Hypoxia-inducible-factor (HIF)-mediated expression of pro-angiogenic genes under hypoxic conditions is the fundamental cause of pathological neovascularization in retinal ischemic diseases and cancers. Recent studies have shown that histone lysine demethylases (KDMs) play a key role in the amplification of HIF signaling and expression of pro-angiogenic genes. Thus, the inhibitors of the HIF pathway or KDMs can have profound therapeutic value for diseases caused by pathological neovascularization. Here, we show that hypoxia-mediated expression of KDMs is a conserved process across multiple cell lines. Moreover, we report that honokiol, a biphenolic phytochemical extracted from Magnolia genus which has been used for thousands of years in the traditional Japanese and Chinese medicine, is a potent inhibitor of the HIF pathway as well as hypoxia-induced expression of KDMs in a number of cancer and retinal pigment epithelial cell lines. Further, treating the cells with honokiol leads to inhibition of KDM-mediated induction of pro-angiogenic genes (adrenomedullin and growth differentiation factor 15) under hypoxic conditions. Our results provide an evidence-based scientific explanation for therapeutic benefits observed with honokiol and warrant its further clinical evaluation for the treatment of pathological neovascularization in retinal ischemic diseases and cancers.

The present paper reports the spectroscopic and theoretical investigations on the formation of supramolecular complexes of a designed bisporphyrin (1) with C(60) and C(70) in toluene. Absorption spectrophotometric studies establish appreciable amount of ground state electronic interaction between fullerenes and 1. The interaction is facilitated through charge transfer (CT) transition as evidenced from well defined CT absorption bands in the visible region of the electronic spectra. In our present case, the CT interaction may be claimed as one of the rare findings, especially on account of interaction between fullerenes and bisporphyrin in a non-polar solvent. Other than fullerenes C(60) and C(70), various other electron acceptors, viz., 2,3-dichloro-5,6-dicyano-p-benzoquinone, tetracyanoethylene, o-chloranil and p-chloranil form CT complexes with 1. Utilizing the CT transition energies for various electron donor-acceptor complexes of 1, vertical ionization potential (I(D)(v)) of 1 is determined to be 6.37eV in solution. Estimation of degrees of CT, oscillator and transition dipole strengths evoke that the fullerene-1 non-covalent complexes are of neutral character in ground state. Higher magnitude of electronic coupling elements for the C(70)-1 complex compared to C(60)-1 complex indicates strong binding between C(70) and 1. Steady state fluorescence studies elicit efficient quenching of the fluorescence of 1 in presence of fullerenes. Both UV-Vis and steady state fluorescence measurements reveal large value of binding constant (K) for C(70)-1 system (∼6.94×10(4)dm(3)mol(-1)) than that of C(60)-1 system (K∼2.1×10(4)dm(3)mol(-1)). Time resolved emission studies establish charge-separated state for the fullerene-1 systems. Transient absorption measurements in the visible region establish the formation of 1(+) and fullerene(-) in toluene medium. Molecular mechanics calculations employing force field method in vacuo evoke the single projection structures of the fullerene-1 complexes and interpret the stability difference between C(60) and C(70) complexes of 1 in terms of heat of formation values of the respective complexes.

Cidofovir (CDF) and its cyclic analogue (cCDF) have shown potential in vitro and in vivo antiviral activity against cytomegalovirus (CMV) retinitis. However, hydrophilic nature of CDF may affect cell permeation across lipophilic epithelium and thus limit its effectiveness in the treatment of CMV retinitis. In the present study, we have tested a novel hypothesis, which involves chemical derivatization of cCDF into lipophilic transporter-targeted prodrug [via conjugation with different carbon chain length of lipid raft and targeting moiety (biotin) for sodium-dependent multivitamin transporter (SMVT)]. We have synthesized and characterized three derivatives of cCDF including biotin B-C2-cCDF, B-C6-cCDF, and B-C12-cCDF. Physicochemical properties such as solubility, partition coefficient (n-octanol/water and ocular tissue), bioreversion kinetics, and interaction with SMVT transporter have been determined. Among these novel conjugates, B-C12-cCDF has shown higher interaction to SMVT transporter with lowest half maximal inhibitory concentration value, higher cellular accumulation, and high tissue partitioning. Improvement in physicochemical properties, lipophilicity, and interaction with transporter was observed in the trend of increasing the lipid chain length, that is, B-C12-cCDF > B-C6-cCDF > B-C2-cCDF. These results indicate that transporter-targeted lipid analogue of cCDF exhibits improved cellular accumulation along with higher transporter affinity and hence could be a viable strategy for the treatment of CMV retinitis. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.

The last few decades have witnessed application of graph theory and topological indices derived from molecular graph in structure-activity analysis. Such applications are based on regression and various multivariate analyses. Most of the topological indices are computed for the whole molecule and used as descriptors for explaining properties/activities of chemical compounds. However, some substructural descriptors in the form of topological distance based vertex indices have been found to be useful in identifying activity related substructures and in predicting pharmacological and toxicological activities of bioactive compounds. Another important aspect of drug discovery e.g. designing novel pharmaceutical candidates could also be done from the distance distribution associated with such vertex indices. In this article, we will review the development and applications of this approach both in activity prediction as well as in designing novel compounds.

Diet plays a vital role in the management of cancer because they are the source of important physiologically functional components. Scientific observations support the idea that dietary supplement can prevent breast cancer recurrences. Strong correlations are established between the high intake of saturated fat and the incidence of different types of cancer. It is found that chronic alcohol consumption is associated with increased risk of cancers of oral cavity, pharynx, esophagus, and larynx. Again, some evidences are also found regarding phosphorous, glutamate level in the body, and incidence of cancer. Different physiologically functional components are found in the dietary materials. Fibers, the major dietary components, have long been recognized for the unique properties in the treatment of cancer, which are related to its antineoplastic functions. Antioxidant rich diet has been added to the list of cancer-preventing dietary components. Also, recently published research has shown that natural carotenoids in the diet leads to a normalization of body epithelial cells and protects against the risk of stomach and esophagus cancer, and improves the immune system's response. Again, fruit juices, processed vegetable juices, orange peel, green tea, vitamins, flavonoids, and trace materials have cancer inhibitory properties. Clearly, there has been increasing recognition of chemoprotective functions. Now, it can be recognized for another kind of functionality for the improvement of the health of mankind.

Novel tamarind seed polysaccharide (TSP)-alginate mucoadhesive microspheres were prepared using TSP and alginate as blend in different ratios with different calcium chloride (CaCl(2)) concentration as a cross linker by ionotropic gelation. The prepared microspheres were of spherical shape having rough surfaces, and average particle sizes within the range of 752.12 ± 6.42 to 948.49 ± 20.92 µm. The drug entrapment efficiency of these microspheres were within the range between 58.12 ± 2.42 to 82.78 ± 3.43% w/w. Fourier transform infrared (FTIR) studies indicated that there were no reactions between gliclazide, and polymers (TSP, and sodium alginate) used. Different formulations of gliclazide loaded TSP-alginate microspheres showed prolonged in vitro release profiles of gliclazide over 12 hours in both stomach pH (pH 1.2), and intestinal pH (pH 7.4). It was found that the gliclazide release in gastric pH was comparatively slow and sustained than intestinal pH. These TSP-alginate microspheres also exhibited good mucoadhesivity. The in vivo studies on alloxan-induced diabetic rats (Animal Ethical Committee registration number: IFTM/837ac/0160) demonstrated the significant hypoglycemic effect of selected formulation of TSP-alginate mucoadhesive microspheres containing gliclazide on oral administration. This developed gliclazide loaded new TSP-alginate mucoadhesive microspheres may be very much useful for prolonged systemic absorption of gliclazide for proper maintaining blood glucose level and advanced patient compliance.

CONTEXT Clerodendrum infortunatum Linn. is a widely used plant in the Indian indigenous system of medicine for the treatment of tumors. OBJECTIVE The present study evaluated the anticancer activity of methanol extract of C. infortunatum (MECI) against Ehrlich's ascites carcinoma (EAC) bearing Swiss albino mice and isolation of bioactive terpenoids from it. Methods: HPLC analysis of the methanol extract showed the presence of three major components. Out of those, two compounds were isolated and characterized as oleanolic acid and clerodinin A. The anticancer activity of MECI was assessed by measuring the tumor growth response, percentage increase of life span, study of hematological parameters, lipid peroxidation, antioxidant enzyme activity like glutathion and CAT. In vitro cytotoxicity assay was also performed using EAC cell lines. RESULT AND CONCLUSION Treatment with MECI causes significant decrease in the tumor cell volume and increase in the life span. The median survival time (MST) of EAC control group was found as 19.42 ± 0.91 d, whereas the MST was increased to 23.44 ± 2.69 d and 27.57 ± 2.57 d for the groups treated with MECI at 100 and 200 mg/kg, respectively. All the hematological parameters, malonaldehyde content and antioxidant enzymes' activity were restored towards the normal level. IC(50) value of MECI was found as 498.33 µg/mL in cytotoxicity study. The experimental results suggested that MECI has significant anticancer activity, which can be attributed to the presence of oleanolic acid and clerodinin A.

Abstract Purpose: The overall objective of this study was to investigate the differential expression of folate receptor-alpha (FR-α), sodium-dependent multivitamin transporter (SMVT), and amino acid transporter [B ((0,+))] in retinoblastoma (Y-79) and retinal pigment epithelial (ARPE-19) cells. Methods: Polymerase chain reaction (PCR) analysis was performed to confirm the existence of FR-α, SMVT, and B ((0,+)) in Y-79 and ARPE-19 cell lines. Quantitative real-time PCR was also performed to determine the relative expression of FR-α, SMVT, and B ((0,+)) at mRNA level in these cell lines. Quantitative uptake of [(3)H] Folic acid,[(3)H] Biotin, and [(14)C] Arginine was studied in Y-79 and ARPE-19 cells. Further, saturation kinetics of [(3)H] Folic acid,[(3)H] Biotin, and [(14)C] Arginine was performed in the presence of various concentrations of respective cold substrates to determine the kinetic parameters (K(m) and V(max)) in Y-79 and ARPE-19 cells. Results: PCR analysis had confirmed the existence of FR-α, SMVT, and B ((0,+)) in Y-79 and ARPE-19 cells. Quantitative real-time PCR analysis had shown significantly higher expression of FR-α, SMVT, and B ((0,+)) mRNA levels in Y-79 cells compared with ARPE-19 cells. Quantitative uptake of [(3)H] Folic acid,[(3)H] Biotin, and [(14)C] Arginine was found to be significantly higher in Y-79 cells relative to ARPE-19 cells.[(3)H] Folic acid uptake process followed saturation kinetics with apparent K(m) of 8.29 nM and V(max) of 393.47 fmol/min/mg protein in Y-79 cells and K(m) of 80.55 nM and V(max) of 491.86 fmol/min/mg protein in ARPE-19 cells.[(3)H] Biotin uptake process also displayed saturation kinetics with K(m) of 8.53 μM and V(max) of 14.12 pmol/min/mg protein in Y-79 cells and K(m) of 138.25 μM and V(max) of 38.85 pmol/min/mg protein in ARPE-19 cells.[(14)C] Arginine uptake process followed saturation kinetics with K(m) of 16.77 μM and V(max) of 348.27 pmol/min/mg protein in Y-79 cells and K(m) of 52.03 μM and V(max) of 379.21 pmol/min/mg protein in ARPE-19 cells. Conclusions: This work demonstrated for the first time the higher expression and affinity of FR-α, SMVT, and B ((0,+)) mRNA levels in retinoblastoma (Y-79) cells compared with retinal pigment epithelial (ARPE-19) cells.

Cajanus cajan (L) Millsp.(Sanskrit: Adhaki, Hindi: Arhar, English: Pigeon pea, Bengali: Tur)(family: Fabaceae) is the most important grain legume crop of rain-fed agriculture in semi-arid tropics. It is both a food crop and a cover/forage crop with high levels of proteins and important amino acids like methionine, lysine and tryptophan. During the last few decades extensive studies have been carried out regarding the chemistry of C. cajan and considerable progress has been achieved regarding its biological activities and medicinal applications. This review article gives an overview on the biological activities of the compounds isolated, pharmacological actions and clinical studies of C. cajan extracts apart from its general details.

The present study was undertaken to evaluate the mucilage isolated from Spinacia oleracea L. leaves, commonly named spinach (family: Amaranthaceae) as an innovative suspending agent. Zinc oxide suspensions (20% w/v) were prepared using the mucilage of S. oleracea L. leaves as a suspending agent, and it was evaluated for its stability by using parameters like, sedimentation profile, degree of flocculation, and redispersibility. The effect of the tested mucilage on the suspension was compared with various commonly used suspending agents, such as, tragacanth, bentonite, and sodium carboxymethyl cellulose (NaCMC) at concentrations of 0.5, 1.0, and 2.0% w/v. The results obtained indicated that the mucilage of S. oleracea L. leaves could be used as a suspending agent, and the performance was found to be superior to both tragacanth and bentonite.