Enhanced photocatalytic efficiencies in a bifunctional ZnO/PVA nanocomposites derived from Capparis zeylanica L.

The modern food sector demands versatile nanocomposites of polymers for food to wrappers to inactivate germs linked to foods in order to ensure quality throughout the packaging process. Recently, it has become quite appealing to use zinc oxide nanocomposite with polyvinyl alcohol (PVA) assistance for food storage containers. Variable combinations of zinc acetate and Capparis zeylanica leaf extract (3:1, 1:7, 1:3, and 1:1) were used to create nanostructured ZnO at the desired pH (10.5). ZnO/PVA nanocomposites films were created with different weight % of (16, 13, 9 and 5%) ZnO nanoparticles by using solution casting method. The generated ZnO and ZnO/PVA nanocomposites (NCs) were characterized using analytical techniques like X-ray diffraction spectroscopy (XRD), ultraviolet spectroscopic analysis (UV-Vis), Fourier-transform infrared analysis (FT-IR), and field emission scanning electron microscopic study (FE-SEM). The generated ZnO and ZnO/PVA NCs were tested for their efficacy as antibacterial agents against Gram + ve (Streptococcus pyogenes, Staphylococcus aureus) and Gram -ve (Pseudomonas aeruginosa, and E. coli) bacteria. Under UV-visible irradiation, the methylene blue (MB) breakdown caused by the fabricated undoped ZnO and ZnO/PVA nanomixture was investigated. The FE-SEM investigation for synthesized ZnO from a 1:1 ratio exhibited spherical shaped appearance. However, the nanocomposite made with 5% ZnO showed equally scattered nanoflake particles in the matrix of PVA film as well as on the surface. The XRD results showed that ZnO synthesized with a higher proportion of plant extract produced smaller crystallites, whereas ZnO synthesized with a lower percentage of plant extract produced bigger crystallite sizes. The optimum concentration for the breakdown of methylene blue (MB) among the various concentrations examined was 5% ZnO/PVA. Furthermore, a study of the biomedical efficiency of undoped ZnO and ZnO/PVA revealed that 5% ZnO/PVA had the potential antibacterial efficacies.

Toxicological effect of endocrine disrupting insecticide (deltamethrin) on enzymatical, haematological and histopathological changes in the freshwater iridescent shark, Pangasius hypothalamus.

This study investigated the deltamethrin (DMN) induced harmful effects on Pangasius hypophthalmus using enzymatic activity, haematological, and histopathological changes. LC50 value was 0.021 mg/L at 96 h, and sublethal toxicity was tested for 45 days at two `concentrations (i.e., 1/5th and 1/10th of LC50). Haematological parameters and enzymatic activities significantly changed between DMN-exposed and control groups (p < 0.05). Histopathologically, both DMN doses induced liver hyperemia, hepatic cell rupture, necrosis, hypertrepheoid bile duct, shifting nuclei, vascular haemorrhage, and hepatocyte degeneration, while in gill, secondary lamellae destruction, a fusion of adjacent gill lamellae, hypertrophy, hyperplasia, adhesion, and fusion were noticed. Kidney developed melanomacrophages, increased periglomerular and peritubular space, vacuolation, decreased glomerulus, hyaline droplets in tubular cells, loss of tubular epithelium, distal convoluted segment hypertrophy, and granular layer in brain pyramid and Purkinje cell nucleus. But, limiting pesticide impacts on freshwater fish and their habitat requires a holistic, cradle-to-grave approach and toxicological studies.

Toll-like receptor 4 is a key regulator of asthma exacerbation caused by aluminum oxide nanoparticles via regulation of NF-κB phosphorylation.

Aluminum oxide nanoparticles (Al2O3 NPs) have recently been reported to cause an inflammatory response in the lungs, and studies are being conducted on their adverse effects, especially in patients with underlying lung diseases such as asthma. However, the underlying mechanism of asthma aggravation caused by Al2O3 NPs remains unclear. This study investigated whether Al2O3 NPs exacerbate ovalbumin (OVA)-induced asthma and focused on the correlation between toll-like receptor 4 (TLR4) signaling and Al2O3 NP-induced asthma exacerbation. Al2O3 NP exposure in asthmatic mice resulted in increased inflammatory cell counts in the lungs, airway hyperresponsiveness, and increased levels of inflammatory cytokines compared with only OVA-induced mice, and excessive secretion of mucus was observed in the airways. Moreover, Al2O3 NP exposure in OVA-induced mice increased the expression levels of TLR4, phospho-nuclear transcription factor-kappa B (p-NFκB), myeloid differentiation factor 88 (MyD88), and phospho-NF kappa B inhibitor alpha (p-IκBα). Furthermore, in the lungs of TLR4 knockout mice exposed to Al2O3 NPs and in a human airway epithelial cell line with down regulated TLR4, the expression levels of MyD88, p-NFκB, and p-IκBα were decreased, and asthma-related allergic responses were reduced. Therefore, we demonstrated that TLR4 is important for aggravation of asthma induced by Al2O3 NPs, and this study provides useful information regarding as yet undiscovered novel target signaling.

Bioremediations analysis using multifactorial porous materials derived from tea residue.

Titanium dioxide nanoparticles (TiO2 NPs) are becoming more and more renowned as biocompatible nanomaterials with diverse biological functions. In the present study, the aqueous extract of tea residue (tea filtered waste powder) was used to synthesize the TiO2 NPs and treated for effluent bioremediations. Maximum absorption in the UV-Vis spectrum of the TiO2 NPs was seen at 358 nm, and the XRD pattern reveals peaks at 2 h values of 25.78, 38.24, 47.98, 54.76, 55.32, 62.64, 69.05, 70.15, 75.24, and 83.59 that may be indexed to the (101), (004), (200), (105), (211), (204), (116), (220), (215) and (303). The FT-IR spectra of TiO2 NPs showed a peak at 3420, 2925, 1621, 1382, 1098, and 687 cm-1. The spherical form and size were disclosed by FE-SEM analyses, and the EDAX pattern verified the purity of the TiO2 NPs. The average particles size of the TiO2 NPs was 32 nm. The photodegradation of paper mill waste water is significantly deteriorated up to 99.08% for 600 min, but textile waste water is degraded up to 98.06% for the same duration. Furthermore, we reported that TiO2 NPs may rapidly breakdown industrially hazardous effluents when exposed to sunshine. Overall, this new, straightforward, and environmentally beneficial strategy may be of interest to the management of efficient degradation of dye solutions in the polluted regions.

Cytogenotoxicity assessment in Allium cepa roots exposed to methyl orange treated with Oedogonium subplagiostomum AP1.

The present study is an attempt to assess the cytogenotoxic effect of untreated and methyl orange treated with Oedogonium subplagiostomum AP1 on Allium cepa roots. On the fifth day, root growth, root length, mitotic index, mitotic inhibition/depression, and chromosomal abnormalities were measured in root cells of Allium cepa subjected to untreated and treated methyl orange dye solutions. Roots exposed to treated dye solution exhibited maximum root growth, root length and mitotic index, whereas roots exposed to untreated dye solution had the most mitotic inhibition and chromosomal abnormalities. Allium cepa exposed to untreated dye solution revealed chromosomal aberrations such as disoriented and abnormal chromosome grouping, vagrant and laggard chromosomes, chromosomal loss, sticky chain and disturbed metaphase, pulverised and disturbed anaphase, chromosomal displacement in anaphase, abnormal telophase, and chromosomal bridge at telophase, spindle disturbances and binucleate cells. The comet test was used to quantify DNA damage in the root cells of A. cepa subjected to untreated and treated methyl orange solutions in terms of tail DNA (percent) and tail length. The results concluded that A. cepa exposed to methyl orange induced DNA damage whereas meager damage was noted in the treated dye solution. As a result, the research can be used as a biomarker to detect the genotoxic effects of textile dyes on biota.

Characterization of two novel strains of Pseudomonas aeruginosa on biodegradation of crude oil and its enzyme activities.

Crude oil contaminant is one of the major problem to environment and its removal process considered as most challenging tool currently across the world. In this degradation study, crude oil hydrocarbons are degraded on various pH optimization conditions (pH 2, 4,6,7,8 and 10) by using two biosurfactant producing bacterial strains Pseudomonas aeruginosa PP3 and Pseudomonas aeruginosa PP4. During crude oil biodegradation, degradative enzymes alkane hydroxylase and alcohol dehydrogenase were examined and found to be higher in PP4 than PP3. Biodegradation efficiency (BE) of crude oil by both PP3 and PP4 were analysed by gas chromatography mass spectroscopy (GCMS). Based on strain PP3, the highest BE was observed in pH 2 and pH 4 were found to be 62% and 69% than pH 6, 7, 8 and 10 (47%, 47%, 49% and 45%). It reveals that PP3 was survived effectively in acidic condition and utilized the crude oil hydrocarbons. In contrast, the highest BE of PP4 was observed in pH 7 (78%) than pH4 (68%) and pH's 2, 6, 8 and 10 (52%, 52%, 43% and 53%) respectively. FTIR spectra results revealed that the presence of different functional group of hydrocarbons (OH, -CH3, CO, C-H) in crude oil. GCMS results confirmed that both strains PP3 and PP4 were survived in acidic condition and utilized the crude oil hydrocarbons as sole carbon sources. This is the first observation on biodegradation of crude oil by the novel strains of Pseudomonas aeruginosa in acidic condition with higher BE. Overall, the extracellular enzymes and surface active compounds (biosurfactant) produced by bacterial strains were played a key role in crude oil biodegradation process.

Synthesis and Structure-Activity Relationship Studies of Benzimidazole-4,7-dione-Based P2X3 Receptor Antagonists as Novel Anti-Nociceptive Agents.

P2X3 receptors (P2X3R) are ATP-gated ion channels predominantly expressed in C- and Aδ-fiber primary afferent neurons and have been introduced as a novel therapeutic target for neurological disorders, including neuropathic pain and chronic cough. Because of its localized distribution, antagonism of P2X3R has been thoroughly considered, and the avoidance of issues related to CNS side effects has been proven in clinical trials. In this article, benzimidazole-4,7-dione-based derivatives were introduced as a new chemical entity for the development of P2X3R antagonists. Starting from the discovery of a hit compound from the screening of 8364 random library compounds in the Korea Chemical Bank, which had an IC50 value of 1030 nM, studies of structure-activity and structure-property relationships enabled further optimization toward improving the antagonistic activities as well as the drug's physicochemical properties, including metabolic stability. As for the results, the final optimized compound 14h was developed with an IC50 value of 375 nM at P2X3R with more than 23-fold selectivity versus P2X2/3R, along with properties of metabolic stability and improved solubility. In neuropathic pain animal models evoked by either nerve ligation or chemotherapeutics in male Sprague-Dawley rats, compound 14h showed anti-nociceptive effects through an increase in the mechanical withdrawal threshold as measured by von Frey filament following intravenous administration.

Anti-asthmatic effects of Phlomis umbrosa Turczaninow using ovalbumin induced asthma murine model and network pharmacology analysis.

BACKGROUND: Phlomis umbrosa Turczaninow has been used as a tradition herbal medicine for treating various inflammatory diseases. PURPOSE: In present study, we explored the effects of P. umbrosa on asthma induced by ovalbumin (OVA) and elucidated the mechanism via in vivo verification and network pharmacology prediction. METHODS: The animals were intraperitoneally injected OVA on day 1 and 14, followed by OVA inhalation on days 21, 22, and 23. The animals were daily treated P. umbrosa extract (PUE, 20 and 40 mg/kg) by oral gavage from day 18 to day 23. RESULTS: PUE significantly decreased airway hyperresponsiveness, eosinophilia, and the production of inflammatory cytokines and OVA specific immunoglobulin E in animals with asthma, along with a reduction in airway inflammation and mucus secretion in lung tissue. In network analysis, antiasthmatic effects of PUE were closely related with suppression of mitogen-activated protein kinases and matrix metalloproteinases (MMPs). Consistent with the results from network analysis, PUE suppressed the phosphorylation of ERK and p65, which was accompanied by a decline in MMP-9 expression. CONCLUSION: Administration of PUE effectively reduced allergic responses in asthmatic mice, which was associated with the suppressed phosphorylation of ERK and p65, and expression of MMP-9. These results indicate that PUE has therapeutic potential to treat allergic asthma.

Subchronic Toxicity Evaluation of Aluminum Oxide Nanoparticles in Rats Following 28-Day Repeated Oral Administration.

Several studies on the potential adverse effects of aluminum oxide nanoparticles (Al2O3NPs) have reported conflicting results. The present study investigated the potential adverse effects of Al2O3NPs in Sprague-Dawley rats following 28-day repeated oral administration. In addition, we aimed to determine the target organ and no-observed-adverse-effect level (NOAEL) of Al2O3NPs. Al2O3NPs was administered once daily by gavage to male and female rats at dose levels of 0, 500, and 1000 mg/kg/day for 28 days. There were no treatment-related adverse effects as indicated by the clinical signs, body weight, food consumption, urinalysis, ophthalmology, hematology, serum biochemistry, gross pathology, organ weight, and histopathology at all the tested doses. Under the experimental conditions of the present study, 28-day repeated oral administration of Al2O3NPs at doses of up to 1000 mg/kg/day did not induce any treatment-related systemic toxicity in male and female rats. The NOAEL of Al2O3NPs was set at 1000 mg/kg/day in both male and female rats and no target organs were identified.

Cimicifugae Rhizoma Extract Attenuates Oxidative Stress and Airway Inflammation via the Upregulation of Nrf2/HO-1/NQO1 and Downregulation of NF-κB Phosphorylation in Ovalbumin-Induced Asthma.

Cimicifugae Rhizoma has been used as a medicinal herb for fever, pain, and inflammation in East Asia. We conducted this study because the effect of Cimicifugae Rhizoma extract (CRE) on allergic asthma has not yet been evaluated. To induce allergic airway inflammation, we intraperitoneally injected ovalbumin (OVA) mixed with aluminum hydroxide into mice twice at intervals of 2 weeks (Days 0 and 14) and then inhaled them thrice with 1% OVA solution using a nebulizer (Days 21 to 23). CRE (30 and 100 mg/kg) was administered orally daily for 6 days (Days 18 to 23). The mice showed remarkable reduction in allergic inflammation at 100 mg/kg of CRE, as evidenced by decreased inflammatory cell counts, pro-inflammatory cytokine levels, OVA-specific immunoglobulin E level, airway hyperresponsiveness, and production of mucus. Additionally, these effects were involved with the enhancement of heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase (NQO1), and nuclear factor erythroid 2-related factor 2 (Nrf2) expression and reduction of nuclear factor-κB (NF-κB) phosphorylation and matrix metalloproteinase-9 expression. Our findings indicated that CRE effectively protected against OVA-induced inflammation and oxidative stress via upregulation of the Nrf2/HO-1/NQO1 signaling and downregulation of NF-κB phosphorylation in asthma caused by OVA.

Characterization of crude oil degrading bacterial communities and their impact on biofilm formation.

In the present study, produced water sample collected from the Indian crude oil reservoir is used to enrich the bacterial communities. The impact of these enriched bacterial communities on the biodegradation of crude oil, biofilm formation, and biocorrosion process are elucidated. A crude oil degradation study is carried out with the minimal salt medium and 94% of crude oil was utilized by enriched bacterial communities. During the crude oil degradation many enzymes including alkane hydroxylase, alcohol dehydrogenase, and lipase are playing a key role in the biodegradation processes. The role of enriched bacterial biofilm on biocorrosion reactions are monitored by weight loss studies and electrochemical analysis. Weight loss study revealed that the biotic system has vigorous corrosion attacks compared to the abiotic system. Both AC-Impedance and Tafel analysis confirmed that the nature of the corrosion reaction take place in the biotic system. Very less charge transfer resistance and higher corrosion current are observed in the biotic system than in the abiotic system. Scanning electron microscope confirms that the dense biofilm formation favoured the pitting type of corrosion. X-ray diffraction analysis confirms that the metal oxides formed in the corrosion systems (biotic). From the metagenomic analysis of the V3-V4 region revealed that presence of diverse bacterial communities in the biofilm, and most of them are uncultured/unknown. Among the known genus, Bacillus, Halomonas, etc are dominant in the enriched bacterial biofilm sample. From this study, we conclude that the uncultured bacterial strains are found to be playing a key role in the pitting type of corrosion and they can utilize crude oil hydrocarbons, which make them succeeded in extreme oil reservoir environments.

Effect of Yijin-Tang, an Oriental Traditional Formula, on Allergic Responses Using an Ovalbumin-Induced Murine Asthma Model.

Yijin-tang is an oriental traditional herb used to treat inflammatory diseases. In the present study, we investigated the protective effects of Yijin-tang water extract (YTE) using an ovalbumin- (OVA-) induced asthma model, focusing on the antioxidant and anti-inflammatory properties of the herb. BALB/c mice were intraperitoneally injected with OVA on days 0 and 14 and then challenged with OVA on days 21, 22, and 23. The animals were orally administered YTE (200 and 400 mg/kg) from days 18 to 23, and this was found to significantly decrease airway hyperresponsiveness and release of inflammatory cells, cytokines, and OVA-specific immunoglobulin E in mice with asthma. In addition, YTE was associated with a marked reduction in airway inflammation and mucus production in lung tissue of mice with asthma. Furthermore, YTE suppressed the expression of matrix metalloproteinase-9 and phosphorylation of ERK in the lungs, which in turn led to a reduction in inducible nitric oxide synthases and an elevation in reduced glutathione and heme oxygenase-1. In conclusion, YTE effectively suppressed allergic responses in mice with asthma and the effect was closely related to antioxidant and anti-inflammatory properties of the herb. Our results indicate that YTE may be a potential agent for the treatment of allergic asthma.

Antihypertensive Effects of Dehydroabietic and 4-Epi-Trans-Communic Acid Isolated from Pinus densiflora.

Korean red pine needle (RPN) exhibits various biological and pharmacological activities. Among the various compounds of RPN, we isolated dehydroabietic and 4-epi-trans-communic acid. At first, we confirmed that two compounds inhibited angiotensin converting enzyme (ACE) and induced p-Akt in human umbilical vein endothelial cells (HUVEC). RPN extract powder significantly reduced systolic blood pressure in spontaneous hypertensive rats (SHRs) through the reduced expression of ACE and angiotensin type I receptors in the lungs of SHRs. The Lineweaver-Burk plots suggested that the two compounds were noncompetitive inhibitors of ACE. Using docking analysis, we found that two compounds showed the best returned pose at ACE active sites, and formed hydrogen and hydrophobic bonds with ACE residues. These results demonstrate that RPNs may be a source of compounds effective for preventing hypertension and may be useful in the development of antihypertensive drugs.

Eco-friendly and enhanced colorimetric detection of aluminum ions using pectin-rich apple extract-based gold nanoparticles.

Aluminum ions are very toxic to human health, especially in relation to neurodegenerative diseases. However, conventional methods of detecting such toxic ions suffer from the use of poisonous chemical probes and complex processes. Herein, we report an eco-friendly and enhanced colorimetric method of aluminum ion detection using green-synthesized gold nanoparticles (AuNPs) from apple (Malus domestica) extract. The apple extract-based AuNPs (AX-AuNPs) contain abundant pectin different from citrate-based AuNPs. The pectin-rich AX-AuNPs improved the sensitivity of the colorimetric detection of aluminum ions. The detection limit was about 20 µM both in artificial and drinking water-based real samples. Interestingly, it is turned out that the AX-AuNPs were aggregated naturally after the chemical assay because of solution getting decayed. For the environmental perspective, it was great that the lump of AX-AuNP aggregates could easily be removed from the solutions before solution discard. Overall, our results indicate that AX-AuNPs offer a high-selectivity, enhanced colorimetric detection of aluminum ions in a short time (less than 1 min), based on an eco-friend synthesis and disposal manner of AuNPs.

Pine needle hexane extract promote cell cycle arrest and premature senescence via p27KIP1 upregulation gastric cancer cells.

Pinus densiflora sieb. et zucc.(pine needle) is a traditional medicine used in several East Asian countries. However, the efficacy of pine needle has rarely been reported. In this study showed that the anti-proliferative effects and the mechanisms of hexane layer of pine needle MeOH extract (PNH) on gastric cancer cells. At first, PNH inhibited the proliferation of gastric cancer cells in a dose-dependent manner. Moreover, PNH treatment induced G1 phase cell cycle arrest through the increased p27KIP1 expression and decreased cyclin dependent kinase (CDKs) activity. Furthermore, PNH treatment induced premature senescence without oncogenic stress, through the expression of p27KIP1 and Skp2. Taken together, these results showed that PNH inhibited gastric cancer cell proliferation through the induction of G1-cell cycle arrest and premature senescence via induced p27KIP1 expression, as controlled by Skp2 reduction. Also, PNH could be a candidate for anti-gastric cancer treatment and may be useful in the development of anti-gastric cancer drugs.

Geranium thunbergii extract-induced G1 phase cell cycle arrest and apoptosis in gastric cancer cells.

Geranium thunbergii is a traditional East Asian medicine for stomach diseases including dysentery and stomach ulcers in East Asia and has been reported to possess biological activity. The benefits of G. thunbergii in gastric cancer are unknown. In this study, we demonstrate that G. thunbergii extract suppresses proliferation and induces death and G1/S cell cycle arrest of gastric cancer cells. Proliferation was significantly inhibited in a time- and dose-dependent manner. Cell cycle arrest was associated with significant decreases in CDK4/cyclinD1 complex and CDK2/cyclinE complex genes expression. In addition, the protein expression of caspase-3 was decreased and that of activated poly (ADP-ribose) polymerase (PARP) was increased, which indicated apoptosis. The expressions of the Bax and Bcl-2, which are apoptosis related proteins, were upregulated and down-regulated, respectively. The results indicate that G. thunbergii extract can inhibit proliferation and induce both G/S cell cycle arrest and apoptosis of gastric cancer cells. Also, the induction of apoptosis involved the intrinsic pathways of the cells. Take the results, we suggest that G. thunbergii extract has anti-gastric cancer activity and may be a potential therapeutic candidate for gastric cancer.

Screening ginseng saponins in progenitor cells identifies 20(R)-ginsenoside Rh2 as an enhancer of skeletal and cardiac muscle regeneration.

Aging is associated with increased prevalence of skeletal and cardiac muscle disorders, such as sarcopenia and cardiac infarction. In this study, we constructed a compendium of purified ginsenoside compounds from Panax ginseng C.A. Meyer, which is a traditional Korean medicinal plant used to treat for muscle weakness. Skeletal muscle progenitor cell-based screening identified three compounds that enhance cell viability, of which 20(R)-ginsenoside Rh2 showed the most robust response. 20(R)-ginsenoside Rh2 increased viability in myoblasts and cardiomyocytes, but not fibroblasts or disease-related cells. The cellular mechanism was identified as downregulation of cyclin-dependent kinase inhibitor 1B (p27Kip1) via upregulation of Akt1/PKB phosphorylation at serine 473, with the orientation of the 20 carbon epimer being crucially important for biological activity. In zebrafish and mammalian models, 20(R)-ginsenoside Rh2 enhanced muscle cell proliferation and accelerated recovery from degeneration. Thus, we have identified 20(R)-ginsenoside Rh2 as a p27Kip1 inhibitor that may be developed as a natural therapeutic for muscle degeneration.

Antiallodynic Effect of Intrathecal Korean Red Ginseng in Cisplatin-Induced Neuropathic Pain Rats.

BACKGROUND: Chemotherapy-induced neuropathic pain (CINP) is a serious side effect of chemotherapy. Korean Red Ginseng (KRG) is a popular herbal medicine in Asian countries. We examined the therapeutic potential of intrathecally administered KRG for CINP and clarified the mechanisms of action with regard to 5-hydroxytryptamine (5-HT)7 receptor at the spinal level. METHODS: CINP was evoked by intraperitoneal injection of cisplatin in male Sprague-Dawley rats. After examining the effects of intrathecally administered KRG on CINP, 5-HT receptor antagonist (dihydroergocristine [DHE]) was pretreated to determine the involvement of 5-HT receptor. In addition, intrathecal 5-HT7 receptor antagonist (SB269970) was administered to define the role of 5-HT7 receptor on the effect of KRG. 5-HT7 receptor mRNA expression levels and 5-HT concentrations were examined in the spinal cord. RESULTS: Intrathecally administered KRG produced a limited, but a dose-dependent, antiallodynic effect. Intrathecally administered DHE antagonized the antiallodynia caused by KRG. Furthermore, intrathecal SB269970 also reversed the effect of KRG. No changes in 5-HT7 receptor mRNA expression were seen in the dorsal horn of the spinal cord after cisplatin injection. After injecting cisplatin, 5-HT levels were decreased in the spinal cord, whereas those of 5-HT were increased by intrathecal KRG. CONCLUSIONS: Intrathecally administered KRG decreased CINP. In addition, spinal 5-HT7 receptors contributed to the antiallodynic effect of KRG.

Excitatory GABAergic Action and Increased Vasopressin Synthesis in Hypothalamic Magnocellular Neurosecretory Cells Underlie the High Plasma Level of Vasopressin in Diabetic Rats.

Diabetes mellitus (DM) is associated with increased plasma levels of arginine-vasopressin (AVP), which may aggravate hyperglycemia and nephropathy. However, the mechanisms by which DM may cause the increased AVP levels are not known. Electrophysiological recordings in supraoptic nucleus (SON) slices from streptozotocin (STZ)-induced DM rats and vehicle-treated control rats revealed that γ-aminobutyric acid (GABA) functions generally as an excitatory neurotransmitter in the AVP neurons of STZ rats, whereas it usually evokes inhibitory responses in the cells of control animals. Furthermore, Western blotting analyses of Cl- transporters in the SON tissues indicated that Na+-K+-2Cl- cotransporter isotype 1 (a Cl- importer) was upregulated and K+-Cl- cotransporter isotype 2 (KCC2; a Cl- extruder) was downregulated in STZ rats. Treatment with CLP290 (a KCC2 activator) significantly lowered blood AVP and glucose levels in STZ rats. Last, investigation that used rats expressing an AVP-enhanced green fluorescent protein fusion gene showed that AVP synthesis in AVP neurons was much more intense in STZ rats than in control rats. We conclude that altered Cl- homeostasis that makes GABA excitatory and enhanced AVP synthesis are important changes in AVP neurons that would increase AVP secretion in DM. Our data suggest that Cl- transporters in AVP neurons are potential targets of antidiabetes treatments.

Isolation and Characterization of Isofraxidin 7-O-(6'-O-p-Coumaroyl)-ß-glucopyranoside from Artemisia capillaris Thunberg: A Novel, Nontoxic Hyperpigmentation Agent That Is Effective In Vivo.

Abnormalities in skin pigmentation can produce disorders such as albinism or melasma. There is a research need to discover novel compounds that safely and effectively regulate pigmentation. To identify novel modulators of pigmentation, we attempted to purify compounds from a bioactive fraction of the Korean medicinal plant Artemisia capillaris Thunberg. The novel compound isofraxidin 7-O-(6'-O-p-coumaroyl)-ß-glucopyranoside (compound 1) was isolated and its pigmentation activity was characterized in mammalian melanocytes. Compound 1 stimulated melanin accumulation and increased tyrosinase activity, which regulates melanin synthesis. Moreover, compound 1 increased the expression of tyrosinase and the key melanogenesis regulator microphthalmia-associated transcription factor (MITF) in melanocytes. Compared to the parent compound, isofraxidin, compound 1 produced greater effects on these pigmentation parameters. To validate compound 1 as a novel hyperpigmentation agent in vivo, we utilized the zebrafish vertebrate model. Zebrafish treated with compound 1 showed higher melanogenesis and increased tyrosinase activity. Compound 1 treated embryos had no developmental defects and displayed normal cardiac function, indicating that this compound enhanced pigmentation without producing toxicity. In summary, our results describe the characterization of novel natural product compound 1 and its bioactivity as a pigmentation enhancer, demonstrating its potential as a therapeutic to treat hypopigmentation disorders.