Chitosan and Chitosan Nanoparticles Differentially Alleviate Salinity Stress in Phaseolus vulgaris L. Plants.

Salinity stress can significantly cause negative impacts on the physiological and biochemical traits of plants and, consequently, a reduction in the yield productivity of crops. Therefore, the current study aimed to investigate the effects of chitosan (Cs) and chitosan nanoparticles (CsNPs) to mitigate salinity stress (i.e., 25, 50, 100, and 200 mM NaCl) and improve pigment fractions, carbohydrates content, ions content, proline, hydrogen peroxide, lipid peroxidation, electrolyte leakage content, and the antioxidant system of Phaseolus vulgaris L. grown in clay-sandy soil. Methacrylic acid was used to synthesize CsNPs, with an average size of 40 ± 2 nm. Salinity stress negatively affected yield traits, pigment fractions, and carbohydrate content. However, in plants grown under salt stress, the application of either Cs or CsNPs significantly improved yield, pigment fractions, carbohydrate content, proline, and the antioxidant system, while these treatments reduced hydrogen peroxide, lipid peroxidation, and electrolyte leakage. The positive effects of CsNPs were shown to be more beneficial than Cs when applied exogenously to plants grown under salt stress. In this context, it could be concluded that CsNPs could be used to mitigate salt stress effects on Phaseolus vulgaris L. plants grown in saline soils.

Using guinea pig as a model for evaluation of equine influenza vaccine

Equine influenza is a highly contagious viral disease, specially among 1-5 years old naive horses. Vaccination is considered the best way to control the disease spread and outbreaks. Although foals are the main animal used for evaluation of equine influenza vaccines, guinea pigs were chosen as an alternative model in the present work, as they have a negligible antibody titer against equine influenza virus and are cheaper and easier to handle than foals. Five equine influenza vaccine batches were evaluated in two animal models, foals and guinea pigs, by injection of two doses/animal with 4 weeks apart using 2 mL/animal/dose and evaluation of immune responses by hemagglutination inhibition test and enzyme-linked immunosorbent assay. On the 7th week post vaccination, equine influenza antibodies titers reached maximum values of 9-10.2 and 8.7-10 hemagglutination inhibition units for foals and guinea pigs, respectively; sample/negative ratios were 0.126-0.464 and 0.128-0.445 for both animals, respectively. The use of guinea pigs as an animal model for the evaluation of equine influenza vaccines could be recommended instead of foals.

La gripe equina es una enfermedad viral muy contagiosa, especialmente entre los caballos jóvenes de 1 a 5 años de edad. La vacunación se considera la mejor forma de controlar la propagación y los brotes de la enfermedad. Aunque los potros son el principal animal utilizado para la evaluación de vacunas contra la gripe equina, en el presente trabajo se eligieron cobayos como modelo alternativo, ya que tienen un título insignificante de anticuerpos contra el virus de la gripe equina y son más baratos y fáciles de manejar que los potros. Se evaluaron cinco lotes de vacunas contra la gripe equina en dos modelos animales, potros y cobayos, mediante la inyección de dos dosis/animal con 4 semanas de intervalo utilizando 2 mL/animal/dosis y la evaluación de las respuestas inmunitarias mediante la prueba de inhibición de la hemaglutinación y el ensayo inmunoenzimático. En la 7ª semana posvacunación, los títulos de anticuerpos contra la gripe equina alcanzaron valores máximos de 9-10,2 y 8,7-10 unidades de inhibición de la hemaglutinación para potros y cobayos, respectivamente; las relaciones muestras/negativos fueron de 0,126-0,464 y 0,128-0,445 para ambos animales, respectivamente. Podría recomendarse el uso de cobayos como modelo animal para la evaluación de vacunas contra la gripe equina, en lugar de potros.

How Can Biological and Chemical Silver Nanoparticles Positively Impact Physio-Chemical and Chloroplast Ultrastructural Characteristics of Vicia faba Seedlings?

Through interactions with plant cells, silver nanoparticles (AgNPs) with both biological and chemical origins can stimulate physiological and metabolic processes in plants. To ensure their safe application in the food chain, it is necessary to investigate their effects on plant systems. Therefore, the effects of chemical AgNPs (chem-AgNPs) and biologically synthesized AgNPs (bio-AgNPs) at different levels (i.e., 0, 10, and 50 ppm) on physiological and biochemical traits {i.e., root and shoot growth traits, photosynthetic pigments (Chl a, Chl b, carotenoids, and total pigments), soluble sugars, total carbohydrates, starch, H2O2, and antioxidant enzyme activities} of Vicia faba L. seedlings were investigated. AgNPs were biosynthesized from silver nitrate (AgNO3) by a green synthesis approach using Jatropha curcas seed extract. The synthesized AgNPs were characterized by UV-vis spectroscopy, transmission electron microscopy (TEM), zeta potential, Fourier-transform infrared spectra (FT-IR), and X-ray diffraction (XRD). The results showed that bio-AgNPs at 10 ppm resulted in the highest growth, physiological, and biological traits of faba bean seedlings in comparison with those obtained from both AgNO3 and chem-AgNPs treatments. On the other hand, all AgNPs treatments adversely affected the chloroplast ultrastructure, however, fewer negative effects were obtained with the application of 10 ppm bio-AgNPs. In addition, the roots and shoots of seedlings contained the lowest Ag content under different treatments at 10 ppm AgNPs in comparison to the highest level of AgNPs (50 ppm), which indicates that additional studies should be incorporated to ensure safe use of lower concentrations of bio-AgNPs in seed priming. In conclusion, the application of biogenic nanoparticles at 10 ppm can be recommended to enhance plant growth and the productivity of strategic crops.

Nicorandil and Bone Marrow-derived Mesenchymal Stem Cells Therapeutic Effect after Ureteral Obstruction in Adult Male Albino Rats.

BACKGROUND: Chronic kidney disease is a global health problem for which renal fibrogenesis is the final treatment target. OBJECTIVE: In our work, we have highlighted two new strategies, nicorandil and Bone marrow-derived mesenchymal stem cells (BM-MSCs), as effective in reversing renal fibrosis induced by partial unilateral ureteral obstruction (PUUO). METHODS: The current study included 96 male albino rats randomly divided into four groups, with 24 rats per group; Group I, the control group; Group II, PUUO, where two-thirds of the left ureter was entrenched in the psoas muscle; Group III, same surgical procedure as in Group II for 7 days, and then the rats received 15 mg/kg/day nicorandil once daily for 21 days; and Group IV, same surgical procedure as in Group II for 7 days, and then rats were given 3 × 106 of labeled MSCs injected intravenous, and left for 21 days. Blood and kidney tissues were collected for biochemical, histological, and molecular analyses. RESULTS: Both the nicorandil and BM-MSCs treatment groups could ameliorate kidney damage evidenced by inhibition of MDA elevation and total antioxidant capacity reduction caused by PUUO. Also, there was a significant reduction observed in TNF, TGF, IL6, collagen I, and α-SMA in addition to improvement in histological examination. However, a significant difference was found between the BM-MSCs and nicorandil-treated groups. CONCLUSION: Our results suggest that BM-MSCs and nicorandil improved renal fibrosis progression through their antiapoptotic, anti-inflammatory, and antifibrotic effects in male albino rats subjected to PUUO, with BM-MSCs being more effective compared to nicorandil.

Preparation, characterization and properties of three different nanomaterials either alone or loaded with nystatin or fluconazole antifungals.

Engineered nanoparticles have enabled the development of novel uses, particularly in disease management. In this investigation, we synthesized and studied three distinct nanomaterials: solid lipid nanoparticles (SLNPs), chitosan nanoparticles (CSNPs), and carbon nanotubes (CNTs), either alone or loaded with two antifungals, nystatin, and fluconazole. The purpose of this study is to investigate the different properties of the produced nanomaterials, either alone or in combination with antifungals. Drug release studies revealed that about 55% from SLNPs, 43% from CSNPs and 97% from CNTs of nystatin drug were released at the longest time point assessed (12 h). In addition, about 89% from SLNPs, 84% from CSNPs and 81% from CNTs of fluconazole drug were released at the longest time point assessed (12 h). This research will expand the understanding of nanomaterials as a viable technique for the management of different fungal diseases that harm several agricultural crops.

Impact of Silica Ions and Nano Silica on Growth and Productivity of Pea Plants under Salinity Stress.

The present study was conducted to evaluate the effects of silicon (Si) and nano-silicon (NSi) on growth, yield, ions content, and antioxidant defense systems, including transcript levels of enzyme-encoding genes in Pisum sativum plants grown under salinity stress. Both Si and NSi were applied at the 3 mM level and NaCl was applied at 4 concentrations (100, 150, 200 and 250 mM). Vegetative growth, including plant height, leaf area, fresh and dry weights, and yield attributes were determined. Gene expression of antioxidant enzymes was analyzed, and their activities were determined. The results showed that salinity had deleterious effects on plant growth and yield. Salt-stressed plant leaves exhibited a greater activity of superoxide dismutase (SOD), peroxidase (POD), but a lower activity of catalase (CAT) when compared to the control. Na+ ions accumulated in roots and shoots of salinized plants. The application of Si and NSi significantly enhanced vegetative growth and relative water content (RWC), and caused significant increases in plant height, fresh and dry weight, total yield, and antioxidant defense systems. Si and NSi enhanced K+ content in roots and shoots under salinity treatment and decreased Na+ content in the studied tissues. It was concluded that the application of NSi was beneficial in improving the salt tolerance of Pisum sativum plants more than Si alone.

Green and sensitive spectrofluorimetric method for the determination of two cephalosporins in dosage forms.

Using two green and sensitive spectrofluorimetric methods, we quantified two cephalosporins, cefepime (CFM) and cefazolin (CFZ), in raw and pharmaceutical formulations. The first method is based on the reaction between CFM and fluorescamine (borate buffer, pH 8), which yields a highly fluorescent product. After excitation at 384 nm, the fluorescent product emits light at 484 nm. At concentration ranges from 12.0 to 120.0 ng ml-1, the relative fluorescence intensity/concentration curve was linear with a limit of quantification (LOQ) of 2.46 ng ml-1. The second method relied on measuring the CFZ quenching action on acriflavine fluorescence through formation of an ion-associate complex using Britton-Robinson buffer at pH 8. We measured acriflavine fluorescence at 505 nm after excitation at 265 nm. The decrease in acriflavine fluorescence intensity was CFZ concentration-dependent. Using this method, we quantified CFZ in concentrations ranging from 1 to 10 µg ml-1 with a LOQ of 0.48 µg ml-1. We studied and optimized the factors influencing reaction product formation. Moreover, we adapted our methods to the investigation of the mentioned drugs in raw and pharmaceutical formulations with greatly satisfying results. We statistically validated our methods according to International Council on Harmonisation Guidelines. The obtained results were consistent with those obtained with the official high-performance liquid chromatography methods.

Waste-Derived NPK Nanofertilizer Enhances Growth and Productivity of Capsicum annuum L.

Waste generation is a global issue that necessitates effective management for both human and animal health as well as environment. There are several ways to reduce waste, but recycling appears to be the best choice. By recycling, not only will the problem of pollution be resolved, but valuable compounds could be generated to be used as nutrients for plants. In this study, eco-friendly methods were established to produce α- and ß-chitosan (CS) (as a source of nitrogen) with different degrees of deacetylation from shrimp shells and squid pin waste, phosphorous through degreasing and calcination of bovine bone and potassium from evaporation of banana peels Kolakhar. The waste bulk products were physically characterized and dry-milled into nano-powders. Different concentrations of the produced nano-NPK fertilizer (10%, 25%, 50% and 100%) were foliar-applied to Capsicum annum L. cv. Cordoba plants and compared to commercial chemical fertilizer and untreated control plants. The obtained results revealed that the nano-composite NPK with 25% concentration significantly promoted growth, yield and harvest of C. annuum as compared with the control and chemical fertilizer-treated plants. This study demonstrated that the use of an eco-friendly preparation of waste NPK composites, with a low concentration, could be applied as foliar fertilizer over chemical fertilizer to enhance the growth and productivity of Capsicum.

Effect of the standard herbal preparation, STW5, treatment on dysbiosis induced by dextran sodium sulfate in experimental colitis.

BACKGROUND: The standardized herbal preparation, STW 5, is effective clinically in functional gastrointestinal disorders and experimentally in ulcerative colitis (UC). The present study explores whether the beneficial effect of STW 5 involves influencing the intestinal microbiota. METHODS: UC was induced in Wistar rats by feeding them 5% dextran sodium sulfate (DSS) in drinking water for 7 days. Rats were treated concurrently with STW 5 and sacrificed 24 h after last drug administration. Fecal samples were used to determine changes in the abundance of selected microbial phyla and genera using real-time PCR. RESULTS: Induction of UC led to dysbiosis and changes in the gut microbiota. The changes included an increase in some genera of the Firmicutes, namely Enterococcus, and a decrease in others, namely Blautia, Clostridium, and Lactobacillus. DSS further induced a marked increase in the abundance of Bacteroidetes and Proteobacteria as well as in the relative abundance of Actinobacteria and its genus Bifidobacterium. Methanobrevibacter levels (phylum Euryarchaeota) were also increased. Microbial dysbiosis was associated with changes in various parameters of colonic inflammation. STW 5 effectively guarded against those changes and significantly affected the indices of edema and inflammation in the UC model. Changes in colon length, colon mass index, inflammatory and apoptotic markers, and histological changes induced by DSS were also prevented. CONCLUSIONS: Dysbiosis plays a contributing role in the development of DSS-induced UC. Derangements in the microbial flora and associated inflammatory processes were largely prevented by STW 5, suggesting that this effect might contribute towards its beneficial usefulness in this condition.

Role of GATA3 exon 6 germline mutations in breast cancer progression in Egyptian female patients.

IMPACT STATEMENT: GATA3 mutations are known to play an important role in breast cancer progression. The exact role and mechanisms of these mutations remain controversial as some studies suggest a relation to breast tumor growth, while others suggest a relation to longer survival. GATA3 germline mutations are not well studied in breast cancer. In this study, it was hypothesized that different types of GATA3 mutations could contribute to the breast cancer progression in different ways. GATA3 exon 6, which is important for GATA3 protein functions, was reported to have hotspots, and hence it was selected for study. Intronic GATA3 germline mutations were found to be related to favorable prognosis, while protein coding mutations were found to be related to unfavorable prognosis. Bioinformatics study of large publically available datasets showed that GATA3 mutations lead to dysregulation of pathways related to T-cells activation, inflammation, and breast cancer development.

STW 5 is effective against nonsteroidal anti-inflammatory drugs induced gastro-duodenal lesions in rats.

BACKGROUND: Proton pump inhibitors are often used to prevent gastro-intestinal lesions induced by nonsteroidal anti-inflammatory drugs. However, they are not always effective against both gastric and duodenal lesions and their use is not devoid of side effects. AIM: To explore the mechanisms mediating the clinical efficacy of STW 5 in gastro-duodenal lesions induced by nonsteroidal anti-inflammatory drugs (NSAIDs), exemplified here by diclofenac, in a comparison to omeprazole. METHODS: Gastro-duodenal lesions were induced in rats by oral administration of diclofenac (5 mg/kg) for 6 successive days. One group was given concurrently STW 5 (5 mL/kg) while another was given omeprazole (20 mg/kg). A day later, animals were sacrificed, stomach and duodenum excised and divided into 2 segments: One for histological examination and one for measuring inflammatory mediators (tumor necrosis factor α, interleukins-1ß and 10), oxidative stress enzyme (heme oxygenase-1) and apoptosis regulator (B-cell lymphoma 2). RESULTS: Diclofenac caused overt histological damage in both tissues, associated with parallel changes in all parameters measured. STW 5 and omeprazole effectively prevented these changes, but STW 5 superseded omeprazole in protecting against histological damage, particularly in the duodenum. CONCLUSION: The findings support the therapeutic usefulness of STW 5 and its superiority over omeprazole as adjuvant therapy to NSAIDs to protect against their possible gastro-duodenal side effects.

Chemically synthesized silver nanoparticles induced physio-chemical and chloroplast ultrastructural changes in broad bean seedlings.

This study was conducted to explore the effects of priming of seven-year-old aged seeds with different concentrations of silver nanoparticles (AgNPs) on growth of broad bean (Vicia faba L.). Seeds were primed with different concentrations of AgNPs for 6 h before growing in the plastic trays. Different growth parameters like growth attributes, photosynthetic pigments, carbohydrates, antioxidant enzymes and chloroplast ultrastructure were estimated after 14 days of germination. Priming with AgNPs affected the root and shoot growth attributes as compared with control depending upon concentrations of AgNPs. In all treatments, photosynthetic pigments increased significantly above control levels, but total soluble sugars decreased in 10 and 50 ppm AgNPs and slightly increased in 100 ppm AgNPs as compared with control. Starch accumulation was apparent in all treated seedlings above that of control levels. Mesophyll cells of all treated seedlings were altered with electron dense particles than control. Priming with AgNPs affected the chloroplast structure which appeared in the form of less stacking of Greene, formation of protrusions and extensions, irregular shape of chloroplasts as compared with spindle shaped regular chloroplasts of control. In all treatments, total phenols were slightly affected as compared with control. The antioxidant enzyme activities in seedlings varied with the dose and type of antioxidants. Overall, AgNPs adversely affected the chloroplast ultrastructure, but increased growth of seedlings and starch accumulation. Further studies are required to explore the effects of AgNPs on the long-term on crop productivity of aged seeds.

Permeation characteristics of hypericin across Caco-2 monolayers in the presence of single flavonoids, defined flavonoid mixtures or Hypericum extract matrix.

OBJECTIVES: The major aim of this study was to get a detailed understanding of the exposure and fate of hypericin in the Caco-2 cell system when combined with various flavonoids, mixtures of flavonoids or Hypericum perforatum extract matrix (STW3-VI). METHODS: The permeation characteristics of hypericin in the absence or presence of quercetin, quercitrin, isoquercitrin, hyperoside and rutin were tested. Hypericin (5 µm) was mixed with single flavonoids (20 µm) or with different flavonoid combinations (each flavonoid 4 or 10 µm, total flavonoid concentration: 20 µm). Further, the uptake of hypericin (5 µm) in the presence of H. perforatum extract matrix (7.25, 29 and 58 µg/ml) was studied. KEY FINDINGS: Following application of hypericin to the apical side of the monolayer, only negligible amounts of the compound were found in the basolateral compartment. From all tested flavonoids, only quercitrin increased the basolateral amount of hypericin. Dual flavonoid combinations were not superior compared to the single combinations. The amount of hypericin in the basolateral compartment increased concentration-dependently in the presence of extract matrix (from 0 to 7.5%). CONCLUSION: Comparing the effects of various flavonoid mixtures vs the extract matrix, it can be concluded that, besides flavonoids, the extract seems to contain further compounds (e.g. phenolic acids or proanthocyanidins) which substantially improve the permeation characteristics of hypericin.

Betulinic Acid Exerts Cytotoxic Activity Against Multidrug-Resistant Tumor Cells via Targeting Autocrine Motility Factor Receptor (AMFR).

Betulinic acid (BetA) is a naturally occurring pentacyclic triterpene isolated from the outer bark of white-barked birch trees and many other medicinal plants. Here, we studied betulinic acid's cytotoxic activity against drug-resistant tumor cell lines. P-glycoprotein (MDR1/ABCB1) and BCRP (ABCG2) are known ATP-binding cassette (ABC) drug transporters that mediating MDR. ABCB5 is a close relative to ABCB1, which also mediates MDR. Constitutive activation of the EGF receptor is tightly linked to the development of chemotherapeutic resistance. BetA inhibited P-gp, BCRP, ABCB5 and mutation activated EGFR overexpressing cells with similar efficacy as their drug-sensitive parental counterparts. Furthermore, the mRNA expressions of ABCB1, BCRP, ABCB5 and EGFR were not related to the 50% inhibition concentrations (IC50) for BetA in a panel of 60 cell lines of the National Cancer Institute (NCI), USA. In addition to well-established MDR mechanisms, we attempted to identify other molecular mechanisms that play a role in mediating BetA's cytotoxic activity. For this reason, we performed COMPARE and hierarchical cluster analyses of the transcriptome-wide microarray-based mRNA expression of the NCI cell lines panel. Various genes significantly correlating to BetA's activity were involved in different biological processes, e.g., cell cycle regulation, microtubule formation, signal transduction, transcriptional regulation, chromatin remodeling, cell adhesion, tumor suppression, ubiquitination and proteasome degradation. Immunoblotting and in silico analyses revealed that the inhibition of AMFR activity might be one of the mechanisms for BetA to overcome MDR phenotypes. In conclusion, BetA may have therapeutic potential for the treatment of refractory tumors.

Molecular Determinants of Sensitivity or Resistance of Cancer Cells Toward Sanguinarine.

For decades, natural products represented a significant source of diverse and unique bioactive lead compounds in drug discovery field. In Clinical oncology, complete tumors remission is hampered by the development of drug-resistance. Therefore, development of cytotoxic agents that may overcome drug resistance is urgently needed. Here, the natural benzophenanthridine alkaloid sanguinarine has been studied for its cytotoxic activity against multidrug resistance (MDR) cancer cells. We investigated the role of the ATP-binding cassette (ABC) transporters BCRP/ABCG2, P-glycoprotein/ABCB1 and its close relative ABCB5 in drug resistance. Further drug resistance mechanisms analyzed in this study were the tumor suppressor TP53 and the epidermal growth factor receptor (EGFR). Multidrug resistant cells overexpressing BCRP, ABCB5 and mutated ΔEGFR were not cross-resistant toward sanguinarine. Interestingly, P-gp overexpressing cells were hypersensitive to sanguinarine. Doxorubicin uptake assay carried by flow cytometry revealed that sanguinarine is a potent inhibitor of the P-gp transporter. Moreover, immunoblotting analysis proved that P-gp was downregulated in a dose dependent manner after treating P-gp overexpressing cells with sanguinarine. It was surmised that The inhibition of NFκB activity might explain the collateral sensitivity in CEM/ADR5000 cells. The COMPARE and hierarchical cluster analyses of transcriptome-wide expression profiles of tumor cell lines of the National Cancer Institute identified genes involved in various cellular processes (immune response, inflammation signaling, cell migration and microtubule formation) significantly correlated with log10IC50 values for sanguinarine. In conclusion, sanguinarine may have therapeutic potential for treating multidrug resistant tumors.

Evaluating the Multitarget Effects of Combinations through Multistep Clustering of Pharmacological Data: the Example of the Commercial Preparation Iberogast.

Herbal combination preparations are widely used in traditional herbal medicine and are even established as modern evidence-based herbal medicinal products. The rationale behind such combinations is often questioned and assessing the contribution of each of the combination partners to overall activity is challenging. STW 5 (Iberogast) is such a combination with confirmed clinical efficacy in functional gastrointestinal disorders. It consists of nine plant extracts responsible for its multitarget function in these multifactorial diseases with their heterogeneous and overlapping pathomechanisms. This makes the combination an ideal candidate for the use of the newly described method of stepwise cluster analysis, a standardized procedure to transfer heterogeneous pharmacological data, from different models, into effect size categories. This allows for a stepwise cluster formation starting from the level of single tests up to the level of different pathomechanisms involved in the development of a certain disease, in this case functional dyspepsia subtypes and irritable bowel syndrome. In the current article, an overview on the pharmacological data on STW 5 and its single components is provided. The data are further analyzed using stepwise cluster formation, resulting in a summary of the different modes of action of STW 5 along with an evaluation of the contribution of the single constituents to the overall multitarget effects of the herbal combination preparation.

Modulation of gastrointestinal motility beyond metoclopramide and domperidone : Pharmacological and clinical evidence for phytotherapy in functional gastrointestinal disorders.

The prokinetic cisapride, an important therapeutic option in functional gastrointestinal (GI) disorders, was withdrawn from the market 15 years ago due to rare severe side effects. Likewise in 2014, the use of metoclopramide (MCP) and domperidone in functional GI disorders (FGID) was restricted, consequently leaving a therapeutic gap in clinical practice. A systematic review revealed that the herbal medicinal product (HMP) STW 5 presents a therapeutic option equivalent to MCP and cisapride. STW 5 is the only HMP for which efficacy has been shown in randomized controlled clinical trials (RCTs) in functional dyspepsia and irritable bowel syndrome, based on its multitarget effect on numerous etiological factors. Due to an outstanding favorable safety profile, STW 5 allows an effective and safe use in FGID without a limitation of the duration of the treatment.

Phytochemical Characterization of Low Molecular Weight Constituents from Marshmallow Roots (Althaea officinalis) and Inhibiting Effects of the Aqueous Extract on Human Hyaluronidase-1.

Extract RE was obtained from the roots of Althaea officinalis in a yield of 8.1%, related to the dried plant material, by extraction with MeOH-H2O (1:1), followed by precipitation with EtOH to remove high molecular weight constituents. Phytochemical investigation of RE revealed the presence of N-phenylpropenoyl-l-amino acid amides 1-5, 8% glycine betaine 6, about 9% total amino acids with proline as the main compound, and about 61% mono- and oligomeric carbohydrates with sucrose as the main compound. Further fractionation revealed the presence of a hypolaetin diglycoside (12) and four hypolaetin glycosides (7-9 and 11) with O-sulfocarbohydrate moieties; additionally, 4'-O-methylisoscutellarein-8-O-ß-d-(3″-O-sulfo)glucuronopyranoside (10) and the diglycosylated coumarin haploperoside D (13) were identified. The hypolaetin-O-sulfoglycosides 7-10 are new natural products. RE inhibited the enzymatic activity of surface-displayed human hyaluronidase-1 on Escherichia coli F470 cells with an IC50 of 7.7 mg/mL. RE downregulated mRNA expression of hyal-1 in HaCaT keratinocytes at 125 and 250 µg/mL, respectively. These data contribute to a deeper phytochemical understanding of marshmallow root extracts and to the positive influence of extracts used for therapy of irritated and inflamed buccal tissue and cough.

Mechanism of Action of STW 5 in Functional Dyspepsia and IBS: The Origin of Multi-Target.

BACKGROUND: STW 5 is a complex herbal combination preparation composed of 9 different herbal extracts. As an herbal medicinal product, this preparation is indicated for treating functional dyspepsia (FD) and irritable bowel syndrome (IBS). Its efficacy and practical applicability was demonstrated in several clinical studies. SUMMARY: Each herbal constituent of STW 5 has distinct effects on the gastrointestinal tract, and each shows activity through different mechanisms of action: among others, the single extracts have effects on nerves, smooth muscles, epithelial, and inflammatory cells. For example, they have relaxing or tonicizing effects on gastrointestinal muscles, and they counteract inflammation through different physiological systems, contributing to the clinical efficacy through modulation of multiple therapeutic targets. Key Messages: STW 5 is a role model for the concept of multi-targeting in therapy. Especially in complex syndromes such as FD and IBS, simultaneous multi-targeting of different functional causes seems to be a more promising approach than the classical paradigm of one disease - one receptor - one effect.