Month: June 2018

Synthesis of amino acid conjugates of tetrahydrocurcumin

Tetrahydrocurcumin (THC), the hydrogenated and stable form of curcumin, exhibits physiological and pharmacological activities similar to curcumin. A protocol has been developed for the synthesis of novel conjugates of THC with alanine (2a), isoleucine (2b), proline (2c), valine (2d), phenylalanine (2e), glycine (2f) and leucine (2g) in high yields (43–82%). All the derivatives of THC exhibited more potent anti-microbial activity than THC against Bacillus cereus, Staphylococcus aureus, Escherichia coli and Yersinia enterocolitica. The MIC values of the derivatives were 24–37% of those for THC in case of both Gram-positive and Gram-negative bacteria. Derivatives 2g and 2d exhibited maximum anti-mutagenicity against Salmonella typhimurium TA 98 and TA 1538, respectively at a low concentration of 313 μg/plate, with comparable activity for THC evident only at 3750 μg/plate. These results clearly demonstrated that the conjugation of THC at the phenolic position with amino acids led to significant improvement of its in vitro biological attributes.(Food Chem. 2013 Aug 15;139(1-4):332-8.)

Phytocompound-based nanocosmeceuticals!

Phytocompounds have been used in cosmeceuticals for decades and have shown potential for beauty applications, including sunscreen, moisturizing and antiaging, and skin-based therapy. The major concerns in the usage of phyto-based cosmeceuticals are lower penetration and high compound instability of various cosmetic products for sustained and enhanced compound delivery to the beauty-based skin therapy. To overcome these disadvantages, nanosized delivery technologies are currently in use for sustained and enhanced delivery of phyto-derived bioactive compounds in cosmeceutical sectors and products. Nanosizing of phytocompounds enhances the aseptic feel in various cosmeceutical products with sustained delivery and enhanced skin protecting activities. Solid lipid nanoparticles, transfersomes, ethosomes, nanostructured lipid carriers, fullerenes, and carbon nanotubes are some of the emerging nanotechnologies currently in use for their enhanced delivery of phytocompounds in skin care. Aloe vera, curcumin, resveratrol, quercetin, vitamins C and E, genistein, and green tea catechins were successfully nanosized using various delivery technologies and incorporated in various gels, lotions, and creams for skin, lip, and hair care for their sustained effects. However, certain delivery agents such as carbon nanotubes need to be studied for their roles in toxicity. This review broadly focuses on the usage of phytocompounds in various cosmeceutical products, nanodelivery technologies used in the delivery of phytocompounds to various cosmeceuticals, and various nanosized phytocompounds used in the development of novel nanocosmeceuticals to enhance skin-based therapy.

Phytobioactive compounds used in cosmeceuticals include catechins, gallic acids, epicatechins, curcumin, hydroxylbenzoic and cinnamic acids, quercetin, ascorbic acids, luteolin, alpha and beta carotene, complex polysaccharides, and fatty acids. These compounds, in addition to their cosmetic effects, enhance antibacterial, antifungal, anticarcinogenic, and anti-inflammatory biological actions. Even though various macrosized phytobioactive compounds are used in cosmeceutical formulations, their solubility and formulation type have limitations in enhancing the effect of phyto-based cosmeceuticals and therapy The major limitations of phyto-based cosmeceutical therapy include less skin penetration, lower prolongevity, less final quality and lower whitening effects. These qualities depend on the solubility and size of the active phytocompounds. This leads us in search of novel, highly promising technologies for enhanced skin health efficiency of cosmeceutical products. (Int J Nanomedicine. 2016; 11: 1987–2007.)

Natural Skin Whitening Agents!

Skin whitening products are commercially available for cosmetic purposes in order to obtain a lighter skin appearance. They are also utilized for clinical treatment of pigmentary disorders such as melasma or postinflammatory hyperpigmentation. Whitening agents act at various levels of melanin production in the skin. Many of them are known as competitive inhibitors of tyrosinase, the key enzyme in melanogenesis. Others inhibit the maturation of this enzyme or the transport of pigment granules (melanosomes) from melanocytes to surrounding keratinocytes. In this review we present an overview of (natural) whitening products that may decrease skin pigmentation by their interference with the pigmentary processes.

In the skin, melanocytes are situated on the basal layer which separates dermis and epidermis. One melanocyte is surrounded by approximately 36 keratinocytes. Together, they form the so-called epidermal melanin unit. The melanin produced and stored inside the melanocyte in the melanosomal compartment is transported via dendrites to the overlaying keratinocytes. The melanin pigment is a polymer produced inside the melanosomes and synthesised from the amino acid l-tyrosine that is converted by the enzyme tyrosinase to dopaquinone. This reaction continues spontaneously via dopachrome to the monomeric indolic precursors (5,6-dihydroxyindole and 5,6-dihydroxyindole 2-carboxylic acid) of the black-brown pigment eumelanin. However, some other enzymes, like the tyrosinase related proteins (TRP-1 and dopachrome tautomerase (TRP-2) may also play an important role in melanogenesis in vivo. Upon reaction with cysteine, dopaquinone forms 2- or 5-S-cysteinyldopa that generates the benzothiazine precursors of the red/yellow pheomelanin polymer. In general, a mixed type of pheo- and eumelanin polymer is produced and deposited onto the melanosomal matrix proteins. Considering the many colour variations that can be seen in the skin and hair, one may expect that the composition of the mixed melanins is regulated in many different ways. However, altered production of cutaneous melanin may cause considerable problems of esthetic nature, especially in hyperpigmentary conditions, like melasma, postinflammatory hyperpigmentation, freckles or lentigines. But also depigmenting conditions, like vitiligo, have high impact on the quality of life of the patients. (Int J Mol Sci. 2009 Dec; 10(12): 5326–5349.)

New natural amino acid-bearing pro-drugs

The biomedical effects of the natural phenol pterostilbene are of great interest but its bioavailability is negatively affected by the phenolic group in position 4′ which is an ideal target for the conjugative enzymes of phase II metabolism. We report the synthesis and characterization of prodrugs in which the hydroxyl moiety is reversibly protected as a carbamate ester linked to the N-terminus of a natural amino acid. Prodrugs comprising amino acids with hydrophobic side chains were readily absorbed after intragastric administration to rats. The Area Under the Curve for pterostilbene in blood was optimal when prodrugs with isoleucine or β-alanine were used. The prodrug incorporating isoleucine was used for further studies to map distribution into major organs. When compared to pterostilbene itself, administration of the isoleucine prodrug afforded increased absorption, reduced metabolism and higher concentrations of pterostilbene, sustained for several hours, in most of the organs examined. Experiments using Caco-2 cells as an in vitro model for human intestinal absorption suggest that the prodrug could have promising absorption profiles also in humans; its uptake is partly due to passive diffusion, and partly mediated by H+-dependent transporters expressed on the apical membrane of enterocytes, such as PepT1 and OATP.