Baicalin Down-Regulates IL-1ß-Stimulated Extracellular Matrix Production in Nasal Fibroblasts.

PURPOSE: Baicalin, a Chinese herbal medicine, has anti-fibrotic and anti-inflammatory effects. The aims of present study were to investigate the effects of baicalin on the myofibroblast differentiation, extracellular matrix production, migration, and collagen contraction of interleukin (IL)-1ß-stimulated nasal fibroblasts and to determine the molecular mechanism of baicalin in nasal fibroblasts. METHODS: Nasal fibroblasts were isolated from the inferior turbinate of patients. Baicalin was used to treat IL-1ß-stimulated nasal fibroblasts. To evaluate cytotoxicity, a 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide assay was used. The expression levels of α-smooth muscle actin (SMA), fibronectin, phospho-mitogen-activated protein kinase (p-MAPK), p-Akt, p-p50, p-p65, and p-IκBα were measured by western blotting, reverse transcription-polymerase chain reaction (RT-PCR),or immunofluorescence staining. Fibroblast migration was analyzed with scratch assays and transwell migration assays. Total collagen was evaluated with the Sircol collagen assay. Contractile activity was measured with a collagen gel contraction assay. RESULTS: Baicalin (0-50 µM) had no significant cytotoxic effects in nasal fibroblasts. The expression of α-SMA and fibronectin were significantly down-regulated in baicalin-treated nasal fibroblasts. Migration, collagen production, and contraction of IL-1ß-stimulated nasal fibroblasts were significantly inhibited by baicalin treatment. Baicalin also significantly down-regulated p-MAPK, p-Akt, p-p50, p-p65, and p-IκBα in IL-1ß-stimulated nasal fibroblasts. CONCLUSIONS: We showed that baicalin down-regulated myofibroblast differentiation, extracellular matrix production, migration, and collagen contraction via the MAPK and Akt/ NF-κB pathways in IL-1ß-stimulated nasal fibroblasts.

Epigallocatechin-3-gallate inhibits collagen production of nasal polyp-derived fibroblasts.

Nasal polyps are chronic inflammatory conditions characterized by myofibroblast differentiation and extracelluar matrix accumulation. The major catechin from green tea is (-)-epigallocatechin-3-gallate (EGCG), which has garnered attention for its potential to prevent oxidative stress-related diseases. The purpose of this study was twofold: (i) to determine the effect of EGCG on fibroblast differentiation into myofibroblasts and extracellular matrix accumulation in transforming growth factor (TGF)-ß1-induced nasal polyp-derived fibroblasts (NPDFs) and (ii) to determine if the antioxidative effect of EGCG on reactive oxygen species (ROS) production in TGF-ß1-induced NPDFs is involved in the aforementioned processes. TGF-ß1-induced NPDFs were treated with or without EGCG. α-smooth muscle actin (α-SMA) and collagen type I mRNA were analyzed by reverse transcription-polymerase chain reaction. α-SMA protein was also detected using immunofluorescent staining. The amount of total soluble collagen was analyzed by Sircol collagen assay. ROS activity was measured by the nitroblue tetrazolium reduction assay and visualized by fluorescent microscopy. EGCG significantly inhibited expressions of α-SMA and collagen type I mRNA and reduced α-SMA and collagen protein levels at concentrations of 10-20 µg/mL. EGCG also inhibited TGF-ß1-induced ROS production at the same concentrations. These results suggest the possibility that EGCG may be effective at inhibiting the development of nasal polyps through an anti-oxidant effect.

Berberine inhibits myofibroblast differentiation in nasal polyp-derived fibroblasts via the p38 pathway.

The purposes of this study were to determine whether berberine has any effect on phenotype changes and extracellular matrix (ECM) production in nasal polyp-derived fibroblasts (NPDFs) and to investigate the underlying molecular mechanism. NPDFs were pre-treated with berberine prior to induction by transforming growth factor (TGF)-ß1. The expression of α-smooth muscle actin (SMA) and collagen type I mRNA was determined by a reverse transcription-polymerase chain reaction, and the expression of α-SMA protein and collagen type I was determined by western blotting and/or immunofluorescent staining. The total soluble collagen production was analysed by the SirCol collagen assay. The expression of several signaling molecules of the TGF-ß1 pathway was evaluated by western blot analysis. In TGF-ß1-induced NPDFs, berberine significantly inhibited the expression of α-SMA and collagen type I mRNA and reduced α-SMA and collagen protein levels. Berberine only suppressed the expression of pp38 among the evaluated signaling molecules. SB203580 (a specific inhibitor of p38 kinase) markedly suppressed the increased expression of collagen type I and α-SMA in TGF-ß1-induced NPDFs. Berberine exerts suppressive effects on phenotype changes and ECM production in NPDFs via p38 signaling pathway interference. The findings provide new therapeutic options for ECM production in nasal polyps.

Naringenin inhibits extracellular matrix production via extracellular signal-regulated kinase pathways in nasal polyp-derived fibroblasts.

Naringenin, a natural predominant flavanone derived from plant food, has antifibrotic activity. The purposes of this study were to determine the effect of naringenin on myofibroblast differentiation and extracellular matrix (ECM) production in nasal polyp-derived fibroblasts (NPDFs) and to determine the molecular mechanism of the effect of naringenin on NPDFs. NPDFs were incubated and treated with transforming growth factor (TGF)-ß1. The expression of alpha smooth muscle actin (α-SMA), fibronectin, and collagen type I mRNA was determined by a reverse transcription-polymerase chain reaction, and the expression of those proteins was determined by immunofluorescence staining or Western blotting. Expression of several signaling molecules of the TGF-ß1 pathway was evaluated by Western blot analysis. Naringenin inhibits expression of an indicator of myofibroblast differentiation (α-SMA) and ECM production, including collagen type 1 and fibronectin. Naringenin only suppressed the expression of extracellular signal-regulated protein kinase (pERK)1/2 among evaluated signaling molecules. PD98059 (a specific inhibitor of ERK1/2 kinase) also suppressed the increased expression of fibronectin, collagen type I, and α-SMA in TGF-ß1-induced NPDFs. These results suggest the possibility that naringenin may play an inhibitory role in the production of the ECM in the development of nasal polyps.

A comparative pilot study of symptom improvement before and after phototherapy in Korean patients with perennial allergic rhinitis.

Although allergic rhinitis is not life threatening, it significantly influences the quality of a patient's life. This study is intended to evaluate the safety and efficacy of phototherapy with low-level energy of a 650 nm laser irradiation system in perennial allergic rhinitis patients. This clinical trial was an open-label, single-center study with 42 perennial allergic rhinitis subjects. Following laser irradiation in the nasal cavity with a laser irradiation system, the efficacy at weeks 1 through 4 was determined. The symptoms were scored with four parameters (nasal obstruction, rhinorrhea, sneezing and itching) before and after illumination of the laser, and the total score was recorded. A survey of Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) was conducted by patients before and after treatment. Following treatment, significant improvement in the clinical symptoms of nasal obstruction (P < 0.001), rhinorrhea (P = 0.005), sneezing (P = 0.001) and itching (P = 0.003) was reported by 68% of perennial allergic rhinitis patients. The overall RQLQ scores significantly improved by 45% from the baseline with the treatment after 4 weeks. These results indicate that phototherapy is an effective modality for treating perennial allergic rhinitis and is another option in the steroid-free management of immune-mediated mucosal diseases.

Common and differential brain responses in men and women to nonverbal emotional vocalizations by the same and opposite sex.

Nonverbal emotional vocalizations are one of the most elementary ways of communicating in humans. We examined the impact of sex differences on neural responses to laughter and crying produced by the same and opposite sex. Thirty subjects (15 women) underwent functional magnetic resonance imaging during a sex identification task for laughter, crying, and neutral voices. The parahippocampal gyrus was involved in both men and women while hearing laughter of the same sex, suggesting greater positive emotional processing and greater attention toward emotional context in response to laughter of the same sex than of the opposite sex. The posterior cingulate was involved in both men and women while hearing crying of the opposite sex, suggesting that empathic processing may occur more in response to crying of the opposite sex than of the same sex. Furthermore, brain responses to crying of the opposite sex seem to reflect upon men's efforts to perform emotional regulation and women's empathic concerns.

Effects of microelectrical current on migration of nasal fibroblasts.

BACKGROUND: Migration of fibroblasts is critical in wound healing. The question of how wounded electric fields guide migration of nasal fibroblasts remains to be elucidated. This study was designed to determine morphology, directedness, and migration rate of nasal fibroblasts during microcurrent application, which is simulated by an endogenous electric field at the vicinity of the wound. METHODS: Nasal fibroblasts were exposed to a microelectric field at 50, 100, and 250 mV/mm for 3 hours at 37°C. In this experiment, the field polarity was reversed for an additional 3 hours. During in vitro testing, the cells were incubated in a newly developed miniature, microcurrent generating chamber system, with 5% CO(2), at 37°C; the media was circulated by a pump system. A wound was created by scratching a cell-free area (∼150 µm wide) into a confluent monolayer. The average migration speed was calculated as the distance traveled by the cell divided by time. RESULTS: A microelectric field of 100 mV/mm or more induced significant cell migration in the direction of the cathode. Trajectory speeds at 50, 100, and 250 mV/mm were 9.8 ± 0.3, 11.8 ± 0.3, and 13.5 ± 0.9 µm/mm, respectively. A significant difference was observed between migratory rate of controls and that of 50 mV/mm (p < 0.05). CONCLUSION: Microelectric fields appear to have a crucial role in control of nasal fibroblast activity in the process of wound healing.

Antioxidative activity of furanocoumarins isolated from Angelicae dahuricae.

The methylene chloride extract of the root of Angelicae dahuricae showed high protective activity against 2,2'-azobis (2-aminodinopropane) dihydrochloride (AAPH)-induced cellular damage. From this extract, 11 furanocoumarins were isolated, namely oxypeucedanin hydrate, 9-hydroxy-4-methoxypsoralen, byakangelicin, pabulenol, alloisoimperatorin, neobyakangelicol, byakangelicol, oxypeucedanin, imperatorin, phellotorin and isoimperatorin, respectively. Among these 11 furanocoumarins, 9-hydroxy-4-methoxypsoralen and alloisoimperatorin displayed potent antioxidant effects against the DPPH radical and against renal epithelial cell injury by using AAPH to generate peroxyl radicals in vitro.

Three new dammarane glycosides from heat processed ginseng.

Three new dammarane glycosides were isolated from the processed ginseng (SG; Sun Ginseng). Their structure were determined to be 3beta,12beta-dihydroxydammar-20(21),24-diene-3-O-beta-D-glucopyranosyl(1 --> 2)-beta-D-glucopyranoside; 3beta,12beta-dihydroxydammar-20(21),24-diene-3-O-beta-D- glucopyranoside and 3beta,6alpha,12beta-trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside based on spectroscopic evidences. The compounds were named as ginsenoside Rk1, Rk2, and Rk3 respectively.

Cytotoxic dammarane glycosides from processed ginseng.

Steaming ginseng at high temperature increased its cytotoxicity to SK-Hep-1 hepatoma cancer cells. HPLC separation and fractionation followed by MTT assay revealed that ginsenosides Rg3, Rg5, Rk1, Rs5, and Rs4 are the active principles. Their 50% growth inhibition concentration (GI50) values were 41, 11, 13, 37, and 13 microM, respectively. Cisplatin had a GI50 of 84 microM in the same assay conditions.

Four new acetylated ginsenosides from processed ginseng (sun ginseng).

Four new acetylated ginsenosides were isolated from the processed ginseng (SG, sun ginseng). Their structures were determined to be 3beta,12beta-dihydroxydammar-20(22),24-diene-3-O-beta-D-glucopyranosyl(1-->2)-beta-D-6"-O-acetylglucopyranoside; 3beta,12beta-dihydroxydammar-20(21), 24-diene-3-O-beta-D-glucopyranosyl(1-->2)-beta-D-6"-O-acetylglucopyranoside; 3beta, 6alpha, 12beta-trihydroxydammar-20(22),24-diene-beta-O-beta-D-6'-O-acetylglucopyranoside and 3beta,6a,12beta-trihydroxydammar-20(21),24-diene-6-O-beta-D-6'-O-acetylglucopyranoside based on spectroscopic evidences. The compounds were named ginsenoside Rs4, Rs5, Rs6 and Rs7, respectively.