The Effect of Herbal Medicinal Products on Psoriasis-Like Keratinocytes.

Psoriasis is a chronic inflammatory skin disease characterized by hyperproliferation of keratinocytes and expression of pro-inflammatory cytokines in the epidermis. New biological drugs were developed for the systemic treatment of moderate to severe psoriasis. However, products for the topical treatment of mild psoriasis are still required. Here, we examined the effect of natural compounds on psoriasis-like keratinocytes in vitro and ex vivo. Psoriasis-like keratinocytes were generated by treating human primary keratinocytes with the psoriasis-associated cytokines IL-17A, TNF-α and IL-22. Initially, 10 botanical extracts from Ayurvedic Medicine, Traditional Chinese Medicine, Northern American traditional medicine and Occidental Monastic Medicine were investigated using BrdU assays and IL-6 and IL-8 ELISAs. Curcuma amada, Humulus lupulus and Hypericum perforatum turned out to be the most effective plant extracts. In vitro, the plant extracts inhibited the expression of anti-microbial peptides (ß-defensin 2), the hyperproliferation marker keratin 17, the glucose transporter 1 and downregulated the nuclear translocation of NF-κB and pSTAT3. In an ex vivo psoriasis model, Humulus lupulus displayed the most prominent anti-proliferative and anti-inflammatory effect. In conclusion, among the plant extracts investigated, Humulus lupulus showed the most promising anti-psoriatic effect. It is an interesting candidate for topical psoriasis treatment that should be further studied in clinical trials.

In-vitro evaluation of antimicrobial and insect repellent potential of supercritical-carbon dioxide (SCF-CO2) extracts of selected botanicals against stored product pests and foodborne pathogens.

In the present study, the antimicrobial and the insect repellent activity of 16 botanical extracts obtained by supercritical CO2 (SCF) extraction were evaluated. The present investigation was conducted as there is a necessity for exploration of natural botanical extracts that target both stored product insects and microbes. The antimicrobial activity was studied by disc diffusion and broth microdilution methods against ten microbial species, including Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis and Listeria monocytogenes), Gram-negative bacteria (Escherichia coli and Salmonella enterica), and fungi (Aspergillus flavus, Aspergillus paraciticus, Aspergillus ochraceous, Aspergillus niger and Penicillium verrucosum). Repellency assay was carried out by area preference method against three coleopteran insects (Tribolium castaneum, Rhyzopertha dominica and Sitophilus oryzae). Among all the extracts, thyme and ajwain were effective against all the tested bacteria with a minimum inhibition concentration (MIC) of 256-1024 µg/mL. Hop extract resulted in better antibacterial activity against all the tested Gram-positive bacteria with a MIC of 32-64 µg/mL. Oregano, thyme and ajwain extracts showed broad-spectrum antifungal activity against all the tested fungi with MIC of 128-1024 µg/mL. Most of the extracts exhibited class V (80.1-100%) repellency against T. castaneum. Extracts of hop, ajwain and thyme were found to have strong repellency against T. castaneum and R. dominica. Therefore, SCF extracts of ajwain and thyme can be explored further for the application of bio-extracts as a growth limiting factors in a microcosm where such consortia thrive.

Anti-Inflammatory Effect of a Novel Topical Herbal Composition (VEL-091604) Consisting of Gentian Root, Licorice Root and Willow Bark Extract.

The anti-inflammatory properties of the topical herbal composition VEL-091604 with gentian root, licorice root, and willow bark extract were assessed in a randomized, prospective, placebo-controlled, double-blind ultraviolet (UV)-erythema test study with 42 healthy volunteers in comparison to 1% hydrocortisone acetate. The efficacy and tolerability of VEL-091604 cream 2 times daily over 2 wk was evaluated in an open-label, prospective proof of concept study in 10 subjects with atopic dermatitis using a lesional SCORAD severity score. In the UV-erythema test VEL-091604 cream significantly reduced inflammation compared to placebo and was as effective as 1% hydrocortisone acetate. The clinical study with atopic subjects revealed a significant and rapid reduction of the lesional SCORAD severity score in the test areas after 1 and 2 wk. No adverse events were recorded. It is concluded that the herbal cream VEL-091604 with licorice root, willow bark, and gentian root extract display anti-inflammatory properties in vivo. It is a promising new treatment option for atopic dermatitis that warrants further investigation in controlled studies.

The Herbal Bitter Drug Gentiana lutea Modulates Lipid Synthesis in Human Keratinocytes In Vitro and In Vivo.

Gentiana lutea is a herbal bitter drug that is used to enhance gastrointestinal motility and secretion. Recently we have shown that amarogentin, a characteristic bitter compound of Gentiana lutea extract (GE), binds to the bitter taste receptors TAS2R1 and TAS2R38 in human keratinocytes, and stimulates the synthesis of epidermal barrier proteins. Here, we wondered if GE also modulates lipid synthesis in human keratinocytes. To address this issue, human primary keratinocytes were incubated for 6 days with GE. Nile Red labeling revealed that GE significantly increased lipid synthesis in keratinocytes. Similarly, gas chromatography with flame ionization detector indicated that GE increases the amount of triglycerides in keratinocytes. GE induced the expression of epidermal ceramide synthase 3, but not sphingomyelinase. Lipid synthesis, as well as ceramide synthase 3 expression, could be specifically blocked by inhibitors of the p38 MAPK and PPARγ signaling pathway. To assess if GE also modulates lipid synthesis in vivo, we performed a proof of concept half side comparison on the volar forearms of 33 volunteers. In comparison to placebo, GE significantly increased the lipid content of the treated skin areas, as measured with a sebumeter. Thus, GE enhances lipid synthesis in human keratinocytes that is essential for building an intact epidermal barrier. Therefore, GE might be used to improve skin disorders with an impaired epidermal barrier, e.g., very dry skin and atopic eczema.

In Vivo Antitumor Effect of Supercritical CO2 Extract of Mango Ginger ( Curcuma amada Roxb) in U-87MG Human Glioblastoma Nude Mice Xenografts.

Glioblastoma multiforme (GBM) is one the most aggressive and lethal human neoplasms with poor prognosis and very limited positive treatment options. The antitumor effect of supercritical CO2 extract of mango ginger ( Curcuma amada Roxb) (CA) with and without irinotecan (IR) was analyzed in U-87MG human glioblastoma multiforme (GBM) cells in vitro and in nude mice xenografts. CA is highly cytotoxic to GBM cells and is synergistic with IR as indicated by the combination index values of <1 in the CompuSyn analysis. CA inhibits tumor growth rate in GBM xenografts, the inhibition rate being higher than in IR treated group. GBM xenograft mice treated with IR + CA combination showed almost complete inhibition of tumor growth rate. Gene expression analysis of xenograft tumors indicated that IR + CA treatment significantly downregulated anti-apoptotic (Bcl-2 and mutant p53), inflammation-associated (COX-2) and cell division-associated (CCNB2) genes and upregulated pro-apoptotic genes (p21 and caspase-3). These results confirmed the therapeutic efficiency of IR + CA combination against GBM and the need for further clinical investigations.

CO2 Plant Extracts Reduce Cholesterol Oxidation in Fish Patties during Cooking and Storage.

Cholesterol oxidation products (COPs) in foods may pose risks for human health. Suitable antioxidants can reduce the formation of COPs in industrial products. Consumer awareness of food additives has brought a need for more natural alternatives. This is the first study on the effects of supercritical CO2 extracts of rosemary, oregano, and an antimicrobial blend of seven herbs, tested at two levels (1 and 3 g/kg fish), against cholesterol oxidation in patties made of a widely consumed fish species, Atlantic salmon (Salmo salar), during baking and storage. Cholesterol oxidation was reduced by the extracts as indicated by lowered levels of 7α-hydroxycholesterol, 7ß-hydroxycholesterol, and 7-ketocholesterol, which were quantified by GC-MS. The total amount of COPs was smaller in all of the cooked samples containing the plant extracts (<1 µg/g extracted fat) than in the cooked control (14 µg/g). Furthermore, the plant extracts exhibited protective effects also during cold storage for up to 14 days.

Effects of CO2 plant extracts on triacylglycerol oxidation in Atlantic salmon during cooking and storage.

Increasing concern of consumers on the safety of synthetic food additives has created high interest in natural preservatives in food industry. Plant extracts produced by supercritical CO2 technology from rosemary (R), oregano (O) and an antimicrobial blend (AB) consisting of seven different plants were studied for their effects on lipid oxidation in Atlantic salmon (Salmo salar). Fish pieces were marinated with rapeseed oil containing 0, 1, 2 or 4 g of plant extracts/kg of fish. After cooking the pieces were stored in refrigerator for 26 days. Peroxide values (PVs) were determined and oxidised triacylglycerols (TAGs) measured by UHPLC-ESI/MS at 0, 7, 14 and 26 days of storage. During the first two weeks of storage, AB delayed oxidation by at least one week compared to control samples as shown by PVs (<10 meq. O2) and by the oxidised TAGs. Oregano and rosemary showed also some antioxidative potential.

Anticancer potential and mechanism of action of mango ginger (Curcuma amada Roxb.) supercritical CO2 extract in human glioblastoma cells.

Mango ginger (Curcuma amada Roxb.) is among the less-investigated species of Curcuma for anticancer properties. We have investigated the anticancer potential and the mechanism of action of a supercritical CO2 extract of mango ginger (CA) in the U-87MG human glioblastoma cell line. CA demonstrated higher cytotoxicity than temozolomide, etoposide, curcumin, and turmeric force with IC50, IC75, and IC90 values of 4.92 µg/mL, 12.87 µg/mL, and 21.30 µg/mL, respectively. Inhibitory concentration values of CA for normal embryonic mouse hypothalamus cell line (mHypoE-N1) is significantly higher than glioblastoma cell line, indicating the specificity of CA against brain tumor cells. CompuSyn analysis indicates that CA acts synergistically with temozolomide and etoposide for the cytotoxicity with combination index values of <1. CA treatment also induces apoptosis in glioblastoma cells in a dose-dependent manner and downregulates genes associated with apoptosis, cell proliferation, telomerase activity, oncogenesis, and drug resistance in glioblastoma cells.

Improved neuroprotective effects by combining Bacopa monnieri and Rosmarinus officinalis supercritical CO2 extracts.

Ethnobotanical evidence suggests that herbs such as brahmi (Bacopa monnieri) and rosemary (Rosmarinus officinalis) may possess antioxidant and neuroprotective properties. We compared the antioxidant and neuroprotective effects of supercritical extract of Bacopa monnieri and rosemary antioxidant extract obtained from Rosmarinus officinalis as well as their combination to examine the effects on human glial (U-87 MG) and embryonic mouse hypothalamus cells. Bacopa monnieri extract, rosemary antioxidant extract, and their combination (1:1) are not cytotoxic in both glial and embryonic mouse hypothalamus cell lines up to 200 µg/mL concentration. The combination of extracts of Bacopa monnieri + rosemary antioxidant has better antioxidant potential and antilipid peroxidation activity than either agent alone. Although the extract of Bacopa monnieri + rosemary antioxidant showed almost similar inhibition of phospho tau expression as Bacopa monnieri or rosemary antioxidant extract alone, the combination has better inhibitory effect on amyloid precursor protein synthesis and higher brain-derived neurotrophic factor production in hypothalamus cells than single agents. These results suggest that the extract of Bacopa monnieri + rosemary antioxidant is more neuroprotective than Bacopa monnieri or rosemary antioxidant extract.

Composition and biological activity of different extracts from Schisandra sphenanthera and Schisandra chinensis.

Plants of the Schisandraceae family contain a variety of pharmacologically active lignans like schizandrin, deoxyschizandrin, deangeloylgomisin B, gomisin A, gomisin O, gamma-schizandrin and isogomisin O. Here we have compared the composition of different polar and non-polar extracts of Schisandra sphenanthera and Schisandra chinensis. We also have screened the extracts for antiproliferative and anti-inflammatory effects in different cell-based and cell-free assays. Extracts produced with the non-polar solvents CO(2), hexane and CO(2)/5% ethanol had a similar composition. In contrast, polar extraction with ethanol provided a considerably higher yield, but a lower content of volatiles and lignans in comparison to the non-polar extracts. The proliferation of the epidermal cell lines HaCaT and A431 was dose-dependently inhibited by both the Schisandra sphenanthera and Schisandra chinensis extracts, the non-polar extracts being superior to the polar ones. The non-polar Schisandra sphenanthera extract was the most active with a half-maximal inhibitory concentration of 20 microg/mL. In a cell-free enzyme inhibition assay with recombinant cyclooxygenase-2 (COX-2) the non-polar Schisandra sphenanthera extract dose-dependently inhibited COX-2 catalysed prostaglandin (PG) production (IC(50) = 0.2 microg/mL). It also reduced the ultraviolet-B (UVB)-induced PGE (2) production (IC(50) = 4 microg/mL) and COX-2 expression in HaCaT keratinocytes. We conclude that non-polar SChisandra extracts obtained by CO(2) extraction might be useful in the prevention and treatment of hyperproliferative and inflammatory skin diseases.

Distribution of aflatoxins between extract and extraction residue of paprika using supercritical carbon dioxide.

Paprika powder, naturally contaminated with aflatoxins, was extracted by supercritical carbon dioxide at standard conditions (300 bar and 50 degrees C). A lipophilic top phase and an aqueous base phase were obtained. These and the extraction residue were analysed by HPLC for aflatoxins. The main quantity of aflatoxins, about 60% of aflatoxin B1 and about 70% of aflatoxin B2 related to the original paprika powder, was found to be located in the extraction residue. This confirms the results of previous studies with other spices and demonstrates that the use for flavouring purposes of supercritical carbon dioxide extracts, rather than natural spice, offers potential application in reducing aflatoxin levels in spiced foods.

Phenolic diterpenes, flavones, and rosmarinic acid distribution during the development of leaves, flowers, stems, and roots of Rosmarinus officinalis. Antioxidant activity.

The distribution of six compounds with three different polyphenol skeletons have been studied in Rosmarinus officinalis: phenolic diterpenes (carnosic acid, carnosol, and 12-O-methylcarnosic acid), caffeoyl derivatives (rosmarinic acid), and flavones (isoscutellarein 7-O-glucoside and genkwanin), each showing a characteristic behavior and distribution during the vegetative cycle. Only in leaves were all six compounds present, and the highest accumulation rate was related with the young stages of development. Rosmarinic acid showed the highest concentrations of all the polyphenols in all organs. The distribution of this acid in leaves, flowers, and stems suggests that in the first stages of flower growth, levels were due to in situ biosynthesis, and in the last stages, the contribution of transport phenomena was increased. The antioxidant activity of six extracts with different polyphenolic composition was evaluated in aqueous and lipid systems. The results clearly suggest that rosemary extracts are excellent antioxidants in both aqueous and lipid systems.