Urolithin A conjugation with NSAIDs inhibits its glucuronidation and maintains improvement of Caco-2 monolayers' barrier function.

Urolithin A (UA) is an ellagitannin-derived postbiotic metabolite which emerged as a promising health-boosting agent, promoting mitophagy, improving skeletal muscle function, and suppressing the inflammatory response. However, phase II intestinal metabolism severely limits its biopotency, leading to the formation of nonactive glucuronides. To address this constraint, a set of new UA derivatives (UADs), conjugated with nonsteroidal anti-inflammatory drugs (NSAIDs), was synthesized. The bioavailability and inhibitory activity of UADs against UA-glucuronidation were evaluated using differentiated Caco-2 cell monolayers. Parallelly, after the administration of tested substances, the transepithelial electrical resistance (TEER) of the cell monolayers was continuously monitored using the CellZscope device. Though investigated UADs did not penetrate Caco-2 monolayers, all of them significantly suppressed the glucuronidation rate of UA, while conjugates with diclofenac increased the concentration of free molecule on the basolateral side. Moreover, esters of UA with diclofenac (DicloUA) and aspirin (AspUA) positively influenced cell membrane integrity. Western blot analysis revealed that some UADs, including DicloUA, increased the expression of pore-sealing tight junction proteins and decreased the level of pore-forming claudin-2, which may contribute to their beneficial activity towards the barrier function. To provide comprehensive insight into the mechanism of action of DicloUA, Caco-2 cells were subjected to transcriptomic analysis. Next-generation sequencing (NGS) uncovered substantial changes in the expression of genes involved, for instance, in multivesicular body organization and zinc ion homeostasis. The results presented in this study offer new perspectives on the beneficial effects of modifying UA's structure on its intestinal metabolism and bioactivity in vitro.

Chemical composition of extracts from leaves, stems and roots of wasabi (Eutrema japonicum) and their anti-cancer, anti-inflammatory and anti-microbial activities.

The purpose of our study was to evaluate the composition of the extracts obtained from the roots and leaves of Eutrema japonicum cultivated in Poland. For this purpose, LC-DAD-IT-MS and LC-Q-TOF-MS analyses were used. The results revealed the presence of forty-two constituents comprising glycosinolates, phenylpropanoid glycosides, flavone glycosides, hydroxycinnamic acids, and other compounds. Then, the resultant extracts were subjected to an assessment of the potential cytotoxic effect on human colon adenocarcinoma cells, the effect on the growth of probiotic and intestinal pathogenic strains, as well as their anti-inflammatory activity. It was demonstrated that 60% ethanol extract from the biennial roots (WR2) had the strongest anti-inflammatory, antibacterial, and cytotoxic activities compared to the other samples. Our results suggest that extracts from E. japonicum may be considered as a promising compound for the production of health-promoting supplements.

The Potential of Medicinal Plants and Natural Products in the Treatment of Burns and Sunburn-A Review.

Treating burns remains a challenge for modern medicine, especially in developing countries that cannot afford expensive, advanced therapies. This review article summarises clinical and animal model studies of botanical preparations and their mixtures in treating burn wounds and sunburn. Articles available in electronic databases such as PubMed, Scopus, Web of Science, Science Direct and Google Scholar, published in English in 2010-2022, were considered. In the described clinical trials, it was shown that some herbal preparations have better effectiveness in treating burn wounds, including shortening the healing time and reducing inflammation, than the conventional treatment used hitherto. These herbal preparations contained extracts from Albizia julibrissin, Alkanna tinctoria, Aloe vera, Arnebia euchroma, Betula pendula and Betula pubescens, Centella asiatica, Hippophaë rhamnoides, Juglans regia, Lawsonia inermis, and mixtures of Matricaria chamomilla and Rosa canina. Research on animal models shows that many extracts may potentially benefit the treatment of burn wounds and sunburn. Due to the diverse mechanism of action, antibacterial activity, the safety of use and cost-effectiveness, herbal preparations can compete with conventional treatment. The growing interest in alternative medicine and herbal medicine encourages further research. Not only single preparations but also their mixtures should be taken into account because the research conducted so far often suggests a synergistic effect of the ingredients.

Fruits of Hippophaë rhamnoides in human leukocytes and Caco-2 cell monolayer models-A question about their preventive role in lipopolysaccharide leakage and cytokine secretion in endotoxemia.

Preparations from Hippophaë rhamnoides L. (sea buckthorn) have been traditionally used in the treatment of skin and digestive disorders, such as gastritis, gastric and duodenal ulcers, uterine erosions, as well as oral, rectal, and vaginal mucositis, in particular in the Himalayan and Eurasian regions. An influence of an aqueous extract from the fruits of H. rhamnoides (HR) on leakage of lipopolysaccharide (LPS) from Escherichia coli through gut epithelium developed from the human colorectal adenocarcinoma (Caco-2) monolayer in vitro and glucose transporter 2 (GLUT2) translocation were the principal objectives of the study. Additionally, the effect of HR on the production of pro- and anti-inflammatory cytokines (interleukins: IL-8, IL-1ß, IL-10, IL-6; tumor necrosis factor: TNF-α) by the Caco-2 cell line, human neutrophils (PMN), and peripheral blood mononuclear cells (PBMC) was evaluated. The concentration of LPS on the apical and basolateral sides of the Caco-2 monolayer was evaluated with a Limulus Amebocyte Lysate (LAL) assay. GLUT2 translocation was evaluated using an immunostaining assay, whereas secretion of cytokines by cell cultures was established with an enzyme-linked immunosorbent (ELISA) assay. HR (500 µg/ml) significantly inhibited LPS leakage through epithelial monolayer in vitro in comparison with non-treated control. The treatment of Caco-2 cells with HR (50-100 µg/ml) showed GLUT2 expression similar to the non-treated control. HR decreased the secretion of most pro-inflammatory cytokines in all tested models. HR might prevent low-grade chronic inflammation caused by metabolic endotoxemia through the prevention of the absorption of LPS and decrease of chemotactic factors released by immune and epithelial cells, which support its use in metabolic disorders in traditional medicine.

Current Knowledge on Interactions of Plant Materials Traditionally Used in Skin Diseases in Poland and Ukraine with Human Skin Microbiota.

Skin disorders of different etiology, such as dermatitis, atopic dermatitis, eczema, psoriasis, wounds, burns, and others, are widely spread in the population. In severe cases, they require the topical application of drugs, such as antibiotics, steroids, and calcineurin inhibitors. With milder symptoms, which do not require acute pharmacological interventions, medications, dietary supplements, and cosmetic products of plant material origin are gaining greater popularity among professionals and patients. They are applied in various pharmaceutical forms, such as raw infusions, tinctures, creams, and ointments. Although plant-based formulations have been used by humankind since ancient times, it is often unclear what the mechanisms of the observed beneficial effects are. Recent advances in the contribution of the skin microbiota in maintaining skin homeostasis can shed new light on understanding the activity of topically applied plant-based products. Although the influence of various plants on skin-related ailments are well documented in vivo and in vitro, little is known about the interaction with the network of the skin microbial ecosystem. The review aims to summarize the hitherto scientific data on plant-based topical preparations used in Poland and Ukraine and indicate future directions of the studies respecting recent developments in understanding the etiology of skin diseases. The current knowledge on investigations of interactions of plant materials/extracts with skin microbiome was reviewed for the first time.

Sambucus nigra L. leaves inhibit TNF-α secretion by LPS-stimulated human neutrophils and strongly scavenge reactive oxygen species.

ETHNOPHARMACOLOGICAL RELEVANCE: Sambucus nigra (elderberry) leaves were used in folk medicine to treat skin inflammations, ulcers, burns or boils, as well as to treat wounds, including infected and chronic ones. For centuries, elderberry leaves have been used mainly in eastern and southern Europe, as well as in western Asia. AIM OF THE STUDY: The study aimed to investigate the anti-inflammatory and antioxidant activity of four different extracts, such as aqueous and ethanolic prepared at room temperature and the solvent's boiling point, from the leaves of elderberry. MATERIALS AND METHODS: The effect of extracts both on the secretion of cytokines (TNF-α, IL-1ß, and IL-8) and reactive oxygen species (ROS) by neutrophils stimulated with bacteria-derived products was investigated. The cytotoxicity of extracts was analyzed by staining with propidium iodide measured by flow cytometry. The anti-inflammatory activity of extracts was also investigated through their influence on lipoxygenase activity. The antioxidant properties, including scavenging superoxide anion, hydrogen peroxide, nitric oxide, and 2,2-diphenyl-1-picrylhydrazyl radical were investigated in cell-free systems. The total content of phenolic compounds was tested using the Folin-Ciocalteu reagent. The qualitative and quantitative determination of the content of individual phenolic acids and flavonoids was performed by HPLC-DAD-MSn and HPLC-DAD method, respectively. RESULTS: Elderberry leaves extracts turned out to affect the inflammatory response of neutrophils by inhibiting the secretion of TNF-α and ROS. The ethanolic and aqueous extracts at a concentration of 50 µg × mL-1 reduce the secretion of TNF-α by approximately 40% and 10%, respectively. ROS secretion was decreased by around 50% for all extracts at concentration of 5 µg × mL-1. All the extracts were able to inhibit the activity of lipoxygenase. The ethanolic extracts were characterized by a higher content of phenolic compounds and a higher antioxidant activity, especially against nitric oxide, compared to the aqueous extracts. CONCLUSIONS: Our research has confirmed that elderberry leaves are a plant material with anti-inflammatory activity, especially against reactive oxygen species, and a potentially rich source of antioxidants. Preliminary analyses performed in this study could be the first step in confirming the traditional use of elderberry leaves in relieving inflammation.

The contribution of phenolics to the anti-inflammatory potential of the extract from Bolivian coriander (Porophyllum ruderale subsp. ruderale).

Porophyllum ruderale subsp. ruderale is a food product used for seasoning in Central and Southern America. The present research aimed to investigate the chemical composition of an extract prepared from aerial parts of P. ruderale using UHPLC-DAD-MS/MS, to isolate and identify major natural products present in the extract, and to furtherly investigate their anti-inflammatory activity in vitro. Twenty-five compounds were detected and characterized using UV-Vis and MS data. All characterized compounds were quantified. Ten major phenolics were isolated and identified by NMR. One previously undescribed natural product was isolated and established as 1-O-(4-hydroxy-3,5-dimethoxy)benzoyl-6-O-galloyl-ß-d-glucose (12). Anti-inflammatory activity was evaluated based on the influence of the extract and isolated compounds on the TLR4-dependent secretion of IL-8 and TNF-α by human primary neutrophils in vitro. Phenolic acids, and caffeic acid derivatives in particular, contributed to the extract's bioactivity.

Arctium lappa and Arctium tomentosum, Sources of Arctii radix: Comparison of Anti-Lipoxygenase and Antioxidant Activity as well as the Chemical Composition of Extracts from Aerial Parts and from Roots.

Arctium lappa is a weed used in traditional medicine in the treatment of skin inflammation and digestive tract diseases. Arctium tomentosum is used in folk medicine interchangeably with Arctium lappa and, according to European Medicines Agency (EMA) monography, provides an equal source of Arctii radix (Bardanae radix), despite the small amount of research confirming its activity and chemical composition. The aim of the study was the comparison of the anti-lipoxygenase and the antioxidant activity, scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide anion (O2•-), and hydrogen peroxide (H2O2), of 70 % (v/v) ethanolic extracts from the aerial parts and the roots of Arctium lappa and Arctium tomentosum. In the tested extracts, the total polyphenols content and the chemical composition, analyzed with the HPLC-DAD-MSn method, were also compared. The extracts were characterized by strong antioxidant properties, but their ability to inhibit lipoxygenase activity was rather weak. A correlation between the content of polyphenolic compounds and antioxidant activity was observed. The extracts from A. lappa plant materials scavenged reactive oxygen species more strongly than the extracts from A. tomentosum plant materials. Moreover, the extracts from A. lappa plant materials were characterized by the statistically significantly higher content of polyphenolic compounds.

Immunomodulatory Activity and Phytochemical Profile of Infusions from Cleavers Herb.

Extracts from aerial parts of G. aparine (cleavers) constitute a herbal remedy with monography in British Herbal Pharmacopeia. On the European market, there are several drugs and food supplements consisting of Galium extracts. In folk medicine, cleavers was used topically in Europe, Asia, and the Americas to treat skin diseases. In several remedies, cleavers is also listed as an immunomodulatory active herb influencing the defense response of the human body. The aim of this study was to investigate the immunostimulatory activity and antioxidant potential in vitro of a raw infusion of cleavers and bioactive fractions. The functional activity of lymphocytes in the reaction of the lymphocyte blast transformation (RLBT) method was used for immunomodulatory activity assays and direct scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO), and hydrogen peroxide (H2O2) was chosen for the examination of antioxidant activity. It was shown that both the raw extract and fractions show significant immunostimulatory and scavenging activities. The obtained data partially justify the traditional use of cleavers as topical remedy for skin infections and for wounds.