Sortase A inhibitory metabolites from the roots of Pulsatilla koreana.

Three new lignans (3, 4, and 6) along with eight known lignans and phenyl propanoids were isolated from the dried roots of Pulsatilla koreana, an oriental folk medicine. Based upon the results of combined spectroscopic and chemical methods, the structures of new compounds were determined to be lignan glycosides. Included among the known compounds are three compounds (5, 7, and 8) isolated first time from this plant as well as two compounds (2 and 11) previously reported only as synthetic derivatives. These compounds significantly inhibited the action of Sortase A from Streptococcus mutans OMZ65, an isolate from human oral cavity.

Effects of magnolialide isolated from the leaves of Laurus nobilis L. (Lauraceae) on immunoglobulin E-mediated type I hypersensitivity in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Laurus nobilis L. (Lauraceae) has been used for folk medicines in the Mediterranean area and Europe to treat various disorders including skin inflammation (dermatitis) and asthma. AIM OF THE STUDY: Our aim was to investigate the scientific evaluation of the compounds from Laurus nobilis L. on immuniglobulin E (IgE)-mediated type I hypersensitivity responses in vitro such as atopic dermatitis and asthma. METHODS AND MATERIALS: Seven compounds were isolated and examined for the mast cell stabilizing effect on IgE-sensitized RBL-2H3 mast cells by measuring the ß-hexosaminidase activity. In addition, the effects on interleukin (IL)-4 production and IL-5-dependent Y16 early B cell proliferation were investigated as well as their cytotoxic effects on RBL-2H3 cells. RESULTS: Among the seven isolated compounds, magnolialide attenuated the release of ß-hexosaminidase from RBL-2H3 cells with an IC50 value of 20.2 µM, while the other compounds revealed no significant effects at concentrations tested. Furthermore, magnolialide significantly inhibited the IL-4 release with an IC50 value of 18.1 µM and IL-4 mRNA expression with an IC50 value of 15.7 µM in IgE-sensitized RBL-2H3 cells. In addition, the inhibition of IL-5-dependent proliferation of early B cells (Y16 cells) by magnolialide was demonstrated with an IC50 value of 18.4 µM. CONCLUSION: These results suggest that the magnolialide might be a candidate for the treatment of IgE-mediated hypersensitivity responses such as atopic dermatitis and asthma by inhibiting mast cell degranulation, the IL-4 production, and IL-5-dependent early B cell proliferation, key factors in the development and amplification of type I hypersensitivity reactions.

Rhododendrin ameliorates skin inflammation through inhibition of NF-κB, MAPK, and PI3K/Akt signaling.

A wide range of active compounds isolated from nature is used in clinical applications and as a source of lead compounds for drug development. Rhododendron brachycarpum has been used as an oriental herbal medicine for skin inflammatory diseases. In this study, we isolated rhododendrin from Rhododendron brachycarpum leaves and investigated its molecular mechanisms for anti-inflammatory effect. Rhododendrin showed intracellular reactive oxygen species scavenging activity and suppressed nuclear translocation of nuclear factor-κB (NF-κB) by inhibiting phosphorylation of NF-κB, inhibitor of NF-κB(IκBα), and IκBα kinase(IKKα/ß). Furthermore, rhododendrin inhibited mitogen-activated protein kinases (MAPKs), including ERK1/2, p38, and decreased c-Jun N-terminal kinase (JNK) and phosphoinositide 3-kinase (PI3K)/Akt signaling. As a result, rhododendrin reduced expression of pro-inflammatory mediators, such as cyclooxygenase-2 (COX-2), intracellular adhesion molecule-1 (ICAM-1), interleukin-1α (IL-1α), IL-1ß, IL-6, IL-8, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), chemokine (C-X-C) motif ligand 1 (CXCL1), and chemokine (C-C motif) ligand 17 (CCL17) in TNF-α/IFN-γ-stimulated keratinocytes. Notably, we demonstrated that topically applied rhododendrin alleviated skin inflammation in trinitrochlorobenzene (TNCB)-treated mouse ear skins. Collectively, these results indicate that rhododendrin is a biologically active compound that exhibits anti-inflammatory activity and is a promising candidate molecule to treat inflammatory skin diseases, such as psoriasis.

Sesquiterpenes from the leaves of Laurus nobilis L.

Ten sesquiterpenes, together with 12 known compounds were isolated from leaves of Laurus nobilis L. Based on spectroscopic analyses, the 10 compounds were determined to be eudesmane lactones and their corresponding methyl esters. Most of these compounds exhibited moderate-to-significant cytotoxicity towards K562 leukemia cells. One compound had a higher cytotoxicity than doxorubicin, while other compounds had moderate to no activity.

Acylated kaempferol glycosides from Laurus nobilis leaves and their inhibitory effects on Na+/K+-adenosine triphosphatase.

Na(+)/K(+)-adenosine triphosphatase (ATPase) inhibitors have considerable therapeutic potential against some heart diseases like congestive heart failure and cardiac arrhythmias. Through bioassay-guided separation of the leaf extract of Laurus nobilis, six acylated kaempferol glycosides (compounds 1-6) were isolated. Their structures were determined on the basis of spectroscopic analysis and comparison with reported data. All the isolates were subjected to in vitro bioassays to evaluate their inhibitory activities against Na(+)/K(+)-ATPase from porcine cerebral cortex and bacterial growth. These studies led to the identification of compounds 1-6 as potent Na(+)/K(+)-ATPase inhibitors, with IC(50) values in the range of 4.0 ± 0.1-10.4 ± 0.6 µM. These compounds also exhibited a broad spectrum of antibacterial activity. In particular, compounds 4 and 6 showed potent inhibitory activities against several bacterial strains, except Escherichia coli, with minimum inhibitory concentration (MIC) values in the range of 0.65-2.08 µg/mL. Thus, L. nobilis-derived acylated kaempferol glycosides may have a potential to be leads for the development of Na(+)/K(+) ATPase inhibitors (1-6) and antibacterial agents (4, 6).

In vitro Na+/K+-ATPase inhibitory activity and antimicrobial activity of sesquiterpenes isolated from Thujopsis dolabrata.

A series of sesquiterpenes and hinokitiol-related compounds (1-15) was isolated from the essential oil of Thujopsis dolabrata Sieb. et Zucc. var. hondai Makino, and their structures were determined by combined spectroscopic analyses. The inhibitory effects of these compounds on microbial cell growth and Na(+)/K(+)-ATPase were evaluated in vitro. It was found that (-)-elema-1,3,11(13)-trien-12-ol (5), α,ß,γ-costol (8), and chamigrenol (11) inhibit the activities of Na(+)/K(+)-ATPase, with IC(50) values of 11.2 ± 0.11, 12.2 ± 0.09, and 15.9 ± 0.54 µg/mL, respectively. Thujopsene (1), cedrol (9), γ-cuparenol (10), and chamigrenol (11) showed potent antibacterial activity, with MIC values in the range of 25-50 µg/mL, and ß-thujaplicin (12) exhibited a broad spectrum of antibacterial and antifungal activity. These results indicate that these isolated compounds are promising candidates for the development of potent Na(+)/K(+) ATPase inhibitors and antimicrobial agents.