Chemical Composition, Anti-bacterial Activity and Molecular Docking Studies of Essential Oil Isolated from Sa Sam Nam (Launaea sarmentosa).

Launaea sarmentosa, also known as Sa Sam Nam, is a widely used remedy in Vietnamese traditional medicine and cuisine. However, the chemical composition and bioactivity of its essential oil have not been elucidated yet. In this study, we identified 40 compounds (98.6% of total peak area) in the essential oil via GC-MS analysis at the first time. Among them, five main compounds including Thymohydroquinone dimethyl ether (52.4%), (E)-α-Atlantone (9.0%), Neryl isovalerate (6.6%), Davanol D2 (isomer 2) (3.9%), and trans-Sesquisabinene hydrate (3.9%) have accounted for 75.8% of total peak area. The anti-bacterial activity of the essential oil against 4 microorganisms including Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa has also investigated via agar well diffusion assay. The results showed that the essential oil exhibited a strong antibacterial activity against Bacillus subtilis with the inhibition zones ranging from 8.2 to 18.7 mm. To elucidate the anti-bacterial effect mechanism of the essential oil, docking study of five main compounds of the essential oil (Thymohydroquinone dimethyl ether, (E)-α-Atlantone, Neryl isovalerate, Davanol D2 (isomer 2), and trans-Sesquisabinene hydrate) against some key proteins for bacterial growth such as DNA gyrase B, penicillin binding protein 2A, tyrosyl-tRNA synthetase, and dihydrofolate reductase were performed. The results showed that the main constituents of essential oil were highly bound with penicillin binding protein 2A with the free energies ranging -27.7 to -44.8 kcal/mol, which suggests the relationship between the antibacterial effect of essential oil and the affinity of main compounds with penicillin binding protein. In addition, the free energies of main compounds of the essential oil with human cyclooxygenase 1, cyclooxygenase 2, and phospholipase A2, the crucial proteins related with inflammatory response were less than diclofenac, a non-steroidal antiinflammatory drug. These findings propose the essential oil as a novel and promising anti-bacterial and anti-inflammatory medicine or cosmetic products.

Anti-Arthritis Effect of Ethanol Extract of Sacha Inchi (Plukenetia volubilis L.) Leaves Against Complete Freund's Adjuvant-Induced Arthritis Model in Mice.

Sacha inchi (Plukenetia volubilis L.) is a well-known oleaginous plant used as food source and traditional medicine by indigenous people for a long time. This study was conducted to evaluate anti-arthritis effect of ethanol extract of Sacha inchi leaves and provide scientific evidence to develop the new anti-arthritis remedy from Sacha inchi. Rheumatoid arthritis model was established by injection of complete Freund's adjuvant into right hind footpads of mice and three doses of ethanol extract of Sacha inchi leaves (100, 200 and 300 mg/kg body weight) were used for treatment. The severity of arthritis was evaluated by measuring the ankle diameter and arthritic score, hematological and biochemical parameters (erythrocytes, leukocytes, lymphocytes, monocytes, granulocytes counts, erythrocyte sedimentation rate, C-reactive protein and rheumatoid factor). The pro-and anti-inflammatory cytokines (TNF-α, INF-γ, IL-1ß, IL-6, and IL-10) and the histology change of joint were also examined. All three doses of extracts significantly alleviated ankle diameter and arthritic score. Furthermore, the extracts could ameliorate the alternation of inflammatory cytokines as well histological features of CFA-induced mice. The efficacy of extract dose of 300 mg/kg body weight is comparable with reference drug (Mobic, 0.2 mg/kg body weight). This study indicates Sacha inchi leaf extract as the promising remedy for treatment of arthritis.

Caffeine Supplementation and FOXM1 Inhibition Enhance the Antitumor Effect of Statins in Neuroblastoma.

High-risk neuroblastoma exhibits transcriptional activation of the mevalonate pathway that produces cholesterol and nonsterol isoprenoids. A better understanding of how this metabolic reprogramming contributes to neuroblastoma development could help identify potential prevention and treatment strategies. Here, we report that both the cholesterol and nonsterol geranylgeranyl-pyrophosphate branches of the mevalonate pathway are critical to sustain neuroblastoma cell growth. Blocking the mevalonate pathway by simvastatin, a cholesterol-lowering drug, impeded neuroblastoma growth in neuroblastoma cell line xenograft, patient-derived xenograft (PDX), and TH-MYCN transgenic mouse models. Transcriptional profiling revealed that the mevalonate pathway was required to maintain the FOXM1-mediated transcriptional program that drives mitosis. High FOXM1 expression contributed to statin resistance and led to a therapeutic vulnerability to the combination of simvastatin and FOXM1 inhibition. Furthermore, caffeine synergized with simvastatin to inhibit the growth of neuroblastoma cells and PDX tumors by blocking statin-induced feedback activation of the mevalonate pathway. This function of caffeine depended on its activity as an adenosine receptor antagonist, and the A2A adenosine receptor antagonist istradefylline, an add-on drug for Parkinson's disease, could recapitulate the synergistic effect of caffeine with simvastatin. This study reveals that the FOXM1-mediated mitotic program is a molecular statin target in cancer and identifies classes of agents for maximizing the therapeutic efficacy of statins, with implications for treatment of high-risk neuroblastoma. SIGNIFICANCE: Caffeine treatment and FOXM1 inhibition can both enhance the antitumor effect of statins by blocking the molecular and metabolic processes that confer statin resistance, indicating potential combination therapeutic strategies for neuroblastoma. See related commentary by Stouth et al., p. 2091.

Potential therapeutic and pharmacological effects of Wogonin: an updated review.

Flavonoids are members of polyphenolic compounds, which are naturally presented in fruits, vegetables, and some medicinal plants. Traditionally, the root of Scutellaria baicalensis is widely used as Chinese herbal medicine and contains several major bioactive compounds such as Wogonin, Scutellarein, Baicalein, and Baicalin. Experimental and clinical evidence has been proving that Wogonin exhibits diverse biological activities such as anti-cancer, anti-inflammation, and treatment of bacterial and viral infections. In this review, we summarize and emphasize the benefits of Wogonin as a therapeutic adjuvant for anti-viral infection, anti-inflammation, neuroprotection as well as anxiolytic and anticonvulsant. Moreover, the molecular mechanism(s) how Wogonin mediates the cellular signal pathways and immune responses are also discussed and highlighted valuable properties of Wogonin in multiple therapies.

Homeostasis of histone acetylation is critical for auxin signaling and root morphogenesis.

KEY MESSAGE: The auxin signaling and root morphogenesis are harmoniously controlled by two counteracted teams including (1) auxin/indole-3-acetic acid (AUX/IAA)-histone deacetylase (HDA) and (2) auxin response factor (ARF)-histone acetyltransferase (HAT). The involvement of histone acetylation in the regulation of transcription was firstly reported a few decades ago. In planta, auxin is the first hormone group that was discovered and it is also the most studied phytohormone. Current studies have elucidated the functions of histone acetylation in the modulation of auxin signaling as well as in the regulation of root morphogenesis under both normal and stress conditions. Based on the recent outcomes, this review is to provide a hierarchical view about the functions of histone acetylation in auxin signaling and root morphogenesis. In this report, we suggest that the auxin signaling must be controlled harmoniously by two counteracted teams including (1) auxin/indole-3-acetic acid (AUX/IAA)-histone deacetylase (HDA) and (2) auxin response factor (ARF)-histone acetyltransferase (HAT). Moreover, the balance in auxin signaling is very critical to contribute to normal root morphogenesis.

Anti-oxidative effects of superoxide dismutase 3 on inflammatory diseases.

Free radicals and other oxidants are critical determinants of the cellular signaling pathways involved in the pathogenesis of several human diseases including inflammatory diseases. Numerous studies have demonstrated the protective effects of antioxidant enzymes during inflammation by elimination of free radicals. The superoxide dismutase (SOD), an antioxidant enzyme, plays an essential pathogenic role in the inflammatory diseases by not only catalyzing the conversion of the superoxide to hydrogen peroxide and oxygen but also affecting immune responses. There are three distinct isoforms of SOD, which distribute in different cellular compartments such as cytosolic SOD1, mitochondrial SOD2, and extracellular SOD3. Many studies have investigated the anti-oxidative effects of SOD3 in the inflammatory diseases. Herein, in this review, we focus on the current understanding of SOD3 as a therapeutic protein in inflammatory diseases such as skin, autoimmune, lung, and cardiovascular inflammatory diseases. Moreover, the mechanism(s) by which SOD3 modulates immune responses and signal initiation in the pathogenesis of the diseases will be further discussed.

The MYB-bHLH-WDR interferers (MBWi) epigenetically suppress the MBW's targets.

Active repressors have been evidenced to function in different plant growth and development programs including hormonal signalling pathways. In Arabidopsis, the MYB-bHLH-WDR (MBW) complex is known to regulate different phenotypic traits such as anthocyanin biosynthesis, seed coat colour, trichome and root hair patterning. A number of transcription factors have been identified to play a negative role in the regulation of these traits via the interruption of MBW formation and function. Since these transcription factors work to interfere with the MBW complex, this review suggests their general name as MBW interferers (MBWi). Recent studies have shed light on the molecular mechanism of these MBWi and this review is aiming to provide a precise view of these MBWi. Moreover, from these, a new characteristic of active repressors is also updated.

Optimization of Fermentation Conditions and Media for Production of Glucose Isomerase from Bacillus megaterium Using Response Surface Methodology.

Glucose isomerase is an enzyme widely used in food industry for producing high-fructose corn syrup. Many microbes, including Bacillus megaterium, have been found to be able to produce glucose isomerase. However, the number of studies of glucose isomerase production from Bacillus megaterium is limited. In this study, we establish the optimal medium components and culture conditions for Bacillus megaterium glucose isomerase production by evaluating the combined influence of multiple factors and different parameters via Plackett-Burman design and response surface methodology in Modde 5.0 software. The optimized conditions, which were experimentally confirmed as follows: D-xylose (1.116%), K2HPO4 (0.2%), MgSO4·7H2O (0.1%), yeast extract (1.161%), peptone (1%), pH 7.0, inoculum size 20% (w/v), shaking 120 rpm at 36.528°C for 48 hours, give rise to production of highest activity of glucose isomerase (0.274 ± 0.003 U/mg biomass). These results provide additional important information for future development of large-scale glucose isomerase production by Bacillus megaterium.

Amelioration of Single Clove Black Garlic Aqueous Extract on Dyslipidemia and Hepatitis in Chronic Carbon Tetrachloride Intoxicated Swiss Albino Mice.

Single clove garlic is the product of atypical bulbing process of garlic under specific conditions. Therefore, the number of researches on single clove garlic bioactivity is limited. Recently, the hepatoprotective effect of single clove garlic has been demonstrated. In this study, we investigated amelioration of single clove black garlic aqueous extract, a processed product from single clove garlic, on dyslipidemia and hepatitis induced by chronic administration of CCl4. Mice were randomly divided into four groups: control, extract control, CCl4 intoxication, and coadministrated CCl4 and extract group. Mice were orally given a dose of 1 ml/kg body weight of CCl4 for 28 days twice a week to establish chronic liver injury model. To evaluate the hepatoprotective effect of single clove black garlic, mice were cotreated with CCl4 and single clove black garlic extract (200 mg/kg body weight) via gastric gauge for 30 days. Cotreatment with CCl4 and extract could improve the changes of body weight, liver weight, and relative liver weight as compared to CCl4 intoxicated mice. Single clove black garlic ameliorated dyslipidemia and the elevation of ALT and AST levels induced by chronic CCl4 intoxication. Histological studies revealed that single clove black garlic could prevent mononuclear cells infiltration and hepatocyte necrosis.

Potential Use of Essential Oil Isolated from Cleistocalyx operculatus Leaves as a Topical Dermatological Agent for Treatment of Burn Wound.

Several herbal remedies have been used as topical agents to cure burn wound, one of the most common injuries in worldwide. In this study, we investigated the potential use of Cleistocalyx operculatus essential oil to treat the burn wound. We identified a total of 13 bioactive compounds of essential oil, several of which exhibited the anti-inflammatory and antimicrobial activities. Furthermore, the essential oil showed the antibacterial effect against S. aureus but not with P. aeruginosa. The supportive effect of essential oil on burn wound healing process also has been proven. Among three groups of mice, wound contraction rate of essential oil treated group (100%) was significantly higher than tamanu oil treated (79%) and control mice (71%) after 20 days (0.22 ± 0.03 versus 0.31 ± 0.02 cm2, resp., p < 0.05). Histological studies revealed that burn wounds treated with essential oil formed a complete epidermal structure, thick and neatly arranged fibers, and scattered immune cells in burn wound. On the contrary, saline treated burn wound formed uneven epidermal layer with necrotic ulcer, infiltration of immune cells, and existence of granulation tissue. This finding demonstrated Cleistocalyx operculatus essential oil as promising topical dermatological agent to treat burn wound.

Interaction of peroxiredoxin V with dihydrolipoamide branched chain transacylase E2 (DBT) in mouse kidney under hypoxia.

BACKGROUND: Peroxiredoxin V (Prdx V) plays a major role in preventing oxidative damage as an effective antioxidant protein within a variety of cells through peroxidase activity. However, the function of Prdx V is not limited to peroxidase enzymatic activity per se. It appears to have unique function in regulating cellular response to external stimuli by directing interaction with signaling protein. In this study, we identified Prdx V interacting partners in mouse kidney under hypoxic stress using immunoprecipitation and shotgun proteomic analysis (LC-MS/MS). RESULTS: Immunoprecipitation coupled with nano-UPLC-MS(E) shotgun proteomics was employed to identify putative interacting partners of Prdx V in mouse kidney in the setting of hypoxia. A total of 17 proteins were identified as potential interacting partners of Prdx V by a comparative interactomics analysis in kidney under normoxia versus hypoxia. Dihydrolipoamide branched chain transacylase E2 (DBT) appeared to be a prominent candidate protein displaying enhanced interaction with Prdx V under hypoxic stress. Moreover, hypoxic kidney exhibited altered DBT enzymatic activity compared to normoxia. An enhanced colocalization of these two proteins under hypoxic stress was successfully observed in vitro. Furthermore, peroxidatic cysteine residue (Cys48) of Prdx V is likely to be responsible for interacting with DBT. CONCLUSIONS: We identified several proteins interacting with Prdx V under hypoxic condition known to induce renal oxidative stress. In hypoxic condition, we observed an enhanced interaction of Prdx V and DBT protein as well as increased DBT enzymatic activity. The results from this study will contribute to enhance our understanding of Prdx V's role in hypoxic stress and may suggest new directions for future research.