Extraction Optimization, Antioxidant, Cosmeceutical and Wound Healing Potential of Echinacea purpurea Glycerolic Extracts.

Echinacea purpurea is a plant with immunomodulating properties, often used in topical preparations for treatment of small superficial wounds. In the presented study, the best conditions for ultrasound-assisted extraction of caffeic acid derivatives (caftaric and cichoric acid) (TPA-opt extract), as well as the conditions best suited for preparation of the extract with high radical scavenging activity (RSA-opt extract), from E. purpurea aerial parts were determined. A Box-Behnken design based on glycerol content (%, w/w), temperature (°C), ultrasonication power (W) and time (min) as independent variables was performed. Antioxidant, antiaging and wound healing effects of the two prepared extracts were evaluated. The results demonstrate that glycerol extraction is a fast and efficient method for preparation of the extracts with excellent radical scavenging, Fe2+ chelating and antioxidant abilities. Furthermore, the extracts demonstrated notable collagenase, elastase and tyrosinase inhibitory activity, indicating their antiaging properties. Well-pronounced hyaluronidase-inhibitory activities, with IC50 values lower than 30 µL extract/mL, as well as the ability to promote scratch closure in HaCaT keratinocyte monolayers, even in concentrations as low as 2.5 µL extract/mL (for RSA-opt), demonstrate promising wound healing effects of E. purpurea. The fact that the investigated extracts were prepared using glycerol, a non-toxic and environmentally friendly solvent, widely used in cosmetics, makes them suitable for direct use in specialized cosmeceutical formulations.

Optimization of Bioactive Phenolics Extraction and Cosmeceutical Activity of Eco-Friendly Polypropylene-Glycol-Lactic-Acid-Based Extracts of Olive Leaf.

Olive leaf is a rich source of phenolic compounds with numerous activities related to skin health and appearance. In this study, a green extraction method was developed using eco-friendly solvents: polypropylene glycol (PPG), lactic acid (LA), and water. The optimal extraction conditions were established, including solvent, extraction time, technique (magnetic stirrer vs. ultrasound-assisted extraction), and herbal material/solvent ratio. The composition of the solvent mixture was optimized using a mixture design. The content of phenolic compounds, including oleuropein and verbascoside, was determined using high-performance liquid chromatography (HPLC) and spectrophotometric methods. Using different extraction conditions, three extracts were prepared and their phytochemical compositions and antioxidant and skin-related bioactivities were investigated. The extracts were excellent inhibitors of elastase, collagenase, tyrosinase, and lipoxygenase. The best activity was shown by the extract richest in phenolics and prepared using magnetic-stirrer-assisted extraction for 20 min, with 0.8 g of herbal material extracted in 10 mL of PPG/LA/water mixture (28.6/63.6/7.8, w/w/w), closely followed by the extract prepared using the same extraction conditions but with 0.42 g of herbal material. The investigated PPG/LA/water mixtures contributed to the overall enzyme-inhibitory activity of the extracts. The prepared extracts were appropriate for direct use in cosmetic products, thus saving the time and energy consumption necessary for the evaporation of conventional solvents.

Optimization of Two Eco-Friendly Extractions of Black Medick (Medicago lupulina L.) Phenols and Their Antioxidant, Cosmeceutical, α-Glucosidase and α-Amylase Inhibitory Properties.

Medicago lupulina is an ancient edible plant from the Fabaceae family. In this work, two eco-friendly methods for extraction of bioactive phenolics from M. lupulina were developed using mixtures of water with two non-toxic, skin- and environmentally-friendly polyol solvents: glycerol and polypropylene glycol. Ultrasound-assisted extractions were optimized using a Box-Behnken design. The independent variables were the concentration of organic solvent in water (X1), extraction temperature (X2) and time (X3), while the response was phenolic content. The optimum conditions for extraction of polyphenols were (X1, X2, X3): (45%, 70 °C, 60 min) and (10%, 80 °C, 60 min) for glycerol and polypropylene glycol extraction, respectively. The extracts prepared at optimum conditions were rich in phenolic compounds, mainly derivatives of apigenin, kaempferol, luteolin, quercetin, caffeic and ferulic acid, as well as coumestrol. Their cosmeceutical and antidiabetic activity was tested. Both extracts demonstrated notable antioxidant, anti-lipoxygenase and anti-α-amylase activity. In addition to those activities, the glycerol extract efficiently inhibited protein coagulation, elastase and α-glucosidase activity. Glycerol present in the extract displayed enzyme-inhibiting activity in several assays and supported the action of the bioactive constituents. Thus, the optimized glycerol extract is a desirable candidate for direct incorporation in antidiabetic food supplements and cosmeceutical products.

The role of glucagon in the possible mechanism of cardiovascular mortality reduction in type 2 diabetes patients.

AIM: Type 2 diabetes (T2D) is one of the major public health issues worldwide. The main cause of mortality and morbidity among T2D patients are cardiovascular (CV) causes. Various antidiabetics are used in T2D treatment, but until recently they lacked clear evidence of the reduction in CV mortality and all-cause mortality as independent study end-points. The aim of this article was to present and critically evaluate potential mechanisms behind the remarkable results documented in trials with new antidiabetics for the treatment of T2D. METHODS: Relevant data were collected using the MEDLINE, PubMed, EMBASE, Web of Science, Science Direct, and Scopus databases with the key words: "type 2 diabetes," "mortality," "glucagon," "empagliflozin," "liraglutide," "insulin" and "QTc." Searches were not limited to specific publication types or study designs. RESULTS: The EMPA-REG OUTCOME trial with empagliflozin and LEADER trial with liraglutide presented remarkable results regarding the reduction in mortality in T2D treatment. However, the potential mechanism for those beneficial effects is difficult to determine. It is not likely that improvements in classic CV risk factors are responsible for the observed effect. A potential mechanism may be caused by the elevation of postprandial (PP) glucagon concentrations that can be seen with an empagliflozin and liraglutide therapy, which could have beneficial effects considering the myocardial electrical stability in T2D patients. CONCLUSION: This hypothesis throws new light upon possible mechanisms of reduction in mortality in T2D patients.

Optimization of Cyclodextrin-Assisted Extraction of Phenolics from Helichrysum italicum for Preparation of Extracts with Anti-Elastase and Anti-Collagenase Properties.

Helichrysum italicum is a plant traditionally used for skin-related disorders that is becoming an increasingly popular ingredient in cosmetic products. In this work, a "green" ultrasound-assisted extraction method for H. italicum phenolics was developed using skin-friendly cyclodextrins (CDs). Extraction conditions needed for the greatest yield of target compounds (total phenolics, phenolic acids, and flavonoids) were calculated. The composition of the extracts was determined using LC-MS and spectrophotometric methods. Among the tested CDs, 2-hydroxylpropyl-beta-CD (HP-ß-CD) was the best suited for extraction of target phenolics and used to prepare two optimized extracts, OPT 1 (the extract with the highest phenolic acid content) and OPT 2 (the extract with the highest total phenol and flavonoid content). The extracts were prepared at 80 °C, using 0.089 g of plant material/g solvent (0.6 mmol of HP-ß-CD), with or without addition of 1.95% (w/w) lactic acid. The main metabolite in both extracts was 3,5-O-dicaffeoylquinic acid. It was found that the addition of lactic acid greatly contributes to the extraction of arzanol, a well-known anti-inflammatory agent. IC50 values of the anti-elastase (22.360 ± 0.125 µL extract/mL and 20.067 ± 0.975 for OPT-1 and OPT-2, respectively) and anti-collagenase (12.035 ± 1.029 µL extract/mL and 14.392 ± 0.705 µL extract/mL for OPT-1 and OPT-2, respectively) activities of the extracts surpassed those of the applied positive controls, namely ursolic and gallic acids. This activity deems the prepared extracts promising ingredients for natural cosmetics, appropriate for direct use in cosmetic products, removing the need for the evaporation of conventional solvents.

Hydroxypropyl-ß-Cyclodextrin-Based Helichrysum italicum Extracts: Antioxidant and Cosmeceutical Activity and Biocompatibility.

Two Helichrysum italicum extracts, OPT-1 (rich in phenolic acids) and OPT-2 (rich in total phenols and flavonoids), were prepared using hydroxypropyl-ß-cyclodextrin (HP-ß-CD)-assisted extraction. The prepared extracts were rich in phenolic compounds, including flavonoids and phenolic acids. GC-MS analysis of the extracts identified neryl acetate, neo-intermedeol, ß-selinene, γ-curcumene, italidione I, and nerol as the main volatile components of the extracts, as well as plant sterols, γ-sitosterol, campesterol, and stigmasterol. The antioxidant (DPPH radical scavenging, reducing power, and a carotene linoleic acid assay) and cosmeceutical (anti-hyaluronidase, anti-tyrosinase, anti-lipoxygenase, ovalbumin anti-coagulation, and a UV-absorption assay) activity of the extracts in most of the assays was better than the activity of the applied positive controls. Especially low were the IC50 values of the extracts in the anti-hyaluronidase (14.31 ± 0.29 µL extract/mL and 19.82 ± 1.53 µL extract/mL for OPT-1 and OPT-2, respectively) and the anti-lipoxygenase (0.96 ± 0.11 µL extract/mL and 1.07 ± 0.01 µL extract/mL for OPT-1 and OPT-2, respectively) assays. The extracts were non-toxic to HaCaT cells in concentrations of up to 62.5 µL extract/mL assuring their status as excellent candidates for cosmeceutical product development appropriate for direct use in cosmetic products without solvent evaporation.

Glycerol and Natural Deep Eutectic Solvents Extraction for Preparation of Luteolin-Rich Jasione montana Extracts with Cosmeceutical Activity.

Jasione montana is a plant from the family Campanulaceae rich in phenols with health-beneficial properties such as luteolin (LUT) derivatives. In this work, a glycerol-based ultrasound-assisted extraction method was developed and optimized for in total phenol (TP) and LUT content, as well as antiradical activity (RSA). The best conditions (glycerol content, temperature, plant material weight, and ultrasonication power) for the preparation of J. montana extracts richest in TP (OPT-TP), LUT (OPT-LUT), and having the best RSA (OPT-RSA) were determined. Furthermore, numerous natural deep eutectic solvents (NADES), containing proline, glycerol, betaine, urea, and glucose were prepared and used for the extraction of J. montana. Contents of TP, LUT, and RSA in the prepared extracts were established. Antioxidant and cosmeceutical activity of the prepared extracts was tested. The OPT-TP, OPT-LUT, and OPT-RSA, as well as the most efficient NADES-based extract, PG-50-TP, were excellent antioxidants and Fe2+ ion chelators. In addition, they were potent inhibitors of collagenase and hyaluronidase, as well as good significant anti-elastase and -lipoxygenase activity. The observed antioxidant- and enzyme-inhibiting activity of J. montana extracts prepared using environmentally friendly methods and non-toxic solvents makes them promising ingredients of cosmeceutical products.

Effect of timing of levothyroxine administration on the treatment of hypothyroidism: a three-period crossover randomized study.

AIM: Hypothyroidism is a common clinical problem that is successfully treated with hormone substitutes in the form of levothyroxine (LT4). LT4 is a drug with a narrow therapeutic index and is usually administered by strict rules, standardly at least half an hour before breakfast. The aim of this study was to investigate a possible effect of different timings of administration on thyroid function status and lipid profile. METHODS: The study included patients with the diagnosis of primary hypothyroidism, which were using a stable dose of levothyroxine. They were randomized into three different groups regarding the timing of LT4 administration in a crossover fashion. Each timing regimen lasted for at least 8 weeks; timing regimen A-half an hour before breakfast; timing regimen B-an hour before the main meal of the day; timing regimen C-at bedtime (minimally 2 h after dinner). The hormones (TSH, fT3, fT4) and lipid profile (triglycerides, HDL-, LDL-, and total cholesterol) were measured before the study, at the beginning of every timing regimen and at the end of the study. RESULTS: Altogether, 84 patients finished the study. Different timings of LT4 administration were non-inferior in comparison to the standard one and between each other. Median differences in TSH level between baseline and timing regimens were: baseline vs. A = -0.017 95% C.I. (-0.400-0.192); baseline vs. B = -0.325 95% C.I. (-0.562-0.023); baseline vs. C = -0.260 95% C.I. (-0.475-0.000). There were no statistically significant differences in either TSH, fT4, or fT3 when compared between all three timing regimens of LT4 administration and the baseline. There were no statistically significant differences in any of the lipid profile parameters (triglycerides, HDL-, LDL-, and total cholesterol) when compared between all three timing regimens of LT4 administration and the baseline. CONCLUSION: The three investigated timing regimens of LT4 administration were equally efficient and offer additional options regarding the treatment individualization.