Bioactivities of Quinic Acids from Vitex rotundifolia Obtained by Supercritical Fluid Extraction.

Acyl-quinic acids (AQAs), present in various plants with many health benefits, are regarded as therapeutic agents in the prevention and treatment of chronic and cardiovascular diseases. The molecular network-guided identification of ten AQA compounds, two new (5 and 7) and eight known compounds, were isolated from V. rotundifolia L. f. by using a newly applied extraction method. Their structures were determined through spectroscopic means, reaction mixtures, and modified Mosher and PGME techniques. These compounds were assessed for their anti-inflammatory and antioxidant capabilities. Notably, compounds 1, 3, 4, 6, 8, and 9 exhibited notable DPPH radical scavenging activity. In LPS-induced HT-29 cells, compounds 2-7 significantly inhibited IL-8 production. Furthermore, compounds 3-5 and 7 markedly suppressed NO production, while compounds 1-10 effectively inhibited IL-6 production in LPS-induced RAW264.7 cells. Western blot analyses revealed that compounds 3-5, and 7 reduced iNOS and COX-2 expression, and compounds 2-5, 7, and 8 also diminished the expression levels of p38 MAPK phosphorylation. Docking studies demonstrated the active compounds' binding affinity with the IL-8, iNOS, COX-2, and p38 MAPK proteins through interactions with essential amino acids within the binding pockets of complexes. The findings suggest that compounds 1, 3, 4, 6, 8, and 9, and compounds 3-5, and 7, hold promise as potential therapeutic agents for treating antioxidative and inflammatory diseases, respectively.

The Potential of Campanula takesimana Callus Extract to Enhance Skin Barrier Function.

Atopic dermatitis (AD) is a prevalent inflammatory skin disease characterized by epidermal barrier dysfunction and Th2-skewed inflammation. Campanula takesimana (C. takesimana), a Korean endemic plant grown on Ulleng Island, has long been associated with a traditional alternative medicine for asthma, tonsillitis, and sore throat. In this study, we reported the effect of C. takesimana callus extract on upregulating epidermal barrier-related proteins dysregulated by Th2 cytokines. C. takesimana callus extract induced the expression of skin barrier proteins, such as filaggrin, claudin-1, and zonula occludens-1, in both human primary keratinocytes and Th2-induced AD-like skin-equivalent models. Additionally, RNA sequencing analysis demonstrated that C. takesimana callus extract partially restored Th2 cytokine-induced dysregulation of the epidermal development and lipid metabolic pathways. Considering the advantages of callus as a sustainable eco-friendly source of bioactive substances, and its effect on skin barrier proteins and lipid metabolic pathways, C. takesimana callus extracts can possibly be utilized to improve the integrity of the skin barrier.

Cannabidiol mediates epidermal terminal differentiation and redox homeostasis through aryl hydrocarbon receptor (AhR)-dependent signaling.

BACKGROUND: Cannabidiol, a non-psychoactive phytocannabinoid, has antioxidant and anti-inflammatory activity in keratinocytes. However, the signaling pathway through which cannabidiol exerts its effect on keratinocytes or whether it can modulate keratinocyte differentiation has not been fully elucidated yet. OBJECTIVE: We investigated whether cannabidiol modulates epidermal differentiation and scavenges reactive oxygen species through the aryl hydrocarbon receptor (AhR) in keratinocytes and epidermal equivalents. METHODS: We investigated the cannabidiol-induced activation of AhR using AhR luciferase reporter assay, qRT-PCR, western blot, and immunofluorescence assays. We also analyzed whether keratinocyte differentiation and antioxidant activity are regulated by cannabidiol-induced AhR activation. RESULTS: In both keratinocytes and epidermal equivalents, cannabidiol increased both the mRNA and protein expression of filaggrin, involucrin, NRF2, and NQO1 and the mRNA expression of the AhR target genes, including CYP1A1 and aryl hydrocarbon receptor repressor. Additionally, cannabidiol showed antioxidant activity that was attenuated by AhR knockdown or co-administration with an AhR antagonist. Moreover, cannabidiol increased the ratio of OVOL1/OVOL2 mRNA expression, which is a downstream regulator of AhR that mediates epidermal differentiation. In addition to increased expression of barrier-related proteins, cannabidiol-treated epidermal equivalent showed a more prominent granular layer than the control epidermis. The increased granular layer by cannabidiol was suppressed by the AhR antagonist. CONCLUSION: Cannabidiol can be a modulator of the AhR-OVOL1-filaggrin axis and AhR-NRF2-NQO1 signaling, thus indicating a potential use of cannabidiol in skin barrier enhancement and reducing oxidative stress.

Phytoncide, Nanochemicals from Chamaecyparis obtusa, Inhibits Proliferation and Migration of Vascular Smooth Muscle Cells.

Phytoncide, nanochemicals extracted from Chamaecyparis obtusa (C. obtusa), is reported to possess many pharmacological activities including immunological stimulating, anti-cancer, antioxidant, and antiinflammatory activities. However, the effect of phytoncide in vascuar diseases, especially on the behavior of vascular smooth muscle cells, has not yet been clearly elucidated. Therefore, in the present study, we investigated the effects of 15 kinds of phytoncide by various extraction conditions from C. obtusa on the proliferation and migration in rat aortic smooth muscle cells (RAoSMCs). First of all, we determined the concentration of each extracts not having cytotoxicity by MTT assay. We observed that the proliferation rate measured using BrdU assay was significantly reduced by supercritical fluid, steam distillation, Me-OH, and hexane extraction fraction in order with higher extent, respectively. Moreover, the treatment of above nanofractions inhibit the migration of RAoSMCs by 40%, 60%, and 30%, respectively, both in 2-D wound healing assay and 3-D boyden chamber assay. Immunoblot revealed that the phosphorylated levels of Akt and ERK were significantly reduced in nanofractions treated RAoSMCs. Taken together, these data suggest that phytoncide extracted from C. obtusa inhibits proliferation and migration in RAoSMCs via the modulation of phosphorylated levels of Akt and ERK. Therefore, phytoncide nanomolecules might be a potential therapeutic approach to prevent or treat atheroscrelosis and restenosis.

Toxicity of Myristica fagrans seed compounds against Blattella germanica (Dictyoptera: Blattellidae).

The insecticidal constituents of hexane-soluble fraction from a methanolic extract of the seeds from Myristica fragrans (Myristicaceae) against adult females of Blattella germanica (L.) (Dictyoptera: Blattellidae) were analyzed by gas chromatography and gas chromatography-mass spectrometry. The insecticidal activity of 13 Myristica seed compounds against female B. germanica was examined by using the filter-paper contact toxicity and vapor phase toxicity bioassays. Results were compared with those of the other 23 known compounds of Myristica seed and currently used insecticides: dichlorvos, deltamethrin, permethrin, and propoxur. In contact toxicity tests using female B. germanica, (IS)-(-) -beta-pinene (0.06 mg/cm2) was the most toxic insecticide, based on 24-h LD50 values. The insecticidal activity of this compound was comparable with that of permethrin (0.05 mg/cm2). (1R)-(+) -Camphor, (1S)-(-) -camphor, dipentene, (1R)-(+) -3-pinene, and (+)-alpha-terpineol (0.10-0.14 mg/cm2) were more toxic than propoxur (0.19 mg/cm2). (E)-Sabinene hydrate and propoxur were almost equitoxic. Potent insecticidal activity also was observed with (R)-(+) -citronellal, (S)-(-) -citronellal, (R)-(-) -alpha-phellandrene, (1S)-(-) -alpha-pinene, (1R)-(+) -alpha-pinene, and safrole (0.27-0.48 mg/cm2). In vapor phase toxicity tests, the compounds tested were effective in closed but not in open containers. These results indicate that the effect of these compounds was largely a result of action in the vapor phase. Myristica seed compounds described merit further study as potential insecticides or as leads for the control of cockroaches.

Vapor phase toxicity of marjoram oil compounds and their related monoterpenoids to Blattella germanica (Orthoptera: Blattellidae).

The toxicity of marjoram, Origanum majorana L., oil, 41 monoterpenoids, and 2 sesquiterpenoids against adult females of the German cockroach, Blattella germanica L., was examined using direct contact and vapor phase toxicity bioassays and compared with those of deltamethrin, dichlorvos, permethrin, and propoxur, four commonly used insecticides. In a filter-paper contact toxicity bioassay, the adulticidal activities of pulegone (0.06 mg/cm2), (+/-)-camphor (0.07 mg/cm2), and verbenone (0.07 mg/cm2) were comparable to that of permethrin (0.05 mg/cm2) but more pronounced than that of propoxur (0.18 mg/cm2), as judged by the 24-h LC50 values. These compounds were less effective than either deltamethrin (0.013 mg/cm2) or dichlorvos (0.007 mg/cm2). The toxicity of marjoram oil, thymol, alpha-terpineol, (-)-alpha-thujone, linalool, 1,8-cineole, (-)-camphor, and (+)-carvone, ranging from 0.08 to 0.18 mg/cm2, was higher than that of propoxur. In vapor phase toxicity tests, verbenone (11.48 mg/L air) was the most toxic compound followed by (-)-alpha-thujone (18.43 mg/L of air), thymol (18.76 mg/L of air), alpha-terpineol (21.89 mg/L of air), (+/-)-camphor (24.59 mg/L of air), linalool (26.20 mg/L of air), and marjoram oil (38.28 mg/L of air) on the basis of the 24-h LC50 values. Dichlorvos (0.07 mg/L of air) was the most potent fumigant. Structure-activity relationships indicate that structural characteristics, such as degrees of saturation and types of functional groups rather than types of carbon skeleton, and hydrophobicity and vapor pressure parameters appear to play a role in determining the monoterpenoid toxicities to adult B. germanica. Marjoram oil and the monoterpenoids described merit further study as potential fumigants or leads for the control of B. germanica.

Acaricidal activity of active constituent isolated in Chamaecyparis obtusa leaves against Dermatophagoides spp.

Acaricidal activities of materials derived from Chamaecyparis obtusa leaves against Dermatophagoides farinae and Dermatophagoides pteronyssinus were examined using the dry film method and compared with that of commercial benzyl benzoate and N,N-diethyl-m-toluamide (DEET). The active constituent of the C. obtusa leaves was identified as beta-thujaplicin (C10H12(O2)) by spectroscopic analyses. Responses varied with dose. On the basis of a 24 h LC50 value, acaricidal activity against D. farinaewas more pronounced with beta-thujaplicin (72.2 mg/m2) than benzyl benzoate (89.9 mg/m2) and DEET (377 mg/m2). Acaricidal activity against D. pteronyssinus was more pronounced in beta-thujaplicin (62.1 mg/m2) than benzyl benzoate (72.4 mg/m2) and DEET (193 mg/m2). These results indicate that acaricidal activity of C. obtusa leaves likely results from by beta-thujaplicin. Beta-thujaplicin merits further study as potential house dust mite control agents or lead compounds.

Mosquito larvicidal activity of active constituent derived from Chamaecyparis obtusa leaves against 3 mosquito species.

Mosqutio larvicidal activity of Chamaecyparis obtusa leaf-derived materials against the 4th-stage larvae of Aedes aegypti (L.), Ochlerotatus togoi (Theobald), and Culex pipiens pallens (Coquillett) was examined in the laboratory. A crude methanol extract of C. obtusa leaves was found to be active (percent mortality rough) against the 3 species larvae; the hexane fraction of the methanol extract showed a strong larvicidal activity (100% mortality) at 100 ppm. The bioactive component in the C. obtusa leaf extract was characterized as beta-thujaplicin by spectroscopic analyses. The LC50 value of beta-thujaplicin was 2.91, 2.60, and 1.33 ppm against Ae. aegypti, Oc. togoi, and Cx. pipiens pallens larvae. This naturally occurring C. obtusa leaves-derived compound merits further study as a potential mosquito larval control agent or lead compound.

Larvicidal activity of leguminous seeds and grains against Aedes aegypti and Culex pipiens pallens.

Larvicidal activity of methanol extracts of 26 leguminous seeds and 20 grains against early 4th-stage larvae of Aedes aegypti and Culex pipiens pallens was examined. At 200 ppm of the extracts from Cassia obtusifolia, Cassia tora, and Vicia tetrasperma, more than 90% mortality was obtained in larvae of Ae. aegypti and Cx. pipiens pallens. Extract of C. tora gave 86.7 and 100% mortality in the larvae of Ae. aegypti and Cx. pipiens pallens at 40 ppm but 59.2 and 78.3% mortality against larvae of Ae. aegypti and Cx. pipiens pallens at 20 ppm, respectively. At 40 ppm, extract of C. obtusifolia caused 51.4 and 68.5% mortality of the 4th-stage larvae of Ae. aegypti and Cx. pipiens pallens, respectively. Larvicidal activity of extract of C obtusifolia was significantly reduced when used at 20 ppm. Further studies of these plants as possible agents for mosquito control are warranted.