NMR and multivariate methods: Identification of chemical markers in extracts of pedra-ume-caá and their antiglycation, antioxidant, and enzymatic inhibition activities.

INTRODUCTION: In Brazil, the plant group popularly known as "pedra-ume-caá" is used in folk medicine for the treatment of diabetes, and its raw material is commonly sold. OBJECTIVE: The aim of the study was to apply a method for chemical identification of extracts of dry pedra-ume-caá leaves using HPLC-high-resolution mass spectrometry (HRMS) and NMR and develop a multivariate model with NMR data to authenticate commercial samples. In addition, to evaluate the biological activities of the extracts. MATERIALS AND METHODS: Dry extracts of Myrcia multiflora, Myrcia amazonica, Myrcia guianensis, Myrcia sylvatica, Eugenia punicifolia leaves, and 15 commercial samples (sold in Manaus and Belém, Brazil) were prepared by infusion. All the extracts were analysed using HPLC-high-resolution mass spectrometry (HRMS), NMR, principal component analysis (PCA), and hierarchical cluster analysis (HCA). The antidiabetic effect of extracts was evaluated according to enzymatic inhibition. Their content of total phenols, cell viability, and antioxidant and antiglycation activities were also determined. RESULTS: HPLC-HRMS and NMR analysis of these extracts permitted the identification of 17 compounds. 1H NMR data combined with multivariate analyses allowed us to conclude that catechin, myricitrin, quercitrin, and gallic and quinic acids are the main chemical markers of pedra-ume-caá species. These markers were identified in 15 commercial samples of pedra-ume-caá. Additionally, only the extracts of M. multiflora and E. punicifolia inhibited α-glucosidase. All the extracts inhibited the formation of advanced glycation end products (AGEs) and showed free-radical-scavenging activity. These extracts did not present cytotoxicity. CONCLUSION: This study revealed the chemical markers of matrices, and it was possible to differentiate the materials marketed as pedra-ume-caá. Moreover, this study corroborates the potential of these species for treating diabetes.

Advanced glycation End-products (AGEs): an emerging concern for processed food industries.

The global food industry is expected to increase more than US $ 7 trillion by 2014. This rise in processed food sector shows that more and more people are diverging towards modern processed foods. As modern diets are largely heat processed, they are more prone to contain high levels of advanced glycation end products (AGEs). AGEs are a group of complex and heterogeneous compounds which are known as brown and fluorescent cross-linking substances such as pentosidine, non-fluorescent cross-linking products such as methylglyoxal-lysine dimers (MOLD), or non-fluorescent, non-cross linking adducts such as carboxymethyllysine (CML) and pyrraline (a pyrrole aldehyde). The chemistry of the AGEs formation, absorption and bioavailability and their patho-biochemistry particularly in relation to different complications like diabetes and ageing discussed. The concept of AGEs receptor - RAGE is mentioned. AGEs contribute to a variety of microvascular and macrovascular complications through the formation of cross-links between molecules in the basement membrane of the extracellular matrix and by engaging the receptor for advanced glycation end products (RAGE). Different methods of detection and quantification along with types of agents used for the treatment of AGEs are reviewed. Generally, ELISA or LC-MS methods are used for analysis of foods and body fluids, however lack of universally established method highlighted. The inhibitory effect of bioactive components on AGEs by trapping variety of chemical moieties discussed. The emerging evidence about the adverse effects of AGEs makes it necessary to investigate the different therapies to inhibit AGEs.

Ultrasmall Solid-Lipid Nanoparticles via the Polysorbate Sorbitan Phase-Inversion Temperature Technique: A Promising Vehicle for Antioxidant Delivery into the Skin.

Solid lipid nanoparticles promote skin hydration via stratum corneum occlusion, which prevents water loss by evaporation, and via the reinforcement of the skin's lipid-film barrier, which occurs through the adhesion of the nanoparticles to the stratum corneum. The efficacy of both phenomena correlates with lower nanoparticle size and the increased skin permeation of loaded compounds. The so-called Polysorbate Sorbitan Phase-Inversion Temperature method has, therefore, been optimized in this experimental work, in order to engineer ultrasmall solid-lipid nanoparticles that were then loaded with α-tocopherol, as the anti-age ingredient for cosmetic application. Ultrasmall solid-lipid nanoparticles have been proven to be able to favor the skin absorption of loaded compounds via the aforementioned mechanisms.

Age-related diseases, therapies and gut microbiome: A new frontier for healthy aging.

The gut microbiome is undoubtedly a key modulator of human health, which can promote or impair homeostasis throughout life. This is even more relevant in old age, when there is a gradual loss of function in multiple organ systems, related to growth, metabolism, and immunity. Several studies have described changes in the gut microbiome across age groups up to the extreme limits of lifespan, including maladaptations that occur in the context of age-related conditions, such as frailty, neurodegenerative diseases, and cardiometabolic diseases. The gut microbiome can also interact bi-directionally with anti-age-related disease therapies, being affected and in turn influencing their efficacy. In this framework, the development of integrated microbiome-based intervention strategies, aimed at favoring a eubiotic configuration and trajectory, could therefore represent an innovative approach for the promotion of healthy aging and the achievement of longevity.

Cyclodipeptides: From Their Green Synthesis to Anti-Age Activity.

Cyclodipeptides (CDPs) or diketopiperazines (DKPs) are often found in nature and in foodstuff and beverages and have attracted great interest for their bioactivities, biocompatibility, and biodegradability. In the laboratory, they can be prepared by green procedures, such as microwave-assisted cyclization of linear dipeptides in water, as performed in this study. In particular, five CDPs were prepared and characterized by a variety of methods, including NMR and ESI-MS spectroscopies and single-crystal X-ray diffraction (XRD), and their cytocompatibility and anti-aging activity was tested in vitro, as well as their ability to penetrate the different layers of the skin. Although their mechanism of action remains to be elucidated, this proof-of-concept study lays the basis for their future use in anti-age cosmetic applications.

The effect of Salaciareticulata, Syzygiumcumini, Artocarpusheterophyllus, and Cassiaauriculata on controlling the rapid formation of advanced glycation end-products.

BACKGROUND: The excessive formation of Advanced Glycation End-products (AGEs) by non-enzymatic glycation mediates many health complications in the human body and the formation of AGEs largely accelerated under the hyperglycaemic condition. OBJECTIVE: The prospect of the study to assess the strength of inhibiting the rapid AGE formations in four Ayurvedic medicinal plants, namely; Salacia reticulata (stems), Syzygium cumini (barks), Artocarpus heterophyllus (mature leaves) and, Cassia auriculata (flowers). MATERIALS AND METHODS: Herbal decoctions of four medicinal plant materials were prepared by simmering with hot water as prescribed by the Ayurvedic medicine. The effectiveness of the decoctions was analyzed in vitro based on their Anti-AGE formation activity, glycation reversing, and anti-oxidant potentials. RESULTS: According to the results, the decoctions of S. reticulata, A. heterophyllus and C. auriculata indicated the strong Anti-AGE forming (IC50: 23.01 ± 2.70, 32.01 ± 2.09, 43.66 ± 2.11 mg/mL, respectively), glycation reversing (EC50: 183.15 ± 7.67, 91.85 ± 1.93, 252.35 ± 4.03 mg/mL, respectively) and antioxidant potentials in terms of total polyphenol content (TPC), total flavonoid content (TFC), ferric ion reducing power (FRAP), ABTS and DPPH radical scavenging activities. However, the decoction of S. cumini reported the significantly high (p < 0.05) Anti-AGE forming, (IC50: 9.75 ± 0.32 mg/mL), glycation reversing (EC50: 66.45 ± 4.51 mg/mL), and antioxidant potentials against the decoctions of the other three plant materials. CONCLUSION: S. cumini bark extract was identified as the best source in controlling the formation of AGEs excessively. Further, the other three plant extracts can also be effectively used as potential therapeutic agents to control the pathological conditions associated with AGEs-mediated health complications.

Formulation and evaluation of a water-in-oil cream containing herbal active ingredients and ferulic acid.

BACKGROUND AND AIMS: The main aims of the present study were to formulate an anti-age cream based on vegetal ingredients and ferulic acid and to evaluate the physical characteristics and the efficacy of the cream. METHODS: The active ingredients were Centella asiatica oil, Spilanthes acmella oil, Zingiber officinale extract and ferulic acid. Formulation 1 (F1) was prepared using glyceryl stearate and Ceteareth-25® as emulsifiers and Formulation 2 (F2) using glyceryl stearate and potassium cetyl phosphate, all other ingredients remaining the same. The physical characterization of the creams was performed and the following parameters were analyzed: viscosity, oil droplet size, polydispersity index; also, texture analysis was performed. The anti-aging effect of the F2 was evaluated by assessing the cutaneous density before and after cream application using DUB-cutis® scanner. RESULTS: The mean diameter of oil drops was 10.26±4.72 mm (F1) and 22.72±7.93 mm (F2) and the polydispersity index was 35.4% and 45.7%, respectively. The mean values for consistency were 594.7±10.3 g (F1) and 300.5±14.5 g (F2), the average values for adhesion were 15.61±0.8 mJ (F1) and 22.25±4.3 mJ (F2), for firmness were 51.2±0.8 g (F1) and 30.3±4.3 g (F2) and the spreadability had values between 72.63 mm2 (F1) and 73.3 mm2 (F2). In vivo study revealed that the mean values of the cutaneous density increased from 9.21±1.39 % to 12.50±1.44 % after 8 weeks of cream application. The herbal ingredients incorporated in the O/W cream base for the antioxidant activity and anti-wrinkle effect, induced changes of the cutaneous density, an important parameter which quantifies the regeneration process of the skin. CONCLUSIONS: An anti-age cream containing herbal active ingredients and ferulic acid with appropriate physical characteristics was obtained. In vivo study of clinical efficacy revealed a positive effect on skin density, which increased after 8 weeks of cream application.

Immunization of AGE-modified albumin inhibits diabetic nephropathy progression in diabetic mice.

BACKGROUND: Diabetic nephropathy (DN) is a serious vascular complication of diabetes and an important cause of end-stage renal disease. One mechanism by which hyperglycemia causes nephropathy is through the formation of advanced glycation end products (AGE). Development of vaccination would be a promising therapy for the future, while to date, anti-AGE therapy is based on medicines that are needed to be consumed lifelong. This study aimed to find out the effect of immunization of AGE-modified albumin against DN pathogenesis in streptozotocin-induced diabetic in mice. METHODS: We used 24 BALB/c male mice as experimental animals, which were divided into six groups, two nondiabetic groups (negative control and AGE-modified bovine serum albumin [BSA] preimmunized groups) and four streptozotocin-induced diabetic groups (diabetic control group and diabetic preimmunized groups for AGE-BSA, Keyhole limpet hemocyanin (KLH), and AGE-BSA-KLH, respectively). RESULTS: Diabetic preimmunized groups for AGE-BSA, KLH, and AGE-BSA-KLH showed amelioration in renal function and histopathology compared with the diabetic control group. Preimmunization also maintained nephrin intensity and decreased serum AGE level, kidney AGE deposition, and kidney cells apoptosis. CONCLUSION: AGE-BSA and AGE-BSA-KLH immunizations inhibit the progression of DN. Our results strengthen the evidence that the anti-AGE antibodies have a protective role against diabetic vascular complication, especially DN. This study provides a basis for the development of DN-based immunotherapy with AGE immunization as a potential candidate.