Cinnamomum verum extract inhibits NOX2/ROS and PKCδ/JNK/AP-1/NF-κB pathway-mediated inflammatory response in PMA-stimulated THP-1 monocytes.

BACKGROUND: Cinnamomum verum J. Presl (Cinnamon) is widely used in the food and pharmaceutical industries. C. verum exhibits various biological activities. However, it is unclear whether C. verum can inhibit NOX, a major source of ROS generation, and exert anti-inflammatory and antioxidant effects in PMA-stimulated THP-1 cells. PURPOSE: This study investigates the anti-inflammatory and antioxidant effects of C. verum in PMA-stimulated THP-1 cells. METHODS: The MeOH extract of C. verum was analyzed using UPLC-QTOF/MS. Anti-inflammatory and antioxidant effects of C. verum extract were examined by DCF-DA staining, immunofluorescence staining, RT-PCR, and immunoblotting in PMA-stimulated THP-1 cells. RESULTS: C. verum and its components, cinnamic acid and coumarin, significantly attenuated the expression of IL-1ß, IL-8, CCL5, and COX-2 in PMA-stimulated THP-1. C. verum decreased ROS levels via NOX2 downregulation, as well as ameliorated plasma membrane translocation of PKCδ and decreased JNK phosphorylation. Besides, C. verum suppressed the nuclear translocation of AP-1 and NF-κB, which modulates diverse pro-inflammatory genes. CONCLUSION: C. verum effectively inhibits inflammation and oxidative stress during monocyte-macrophage differentiation and downregulates inflammatory mediators via NOX2/ROS and PKCδ/JNK/AP-1/NF-κB signaling.

ICT-based person-centered community care platform (IPC3P) to enhance shared decision-making for integrated health and social care services.

BACKGROUND: Community care is a care model with the aim of shifting care services from being hospital based toward community-based care. Advances in platforms based on information and communications technology (ICT) with a person-centered approach provide the potential to improve the delivery of health and social care services toward community-based settings. OBJECTIVES: The aims of this study were to describe the ICT-Based Person-Centered Community Care Platform (IPC3P) and to determine its impact on health- and social-care-related shared decision-making and quality of life among community residents. METHODS: An online platform was developed with the aim of enhancing community care. The platform had four components: (1) comprehensive health and social needs assessment system, (2) personalized community care planning, (3) needs-based health and social care services delivery, and (4) health community engagement. Community residents were invited to use and evaluate the impact of the IPC3P on their quality of life and shared decision-making regarding health and social care services. They provided feedback about the platform by completing two surveys: at baseline (before using the platform) and 6 months after using the platform. RESULTS: Data of 164 community residents were analyzed in this study. Between baseline and after using the platform, the quality of life reported by the participants increased significantly in all domains, with clear improvements also noted for shared decision-making about health and social care services. The IPC3P received positive feedback from the participants for its usability, familiarity, and ease of use. Some participants also reported their desire for the addition of more functions that support health communities. CONCLUSION: The IPC3P has the potential to enhance the involvement of community residents in their own care. The findings of this study can be used to support the wider implementation of the IPC3P to promote person-centered community care.

p-Coumaric Acid, a Major Active Compound of Bambusae Caulis in Taeniam, Suppresses Cigarette Smoke-Induced Pulmonary Inflammation.

[Formula: see text]-coumaric acid ([Formula: see text]-CA) is a common compound found in medicinal herbs, including Bambusae Caulis in Taeniam (BC). It has been used to treat various diseases in China and Korea. Our previous study demonstrated that BC inhibits pulmonary and intestinal inflammation. In the present study, we used cigarette smoke (CS) to induce lung inflammation in vivo, and investigated the anti-inflammatory effects of [Formula: see text]-CA on CS-induced inflammatory mice model. Mice were treated with BC and [Formula: see text]-CA via oral injection 2[Formula: see text]h before CS exposure. The body weight and the inflammatory cells in the bronchoalveolar lavage fluid were measured. The levels of relative inflammatory factors were confirmed by enzyme-linked immunosorbent assay. The lung histological changes were examined by hematoxylin and eosin staining. Also, the protein level of nuclear factor-[Formula: see text]B (NF-[Formula: see text]B) was evaluated by Western blotting. Our results indicated that BC and [Formula: see text]-CA inhibited CS-induced lung inflammation by regulating pro-inflammatory productions such as cytokines, chemokine, protease and NF-[Formula: see text]B. Consequently, these data demonstrated that [Formula: see text]-CA inhibited pulmonary inflammation by suppressing NF-[Formula: see text]B activity, through which pro-inflammatory mediators were regulated. Therefore, [Formula: see text]-CA, which was shown to be a major component of BC, can be considered as a strong therapeutic candidate for treating pulmonary inflammatory diseases.

Discrimination of Cynanchum wilfordii and Cynanchum auriculatum by terahertz spectroscopic analysis.

INTRODUCTION: Precise identification of botanical origin of plant species is crucial for the quality control of herbal medicine. In Korea, the root part of Cynanchum auriculatum has been misused for C. wilfordii in the herbal drug market due to their morphological similarities. Currently, DNA analysis using the polymerase chain reaction (PCR) method is employed to discriminate between these species. OBJECTIVE: In order to develop a new analytical tool for the rapid discrimination of C. wilfordii and C. auriculatum, terahertz (THz) spectroscopy was employed. METHODOLOGY: Authentic samples of C. wilfordii and C. auriculatum were provided from the National Institute and standardized pellets for each species were prepared to get optimum results with terahertz time-domain spectroscopy (THz-TDS) in frequency range 0.2-1.20 THz. RESULTS: The C. wilfordii pellet showed longer time delay compare to the sample of C. auriculatum and this was due to the difference in permittivity. The pellet samples of C. wilfordii and C. auriculatum showed a permittivity difference of about 0.08 at 0.2-1.20 THz. CONCLUSION: The experimental results indicated that THz-TDS analysis can be an effective and rapid method for the discrimination of C. wilfordii and C. auriculatum, and this application can be expanded for the discrimination of other similar herbal medicines.

Cynanchum atratum inhibits the development of atopic dermatitis in 2,4-dinitrochlorobenzene-induced mice.

Cynanchum atratum Bunge (Apocynaceae) is a folk medicine to treat skin inflammatory diseases. However, the effects of C. atratum on atopic dermatitis have not been elucidated. In this study, we evaluate the effects of aqueous extract of C. atratum (CA) and its molecular mechanism on atopic dermatitis (AD). 1 and 100mg/mL CA were topically applied to 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions for 11 days. The number of scratching behavior was evaluated for 20min. AD-like symptoms including elevated serum IgE, skin hyperplasia and mast cell infiltration were investigated. The expressions of pro-inflammatory cytokines and mediators were analyzed in AD-like skin legions. In addition, pro-inflammatory cytokine production was confirmed in human mast cells (HMC)-1 stimulated with PMA plus A23187 (PMACI). Topical application of CA attenuated total serum IgE level and scratching behavior. Skin hyperplasia including epidermis and dermis was ameliorated in CA-treated skin legions. The number of infiltrated mast cells was significantly decreased by CA treatment. In addition, CA reduced pro-inflammatory cytokines, such as IL-6, IL-1ß and TNF-α and Th2 cytokine, IL-4, in both of AD-like skin lesions and PMACI-sensitized HMC-1 cells. Furthermore, CA decreased the expressions of NF-κB, phospho-IκBα and MAP kinase. These results suggest the inhibitory effects of CA on the development of AD by regulating pro-inflammatory cytokines and mediators. CA could be an effective substance for the treatment of AD.

Original Research: Extract of Bambusae Caulis in Taeniam inhibits cigarette smoke-induced pulmonary and intestinal inflammation.

The pulmonary and intestinal systems have several characteristics in common. It is believed that these similarities somehow function to cause pulmonary-intestinal crosstalk during inflammation. Many studies have shown that pulmonary disease occurs in association with inflammatory bowel disease more often than is commonly recognized. Bambusae Caulis in Taeniam, a medicinal herb originated from the inner bark of Phyllostachys nigra var. henosis (Milford) Rendle (Poaceae), has been used to cure fever, diarrhea, and chest inflammation in Korea as well as in China. Cigarette smoke is a well-known risk factor for several inflammatory disorders. In this study, we induced pulmonary and bowel inflammation in mice using cigarette smoke and investigated whether Bambusae Caulis in Taeniam extract modulates the inflammatory response in both the lung and the bowel. C57BL/6 mice were exposed to cigarette smoke for 90 min per day for three weeks, and Bambusae Caulis in Taeniam extract was administered via oral injection 2 h before cigarette smoke exposure. The bronchoalveolar lavage cells were counted and hematoxylin and eosin staining were performed. Levels of inflammatory mediators in lung and large intestine were determined by enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and Western blotting. Our results showed that Bambusae Caulis in Taeniam attenuated cigarette smoke-induced inflammatory response in both the lung and the bowel of mice by inhibiting the production of pro-inflammatory cytokines, chemokines, and protease as well as NF-κB signaling factor. Therefore, we suggest that Bambusae Caulis in Taeniam extract might be a candidate therapeutic agent for inhibiting pulmonary and intestinal inflammation.

Topical Application of Angelica sinensis Improves Pruritus and Skin Inflammation in Mice with Atopic Dermatitis-Like Symptoms.

Angelica sinensis (AS) is one of the most popular medicinal foods used as a hematopoietic herb and also traditionally applied topically for skin disorders. However, the effectiveness of AS on atopic dermatitis (AD) has not been reported yet. This study was conducted to evaluate the antipruritic and anti-inflammatory effects of AS on regulating AD-related mediators in DNCB (2,4-dinitrochlorobenzene)-induced mice. AS was topically applied to the dorsal skin of DNCB-challenged mice for 11 days. Alteration of skin thickness was measured for assessment of histological improvement. In addition, the number of mast cells, the level of serum immunoglobulin E (IgE), the counting of scratching behavior, and the expression of substance P were evaluated. Also, the expressions of cytokines, nuclear factor κB (NF-κB), phospho-IκBα, and mitogen-activated protein kinases (MAPKs) were measured for evaluating the improvement of skin inflammation. The repeated treatment of AS significantly inhibited the skin thickness, the number of mast cells, and the level of serum IgE. Moreover, AS significantly suppressed the increased scratching behavior and the expression of substance P compared to the DNCB group. Topical application of AS also reduced the level of cytokines (IL-4, IL-6, TNF-α, and IFN-γ) as well as the expressions of NF-κB, phospho-IκBα, and phospho-MAPKs in the dorsal skin. The results of our study suggest that topical application of AS might have efficacy for modulating pruritus and inflammation in AD. Further studies are required to further characterize the mechanism of actions of AS.

Sceptridium ternatum attenuates allergic contact dermatitis-like skin lesions by inhibiting T helper 2-type immune responses and inflammatory responses in a mouse model.

BACKGROUND: Sceptridium ternatum (ST) is a medicinal herb used in folk remedies for the treatment of various disorders such as pertussis, allergic asthma, abdominalgia, diarrhea, and external use for wound healing. However, the biological and pharmacological activities of ST are not fully clarified besides anti-asthmatic effect. OBJECTIVE: We studied a Sceptridium ternatum ethanol extract (ST) with respect to its anti-inflammatory and immune regulatory activities in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, concanavalin A (conA)-stimulated BALB/c mice splenocytes, and a 2,4-dinitrochlorobenzene (DNCB)-induced allergic contact dermatitis (ACD) mouse model. METHODS: RAW 264.7 cells were pretreated with ST for 1h and then stimulated with LPS. To determine the anti-inflammatory effects of ST, the production of nitric oxide (NO), interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) were measured using an enzyme-linked immunosorbent assay (ELISA). To determine its anti-allergic effects, splenocytes from BALB/c mice were incubated and stimulated with conA in the absence or presence of ST for 48h. The production of IL-4 and interferon (IFN)-γ in culture supernatants were evaluated by ELISA. To test the effects of ST on ACD, 100µL of 1% DNCB was applied to the dorsal skin of BALB/c mice for 2 weeks, and ST was administered 2 h before DNCB application. The thicknesses of the epidermis and dermis were determined by skin histological analysis. Serum immunoglobulin (Ig) E levels, the production of IL-1ß, IL-4, and IL-6 in dorsal skin tissue, and T helper (Th) 2 cytokines production of CD4(+) T cells were analyzed by ELISA. The expression of nuclear transcription factor-κB (NF-κB) both in vitro and in vivo was determined via immunoblotting. RESULTS: In RAW 264.7 cells, ST inhibited LPS-induced inflammation mediator production and NF-κB expression. ST upregulated IFN-γ production and downregulated IL-4 production in conA-stimulated splenocytes. ST application reduced the thicknesses of the epidermis and dermis by decreasing serum IgE level and the expressions of IL-1ß, IL-4, IL-6, and NF-κB in the dorsal skin of the DNCB-induced ACD model mice. Furthermore, ST treated group showed reduction of the Th2 cytokines production in activated CD4(+) T cells. CONCLUSION: These findings not only indicate that application of ST reduced skin thickening by regulating Th 2-type allergic responses and inhibiting expression of inflammatory mediators in a DNCB-induced ACD mouse model, but also suggest that Sceptridium ternatum is a natural option for the treatment of skin inflammation.

Stemona tuberosa prevented inflammation by suppressing the recruitment and the activation of macrophages in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Stemona tuberosa (ST) is a traditional herbal medicine used for the treatment of various respiratory diseases in eastern Asia. AIM OF THE STUDY: We investigated the anti-inflammatory effects of a ST water extract in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and in cigarette smoke (CS)-induced lung inflammation mouse models. MATERIALS AND METHODS: RAW 264.7 macrophages were treated with the ST extract and stimulated by LPS. The expressions of pro-inflammatory mediators were evaluated by using nitric oxide (NO) assay, enzyme-linked immunosorbent assay and Western blot analysis. After the C57BL/6 mice were exposed to CS, they were administrated with the ST extract. The accumulated inflammatory cells in the bronchoalveolar lavage fluid (BALF) were counted. Also, real-time polymerase chain reaction and hematoxylin and eosin staining were performed in lung tissues. RESULTS: The ST extract treatment reduced the production of NO via blocking the expressions of cyclooxygenase-2 and inducible nitric oxide synthase protein in RAW 264.7 macrophages. In addition, ST extract treatment decreased the secretions of inflammatory cytokines and regulated NF-κB activation by inhibiting the phosphorylation of IκB and the mitogen-activated protein kinase pathway. Also, ST extract administration to mice reduced the infiltrations of macrophages into BALF and the histological inflammatory changes in lung tissues. Furthermore, administration of the ST extract regulated the levels of tumor necrosis factor-α, interleukin (IL)-6, IL-1ß, monocyte chemoattractant protein-1 and matrix metalloproteinases-12 in the lungs. CONCLUSION: These findings suggested that ST extract attenuated pulmonary inflammatory responses by inhibiting the expression of diverse inflammatory mediators in vivo and in vitro.

Galla Chinensis attenuates cigarette smoke-associated lung injury by inhibiting recruitment of inflammatory cells into the lung.

Inflammation is a common feature in the pathogenesis of cigarette smoke (CS)-associated diseases. In this study, we investigated the effects of Galla Chinensis (GC) extract on pulmonary inflammatory responses in a CS-exposed mouse model. In vitro studies showed that GC extract reduced MCP-1 production in a dose-dependent manner. In addition, the recruitment of inflammatory cells into the lung was significantly inhibited in the bronchoalveolar lavage fluid (BALF) of the GC-treated mice after 3 weeks of daily CS exposure. GC treatment down-regulated TNF-α, IL-6 and MCP-1 mRNA expression levels in lung tissue. Finally, GC-treated mice showed less emphysematous change of alveolar compared to mice only exposed to CS. Our results show that GC extract reduces lung inflammation and emphysematous change by inhibiting the infiltration of inflammatory cells to the lung. These data indicate that GC extract is a therapeutic candidate for CS-induced lung injury.

Nobiletin suppresses MMP-9 expression through modulation of p38 MAPK activity in human dermal fibrobalsts.

We aimed to identify a novel flavonoid from the in-house natural products to suppress matrix metalloproteases (MMPs), which is responsible for degradation of collagen and other extracellular matrix proteins. Total eight natural products were screened for identification of a novel MMP-9 suppressor using MMP-9 reporter system, where the prompt initial screening with multiple samples is readily examined. Among the extracts used in the present study, one extract (Citrus unshiu) was found active in this assay system. Furthermore, three representative flavonoids in this active extract of Citrus unshiu peel were tested in MMP-9 reporter system. Nobiletin (NB) of the tested flavonoids suppressed MMP-9 expression without cytotoxicity, which was validated by both real-time polymerase chain reaction (PCR) and zymography analyses. Sustained p38 mitogen activated protein kinase (MAPK) activity, closely associated with induction of MMP-9 under stress condition, was markedly reduced by NB treatment, which implies that modulation of p38MAPK by nobiletin is responsible for reduction of MMP9 expression. Hence, nobiletin, identified from MMP-9 reporter system based screening, may be further applied for the purpose of delaying collagen degradation in skin fibroblasts.

Lilium lancifolium Thunb. extract attenuates pulmonary inflammation and air space enlargement in a cigarette smoke-exposed mouse model.

ETHNOPHARMACOLOGICAL RELEVANCE: Lilium lancifolium Thunb. (Liliaceae) has long been used as a traditional medicine in Korea and China to treat bronchitis, pneumonia, and other pulmonary ailments. AIM OF THE STUDY: Cigarette smoke (CS) is a major risk factor for the development of pulmonary inflammatory response; it also triggers pulmonary alveoli enlargement. In the present study, we investigate the effects of Lilium lancifolium Thunb. root extract on pulmonary inflammatory responses in a CS-exposed mouse model. MATERIALS AND METHODS: Water extract of Lilium lancifolium Thunb. root was fed to C57BL/6 mice prior CS exposure every day for 3 weeks. The numbers of macrophages and neutrophils in bronchoalveolar lavage fluid (BALF) were counted. The relative inflammatory factors, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1ß), monocyte chemotactic protein-1 (MCP-1), and matrix metalloproteinase-12 (MMP-12) were measured by real-time PCR, ELISA, or Western blot analysis. The average alveoli size was determined by lung histology. RESULTS: Lilium lancifolium Thunb. root extract was found to significantly inhibit the numbers of macrophages and neutrophils in BALF due to CS exposure. Lilium lancifolium Thunb. root extract also reduced the protein secretion levels of TNF-α, IL-6, IL-1ß, and MCP-1 in BALF and the RNA expression levels of TNF-α, IL-6, IL-1ß, MCP-1, and MMP-12 in lung tissue compared with mice only exposed to CS. Moreover, MMP-12 in serum was down regulated in Lilium lancifolium Thunb. root extract treated mice compared with CS-exposed mice. Finally, a morphometric analysis of the lungs of Lilium lancifolium Thunb. root extract treated mice demonstrated a significant reduction in airspace size compared to mice only exposed to CS. CONCLUSION: Our results show that Lilium lancifolium Thunb. root extract reduces lung inflammation and airspace enlargement in a CS-exposed mouse model. These data indicate that Lilium lancifolium Thunb. root extract is a therapeutic candidate for pulmonary inflammation and emphysema caused by CS.

Extract of Aneilema keisak inhibits transforming growth factor-ß-dependent signalling by inducing Smad2 downregulation in keloid fibroblasts.

Keloids are characterised by the excessive accumulation of extracellular matrix (ECM), especially overabundant collagen formation. In keloid fibroblasts (KFs), transforming growth factor (TGF)-ß-dependent signalling is closely associated with a variety of keloid pathologic responses such as ECM production and fibroblast overgrowth. Thus, inhibition of TGF-ß signalling would be a potential therapeutic approach to prevent keloid scar formation. Thereby, we aimed to identify a novel TGF-ß signalling blocker among natural products using a simplified screening approach. We discovered that the extract of Aneilema keisak (A.K-Ex) lowered TGF-ß-dependent signalling by reducing Smad2 protein levels. Given that KFs showed altered dependency on TGF-ß for survival and proliferation, A.K-Ex-mediated reduction in Smad2 protein levels significantly inhibited the major characteristics of KFs such as cell growth, migration and collagen synthesis, suggesting that A.K-Ex exhibits possible therapeutic activity on keloids.

Schizonepeta tenuifolia inhibits the development of atopic dermatitis in mice.

Historically, Schizonepeta tenuifolia (ST) has been used for the treatment of skin disorders, such as allergic dermatitis, eczema, and inflammatory diseases. In this study, we examined whether ST inhibited 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD) in BALB/c mice. In histopathological analyses of the epidermis and dermis, skin thickness was significantly increased in DNCB-induced mice as compared with normal group. Treatment with ST inhibited this inflammatory change and markedly suppressed the secretion of immunoglobulin E, tumor necrosis factor α, and interleukin 6 levels in the serum of DNCB-induced mice. In addition, ST treatment significantly restored the upregulation of proinflammatory factors, such as nuclear factor (NF)-κB and mitogen-activated protein kinase expression. Taken together, due to its ability to suppress inflammatory factors and upregulate proinflammatory factors, ST may be useful as a therapeutic treatment for AD. ST extract application decreased both epidermis and dermis thickness in DNCB-induced mice. In serum, ST reduced immunoglobulin E, tumor necrosis factor, and interleukin 6 level. In addition, ST suppressed NF-κB activation as well as the mitogen-activated protein kinase activities.

Vitex rotundifolia L. prevented airway eosinophilic inflammation and airway remodeling in an ovalbumin-induced asthma mouse model.

Vitex rotundifolia L. (VR) as long been used in China and Korea in traditional medicine. This study was conducted to evaluate the ability of Vitex rotundifolia L. to prevent airway inflammation and remodeling in an ovalbumin (OVA)-induced murine asthma model. The total cell number and number of inflammatory cells in the bronchoalveolar lavage (BAL) fluid were counted. The levels of cytokines in the BAL fluid and serum IgE levels were measured using an ELISA. For histological analysis, hematoxylin and eosin staining, periodic acid-Schiff staining and immunohistochemistry were evaluated. The release of total cells into the BAL fluid was significantly inhibited in OVA-induced asthmatic mice treated with VR extract. In addition, eosinophilia and lymphocytosis were reduced significantly in mice that received VR extract. Furthermore, levels of the T(h)2 cytokines IL-4 and IL-5 and pro-inflammatory cytokine TNF-α in the BAL fluid and total IgE in serum were markedly suppressed by VR extract. OVA-specific IgE in the serum and IL-13 in the BAL fluid were decreased, but not significantly. The allergic effects of VR extract were accompanied by a reduction in airway hyperresponsiveness. Additionally, morphologic findings demonstrated that VR extract substantially inhibited OVA-induced eosinophilia, goblet cell hyperplasia and smooth muscle mass production. This finding suggests that VR extract may have pharmacological effects that would be useful for the treatment of asthma via the inhibition of the T(h)2 response and airway remodeling.

Effects of Schisandra chinensis Baillon (Schizandraceae) on lipopolysaccharide induced lung inflammation in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis Baillon (Sc), an anti-inflammatory herb that has been used in traditional Chinese medicine for thousands of years, is frequently used to treat upper respiratory tract infections. AIM OF THE STUDY: This study was conducted to evaluate the ability of a water extract of Sc to prevent airway inflammation both in vitro and in vivo. MATERIALS AND METHODS: Human lung alveolar epithelial-derived A549 cells were stimulated with to interleukin-1ß, tumor necrosis factor-α, and interferon-γ (IL-1ß, TNF-α, and INF-γ; cytokine mixture; CM) and treated with Sc extracts. They were then evaluated using nitric oxide (NO), IL-8 and monocyte chemotactic protein-1 (MCP-1) secretions. In the in vivo study, BALB/c mice were challenged with lipopolysaccharide (LPS) to induce acute airway inflammation. After this challenge, the mice were treated with Sc extracts (10, 50 and 100mg/kg) by oral administration, and inflammatory cells in the bronchoalveolar lavage (BAL) fluid were counted. IL-6 and TNF-α secretions were measured using an enzyme-linked immunosorbent assay. Lung tissues of the LPS treated mice were prepared and stained with hematoxylin and eosin (HE) for histological examination. RESULTS: In the A549 cells, Sc extracts dose-dependently and significantly inhibited CM-induced NO production and reduced IL-8 and MCP-1 secretions. Sc extracts efficiently suppressed neutrophil and macrophage infiltrations of lung tissues and increased IL-6 and TNF-α levels in BAL fluid in LPS-instilled BALB/c mice. In addition, Sc extracts treatment inhibited pathologic progress in the lung tissues, as confirmed by H&E staining. These findings indicate that Sc extracts could be potentially useful for the treatment of acute lung inflammation and acute lung injury.

Extract of Salvia miltiorrhiza (Danshen) induces Nrf2-mediated heme oxygenase-1 expression as a cytoprotective action in RAW 264.7 macrophages.

ETHNOPHARMACOLOGICAL RELEVANCE: Danshen (Salvia miltiorrhiza) is widely used in traditional herbal medicines for relief of a variety of symptoms related to complications arising from vascular diseases such as hypertension, diabetes, and atherosclerosis. Induction of heme oxygenase-1 (HO-1) expression protects against oxidative stress-induced cell damage, which plays an important role in cytoprotection in a variety of pathological models. MATERIALS AND METHODS: In the present study, we investigated the effect of Danshen on the up-regulation of HO-1, an inducible and cytoprotective enzyme in RAW 264.7 macrophages. Molecular mechanisms underlying the effects, especially protective effects, was elucidated by analyzing the activation of transcription factors and their upstream signalling, and by evaluating the inhibitory effect of HO-1 on ROS production. RESULTS: Danshen induced HO-1 mRNA expression and protein production, and nuclear translocation of NF-E2-related factor 2 in RAW 264.7 macrophages. Pharmacological inhibitors of PI3K/Akt and MEK1 attenuated HO-1 induction in Danshen-stimulated RAW 264.7 macrophages. Furthermore, Danshen pretreatment reduced intracellular production of reactive oxygen species after stimulation with hydrogen peroxide; this effect was reversed by the HO-1 inhibitor ZnPP. CONCLUSION: Danshen induced HO-1 expression through PI3K/Akt-MEK1-Nrf2 pathway and reduced intracellular production of reactive oxygen species via induction of HO-1 expression. The results support a role of HO-1 in the cytoprotective effect of Danshen.

Reduction of interleukin-1ß induced matrix metalloproteinase-3 release by extracts of six plants: inhibitory screening of 35 traditional medicinal plants.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease associated with matrix metalloproteinase (MMP)-3, leading to destruction of the cartilage. The objective of this study was to investigate and discuss the suitability of the 35 medicinal plants as therapeutic candidates to treat RA. Fibroblast-like synoviocytes (FLSs), derived from patients with RA, were adjusted to 2 × 10(6) cells/mL in a 24-well plate and pretreated with the distilled water extracts of the 35 plants (1, 10, and 100 µg/mL) for 1 h followed by interleukin-1ß (IL-1ß) (1 ng/mL) for 24 h. The concentration of MMP-3 was then determined using a Duoset ELISA Kit. The six plants (Artemisiae Capillaris Herba, AC; Bambusae Caulis In Taeniam, BC; Cassiae Semen, CS; Corni Fructus, CF; Leonuri Herba, LH; Schizonepetae Spica, SS) showed no toxicity, including MMP-3. The MMP-3 level was increased by 3.38-fold (212.23 µg/mL) in IL-1ß-stimulated FLSs. The IL-1ß-induced MMP-3 level was significantly and dose-dependently reduced by >50% by the six plants (P < 0.01: at 100  µg/ mL of CS and LH, P < 0.001: at 10 µg/mL of all plants, and at 100 µg/mL of AC, BC, CF, and SS). This is the first study on the MMP-3 inhibitory effect of the examined plants in FLSs isolated from RA patients. From our original research, the six candidate plants were identified.

An Angiotensin I converting enzyme polymorphism is associated with clinical phenotype when using differentiation-syndrome to categorize korean bronchial asthma patients.

In this study, genetic analysis was conducted to investigate the association of angiotensin I converting enzyme (ACE) gene polymorphism with clinical phenotype based on differentiation-syndrome of bronchial asthma patients. Differentiation-syndrome is a traditional Korean medicine (TKM) theory in which patients are classified into a Deficiency Syndrome Group (DSG) and an Excess Syndrome Group (ESG) according to their symptomatic classification. For this study, 110 participants were evaluated by pulmonary function test. Among them, 39 patients were excluded because they refused genotyping. Of the remaining patients, 52 with DSG of asthma (DSGA) and 29 with ESG of asthma (ESGA), as determined by the differentiation-syndrome techniques were assessed by genetic analysis. ACE insertion/deletion (I/D) polymorphism analysis was conducted using polymerase chain reaction (PCR). Student's t, chi-square, Fisher and Hardy-Weinberg equilibrium tests were used to compare groups. No significant differences in pulmonary function were observed between DSGA and ESGA. The genotypic frequency of ACE I/D polymorphism was found to differ slightly between DSGA and ESGA (P = .0495). However, there were no significant differences in allelic frequency observed between DSGA and ESGA (P = .7006, OR = 1.1223). Interestingly, the allelic (P = .0043, OR = 3.4545) and genotypic (P = .0126) frequencies of the ACE I/D polymorphism in female patients differed significantly between DSGA and ESGA. Taken together, the results presented here indicate that the symptomatic classification of DSGA and ESGA by differentiation-syndrome in Korean asthma patients could be useful in evaluation of the pathogenesis of bronchial asthma.