New Avenues and Major Achievements in Phytocompounds Research for Glioblastoma Therapy.

Phytocompounds have been evaluated for their anti-glioblastoma actions for decades, with promising results from preclinical studies but only limited translation into clinics. Indeed, by targeting multiple signaling pathways deregulated in cancer, they often show high efficacy in the in vitro studies, but their poor bioavailability, low tumor accumulation, and rapid clearance compromise their efficacy in vivo. Here, we present the new avenues in phytocompound research for the improvement of glioblastoma therapy, including the ways to enhance the response to temozolomide using phytochemicals, the current focus on phytocompound-based immunotherapy, or the use of phytocompounds as photosensitizers in photodynamic therapy. Moreover, we present new, intensively evaluated approaches, such as chemical modifications of phytochemicals or encapsulation into numerous types of nanoformulations, to improve their bioavailability and delivery to the brain. Finally, we present the clinical trials evaluating the role of phytocompounds or phytocompound-derived drugs in glioblastoma therapy and the less studied phytocompounds or plant extracts that have only recently been found to possess promising anti-glioblastoma properties. Overall, recent advancements in phytocompound research are encouraging; however, only with more 3D glioblastoma models, in vivo studies, and clinical trials it is possible to upgrade the role of phytocompounds in glioblastoma treatment to a satisfactory level.

Antiangiogenic, Anti-Inflammatory and Antioxidant Properties of Bidens tripartite Herb, Galium verum Herb and Rumex hydrolapathum Root.

Plants are commonly used in folk medicine. Research indicates that the mechanisms of biological activity of plant extracts may be essential in the treatment of various diseases. In this respect, we decided to test the ethanolic extracts of Bidens tripartita herb (BTH), Galium verum herb (GVH), and Rumicis hydrolapathum root (RHR) on angiogenic, anti-inflammatory, and antioxidant properties and their total polyphenols content. In vitro studies using endothelial cells were used to see tested extracts' angiogenic/angiostatic and anti-inflammatory properties. The DPPH assay and FRAP analysis were used to detect antioxidant properties of extracts. The Folin-Ciocalteu analysis was used to determine the content of total polyphenols. The results of gas chromatography-mass spectrometry analysis was also presented. In vitro study demonstrated that BTH, GVH, and RHR ethanolic extracts significantly increased cell invasiveness, compared with the control group. Increased endothelial proangiogenic invasiveness was accompanied by reduced metalloproteinase inhibitor 1 (TIMP-1) and raised in metalloproteinase 9 (MMP-9). Only BTH and GVH significantly reduced cell proliferation, while BTH and RHR facilitated migration. Additionally, tested extracts reduced the production of proangiogenic platelet-derived growth factor (PDGF) and hepatocyte growth factor (HGF). The most potent anti-inflammatory capacity showed BTH and GVH, reducing proinflammatory interleukin 8 (CXCL8) and interleukin 6 (Il-6), compared to RHR extract that has slightly less inhibited CXCL8 production without affecting IL-6 production. Moreover, we confirmed the antioxidant properties of all examined extracts. The highest activity was characterized by RHR, which has been correlated with the high content of polyphenols. In conclusion, the modifying influence of examined extracts can be promising in disorders with pathogenesis related to angiogenesis, inflammation and free radicals formation. BTH is the best choice among the three tested extracts with its antiangiogenic and anti-inflammatory properties.

Anticholinesterase and Antityrosinase Secondary Metabolites from the Fungus Xylobolus subpileatus.

Xylobolus subpileatus is a widely distributed crust fungus reported from all continents except Antarctica, although considered a rare species in several European countries. Profound mycochemical analysis of the methanol extract of X. subpileatus resulted in the isolation of seven compounds (1-7). Among them, (3ß,22E)-3-methoxy-ergosta-4,6,814,22-tetraene (1) is a new natural product, while the NMR assignment of its already known epimer (2) has been revised. In addition to a benzohydrofuran derivative fomannoxin (3), four ergostane-type triterpenes 4-7 were identified. The structure elucidation of the isolated metabolites was performed by one- and two-dimensional NMR and MS analysis. Compounds 2-7 as well as the chloroform, n-hexane, and methanol extracts of X. subpileatus were evaluated for their tyrosinase, acetylcholinesterase, and butyrylcholinesterase inhibitory properties. Among the examined compounds, only fomannoxin (3) displayed the antityrosinase property with 51% of inhibition, and the fungal steroids proved to be inactive. Regarding the potential acetylcholinesterase (AChE) inhibitory activity of the fungal extracts and metabolites, it was demonstrated that the chloroform extract and compounds 3-4 exerted noteworthy inhibitory activity, with 83.86 and 32.99%, respectively. The butyrylcholinesterase (BChE) inhibitory assay revealed that methanol and chloroform extracts, as well as compounds 3 and 4, exerted notable activity, while the rest of the compounds proved to be only weak enzyme inhibitors. Our study represents the first report on the chemical profile of basidiome of the wild-growing X. subpileatus, offering a thorough study on the isolation and structure determination of the most characteristic biologically active constituents of this species.

Herbal Infusions as a Valuable Functional Food.

Herbal infusions are an underestimated and easy to intake a source of biologically active natural compounds (polyphenols), which, in the dissolved form, are more easily absorbed. Therefore, this study aimed to assess the potential of herbal infusions as a functional food to reduce postprandial hyperglycemia (inhibition of α-amylase and α-glucosidase) and to reduce the effects of increased blood glucose level (antioxidant effect-DPPH, CUPRAC, and Fe2+ chelating assays, as well as anti-inflammatory activity-inhibition of collagenase). We showed that polyphenols are present in the examined aqueous herbal infusions (including chlorogenic and gallic acids). Subsequently, our research has shown that herbal infusions containing cinnamon bark, mulberry leaves, and blackberry fruits most strongly inhibit glucose release from complex carbohydrates, and that all herbal infusions can, to different degrees, reduce the effects of elevated blood sugar. In conclusion, infusions prepared from herbal blends could be recommended to prevent type II diabetes.

Usnea sp.: Antimicrobial potential, bioactive compounds, ethnopharmacological uses and other pharmacological properties; a review article.

ETHNOPHARMACOLOGICAL RELEVANCE: Usnea sp. is a fruticose thalli lichen with interesting medicinal properties. Since ancient times, Usnea sp. has been used in traditional medicine worldwide to treat various diseases. The broad scientific studies on this lichen have proved its multidirectional biological effect, such as antimicrobial activity, which is attributed to its usnic acid content. PURPOSE: The main aim of this review is to provide an up-to-date overview of the antimicrobial activities of Usnea sp., including the traditional and medicinal uses, and a critical evaluation of the presented data. Also, the mechanism of this type of action will be explained. METHODS: To prepare this manuscript, the information was extracted from scientific databases (Pubmed, ScienceDirect, Wiley, Springer, and Google Scholar), books, and theses. The available scientific information was critically analysed. RESULTS: Analysis of the scientific literature regarding traditional uses and bioactivity research showed that Usnea sp. extracts exhibit high antibacterial activity. The Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis, Bacillus cereus, and Mycobacterium tuberculosis) and aquatic oomycetous fungi were the most sensitive Usnea sp. extracts. Moderate activity against Malassezia furfur and dermatophytes was observed, as well. Gram-negative bacteria, yeast, and fungi were more frequently resistant to Usnea sp. extracts (included Escherichia coli, Candida sp., Saccharomyces cerevisiae, and Aspergillus sp.). The antiviral activity of Usnea sp. was limited. CONCLUSION: The results show that the use of Usnea sp. in traditional medicine can be scientifically documented. Studies show that usnic acid is the active compound present in Usnea sp. extracts. This compound, which has a high antibacterial and cytotoxic activity, exists in large quantities in low-polarity extracts, and low concentration in these of high-polarity. Usnea sp. extracts contain compounds other than usnic acid as well with biological effects. Usnea barbata is a species that has been employed in modern-day cosmetic and pharmaceutical preparations. The information presented in the review can be considered as a source of knowledge about the Usnea sp. It presents research on biological properties reported for different species of Usnea genus and thus can facilitate their use in medicine.

Micropropagation of Chaenomeles japonica: A Step towards Production of Polyphenol-rich Extracts Showing Antioxidant and Antimicrobial Activities.

A protocol for C. japonica micropropagation with a confirmation of genome size stability of the in vitro-propagated plantlets was developed. The highest number of shoots multiplied in vitro was obtained on Murashige & Skoog medium (MS) with 1.0 mg L-1 N6-benzyladenine plus 1.0 mg L-1 indole-3-acetic acid. The highest number of roots was observed for the shoots on MS with 15 g L-1 sucrose plus 1.0 mg L-1 indole-3-acetic acid. The acclimatization rate was significantly high. The qualitative HPLC analyses confirmed the presence of phenolic acids and flavonoids in the extracts. The extracts from both shoot cultures and the leaves from field-grown plants revealed antioxidant activity and they exhibited moderate antimicrobial activity. The conducted research confirmed the regeneration potential of genetically-stable plants of C. japonica under in vitro conditions, the ability of the plantlets to produce polyphenols as those present in field-grown plants, as well as their antioxidant potential.

Effect of Pentacyclic Triterpenoids-Rich Callus Extract of Chaenomeles japonica (Thunb.) Lindl. ex Spach on Viability, Morphology, and Proliferation of Normal Human Skin Fibroblasts.

The effect of the well-characterized callus extract of Chaenomeles japonica on viability, morphology, and proliferation of normal human skin fibroblasts was investigated. The phytochemical analysis was performed using the ultra-high performance liquid chromatography method. The total phenolic, phenolic acid, and flavonoid contents were determined spectrophotometrically. The antioxidant activity was investigated using the DPPH (1,1-Diphenyl-1-picrylhydrazyl Radical Scavenging), FRAP (Ferric Reducing Antioxidant Power), and CUPRAC (CUPric Reducing Antioxidant Capacity) assays. The callus growth index during passages was high as well as the content of pentacyclic triterpenoids. The microscopic observations of the fibroblast viability, morphology and the evaluation of the proliferation ratio (xCELLigence system) proved that the influence of callus extract on the fibroblasts was dose-dependent. The evaluated level of fibroblasts proliferation rate after 72 h of incubation with callus extract at concentration 12.5 µg L-1 was the highest compared to all the analyzed ligands. Moreover, callus extract administrated for 72 h caused a significant increase in the proliferation rate in comparison with the control group (5.7 ± 0.1 vs. 4.4 ± 0.9; p < 0.01). The preliminary studies carried out may suggest that the callus extract rich in triterpenoids may be a potential source of cosmetic ingredients with a beneficial effect on human skin.

Anti-inflammatory Activity and Phytochemical Profile of Galinsoga Parviflora Cav.

The objective of this study was to evaluate the usefulness of a hydroalcoholic extract from Galinsoga parviflora herb (GP) in some aspects of the endothelial cell function necessary for anti-inflammatory activity and wound healing and relate these to the GP phytochemical profile. This study demonstrated that the GP extract caused a dose-dependent reduction of IL-6 secretion on IL-1ß-stimulated endothelial cells. The IL-6 release was decreased to 33% ± 9% while this did not influence the IL-6 secretion without stimulation. Additionally, the GP extract exhibited an anti-hyaluronidase activity (IC50 = 0.47 mg/mL), which was evidently stronger than the positive control kaempferol (IC50 = 0.78 mg/mL) as well as a moderate and concentration-dependent, antioxidant activity. The results of the scratch assay showed that exposure of the endothelial cells to GP induced complete healing of the damage after 12 h of the study. The phytochemical profile of the extract was studied by using spectrophotometric (total amount of polyphenols and flavonoids) and UPLC (phenolic acids) methods. The main compound in the GP extract was a chlorogenic acid (2.00 ± 0.01 mg/g by UPLC). The total content of polyphenols was 98.30 ± 0.14 mg of chlorogenic acid equivalent/g of the dry herb and content of flavonoids amounted to 6.15 ± 0.41 mg quercetin equivalent/g of the dry herb. Moreover, the presence of flavonoids in G. parviflora was provided after their isolation and identification by spectroscopic methods. In conclusion, it demonstrated that application of GP in the treatment of skin lesions gives possibility of wound healing based on antioxidant, anti-inflammatory, and hyaluronidase-inhibiting activities of G. parviflora herb extract.

Cytotoxic activity of physodic acid and acetone extract from Hypogymnia physodes against breast cancer cell lines.

CONTEXT: Lichens produce specific secondary metabolites with different biological activity. OBJECTIVE: This study investigated the cytotoxic effects of physodic acid, in addition to the total phenolic content and cytotoxic and antioxidant activity of acetone extract from Hypogymnia physodes (L.) Nyl. (Parmeliaceae). MATERIALS AND METHODS: Cytotoxicity of physodic acid (0.1-100 µM) was assessed in MDA-MB-231, MCF-7 and T-47D breast cancer cell lines and a nontumorigenic MCF-10A cell line using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, neutral red uptake and crystal violet assays during 72 h of incubation. An MTT assay was also used to assess the cytotoxic effects of the acetone extract (0.1-100 µg/mL) in the MDA-MB-231, MCF-7, T-47D breast cancer cell lines after 72 h. The total phenolic content of the acetone extract, expressed as the gallic acid equivalent, was investigated using Folin-Ciocalteu reagent. The antioxidant activity of the extract was assessed by 2,2-diphenyl-1-picrylhydrazyl and ferric-reducing antioxidant power assays. RESULTS: The cytotoxic activity of physodic acid appeared to be strong in the tumorigenic cell lines (IC50 46.0-93.9 µM). The compound was inactive against the nontumorigenic MCF-10A cell line (IC50 >100 µM). The acetone extract showed cytotoxicity in the breast cancer cell lines (IC50 46.2-110.4 µg/mL). The acetone extract was characterized by a high content of polyphenols, and it had significant antioxidant activity. DISCUSSION AND CONCLUSION: Physodic acid and acetone extract from H. physodes displayed cytotoxic effects in the breast cancer cell lines. Furthermore, acetone extract from H. physodes possessed significant antioxidant properties.

Centella asiatica in dermatology: an overview.

Centella asiatica is a medicinal plant that was already used as a 'panacea' 3000 years ago. The active compounds include pentacyclic triterpenes, mainly asiaticoside, madecasosside, asiatic acid and madecassic acid. We have conducted an overview to summarize current knowledge on the results of scientific in vitro and in vivo experiments focused on the improvement of the healing process of small wounds, hypertrophic scars and burns by C. asiatica. In this paper, we discuss the data on constituents, recommended preparations and the potential side effects of C. asiatica.

Centella asiatica in cosmetology.

Centella asiatica known as Gotu Kola is a medicinal plant that has been used in folk medicine for hundreds of years as well as in scientifically oriented medicine. The active compounds include pentacyclic triterpenes, mainly asiaticoside, madecassoside, asiatic and madecassic acids. Centella asiatica is effective in improving treatment of small wounds, hypertrophic wounds as well as burns, psoriasis and scleroderma. The mechanism of action involves promoting fibroblast proliferation and increasing the synthesis of collagen and intracellular fibronectin content and also improvement of the tensile strength of newly formed skin as well as inhibiting the inflammatory phase of hypertrophic scars and keloids. Research results indicate that it can be used in the treatment of photoaging skin, cellulite and striae.

[Studies on the antimigraine action of Feverfew (Tanacetum parthenium (L.) Sch. Bip.)]. / Badania nad dzialaniem przeciwmigrenowym zlocienia maruny (Tanacetum parthenium (L.) Sch. Bip.).

Feverfew was already known at the beginning of our era. In folk medicine, infusions from the leaves of Tanacetum parthenium were used in rheumatism, fever, and in migraine, menstrual pain, toothaches also digestive troubles, cough, or parasitic diseases. It has been proved that the biological activity of the plants resultsfrom the presence of the chemical compounds with different structures, including the the sesquiterpene lactones, which include partenolid, determining the antimigraine properties of plants. Research up to date on preclinical and clinical nature demonstrate the efficacy of plants in the prevention of migraine attacks. Based on the results can also conclude that the use of feverfew is safe and recorded side effects are mild and transient.

[Phytotherapy of respiratory tract diseases]. / Fitoterapia chorób dróg oddechowych.

Herbal medicines have been used in cough due to their antitussive and expectorant activity. Antitussives act either centrally on the cough center of the brain or peripherally on the cough receptors in the respiratory passages. The antitussive effect of many herbs results from the content of mucilage, which exerts protective and demulcent activity. The activity of expectorant herbs results primarily from their influence on the gastric mucose (saponins and ipec alkaloids). This proves reflex stimulation which leads to an increase in the secretion of bronchial glands. Volatile-oil type expectorant herbs exert a direct stimulatory effect on the bronchial glands by means of local irritation with antibacterial activity. In colds and flu, herbs containing volatile oil can be used; also, volatile oils are ingredients of syrups and liquids as well as external phytomedicines in the form of liniments, ointments, and inhalations. The paper shows the herbs and phytomedicines present on the Polish market used for the treatment of respiratory tract diseases.