Effect of Ampelopsis brevipedunculata (Maxim.) Trautv extract on a model of atopic dermatitis in HaCaT cells and mice.

Ampelopsis brevipedunculata (Maxim.) Trautv. has been used for a long time as a folk remedy. According to studies, it possesses anti-inflammatory, antioxidant, and antibacterial properties. However, its effects on atopic dermatitis (AD) are poorly studied. Thus, we investigated the therapeutic effect of A. brevipedunculata (Maxim.) Trautv. extract (ABE-M) on 2,4-dinitrochlorobenzene (DNCB)-induced AD. For in vitro analysis, keratinocytes cell lines (HaCaT cells) were used. To evaluate the gene and protein expression levels of cytokines and chemokines, TNF-α/IFN-γ-stimulated HaCaT cells were treated with ABE-M. The cells and the supernatant were collected, then gene and protein levels were analyzed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay analysis. For in vivo analysis, BALB/c mice (6 weeks) were randomly separated into five groups (n = 5). The mice were applied DNCB and phosphate-buffered saline, dexamethasone (DX) or ABE-M (50, 100, and 200 mg/kg) was orally administrated for 28 days. At the end, ear tissues and blood were collected for histological analysis and evaluation of cytokines and chemokines. In keratinocytes, ABE-M inhibited the protein and mRNA levels of chemokines, and cytokines exposed by TNF-α/IFN-γ. Similarly, the expression of chemokines was suppressed by ABE-M in AD animal model induced by DNCB and the level of pro-inflammatory cytokines was decreased in a dose-dependent manner. Our research indicates that ABE-M could be a candidate material that can be used to improve skin immunity enhancement, health, and beauty.

Effects of Vigna angularis extract and its active compound hemiphloin against atopic dermatitis-like skin inflammation.

Vigna angularis is an edible crop and herbal medicine that is known to have antipyretic, anti-inflammatory, and anti-edema effects. Many studies have been conducted on the 95% ethanol extract of V. angularis, but there is little research on the 70% ethanol extract and hemiphloin, which is a new indicator component of the 70% ethanol extract of V. angularis. To investigate the in vitro anti-atopic effect and verify the mechanism action of 70% ethanol extract of V. angularis (VAE), TNF-α/IFN-γ-induced HaCaT keratinocytes were used. The VAE treatment alleviated TNF-α/IFN-γ-induced IL-1ß, IL-6, IL-8, CCL17/TARC, and CCL22/MDC gene expressions and productions. VAE also inhibited the phosphorylation of MAPKs, including p38, ERK, JNK, STAT1, and NF-κB in TNF-α/IFN-γ-induced HaCaT cells. 2,4-dinitochlorobenzene (DNCB)-induced skin inflammation mice model, and HaCaT keratinocytes were used. In the DNCB-induced mouse model, VAE treatment alleviated ear thicknesses and IgE levels. Furthermore, VAE decreased IL-1ß, IL-6, IL-8, CCL17/TARC, and CCL22/MDC gene expressions of DNCB-applied ear tissue. Additionally, we investigated the anti-atopic and anti-inflammatory effects of hemiphloin using TNF-α/IFN-γ-induced HaCaT keratinocytes and LPS-induced J774 macrophages. Treatment hemiphloin decreased gene expressions and productions of IL-1ß, IL-6, IL-8, CCL17/TARC, and CCL22/MDC in TNF-α/IFN-γ-induced HaCaT cells. The phosphorylations of p38, ERK, STAT1, and NF-κB were inhibited by hemiphloin in TNF-α/IFN-γ-induced HaCaT cells. Finally, hemiphloin showed anti-inflammatory activities in LPS-induced J774 cells. It decreased LPS-induced NO productions and iNOS and COX-2 expressions. Treatment of hemiphloin also inhibited LPS-induced TNF-α, IL-1ß, and IL-6 gene expressions. These results suggest that VAE is an anti-inflammatory agent for inflammatory skin diseases and that hemiphloin could be a therapeutic candidate for inflammatory skin diseases.

Regulatory Effects of Lycium barbarum Extract and Isolated Scopoletin on Atopic Dermatitis-Like Skin Inflammation.

Lycium barbarum and scopoletin are widely used in oriental Eastern medicine and are often consumed as teas. In this study, proinflammatory cytokines expressed in human keratinocytes (HaCaT) were induced by skin diseases caused by 2,4-dinitrochlorobenzene (DNCB) and tumor necrosis factor alpha (TNF-α)/interferon gamma (IFN-γ). The inhibitory activity of L. barbarum EtOH extract (LBE) and scopoletin on proinflammatory cytokines and chemokines was investigated. In the DNCB-induced animal model, oral administration of LBE inhibited skin lesions and proinflammatory cytokines and chemokines and showed inhibitory effects in vitro. Additionally, as a result of examining the efficacy of scopoletin isolated from L. barbarum, scopoletin in HaCaT cells showed inhibitory effects on proinflammatory cytokines and chemokines. It shows promise in the treatment of chronic skin diseases.

Beneficial effects of Vigna angularis extract in osteoporosis and osteoarthritis.

In Asia, Vigna angularis (azuki bean) has been used as a traditional medicine to treat various diseases because of its biological properties. Osteoarthritis (OA) and osteoporosis (OP) are common regenerative bone diseases that are characterized by deterioration of joint and bone structure. In this study, we evaluated the effects of Vigna angularis extract (VAE) on monosodium iodoacetate (MIA)-induced OA and ovariectomy (OVX)-induced OP models. In the MIA-induced OA results, severe OA was alleviated by the administration of VAE. Extensive local damage in the cartilage and hemorrhagic and edematous of surrounding tissues were decreased by VAE treatment. Articular cartilage was almost intact except for a focal mild abrasion, and the surface was glistening, similar to that of the normal joint. In the OVX-induced OP results, bone mineral content (BMC) and bone mineral density (BMD) were recovered by VAE treatment, and it improved the microstructures of bone. These results show that VAE could inhibit OA and OP symptoms.

Acyclic Triterpenoid Isolated from Alpinia katsumadai Alleviates Formalin-Induced Chronic Mouse Paw Inflammation by Inhibiting the Phosphorylation of ERK and NF-κB.

Chronic and excessive inflammation can destroy host organs and cause inflammatory diseases such as inflammatory bowel disease, asthma, and rheumatoid arthritis. In this study, we investigated the anti-inflammatory effects of Alpinia katsumadai seed-derived 2,3,5,22,23-pentahydroxy-2,6,10,15,19,23-hexamethyl-tetracosa-6,10,14,18-tetraene (PHT) using lipopolysaccharide (LPS)-stimulated J774 cells and a formalin-induced chronic paw inflammation mouse model. The in vitro results showed that PHT exhibited no cytotoxicity and decreased LPS-induced NO secretion. Additionally, PHT inhibited LPS-induced inducible NO synthase (iNOS) and cyclooxygenase 2 (COX2) protein expression. The quantitative real-time PCR results showed that PHT downregulated the gene expression of the proinflammatory cytokines interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) but not tumor necrosis factor α (TNF-α). PHT inhibited the LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB). In a mouse model, oral administration of 50 mg/kg PHT significantly alleviated both mouse paw thickness and volume. These results indicate that PHT has potential anti-inflammatory effects and should be considered a possible functional material.

Diarylheptanoids from Curcuma phaeocaulis Suppress IL-6-Induced STAT3 Activation.

Three undescribed diarylheptanoids (3: -5: ) and six known curcuminoids (1, 2: , and 6: -9: ) were obtained from the ethyl acetate-soluble fraction of an ethanolic extract of Curcuma phaeocaulis. Their chemical structures and absolute configurations were elucidated by high-resolution electrospray ionization mass spectrometry, nuclear magnetic resonance spectroscopy, circular dichroism spectroscopy, and the modified Mosher's method. Previous studies constructed Hep3B cells stably transfected with pSTAT3-Luc plasmid containing STAT3 binding site to discover STAT3 inhibitors from natural products. The STAT3 inhibitory activities of all isolates were measured in transfected Hep3B cells after treatment with IL-6. Compound 5: ((5R)-1,7-Bis(3,4-dimethoxyphenyl)-3-methoxy-1-hepten-5-ol), demethoxycurcumin (7: ), and curcumin (8: ) exhibited significant inhibitory activity (IC50 values: 11.1, 1.9, and 1.6 µM, respectively). Furthermore, IL-6-induced phosphorylation of STAT3, and the mRNA expression levels of inflammation-related genes such as CRP, IL-1ß, ICAM-1, and SOCS3 were significantly reduced by exposure to compound 5: . These data suggested that the inhibitory activity of 5: is associated with the suppression of STAT3 phosphorylation. Thus, compound 5: may be a promising candidate for the treatment of cancer or inflammatory diseases related to the IL-6/STAT3 signaling pathway.

Inhibitory Effects of Compounds and Extracts from Ampelopsis brevipedunculata on IL-6-Induced STAT3 Activation.

Ampelopsis brevipedunculata (Maxim.) Trautv. (AB), a traditional East Asian medicine, exhibits protective effects against several inflammatory diseases. Our search for an inhibitor of IL-6-induced JAK2/STAT3 activation revealed that AB ethanolic extract (ABE) had a significant inhibitory effect on IL-6-induced STAT3 expression in Hep3B cells. The isolation and purification of an EtOAc-soluble fraction of ABE (ABEA) using reversed-phase high-performance liquid chromatography (RP-HPLC) afforded 17 compounds. The structures of these compounds (1-17) were elucidated based on 1H and 13C nuclear magnetic resonance (NMR) spectroscopy as well as electrospray-ionization mass spectrometry (ESI-MS) data. ABE and ABEA were screened by a luciferase assay using Hep3B cells transfected with the STAT3 reporter gene. ABEA exhibited potent inhibitory effects on IL-6-induced STAT3 expression; moreover, these effects arose from the inhibition of the phosphorylation of the STAT3, JAK2, and ERK proteins in U266 cells. In addition, the compounds isolated from ABEA were measured for their inhibitory effects on IL-6-stimulated STAT3 expression. Of the compounds isolated, betulin showed the greatest inhibitory effects on IL-6-induced STAT3 activation in the luciferase assay (IC50 value: 3.12 µM). Because of its potential for inhibiting STAT3 activation, A. brevipedunculata could be considered a source of compounds of pharmaceutical interest.

Portulaca oleracea extracts and their active compounds ameliorate inflammatory bowel diseases in vitro and in vivo by modulating TNF-α, IL-6 and IL-1ß signalling.

Portulaca oleracea L. (P. oleracea) is an herb that is widely used in traditional medicine to treat various diseases. However, its effects on inflammatory diseases, such as inflammatory bowel disease (IBD), are not yet well characterized. Here, we investigated the impact of the ethyl acetate (EtOAc) and ethanol (EtOH) extracts of P. oleracea on lipopolysaccharide (LPS)-induced inflammatory responses and phosphorylation of ERK, JNK, and p38 expression in RAW264.7 macrophages. In addition, the inhibitory effects of these extracts and fractions on 3% dextran sulphate sodium (DSS)-induced ulcerative colitis were examined using an ICR mouse model. DSS-induced colitis, including body weight loss, reduced colon length, and histological colon injury, was significantly ameliorated in mice fed the P. oleracea extracts (200 and 500mg/kg). In particular, P. oleracea extracts also inhibited pro-inflammatory cytokine (TNF-α, IL-6, and 1L-1ß) production in mice with DSS-induced colitis; the P. oleracea extracts displayed higher and/or similar inhibitory activity to sulfasalazine at high concentrations. Furthermore, the chemical structures of active compounds separated from the EtOAc extract of P. oleracea were elucidated using nuclear magnetic resonance (NMR) spectroscopy (see Figure in supplementary materials), resulting in the identification of three known compounds. Among these active compounds, cis-N-feruloyl-3'-methoxytyramine (2) exhibited the strongest effects on preventing DSS-induced IBD in animal models. Thus, extract of P. oleracea and their active compounds represents a new therapeutic approach for patients with inflammatory bowel diseases.