Developments in the anticancer activity of structurally modified curcumin: An up-to-date review.

Curcumin is a pharmacologically active polyphenol derived from the popular spice element-Turmeric. The therapeutic activity of curcumin has been extensively investigated over the last few decades and reports suggest the role of curcumin in a large number of biological activities, particularly its prominent anticancer activity. Curcumin, being a pleiotropic molecule, is a regulator of multiple molecular targets which play crucial roles in various cell signaling pathways. It is known to suppress transformation, inhibit proliferation as well as induce apoptosis. However, despite all these benefits, the efficacy of curcumin remains limited due to its poor bioavailability, poor absorption within the systemic circulation and rapid elimination from the body. To overcome these limiting factors, researchers all around the world are working towards designing a synthetic and superior curcuminoid by making suitable structural modifications to the parent skeleton. These curcuminoids, mainly analogues and derivatives, will not only improve the physicochemical properties but also enhance the efficacy simultaneously. The present review will provide a comprehensive account of the analogues and derivatives of curcumin that have been reported since 2014 which have indicated a better anticancer activity than curcumin.

Correction: Physiochemical characterization and cytotoxicity evaluation of mercury-based formulation for the development of anticancer therapeuticals.

[This corrects the article DOI: 10.1371/journal.pone.0195800.].

Physiochemical characterization and cytotoxicity evaluation of mercury-based formulation for the development of anticancer therapeuticals.

BACKGROUND: The present study is aimed to evaluate the physiochemical properties and cytotoxicity of mercury-based formulation for the development of anticancer therapeuticals. METHODS: The elemental and morphological features of the formulation were characterized by FE-SEM, XPS and EDS. The described formulation was evaluated for its cytotoxicity on Hek293 and MCF7 cell lines using MTT assay to study the in vitro effects. The in vivo developmental toxicity was also studied on zebrafish embryos and the lethal concentration (LC50) values were calculated as per the OECD regulations. RESULTS: The elemental and morphological characterizations confirmed the presence of mercuric compounds. The particles were spherical and stable with the size ranges between 20 and 80nm. Although the PK formulation contains mercurials it was very effective only to cancerous cells (MCF-7) and it is less toxic to normal cells (HEK 293). The in vivo assessment of developmental toxicity on zebrafish embryo confirmed the safer dosage of 100µg/ml. However, a higher dosage of 1mg/ml led to the malformation of embryos such as pericardial, tail and yolk sac edema. CONCLUSION: The physiochemical characterization of PK formulation confirmed the presence of HgS. The results of both in vitro and in vivo studies showed that the formulation is less toxic. Although the test sample contains mercurials it was very effective against cancerous cells (MCF-7) and it is less toxic to normal cells (HEK 293). FUTURE STUDIES: Further studies on effectiveness of the formulation along with inflammatory response in mice models are to be conducted.

Significance of Microbiota in Obesity and Metabolic Diseases and the Modulatory Potential by Medicinal Plant and Food Ingredients.

Metabolic syndrome is a cluster of three or more metabolic disorders including insulin resistance, obesity, and hyperlipidemia. Obesity has become the epidemic of the twenty-first century with more than 1.6 billion overweight adults. Due to the strong connection between obesity and type 2 diabetes, obesity has received wide attention with subsequent coining of the term "diabesity." Recent studies have identified unique contributions of the immensely diverse gut microbiota in the pathogenesis of obesity and diabetes. Several mechanisms have been proposed including altered glucose and fatty acid metabolism, hepatic fatty acid storage, and modulation of glucagon-like peptide (GLP)-1. Importantly, the relationship between unhealthy diet and a modified gut microbiota composition observed in diabetic or obese subjects has been recognized. Similarly, the role of diet rich in polyphenols and plant polysaccharides in modulating gut bacteria and its impact on diabetes and obesity have been the subject of investigation by several research groups. Gut microbiota are also responsible for the extensive metabolism of polyphenols thus modulating their biological activities. The aim of this review is to shed light on the composition of gut microbes, their health importance and how they can contribute to diseases as well as their modulation by polyphenols and polysaccharides to control obesity and diabetes. In addition, the role of microbiota in improving the oral bioavailability of polyphenols and hence in shaping their antidiabetic and antiobesity activities will be discussed.

In vitro analysis of 4-methylumbelliferone as a sole carbon source for Lactobacillus helveticus 2126.

In the recent years, 4-methylumbelliferone (4-MU) has been gaining importance, both as an anti-cancer agent and as a dietary supplement. The aim of this study was to determine the effectiveness of 4-MU as a carbon source for potential probiotic bacteria Lactobacillus helveticus 2126. For this purpose, a series of plate assays and infrared spectroscopy (FTIR) were used for 4-MU before and after the treatment with L. helveticus 2126. The plate assays indicated an initial inhibition followed by utilization of 4-MU that stimulated bacterial growth. A significant shift was observed in the FTIR peaks, which also have suggested possible extracellular activity of the bacteria for 4-MU utilization. SIGNIFICANCE AND IMPACT OF THE STUDY: 4-Methylumbelliferone (4-MU) is a widely used chloretic and is currently under research for treating colon cancer. Preliminary studies suggest that it has the potential to be used as an effective and sustainable prebiotic for the human microbiome, as it can be naturally obtained from plants. This manuscript describes the effectiveness of 4-MU as a carbon source for the probiotic bacteria Lactobacillus helveticus. Our study also suggests the role of bacterial superoxide dismutase in transforming 4-MU as a possible prebiotic for the human microbiome.

Structural and elemental characterization of traditional Indian Siddha formulation: Thalagak karuppu.

BACKGROUND: The traditional Indian medicine 'Siddha' uses metals, metalloids and minerals including toxic ones with no proven toxicity. Thalagak karuppu (TK) is remarkably stable over a century and used for treating Suram (Fever), Kaasam (Cough), Elai (Tuberculosis) and Eraippu Erumal (Bronchial Asthma). OBJECTIVE: The present study addresses elemental and morphological characterization of therapeutic Siddha formulation: Thalagak karuppu (TK). MATERIALS AND METHODS: TK was purchased from the Indian Medical Practitioners Co-operative Pharmacy and Stores (IMCOPS) Ltd, Chennai, Tamilnadu, India. The physicochemical properties were evaluated using UV-visible spectrophotometer, Fourier Transform Infrared Spectrometer (FTIR), Scanning Electron Microscope (SEM) with Energy Dispersive X-ray analysis (EDX), Zeta sizer and X-ray diffractometer (XRD). RESULTS: The mixed nature of arsenic was analyzed using UV-visible spectroscopy. The fingerprint region for arsenic derivatives was inferred from IR spectroscopy and X-ray diffraction patterns. The shape and size heterogeneity in the anisotropic mixture was observed in SEM images and the polydispersity was analyzed by Zeta sizer. CONCLUSIONS: The structural, elemental and morphological analyses suggests that the arsenic may predominantly exist either as orpiment (As2S2) or realgar (As2S4) form. The possibility is less for the toxic arsenolite. Hence, the formulation may be considered safe.

Synthesis and characterization of adenosine adducts of arylamines.

The synthesis of adducts of arylamines with adenosine are reported.