure of the new compound was elucidated by interpretation of its NMR (1D and 2D), MS, and IR data. Combined fractions C and D from the column chromatography of the hexane extract exhibited significant antifungal activities (average MIC of 0.10 mg/ml) against Candida albicans and Cryptococcus neoformans. C. albicans was relatively resistant to clerodendrumic acid ( 1; MIC 125 μg/ml) and was resistant to heptadecanoic acid ( 2; MIC 188 μg/ml). Both compounds had low antibacterial activities against two Gram-positive and two Gram-negative bacteria with average MIC values of 157 and 172 μg/ml, respectively. Compounds 1 and 2 were relatively nontoxic against monkey kidney Vero cells in vitro with IC50 values of 202.6 and 108.4 μg/ml, respectively. [ABSTRACT FROM AUTHOR]

• Spirostachys africana is an indigenous South African medicinal plant. • S. africana has revealed antimicrobial effects against several pathogenic bacteria. • Indicated antioxidant potential when tested for radical scavenging activity. • DCM extract exhibited the highest antibacterial activity in tested bacterial strains. • S. africana has the potential in cosmetic formulations. Spirostachys africana Sond. belongs to the Euphorbiaceae family. It is extensively used in South African traditional medicine to address skin conditions. It is locally known as '' tamboti '' or '' umthombothi ''. The microdilution method was used to evaluate the antibacterial activity of the PE, petroleum ether; DCM, dichloromethane; EtOH, Ethanol; DH 2 O, distillied water of S. africana stem-bark extracts against Klebsiella pneumoniae (ATCC 13883), Escherichia coli (ATCC 11775), and Staphylococcus aureus (ATCC 12600). The results revealed potent antibacterial activity, particularly in DCM and EtOH extracts, with MIC values ranging from 0.19 to 1.56 µg/ml. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay revealed potent radical scavenging activity, with an EC 50 value of 83.26 ± 1.22 μg/ml and a 72.60 ± 0.24 % at the highest tested concentrations. The anti-inflammatory activity of extracts was evaluated via the 15-lipoxygenase (15-LOX) inhibitory and the nitric oxide (NO) inhibition assays using lipopolysaccharide (LPS)-activated RAW 264.7 murine macrophages. The antioxidant activity of the extracts was performed using radical scavenging DPPH (2,2-diphenyl-1-picrylhydrazyl) and electron reducing ABTS (2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) assays. Water and ethanol stem-bark extracts of S. africana were evaluated for their skin irritation potential using a single application test on rats. The positive control (1 % sodium lauryl sulfate) exhibited significant skin irritation, while the negative control (deionized water) showed minimal irritation. The ethanol extract demonstrated moderate skin irritation potential, with visual scores reaching around 1.5–1.6 after 72 h. This study contributes to the growing body of indigenous medicinal plants and highlights the importance of further exploring natural sources of bioactive compounds for the development of effective and accessible treatments, particularly for vulnerable populations in resource-limited settings. [ABSTRACT FROM AUTHOR]

• Apoptosis of germ cells in the normal testis of Japanese quails was observed for the first time. • High frequency of apoptosis of germ cells in pre-pubertal and aged birds were detected. • Electron microscopy is one of the most sensitive techniques in confirming the TUNEL essay, • An imbalance between degeneration and regeneration of germ cells can lead to infertility. It has been established that excess germ cells in normal and in pathological conditions are removed from testicular tissue by the mechanism of apoptosis. Studies on germ cell apoptosis in avian species are grossly lacking, and there are only a few reports on induced germ cell degenerations in the testis tissue of birds. This study was designed to investigate the process of apoptosis of germ cells in the Japanese quail (Coturnix coturnix japonica). Germ cell degenerations were investigated in birds of all age groups, namely pre-pubertal, pubertal, adult, and aged. Apoptosis of germ cells in the quails, as shown by hematoxylin & eosin (H&E), TdT dUTP Nick End Labeling (TUNEL) assay and electron microscopy, was similar to that observed in previous studies of germ cells and somatic cells of mammalian species. The observed morphological features of these apoptotic cells ranged from irregular plasma and nuclear membranes in the early stage of apoptosis to rupture of the nuclear membrane, condensation of nuclear material, as well as fragments of apoptotic bodies, in later stages of apoptosis. In the TUNEL-positive cell counts, there was a significant difference between the mean cell counts for the four age groups (P < 0.05). Post hoc analysis revealed a highly significant difference in the aged group relative to the pubertal and adult age groups, while the cell counts of the pre-pubertal group were significantly higher than those of the pubertal group. However, there was no significant difference between cell counts of the pre-pubertal and the adult, and between the pre-pubertal and the aged groups. [ABSTRACT FROM AUTHOR]

Background: Diarrhoea is a major health issue in both humans and animals and may be caused by bacterial, viral and fungal infections. Previous studies highlighted excellent activity of Newtonia buchananii and N. hildebrandtii leaf extracts against bacterial and fungal organisms related to diarrhoea-causing pathogens. The aim of this study was to isolate the compound(s) responsible for antimicrobial activity and to investigate efficacy of the extracts and purified compound against bacterial biofilms. Methods: The acetone extract of N. buchananii leaf powder was separated by solvent-solvent partitioning into eight fractions, followed by bioassay-guided fractionation for isolation of antimicrobial compounds. Antibacterial activity testing was performed using a broth microdilution assay. The cytotoxicity was evaluated against Vero cells using a colorimetric MTT assay. A crystal violet method was employed to test the inhibitory effect of acetone, methanol: dichloromethane and water (cold and hot) extracts of N. buchananii and N. hildebrandtii leaves and the purified compound on biofilm formation of Pseudomonas aeruginosa, Escherichia coli, Salmonella Typhimurium, Enterococcus faecalis, Staphylococcus aureus and Bacillus cereus. Results: Myricetin-3-o-rhamnoside (myricitrin) was isolated for the first time from N. buchananii. Myricitrin was active against B. cereus, E. coli and S. aureus (MIC = 62.5 μg/ml in all cases). Additionally, myricitrin had relatively low cytotoxicity with IC50 = 104 μg/ml. Extracts of both plant species had stronger biofilm inhibitory activity against Gram-positive than Gram-negative bacteria. The most sensitive bacterial strains were E. faecalis and S. aureus. The cold and hot water leaf extracts of N. buchananii had antibacterial activity and were relatively non-cytotoxic with selectivity index values of 1.98–11.44. Conclusions: The purified compound, myricitrin, contributed to the activity of N. buchananii but it is likely that synergistic effects play a role in the antibacterial and antibiofilm efficacy of the plant extract. The cold and hot water leaf extracts of N. buchananii may be developed as potential antibacterial and antibiofilm agents in the natural treatment of gastrointestinal disorders including diarrhoea in both human and veterinary medicine. [ABSTRACT FROM AUTHOR]

Background: Antibiotics are commonly added to livestock feeds in sub-therapeutic doses as growth promoters and for prophylaxis against pathogenic microbes, especially those implicated in diarrhoea. While this practice has improved livestock production, it is a major cause of antimicrobial resistance in microbes affecting livestock and humans. This has led to the banning of prophylactic antibiotic use in animals in many countries. To compensate for this, alternatives have been sought from natural sources such as plants. While many studies have reported the antimicrobial activity of medicinal plants with potential for use as phytogenic/botanical feed additives, little information exists on their mode of action. This study is based on our earlier work and describes ultrastructural damage induced by acetone crude leaf extracts of Syzygium legatii and Eugenia zeyheri (Myrtaceae) active against diarrhoeagenic E. coli of swine origin using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and fluorescent microscopy (FM). Gas chromatography/mass spectrometry (GC-MS) was used to investigate the chemical composition of plant extracts. Results: The extracts damaged the internal and external anatomy of the cytoplasmic membrane and inner structure at a concentration of 0.04 mg/mL. Extracts also led to an increased influx of propidium iodide into treated bacterial cells suggesting compromised cellular integrity and cellular damage. Non-polar compounds such as α-amyrin, friedelan-3-one, lupeol, and β-sitosterol were abundant in the extracts. Conclusions: The extracts of S. legatii and E. zeyheri caused ultrastructural damage to E. coli cells characterized by altered external and internal morphology. These observations may assist in elucidating the mode of action of the extracts. [ABSTRACT FROM AUTHOR]

Peptides are important biomolecules which facilitate the understanding of complex biological processes, which in turn could be serendipitous biological targets for future drugs. They are classified as a unique therapeutic niche and will play an important role as fascinating agents in the pharmaceutical landscape. Until now, more than 40 cyclic peptide drugs are currently in the market, and approximately one new cyclopeptide drug enters the market annually on average. Interestingly, the majority of clinically approved cyclic peptides are derived from natural sources, such as peptide antibiotics and human peptide hormones. In this report, the importance of cyclic peptides is discussed, and their role in drug discovery as interesting therapeutic biomolecules will be highlighted. Recently isolated naturally occurring cyclic peptides from microorganisms, sponges, and other sources with a wide range of pharmacological properties are reviewed herein. [ABSTRACT FROM AUTHOR]

A series of indole-aminoquinazolines was prepared via amination of the 2-aryl-4-chloroquinazolines with the 7-amino-2-aryl-5-bromoindoles. It was then evaluated for cytotoxicity in vitro against human lung cancer (A549), epithelial colorectal adenocarcinoma (Caco-2), hepatocellular carcinoma (C3A), breast adenocarcinoma (MCF-7), and cervical cancer (HeLa) cells. A combination on the quinazoline and indole moieties of a 2-phenyl and 2-(4-fluorophenyl) rings in compound 4b; 2-(4-fluorophenyl) and 3-chlorophenyl rings in compound 4f; or the two 2-(4-fluorophenyl) rings in compound 4g, resulted in significant and moderate activity against the Caco-2 and C3A cell lines. The indole-aminoquinazoline hybrids compounds 4f and 4g induced apoptosis in Caco-2 and C3A cells, and were also found to exhibit moderate (IC50 = 52.5 nM) and significant (IC50 = 40.7 nM) inhibitory activity towards epidermal growth factor receptor (EGFR) against gefitinib (IC50 = 38.9 nM). Molecular docking suggests that 4a–h could bind to the ATP region of EGFR like erlotinib. [ABSTRACT FROM AUTHOR]