Synergistic interactions of Ferulic acid with Ascorbic acid: Its cardioprotective role during isoproterenol induced myocardial infarction in rats

Studies on the lipid peroxidation and antioxidant changes and their significance during myocardial injury have provided a new insight into the pathogenesis of heart disease. The heart failure subsequent to myocardial infarction may be associated with an antioxidant deficit as well as increased myocardial oxidative stress. The present study was designed to evaluate the effect of the combination of ferulic acid and ascorbic acid on antioxidant defense system and lipid peroxidation against isoproterenol (ISO)-induced myocardial infarction in rats. Induction of rats with isoproterenol (150 mg/kg body weight daily, i.p.) for 2 days resulted in a marked elevation in lipid peroxidation, serum marker enzymes (LDH, CPK, GOT, and GPT), and a significant decrease in activities of endogenous antioxidants (SOD, GPx, GST, CAT, and GSH). Pre-co-treatment with the combination of ferulic acid (20 mg/kg body weight/day) and ascorbic acid (80 mg/kg body weight/day) orally for 6 days, significantly attenuated these changes when compared to the individual treatment groups. Histopathological observations were also in correlation with the biochemical parameters. Thus, ferulic acid and ascorbic acid significantly counteracted the pronounced oxidative stress effect of ISO by the inhibition of lipid peroxidation, restoration of antioxidant status, and myocardial marker enzymes levels. In conclusion, these findings indicate the synergistic protective effect of ferulic acid and ascorbic acid on lipid peroxidation and antioxidant defense system during ISO-induced myocardial infarction and associated oxidative stress in rats.     

Multiple light inputs control phototaxis in Synechocystis sp. strain PCC6803

The phototactic behavior of individual cells of the cyanobacterium Synechocystis sp. strain PCC6803 was studied with a glass slide-based phototaxis assay. Data from fluence rate-response curves and action spectra suggested that there were at least two light input pathways regulating phototaxis. We observed that positive phototaxis in wild-type cells was a low fluence response, with peak spectral sensitivity at 645 and 704 nm. This red-light-induced phototaxis was inhibited or photoreversible by infrared light (760 nm). Previous work demonstrated that a taxD1 mutant (Cyanobase accession no. sll0041; also called pisJ1) lacked positive but maintained negative phototaxis. Therefore, the TaxD1 protein, which has domains that are similar to sequences found in both bacteriophytochrome and the methyl-accepting chemoreceptor protein, is likely to be the photoreceptor that mediates positive phototaxis. Wild-type cells exhibited negative phototaxis under high-intensity broad-spectrum light. This phenomenon is predominantly blue light responsive, with a maximum sensitivity at approximately 470 nm. A weakly negative phototactic response was also observed in the spectral region between 600 and 700 nm. A deltataxD1 mutant, which exhibits negative phototaxis even under low-fluence light, has a similar action maximum in the blue region of the spectrum, with minor peaks from green to infrared (500 to 740 nm). These results suggest that while positive phototaxis is controlled by the red light photoreceptor TaxD1, negative phototaxis in Synechocystis sp. strain PCC6803 is mediated by one or more (as yet) unidentified blue light photoreceptors.     

Adriamycin induced myocardial failure in rats: Protective role of Centella asiatica

Generation of reactive oxygen species and mitochondrial dysfunction has been implicated in adriamycin induced cardiotoxicity. Mitochondrial dysfunction is characterized by the accumulation of oxidized lipids, proteins and DNA, leading to disorganization of mitochondrial structure and systolic failure. The present study was aimed to evaluate the efficacy of Centella asiatica on the mitochondrial enzymes; mitochondrial antioxidant status in adriamycin induced myocardial injury. Adriamycin (2.5 mg/kg body wt., i.p.) induced mitochondrial damage in rats was assessed in terms of decreased activities (p< 0.05) of cardiac marker enzymes (lactate dehydrogenase, creatine phosphokinase, amino transferases), TCA cycle enzymes (isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, malate dehydrogenase, respiratory marker enzymes (NADH-dehydrogenase, cytochrome-C-oxidase), mitochondrial antioxidant enzymes (GPx, GSH, SOD,CAT) and increased (p< 0.05) level of lipid peroxidation. Mitochondrial damage was confirmed by transmission electron microscopic examination. Pre-co-treatment with aqueous extract of Centella asiatica (200 mg/kg body wt, oral) effectively counteracted the alterations in mitochondrial enzymes and mitochondrial defense system. In addition, transmission electron microscopy study confirms the restoration of cellular normalcy and accredits the cytoprotective role of Centella asiatica against adriamycin induced myocardial injury. Our results demonstrated elevated oxidative stress and mitochondrial dysfunction in adriamycin treated rats. Moreover, on the basis of our findings it may be concluded that the aqueous extract of C. asiatica not only possesses antioxidant properties but it may also reduce the extent of mitochondrial damage     

The gramicidin ion channel: A model membrane protein

The linear peptide gramicidin forms prototypical ion channels specific for monovalent cations and has been extensively used to study the organization, dynamics and function of membrane-spanning channels. In recent times, the availability of crystal structures of complex ion channels has challenged the role of gramicidin as a model membrane protein and ion channel. This review focuses on the suitability of gramicidin as a model membrane protein in general, and the information gained from gramicidin to understand lipid-protein interactions in particular. Special emphasis is given to the role and orientation of tryptophan residues in channel structure and function and recent spectroscopic approaches that have highlighted the organization and dynamics of the channel in membrane and membrane-mimetic media.     

The MADS box gene, FOREVER YOUNG FLOWER, acts as a repressor controlling floral organ senescence and abscission in Arabidopsis

The ectopic expression of a MADS box gene FOREVER YOUNG FLOWER (FYF) caused a significant delay of senescence and a deficiency of abscission in flowers of transgenic Arabidopsis. The defect in floral abscission was found to be due to a deficiency in the timing of cell separation of the abscission zone cells. Down-regulation of INFLORESCENCE DEFICIENT IN ABSCISSION (IDA) may contribute to the delay of the floral abscission in 35S:FYF flowers. FYF was found to be highly expressed in young flowers prior to pollination and was significantly decreased after pollination, a pattern that correlated with its function. Ethylene insensitivity in senescence/abscission and the down-regulation of ETHYLENE RESPONSE DNA-BINDING FACTOR 1 (EDF1) and EDF2, downstream genes in the ethylene response, in 35S:FYF Arabidopsis suggested a role for FYF in regulating senescence/abscission by suppressing the ethylene response. This role was further supported by the fact that 35S:FYF enhanced the delay of flower senescence/abscission in ethylene response 1 (etr1), ethylene-insensitive 2 (ein2) and constitutive triple response 1 (ctr1) mutants, which have defects in upstream genes of the ethylene signaling pathway. The presence of a repressor domain in the C-terminus of FYF and the enhancement of the delay of senescence/abscission in FYF+SRDX (containing a suppression motif) transgenic plants suggested that FYF acts as a repressor. Indeed, in FYF-DR+VP16 transgenic dominant-negative mutant plants, in which FYF was converted to a potent activator by fusion to a VP16-AD motif, the senescence/abscission of the flower organs was significantly promoted, and the expression of BOP2, IDA and EDF1/2 was up-regulated. Our data suggest a role for FYF in controlling floral senescence/abscission by repressing ethylene responses and regulating the expression of BOP2 and IDA in Arabidopsis.     

Effect of <Emphasis Type="Italic">Tridax procumbens</Emphasis> on liver antioxidant defense system during lipopolysaccharide-induced hepatitis in D-galactosamine sensitised rats

The present study was carried out to assess the effect of chloroform insoluble fraction of ethanolic extract of Tridax procumbens (TP) against D-Galactosamine/Lipopolysaccharide (D-GalN/LPS)-induced hepatitis in rats. Induction of rats with D-GalN/LPS (300 mg/kg body weight/30 g/kg body weight) led to a marked increase in lipid peroxidation as measured by thiobarbituric acid reactive substances (TBARS) in liver. Further there was a decline in the activities of enzymic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, glutathione s-transferase and the levels of non-enzymic antioxidants namely reduced glutathione, vitamin C and vitamin E. These biochemical alterations were normalised upon pretreatment with TP extract. Thus, the above results suggest that TP (300 mg/kg body weight orally for 10 days) is very effective in allievating the D-GalN/LPS-induced oxidative stress suggesting its antioxidant property. (Mol Cell Biochem 269: 131–136, 2005)     

Protective effect of Premna tomentosa extract (L. verbanacae) on acetaminophen-induced mitochondrial dysfunction in rats

Allurement of herbs as health beneficial foods (physiologically functional foods) and as a source material for the development of new drugs, has led to greater furtherance in the study of herbal medicines during recent years. Plant extracts are being utilized to treat a wide variety of diseases like hepatotoxicity. Premna tomentosa is one such medicinal plant used widely in Indian ayurvedic medicine for the treatment of liver disorders. This study appraised the effectiveness of P. tomentosa leaf extract in protecting the liver against mitochondrial damage induced by acetaminophen, since mitochondrial injury has been investigated as a potential initiator of hepatotoxicity. Normal Wistar strain rats were pre-treated with P. tomentosa extract (750 mg/kg, orally) for 15 days and then intoxicated with acetaminophen (640 mg/kg, orally). Mitochondria were isolated from liver of experimental animals and assessed for the levels of lipid peroxide products, GSH and mitochondrial enzymes (isocitrate dehydrogenase, -keto glutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, NADH dehydrogenase and cytochrome-C-oxidase). The levels of Lipid peroxidation products were increased and the levels of the other assessed parameters were significantly decreased in hepatotoxicity induced animals. Whereas, the levels were brought back to normal in P. tomentosa pre-treated rats, which shows the protective effect of the extract against mitochondrial damage. Presence of anti-oxidant compound d-limonene (58%) in P. tomentosa leaves, which is known to enhance conjugation of toxic metabolites by maintaining liver GSH concentrations may explain the hepatoprotective property of the extract.     

Overexpression of Oncidium MADS box (OMADS1) gene promotes early flowering in transgenic orchid (Oncidium Gower Ramsey)

Oncidium is a popular ornamental orchid and is produced as a high value cash crop for cut flower sold worldwide. Genetically transformed plants of Oncidium were regenerated after cocultivating protocorm-like bodies (PLBs) with Agrobacterium tumefaciens strain LBA4404 harboring pBI121 with OMADS1. The chopped PLBs pre-cultured for 3?days in darkness produced more kanamycin-resistant PLBs. G10 medium containing 200?mg?l^?1 kanamycin was effective for the selection of transformed lines at a frequency of 9%. The rooted plantlets were transferred to pots, acclimated for 3?weeks in the culture room and then moved to the greenhouse. OMADS1 transgene was detected in transgenic lines by PCR, Southern blot analysis and RT-PCR were performed, and the results confirmed that OMADS1 was expressed in these 35S::OMADS1 transgenic plants. CaMV35S::OMADS1 transgenic Oncidium orchid plants flowered significantly earlier, produced more flowers and pseudobulbs than non-transgenic plants. The flower organ conversions were not observed in 35S::OMADS1 transgenic flowers of Oncidium. This is the first report on the ectopic expression of MADS box gene in O. Gower Ramsey using a simple and efficient gene transfer protocol.     

Met receptor tyrosine kinase signaling induces secretion of the angiogenic chemokine interleukin-8/CXCL8 in pancreatic cancer

At diagnosis, the majority of pancreatic cancer patients present with advanced disease when curative resection is no longer feasible and current therapeutic treatments are largely ineffective. An improved understanding of molecular targets for effective intervention of pancreatic cancer is thus urgent. The Met receptor tyrosine kinase is one candidate implicated in pancreatic cancer. Notably, Met is over expressed in up to 80% of invasive pancreatic cancers but not in normal ductal cells correlating with poor overall patient survival and increased recurrence rates following surgical resection. However the functional role of Met signaling in pancreatic cancer remains poorly understood. Here we used RNA interference to directly examine the pathobiological importance of increased Met signaling for pancreatic cancer. We show that Met knockdown in pancreatic tumor cells results in decreased cell survival, cell invasion, and migration on collagen I in vitro. Using an orthotopic model for pancreatic cancer, we provide in vivo evidence that Met knockdown reduced tumor burden correlating with decreased cell survival and tumor angiogenesis, with minimal effect on cell growth. Notably, we report that Met signaling regulates the secretion of the pro-angiogenic chemokine interleukin-8/CXCL8. Our data showing that the interleukin-8 receptors CXCR1 and CXCR2 are not expressed on pancreatic tumor cells, suggests a paracrine mechanism by which Met signaling regulates interleukin-8 secretion to remodel the tumor microenvironment, a novel finding that could have important clinical implications for improving the effectiveness of treatments for pancreatic cancer.