Purusotam Basnet

Curcumin: An Anti-Inflammatory Molecule from a Curry Spice on the Path to Cancer Treatment

Oxidative damage and inflammation have been pointed out in preclinical studies as the root cause of cancer and other chronic diseases such as diabetes, hypertension, Alzheimer’s disease, etc. Epidemiological and clinical studies have suggested that cancer could be prevented or significantly reduced by treatment with anti-oxidant and anti-inflammatory drugs, therefore, curcumin, a principal component of turmeric (a curry spice) showing strong anti-oxidant and anti-inflammatory activities, might be a potential candidate for the prevention and/or treatment of cancer and other chronic diseases. However, curcumin, a highly pleiotropic molecule with an excellent safety profile targeting multiple diseases with strong evidence on the molecular level, could not achieve its optimum therapeutic outcome in past clinical trials, largely due to its low solubility and poor bioavailability. Curcumin can be developed as a therapeutic drug through improvement in formulation properties or delivery systems, enabling its enhanced absorption and cellular uptake. This review mainly focuses on the anti-inflammatory potential of curcumin and recent developments in dosage form and nanoparticulate delivery systems with the possibilities of therapeutic application of curcumin for the prevention and/or treatment of cancer.

Liposomal Delivery System Enhances Anti-Inflammatory Properties of Curcumin

Curcumin is a well-established natural antioxidant and anti-inflammatory agent. Up till now its potential in treatment of vaginal inflammation has not been evaluated. We are aiming at developing liposomal delivery system for curcumin targeting vaginal administration. Liposomes as nanosized phospholipid-based vesicles are expected to solubilize curcumin and enhance its activity, thus serving as an advanced topical formulation in the treatment of vaginal inflammation. Curcumin and curcuminoids were analyzed by the high-performance liquid chromatography method. Liposomes containing curcumin/curcuminoids of various sizes were prepared and characterized. Antioxidant activities of curcumin and liposomal curcumin were compared based on 1,1-diphenyl-2-picrylhydrazyl radical scavenging and superoxide dismutase activities. The anti-inflammatory activities were determined by measuring the inhibition of lipopolysaccharide -induced nitric oxide, interleukin-1β, and tumor necrosis factor-α production in macrophage RAW 264.7 cells. Curcumin/curcuminoids were encapsulated in phosphatidylcholine vesicles with high yields. Vesicles in the size range around 200 nm were selected for stability and cell experiments. Liposomal curcumin were found to be twofold to sixfold more potent than corresponding curcuminoids. Moreover, the mixture of curcuminoids was found to be more potent than pure curcumin in regard to the antioxidant and anti-inflammatory activities. Liposomal delivery systems for curcumin are promising formulations for the treatment of vaginal inflammation.

Screening of Nepalese crude drugs traditionally used to treat hyperpigmentation: in vitro tyrosinase inhibition.

South‐East Asian population is daily exposed to strong sunlight. As a result, the majority of population will have darker, ethnic skin. Moreover, many people suffer from dark spots, hyperpigmentation, which is considered to be a skin disorder and causes psychological disturbance. To treat dark spots, most of the population will still rely on traditionally used crude drugs, knowledge about which is transferred from generation to generation. Fifty‐two crude drugs were selected based on the survey performed among local healers and beauticians of different ethnic origin. These crude drugs were screened for mushroom tyrosinase inhibitory activity, as tyrosinase inhibitors are becoming increasingly important as cosmetic and medicinal products, primarily to control hyperpigmentation. Among the tested crude drugs, methanolic extracts of Glycyrrhiza glabra, Morus alba, Syzygium aromaticum, Citrus aurantifolia, Cypreae moneta, Punica granatum and Citrus aurantium, at the final concentration of 50 μg mL−1, showed mushroom tyrosinase inhibitory activity of 78.9%, 71.0%, 69.4%, 59.0%, 56.0%, 53.4 and 51.9%, respectively, with 91.4% inhibitory activity of kojic acid taken as positive control. To our knowledge, this is the first report that extracts of Cypreae moneta shell and Syzygium aromaticum flowering bud have tyrosinase inhibitory activity. These potent extracts were further evaluated at different concentration. The final concentration of the extracts in reaction mixtures was 50, 25 and 5 μg mL−1 for the initial concentration of 1000, 500 and 100 μg mL−1, respectively. They showed concentration‐dependant inhibition of mushroom tyrosinase. Those extracts expressing relatively weak tyrosinase inhibitory activity may act through different inhibition pathway which is not based on tyrosinase activity. Further evaluation of the most potent tyrosinase inhibitors in in vivo conditions would be recommended.

Six novel diarylheptanoids bearing chalcone or flavanone moiety from the seeds of Alpinia blepharocalyx

Abstract Six novel diarylheptanoids bearing chalcone or flavanone moiety (1–6) were isolated from the seeds of Alpinia blepharocalyx K. Schum. Their structures were determined by spectroscopic analysis. Stereo-chemical assignment of diarylheptanoid part of these compounds was done by NMR spectral analysis of their MTPA esters. These compounds inhibited nitric oxide (NO) production in endotoxin-activated murine macrophages, J774.1.

Antioxidant activity and polyphenol content in edible wild fruits from Nepal

Abstract Fifteen fruits commonly used by the ethnic population in Nepal were studied for the antioxidant activity and total polyphenol content (TPC). Among them, Terminalia bellirica, Terminalia chebula, Phyllanthus emblica and Spondias pinnata were the most potent antioxidants as compared with vitamin C based on the 1,1-diphenyl-2-picryl hydrazyl radical assay. These fruits also contained high TPCs. Spondias pinnata, Pyrularia edulis, Melastoma malabathricum, Cipadema bacifera and Choerospondias axillaries fruits were evaluated for the first time. Moreover, Spondias pinnata was found to be more potent (16% radical scavenging activity at 5 μg/ml) than vitamin C (5% radical scavenging activity at 5 μg/ml). Antioxidant activity showed correlation to TPC with the correlation coefficients (R2) as 0.7189 and 0.7246 for the methanol and water extracts, respectively. This study suggests that a number of these fruits may have the potential to confer beneficial health effects due to their antioxidant activity and TPC.

Propolis protects pancreatic β-cells against the toxicity of streptozotocin (STZ)

Propolis is a glue, prepared by honeybees from plant materials to stick their hives on the beehive wall. It has gained popularity in Japan as a healthy drink and people believe that propolis can cure inflammation, heart diseases and even diabetes and cancer. We have evaluated the β-cell protective effect of propolis against the toxicity of streptozotocin (STZ) in rats. The water extract of propolis (PWE) completely protected β-cell destruction against STZ toxicity. The protective effect of PWE was found to be almost equal to that of nicotinamide. PWE also inhibited the interleukin-1 β (IL-1 β) generation from human leukocytes. The free radical scavenging activity together with IL-1 β and nitric oxide (NO) synthase inhibitory activities are thought to be the prime factors for the protective effect of PWE against STZ toxicity.

Using RNA sequencing for identifying gene imprinting and random monoallelic expression in human placenta

Given the possible critical importance of placental gene imprinting and random monoallelic expression on fetal and infant health, most of those genes must be identified, in order to understand the risks that the baby might meet during pregnancy and after birth. Therefore, the aim of the current study was to introduce a workflow and tools for analyzing imprinted and random monoallelic gene expression in human placenta, by applying whole-transcriptome (WT) RNA sequencing of placental tissue and genotyping of coding DNA variants in family trios. Ten family trios, each with a healthy spontaneous single-term pregnancy, were recruited. Total RNA was extracted for WT analysis, providing the full sequence information for the placental transcriptome. Parental and child blood DNA genotypes were analyzed by exome SNP genotyping microarrays, mapping the inheritance and estimating the abundance of parental expressed alleles. Imprinted genes showed consistent expression from either parental allele, as demonstrated by the SNP content of sequenced transcripts, while monoallelically expressed genes had random activity of parental alleles. We revealed 4 novel possible imprinted genes (LGALS8, LGALS14, PAPPA2 and SPTLC3) and confirmed the imprinting of 4 genes (AIM1, PEG10, RHOBTB3 and ZFAT-AS1) in human placenta. The major finding was the identification of 4 genes (ABP1, BCLAF1, IFI30 and ZFAT) with random allelic bias, expressing one of the parental alleles preferentially. The main functions of the imprinted and monoallelically expressed genes included: i) mediating cellular apoptosis and tissue development; ii) regulating inflammation and immune system; iii) facilitating metabolic processes; and iv) regulating cell cycle.

Antibacterial activity of trichorabdal A from Rabdosia trichocarpa against Helicobacter pylori

Rabdosia trichocarpa is used in a popular home-made remedy for gastric and stomachic complaints in Japan. A diterpene, trichorabdal A from R. trichocarpa, showed a very strong in vitro antibacterial activity against Helicobacter pylori. With regard to the antibacterial activity of the extract and constituents of R. trichocarpa against H. pylori, the effect of traditional use of this plant for the treatment of gastritis is probably due to the suppression of H. pylori since the extract of R. trichocarpa particularly inhibits the growth of H. pylori. It could be a promising native herb treatment for patients with gastric complaints including gastric ulcer caused by H. pylori.

Development and Evaluation of an In Vitro Vaginal Model for Assessment of Drug’s Biopharmaceutical Properties: Curcumin

Vaginal administration is a promising alternative to the per-oral route in achieving systemic or local therapeutic effects, when intestinal drug absorption is hindered by problematic biopharmaceutical drug properties. The aim of this study was to establish an in vitro vaginal model and use it to characterize biopharmaceutical properties of liposomally associated curcumin destined for vaginal delivery. The in vitro permeability, metabolism, and tissue retention of high/low permeable compounds were assessed on cow vaginal mucosa and compared to the permeabilities determined through Caco-2 cells and rat jejunum in vitro. The results showed that the intestinal mucosa was superior to the vaginal one in categorizing drugs based on their permeabilities in high/low permeable classes. Passive diffusion was found to be the main mechanism of drug penetration through vaginal mucosa and it was not affected by transporter–enzyme alliance, as their expression/activity was significantly reduced compared to the intestinal tract. Curcumin permeability from the solution form was the lowest of all tested substances due to its significant tissue retention and curcumin–mucus interactions. The permeability of liposomally associated curcumin was even lower but the binding of liposomally associated curcumin to the vaginal tissue was significantly higher. The permeability and tissue retention of liposomal curcumin were vesicle size dependent. Vaginal application of liposomally associated curcumin provides relatively high levels of curcumin in vaginal tissue, with limited systemic absorption.

Hepatoprotective effects of traditional medicines. Isolation of the active constituent from seeds of Celosia argentea

The hepatoprotective effects of water extracts from twelve crude drugs were investigated. Among them, the water extracts of Cassia obtusifolia, Celosia argentea, Cucurbita moschata and Curcuma aeruginosa showed a significant protective effect on carbon tetrachloride induced liver injury in rats and D‐galactosamine (D‐GalN)/lipopolysaccharide (LPS) induced liver injury in mice. The water extract of C. argentea was found to be the most effective. The hepatoprotective activity guided fractionation of this extract led to the isolation of an active constituent. This component was named as celosian, and was found to be an acidic heteroglycan (molecular weight: 1.9×105) containing 4% of proteins.