Release studies of the anticancer drug 5-fluorouracil from chitosan-banana peel extract films.

5-F-lourouracil is an anticancer drug used for the treatment of different types of cancers. 5-flourouracil loaded chitosan-banana peel extract films were prepared for the in vitro drug release studies. Solvent casting technique was employed to prepare the films. The structure and morphology of the prepared films were analysed by FTIR, XRD and SEM methods and confirmed the presence of drug in the films. The drug loaded films show excellent thermal stability and good shelf life. Studies revealed that the percentage of banana peel extract influences the swelling properties of the film, thickness of the films and release of the drug from the films. Increase in the concentration of chitosan and banana peel extract decreases the swelling properties of the film and rate of release of the drug from the film. The release rate of 5-fluorouracil from the drug loaded chitosan-banana peel extract films were followed spectrophotometrically at λmax 266 nm and the film derived from 1 % chitosan solution and 1 mL aqueous banana peel extract (saturated) exhibited maximum drug release. Cytotoxicity studies proved that the films are non-toxic in nature and augurs well for their applications as excellent drug delivery systems. Antimicrobial studies show that the drug loaded chitosan-banana peel extract films were found to be active against microbes E. coli, Streptococcus mutans, Staphylococcus aureus, Candida albicans and Aspergillus niger and inactive against Pseudomonas aeruginosa.

Impact of potential stimulants on asiaticoside and madecassoside levels and expression of triterpenoid-related genes in axenic shoot cultures of Centella asiatica (L.) Urb.

The triterpenoid saponins, asiaticoside and madecassoside from Centella asiatica (L.) Urb. are known to have a wide range of applications in pharmaceutical and cosmetic industries. The effect of addition of Potential Metabolite Stimulants (PMSs) - casein acid hydrolysate, meat peptone, salicylic acid, copper sulphate, and silver nitrate, on the concentrations of these saponins and transcript levels of associated genes encoding important biosynthetic enzymes, was assessed in axenic shoot cultures of C. asiatica. Among the stimulants, silver nitrate induced asiaticoside content approximately 6-fold increase in madecassoside levels, after three weeks post-treatment with a decrease in biomass compared to its control. Gene expression analysis of essential genes involved in triterpenoid synthesis such as ß-amyrin synthase showed an upregulation of approximately 50-fold at the third week of silver nitrate treatment compared to control. These findings suggest that silver nitrate can act as a metabolite stimulant, to enhance the formation of triterpenoids in axenic shoot culture of C. asiatica, which could be utilized in studying the regulation of terpenoid biosynthesis and biotechnological application for the increased production of these bioactive molecules.

Piriformospora indica cell wall extract as the best elicitor for asiaticoside production in Centella asiatica (L.) Urban, evidenced by morphological, physiological and molecular analyses.

Vascular plants synthesise a multitude of organic molecules or phytochemicals, referred to as "secondary metabolites". These molecules are involved in a variety of roles in the life span of plants, ranging from structural ones to protection. Centella asiatica (L.) Urban has probably been used since prehistoric times and has been reported to have been used for various medicinal and cosmetic purposes. The plant contains several active constituents, of which the most important is asiaticoside, a triterpenoid. Asiaticoside content in C. asiatica can be enhanced by the use of biotic elicitors like Piriformospora indica. P. indica has been used as a model to study the mechanisms and evolution of mutualistic symbiosis. P. indica is similar to Arbuscular Mycorrhizal (AM) fungi in terms of plant growth promotional effects. The autoclaved fraction from P. indica (PiCWE) was found to be the most active fraction in promoting the plant biomass and asiaticoside content. To date, there are no reports on the potential role of PiCWE in enhancement of asiaticoside over the control and P. indica colonized plants, which was evidenced by the differential expression of key genes involved and final asiaticoside content along with the determination of phytohormones. Moreover, differential expression of selected miRNAs in PiCWE - C. asiatica root interactions over the control and P. indica treated C. asiatica leaf samples was also scrutinized. The important consequence of induction with PiCWE was the significant enhancement of asiaticoside in the PiCWE induced plants in comparison with the asiaticoside content in control and P. indica-C. asiatica interaction. In addition, the role of miRNAs in C. asiatica - PiCWE would enable more in-depth studies for deciphering the molecular and physiological mechanisms of the association and regulation of PiCWE - C. asiatica interactions.

Solanum nigrum Unripe fruit fraction attenuates Adriamycin resistance by down-regulating multi-drug resistance protein (Mdr)-1 through Jak-STAT pathway.

BACKGROUND: Solanum nigrum, herbal plant that commonly grows in temperate climate zone, has been used as a traditional folk medicine whose ripen fruits were proven to exhibit anti-tumor properties. In traditional Chinese medicine, it has been used for centuries to cure inflammation, edema, mastitis and hepatic cancer and in the Ayurvedic system of traditional medicine in India, S. nigrum is applied against enteric diseases, ulcer, diarrhea and skin diseases. A methanolic glycosidic extract fraction of unripe fruit of S. nigrum (SNME) was investigated for its anticancer property and possible mechanism to surmount adriamycin resistance in NCI/ADR-RES cells. METHODS: The NCI/ADR-RES cells were treated with 7.8125, 15.625, 31.25, 62.5, 125 and 250 µg/ml of methanolic extract of S. nigrum (SNME) for 12, 24 and 48 h, to check the cell viability and proliferation. The cells were also exposed to adriamycin alone or in combination with SNME and the effects on cell growth were determined by MTT. Cell cycle analysis, Ethidium bromide and Acridine orange staining, Annexin-binding efficiency, nuclear condensation and DNA fragmentation of the apoptotic NCI/ADR-RES cells were also determined. To elucidate the relationship between SNME and multi drug resistance, we analyzed the expression levels of Mdr-1, JAK1, STAT3, and pSTAT3 in NCI/ADR-RES cells after treatment with SNME. RESULTS: Results from the cytotoxicity assay showed a direct correlation between the concentration of methanolic glycosidic extract fraction of S. nigrum (SNME) and the surviving cell population. Combination with Adriamycin, SNME exhibits a synergistic action on NCI/ADR-RES cells, giving the first line of evidence to overcoming Adriamycin resistance. The SNME mediated cell growth suppression was proven to be apoptotic, based on results obtained from DNA fragmentation, annexin V apoptosis assaay and PARP cleavage analysis. Looking into the molecular insight SNME surpasses the chemoresistance of NCI/ADR-RES cells by inhibiting the JAK-STAT3 signaling pathway through the down regulation of JAK1, STAT3, pSTAT3, and Mdr1 expression. CONCLUSIONS: Collectively our findings suggest that unripe fruit of Solanum nigrum could possibly be used as a chemosensitizing agent against Adriamycin resistant cancers.

Scope of detection and determination of gallium(III) in industrial ground water by square wave anodic stripping voltammetry on bismuth film electrode.

Gallium(III) in ground water may cause human health hazards due to the antineoplastic and antimicrobial activities of gallium. However, the exposure limit of Ga(III) has not been set. This paper demonstrates the scope of employing the square wave anodic stripping voltammetry (SWASV) on bismuth film electrode (BiFE) for selective and sensitive detection of Ga(III) as well as its accurate and precise determination. The key parameters were optimized and the bismuth film morphology was characterized. The performance of BiFE was also compared with that of the mercury film electrode (MFE). The performance of BiFE was also studied for interferences of Zn(II), Cd(II), Tl(I) and Cu(II) ions. Gaussian peak fitting was performed to improve the calibration curve and the fitting process revealed almost similar stripping peak heights as obtained from the experimentally observed data though slight improvement in calibration was obtained from the peak area analysis. A good linear dynamic range (R(2)=0.996) was obtained in the concentration range of 20-100 µg/L with a limit of detection (LOD) of 6.6 µg/L (S/N=3) of Ga(III). A relative standard deviation of 2.9% (n=10) was obtained for 20 µg/L of Ga(III) solution. The practical analytical utility of the method was verified by the determination of Ga(III) in spiked water samples, where 100-105% recovery of Ga(III) was achieved.

In vitro & in vivo estrogenic activity of glycoside fractions of Solanum nigrum fruit.

BACKGROUND & OBJECTIVES: The mature fruits of Solanum nigrum contains steroidal glycosides. These are often used as vegetable and there are evidences on tribal use of these fruits as an oral contraceptive. The present study was carried out to evaluate the estrogenic potential of S. nigrum fruits by in vitro and in vivo assays. METHODS: Defatted methanol extract of dried S. nigrum fruits was column fractionated and the glycoside positive fractions pooled. Definite concentrations of the fraction were used for in vitro and in vivo assays. The effect on cell viability was analyzed in MCF-7 cell lines by MTT assay followed by in vitro evaluation of estrogenicity by hydroxy apatite (HAP) binding assay. The results were further evaluated in vivo by performing uterotrophic assay in ovariectomized mouse models. RESULTS: At low concentration (40 µg/ml), SNGF induced a dose-dependent increase in MCF-7 cell proliferation, while higher extract concentrations (80-320 µg/ml) caused progressive cell growth inhibition. The competitive binding assay using ³H-E2 suggests that this effect is mediated by estrogen receptor. Mouse uterotrophic assay revealed a classical uterotrophic response in ovariectomized mice in response to S. nigrum glycoside fraction (SNGF). SNGF at a dose of 100 mg/kg of body wt induced the maximum height of luminal epithelial cells which indicated an increase of 30.8 per cent over control (P<0.01) with a correlated increase in uterine wet wt (150% increase over control). Higher doses (250 and 500 mg/kg body wt) of SNGF did not induce any uterotrophic effect. INTERPRETATION & CONCLUSIONS: Our preliminary data demonstrate the hormone like activity of Solanum glycosides both in vitro and in vivo in mouse, which needs to be further explored to evaluate the possible mechanism and clinical implications.