Pomegranate juice attenuates acetaminophen induced hepatotoxicity in rat model of experiment

Background: Pomegranate fruit has high contents of various polyphenols and antioxidants due to which it possesses variety of therapeutic properties. In particular, pomegranate fruit peel and flowers have exhibited high antioxidant activity in different studies. Acetaminophen (APAP) overdose is the most common cause of drug induced liver toxicity including both accidental and intentional types. In our study, we investigated the protecting mechanism of pomegranate fruit juice (PJ) against toxicity caused by APAP in Wistar rats.Methods: Rats were fed with 0.2% (w/v) pomegranate fruit extract as prophylaxis to counter single dose of APAP (2 g/kg, p.o). After that variation in levels of glutathione, glutathione peroxidase (GPx), and glutathione reductase (GR) were marked.Results: A single dose of APAP elevated serum toxicity markers including lipid peroxidation. A simultaneous sharp depletion of glutathione and its metabolizing enzymes glutathione peroxidase (GPx), glutathione reductase (GR) was observed. Oral doses of PJ at (0.1% & 0.2% w/v) caused a significant (P<0.001) reduction in toxicity marker enzymes. A striking elevation in antioxidant armory was seen as in response to PJ.Conclusion: The results provide a clear picture of the defensive effect of PJ against APAP induced hepatic toxicity

Toxicity of Vernonia anthelmintica Linn. (Asteracea) seeds against mosquitoes vectors

The Toxicological activity (larvicidal, adulticidal and repellent toxicity) of Vernonia anthelmintica seeds fraction was tested against different species of mosquito vectors viz, malaria (Anopheles culicifacies and Anopheles stephensi), filaria (Culex quinquefasciatus) and dengue (Aedes aegypti). The larvicidal toxicity of Vernonia anthelmintica seeds fraction was evaluated against the early 4th instars larvae of different mosquitoes species. Mean LC50 value of the column fraction KAL-4 from seeds of V. anthelmintica against the larvae of An. culicifacies, An. stephensi, Culex quinquifaciatus and Aedes aegpyti were found to be 64 ppm, 70 ppm, 143 ppm and 166 ppm respectively. The larvicidal toxicity was more against An. culicifacies, An. stephensi than Culex quinquifaciatus and Aedes aegypti. The seed extracts did not show any adulticidal toxicity and repellent toxicity even at 10% concentrated impregnated paper and 5% on human hand, respectively

Antidiabetic potential of Moringa oleifera Lam. leaf extract in type 2 diabetic rats, and its mechanism of action

Purpose: To explore the antidiabetic potential of Moringa oleifera leaf extract in type 2 diabetic rats, and the underlying mechanisms.Methods: Streptozotocin (STZ) at a dose of 40 mg/kg was given to high fat diet (HFD)- fed rats to induce type 2 diabetes. M. oleifera leaf extract at doses 100, 200 and 400 mg/kg were given to 3 groups of type 2 diabetic rats. The area under curve (AUC) of glucose and homeostasis model assessment of insulin resistance (HOMA-R) were calculated using appropriate formulas, whereas levels of glucose,insulin, peroxisome proliferator activated receptor-γ (PPARγ, dipeptidyl peptidase-IV (DPP-IV) and inflammatory cytokines (IL-6, IL-1β and TNFα) were assayed using ELISA kits.Results: The leaf extract of M. oleifera significantly reduced the levels of glucose, insulin and cytokines in treated type 2 diabetic groups (p &lt; 0.05). DC group had significantly increased AUC for glucose, whereas the extract-treated groups showed significant&nbsp; decrease in glucose AUC. There was significant decrease in insulin sensitivity parameters, as indicated by increase in HOMA-R and decrease in PPARγ levels in the DC group (p &lt; 0.05). However, treatment with the M. oleifera extract reversed this trend via marked decrease in HOMA-R level and significant rise in PPARγ level. In contrast, the extract had no effect on DPP-IV concentration in diabetic treated groups (p &lt; 0.05).Conclusion: These results indicate that M. oleifera leaf extract mitigates hyperglycemia in type 2 DM by modulating hyperinsulinemia, PPARγ and inflammatory cytokines. Thus, the extract is a potential source of drug for the management of type 2 DM. Keywords: Moringa oleifera, Diabetes mellitus, Streptozotocin, Peroxisome proliferator activated receptor-γ, Dipeptidyl peptidase I

Green Synthesized of Thymus vulgaris Chitosan Nanoparticles Induce Relative WRKY-Genes Expression in Solanum lycopersicum against Fusarium solani, the Causal Agent of Root Rot Disease

: Fusarium solani is a plant pathogenic fungus that causes tomato root rot disease and yield losses in tomato production. The current study's main goal is testing the antibacterial efficacy of chitosan nanoparticles loaded with Thyme vulgaris essential oil (ThE-CsNPs) against F. solani in vitro and in vivo. GC-MS analysis was used to determine the chemical constituents of thyme EO. ThE-CsNPs were investigated using transmission electron microscopy before being physicochemically characterized using FT-IR. ThE-CsNPs were tested for antifungal activity against F. solani mycelial growth in vitro. A pot trial was conducted to determine the most effective dose of ThE-CsNPs on the morph/physiological characteristics of Solanum lycopersicum, as well as the severity of fusarium root rot. The relative gene expression of WRKY transcript factors and defense-associated genes were quantified in root tissues under all treatment conditions. In vitro results revealed that ThE-CsNPs (1%) had potent antifungal efficacy against F. solani radial mycelium growth. The expression of three WRKY transcription factors and three tomato defense-related genes was upregulated. Total phenolic, flavonoid content, and antioxidant enzyme activity were all increased. The outfindings of this study strongly suggested the use of ThE-CsNPs in controlling fusarium root rot on tomatoes; however, other experiments remain necessary before they are recommended

Catha edulis active principle, cathinone, suppresses motor coordination, accelerates the anxiety and alters the levels of dopamine and its metabolites in the limbic areas of male Swiss albino mice

Cathinone, the active principle of khat (Catha edulis), stimulates, excites and produces euphoric feelings in khat users. Locomotor and rearing activities, either individual or in groups, of male Swiss albino mice were decreased significantly compared to the control. Motor coordination tests (rotarod, rope climb and grip tests) have shown decreased motor performance in the mice treated with cathinone compared to the control. The elevated plus maze test has shown significant anxiety in the mice compared to the control. Contents of dopamine and its metabolite, homovanillic acid, were increased in the limbic areas compared to the control group. In contrast, contents of 3,4-dihydroxyphenyl acetic acid were depleted significantly and dose dependently compared to the control group in the limbic areas of mice. In conclusion, natural cathinone has depleted motor coordination, accelerated anxiety in mice and altered the contents of dopamine and its metabolites

Enhancement of antifungal activity and transdermal delivery of 5-flucytosine via tailored spanlastic nanovesicles: statistical optimization, in-vitro characterization, and in-vivo biodistribution study

Aim and background: This current study aimed to load 5-flucytosine (5-FCY) into spanlastic nanovesicles (SPLNs) to make the drug more efficient as an antifungal and also to load the 5-FCY into a hydrogel that would allow for enhanced transdermal permeation and improved patient compliance.Methods: The preparation of 5-FCY-SPLNs was optimized by using a central composite design that considered Span 60 (X1) and the edge activator Tween 80 (X2) as process variables in achieving the desired particle size and entrapment efficiency. A formulation containing 295.79 mg of Span 60 and 120.00 mg of Tween 80 was found to meet the prerequisites of the desirability method. The optimized 5-FCY-SPLN formulation was further formulated into a spanlastics gel (SPG) so that the 5-FCY-SPLNs could be delivered topically and characterized in terms of various parameters.Results: As required, the SPG had the desired elasticity, which can be credited to the physical characteristics of SPLNs. An ex-vivo permeation study showed that the greatest amount of 5-FCY penetrated per unit area (Q) (mg/cm2) over time and the average flux (J) (mg/cm2/h) was at the end of 24 h. Drug release studies showed that the drug continued to be released until the end of 24 h and that the pattern was correlated with an ex-vivo permeation and distribution study. The biodistribution study showed that the 99mTc-labeled SFG that permeated the skin had a steadier release pattern, a longer duration of circulation with pulsatile behavior in the blood, and higher levels in the bloodstream than the oral 99mTc-SPNLs. Therefore, a 5-FCY transdermal hydrogel could possibly be a long-acting formula for maintenance treatment that could be given in smaller doses and less often than the oral formula

The novel curcumin analog FLLL32 decreases STAT3 DNA binding activity and expression, and induces apoptosis in osteosarcoma cell lines

<p>Abstract</p> <p>Background</p> <p>Curcumin is a naturally occurring phenolic compound shown to have a wide variety of antitumor activities; however, it does not attain sufficient blood levels to do so when ingested. Using structure-based design, a novel compound, FLLL32, was generated from curcumin. FLLL32 possesses superior biochemical properties and more specifically targets STAT3, a transcription factor important in tumor cell survival, proliferation, metastasis, and chemotherapy resistance. In our previous work, we found that several canine and human osteosarcoma (OSA) cell lines, but not normal osteoblasts, exhibit constitutive phosphorylation of STAT3. Compared to curcumin, we hypothesized that FLLL32 would be more efficient at inhibiting STAT3 function in OSA cells and that this would result in enhanced downregulation of STAT3 transcriptional targets and subsequent death of OSA cells.</p> <p>Methods</p> <p>Human and canine OSA cells were treated with vehicle, curcumin, or FLLL32 and the effects on proliferation (CyQUANT^®), apoptosis (SensoLyte^®Homogeneous AMC Caspase- 3/7 Assay kit, western blotting), STAT3 DNA binding (EMSA), and vascular endothelial growth factor (VEGF), survivin, and matrix metalloproteinase-2 (MMP2) expression (RT-PCR, western blotting) were measured. STAT3 expression was measured by RT-PCR, qRT- PCR, and western blotting.</p> <p>Results</p> <p>Our data showed that FLLL32 decreased STAT3 DNA binding by EMSA. FLLL32 promoted loss of cell proliferation at lower concentrations than curcumin leading to caspase-3- dependent apoptosis, as evidenced by PARP cleavage and increased caspase 3/7 activity; this could be inhibited by treatment with the pan-caspase inhibitor Z-VAD-FMK. Treatment of OSA cells with FLLL32 decreased expression of survivin, VEGF, and MMP2 at both mRNA and protein levels with concurrent decreases in phosphorylated and total STAT3; this loss of total STAT3 occurred, in part, via the ubiquitin-proteasome pathway.</p> <p>Conclusions</p> <p>These data demonstrate that the novel curcumin analog FLLL32 has biologic activity against OSA cell lines through inhibition of STAT3 function and expression. Future work with FLLL32 will define the therapeutic potential of this compound <it>in vivo</it>.</p

Nephroprotective Effect of Zingerone against CCl4-Induced Renal Toxicity in Swiss Albino Mice: Molecular Mechanism

The protective effects of Zingerone against CCl4 induced nephrotoxicity in Swiss albino mice via modulation of metabolizing enzyme, oxidative stress, inflammatory cytokines, and apoptosis. The biochemical estimation indicated that the BUN and creatinine were significantly increased in group 2 (CCl4) compared to group 1 (normal) which was significantly reduced after treatment with Zingerone in group 3 when compared with group 2. The CCl4 treatment has significantly increased TBARS levels and reduced the antioxidant enzyme such as GSH, GPx, GR, GST, CAT, and SOD in group 2 compared to group 1, while the Zingerone treatment showed significant reduction in TBARS levels and increased the antioxidant enzymes in group 3 (CCl4 + Zingerone) as compared to group 2. Similarly, it was observed that CCl4 significantly increased the cytokines such as IL-1β, IL-2, and TNFα levels in group 2 as compared to group 1. The treatment with Zingerone significantly attenuated the levels of IL-1β, IL-2, and TNFα in group 3 compared to group 2. Caspase 3 and caspase 9 were also significantly increased in CCl4-treated group 2, whereas Zingerone treatment significantly reduced the elevated levels of caspases 3 and 9 in group 3 compared to group 2