Ursolic Acid Formulations Effectively Induce Apoptosis and Limit Inflammation in the Psoriasis Models In Vitro.

Psoriasis, a prevalent inflammatory skin disorder affecting a significant percentage of the global population, poses challenges in its management, necessitating the exploration of novel cost-effective and widely accessible therapeutic options. This study investigates the potential of ursolic acid (UA), a triterpenoid known for its anti-inflammatory and pro-apoptotic properties, in addressing psoriasis-related inflammation and keratinocyte hyperproliferation. The research involved in vitro models employing skin and immune cells to assess the effects of UA on psoriasis-associated inflammation. The presented research demonstrates the limiting effects of UA on IL-6 and IL-8 production in response to the inflammatory stimuli and limiting effects on the expression of psoriatic biomarkers S100A7, S100A8, and S100A9. Further, the study reveals promising outcomes, demonstrating UA's ability to mitigate inflammatory responses and hyperproliferation of keratinocytes by the induction of non-inflammatory apoptosis, as well as a lack of the negative influence on other cell types, including immune cells. Considering the limitations of UA's poor solubility, hybrid systems were designed to enhance its bioavailability and developed as hybrid nano-emulsion and bi-gel topical systems to enhance bioavailability and effectiveness of UA. One of them in particular-bi-gel-demonstrated high effectiveness in limiting the pathological response of keratinocytes to pro-psoriatic stimulation; this was even more prominent than with ursolic acid alone. Our results indicate that topical formulations of ursolic acid exhibit desirable anti-inflammatory activity in vitro and may be further employed for topical psoriasis treatment.

Topical Formulations Based on Ursolic Acid-Loaded Nanoemulgel with Potential Application in Psoriasis Treatment.

Psoriasis is a chronic disorder that causes a rash with itchy, scaly patches. It affects nearly 2-5% of the worldwide population and has a negative effect on patient quality of life. A variety of therapeutic approaches, e.g., glucocorticoid topical therapy, have shown limited efficacy with systemic adverse reactions. Therefore, novel therapeutic agents and physicochemical formulations are in constant need and should be obtained and tested in terms of effectiveness and minimization of side effects. For that reason, the aim of our study was to design and obtain various hybrid systems, nanoemulgel-macroemulsion and nanoemulgel-oleogel (bigel), as vehicles for ursolic acid (UA) and to verify their potential as topical formulations used in psoriasis treatment. Obtained topical formulations were characterized by conducting morphological, rheological, texture, and stability analysis. To determine the safety and effectiveness of the prepared ursolic acid carriers, in vitro studies on human keratinocyte cell-like HaCaT cells were performed with cytotoxicity analysis for individual components and each formulation. Moreover, a kinetic study of ursolic acid release from the obtained systems was conducted. All of the studied UA-loaded systems were well tolerated by keratinocyte cells and had suitable pH values and stability over time. The obtained formulations exhibit an apparent viscosity, ensuring the appropriate time of contact with the skin, ease of spreading, soft consistency, and adherence to the skin, which was confirmed by texture tests. The release of ursolic acid from each of the formulations is followed by a slow, controlled release according to the Korsmeyer-Peppas and Higuchi models. The elaborated systems could be considered suitable vehicles to deliver triterpene to psoriatic skin.

Nanomicellar Extraction of Polyphenols-Methodology and Applications Review.

The selection of the appropriate extraction method is crucial, especially for the receiving of active substances from plant material. The extraction using supercritical liquids and micellar-mediated extraction (MME) is the most advantageous among the alternative methods to classical solid-liquid extraction. However, the latter seems to be the best solution when the desired actives are polar. The following article presents a comprehensive review of the micellar-mediated extraction method in the last decade. The theoretical principle of the process was also refreshed and the current state of knowledge on the applications for analytical and manufacturing purposes was summarized.

The Accumulated Effect of the Number of Ethylene Oxide Units and/or Carbon Chain Length in Surfactants Structure on the Nano-Micellar Extraction of Flavonoids.

Classical extraction methods used for isolation of active substances from plant material are expensive, complicated and often environmentally unfriendly. The ultrasonic assistance micelle-mediated extraction method (UAMME), based on green chemistry principles, seems to be an interesting alternative. This work aimed to find a connection between the chemical structure of non-ionic surfactants and the efficiency of the extraction process. The effect of hydrophobic chain length and number of ethoxy groups on the quality of Bidens tripartite extracts was investigated. Several ethoxylated fatty alcohols were used: Ceteareth-20, Steareth-20, Oleth-20, Oleth-10, Oleth-5, C12-C13 Pareth-12, C12-C15 Pareth-12 and Ceteareth-12. The bioflavonoid compositions with the HPLC method was determined. The hydrophilic lipophilic balance (HLB) of studied surfactants, as well as the surface tension of surfactant solutions, were compared, to determine the explanation for the obtained differences in bioflavonoids concentration. The structural changes influenced by polyphenol extraction were monitored using Dynamic Light Scattering (DLS) measurements. In this work, probably for the first time, the connection between the chemical structure of non-ionic surfactants and the efficiency of the extraction process was found. The experimental and theoretical approach rationalized the choice of an appropriate eluent. We propose some structurally dependent factors, whose optimal value gave a high efficiency to the UAMME.

Incorporation of bioflavonoids from Bidens tripartite into micelles of non-ionic surfactants - experimental and theoretical studies.

Classical extraction methods used for an isolation of active substances from the plant material are expensive, complicated and often environmentally unfriendly. The ultrasonic assistance micelle-mediated extraction method (UAMME) seems to be an interesting alternative. The aim of this work was to compare an efficiency of water solutions of three non-ionic surfactants: C9-11 Pareth-5, PPG-6 Steareth-7 and PPG-4 Laureth-5 in UAMME of Bidens tripartita. Subsequently, the obtained extracts were separated into two immiscible phases, a polyphenols rich surfactants phase and an aqueous phase by its heating above surfactants cloud points (CPC) or by salting out with NaCl. Along with decreasing the Hydrophilic/Lipophilic Balance (HLB) factor value of surfactants, i.e. increase of the hydrophobicity, a significant decreasing of the flavonoid content was observed. While polyphenols content and antioxidant activity increased. The good surface properties of all surfactants correspond to the high content of phenolic compounds in extracts and both concentration methods resulted in even a 50-fold increase of polyphenols content. Dynamic light scattering measurements (DLS) provided that solubilization of polyphenols, i.e. their incorporation into surfactants' micelles, occurred with significant enlarging of particle size. Based on the molecular dynamic simulations, the mechanism of polyphenols incorporation into micelles was discussed.

A micelle mediated extraction as a new method of obtaining the infusion of Bidens tripartita.

In this paper, the extracts of three-part beggarticks (Bidens tripartita) were prepared using ultrasonic assisted micelle-mediated extraction method (UAMME). Different kind of surfactants and WPC (whey protein concentrate) were applied. In the B. tripartita extracts twenty polyphenols were identified by UPLC-DAD-MS. Both aqueous and UAMME extracts mainly contained chlorogenic acid, caftaric acid and its derivatives as well as luteolin 7-O-glucoside. The luteolin was extracted with Rokanol B2 and Triton X-100. Furthermore, antioxidative properties of the extracts were analyzed with two methods: reactions with di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium (DPPH) reagent and Follin's method. The DPPH radical scavenging by micellar extracts was in general comparable with the antioxidant activity of conventional extracts. The most active was sample with Tego Care CG90, reducing about 73% of the radical. Obtained results confirmed that the UAMME might be an alternative method, to the liquid-liquid or solid-liquid extraction, of obtaining specified extracts rich in active compounds. Selecting a suitable surfactant may thus provide the expected composition of the extract.

Micelle-mediated extraction of elderberry blossom by whey protein and naturally derived surfactants.

Classical methods of the extraction of active ingredients from the plant material are expensive, complicated and often environmentally unfriendly. The micelle-mediated extraction method (MME) seems to be a good alternative. In this work, extractions of elderberry blossoms (Flos Sambuci) were performed using MME methods. Several popular surfactants and whey protein concentrate (WPC) was applied in the process. The obtained results were compared with those obtained in extraction by means of water. Antioxidant properties of the extracts were analyzed by using two different methods: reaction with di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium (DPPH) reagent and Follin's method. Furthermore, the flavonoid content in the extracts was determined. The results confirmed that the MME method with using whey protein might be an alternative method for obtaining, rich in natural antioxidants, plant extracts.