Medicinal plants from the Himalayan region as potential novel antimicrobial and anti-inflammatory skin treatments

Background and Objectives: Adequate treatment of wounds remains one of the major medical needs globally, most notably in the regions with poor or limited access to health care. In many local and traditional systems of medicine, plants are often widely used for treating infected wounds. / Aim and objectives: The overarching aim of this project was selection of potential species for use in a future treatment by combining with plant resources with aspects of antimicrobial photodynamic therapy (aPDT). Specifically, we focussed on species used locally in the Himalayan region for the treatment of skin disorders and then assessed the existing pharmacological evidence for key species based on the published evidence available. / Methods: Database searches were performed to identify relevant publications describing local and traditional uses of plants in the Himalayan region of Bhutan, PR China, India, Nepal and Pakistan. Using the Global Biodiversity Information Facility (GBIF), species were researched in terms of their distribution including in different climatic regions, focussing on species mostly found in higher climatic zones (based on the Köppen–Geiger climate classification). For species used in three or more countries and restricted to the higher altitudes, data on safety, pharmacology, as it relates to dermatological conditions, and phytochemistry were retrieved. / Key findings: The study identified a total of 606 species that are used in the treatment of various skin conditions often associated with infections reported in 84 articles. Common weeds like Ageratum conyzoides and Bidens pilosa, widely used and cultivated species like Centealla asiatiaca and Prunus armenica were excluded. This ultimately led to the identification of a core group of five widely used species restricted to the Himalayan region (Cedrus deodara, Nardostachys jatamansi, Pinus wallichiana, Pinus roxburghii and Valeriana jatamansi). / Conclusions: Here we apply a novel approach comprising an assessment of the published information on the use of medicinal plants (i.e. local and traditional knowledge) in the context of their potential to be used in a biomedical form of clinical treatment – aPDT. Then, once sustainable sourcing based on access and benefit-sharing arrangements is in place, these species are investigated for their potential in wound treatment. Ultimately, the goal is to develop a new baseline for primary health care in some of the regions of the world with poor or limited access to health care

Treating Chronic Wounds Using Photoactive Metabolites: Data Mining the Chinese Pharmacopoeia for Potential Lead Species (#)

Efficient wound treatment that addresses associated infections and inflammation remains one of the big unmet needs, especially in low- and middle-income countries. One strategy for securing better healthcare can be using medicinal plants if sufficient evidence on their safety and therapeutic benefits can be ascertained. A unique novel opportunity could be photo-enhanced wound treatment with a combination of light-sensitive plant preparations and local exposure to daylight. Data mining strategies using existing resources offer an excellent basis for developing such an approach with many potential plant candidates. In the present analysis, we researched the 535 botanical drugs included in the Chinese pharmacopeia and identified 183 medicinal plant species, 82 for treating open wounds caused by trauma and 101 for inflammatory skin conditions. After further screening for reports on the presence of known photoactive compounds, we determined a core group of 10 scientifically lesser-known botanical species that may potentially be developed into more widely used topical preparations for photodynamic treatment of infected wounds. Our predictive approach may contribute to developing a more evidence-based use of herbal medicines

Histomorphological analysis of the urogenital diaphragm in elderly women: a cadaver study

The objective of this study was to describe the histomorphological structure of the urogenital diaphragm in elderly women using a modern morphometric procedure. Biopsies were taken from the posterior margin of the urogenital diaphragm of 22 female cadavers (mean age, 87years) using a 60-mm punch. Hematoxylin/eosin and Goldner sections were analyzed with the Cavalieri estimator. The mean thickness of the urogenital diaphragm was 5.5mm. The main component was connective tissue. All biopsies contained smooth muscle. Eighteen biopsies contained more smooth muscle than striated muscle. In six of 22 biopsies, no striated muscle was found. The ratio of striated to smooth muscle to connective tissue was 1:2.3:13.3. Muscle fibers were dispersed in all parts of the urogenital diaphragm. The urogenital diaphragm of elderly women mainly consists of connective tissue. Smooth muscle was also found but to a lesser extent. The frequently used English term "perineal membrane” for the urogenital diaphragm is justified and well describes our findings in elderly wome

The effect of hypophysectomy on pancreatic islet hormone and insulin-like growth factor I content and mRNA expression in rat

The growth arrest after hypophysectomy in rats is mainly due to growth hormone (GH) deficiency because replacement of GH or insulin-like growth factor (IGF) I, the mediator of GH action, leads to resumption of growth despite the lack of other pituitary hormones. Hypophysectomized (hypox) rats have, therefore, often been used to study metabolic consequences of GH deficiency and its effects on tissues concerned with growth. The present study was undertaken to assess the effects of hypophysectomy on the serum and pancreatic levels of the three major islet hormones insulin, glucagon, and somatostatin, as well as on IGF-I. Immunohistochemistry (IHC), in situ hybridization (ISH), radioimmunoassays (RIA), and Northern blot analysis were used to localize and quantify the hormones in the pancreas at the peptide and mRNA levels. IHC showed slightly decreased insulin levels in the beta cells of hypox compared with normal, age-matched rats whereas glucagon in alpha cells and somatostatin in delta cells showed increase. IGF-I, which localized to alpha cells, showed decrease. ISH detected a slightly higher expression of insulin mRNA and markedly stronger signals for glucagon and somatostatin mRNA in the islets of hypox rats. Serum glucose concentrations did not differ between the two groups although serum insulin and C-peptide were lower and serum glucagon was higher in the hypox animals. These changes were accompanied by a more than tenfold drop in serum IGF-I. The pancreatic insulin content per gram of tissue was not significantly different in hypox and normal rats. Pancreatic glucagon and somatostatin per gram of tissue were higher in the hypox animals. The pancreatic IGF-I content of hypox rats was significantly reduced. Northern blot analysis gave a 2.6-, 4.5-, and 2.2-fold increase in pancreatic insulin, glucagon, and somatostatin mRNA levels, respectively, in hypox rats, and a 2.3-fold decrease in IGF-I mRNA levels. Our results show that the fall of serum IGF-I after hypophysectomy is accompanied by a decrease in pancreatic IGF-I peptide and mRNA but by partly discordant changes in the serum concentrations of insulin and glucagon and the islet peptide and/or mRNA content of the three major islet hormones. It appears that GH deficiency resulting in a "low IGF-I state" affects translational efficiency of these hormones as well as their secretory responses. The maintenance of normoglycemia in the presence of reduced insulin and elevated glucagon serum levels, both of which would be expected to raise blood glucose, may result mainly from the enhanced insulin sensitivity, possibly due to GH deficiency and the subsequent decrease in IGF-I production

Histomorphological analysis of the urogenital diaphragm in elderly women: a cadaver study

The objective of this study was to describe the histomorphological structure of the urogenital diaphragm in elderly women using a modern morphometric procedure. Biopsies were taken from the posterior margin of the urogenital diaphragm of 22 female cadavers (mean age, 87 years) using a 60-mm punch. Hematoxylin/eosin and Goldner sections were analyzed with the Cavalieri estimator. The mean thickness of the urogenital diaphragm was 5.5 mm. The main component was connective tissue. All biopsies contained smooth muscle. Eighteen biopsies contained more smooth muscle than striated muscle. In six of 22 biopsies, no striated muscle was found. The ratio of striated to smooth muscle to connective tissue was 1:2.3:13.3. Muscle fibers were dispersed in all parts of the urogenital diaphragm. The urogenital diaphragm of elderly women mainly consists of connective tissue. Smooth muscle was also found but to a lesser extent. The frequently used English term "perineal membrane" for the urogenital diaphragm is justified and well describes our findings in elderly women

Structural basis for delta cell paracrine regulation in pancreatic islets

International audienceLittle is known about the role of islet delta cells in regulating blood glucose homeostasis in vivo. Delta cells are important paracrine regulators of beta cell and alpha cell secretory activity, however the structural basis underlying this regulation has yet to be determined. Most delta cells are elongated and have a well-defined cell soma and a filopodia-like structure. Using in vivo optogenetics and high-speed Ca2+ imaging, we show that these filopodia are dynamic structures that contain a secretory machinery, enabling the delta cell to reach a large number of beta cells within the islet. This provides for efficient regulation of beta cell activity and is modulated by endogenous IGF-1/VEGF-A signaling. In pre-diabetes, delta cells undergo morphological changes that may be a compensation to maintain paracrine regulation of the beta cell. Our data provides an integrated picture of how delta cells can modulate beta cell activity under physiological conditions

mRNA profiling for the identification of sperm and seminal plasma

mRNA profiling is a promising new method for the identification of body fluids from biological stains. In this study we aimed to establish a multiplex RT-PCR protocol for the detection and differentiation of sperm and seminal plasma. The Agilent Bioanalyzer and Nanodrop spectrophotometer were shown not to be suitable for assessing RNA quality and quantity of forensic stains. Semen specificity of the mRNA markers was successfully confirmed with singleplex PCR. Our data indicated that semen samples down to 0.1 ml and up to 20-year-old could be identified with mRNA profiling. With the semen multiplex, including 2 sperm markers (PRM1, PRM2) and 2 novel seminal plasma markers (SEMG1, PSA), samples from azoospermic men (absence of sperm in semen) are clearly distinguishable from those of normozoospermic men (having a normal sperm production). We think that our multiplex RT-PCR protocol is a reliable and sensitive method for the identification of semen in forensic samples

Synthesis, characterization and bioimaging of fluorescent labeled polyoxometalates

A fluorescent labeled Wells–Dawson type POM ({P2W17O61Fluo}) was newly synthesized and characterized by a wide range of analytical methods. {P2W17O61Fluo} was functionalized with fluorescein amine through a stable amide bond, and its long time stability was verified by UV/vis spectroscopic techniques at physiologically relevant pH values. No significant impact on the cell viability or morphology of HeLa cells was observed for POM concentrations up to 100 μg mL−1. Cellular uptake of fluorescent {P2W17O61Fluo} was monitored by confocal laser scanning microscopy. POM uptake occurs mainly after prolonged incubation times of 24 h resulting in different intracellular patterns, i.e. randomly distributed over the entire cytoplasm, or aggregated in larger clusters. This direct monitoring strategy for the interaction of POMs with cells opens up new pathways for elucidating their unknown mode of action on the way to POM-based drug development

Hypericin-bearing magnetic iron oxide nanoparticles for selective drug delivery in photodynamic therapy.

© 2015 Unterweger et al.Combining the concept of magnetic drug targeting and photodynamic therapy is a promising approach for the treatment of cancer. A high selectivity as well as significant fewer side effects can be achieved by this method, since the therapeutic treatment only takes place in the area where accumulation of the particles by an external electromagnet and radiation by a laser system overlap. In this article, a novel hypericin-bearing drug delivery system has been developed by synthesis of superparamagnetic iron oxide nanoparticles (SPIONs) with a hypericin-linked functionalized dextran coating. For that, sterically stabilized dextran-coated SPIONs were produced by coprecipitation and crosslinking with epichlorohydrin to enhance stability. Carboxymethylation of the dextran shell provided a functionalized platform for linking hypericin via glutaraldehyde. Particle sizes obtained by dynamic light scattering were in a range of 55-85 nm, whereas investigation of single magnetite or maghemite particle diameter was performed by transmission electron microscopy and X-ray diffraction and resulted in approximately 4.5-5.0 nm. Surface chemistry of those particles was evaluated by Fourier transform infrared spectroscopy and ζ potential measurements, indicating successful functionalization and dispersal stabilization due to a mixture of steric and electrostatic repulsion. Flow cytometry revealed no toxicity of pure nanoparticles as well as hypericin without exposure to light on Jurkat T-cells, whereas the combination of hypericin, alone or loaded on particles, with light-induced cell death in a concentration and exposure time-dependent manner due to the generation of reactive oxygen species. In conclusion, the combination of SPIONs’ targeting abilities with hypericin’s phototoxic properties represents a promising approach for merging magnetic drug targeting with photodynamic therapy for the treatment of cancer