Synthesis and evaluation of some novel <Emphasis Type="Italic">N</Emphasis>-substituted rhodanines for their anticancer activity

Novel N-substituted rhodanines 2a–g were synthesized by conventional and microwave-assisted methods and tested for their anticancer activity. Structure–activity relationship of the synthesized rhodanine 2a–g as antiproliferative agents was investigated. The results revealed that all the seven compounds showed potent antiproliferative activity in a concentration-dependent manner on leukemic cell line K562. Among the tested compounds, 2b was found to be more potent when compared by trypan blue and MTT assay. IC₅₀ values of 2b using trypan blue and MTT assay were found to be 11.1 and 20.3 µg/ml, respectively. A dose-dependent increase in the LDH release was also observed upon treatment with 2a–g. Cell cycle analysis revealed that 2b affects DNA replication and leads to accumulation of cells in G ₀ and decline of G ₂/M, G ₁ and S phases which indicates apoptosis. The selective cytotoxic activity against human chronic myelogenous cell line (K562), via apoptosis, suggests that compound 2b is a promising scaffold for the development of novel anticancer drug.     

Induction of apoptosis and cell cycle arrest by <Emphasis Type="Italic">Negombata magnifica</Emphasis> sponge in hepatocellular carcinoma

Marine sponges have been considered as a gold mine, with respect to the diversity of their secondary metabolites. Many sponge extracts and isolated compounds are potential anticancer agents. In the present study, the antiproliferative activity of Negombata magnifica was investigated as petroleum ether extract (PE), total methanolic extract (ME) and two sub-fractions II and III, isolated pure compounds (palmitic acid and pregnanediol), sponge mesohyl and primmorphs ethyl acetate extract. Palmitic acid was used as a positive control. Cell viability was assessed via MTT assay, and apoptosis was investigated in terms of DNA fragmentation and BCl2 gene expression. Cell cycle analysis was performed via flow cytometry. GLC analysis of PE revealed that it contains 84.46 % hydrocarbons and 15.54 % sterols, whereas the fatty acids contain 38.62 % saturated and 61.38 % unsaturated fatty acids. Results revealed that except for pregnanediol and fraction II, all treatments exhibited cytotoxic activity. Primmorphs ethyl acetate extract and fraction III arrested cells in G0–G1, while fraction II arrested cell cycle in G2/M. PE extract arrested cells in G0–G1 and G2/M. Mesohyl, PE and fraction III could be apoptotic agents as indicated by DNA fragmentation independent on BCL2 expression, while ME and pregnanediol could exhibited pro-apoptotic effect through decreasing BCL2 expression although no DNA ladder was observed.     

Anthraquinone and naphthopyrone glycosides from <Emphasis Type="Italic">Cassia obtusifolia</Emphasis> seeds mediate hepatoprotection via Nrf2-mediated HO-1 activation and MAPK modulation

Cassia obtusifolia L. seed is one of the most popular traditional Chinese medicine for mutagenicity, genotoxicity, hepatotoxicity, and acute inflammatory diseases. We evaluated the hepatoprotective activity of anthraquinone and naphthopyrone glycosides isolated from the butanol fraction of C. obtusifolia seeds and explored their effects on cell signaling pathways. Continuous chromatographic separation led to the isolation of 1-desmethylaurantio-obtusin 2-O-β-D-glucopyranoside (1), rubrofusarin 6-O-β-D-apiofuranosyl-(1?→?6)-O-β-D-glucopyranoside (2) and rubrofusarin 6-O-β-gentiobioside (3). All glycosides were non-toxic at concentrations up to 80 µM. The increased intracellular reactive oxygen species (ROS) and decreased glutathione levels observed after tert-butylhydroperoxide (t-BHP) intoxication were ameliorated by all three glycosides, with compound 3 being the most active. Pretreatment with the three glycosides increased nuclear factor erythroid-2-related factor 2 (Nrf2)-mediated heme oxidase-1 (HO-1) expression. All the glycosides enhanced the phosphorylation of c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK), and the dephosphorylation of p38. The protective effects of the anthraquinone and naphthopyrone glycosides against t-BHP-induced oxidative damage in human liver-derived HepG2 cells were due to the prevention of ROS generation and up-regulated activity of HO-1 via Nrf2 activation and modulation of the JNK/ERK/MAPK signaling pathway. The data indicate the potential of these compounds as hepatoprotective agents in pharmaceuticals and/or nutraceuticals.     

Synthesis,molecular docking,antiproliferative, and antimicrobial activity of novel pyrano[3,2-<Emphasis Type="Italic">c</Emphasis>]carbazole derivatives

A new series of pyrano[3,2-c]carbazole derivatives which are biologically valuable and synthetically challenging frameworks have been synthesized by domino Knoevenagel-hetero-Diels-Alder reaction. The key strategy involve copper iodide catalyzed cyclization of O-propargyl derivative of N-Boc-carbazole-3-carboxaldehyde with cyclic 1,3-diketones or pyrazol-5-ones to afford N-Boc-pyrano[3,2-c]carbazole derivatives. The antiproliferative activity of the all synthesized compounds on three cancer cell lines such as PANC 1 (pancreatic), HeLa (cervical), and MDA-MB-231 (breast cancer) was investigated. The results clearly demonstrated that compounds 11b, 11d, and 13d were displayed pronounced antriproliferative activity. In addition, antimicrobial activity of these compounds also assayed against three representative gram-positive organisms and gram-negative organisms. Specifically, compound 11c exhibited significant antimicrobial activity. Molecular docking studies revealed that compound 13d selectively occupy the colchicine binding site of the tubulin polymer.     

Hg and Se exposure in brain tissues of striped dolphin (<Emphasis Type="Italic">Stenella coeruleoalba</Emphasis>) and bottlenose dolphin (<Emphasis Type="Italic">Tursiops truncatus</Emphasis>) from the Tyrrhenian and Adriatic Seas

In this study we analyzed Hg and Se concentrations in dolphin brain tissues of fifteen specimens of striped dolphin (Stenella coeruleoalba) and eight specimens of bottlenose dolphin (Tursiops truncatus) stranded in the Tyrrhenian and Adriatic Seas, in order to assess the toxicological risks associated with Hg exposure. High Hg concentrations were found in brain tissues of both analyzed specie (1.86–243?mg/kg dw for striped dolphin and 2.1–98.7?mg/kg dw for bottlenose dolphin), exceeding levels associated with marine mammals neurotoxicity. Althougth the results clearly suggest that the protective effects of Se against Hg toxicity occur in cetaceans’ brain tissues, a molar excess of mercury with respect to selenium was found, particularly in adult specimens of Stenella coeruleoalba. On contrary, negligible neurotoxicological risks were found for Tursiops truncatus specimens, due to detoxification processes. Data obtained allowed to prove a more marked neurotoxicological risk for adult specimens of Stenella coeruleoalba in both Tyrrhenian and Adriatic Seas.     

Reformulation of Fungizone by PEG-DSPE Micelles: Deaggregation and Detoxification of Amphotericin B

Purpose

Fungizone® (AmB-SD), amphotericin B solubilized by sodium deoxycholate, contains a highly aggregated form of the antifungal agent that causes dose-limiting renal toxicity. With the aim of reducing the formulation’s toxicity by co-delivering monomeric amphotericin B (AmB) and sodium supplementation, we deaggregated AmB-SD with FDA-approved excipient PEG-DSPE in 0.9% NaCl-USP. Herein, we describe a reformulated AmB-SD with PEG-DSPE micelles that results in a less toxic drug with maintained antifungal activity.

Methods

We compared the aggregation state and particle size of AmB-SD alone or combined with PEG-DSPE micelles. In vitro hemolytic activity and in vivo renal toxicity were measured to determine the toxicity of different formulations. In vitro antifungal assays were performed to determine differences in efficacy among formulations.

Results

PEG-DSPE micelles in saline deaggregated AmB-SD. Deaggregated AmB-SD exhibited significantly reduced in vitro and in vivo toxicity. In vitro antifungal studies showed no difference in minimum inhibitory and fungicidal concentrations of AmB-SD combined with PEG-DSPE relative to the drug alone.

Conclusions

Reformulation of AmB-SD with PEG-DSPE micelles in saline facilitates co-delivery of monomeric AmB and sodium supplementation, potentially reducing the dose-limiting nephrotoxicity of AmB-SD. Ease of preparation and commercially available components lead us to acknowledge its potential for clinical use.

     

<Emphasis Type="Italic">Rubus imperialis</Emphasis> (Rosaceae) extract and pure compound niga-ichigoside F1: wound healing and anti-inflammatory effects

Here, we evaluate the anti-inflammatory and wound-healing effects of methanolic crude extract obtained from aerial parts (leaves and branches) of Rubus imperialis Chum. Schl. (Rosaceae) and the pure compound niga-ichigoside F1. Anti-inflammatory activity was determined in vivo and in vitro, and the healing effect was evaluated in surgical lesions in mice skin. The 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay and H₂O₂-induced oxidative stress were used to determine antioxidant activity. The efferocytosis activity was also determined. The data obtained show that the extract of R. imperialis promote reduction in the inflammatory process induced by lipopolysaccharide (LPS) or carrageenan in the air pouch model; the effects could be reinforced by nitric oxide reduction in LPS-stimulated neutrophils, and an increase in the efferocytosis. The extract showed wound healing property in vitro and in vivo, scavenging activity for DPPH, and cytoprotection in the H₂O₂-induced oxidative stress in L929 cells. In addition, the compound niga-ichigoside F1 was able to reduce the NO secretion; however, it did not present wound-healing activity in vitro. Together, the data obtained point out the modulatory actions of R. imperialis extract on leukocyte migration to the inflamed tissue, the antioxidant, and the pro-resolutive activity. However, the R. imperialis anti-inflammatory activity may be mediated in parts by niga-ichigoside F1, and on wound healing do not correlated with niga-ichigoside F1.     

Anti-diabetic Effect of <Emphasis Type="Italic">Boerhavia diffusa</Emphasis> L. Root Extract via Free Radical Scavenging and Antioxidant Mechanism

Objective

The present study was proposed to assess the in vitro free radical-scavenging activity of B. diffusa methanolic extract (BDME) and its modulatory effect against streptozotocin (STZ) induced diabetes in male Wistar rats.

Methods

Experimental diabetes was induced in Wistar albino rats by administering single dose of STZ 40 mg/kg. One week later rats with blood glucose level >200 mg/dL were segregated as diabetes in three groups each containing 6 rats in number.

Results

Total phenolic content in B. diffusa methanol extract (BDME) was found to be 87 mg of gallic acid equivalents/g extract and total flavonoid content found to be 54.1 mg of quercetin equivalents/g extract. Its extract also exhibited DPPH (IC₅₀, 163.1±6.7 μg/mL), nitric oxide (295 μg/mL) and H₂O₂ (159±5.25 μg/mL) radical scavenging activity. Pre-treatment with BDME (100 and 200 mg/kg b.w.) in streptozotocin-induced diabetic rats resulted in significant improvement in blood glucose, blood plasma enzymes SGOT, SGPT and ALP, weight loss, total protein, serum insulin and liver glycogen levels. Furthermore, it restores the activity of antioxidant enzymes viz. SOD, CAT and GPx.

Conclusion

Thus, the result suggests that BDME employed significant anti-diabetic effect in Wistar rats which is associated with its free radical scavenging and antioxidant activity.

     

Anti-obesity activity of Yamabushitake (<Emphasis Type="Italic">Hericium erinaceus</Emphasis>) powder in ovariectomized mice,and its potentially active compounds

Hericium erinaceus (H. erinaceus) improves the symptoms of menopause. In this study, using ovariectomized mice as a model of menopause, we investigated the anti-obesity effect of this mushroom in menopause. Mice fed diets containing H. erinaceus powder showed significant decreases in the amounts of fat tissue, plasma levels of total cholesterol, and leptin. To determine the mechanism, groups of mice were respectively fed a diet containing H. erinaceus powder, a diet containing ethanol extract of H. erinaceus, and a diet containing a residue of the extract. As a result, H. erinaceus powder was found to increase fecal lipid levels in excreted matter. Further in vitro investigation showed that ethanol extract inhibited the activity of lipase, and four lipase-inhibitory compounds were isolated from the extract: hericenone C, hericenone D, hericenone F, and hericenone G. In short, we suggest that H. erinaceus has an anti-obesity effect during menopause because it decreases the ability to absorb lipids.     

Evaluation of the inhibitory effects of eckol and dieckol isolated from edible brown alga <Emphasis Type="Italic">Eisenia bicyclis</Emphasis> on human monoamine oxidases A and B

Eckol and dieckol are important phlorotannins found in edible brown algae including Eisenia bicyclis, Ecklonia stolonifera, and others. Inhibition of monoamine oxidase (MAO) play an important role in the early management of Parkinson’s disease (PD). The aim of this study was to determine the effectiveness of eckol and dieckol isolated from the methanolic extract of E. bicyclis against PD by the inhibition of human MAO-A and MAO-B (hMAO-A and hMAO-B). A sensitive enzyme-based chemiluminescent assay and kinetics methods were used to investigate enzyme inhibition and mode of inhibition. A molecular docking simulation was performed to clarify the binding characteristics of eckol and dieckol to hMAO-A and hMAO-B. The results suggested that methanolic extract of E. bicyclis and its isolated phlorotannins, eckol and dieckol, have potent inhibitory activity against hMAO-A and hMAO-B. The enzyme-based kinetics results demonstrated eckol mixed and non-competitive inhibition of hMAO-A and hMAO-B, respectively, while dieckol non-competitively inhibited both hMAOs. Molecular docking simulation predicted that eckol and dieckol exhibit higher binding affinity towards hMAO-A and hMAO-B through hydrogen bonding and hydrophobic interactions. These findings implicate eckol and dieckol as inhibitors of hMAOs that might be of potential value in the management of PD.     

<Emphasis Type="Italic">Apium graveolens</Emphasis> extract influences mood and cognition in healthy mice

Apium graveolens is a food flavoring which possesses various health promoting effects. This study investigates the effect of a sub-acute administration of A. graveolens on cognition and anti-depression behaviors via antioxidant and related neurotransmitter systems in mice brains. Cognition and depression was assessed by various models of behavior. The antioxidant system of glutathione peroxidase (GPx), % inhibition of superoxide anion (O₂ ^?), and lipid peroxidation were studied. In addition, neurochemical parameters including acetylcholinesterase (AChE) and monoamine oxidase-type A (MAO-A) were also evaluated. Nine groups of male mice were fed for 30 days with different substances—a control, vehicle, A. graveolens extract (65–500 mg/kg), and reference drugs (donepezil and fluoxetine). The results indicated that the effect of the intake of A. graveolens extract (125–500 mg/kg) was similar to the reference drugs, as it improved both spatial and non-spatial memories. Moreover, there was a decrease in immobility time in both the forced swimming and tail suspension tests. In addition, the A. graveolens extract reduced lipid peroxidation of the brain and increased GPx activity and the % inhibition of O₂ ^?, whereas the activities of AChE and MAO-A were decreased. Thus, our data have shown that the consumption of A. graveolens extract improved cognitive function and anti-depression activities as well as modulating the endogenous antioxidant and neurotransmitter systems in the brain, resulting in increased neuronal density. This result indicated an important role for A. graveolens extract in preventing age-associated decline in cognitive function associated with depression.     

Synthesis,characterization and evaluation of antiproliferative activity of diisopropylphenyl esters of fatty acids from selected oils

The present investigation describes the synthesis, characterization and evaluation of antiproliferative activity of novel diisopropylphenol (propofol) conjugates of fatty acids. The fatty acids were obtained from oils of Jatropha curcas (jatropha) and Pongamia glabra (karanja) containing unsaturated-rich fatty acids, Sterculia foetida (containing cyclopropene-rich fatty acids), Samia cynthia (eri pupae, containing polyunsaturated-rich fatty acid, 18:3) and Cocos nucifera (coconut, containing medium-chain saturated-rich fatty acids). The synthesized conjugates viz. propofol-jatropha mixed fatty acid conjugates (2,4P-JTA and 2,6P-JTA), propofol-karanja mixed fatty acid conjugates (2,4P-KTA and 2,6P-KTA), propofol-sterculia foetida mixed fatty acid conjugates (2,4P-STA and 2,6P-STA), propofol-eri pupal mixed fatty acid conjugates (2,4P-EFA and 2,6-EFA) and propofol-coconut mixed fatty acid conjugates (2,4P-CCFA and 2,6P-CCFA) were obtained by esterification of the fatty acid mixture to propofol isomers (2,4-diisopropylphenol and 2,6-diisopropylphenol). The prepared derivatives were characterized by FT-IR, NMR (¹H, ¹³C) and GC–MS and were tested for in vitro antiproliferative studies on A549, MDA-MB-231, HeLa, Mia-Pa–Ca and HePG2 cancer cell lines. All the synthesized propofol-mixed fatty acid conjugates showed good to moderate specific growth inhibition of cancer cells on studied cell lines. The results suggest that all the novel propofol-mixed fatty acid conjugates possess antiproliferative properties that reduce the proliferation of cancer cells in vitro.     

Antifungal Efficacy of an Intravenous Formulation Containing Monomeric Amphotericin B, 5-Fluorocytosine,and Saline for Sodium Supplementation

Purpose

Amphotericin B (AmB) and 5-fluorocytosine (5-FC) exhibit additive to synergistic activity against systemic mycoses. Incompatibility of prescribed formulations precludes concomitant IV administration, a route with distinct advantages. Previously, we used PEG-DSPE micelles to produce a reformulation of Fungizone (AmB-SD), AmB solubilized by sodium deoxycholate, called mAmB-90. Herein, we describe a second reformulation that facilitates co-delivery of mAmB-90 and 5-FC, and evaluate the effect of PEG-DSPE micelles on the combination’s activity against Candida albicans.

Methods

We assessed the effect of 5-FC addition on the stability, in vitro toxicity, and antifungal efficacy of mAmB-90. The aggregation state and particle size of mAmB-90 combined with 5-FC (FmAmB-90) was evaluated over 48 h. Hemolytic activity was measured in vitro. Antifungal activity was determined in vitro against C. albicans. The efficacy of monotherapy and combination treatment was evaluated in a neutropenic mouse model of disseminated candidiasis.

Results

The aggregation state, particle size, and hemolytic activity of mAmB-90 were unaffected by 5-FC. While antifungal activity was similar in vitro, mAmB-90 alone and combined with 5-FC was more potent than AmB-SD in vivo.

Conclusions

Short-term stability and in vivo efficacy of our formulation suggest potential to simultaneously deliver AmB and 5-FC for potent antifungal efficacy.

     

Succinate dehydrogenase activity regulates PCB3-quinone-induced metabolic oxidative stress and toxicity in HaCaT human keratinocytes

Polychlorinated biphenyls (PCBs) and their metabolites are environmental pollutants that are known to have adverse health effects. 1-(4-Chlorophenyl)-benzo-2,5-quinone (4-ClBQ), a quinone metabolite of 4-monochlorobiphenyl (PCB3, present in the environment and human blood) is toxic to human skin keratinocytes, and breast and prostate epithelial cells. This study investigates the hypothesis that 4-ClBQ-induced metabolic oxidative stress regulates toxicity in human keratinocytes. Results from Seahorse XF96 Analyzer showed that the 4-ClBQ treatment increased extracellular acidification rate, proton production rate, oxygen consumption rate and ATP content, indicative of metabolic oxidative stress. Results from a q-RT-PCR assay showed significant increases in the mRNA levels of hexokinase 2 (hk2), pyruvate kinase M2 (pkm2) and glucose-6-phosphate dehydrogenase (g6pd), and decreases in the mRNA levels of succinate dehydrogenase (complex II) subunit C and D (sdhc and sdhd). Pharmacological inhibition of G6PD-activity enhanced the toxicity of 4-ClBQ, suggesting that the protective function of the pentose phosphate pathway is functional in 4-ClBQ-treated cells. The decrease in sdhc and sdhd expression was associated with a significant decrease in complex II activity and increase in mitochondrial levels of ROS. Overexpression of sdhc and sdhd suppressed 4-ClBQ-induced inhibition of complex II activity, increase in mitochondrial levels of ROS, and toxicity. These results suggest that the 4-ClBQ treatment induces metabolic oxidative stress in HaCaT cells, and while the protective function of the pentose phosphate pathway is active, inhibition of complex II activity sensitizes HaCaT cells to 4-ClBQ-induced toxicity.     

Joint toxicity of cadmium and SDBS on <Emphasis Type="Italic">Daphnia magna</Emphasis> and <Emphasis Type="Italic">Danio rerio</Emphasis>

Information on joint toxicity is limited. To clarify the joint toxicity and the interactions among toxicants on different aquatic organisms, we investigated the acute toxicity of cadmium and sodium dodecyl benzene sulfonate, two chemicals with high concerns in Chinese waters, on the immobilization of Daphnia magna (D. magna) and the swimming behavior of Danio rerio (D. rerio). Our results illustrated that cadmium and sodium dodecyl benzene sulfonate expressed a synergistic effect on the immobilization of D. magna; and an antagonistic effect on the swimming speed D. rerio, but a synergistic effect on its vertical position in the water column. Based on the observed data, we found the independent action model was more appropriate than the concentration addition model in the prediction of their joint toxicity. Our results gave an example of the joint toxicity investigation, and aided to comprehensive the toxicity action mode of chemical mixtures.     

Risk assessment of various insecticides used for management of Asian citrus psyllid, <Emphasis Type="Italic">Diaphorina citri</Emphasis> in Florida citrus,against honey bee, <Emphasis Type="Italic">Apis mellifera</Emphasis>

The Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Liviidae), is a major pest of citrus trees worldwide. A wide variety of insecticides are used to manage D. citri populations within citrus groves in Florida. However, in areas shared by citrus growers and beekeepers the use of insecticides may increase the risks of Apis mellifera  L. (Hymenoptera: Apidae) loss and contaminated honey. The objective of this research was to determine the environmental toxicity of insecticides, spanning five different modes of action used to control D. citri, to A. mellifera. The insecticides investigated were imidacloprid, fenpropathrin, dimethoate, spinetoram and diflubenzuron. In laboratory experiments, LD₅₀ values were determined and ranged from 0.10 to 0.53?ng/μl for imidacloprid, fenpropathrin, dimethoate and spinetoram. LD₅₀ values for diflubenzuron were >1000?ng/μl. Also, a hazard quotient was determined and ranged from 1130.43 to 10893.27 for imidacloprid, fenpropathrin, dimethoate, and spinetoram. This quotient was <0.447 for diflubenzuron. In field experiments, residual activity of fenpropathrin and dimethoate applied to citrus caused significant mortality of A. mellifera 3 and 7 days after application. Spinetoram and imidacloprid were moderately toxic to A. mellifera at the recommended rates for D. citri. Diflubenzuron was not toxic to A. mellifera in the field as compared with untreated control plots. Phenoloxidase (PO) activity of A. mellifera was higher than in untreated controls when A. mellifera were exposed to 14 days old residues. The results indicate that diflubenzuron may be safe to apply in citrus when A. mellifera are foraging, while most insecticides used for management of D. citri in citrus are likely hazardous under various exposure scenarios.     

Chemomodulatory effect <Emphasis Type="Italic">Melastoma Malabathricum</Emphasis> Linn against chemically induced renal carcinogenesis rats via attenuation of inflammation,oxidative stress,and early markers of tumor expansion

Melastoma malabathricum Linn (MM) has high valued for its commercial significance. Indian market (northeast) has great demand for the plants, which extended, its use as a traditional home remedy due to its anti-inflammatory effects. In this study, we scrutinize the therapeutic and protective effect of MM against diethylnitrosamine (DEN) and ferric nitrilotriacetate (Fe-NTA)-induced renal carcinogenesis, renal hyperproliferation, and oxidative stress in rats. Liquid chromatography mass spectroscopy (LC–MS) was used for identification of phytoconstituents. Administration of DEN confirmed the initiation the renal carcinogenesis via enhancing the expansion of tumor incidence. Intraperitoneally, administration of Fe-NTA boost the antioxidant enzymes (phase I), viz., superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx) and phase II, viz., quinone reductase (QR) and glutathione-S-transferase (GST). It also increased the content of renal lipid peroxidation (LPO), hydrogen peroxidase (H₂O₂) with decrease content in glutathione content (GSH). It also increased the renal biochemical and non-biochemical parameter. It also confirmed the augment the level of thymidine [3H] incorporation into renal DNA, ornithine decarboxylase (ODC) activity and increased the generation of proinflammatory (TNF-α, IL-6 and IL-β) and inflammatory mediator (PGE₂). We also analyzed the macroscopic and histologic of renal tissue. In addition, the effect of phytoconstituent of MM extract was evaluated in silico and free radical scavenging activity against the DPPH and ABTS free radicals. LC–MS confirmed the presence of quercetin >gallic acid in MM extract. Renal carcinogenesis rats treated with MM (100, 250, and 500 mg/kg) confirmed the significantly (P < 0.001) protective effect via reduction the antioxidant (phase I and phase II) enzymes, biochemical parameter and restore the proinflammatory and inflammatory mediator at dose dependent manner. MM altered the ODC and thymidine activity in renal DNA. The chemoprotective effect of MM was confirmed via decreased the renal tumor incidence, which was confirmed by the macroscopic and histopathological observation. Consequently, our result suggests that MM is a potent chemoprotective agent and suppresses DEN+ Fe-NTA-induced renal carcinogenesis, inflammatory reaction, and oxidative stress injury in Wister rats.     

Hepatoprotective and cytotoxic activities of <Emphasis Type="Italic">Anvillea garcinii</Emphasis> and isolation of four new secondary metabolites

Anvillea garcinii is a medicinal plant traditionally used for the treatment of dysentery, gastrointestinal troubles, hepatitis, lung disease, colds, digestive problems and pulmonary affections and in liver diseases. Four new sesquiterpene lactones, garcinamines A–D, along with seven known compounds, were isolated from the leaves of A. garcinii. This is the first report of the isolation of amino acid analogues of parthenolide-type sesquiterpene lactones from the family Asteraceae. Total ethanol extract of leaves as well as the chloroform and n-butanol fractions were tested for their hepatoprotective effect using the carbon tetrachloride liver toxicity model. The chloroform fraction, at a dose of 400 mg/kg, demonstrated a significant hepatoprotective effect comparable to silymarin in all serum and tissue parameters. The cytotoxicity of all extracts and compounds were evaluated against five human cancer cell lines: MCF-7, HCT-116, HepG2, Hela and A-549. The results indicated that the chloroform and n-butanol fractions and compounds 3, 4, 7 and 8 displayed significant cytotoxic activity against these cell lines.     

Inhibition of <Emphasis Type="Italic">Klebsiella pneumoniae</Emphasis> growth by selected Australian plants: natural approaches for the prevention and management of ankylosing spondylitis

A wide variety of herbal remedies are used in traditional Australian medicine to treat inflammatory disorders, including autoimmune inflammatory diseases. One hundred and six extracts from 40 native Australian plant species traditionally used for the treatment of inflammation and/or to inhibit bacterial growth were investigated for their ability to inhibit the growth of a microbial trigger for ankylosing spondylitis (K. pneumoniae). Eighty-six of the extracts (81.1%) inhibited the growth of K. pneumoniae. The D. leichardtii, Eucalyptus spp., K. flavescens, Leptospermum spp., M. quinquenervia, Petalostigma spp., P. angustifolium, S. spinescens, S. australe, S. forte and Tasmannia spp. extracts were effective K. pneumoniae growth inhibitors, with MIC values generally <1000 µg/mL. The T. lanceolata peppercorn extracts were the most potent growth inhibitors, with MIC values as low as 16 µg/mL. These extracts were examined by non-biased GC–MS headspace analysis and comparison with a compound database. A notable feature was the high relative abundance of the sesquiterpenoids polygodial, guaiol and caryophyllene oxide, and the monoterpenoids linalool, cineole and α-terpineol in the T. lanceolata peppercorn methanolic and aqueous extracts. The extracts with the most potent K. pneumoniae inhibitory activity (including the T. lanceolata peppercorn extracts) were nontoxic in the Artemia nauplii bioassay. The lack of toxicity and the growth inhibitory activity of these extracts against K. pneumoniae indicate their potential for both preventing the onset of ankylosing spondylitis and minimising its symptoms once the disease is established.