Exploring Beneficial Properties of Haskap Berry Leaf Compounds for Gut Health Enhancement.

This study investigates the potential of formulated systems utilising haskap berry leaf extracts and dextran as carriers, to modulate both antioxidant and enzymatic inhibitory activities and their impact on the growth of specific bacterial strains. The analysis of antioxidant capacity, assessed through ABTS, CUPRAC, DPPH, and FRAP assays, revealed varying but consistently high levels across extracts, with Extract 3 (loganic acid: 2.974 mg/g, chlorogenic acid: 1.125 mg/g, caffeic acid: 0.083 mg/g, rutin: 1.137 mg/g, and quercetin: 1.501 mg/g) exhibiting the highest values (ABTS: 0.2447 mg/mL, CUPRAC: 0.3121 mg/mL, DPPH: 0.21001 mg/mL, and FRAP: 0.3411 mg/mL). Subsequent enzymatic inhibition assays demonstrated a notable inhibitory potential against α-glucosidase (1.4915 mg/mL, expressed as acarbose equivalent), hyaluronidase (0.2982 mg/mL, expressed as quercetin equivalent), and lipase (5.8715 µg/mL, expressed as orlistat equivalent). Further system development involved integration with dextran, showcasing their preserved bioactive compound content and emphasising their stability and potential bioactivity. Evaluation of the dextran systems' impact on bacterial growth revealed a significant proliferation of beneficial strains, particularly the Bifidobacterium and lactobacilli genus (Bifidobacterium longum: 9.54 × 107 to 1.57 × 1010 CFU/mL and Ligilactobacillus salivarius: 1.36 × 109 to 1.62 × 1010 CFU/mL), suggesting their potential to modulate gut microbiota. These findings offer a foundation for exploring the therapeutic applications of haskap berry-based dextran systems in managing conditions like diabetes, emphasising the interconnected roles of antioxidant-rich botanical extracts and dextran formulations in promoting overall metabolic health.

The Antioxidant and Neuroprotective Potential of Leaves and Inflorescences Extracts of Selected Hemp Varieties Obtained with scCO2.

Cannabis sativa, a versatile plant with numerous varieties, holds promising potential for a wide range of biological activity. As raw materials for research, we chose leaves and inflorescences of hemp varieties such as Bialobrzeskie, Henola, and Tygra, which are cultivated mainly for their fibers or seeds. The choice of extraction is a key step in obtaining the selected compositions of active compounds from plant material. Bearing in mind the lipophilic nature of cannabinoids, we performed supercritical carbon dioxide (scCO2) extraction at 50 °C under 2000 (a) and 6000 PSI (b). The cannabinoid contents were determined with the use of the HPLC-DAD method. The antioxidant capabilities were assessed through a series of procedures, including the DPPH, ABTS, CUPRAC, and FRAP methods. The capacity to inhibit enzymes that play a role in the progression of neurodegenerative diseases, such as acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and tyrosinase was also studied. The dominant cannabinoids in the extracts were cannabidiol (CBD) and cannabidiolic acid (CBDA). The highest concentration of eight cannabinoids was detected in the Tygra inflorescences extract (b). The most notable antioxidant properties were provided by the Tygra inflorescences extract (b). Nonetheless, it was the Henola inflorescences extract (b) that demonstrated the most efficient inhibition of AChE and BChE, and tyrosinase was inhibited the most significantly by the Bialobrzeskie inflorescences extract (b). Multidimensional comparative analysis enrolled all assays and revealed that the Henola inflorescences extract (b) showed the most substantial neuroprotective potential.

Determining Antioxidant Activity of Cannabis Leaves Extracts from Different Varieties-Unveiling Nature's Treasure Trove.

Cannabis leaves contain a diverse range of antioxidants, including cannabinoids, flavonoids, and phenolic compounds, which offer significant health benefits. Utilising cannabis leaves as a source of antioxidants presents a cost-effective approach because they are typically discarded during the cultivation of cannabis plants for their seeds or fibres. Therefore, this presented study aimed to assess the antioxidant activity of the leaves of selected hemp cultivars, such as Bialobrzeska, Tygra, and Henola, based on the results obtained with the 2,2'-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid, ferric reducing antioxidant power, cupric reducing antioxidant capacity, and 2,2-Diphenyl-1-picrylhydrazyl assays. The cannabinoid profile was analysed for the antioxidant activity to the contents of cannabidiol (CBD), cannabigerol (CBG), Δ9-tetrahydrocannabinol (Δ9-THC), and cannabichromene (CBC), determined based on chromatographic assays. The following variables were tested: the impact of various extractants (methanol, ethanol, and isopropanol), and their mixtures (50:50, v/v, as well as extraction methods (maceration and ultra-sound-assisted extraction) significant in obtaining hemp extracts characterised by different cannabinoid profiles. The results revealed that the selection of extractant and extraction conditions significantly influenced the active compounds' extraction efficiency and antioxidant activity. Among the tested conditions, ultrasound-assisted extraction using methanol yielded the highest cannabinoid profile: CBD = 184.51 ± 5.61; CBG = 6.10 ± 0.21; Δ9-THC = 0.51 ± 0.01; and CBC = 0.71 ± 0.01 µg/g antioxidant potential in Bialobrzeska leaf extracts.

Zein as an Effective Carrier for Hesperidin Delivery Systems with Improved Prebiotic Potential.

Hesperidin is a polyphenol derived from citrus fruits that has a broad potential for biological activity and the ability to positively modify the intestinal microbiome. However, its activity is limited by its low solubility and, thus, its bioavailability-this research aimed to develop a zein-based hesperidin system with increased solubility and a sustained release profile. The study used triple systems enriched with solubilizers to maximize solubility. The best system was the triple system hesperidin-zein-Hpß-CD, for which the solubility improved by more than six times. A significant improvement in the antioxidant activity and the ability to inhibit α-glucosidase was also demonstrated, due to an improved solubility. A release profile analysis was performed in the subsequent part of the experiments, confirming the sustained release profile of hesperidin, while improving the solubility. Moreover, the ability of selected probiotic bacteria to metabolize hesperidin and the effect of this flavonoid compound on their growth were investigated.

A Fisetin Delivery System for Neuroprotection: A Co-Amorphous Dispersion Prepared in Supercritical Carbon Dioxide.

Fisetin (FIS), a senolytic flavonoid, mitigates age-related neuroprotective changes. An amorphous FIS dispersion with a co-carrier was prepared using supercritical fluid extraction with carbon dioxide (scCO2). Characterisation, including powder X-ray diffraction and Fourier-transform infrared spectroscopy, confirmed amorphization and assessed intermolecular interactions. The amorphous FIS dispersion exhibited enhanced solubility, dissolution profiles, and bioavailability compared to the crystalline form. In vitro, the amorphous FIS dispersion demonstrated antioxidant activity (the ABTS, CUPRAC, DDPH, FRAP assays) and neuroprotective effects by inhibiting acetylcholinesterase and butyrylcholinesterase. FIS modulated gut microbiota, reducing potentially pathogenic gram-negative bacteria without affecting probiotic microflora. These improvements in solubility, antioxidant and neuroprotective activities, and gut microbiome modulation suggest the potential for optimising FIS delivery systems to leverage its health-promoting properties while addressing oral functionality limitations.

Assisted Extraction with Cyclodextrins as a Way of Improving the Antidiabetic Activity of Actinidia Leaves.

Five varieties of Actinidia leaves (Geneva, Jumbo, Ken's Red, Kijivska Hibridna, and Sentyabraskaya) were analyzed. The profiles of active compounds were determined, namely quercetin, rutin, epicatechin, chlorogenic acid, and kaempferol, in the raw material. Suspecting that the raw material might prove important in the treatment of diabetes, the authors assessed the antioxidant activity and the ability to inhibit enzymes responsible for the development of diabetes (α-glucosidase and α-amylase). As a result of the conducted analysis, the Ken's Red variety was indicated as having the highest biological activity (DPPH IC50 = 0.332 ± 0.048; FRAP IC0.5 = 0.064 ± 0.005; α-glucosidase inhibition IC50 = 0.098 ± 0.007; α-amylase inhibition IC50 = 0.083 ± 0.004). In order to increase the efficiency of the extraction of active compounds from Ken's Red variety leaves, cyclodextrins (α-CD, ß-CD, and γ-CD) were used as extraction process enhancers. The obtained results showed a significant increase in the contents of extracted active compounds. In addition, the type of CD used enhanced the extraction of selected compounds (quercetin, kaempferol, rutin, chlorogenic acid, and epicatechin. This study shows that the application of cyclodextrin-based extraction significantly improved the leaf activity of the Ken's Red variety (DPPH IC50 = 0.160 ± 0.019; FRAP IC0.5 = 0.008 ± 0.001; α-glucosidase inhibition IC50 = 0.040 ± 0.002; α-amylase inhibition IC50 = 0.012 ± 0.003).

Haskap Berry Leaves (Lonicera caerulea L.)-The Favorable Potential of Medical Use.

The presented research evaluates the medical use potential of Lonicera caerulea leaves, which are waste plants in cultivating berries. The study's screening activity included the leaves of five varieties of Lonicera caerulea: Atut, Duet, Wojtek, Zojka, and Jugana. The microbiological analysis confirmed the safety of using Lonicera caerulea leaves without significant stabilization. Lonicera caerulea leaves standardization was carried out based on the results of the chromatographic analysis, and it showed differences in the contents of active compounds (loganic, chlorogenic and caffeic acids, and rutin), which are attributed to biological activity. For the Lonicera caerulea leaves varieties tested, the differences in the content of total polyphenol content, chlorophylls, and carotenoids were also confirmed. The screening of biological activity of five Lonicera caerulea leaf varieties was carried out concerning the possibility of inhibiting the activity of α-glucosidase, lipase, and hyaluronidase as well, and the antioxidant potential was determined. The defined profile of the biological activity of Lonicera caerulea leaves makes it possible to indicate this raw material as an essential material supporting the prevention and treatment of type II diabetes. However, this research showed that tested enzymes were strongly inhibited by the variety Jugana. The health-promoting potential of Lonicera caerulea leaves was correlated with the highest chlorogenic acid and rutin content in the variety Jugana.

The Development of Innovative Dosage Forms of the Fixed-Dose Combination of Active Pharmaceutical Ingredients.

The development of innovative forms of combination drugs is closely related to the invention of the multilayer tablet press, polymers for pharmaceutical applications, the hot-melt extrusion process, and 3D printing in the pharmaceutical industry. However, combining multiple drugs within the same dosage form can bring many physicochemical and pharmacodynamic interactions. More and more new forms of fixed-dose combinations (FDCs) have been developed due to work to overcome the incompatibility of active substances or to obtain different drug release profiles in the same dosage form. This review provides discussions of the application of various innovation formulation technologies of FDC drugs such as bilayer system, multilayer tablet, active film coating, hot-melt extrusion, and 3D printing, taking into account the characteristics of the key ingredients in the FDC formulation and presenting technological problems and challenges related to the development of combination drugs. Moreover, the article summarizes the range of dosage forms that have been made using these technologies over the past 30 years.

Single-Pill Combination to Improve Hypertension Treatment: Pharmaceutical Industry Development.

Multiple illness is an increasingly common phenomenon. Its consequence is the need for polytherapy, which is particularly common among people suffering from arterial hypertension. The development of combined preparations (containing at least two API-active pharmaceutical ingredients) dedicated to the treatment of hypertension is a response to increased compliance, especially in elderly patients. In our work, we describe in particular the possibilities of using ß-adrenergic receptors blockers and angiotensin-converting enzyme inhibitors in combinations. The combinations of APIs are used as single pills in patients with arterial hypertension with concomitant diseases such as hyperlipidemia; blood coagulation problems and diabetes mellitus were also discussed successively. Pharmacoeconomic analysis for the API combinations shown is also presented. As a final conclusion, numerous benefits of using the combined preparations should be indicated, especially by the elderly and/or in patients with coexistence of other diseases.

Aloe arborescens: In Vitro Screening of Genotoxicity, Effective Inhibition of Enzyme Characteristics for Disease Etiology, and Microbiological Activity.

The present study assessed the genotoxicity, the possibility of inhibiting selected enzymes, and the microbial activity of lyophilisate from 3-year-old A. arborescens leaves obtained from controlled crops. The lyophilisate from 3-year-old A. arborescens leaves was standardized for aloin A and aloenin A content. Moreover, concentrations of polyphenolic compounds and phenolic acids were determined. The first stage of the research was to determine genotoxicity using the comet test, which confirmed the safety of A. arborescens. Assays of enzymatic inhibition were performed for hyaluronidase (IC50 = 713.24 ± 41.79 µg/mL), α-glucosidase (IC50 = 598.35 ± 12.58 µg/mL), acetylcholinesterase and butyrylcholinesterase (1.16 vs. 0.34 µM of eserine/g d.m., respectively). The next stage of the research was to determine the ability of the healing properties using the scratch test, which showed a positive response using the extract. Microbial activity was evaluated and obtained against Gram-negative and Gram-positive bacteria and yeasts. We concluded that A. arborescens leaf gel meets the important conditions for plant raw materials to obtain semi-solid forms of herbal medicinal products.

Potential for Prebiotic Stabilized Cornus mas L. Lyophilized Extract in the Prophylaxis of Diabetes Mellitus in Streptozotocin Diabetic Rats.

As a systemic disease, diabetes mellitus (DM) is characterized by the disruption of many glucose metabolic pathways. Therefore, it seems critical to study new therapies to support treatment to develop therapeutic systems that can operate across a broad metabolic spectrum. The current state of knowledge indicates an essential role of the gut microbiota in the development and course of the disease. Cornus mas fruits have demonstrated a rich biological activity profile and potential for application in the treatment of DM. As part of a preliminary analysis, the activity of four cultivars of Cornus mas fruits was analyzed. The cultivar Wydubieckij was selected as having the highest activity in in vitro conditions for further prebiotic system preparation. The study aimed to develop a unique therapeutic system based, first of all, on the mechanism of α-glucosidase inhibition and the antioxidant effect resulting from the activity of the plant extract used, combined with the prebiotic effect of inulin. The obtained system was characterized in vitro in terms of antioxidant activity and enzyme inhibition capacity, and was then tested on diabetic rats. The study was coupled with an analysis of changes in the intestinal microflora. The system of prebiotic stabilized Cornus mas L. lyophilized extract with inulin offers valuable support for the prophylaxis and treatment of DM.

Amorphous Form of Carvedilol Phosphate-The Case of Divergent Properties.

The amorphous form of carvedilol phosphate (CVD) was obtained as a result of grinding. The identity of the obtained amorphous form was confirmed by powder X-ray diffraction (PXRD), different scanning calorimetry (DSC), and FT-IR spectroscopy. The process was optimized in order to obtain the appropriate efficiency and time. The crystalline form of CVD was used as the reference standard. Solid dispersions of crystalline and amorphous CVD forms with hydrophilic polymers (hydroxypropyl-ß-cyclodextrin, Pluronic® F-127, and Soluplus®) were obtained. Their solubility at pH 1.2 and 6.8 was carried out, as well as their permeation through a model system of biological membranes suitable for the gastrointestinal tract (PAMPA-GIT) was established. The influence of selected polymers on CVD properties was defined for the amorphous form regarding the crystalline form of CVD. As a result of grinding (four milling cycles lasting 15 min with 5 min breaks), amorphous CVD was obtained. Its presence was confirmed by the "halo effect" on the diffraction patterns, the disappearance of the peak at 160.5 °C in the thermograms, and the changes in position/disappearance of many characteristic bands on the FT-IR spectra. As a result of changes in the CVD structure, its lower solubility at pH 1.2 and pH 6.8 was noted. While the amorphous dispersions of CVD, especially with Pluronic® F-127, achieved better solubility than combinations of crystalline forms with excipients. Using the PAMPA-GIT model, amorphous CVD was assessed as high permeable (Papp > 1 × 10-6 cm/s), similarly with its amorphous dispersions with excipients (hydroxypropyl-ß-cyclodextrin, Pluronic® F-127, and Soluplus®), although in their cases, the values of apparent constants permeability were decreased.

Chitosan as Valuable Excipient for Oral and Topical Carvedilol Delivery Systems.

Chitosan is a valued excipient due to its biocompatibility properties and increasing solubility of poorly water-soluble drugs. The research presented in this paper concerns the preparation of binary combinations of chitosan (deacetylated chitin) with carvedilol (beta-blocker) to develop a formulation with a modified carvedilol release profile. As part of the research, six physical mixtures of chitosan with carvedilol were obtained and identified by spectral (PXRD, FT-IR, and Raman), thermal (DSC), and microscopic (SEM) methods. The next stage of the research estimated the profile changes and the dissolution rate for carvedilol in the obtained drug delivery systems; the reference sample was pure carvedilol. The studies were conducted at pH = 1.2 and 6.8, simulating the gastrointestinal tract conditions. Quantitative changes of carvedilol were determined using the developed isocratic UHPLC-DAD method. Established apparent permeability coefficients proved the changes in carvedilol's permeability after introducing a drug delivery system through membranes simulating the gastrointestinal tract and skin walls. A bioadhesive potential of carvedilol-chitosan systems was confirmed using the in vitro model. The conducted research and the obtained results indicate a significant potential of using chitosan as an excipient in modern oral or epidermal drug delivery systems of carvedilol.

Fixed-Dose Combination of NSAIDs and Spasmolytic Agents in the Treatment of Different Types of Pain-A Practical Review.

This review presents the most common disease entities in which combinations of NSAIDs and spasmolytic drugs are used to reduce pain. The benefits of fixed-dose combination products (FDCs) are that they improve the response in people with insufficient monotherapy. Using the synergy or additive effect of drugs, it is possible to obtain a significant therapeutic effect and faster action with the use of smaller doses of individual drugs. In addition, one active ingredient may counteract adverse reactions from the other. Another essential aspect of the use of FDCs is the improvement of medical adherence due to the reduction in the pill burden on patients. It is also possible to develop a fixed-dosed combination product de novo to address a new therapeutic claim and be protected by patents so that the manufacturer can obtain exclusive rights to sell a particular FDC or a formulation thereof. The proposed fixed-dose combinations should always be based on valid therapeutic principles and consider the combined safety profile of all active substances included in the medicinal product. This review aims to identify which combinations of NSAIDs and spasmolytics have been developed and tested and which combinations are still under development.