Anti-oxidative, anti-apoptotic, and anti-inflammatory activities of Connarus semidecandrus Jack ethanol extract in UVB-irradiated human keratinocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: Connarus semidecandrus Jack (Family: connaraceae) is a medicinal plant known for its wide distribution throughout Southeast Asia. Renowned for its diverse therapeutic properties, it has been traditionally used for treating fever, skin irritation, and colic. AIM OF THE STUDY: Numerous individuals suffer from skin issues, including wrinkles, hyperpigmentation, and inflammation, due to environmental factors. Although many drugs are available to treat skin problems, chemical drugs have many shortcomings and side effects. Therefore, natural products are attractive potential medicines for alleviating skin troubles. We recently showed that Connarus semidecandrus Jack ethanol extract (Cs-EE) has anti-alopecia potential. This paper aims to explore the potential skin-protective effects and underlying molecular mechanisms of Connarus semidecandrus Jack in UVB-induced human keratinocytes (HaCaT). MATERIALS AND METHODS: Before utilization, Cs-EE was dissolved in dimethyl sulfoxide (DMSO) and was preserved at a temperature of -20 °C. The phytochemical constituents of Cs-EE were detected by gas chromatography-mass spectrometry analysis (GC-MS). Sequentially, HaCaT cells were exposed to varying concentrations of Cs-EE prior to ultraviolet B (UVB) irradiation. Evaluations of cellular responses in HaCaT cells, including assessments of cell viability, deoxyribonucleic acid (DNA) damage, and gene and protein expressions, were carried out. To explore the specific signaling pathway involved, we conducted a luciferase assay in addition to validating these pathways using Western blot analysis. RESULTS: Nitric oxide (NO) and intracellular reactive oxygen species were decreased. Melanin production through the activation of melanocytes by α-melanocyte-stimulating hormone (MSH) was also inhibited by Cs-EE. Furthermore, the mRNA expression levels of key factors such as cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), MMP-1, MMP-3, and MMP-9 exhibited a remarkable decrease. In addition, the phosphorylation of TAK1 within the signaling cascade exhibited a decline, and the activities of the transcription factor AP-1 were decreased according to a luciferase reporter assay. CONCLUSIONS: Taken together, these findings suggest that the anti-inflammatory, anti-aging, and anti-apoptotic effects of Cs-EE indicate the compound's potential usefulness as a natural component in pharmaceutical and cosmetic products.

Qualitative and Quantitative Analysis of the Major Bioactive Components of Juniperus chinensis L. Using LC-QTOF-MS and LC-MSMS and Investigation of Antibacterial Activity against Pathogenic Bacteria.

Plants in the genus Juniperus have been reported to produce a variety of chemical components, such as coumarins, flavonoids, lignans, sterols, and terpenoids. Here, ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) were applied to qualitatively and quantitatively analyze the major bioactive components in an ethanolic crude extract from the leaves of Juniperus chinensis L., which grows naturally in Korea. In addition, the antibacterial activity of the crude extract against pathogenic bacteria was investigated. Using LC-QTOF-MS analysis, we identified ten compounds, of which six were confirmed to be flavonoid and lignan-based components as the major bioactive components, i.e., isoquercetin, quercetin-3-O-α-l-rhamnoside, hinokiflavone, amentoflavone, podocarpusflavone A, and matairesinoside. Among them, a quantitative analysis performed using LC-MS/MS revealed that the levels of quercetin-3-O-α-l-rhamnoside and amentoflavone in the crude extract were 203.78 and 69.84 mg/g, respectively. Furthermore, the crude extract exhibited potential antibacterial activity against 10 pathogenic bacteria, with the highest antibacterial activity detected against Bordetella pertussis. Thus, further studies of the leaf extract of J. chinensis L. must be carried out to correlate the compounds present in the extract with the antibacterial activity and elucidate the mechanisms of action of this extract against bacteria.

Antiphotoaging and Skin-Protective Activities of Ardisia silvestris Ethanol Extract in Human Keratinocytes.

Ardisia silvestris is a traditional medicinal herb used in Vietnam and several other countries. However, the skin-protective properties of A. silvestris ethanol extract (As-EE) have not been evaluated. Human keratinocytes form the outermost barrier of the skin and are the main target of ultraviolet (UV) radiation. UV exposure causes skin photoaging via the production of reactive oxygen species. Protection from photoaging is thus a key component of dermatological and cosmetic products. In this research, we found that As-EE can prevent UV-induced skin aging and cell death as well as enhance the barrier effect of the skin. First, the radical-scavenging ability of As-EE was checked using DPPH, ABTS, TPC, CUPRAC, and FRAP assays, and a 3-(4-5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide assay was used to examine cytotoxicity. Reporter gene assays were used to determine the doses that affect skin-barrier-related genes. A luciferase assay was used to identify possible transcription factors. The anti-photoaging mechanism of As-EE was investigated by determining correlated signaling pathways using immunoblotting analyses. As-EE had no harmful effects on HaCaT cells, according to our findings, and As-EE revealed moderate radical-scavenging ability. With high-performance liquid chromatography (HPLC) analysis, rutin was found to be one of the major components. In addition, As-EE enhanced the expression levels of hyaluronic acid synthase-1 and occludin in HaCaT cells. Moreover, As-EE dose-dependently up-regulated the production of occludin and transglutaminase-1 after suppression caused by UVB blocking the activator protein-1 signaling pathway, in particular, the extracellular response kinase and c-Jun N-terminal kinase. Our findings suggest that As-EE may have anti-photoaging effects by regulating mitogen-activated protein kinase, which is good news for the cosmetics and dermatology sectors.

Sophora flavescens Aiton methanol extract exerts anti-inflammatory effects via reduction of Src kinase phosphorylation.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophora flavescens Aiton (Family: Leguminosae), an herbal plant, has been used in East Asian home remedies for centuries for treating ulcers, skin burns, fevers, and inflammatory disorders. In addition, the dried root of S. flavescens was also applied for antipyretic, analgesic, antihelmintic, and stomachic uses. AIM OF STUDY: Nonetheless, how this plant can show various pharmacological activities including anti-inflammatory responses was not fully elucidated. In this study, therefore, we aimed to investigate the curative effects of S. flavescens on inflammation and its molecular mechanism. MATERIALS AND METHODS: For reaching this aim, various in vitro and in vivo experimental models with LPS-treated RAW264.7 cells, HCl/EtOH-induced gastric ulcer, and LPS-triggered lung injury conditions were employed and anti-inflammatory activity of S. flavescens methanol extract (Sf-ME) was also tested. Fingerprinting profile of Sf-ME was identified via LC-MS analysis. Its anti-inflammatory molecular mechanism was also examined by immunoblotting analysis. RESULTS: Nitric oxide production and mRNA expression levels of iNOS, COX-2, IL-1ß, and TNF-α were decreased. Additionally, phosphorylation of Src in the signaling cascade was decreased, and activities of the transcriptional factor NF-κB were reduced as determined by a luciferase reporter assay. Moreover, in vivo, gastritis and lung injury lesions were attenuated by Sf-ME. CONCLUSION: Taken together, these findings suggest that Sf-ME could be a potential anti-inflammatory therapeutic agent via suppression of Src kinase activity and regulation of IL-1ß secretion.

Identification and Comparison of Bioactive Components of Two Dryopteris sp. Extract Using LC-QTOF-MS.

Dryopteris sp. is known for its various pharmacological effects and is used as a traditional medicine in Asia. The present study investigated the chemical composition and antimicrobial activity of Dryopteris sp. distributed in Korea. The chemical compounds in the ethanolic extracts of Dryopteris lacera and Dryopteris bissetiana were investigated by ultra-high performance liquid chromatography-quadrupole time-of-flight-mass spectrometry analysis and identified by exploring the UNIFI traditional medicine library. Flavonoids such as juglanin, 6-hydroxyluteolin 7-O-laminaribioside, peltatoside, kaempferitrin, hyperoside, and astragalin were identified in both D. lacera and D. bissetiana. Neochlorogenic acid was identified as a caffeoylquinic acid in D. bissetiana. Both extracts of D. lacera and D. bissetiana exhibited antibacterial activity against Gram-positive pathogens, Staphylococcus aureus and Streptococcus mutans. The minimum inhibitory concentration of D. bissetiana against S. aureus was less than 625 ppm. The antibacterial activity was attributed to the identified phenolic compounds, juglanin, 6-hydroxyluteolin 7-O-laminaribioside, kaempferitrin, astragalin, and neochlorogenic acid. Therefore, D. lacera and D. bissetiana can be used as Gram-positive selective antibiotics for further investigation.

Inhibitory Effects of Grewia tomentosa Juss. on IgE-Mediated Allergic Reaction and DNCB-Induced Atopic Dermatitis.

Grewia tomentosa Juss. is a deciduous shrub that mainly grows in Asia. Despite studies of other Grewia species for treatment of various diseases, Grewia tomentosa Juss. has not been studied as a medicinal herb. This study evaluates the anti-allergic and anti-topic dermatitis activity of Grewia tomentosa Juss. ethanol extract (Gt-EE). The results show that Gt-EE suppressed IgE-antigen-induced ß-hexosaminidase release. The mRNA expression of IL-1ß, IL-4, IL-5, IL-6, IL-13, TNF-α, MCP-1, and TSLP, which are involved in allergic responses, was inhibited by Gt-EE in IgE-stimulated RBL-2H3 cells. In addition, the phosphorylation of Syk, PLCγ1, PKCδ, PI3K, AKT, NF-κB p65, NF-κB p50, p38, JNK, and ERK1/2 was decreased by Gt-EE in these cells. Gt-EE also showed anti-inflammatory effects in in vivo mouse models. In passive cutaneous anaphylaxis (PCA), a commonly used mouse model, Gt-EE decreased the allergic response, infiltration of mast cells, and mRNA level of IL-4. Furthermore, Gt-EE ameliorated symptoms of DNCB-induced atopic dermatitis (AD). In DNCB-induced AD, Gt-EE suppressed the increase in mast cells, serum IgE level, expression of allergic mediators (IL-1ß, IL-4, IL-5, IL-6, TNF-α), and phosphorylation of proteins (IκBα, NF-κB p65, NF-κB p50, p38, JNK, and ERK1/2) implicated in allergic reactions.

Callerya atropurpurea suppresses inflammation in vitro and ameliorates gastric injury as well as septic shock in vivo via TLR4/MyD88-dependent cascade.

BACKGROUND: Callerya atropurpurea is a traditional plant in a tropical zone discovered to have anti-inflammatory functions. PURPOSE: we want to investigate the mechanism related to anti-inflammation of C. atropurpurea ethanol extract (Ca-EE) both in vitro and in vivo. STUDY DESIGN: Murine macrophage cells and mouse models for gastritis and septic shock were conducted to evaluate the abilities of Ca-EE in anti-inflammation. METHODS: Ca-EE was tested by HPLC and LC-MS/MS. NO outcome was checked by Griess reagent test. Cell viabilities were evaluated using MTT assay. Inflammatory cytokines were determined via RT-PCR and ELISA. The mechanism of Ca-EE in anti-inflammation was investigated by luciferase reporter gene assay and immunoblot in transcription level and protein level respectively. Gastric injury and septic shock administrated with Ca-EE were studied by H&E, PCR, and immunoblot. RESULTS: Ca-EE significantly decreased LPS-induced NO production, but hardly stimulated the expression of NO itself. It not only showed no cytotoxicity, but also protected cells from LPS damage. Moreover, Ca-EE decreased TLR4 expression, altered MyD88 recruitment and TRAF6, and suppressed the phospho-Src/PI3K/AKT. Ca-EE inhibited downstream signaling P38, JNK and NF-κB. Finally, Ca-EE alleviated HCl/EtOH-induced gastritis and LPS/poly (I:C)-induced septic shock through the previously mentioned signaling cascades. CONCLUSION: Ca-EE exhibited an integrated and promising mechanism against TLR4-related inflammation, which shows potential for treating gastritis, septic shock, and other inflammatory diseases.

Connarus semidecandrus Jack Exerts Anti-Alopecia Effects by Targeting 5α-Reductase Activity and an Intrinsic Apoptotic Pathway.

There is a growing demand for hair loss treatments with minimal side effects and recurrence potential. Connarus semidecandrus Jack has been used as a folk medicine for fever in tropical regions, but its anti-alopecia effects remain unclear. In this study, the anti-androgenic alopecia effect of an ethanol extract of Connarus semidecandrus Jack (Cs-EE) was demonstrated in a testosterone-induced androgenic alopecia (AGA) model, in terms of the hair-skin ratio, hair type frequency, and hair thickness. The area of restored hair growth and thickened hair population after Cs-EE treatment showed the hair-growth-promoting effect of Cs-EE. Histological data support the possibility that Cs-EE could reduce hair loss and upregulate hair proliferation in mouse skin by shifting hair follicles from the catagen phase to the anagen phase. Western blotting indicated that Cs-EE reduced the expression of the androgenic receptor. Cs-EE treatment also inhibited programmed cell death by upregulating Bcl-2 expression at the mRNA and protein levels. The anti-alopecia effect of Cs-EE was confirmed by in vitro experiments showing that Cs-EE had suppressive effects on 5-α reductase activity and lymph node carcinoma of the prostate proliferation, and a proliferative effect on human hair-follicle dermal papilla (HDP) cells. Apoptotic pathways in HDP cells were downregulated by Cs-EE treatment. Thus, Cs-EE could be a potential treatment for AGA.

Effect of Judo Athletes' Psychological Function on Sports Coping Skills: Moderated Mediating Effect of Tension.

This study aimed to investigate the effects of Judo athletes' psychological function on sports coping skills through self-management: the moderated mediating effect of tension. A total of 124 participants (66 males and 58 females) were included, comprising high school students, college students, and judo team players (age 16 to 30, 20.51 ± 3.17) in the Republic of Korea. The psychological function was measured using the Profile of Mood Test, Athletes' Self-Management Questionnaire, and Athletic Coping Skills Inventory-28. The results of the analysis of the moderating effect of the athlete's self-management behavior showed that tension had a moderating effect on the relationship between the athlete's self-management behavior and sports coping skills. The mediating effect analysis revealed a mediating effect of self-management behavior on the relationship between player vitality and sports coping skills. It was also confirmed that tension had a moderating effect on athletes' self-management behavior and sports coping skills. Therefore, it was confirmed that the higher the self-management, the more moderated the mediating effect on sports coping skills. In conclusion, it was confirmed that psychological function affects sports coping skills, and thereby, the mediating effect of the athlete's self-management behavior is regulated by tension. In future research, it will be necessary to study the sports coping ability and performance of judo athletes according to tension control.

Characterization of anti-microbial peptides and proteins from maggots of Calliphoridae and Sarcophagidae fly species (Diptera).

Removal of infected wounds using maggots has been known for centuries. Early research has shown that the maggot exosecretion, whole body, and fecal waste products of Calliphoridae and Sarcophagidae species contain a variety of alkaline peptides capable of inhibiting bacterial growth. Since the wide application of antibiotics such as penicillin, a number of bacterial infections have become insensitive to antibiotic treatment. In many of these instances, maggot therapy has been successfully applied for the treatment of chronic wounds. To identify and compare the expression patterns of anti-microbial peptides (AMPs) from some dipteran species, transcriptome analyses were conducted for the maggots of 11 Calliphoridae and Sarcophagidae species. Species of the subfamily Calliphorinae showed relatively higher expression levels of AMPs and anti-microbial proteins compared with those of Luciliinae and Sarcophagidae species. Furthermore, among all of the dipteran species examined, Lucilia illustris exhibited the highest transcription levels of AMPs. Cecropin A2 and defensin, whose expression levels were the highest among the anti-microbial peptides, were synthesized to test their biological activity. The synthesized peptides showed anti-microbial activities without hemolytic activities. In particular, cecropin A2 of L. illustris exhibited the highest anti-microbial activity against all of the bacteria and fungi examined, thereby possessing the potential to be developed as a new alternative to antibiotics. This comparative transcriptomic study may provide new insights into anti-microbial compositions of some dipteran species.

Hymenocallis littoralis ameliorates inflammatory responses in LPS-stimulated RAW264.7 cells and HCl/EtOH-induced gastric mucosal injury via targeting the MAPK pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Hymenocallis littoralis (Jacq.) Salisb. Also known as Pancratium littorale Jacq. And Hymenocallis panamensis Lindl., is a medicinal plant from the family Amarylideceae used for emetic and wound healing and has manifested anti-neoplastic, anti-oxidant, and anti-viral properties. AIM OF THE STUDY: The aim of this paper is to investigate the anti-inflammatory potential and molecular mechanism of H. littoralis against lipopolysaccharide (LPS)-induced macrophages and in vivo HCl/EtOH-induced gastritis mucosal injury models. MATERIALS AND METHODS: The production of pro-inflammatory cytokines and mediators was evaluated by Griess assay, RT-PCR, and real-time PCR. Moreover, the relevant proteins of mitogen-activated protein kinases (MAPKs) including ERK, JNK, p38, c-Jun, and c-Fos were detected using immunoblotting. RESULTS: We demonstrated that H. littoralis prominently dampened production of nitric oxide (NO) in LPS-, poly I:C-, or pam3CSK-stimulated RAW264.7 cells; down-regulated the expression levels of interleukin 6 (IL-6) and inducible nitric oxide synthase; and markedly attenuated the luciferase activities of AP-1 reporter promoters. Moreover, H. littoralis administration prominently downregulated c-Fos and c-Jun phosphorylation as well as JNK1, ERK2, and MKK7 overexpression in HEK 293T cells. Furthermore, H. littoralis displayed anti-inflammatory effects in the HCl/EtOH-induced gastritis mice model. CONCLUSIONS: Cumulatively, these results demonstrated that H. littoralis exerts eminently anti-inflammatory activities in LPS-stimulated RAW264.7 cells in vitro and in HCl/EtOH-induced gastritis mice models in vivo. These activities could be attributed to its modulatory effects on the MAPK signaling pathway.

The comparisons of expression pattern reveal molecular regulation of fruit metabolites in S. nigrum and S. lycopersicum.

Solanum nigrum, known as black nightshade, is a medicinal plant that contains many beneficial metabolites in its fruit. The molecular mechanisms underlying the synthesis of these metabolites remain uninvestigated due to limited genetic information. Here, we identified 47,470 unigenes of S. nigrum from three different tissues by de novo transcriptome assembly, and 78.4% of these genes were functionally annotated. Moreover, gene ontology (GO) analysis using 18,860 differentially expressed genes (DEGs) revealed tissue-specific gene expression regulation. We compared gene expression patterns between S. nigrum and tomato (S. lycopersicum) in three tissue types. The expression patterns of carotenoid biosynthetic genes were different between the two species. Comparison of the expression patterns of flavonoid biosynthetic genes showed that 9 out of 14 enzyme-coding genes were highly upregulated in the fruit of S. nigrum. Using CRISPR-Cas9-mediated gene editing, we knocked out the R2R3-MYB transcription factor SnAN2 gene, an ortholog of S. lycopersicum ANTHOCYANIN 2. The mutants showed yellow/green fruits, suggesting that SnAN2 plays a major role in anthocyanin synthesis in S. nigrum. This study revealed the connection between gene expression regulation and corresponding phenotypic differences through comparative analysis between two closely related species and provided genetic resources for S. nigrum.

The Effect of Hamstring Relaxation Program on Headache, Pressure Pain Threshold, and Range of Motion in Patients with Tension Headache: A Randomized Controlled Trial.

The purpose of this study was to determine if the severity of headache is reduced by decreasing hamstring tension in patients with tension headache. Thirty patients participated in this study. The participants were randomly allocated to two groups: hamstring relaxation program (HR) group (n = 15) and control group (n = 15). The participants in the HR group participated in a HR program for 25 min per day, three times per week, for a period of 4 weeks, and the control group participated in an electrotherapy for 25 min per day, three times per week, for a period of 4 weeks. Both groups participated in a self-myofacial release for 5 min per day, three times per week, for a period of 4 weeks. Headache was evaluated using the headache impact test (HIT-6) and visual analog scale (VAS). The pain pressure threshold (PPT) was evaluated using a digital pressure algometer. The range of motion (ROM) was evaluated using a goniometer and two special tests: straight leg raise test (SLRT) and popliteal angle test (PAT). The two groups showed no significant differences in terms of age, sex, height, and weight. The VAS and HIT-6 scores (p < 0.05) and neck and hamstring PPT showed significant improvements (p < 0.05). Neck flexion ROM and SLRT and PAT scores showed significant improvements (p < 0.05) in both groups, and the HR group showed significantly more improvements than the control group. This study confirmed that the HR program has positive effects on tension headache and is a good intervention for alleviating headaches in patients with tension headache.

Anti-Gastritis and Anti-Lung Injury Effects of Pine Tree Ethanol Extract Targeting Both NF-κB and AP-1 Pathways.

An ethanol extract (Pd-EE) of Pinus densiflora Siebold and Zucc was derived from the branches of pine trees. According to the Donguibogam, pine resin has the effects of lowering the fever, reducing pain, and killing worms. The purpose of this study is to investigate whether Pd-EE has anti-inflammatory effects. During in vitro trials, NO production, as well as changes in the mRNA levels of inflammation-related genes and the phosphorylation levels of related proteins, were confirmed in RAW264.7 cells activated with lipopolysaccharide depending on the presence or absence of Pd-EE treatment. The activities of transcription factors were checked in HEK293T cells transfected with adapter molecules in the inflammatory pathway. The anti-inflammatory efficacy of Pd-EE was also estimated in vivo with acute gastritis and acute lung injury models. LC-MS analysis was conducted to identify the components of Pd-EE. This extract reduced the production of NO and the mRNA expression levels of iNOS, COX-2, and IL-6 in RAW264.7 cells. In addition, protein expression levels of p50 and p65 and phosphorylation levels of FRA1 were decreased. In the luciferase assay, the activities of NF-κB and AP-1 were lowered. In acute gastritis and acute lung injury models, Pd-EE suppressed inflammation, resulting in alleviated damage.

Nontargeted Metabolomics as a Screening Tool for Estimating Bioactive Metabolites in the Extracts of 50 Indigenous Korean Plants.

Many indigenous Korean plants have been used in medicinal preparations and health-promoting foods. These plant species contain beneficial metabolites with various bioactivities, such as antioxidant and anti-inflammatory activities. Herein, we suggest a new screening strategy using metabolomics to explore the bioactive compounds in 50 Korean plants. Secondary metabolites were analyzed using UHPLC-LTQ-Orbitrap-MS/MS. The plant extracts were subjected to antioxidant and anti-inflammatory assays. We identified metabolites that contributed to bioactivities according to the results of bioassays and multivariate analyses. Using Pearson's correlation, phenolics (e.g., casuarictin, 3-O-methylellagic acid) showed positive correlation with antioxidant activity, while biflavonoids (e.g., amentoflavone, rosbustaflavone) were correlated with nitric oxide (NO) inhibition activity. To compensate for the limitation of this new strategy, we further validated these by investigating three parts (branches, fruits, leaves) of Platycladus orientalis which showed high activities on both bioassays. Unlike the above observation, we identified significantly different metabolites from different parts, which was not the results of bioassays. In these validation steps, interestingly, biflavonoids (e.g., robustaflavone, sciadopitysin) contributed to both activities in P. orientalis. The findings of this work suggest that new strategy could be more beneficial in the identification of bioactive plant species as well as that of their corresponding bioactive compounds that impart the bioactivity.

Dipterocarpus tuberculatus Roxb. Ethanol Extract Has Anti-Inflammatory and Hepatoprotective Effects In Vitro and In Vivo by Targeting the IRAK1/AP-1 Pathway.

Dipterocarpus tuberculatus Roxb. has been used traditionally as a remedy for many diseases, especially inflammation. Therefore, we analyzed and explored the mechanism of the anti-inflammatory effect of a Dipterocarpus tuberculatus Roxb. ethanol extract (Dt-EE). Dt-EE clearly and dose-dependently inhibited the expression of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1ß in lipopolysaccharide (LPS)-treated RAW264.7 cells. Also, Dt-EE suppressed the activation of the MyD88/TRIF-mediated AP-1 pathway and the AP-1 pathway related proteins JNK2, MKK4/7, and TAK1, which occurred as a result of inhibiting the kinase activity of IRAK1 and IRAK4, the most upstream factors of the AP-1 pathway. Finally, Dt-EE displayed hepatoprotective activity in a mouse model of hepatitis induced with LPS/D-galactosamine (D-GalN) through decreasing the serum levels of alanine aminotransferase and suppressing the activation of JNK and IRAK1. Therefore, our results strongly suggest that Dt-EE could be a candidate anti-inflammatory herbal medicine with IRAK1/AP-1 inhibitory and hepatoprotective properties.

Syk/NF-κB-targeted anti-inflammatory activity of Melicope accedens (Blume) T.G. Hartley methanol extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Melicope accedens (Blume) Thomas G. Hartley is a plant included in the family Rutaceae and genus Melicope. It is a native plant from Vietnam that has been used for ethnopharmacology. In Indonesia and Malaysia, the leaves of M. accedens are applied externally to decrease fever. AIM OF THE STUDY: The molecular mechanisms of the anti-inflammatory properties of M. accedens are not yet understood. Therefore, we examined those mechanisms using a methanol extract of M. accedens (Ma-ME) and determined the target molecule in macrophages. MATERIALS AND METHODS: We evaluated the anti-inflammatory effects of Ma-ME in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and in an HCl/EtOH-triggered gastritis model in mice. To investigate the anti-inflammatory activity, we performed a nitric oxide (NO) production assay and ELISA assay for prostaglandin E2 (PGE2). RT-PCR, luciferase gene reporter assays, western blotting analyses, and a cellular thermal shift assay (CETSA) were conducted to identify the mechanism and target molecule of Ma-ME. The phytochemical composition of Ma-ME was analyzed by HPLC and LC-MS/MS. RESULTS: Ma-ME suppressed the production of NO and PGE2 and the mRNA expression of proinflammatory genes (iNOS, IL-1ß, and COX-2) in LPS-stimulated RAW264.7 cells without cytotoxicity. Ma-ME inhibited NF-κB activation by suppressing signaling molecules such as IκBα, Akt, Src, and Syk. Moreover, the CETSA assay revealed that Ma-ME binds to Syk, the most upstream molecule in the NF-κB signal pathway. Oral administration of Ma-ME not only alleviated inflammatory lesions, but also reduced the gene expression of IL-1ß and p-Syk in mice with HCl/EtOH-induced gastritis. HPLC and LC-MS/MS analyses confirmed that Ma-ME contains various anti-inflammatory flavonoids, including quercetin, daidzein, and nevadensin. CONCLUSIONS: Ma-ME exhibited anti-inflammatory activities in vitro and in vivo by targeting Syk in the NF-κB signaling pathway. Therefore, we propose that Ma-ME could be used to treat inflammatory diseases such as gastritis.

The Anti-Cancer Effect of Linusorb B3 from Flaxseed Oil through the Promotion of Apoptosis, Inhibition of Actin Polymerization, and Suppression of Src Activity in Glioblastoma Cells.

Linusorbs (LOs) are natural peptides found in flaxseed oil that exert various biological activities. Of LOs, LOB3 ([1-9-NαC]-linusorb B3) was reported to have antioxidative and anti-inflammatory activities; however, its anti-cancer activity has been poorly understood. Therefore, this study investigated the anti-cancer effect of LOB3 and its underlying mechanism in glioblastoma cells. LOB3 induced apoptosis and suppressed the proliferation of C6 cells by inhibiting the expression of anti-apoptotic genes, B cell lymphoma 2 (Bcl-2) and p53, as well as promoting the activation of pro-apoptotic caspases, caspase-3 and -9. LOB3 also retarded the migration of C6 cells, which was achieved by suppressing the formation of the actin cytoskeleton critical for the progression, invasion, and metastasis of cancer. Moreover, LOB3 inhibited the activation of the proto-oncogene, Src, and the downstream effector, signal transducer and activator of transcription 3 (STAT3), in C6 cells. Taken together, these results suggest that LOB3 plays an anti-cancer role by inducing apoptosis and inhibiting the migration of C6 cells through the regulation of apoptosis-related molecules, actin polymerization, and proto-oncogenes.

Therapeutic effects of brain-computer interface-controlled functional electrical stimulation training on balance and gait performance for stroke: A pilot randomized controlled trial.

BACKGROUND: Brain-computer interface-controlled functional electrical stimulation (BCI-FES) approaches as new feedback training is increasingly being investigated for its usefulness in improving the health of adults or partially impaired upper extremity function in individuals with stroke. OBJECTIVE: To evaluate the effects of BCI-FES on postural control and gait performance in individuals with chronic hemiparetic stroke. METHODS: A total of 25 individuals with chronic hemiparetic stroke (13 individuals received BCI-FES and 12 individuals received functional electrical stimulation [FES]). The BCI-FES group received BCI-FES on the tibialis anterior muscle on the more-affected side for 30 minutes per session, 3 times per week for 5 weeks. The FES group received FES using the same methodology for the same periods. This study used the Mann-Whitney test to compare the two groups before and after training. RESULTS: After training, gait velocity (mean value, 29.0 to 42.0 cm/s) (P = .002) and cadence (mean value, 65.2 to 78.9 steps/min) (P = .020) were significantly improved after BCI-FES training compared to those (mean value, 23.6 to 27.7 cm/s, and mean value, 59.4 to 65.5 steps/min, respectively) after FES approach. In the less-affected side, step length was significantly increased after BCI-FES (mean value, from 28.0 cm to 34.7 cm) more than that on FES approach (mean value, from 23.4 to 25.4 cm) (P = .031). CONCLUSION: The results of the BCI-FES training shows potential advantages on walking abilities in individuals with chronic hemiparetic stroke.

Effects of Mulligan Mobilization and Low-Level Laser Therapy on Physical Disability, Pain, and Range of Motion in Patients with Chronic Low Back Pain: A Pilot Randomized Controlled Trial.

This study aimed to determine the combined treatment effects of Mulligan sustained natural apophyseal glides (SNAGs) and low-level laser therapy (LLLT) on function, pain, and range of motion (ROM) in patients with chronic low back pain. A total of 49 adults participated in this study and were randomly divided into three groups (SNAGs with LLLT group, SNAGs group, and control group). The participants in the SNAGs with LLLT group received SNAGs for 10 min, LLLT for 10 min, and electrotherapy for 10 min. The SNAGs group received SNAGs for 10 min and electrotherapy for 20 min. The control group received electrotherapy for 30 min. All participants received the assigned treatment for 30 min a day, 3 times a week, for 4 weeks. We used the visual analogue scale (VAS) to measure pain, the modified-modified Schober test (MMST) to measure ROM, and the Roland Morris disability questionnaire (RMDQ) to measure physical disability. Compared to the pre-intervention values, the VAS and MMST scores significantly increased after the intervention in the SNAGs with LLLT group (p = 0.000) and the SNAGs group (p = 0.000). The RMDQ score significantly improved in the SNAGs with LLLT (p = 0.000), SNAGs (p = 0.000) and control (p = 0.025) group after the intervention. The inter-group differences were greater for the SNAGs with LLLT and SNAGs groups than for the control group (p = 0.001), and the difference was greater for the SNAGs with LLLT than for the SNAGs (p = 0.001) with respect to the VAS, MMST, and RMDQ scores. These results indicate that significant improvement in pain, function, and ROM may be achieved by a combination of SNAGs and LLLT to treat chronic low back pain.