Corrigendum to "Evaluation of the Genotoxic Potential against H2O2-Radical-Mediated DNA Damage and Acute Oral Toxicity of Standardized Extract of Polyalthia longifolia Leaf".

[This corrects the article DOI: 10.1155/2013/925380.].

Enantiomeric glycosylated cationic block co-beta-peptides eradicate Staphylococcus aureus biofilms and antibiotic-tolerant persisters.

The treatment of bacterial infections is hindered by the presence of biofilms and metabolically inactive persisters. Here, we report the synthesis of an enantiomeric block co-beta-peptide, poly(amido-D-glucose)-block-poly(beta-L-lysine), with high yield and purity by one-shot one-pot anionic-ring opening (co)polymerization. The co-beta-peptide is bactericidal against methicillin-resistant Staphylococcus aureus (MRSA), including replicating, biofilm and persister bacterial cells, and also disperses biofilm biomass. It is active towards community-acquired and hospital-associated MRSA strains which are resistant to multiple drugs including vancomycin and daptomycin. Its antibacterial activity is superior to that of vancomycin in MRSA mouse and human ex vivo skin infection models, with no acute in vivo toxicity in repeated dosing in mice at above therapeutic levels. The copolymer displays bacteria-activated surfactant-like properties, resulting from contact with the bacterial envelope. Our results indicate that this class of non-toxic molecule, effective against different bacterial sub-populations, has promising potential for the treatment of S. aureus infections.

In vitro and in vivo anticandidal activities of alginate-enclosed chitosan-calcium phosphate-loaded Fe-bovine lactoferrin nanocapsules.

AIM: To study the in vitro and in vivo anticandidal activity of nanocapsulated bovine lactoferrin. MATERIALS & METHODS: In vitro and in vivo antimicrobial activities were conducted to study the anticandidal activities of nanocapsules (NCs). RESULTS: The NCs showed good anticandidal activities. The disruption of cell wall and cell membrane was noted via microscopy studies. The NCs changed the normal growth profile of Candida albicans. NCs reduced the colony forming unit in kidney and blood samples. Histopathological examination showed better cell structure and coordination compared with untreated mice kidney. NCs also enhanced the natural killing properties of C. albicans by epithelial cells. CONCLUSION: NCs have effective anticandidal properties and have the potential as a therapeutic agent against candidiasis.

In vitro and in vivo toxicity assessment of alginate/eudragit S 100-enclosed chitosan-calcium phosphate-loaded iron saturated bovine lactoferrin nanocapsules (Fe-bLf NCs).

Lactoferrin has been known to have antimicrobial properties. This research was conducted to investigate the toxicity of Alginate/EUDRAGIT® S 100-enclosed chitosan-calcium phosphate-loaded Fe-bLf nanocapsules (NCs) by in vitro and in vivo assays. Brine shrimp lethality assay showed that the LC50 value of NCs was more than 1mg/mL which indicated that NCs was not toxic to Brine shrimp. However, the LC50 values for the positive control potassium dichromate at 24h is 64.15µg/mL, which was demostrated the toxic effect against the brine shrimp. MTT cytotoxicity assay also revealed that NCs was not toxic against non-cancerous Vero cell line with IC50 values of 536µg/mL. Genotoxicity studies by comet assay on Vero cells revealed that NCs exerted no significant genotoxic at 100µg/mL without tail or shorter comet tail. Allium cepa root assay carried out at 125, 250, 500 and 1000µg/mL for 24h revealed that the NCs was destitute of significant genotoxic effect under experimental conditions. The results show that there is no significant difference (p>0.05) in mitotic index between the deionized water and NCs treated Allium cepa root tip cells. In conclusion, no toxicity was observed in NCs in this study. Therefore, nontoxic NCs has the good potential to develop as a therapeutic agent.

Exploration of the anticandidal mechanism of Cassia spectabilis in debilitating candidiasis.

Candida albicans has become resistant to the commercially available, toxic, and expensive anti-Candida agents that are on the market. These factors force the search for new antifungal agents from natural resources. Cassia spectabilis had been traditionally employed by healers for many generations. The possible mechanisms of the C. spectabilis leaf extract were determined by potassium leakage study and the effect of the extract on the constituents of the cell wall and enzymes as well as the morphological changes on C. albicans cells were studied along with cytotoxicity assays. The cytotoxicity result indicated that the extract is nontoxic as was clearly substantiated by a half maximal inhibitory concentration (IC50) value of 59.10 µg/mL. The treated cells (C. spectabilis extract) demonstrated potassium leakage of 1039 parts per million (ppm) compared to Amphotericin B (AmpB)-treated cells with a released potassium value of 1115 ppm. The effects of the extract on the cell wall proteins illustrated that there were three major types of variations in the expression of treated cell wall proteins: the presence of new proteins, the absence of proteins, and the amount of expressed protein. The activities of two enzymes, α-glucosidase and proteinase, were determined to be significantly high, thereby not fully coinciding with the properties of the antifungal reaction triggered by C. spectabilis. The morphology of C. albicans cells treated with the C. spectabilis extract showed that the cells had abnormalities and were damaged or detached within the microcolonies. Our study verifies C. spectabilis leaf extract as an effective anti-C. albicans agent.

Radioprotective activity of Polyalthia longifolia standardized extract against X-ray radiation injury in mice.

The radioprotective effect of Polyalthia longifolia was studied in mice. P. longifolia treatment showed improvement in mice survival compared to 100% mortality in the irradiated mice. Significant increases in hemoglobin concentration, and red blood cell, white blood cell and platelet counts were observed in the animals pretreated with leaf extract. Pre-irradiation administration of P. longifolia leaf extract also increased the CFU counts of the spleen colony and increased the relative spleen size. A dose-dependent decrease in lipid peroxidation levels was observed in the animals pretreated with P. longifolia. However, although the animals pretreated with P. longifolia exhibited a significant increase in superoxide dismutase and catalase activity, the values remained below normal in both liver and the intestine. Pre-irradiation administration of P. longifolia also resulted in the regeneration of the mucosal crypts and villi of the intestine. Moreover, pretreatment with P. longifolia leaf extract also showed restoration of the normal liver cell structure and a significant reduction in the elevated levels of ALT, AST and bilirubin. These results suggested the radioprotective ability of P. longifolia leaf extract, which is significant for future investigation for human applications in developing efficient, economically viable, non-toxic natural and clinically acceptable novel radioprotectors.

Evaluation of the cytotoxicity, cell-cycle arrest, and apoptotic induction by Euphorbia hirta in MCF-7 breast cancer cells.

CONTEXT: Euphorbia hirta L. (Euphorbiaceae) has been used as a folk remedy in Southeast Asia for the treatment of various ailments. OBJECTIVE: The current study evaluates the cytotoxicity, cell-cycle arrest, and apoptotic induction by E. hirta in MCF-7 breast cancer cells. MATERIALS AND METHODS: Cytotoxic activity of methanol extract of whole part of E. hirta was determined by the MTT assay at various concentrations ranging from 1.96 to 250.00 µg/mL in MCF-7 cells. Cell morphology was assessed by light and fluorescence microscopy. Apoptosis and cell-cycle distribution were determined by annexin V staining and flow cytometry. DNA fragmentation, caspase activity, and reactive oxygen species (ROS) assays were performed using the commercially available kits. To identify the cytotoxic fraction, E. hirta extract was subjected to bioassay-guided fractionation. RESULTS: Euphorbia hirta exhibited significant inhibition of the survival of MCF-7 cells and the half inhibitory concentration (IC50) values was 25.26 µg/mL at 24 h. Microscopic studies showed that E. hirta-treated cells exhibited marked morphological features characteristic of apoptosis. Euphorbia hirta extract also had an ignorable influence on the LDH leakage and generating intracellular ROS. The flow cytometry study confirmed that E. hirta extract induced apoptosis in MCF-7 cells. Euphorbia hirta also resulted in DNA fragmentation in MCF-7 cells. Moreover, E. hirta treatment resulted in the accumulation of cells at the S and G2/M phases as well as apoptosis. The caspase activity study revealed that E. hirta extract induced apoptosis through the caspase-3-independent pathway by the activation of caspase-2, 6, 8, and 9. Euphorbia hirta hexane fraction, namely HFsub4 fraction, demonstrated highest activity among all the fractions tested with an IC50 value of 10.01 µg/mL at 24 h. DISCUSSION AND CONCLUSION: This study revealed that E. hirta induced apoptotic cell death and suggests that E. hirta could be used as an apoptosis-inducing anticancer agent for breast cancer treatment with further detailed studies.

Can Cancer Therapy be Achieved by Bridging Apoptosis and Autophagy: a Method Based on microRNA-Dependent Gene Therapy and Phytochemical Targets.

A failure of a cell to self destruct has long been associated with cancer progression and development. The fact that tumour cells may not instigate cell arrest or activate cell death mechanisms upon cancer drug delivery is a major concern. Autophagy is a mechanism whereby cell material can be engulfed and digested while apoptosis is a self-killing mechanism, both capable of hindering multiplication after cell injury. In particular situations, autophagy and apoptosis seem to co-exist simultaneously or interdependently with the aid of mutual proteins. This review covers roles of microRNAs and chemopreventive agents and makes an attempt at outlining possible partnerships in maximizing cancer cell death with minimal normal cell damage.

MicroRNAs: association with radioresistant and potential uses of natural remedies as green gene therapeutic approaches.

Radiotherapy plays an essential primary role in cancer patients. Regardless of its significant advances in treatment options, tumor recurrence and radio-resistance in cancer cells still occur in a high percentage of patients. Furthermore, the over expression of miRNAs accompanies the development of radio-resistant cancer cells. Consequently, miRNAs might serve as therapeutic targets for the treatment of radio-resistance in cancer cells. The findings of the current research also signify that the use of a natural anti-miRNA substance could inhibit specific miRNAs, and, concurrently, these natural remedies could exhibit radioprotective activity against the healthy cells during radiotherapy. Therefore, in this review, we have reported the association of miRNAs with radio-resistance and the potential uses of natural remedies as green gene therapeutic approaches, as well as radioprotectors against the adverse effects of irradiation on healthy cells during radiotherapy.

In vitro and in vivo antifungal activity of Cassia surattensis flower against Aspergillus niger.

Invasive aspergillosis (IA) in immunocompromised host is a major infectious disease leading to reduce the survival rate of world population. Aspergillus niger is a causative agent causing IA. Cassia surattensis plant is commonly used in rural areas to treat various types of disease. C. surattensis flower extract was evaluated against the systemic aspergillosis model in this study. Qualitative measurement of fungal burden suggested a reduction pattern in the colony forming unit (CFU) of lung, liver, spleen and kidney for the extract treated group. Galactomannan assay assessment showed a decrease of fungal load in the treatment and positive control group with galactomannan index (GMI) value of 1.27 and 0.25 on day 28 but the negative control group showed high level of galactomannan in the serum with GMI value of 3.58. Histopathology examinations of the tissues featured major architecture modifications in the tissues of negative control group. Tissue reparation and recovery from infection were detected in extract treated and positive control group. Time killing fungicidal study of A. niger revealed dependence of the concentration of C. surattensis flower extract.

MicroRNA pathways: an emerging role in identification of therapeutic strategies.

For years researchers have exerted every effort to improve the influential roles of microRNA (miRNA) in regulating genes that direct mammalian cell development and function. In spite of numerous advancements, many facets of miRNA generation remain unresolved due to the perplexing regulatory networks. The biogenesis of miRNA, eminently endures as a mystery as no universal pathway defines or explicates the variegation in the rise of miRNAs. Early evidence in biogenesis ignited specific steps of being omitted or replaced that eventuate in the individual miRNAs of different mechanisms. Understanding the basic foundation concerning how miRNAs are generated and function will help with diagnostic tools and therapeutic strategies. This review encompasses the canonical and the non-canonical pathways involved in miRNA biogenesis, while elucidating how miRNAs regulate genes at the nuclear level and also the mechanism that lies behind circulating miRNAs.

Evaluation of the Genotoxic Potential against H2O2-Radical-Mediated DNA Damage and Acute Oral Toxicity of Standardized Extract of Polyalthia longifolia Leaf.

Medicinal plants have been used in medicoculturally diverse countries around the world, where it is a part of a time-honoured tradition that is respected even today. Polyalthia longifolia leaf extract has been previously reported as an efficient antioxidant in vitro. Hence, the genotoxic effects of P. longifolia leaf were investigated by using plasmid relation, comet, and Allium cepa assay. In the presence of (∙) OH radicals, the DNA in supercoil was start nicked into open circular form, which is the product of the single-stranded cleavage of supercoil DNA and quantified as fragmented separate bands on agarose gel in plasmid relation assay. In the plasmid relation and comet assay, the P. longifolia leaf extract exhibited strong inhibitory effects against H2O2-mediated DNA damage. A dose-dependent increase of chromosome aberrations was also observed in the Allium cepa assay. The abnormalities scored were stickiness, c-mitosis, bridges, and vagrant chromosomes. Micronucleated cells were also observed at the interphase. The results of Allium cepa assay confirmed that the methanol extracts of P. longifolia exerted no significant genotoxic or mitodepressive effects at 100 µ g/mL. Thus, this study demonstrated that P. longifolia leaf extract has a beneficial effect against oxidative DNA damage. This experiment is the first report for the protective effect of P. longifolia on DNA damage-induced by hydroxyl radicals. Additionally in acute oral toxicity study, female rats were treated at 5000 mg/kg body weight of P. longifolia leaf extract and observed for signs of toxicity for 14 days. P. longifolia leaf extract did not produce any treatment-related toxic effects in rats.

Antioxidant Activity and Hepatoprotective Potential of Polyalthia longifolia and Cassia spectabilis Leaves against Paracetamol-Induced Liver Injury.

In the present study, in vitro antioxidant, free radical scavenging capacity, and hepatoprotective activity of methanol extracts from Polyalthia longifolia and Cassia spectabilis were evaluated using established in vitro models such as ferric-reducing antioxidant power (FRAP), 2,2-diphenyl-1-picryl-hydrazyl (DPPH(•)), hydroxyl radical (OH(•)), nitric oxide radical (NO(•)) scavenging, metal chelating, and antilipidperoxidation activities. Interestingly, all the extracts showed considerable in vitro antioxidant and free radical scavenging activities in a dose-dependent manner when compared to the standard antioxidant which verified the presence of strong antioxidant compound in leaf extracts tested. Phenolic and flavonoid content of these extracts is significantly correlated with antioxidant capacity. Since P. longifolia extract was exhibited better in vitro antioxidant activities, it was subjected for in vivo hepatoprotective activity in paracetamol-intoxicated mice. Therapy of P. longifolia showed the liver protective effect on biochemical and histopathological alterations. Moreover, histological studies also supported the biochemical finding, that is, the maximum improvement in the histoarchitecture of the liver. Results revealed that P. longifolia leaf extract could protect the liver against paracetamol-induced oxidative damage by possibly increasing the antioxidant protection mechanism in mice. Our findings indicated that P. longifolia and C. spectabilis have potential as good sources of natural antioxidant/antiaging compounds.

Evaluation of the hepatoprotective Effects of Lantadene A, a pentacyclic triterpenoid of Lantana plants against acetaminophen-induced liver damage.

The aim of the present study was to evaluate the hepatoprotective activity of lantadene A against acetaminophen-induced liver toxicity in mice was studied. Activity was measured by monitoring the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin, along with histo-pathological analysis. Silymarin was used as positive control. A bimodal pattern of behavioural toxicity was exhibited by the lantadene A-treated group at the beginning of the treatment. However, treatment with lantadene A and silymarin resulted in an increase in the liver weight compared with the acetaminophen treated group. The results of the acetaminophen-induced liver toxicity experiments showed that mice treated with lantadene A (500 mg/kg) showed a significant decrease in the activity of ALT, AST and ALP and the level of bilirubin, which were all elevated in the acetaminophen treated group (p < 0.05). Histological studies supported the biochemical findings and a maximum improvement in the histoarchitecture was seen. The lantadene A-treated group showed remarkable protective effects against histopathological alterations, with comparable results to the silymarin treated group. The current study confirmed the hepatoprotective effects of lantadene A against the model hepatotoxicant acetaminophen, which is likely related to its potent antioxidative activity.

In vitro antioxidant activity potential of lantadene A, a pentacyclic triterpenoid of Lantana plants.

Lantadenes are pentacyclic triterpenoids present in the leaves of the plant Lantana camara. In the present study, in vitro antioxidant activity and free radical scavenging capacity of lantadene A was evaluated using established in vitro models such as ferric reducing antioxidant power (FRAP), 2,2-diphenyl-1-picryl-hydrazyl (DPPH•), hydroxyl radical (OH•), nitric oxide radical (NO•), superoxide anion scavenging activities and ferrous ion chelating assay. Interestingly, lantadene A showed considerable in vitro antioxidant, free radical scavenging capacity activities in a dose dependant manner when compared with the standard antioxidant in nitric oxide scavenging, superoxide anion radical scavenging and ferrous ion chelating assay. These findings show that the lantadene A possesses antioxidant activity with different mechanism of actions towards the different free radicals tested. Since lantadene A is a very popular drug in modern medicine, it is a promising candidate for use as an antioxidant and hepatoprotective agent.

Cassia spectabilis (DC) Irwin et Barn: a promising traditional herb in health improvement.

The genus Cassia, comprising about 600 species widely distributed worldwide is well known for its diverse biological and pharmacological properties. Cassia spectabilis (sin Senna spectabilis) (DC) Irwin et Barn (Fabaceae) is widely grown as an ornamental plant in tropical and subtropical areas. C. spectabilis has been commonly used in traditional medicine for many years. Information in the biomedical literature has indicated the presence of a variety of medicinally-important chemical constituents in C. spectabilis. Pharmacological studies by various groups of investigators have shown that C. spectabilis possesses significant biological activity, such as antibacterial, antibiofilm, antifungal and antioxidant properties. Beside this, toxicity studies of this plant have revealed no toxic effect on mice. In view of the immense medicinal importance of C. spectabilis, this review aimed at compiling all currently available information on C. spectabilis's botany, phytochemistry, pharmacology, and mechanism of actions, toxicology and its ethnomedicinal uses.

Acute toxicity impacts of Euphorbia hirta L extract on behavior, organs body weight index and histopathology of organs of the mice and Artemia salina.

BACKGROUND: The methanol extract of Euphorbia hirta L (Euphorbiaceae), which is used in traditional medicines, was tested for in vivo toxicity. MATERIALS AND METHODS: In vivo brine shrimp lethality assay and oral acute toxicity study at single high dose of 5000 mg/kg and observation for 14 days in mice were used to study the toxic effect of E. hirta. RESULTS: Brine shrimp lethality assay was used to calculate the median lethal concentration (LC(50)) of E. hirta (for leaves, stems, flowers and roots) methanolic extracts at concentrations from 100 to 0.07 mg/ml. The LC(50) values of 1.589, 1.420, 0.206 and 0.0827 mg/ml were obtained for stems, leaves, flowers and roots, respectively. Potassium dichromate (the positive control) had LC(50) value of 0.00758 mg/ml. The acute oral toxicity study of the leaf extract resulted in one third mortality and mild behavioral changes among the treated mice. No significant statistical differences found between body weight, relative (%) and absolute (g) organ weights of treated and untreated groups (P> 0.05). Gross and microscopic examination of the vital organ tissues revealed no differences between control and treated mice. All the tissues appeared normal. CONCLUSIONS: E. hirta leaves methanol extract has exhibited mild toxic effects in mice.