Anti-Cancer Properties of Resveratrol: A Focus on Its Impact on Mitochondrial Functions.

Cancer is one of the most serious public health issues worldwide, demanding ongoing efforts to find novel therapeutic agents and approaches. Amid growing interest in the oncological applications of phytochemicals, particularly polyphenols, resveratrol-a naturally occurring polyphenolic stilbene derivative-has emerged as a candidate of interest. This review analyzes the pleiotropic anti-cancer effects of resveratrol, including its modulation of apoptotic pathways, cell cycle regulation, inflammation, angiogenesis, and metastasis, its interaction with cancer stem cells and the tumor microenvironment. The effects of resveratrol on mitochondrial functions, which are crucial to cancer development, are also discussed. Future research directions are identified, including the elucidation of specific molecular targets, to facilitate the clinical translation of resveratrol in cancer prevention and therapy.

Formulation and evaluation of novel collagen/ carboxymethylcellulose blend film wound dressing.

Films are thin, flexible, and transparent wound dressings. They can be prepared from both synthetic and natural materials. In practice, synthetic polyurethane dominates, but research is mainly focused on substances of natural origin. An endogenous substance with excellent filmforming properties, which is involved in the wound healing process, is collagen. However, collagen films themselves have weak mechanical properties, which can be improved by, among other things, combining collagen with other materials. Such material could be carboxymethylcellulose, which has been shown to affect wound healing positively. Films consisting only of CMC also have weak mechanical properties, so combining both materials seems to be a suitable solution to the given problems, and a wound dressing with many beneficial properties for wound healing could be created. Therefore, our experiment aimed to prepare composite films for wound therapy consisting of a combination of collagen and CMC. The films were prepared by the solvent evaporation method, and their properties were compared with those formed only by CMC. In both cases, films with suitable organoleptic, physicochemical, and application properties for wound therapy were produced. The composite films showed lower absorption capacity and better mechanical resistance compared to those formed only by CMC. The combination of collagen and CMC in composite films intended for wound therapy has thus resulted in improved properties of the resulting dressing and holds potential for further research.

Cannabis sativa L. Bioactive Compounds and Their Protective Role in Oxidative Stress and Inflammation.

Cannabis (Cannabis sativa L.) plants from the family Cannabidaceae have been used since ancient times, to produce fibers, oil, and for medicinal purposes. Psychoactive delta-9-tetrahydrocannabinol (THC) and nonpsychoactive cannabidiol (CBD) are the main pharmacologically active compounds of Cannabis sativa. These compounds have, for a long time, been under extensive investigation, and their potent antioxidant and inflammatory properties have been reported, although the detailed mechanisms of their actions have not been fully clarified. CB1 receptors are suggested to be responsible for the analgesic effect of THC, while CB2 receptors may account for its immunomodulatory properties. Unlike THC, CBD has a very low affinity for both CB1 and CB2 receptors, and behaves as their negative allosteric modulator. CBD activity, as a CB2 receptor inverse agonist, could be important for CBD anti-inflammatory properties. In this review, we discuss the chemical properties and bioavailability of THC and CBD, their main mechanisms of action, and their role in oxidative stress and inflammation.

Formulation and Evaluation of Novel Film Wound Dressing Based on Collagen/Microfibrillated Carboxymethylcellulose Blend.

Collagen is essential as a physiological material in wound healing, so it is often used in wound management, mainly as a lyophilisate. Collagen also has excellent film-forming properties; unfortunately, however, its utilisation as a film wound dressing is limited because of its weak mechanical properties, especially in its wet state. For this reason, modifications or combinations with different materials are investigated. The combination of collagen with partially modified microfibrillar carboxymethylcellulose (CMC), which has not previously been described, provided a new possibility for strengthening collagen films and was the aim of this work. The collagen-CMC films based on three types of collagens, two plasticizers and two collagen. Plasticiser ratios were prepared using the solvent casting method; partially modified CMC served here as both a film-forming agent and a filler, without compromising the transparency of the films. The presence of microfibrils was confirmed microscopically by SEM. Organoleptic and physicochemical evaluation, especially in terms of practical application on wounds, demonstrated that all the samples had satisfactory properties for this purpose even after wetting. All the films retained acidic pH values even after 24 h, with a maximum of 6.27 ± 0.17, and showed a mild degree of swelling, with a maximum of about 6 after 24 h.

Films from poly-γ-glutamic acid and poly-ε-lysine as the potential wound dressings ­ formulation, preparation and evaluation

Film wound dressings represent one of the options in wound therapy. Various polymers can be used for their production. Currently, research focuses on materials of natural origin, more friendly to the human body, which are in many cases able to participate actively in the wound healing process. These include polyamino acids of bacterial origin, substances that are biodegradable, non-toxic, and have a great potential for an application not only in the medical field. From the point of view of film wound dressing formulation, poly-γ-glutamic acid (PGA), as a film-forming agent, and poly-ε-lysine (PL), characterized by antimicrobial activity, are of interest from this group. Therefore, the aim of our experiment was to prepare films consisting of PGA or a combination of PGA and PL with the addition of different plasticizers. The films were prepared by solvent evaporation method and then evaluated for their organoleptic (appearance, colour, transparency, ease of handling), physicochemical (thickness, density, opacity, surface pH), and mechanical properties (tensile strength and tear resistance). As a result, films showing mutual compatibility between the two polymers were obtained, with satisfactory properties for wound application.

Collagen in combination with the acid form of carboxymethylcellulose in the form of a nonwoven textile as a modern wound dressing - formulation, preparation and evaluation.

The acid form of carboxymethylcellulose (HCMC) is less known than its sodium salt (NaCMC). However, it is commonly used as a sorbent for chromatographic columns and has a number of valuable properties for its use in wound care. As a wound dressing in the form of hydrofibers, it is already commercially available on our market. Collagen, the most abundant protein in the human body, fulfils both a building and a physiological function in the body, also has an irreplaceable place in the treatment of wounds. It is important in the process of wound healing and is used in wound therapy in various forms. It exhibits very good film-forming properties as well, but the collagen-based films themselves have weaker mechanical resistance, which limits their successful application to a wound. Therefore, the effort is to combine collagen with other materials in order to ensure better mechanical and application properties even in the wet state. The aim of this experiment was to create a wound dressing by combining a collagen film with HCMC in the form of a nonwoven textile. The resulting dressing had satisfactory organoleptic, physicochemical (pH, absorbency) and application properties for its use in wound therapy. The textile HCMC formed a mechanical support for collagen, which enabled its saving during the dressing preparation and partly served as an absorbent layer.

Natural Compounds Rosmarinic Acid and Carvacrol Counteract Aluminium-Induced Oxidative Stress.

Aluminum accumulation, glutathione (GSH) and malondialdehyde (MDA) concentrations as well as catalase (CAT) and superoxide dismutase (SOD) activities were determined in erythrocytes and brain and liver homogenates of BALB/c mice treated with Al3+ (7.5 mg/kg/day (0.15 LD50) as AlCl3 (37.08 mg/kg/day), whereas HCl (30.41 mg/kg/day) was used as Cl- control, the treatments were performed for 21 days, i.p., in the presence and absence of rosmarinic acid (0.2805 mg/kg/day (0.05 LD50), 21 days, i.g.) or carvacrol (0.0405 mg/kg/day (0.05 LD50), 21 days, i.g.). The treatment with AlCl3 increased GSH concentration in erythrocytes only slightly and had no effect on brain and liver homogenates. Rosmarinic acid and carvacrol strongly increased GSH concentration in erythrocytes but decreased it in brain and liver homogenates. However, AlCl3 treatment led to Al accumulation in mice blood, brain, and liver and induced oxidative stress, assessed based on MDA concentration in the brain and liver. Both rosmarinic acid and carvacrol were able to counteract the negative Al effect by decreasing its accumulation and protecting tissues from lipid peroxidation. AlCl3 treatment increased CAT activity in mice brain and liver homogenates, whereas the administration of either rosmarinic acid or carvacrol alone or in combination with AlCl3 had no significant effect on CAT activity. SOD activity remained unchanged after all the treatments in our study. We propose that natural herbal phenolic compounds rosmarinic acid and carvacrol could be used to protect brain and liver against aluminum induced oxidative stress leading to lipid peroxidation.

Film wound dressing containing dexpanthenol - preparation and evaluation.

Currently, a wide variety of wound dressings of varying composition and effects is used to treat wounds. These include also film dressings where one of the promising materials for its preparation is sodium carboxymethylcellulose (NaCMC) as a material of natural origin with excellent film-forming properties. Its application is particularly in the field of absorbent dressings, films for wounds from this material are not used in practice yet. Hidden potential offers also dexpanthenol, a substance widely used in dermatological practice. Therefore, the aim of this research was to prepare films from textile NaCMC with dexpanthenol by the solvent evaporation method and their subsequent physicochemical evaluation. The presence of microfibrillar fibers of partially substituted carboxymethylcellulose together with HCMC has ensured optimal parameters for wound application such as pH, swelling and mechanical properties. The films showed satisfactory mass content uniformity and those with dexpanthenol also drug content uniformity.

Preparation and evaluation of bilayer films based on collagen and carboxymethylcellulose for wound therapy.

Collagen is the most abundant protein of the human body and a widely used biomaterial across sectors due to its favourable properties resulting from its physiological proximity. It plays a key role in the process of wound healing and tissue repair and is therefore used in modern wound dressings in various forms, either alone or in combination with other materials. Collagen films also offer potential applications for these purposes, because collagen has good film-forming properties and is commonly used in the food industry. The collagen films themselves, without further treatment, have weak mechanical properties, which is unsatisfactory when applied to a wound. For this reason, there is an effort to modify or to combine collagen with other materials. Therefore, the aim of our experiment was the preparation of bilayer films from collagen in combination with carboxymethylcellulose (CMC). The CMC in the bottom layer had a goal to strengthen the films, reduce the consumption of used collagen and to ensure suitable application properties. Organoleptic evaluation, pH determination, swelling properties evaluation and testing of the mechanical properties of the prepared films confirmed that the prepared films exhibited satisfactory application parameters for the wound.

Formulation and characterization of Turkish oregano microcapsules prepared by spray-drying technology.

The aim of this study was optimization of spray-drying process conditions for microencapsulation of Turkish oregano extract. Different concentrations of maltodextrin and gum arabic as encapsulating agents (wall material) as well as influence of selected processing variables were evaluated. The optimal conditions were maintained on the basis of the load of main bioactive compounds - ursolic, rosmarinic acids and carvacrol - in prepared microparticles after comparison of all significant response variables using desirability function. Physicomechanical properties of powders such as flowability, wettability, solubility, moisture content as well as product yield, encapsulation efficiency (EE), density, morphology and size distribution of prepared microparticles have been determined. The results demonstrated that the optimal conditions for spray-drying mixture consisted of two parts of wall material solution and one part of ethanolic oregano extract when the feed flow rate was 40 mL/min and air inlet temperature -170 °C. Optimal concentration of wall materials in solution was 20% while the ratio of maltodextrin and gum arabic was 8.74:1.26.

Optimization of carvacrol, rosmarinic, oleanolic and ursolic acid extraction from oregano herbs (Origanum onites L., Origanum vulgare spp. hirtum and Origanum vulgare L.).

The aim of our study was to increase the extraction efficiency of carvacrol, rosmarinic, oleanolic and ursolic acid from the different species of oregano herbs (Origanum onites L., Origanum vulgare spp. hirtum and Origanum vulgare L.). Various extraction methods (ultrasound-assisted, heat-reflux, continuous stirring, maceration, percolation) and extraction conditions (different solvent, material:solvent ratio, extraction temperature, extraction time) were used, and the active substances were determined by HPLC. The lowest content of carvacrol, rosmarinic, oleanolic and ursolic acid was obtained by percolation. During heat-reflux extraction, the content of active substances depended on the solvent used: ethanol/non-aqueous solvent (glycerol or propylene glycol) mixture was more effective compared with ethanol alone. The results showed that for each species of oregano the most optimal extraction method should be selected to maximize the content of biologically active substances in the extracts.

Formulation of Novel Layered Sodium Carboxymethylcellulose Film Wound Dressings with Ibuprofen for Alleviating Wound Pain.

Effective assessment and management of wound pain can facilitate both improvements in healing rates and overall quality of life. From a pharmacological perspective, topical application of nonsteroidal anti-inflammatory drugs in the form of film wound dressings may be a good choice. Thus, the aim of this work was to develop novel layered film wound dressings containing ibuprofen based on partially substituted fibrous sodium carboxymethylcellulose (nonwoven textile Hcel NaT). To this end, an innovative solvent casting method using a sequential coating technique has been applied. The concentration of ibuprofen which was incorporated as an acetone solution or as a suspension in a sodium carboxymethylcellulose dispersion was 0.5 mg/cm(2) and 1.0 mg/cm(2) of film. Results showed that developed films had adequate mechanical and swelling properties and an advantageous acidic surface pH for wound application. An in vitro drug release study implied that layered films retained the drug for a longer period of time and thus could minimize the frequency of changing the dressing. Films with suspended ibuprofen demonstrated higher drug content uniformity and superior in vitro drug release characteristics in comparison with ibuprofen incorporation as an acetone solution. Prepared films could be potential wound dressings for the effective treatment of wound pain in low exuding wounds.

In vitro permeation studies of phenolics from horse chestnut seed gels prepared with different polyacrylic acid polymer derivatives.

The aim of this study was to investigate the effects of polyacrylic acid polymers (Ultrez 10, Ultrez 20, Carbopol 980, and Carbopol 940) on the viscosity and the in vitro permeation of phenolic compounds from the gel prepared from natural horse chestnut seed extract. Experiments were performed in the presence and in the absence of peppermint oil (Mentha piperita). Our results showed that peppermint oil decreased the viscosity of the gels and permeation of phenolic compounds from all gel samples. Results show that the highest content of phenolic compounds (1.758 µg cm(-2)) permeated in vitro from gel based on Carbopol Ultrez 20 without peppermint oil added (p<0.05 vs. other tested polymers).

Direct effects of (-)-epicatechin and procyanidin B2 on the respiration of rat heart mitochondria.

Flavonol (-)-epicatechin and its derived dimer procyanidin B2, present in high amounts in cocoa products, have been shown to exert beneficial effects on the heart and cardiovascular system; however, their mechanism of action has not been fully elucidated. We studied effects of (-)-epicatechin and procyanidin B2 on the oxidative phosphorylation of isolated rat heart mitochondria. (-)-Epicatechin and procyanidin B2 had stimulating effect (up to 30% compared to control) on substrate-driven (State 2) mitochondrial respiration. Their effect was dependent on the respiratory substrates used. (-)-Epicatechin at higher concentrations (from 0.27 µg/mL) significantly decreased (up to 15%) substrate- and ADP-driven (State 3) mitochondrial respiration in case of pyruvate and malate oxidation only. Procyanidin B2 (0.7-17.9 ng/mL) inhibited State 3 respiration rate up to 19%, the most profound effect being expressed with succinate as the substrate. (-)-Epicatechin at concentrations of 0.23 µg/mL and 0.46 µg/mL prevented loss of the cytochrome c from mitochondria when substrate was succinate, supporting the evidence of membrane stabilizing properties of this flavonol. Thus, both (-)-epicatechin and procyanidin B2 directly influenced mitochondrial functions and the observed effects could help to explain cardiometabolic risk reduction ascribed to the consumption of modest amounts of cocoa products.

The development and in vitro evaluation of herbal pellets coated with Eudragit FS 30.

The objective of this study was to prepare pellets of thyme (Thymus vulgaris L.), stinging nettle (Urtica dioica L.) and sage (Salvia officinalis L.) dry extracts by extrusion-spheronization technique to improve technological properties and investigate dissolution profiles of pellets covered different levels of pH-sensitive polymer Eudragit® FS. Optimal sample of pellets were prepared using microcrystalline cellulose and lactose as excipients and demonstrated excellent technological quality properties such as Hausner ratio (1.07 ± 0.11) and compressibility index (6.73 ± 0.94%) value, spericity (0.87 ± 0.001) and friability (0.22 ± 0.08 N). Pellets were coated by 10-35% (w/w) of Eudragit® FS. Dissolution studies showed that less than 20% of coating could not prevent dissolution of phenols in pH 1.2, 20% Eudragit® FS coating is enough to prevent herbal extract against dissolution in the stomach. There were observed no statistical significant differences between 20% and 25% or higher amount of coating polymer to a dissolution of phenols in low pH.

[Preparation and evaluation of the oral gel containing the essential oil from Siberian fir (Abies sibirica Ledeb.)]. / Príprava a hodnocení orálního gelu obsahujícího silici z jedle sibirské (Abies sibirica Ledeb.).

Essential oil of the Siberian fir (Abies sibirica Ledeb.) ranks among the substances with potential use in prevention and treatment of oral candidiasis. Therefore, the aim of the study was the formulation, preparation and evaluation of an oral gel containing 0.3% of this essential oil. Carbopol 974P NF in 1% concentration was used as the gelling agent, some samples were additionally stabilized by an addition of polysorbate 80 (0.1-0.5%). Xylitol in concentrations of 10% or 20% was added with the aim to modify the taste properties of the gel. Following microscopic evaluation (mean oil droplet size, degree of dispersity) immediately after preparation and after 6-month storage, it has been found that the optimal concentration of polysorbate 80 is 0.3%. The results of the experiment also demonstrated that xylitol was not only an excipient adjusting the organoleptic properties of the preparation - its use enabled significant improvement of the quality parameters and stability.

The effect of Leonurus cardiaca herb extract and some of its flavonoids on mitochondrial oxidative phosphorylation in the heart.

Motherwort (Leonurus cardiaca) possesses antibacterial, antioxidant, anti-inflammatory, and analgesic activities, and is used as a complementary remedy to improve heart function and blood circulation. Since cardiovascular diseases are often associated with an alteration of mitochondria, the main producers of ATP in cardiac muscle cells, the aim of our work was to determine bioactive constituents present in motherwort aerial parts extract in ethanol and investigate their effects on the functions of cardiac mitochondria. Quantitative determination of polyphenols in L. cardiaca herb extract was performed by HPLC. Mitochondrial respiration rates were evaluated using a Clark-type oxygen electrode. Mitochondrial ROS generation was determined fluorimetrically with Amplex Red and horseradish peroxidase. The results showed that constituents (chlorogenic acid, orientin, quercetin, hyperoside, and rutin) of L. cardiaca herb extract uncouple (by 20-90 %) mitochondrial oxidation from phosphorylation, partially inhibit (by ~ 40 %) the mitochondrial respiratory chain in cases of pyruvate and malate as well as succinate oxidation, and effectively attenuate the generation of free radicals in mitochondria. Since partial uncoupling of mitochondria, respiratory inhibition, and decreased ROS production are proposed as possible mechanisms of cardioprotection, our results imply that L. cardiaca herb extract could be a useful remedy to protect cardiac muscles from the effects of pathogenic processes.

A combination of grapefruit seed extract and concentrated cranberry juice as a potential antimicrobial preservative for the improvement of microbiological stability of hypromellose gel.

Aqueous hypromellose gels are not microbiologically stable - they show signs of microorganism growth during storage. To extend the shelf-life of the gels, antimicrobial preservatives are needed. Some substances of plant origin are known for their antimicrobial properties, and thus they may be used as an alternative to synthetic preservatives. Therefore, the aim of this study was to evaluate the microbiological stability of aqueous hypromellose gel and the effectiveness of natural substances - grapefruit seed extract (GSE), concentrated cranberry juice, and a combination thereof - on the antimicrobial protection of the gel. The evaluation of the antimicrobial activity of GSE and cranberry juice showed that their antimicrobial effects differed. Both cranberry juice and GSE inhibited the growth of the standard gram-positive and gram-negative bacteria, but the effect of GSE was significantly stronger. Candida albicans was sensitive only to GSE. For this reason, in order to affect all the microorganisms studied, either a combination of 0.7% GSE and 10% cranberry juice, or 5% GSE alone may be used. The combination of GSE and cranberry juice was effective only in acidic medium (pH being 2.5-5), while the antimicrobial effect of GSE was not dependent on the pH value.

New formula herbal pellets demonstrate a uniform and stable release of the active ingredients in vitro.

The aim of this study was to evaluate the effect of different capsule filling manufacturing techniques and storage conditions on the release of the active ingredients from herbal capsules during the dissolution test in vitro. Different techniques for the preparation of the original mixture of dry extracts were applied, and subsequently capsules with six different fillings were prepared. The stability of the capsules was evaluated in different long-term storage conditions, registering changes in the water content (loss of drying), capsule disintegration time, and phenolic compounds dissolution test in vitro. The baseline of phenolic compounds release in the control capsules (filled with the mixture of the powder of dry herbal extracts) was the highest, compared to other capsule groups, yet during long-term storage, these capsules accumulated too much moisture, which impeded capsule disintegration time and phenolic compounds release. The study showed that moisture and temperature changes occurring during the storage of the preparation had a negative effect on the release of phenolic compounds from herbal capsules. Capsules filled with pellets demonstrated a uniform and stable release of the active ingredients in different long-term storage conditions, which indicates that the manufacturing technology of dry herbal extracts affects the stability of the active ingredients.

[Influence of the degree of substitution on the absorptivity of acidic carboxymethyl cellulose in the form of nonwoven fabric]. / Vliv stupne substituce na nasákavost kyselé formy karboxymethylcelulosy v podobe netkané textilie.

Modern wound treatment is based on the creation of moist wound environment which accelerates healing. For these purposes some devices and materials may be used, including carboxymethyl cellulose (CMC). Wound dressings currently available on the market contain CMC in the form of sodium salt. CMC in the acidic form has not been used in wound healing therapy yet. Likewise, there are only a few papers describing the acidic CMC preparation and properties, which are inter alia dependent on the degree of substitution (DS). Therefore, the aim of the study was to evaluate the influence of DS on absorptivity, which is one of the main features of dressings after application on the wound. Samples with DS from 0.1 to 0.45 were examined using five media: purified water, normal saline, buffer solution with pH 7.4, physiological buffer solution with pH 7.2, and solution A. Absorptivity was evaluated using a model wound created by us. It has been found that from the viewpoint of absorptivity the optimal DS of acidic CMC in the form of nonwoven fabric lies in the range from 0.25 to 0.35. Below or above these values the absorptivity is worse.