Ethanol Extract of Ampelopsis brevipedunculata Rhizomes Suppresses IgE-Mediated Mast Cell Activation and Anaphylaxis.

More than 20% of the world's population suffers from allergic diseases, including allergic asthma, rhinitis, and atopic dermatitis that severely reduce the patient's quality of life. The treatment of allergy has been developed, but there are still unmet needs. Ampelopsis brevipedunculata (Maxim.) Trautv. is a traditional medicinal herb with beneficial bioactivities, such as antioxidant, anti-hypertension, anti-viral, anti-mutagenic, and skin and liver (anti-hepatotoxic) protective actions. However, its anti-allergic effect has not been addressed. This study designed to investigate the pharmacological effect of an ethanol extract of A. brevipedunculata rhizomes (ABE) on mast cell and anaphylaxis models. For in vivo studies, we used ovalbumin-induced active systemic anaphylaxis (ASA) and immunoglobulin (Ig) E-mediated passive cutaneous anaphylaxis (PCA) models. In ASA model, oral administration of ABE (1, 10, and 100 mg/kg) attenuated the anaphylactic responses, such as hypothermia, serum histamine, and IgE productions. In PCA model, ABE also suppressed the plasma extravasation and swelling. The underlying mechanisms of action were identified in various mast cell types. In vitro, ABE (10, 30, and 60 µg/mL) inhibited the release of essential allergic mediators, such as histamine and ß-hexosaminidase, in a concentration-dependent manner. ABE prevented the rapid increase in intracellular calcium levels induced by the DNP-HSA challenge. In addition, ABE downregulated the tumor necrosis factor-α and interleukin-4 by suppressing the activation of nuclear factor-κB. Collectively, this study is the first to identify the anti-allergic effect of ABE, suggesting that ABE is a promising candidate for treating allergic diseases.

Anti-Inflammatory Effects of Clematis terniflora Leaf on Lipopolysaccharide-Induced Acute Lung Injury.

For centuries, natural products are regarded as vital medicines for human survival. Clematis terniflora var. mandshurica (Rupr.) Ohwi is an ingredient of the herbal medicine, Wei Ling Xian, which has been used in Chinese medicine to alleviate pain, fever, and inflammation. In particular, C. terniflora leaves have been used to cure various inflammatory diseases, including tonsillitis, cholelithiasis, and conjunctivitis. Based on these properties, this study aimed to scientifically investigate the anti-inflammatory effect of an ethanol extract of leaves of C. terniflora (EELCT) using activated macrophages that play central roles in inflammatory response. In this study, EELCT inhibited the essential inflammatory mediators, such as nitric oxide, cyclooxygenase-2, tumor necrosis factor-α, interleukin- (IL-) 6, IL-1ß, and inducible nitric oxide synthase, by suppressing the nuclear factor-κB and mitogen-activated protein kinase activation in macrophages. Acute lung injury (ALI) is a fatal respiratory disease accompanied by serious inflammation. With high mortality rate, the disease has no effective treatments. Therefore, new therapeutic agents must be developed for ALI. We expected that EELCT can be a promising therapeutic agent for ALI by reducing inflammatory responses and evaluated its action in a lipopolysaccharide- (LPS-) induced ALI model. EELCT alleviated histological changes, immune cell infiltration, inflammatory mediator production, and protein-rich pulmonary edema during ALI. Collectively, our results may explain the traditional usage of C. terniflora in inflammatory diseases and suggest the promising potential of EELCT as therapeutic candidate for ALI.

Luminescent silicon nanoparticles for distinctive tracking of cellular targeting and trafficking.

Developing therapeutic nanoparticles that actively target disease cells or tissues by exploiting the binding specificity of receptors presented on the cell surface has extensively opened up biomedical applications for drug delivery and imaging. An ideal nanoparticle for biomedical applications is required to report confirmation of relevant targeting and the ultimate fate in a physiological environment for further verification, e.g. to adapt dosage or predict response. Herein, we demonstrate tracking of silicon nanoparticles through intrinsic photoluminescence (PL) during the course of cellular targeting and uptake. Time-resolved analysis of PL characteristics in cellular microenvironments provides dynamic information on the physiological conditions where the silicon nanoparticles are exposed. In particular, the PL lifetime of the silicon nanoparticles is in the order of microseconds, which is significantly longer than the nanosecond lifetimes exhibited by fluorescent molecules naturally presented in cells, thus allowing discrimination of the nanoparticles from the cellular background autofluorescence in time-gated imaging. The PL lifetime is a physically intensive property that reports the inherent characteristics of the nanoparticles regardless of surrounding noise. Furthermore, we investigate a unique means to inform the lifespan of the biodegradable silicon nanoparticles responsive to local microenvironment in the course of endocytosis. A multivalent strategy of nanoparticles for enhanced cell targeting is also demonstrated with complementary analysis of time-resolved PL emission imaging and fluorescence correlation spectroscopy. The result presents the promising potential of the photoluminescent silicon nanoparticles toward advanced cell targeting systems that simultaneously enable tracking of cellular trafficking and tissue microenvironment monitoring.

Prunus serrulata var. spontanea inhibits mast cell activation and mast cell-mediated anaphylaxis.

ETHNOPHARMACOLOGICAL RELEVANCE: A promising approach to treat a variety of diseases are considered as complementary and alternative herbal medicines. Prunus serrulata var. spontanea L. (Rosaceae) is used as herbal medicine to treat allergic diseases according to the Donguibogam, a tradition medical book of the Joseon Dynasty in Korea. AIM OF THE STUDY: We prepared the aqueous extract of the bark of P. serrulata (AEBPS) and aimed to investigate the effects in mouse anaphylaxis models and various types of mast cells, including RBL-2H3, primary cultured peritoneal and bone marrow-derived mast cells. MATERIALS AND METHODS: We used ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) and immunoglobulin (Ig) E-mediated passive cutaneous anaphylaxis (PCA) models, in vivo. The control drug dexamethasone (10 mg/kg) was used to compare the effectiveness of AEBPS (1-100 mg/kg). In vitro, IgE-stimulated mast cells were used to confirm the role of AEBPS (1-100 µg/mL). For statistical analyses, p values less than 0.05 were considered to be significant. RESULTS: In ASA model, oral administration of AEBPS suppressed the hypothermia and increased level of serum histamine in a dose-dependent manner. AEBPS attenuated the serum IgE, OVA-specific IgE, and interleukin (IL)-4. Oral administration of AEBPS also blocked mast cell-dependent PCA. AEBPS suppressed degranulation of mast cells by reducing intracellular calcium level in mast cells. AEBPS inhibited tumor necrosis factor-α and IL-4 expression and secretion in a concentration-dependent manner through the reduction of nuclear factor-κB. CONCLUSIONS: On the basis of these findings, AEBPS could serve as a potential therapeutic target for the management of mast cell-mediated allergic inflammation and as a regulator of mast cell activation.

Hispidulin Inhibits Mast Cell-Mediated Allergic Inflammation through Down-Regulation of Histamine Release and Inflammatory Cytokines.

Hispidulin (4',5,7-trihydroxy-6-methoxyflavone) is a natural compound derived from traditional Chinese medicinal herbs, and it is known to have an anti-inflammatory effect. Here, we investigated the effect of hispidulin on the immunoglobulin E (IgE)-mediated allergic responses in rat basophilic leukemia (RBL)-2H3 mast cells. When RBL-2H3 cells were sensitized with anti-dinitrophenyl (anti-DNP) IgE and subsequently stimulated with DNP-human serum albumin (HSA), histamine and ß-hexosaminidase were released from the cells by degranulation of activated mast cells. However, pretreatment with hispidulin before the stimulation of DNP-HSA markedly attenuated release of both in anti-DNP IgE-sensitized cells. Furthermore, we investigated whether hispidulin inhibits anti-DNP IgE and DNP-HSA-induced passive cutaneous anaphylaxis (PCA), as an animal model for Type I allergies. Hispidulin markedly decreased the PCA reaction and allergic edema of ears in mice. In addition, activated RBL-2H3 cells induced the expression of inflammatory cytokines (tumor necrosis factor-α and interleukin-4), which are critical for the pathogenesis of allergic disease, through the activation of c-Jun N-terminal kinase (JNK). Inhibition of JNK activation by hispidulin treatment reduced the induction of cytokine expression in the activated mast cells. Our results indicate that hispidulin might be a possible therapeutic candidate for allergic inflammatory diseases through the suppression of degranulation and inflammatory cytokines expression.

Diospyros kaki calyx inhibits immediate-type hypersensitivity via the reduction of mast cell activation.

CONTEXT: Diospyros kaki L. (Ebenaceae) fruit is widely distributed in Asia and is known to exert anti-inflammatory and antithrombotic effects. OBJECTIVE: We evaluated the inhibitory effect of aqueous extract of D. kaki calyx (AEDKC) on mast cell-mediated immediate-type hypersensitivity and underlying mechanism of action. MATERIALS AND METHODS: For in vivo, ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) and immunoglobulin (Ig) E-mediated passive cutaneous anaphylaxis (PCA) models were used. In the ASA, AEDKC (1-100 mg/kg) was orally administered 3 times during 14 days. In the PCA, AEDKC was orally treated 1 h before the antigen challenge. The control drug dexamethasone was used to compare the effectiveness of AEDKC. For in vitro, IgE-stimulated RBL-2H3 cells and primary cultured peritoneal mast cells were used to determine the role of AEDKC (0.01-1 mg/mL). RESULTS: Oral administration of AEDKC dose dependently suppressed rectal temperature decrease and increases in serum histamine, total IgE, OVA-specific IgE, and interleukin (IL)-4 in the ASA. In the PCA, AEDKC reduced Evans blue pigmentation. Compared to dexamethasone (10 mg/kg), AEDKC (100 mg/kg) showed similar inhibitory effects in vivo. AEDKC concentration dependently suppressed the release of histamine and ß-hexosaminidase through the reduction of intracellular calcium in mast cells. In addition, AEDKC decreased the expression and secretion of tumour necrosis factor-α and IL-4 by the reduction of nuclear factor-κB. The inhibitory potential of AEDKC (1 mg/mL) was similar with dexamethasone (10 µM) in vitro. CONCLUSIONS: We suggest that AEDKC may be a potential candidate for the treatment of mast cell-mediated allergic diseases.

Methanol extract of Dioscoreae Rhizoma inhibits pro-inflammatory cytokines and mediators in the synoviocytes of rheumatoid arthritis.

Dioscoreae Rhizoma (MDR), the root of Dioscorea tokoro MAKINO, has been used for the treatment of arthritis, muscular pain and urinary diseases in oriental medicine. The present work evaluates a methanol extract of Dioscoreae Rhizoma (MDR). MDR did not show any cytotoxic effect on mouse lung fibroblast cells (mLFCs) or human fibroblast-like synovial cells (hFLSCs). However, it significantly reduced the proliferation of hFLSCs stimulated by interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha). MDR significantly inhibited the production of TNF-alpha and IL-1beta as well as down-regulating the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in IL-1beta- and TNF-alpha-stimulated hFLSCs. MDR also effectively reduced the level of reactive oxygen species (ROS) in these cells. Taken together, these findings provide evidence that MDR may be a candidate for the treatment of rheumatoid arthritis (RA).