[Effect of ketogenic diet on obesity asthma].

Recently investigators pay more attention to the relationship between obesity and bronchial asthma (asthma).Obesity is increasingly recognized as a possible risk factor for childhood asthma, and 70% of patients with difficult-to-treat asthma are overweight or obese. In recent years, ketogenic diet, as one of the natural therapies, has been shown to have positive effects on weight loss process; and recent studies showed that ketogenic diet reduced airway inflammation in asthma. This review summarized the mechanisms of associations between obesity and asthma, and described the potential mechanisms of ketogenic diet affecting obese asthma, such as controlling body weight, reducing inflammatory response, regulating intestinal flora and modifying epigenetics, to provide new ideas for the prevention and treatment of obesity asthma.

[Efficacy of periprocedural bivalirudin infusion in patients with chronic total occlusion lesion undergoing percutaneous coronary intervention].

Objective: To investigate the efficacy of periprocedural use of bivalirudin for patients with chronic total occlusion(CTO) lesion undergoing percutaneous coronary intervention(PCI) therapy. Methods: In this randomized controlled study, 74 patients with CTO lesions confirmed by coronary angiography or CT angiography, hospitalized in the general hospital of Shenyang military region from September 2015 to December 2016, were randomly divided into unfractionated heparin(UFH) group (n=38) and bivalirudin group (n=36) by the random number table.Patients in the UFH group were treated with injection of UFH 5 000 U through the artery sheath catheter before coronary angiography,and the UFH was intravenously administered at 100 U/kg before PCI. Patients in the bivalirudin group received intravenous injection of bivalirudin (0.75 mg/kg) before coronary angiography, followed by intravenous infusion of 1.75 mg·kg(-1)·h(-1) until at least 2 hours after the PCI. The values of the activated coagulation time (ACT) were measured,and the value was remained at 250 to 350 seconds during the PCI. The incidence rate of adverse events including hemorrhage events, no-reflow/slow flow, and contact thrombus in perioperative period were observed in all patients. In addition, the incidence rate of the major adverse cardiovascular events (MACE) including recurrent angina, heart failure, target vessel revascularization, cardiac death, non-fatal myocardial infarction,and stroke within 1 year follow-up period were also observed in the 2 groups. Results: Baseline clinical and PCI data were similar between the 2 groups (all P>0.05). During the perioperative period, the incidence of the bleeding was significantly lower in the bivalirudin group than in the UFH group(5.6% (2/36) vs. 23.7% (9/38) , P=0.028).The incidence of no-reflow/slow flow was also significantly lower in the bivalirudin group than in the UFH group(0 vs. 15.8% (6/38) , P=0.025). There was no significant difference in the incidence of contact thrombosis between bivalirudin group and UFH group(8.3% (3/36) vs. 0, P=0.110). There was no cardiac death or non-fatal myocardial infarction in the 2 groups within 1 year after PCI, and there was no significant difference in the incidence of MACE in 1 year follow-up after operation between bivalirudin group and UFH group (11.1% (4/36) vs. 21.1% (8/38) , P=0.246). Conclusion: The application of the anticoagulant bivalirudin during PCI in patients with CTO lesion can reduce the incidence of perioperative bleeding and no-reflow/slow flow, and does not increase the risk of MACE within 1 year after PCI.

The adverse effects of long-term l-carnitine supplementation on liver and kidney function in rats.

Levo-Carnitine (l-carnitine) is widely used in health and food. This study was to focus on the adverse effects of 8-week oral supplementation of l-carnitine (0.3 and 0.6 g/kg) in female and male Sprague Dawley rats. l-carnitine reduced body and fat weights, as well as serum, liver, and kidney lipid levels in rats. Simultaneously, hepatic fatty acid ß-oxidation and lipid synthesis were disturbed in l-carnitine-fed rats. Moreover, l-carnitine accelerated reactive oxygen species production in serum and liver, thereby triggering hepatic NOD-like receptor 3 (NLRP3) inflammasome activation to elevate serum interleukin (IL)-1ß and IL-18 levels in rats. Alteration of serum alkaline phosphatase levels further confirmed liver dysfunction in l-carnitine-fed rats. Additionally, l-carnitine may potentially disturb kidney function by altering renal protein levels of rat organic ion transporters. These observations may provide the caution information for the safety of long-term l-carnitine supplementation.

Behavioral, neurochemical and neuroendocrine effects of the ethanolic extract from Curcuma longa L. in the mouse forced swimming test.

Curcuma longa L. (turmeric) has been used for centuries in traditional Chinese medicine as a treatment for mental disorders including depression. The studies described here were undertaken to determine the behavioral, neurochemical and neuroendocrine effects of the ethanolic extract from Curcuma longa using the forced swimming test (FST) in male ICR strain of mice. The ethanolic extract was found to reduce the duration of immobility in the mouse FST when orally administered for 21 days. The extract markedly attenuated swim stress-induced decreases in serotonin, 5-hydroxyindoleacetic acid, noradrenaline and dopamine concentrations, as well as increases in serotonin turnover. Furthermore, the ethanolic extract of Curcuma longa significantly reversed the swim stress-induced increases in serum corticotropin-releasing factor and cortisol levels. Under these conditions, the ethanolic extract of Curcuma longa was partly different from fluoxetine and amitriptyline. These results suggested that antidepressant properties of the ethanolic extract of Curcuma longa was mediated through regulations of neurochemical and neuroendocrine systems and it may be a useful agent against depression.

Behavioral and biochemical studies of total furocoumarins from seeds of Psoralea corylifolia in the chronic mild stress model of depression in mice.

Depression is related to alterations of the monoamine oxidase (MAO), hypothalamic-pituitary-adrenal (HPA) axis, and oxidative systems, and some antidepressants achieve their therapeutic effects through alteration of following biochemical markers of depression: MAO-A and MAO-B activities, cortisol levels, superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels. The seeds of Psoralea corylifolia, otherwise known as Buguzhi, have long been used for treatments of various symptoms associated with aging in China. Furocoumarins are the most widespread secondary metabolites in this species. The present study was designed to evaluate the potential antidepressant-like activity of total furocoumarins of P. corylifolia (TFPC) in the chronic mild stress (CMS) model of depression. Mice subjected to CMS exhibited a reduction in sucrose intake. Conversely, brain MAO-A and MAO-B activities, plasma cortisol levels, and liver SOD activity and MDA levels were increased following CMS exposures. The time-course for reversal of CMS-induced deficits in sucrose consumption by TFPC was dose-dependent. Thus, the statistically significant effect of the higher dose of TFPC (50 mg/kg body wt.) was observed after 3 days of treatment, while 6 days of treatment were required in the group receiving a lower dose (30 mg/kg body wt.) of TFPC. TFPC reversed these biochemical changes. These results suggest that TFPC may possess potent and rapid antidepressant properties that are mediated via MAO, the HPA axis and oxidative systems and these antidepressant actions could make TFPC a potentially valuable drug for the treatment of depression in the elderly.

Effects of cassia oil on serum and hepatic uric acid levels in oxonate-induced mice and xanthine dehydrogenase and xanthine oxidase activities in mouse liver.

We investigated the hypouricemic effects of cassia oil extracted from Cinnamomum cassia using hyperuricemic mice induced by potassium oxonate, and its inhibitory actions against liver xanthine dehydrogenase (XDH) and xanthine oxidase (XOD) activities. Oral administration of cassia oil significantly reduced serum and hepatic urate levels in hyperuricemic mice in a time- and dose-dependent manner. At doses of 450 mg/kg of cassia oil or above, serum urate levels of the oxonate-pretreated mice were not different from the normal control mice. Cassia oil at 600 mg/kg was found to be as potent as allopurinol, which reduced hepatic urate levels to lower than normal. In normal mice, urate levels in liver, but not in serum, were altered with dose-dependent decrease after cassia oil treatment. Furthermore, the ratio, liver uric acid/serum uric acid, was determined after cassia oil administration with time- and dose-dependent decreases in hyperuricemic mice. The positive dose-dependent decrease ratio was also observed after cassia oil treatment in the normal animals. The decreased extent of ratio elicited by cassia oil in normal mice appeared to be greater than that in the hyperuricemic animal. In addition, cassia oil significantly exhibited marked reductions in liver XDH/XOD activities, with an apparent dose-dependence in the normal and hyperuricemic mice. The onset of inhibition in enzyme activities elicited by allopurinol was much higher than that elicited by cassia oil. These results suggested that hypouricemic effects of cassia oil could be explained, at least partly, by inhibiting liver in vivo activities of XDH/XOD.

Inhibition of MAO A and B by some plant-derived alkaloids, phenols and anthraquinones.

A total of seventeen phytochemicals including seven alkaloids (piperine, strychnine, brucine, stachydrine, tetrandrine, frangchinoline and sinomenine), four phenols (paeonol, honokiol, magnolol and eugenol) and six anthraquinones (emodin, rhein, chrysorphanol, aloe-emodin, physcion and 1,8-dihydroxyanthraquinone) was examined for inhibitory activity of monoamine oxidase (MAO) A and B from rat brain mitochondrial. Among these compounds, piperine and paeonol were found to be inhibitory against MAO A in a dose-dependent manner with IC(50) values of 49.3 and 54.6 microM, respectively. Piperine, paeonol and emodin were shown to inhibit MAO B in a dose-dependent manner with the IC(50) data of 91.3, 42.5 and 35.4 microM, respectively. Lineweaver-Burk transformation of the inhibition data indicated that the inhibitory action of piperine on MAO A was of mixed type, and that of paeonol on the same type of the enzyme was of non-competitive type. For piperine, the K(i) and K(I) were determined to be 35.8 and 25.7microM, respectively. For paeonol, the K(i) was estimated to be 51.1 microM. The inhibition of piperine and paeonol on MAO B was of competitive type with K(i) values of 79.9 and 38.2 microM, respectively. The inhibition of emodin on MAO B was of mixed type with the K(i) and K(I) data of 15.1 and 22.9 microM, respectively. The present investigation showed that the phytochemicals piperine, paeonol and emodin are potent MAO inhibitors whereas other compounds were inactive against any type of MAO at 100 microM in the present assay.

Antidepressant activity of aqueous extracts of Curcuma longa in mice.

Curcuma longa (turmeric) is a well-known indigenous herbal medicine. The aqueous extracts, when administered orally to the mice from 140 to 560 mg/kg for 14 days, were able to elicit dose-dependent relation of immobility reduction in the tail suspension test and the forced swimming test in mice. The effects of the extracts at the dose of 560 mg/kg were more potent than that of reference antidepressant fluoxetine. The extracts, at the dose of 140 mg/kg or above for 14 days, significantly inhibited the monoamine oxidize A (MAO) activity in mouse whole brain at a dose-dependent manner, however, oral administration of the extract only at a dose of 560 mg/kg produced observable MAO B inhibitory activity in animal brain. Fluoxetine showed only a tendency to inhibit MAO A and B activity in animal brain in the study. Neither the extracts of C. longa nor fluoxetine, at the doses tested, produced significant effects on locomotor activity. These results demonstrated that C. longa had specifically antidepressant effects in vivo. The activity of C. longa in antidepression may mediated in part through MAO A inhibition in mouse brain.

Cell brain crystallization for cancer therapy.

Cancer remains one of the leading causes of death throughout the world. One of the important reasons why conventional treatments fail is the development of resistance to therapeutics. The dual effect concept and self-defense mechanism plus the threshold theory might in part explain the development of resistance, however, the primary cause is unclear. A novel theory, 'cell brain', where, selective crystallization of the 'brain' of a cell (comprising centrosome, centrioles and the connecting filaments) occurs, may be a potential alternate approach to cancer therapy.

Glycosides and xanthine oxidase inhibitors from Conyza bonariensis.

Fractionation of the xanthine oxidase inhibitory methanol extract of Conyza bonariensis afforded three glycosides, in addition to nine known compounds including amyrin, beta-sitostero1 daucosterol, syringic acid 3-hydroxy-5-methoxybenzoic acid, eugenol 4-O-glucopyranoside, and luteolin, apigenin and takakin 8-O-glucuronide. The structures of the glycosides were established by a combination of spectroscopic methods (IR, MS, 1H and 13C NMR, DEPT, COSY, HMQC and HMBC) as 4-hydroxypyridin-3-carboxylic acid 4-O-glucopyranoside, 8-hydroxy-6,7-dihydrolinalool 8-O-glucopyranoside and bonaroside [viz. 1,3,4,12-tetrahydroxy-2-(9-hexadecenoylamino)octadecane 1-O-glucopyranoside]. The in vitro enzyme assay showed that syringic acid and takakin 8-O-glucuronide displayed weak inhibitory activity against xanthine oxidase with IC50 values of 500+/-41 microM and 170+/-12 microM, respectively.

Inhibition of xanthine and monoamine oxidases by stilbenoids from Veratrum taliense.

The bioassay guided refractionation of the methanol extract of roots and rhizomes of Veratrum taliense (Liliaceae) yielded five stilbenoids: veraphenol, resveratrol, piceid, isorhapontin, and mulberroside E, all inhibiting xanthine oxidase (XO, EC 1.2.3.2.) in vitro in a dose-dependent manner with IC50 values of 11.0, 96.7, 66.1, 70.0, and 78.4 microM, respectively. Veraphenol and mulberroside E were found to be mixed XO inhibitors with the Ki and Ki data of the former being 32.8 and 239.3 microM, and those of latter 32.5 and 13.8 microM, respectively. However, the inhibition on the enzyme by resveratrol, isorhapontin, and piceid was shown to be competitive with their Ki values of 9.7, 19.1, and 14.3 microM, respectively. Among the five stilbenoids, veraphenol and resveratrol were also revealed to inhibit competitively monoamine oxidase A (MAO, EC 1.4.3.4) with IC50 values at 38.0 and 26.6 microM, and Ki data 36.4 and 47.3 microM, respectively. However, none of the stilbenoids was inhibitory on MAO B in our assay. The structure-activity relationship examination showed that glycosylation of the stilbenoids could reduce the inhibition on XO and diminish the activity against MAO A, indicating that the free phenolic hydroxy group of the compounds was most likely essential for these bioactivities.

Monoamine oxidase inhibitors from rhizoma of Coptis chinensis.

Three protoberberine alkaloids jatrorrhizine, berberine and palmatine were isolated from the monoamine oxidase (MAO) inhibitory fraction of the methanol extract of Coptis chinensis rhizoma. Jatrorrhizine was shown to inhibit non-competitively both MAO-A and -B from rat brain mitochondria with the IC50 values of 4 and 62 microM, respectively. Berberine only competitively inhibited MAO-A with an IC50 values of 126 microM whereas palmatine exhibited, up to 200 microM, no inhibition on any type of the enzyme. The structure-activity relationship was briefly discussed.

Inhibition of rat brain monoamine oxidase activities by psoralen and isopsoralen: implications for the treatment of affective disorders.

Psoralen and isopsoralen, furocoumarins isolated from the plant Psoralea corylifolia L., were demonstrated to exhibit in vitro inhibitory actions on monoamine oxidase (MAO) activities in rat brain mitochondria, preferentially inhibiting MAO-A activity over MAO-B activity. This inhibition of enzyme activities was found to be dose-dependent and reversible. For MAO-A, the IC50 values are 15.2 +/- 1.3 microM psoralen and 9.0 +/- 0.6 microM isopsoralen. For MAO-B, the IC50 values are 61.8 +/- 4.3 microM psoralen and 12.8 +/- 0.5 microM isopsoralen. Lineweaver-Burk transformation of the inhibition data indicates that inhibition by both psoralen and isopsoralen is non-competitive for MAO-A. The Ki values were calculated to be 14.0 microM for psoralen and 6.5 microM for isopsoralen. On the other hand, inhibition by both psoralen and isopsoralen is competitive for MAO-B. The Ki values were calculated to be 58.1 microM for psoralen and 10.8 microM for isopsoralen. These inhibitory actions of psoralen and isopsoralen on rat brain mitochondrial MAO activities are discussed in relation to their toxicities and their potential applications to treat affective disorders.

[Effects of different processing products of Cortex Phellodendri on scavenging oxygen free radicals and anti-lipid peroxidation].

OBJECTIVE: To investigate the effects of different processing products of Cortex Phellodendri on scavenging oxygen free radicals and anti-lipid peroxidation. METHOD: The oxygen free radicals generation system and mouse liver homogenate lipid peroxidation in vitro were used. RESULT: The aqueous and 80% alcohol extracts of raw, stir-fried, stir-fried with salt, stir-fried with yellow alcohol products of Cortex Phellodendri could scavenge superoxide radical(O2-.) generated through hypoxanthine-oxidase system and(.OH) generated through Fenton action, and inhibit lipid peroxidation induced by hydroxyl radical generation system, respectively. But the carbonized product has no effect. There are differences among these processed products. CONCLUSION: 80% alcohol extract of stir-fried with yellow alcohol products of Cortex Phellodendri was more intense.

[Effects of processing on antioxidation of Radix et Rhizoma Rhei and Rhizoma Polygoni Cuspidati].

OBJECTIVE: To investigate the effects of Processing on antioxidation of Radix et Rhizoma Rhei and Rhizoma Polygoni Cuspidati. METHOD: The oxygen free radicals generation system and mouse liver homogenate lipid peroxidation in vitro were used. RESULT: The processed products of Radix et Rhizoma Rhei and Rhizoma Polygoni Cuspidati could scavenge superoxide radical (O2-.) generated through hypoxanthine-oxidase system and (.OH) generated through Fenton action, and inhibit lipid peroxidation induced by hydroxyl radical generation system, respectively. There existed significant differences among the different processed products. CONCLUSION: After Radix et Rhizoma Rhei and Rhizoma Polygoni Cuspidati were processed, their effects became weaker.

Inhibition of xanthine oxidase by some Chinese medicinal plants used to treat gout.

The enzyme xanthine oxidase catalyses the oxidation of hypoxanthine to xanthine and then to uric acid, which plays a crucial role in gout. A total of 122 traditional Chinese medicinal plants, selected according to the clinical efficacy and prescription frequency for the treatment of gout and other hyperuricemia-related disorders, have been evaluated for the enzyme inhibitory activity. Among the 122 methanol extracts derived from these species, 69 were shown to be inhibitory at 100 microg/ml, with 29 having greater than 50% inhibition. As to the equal amount of water extracts, 40 were disclosed to be active at 100 microg/ml, with 13 possessing more than 50% inhibition. At 50 microg/ml, 58 methanol and 24 water extracts exhibited inhibitory activity, with 15 of the former and two of the latter showing greater than 50% inhibition. The most active was the methanol extract of the twig of Cinnamomum cassia (Lauraceae) (IC(50), 18 microg/ml), which was followed immediately by those of the flower of Chrysanthemum indicum (Asteraceae) (IC(50), 22 microg/ml) and the leaves of Lycopus europaeus (Lamiatae) (IC(50), 26 microg/ml). Among the water extracts, the strongest inhibition of the enzyme was observed with that of the rhizome of Polygonum cuspidatum (Polygonaceae) (IC(50), 38 microg/ml). The IC(50) value of allopurinol used as a positive control was 1.06 microg/ml. The study demonstrated that the effects for these medicinal plants used for the gout treatment were based, at least in part, on the xanthine oxidase inhibitory action.

Antidepressant effects of Banxia Houpu decoction, a traditional Chinese medicinal empirical formula.

Banxia Houpu Decoction, having been used for the treatment of depression-related diseases since ancient times, is a traditional Chinese medicinal empirical formula consisting of Pinellia ternata, Poria cocos, Magnolia officinalis, Perilla frutescens and Zingiber officinale. The effects of the total decoction extract and five fractions therefrom, were evaluated in mice by tail suspension and forced swimming tests. The total 90% ethanol extract of the decoction was shown to possess an antidepressant activity that was close to that of Prozac, an antidepressant agent being applied clinically. Furthermore, the active principles were desmonstrated to be mainly in the aqueous (Bx4) and lipophic (Bx5) parts of the decoction extract while the polyphenol fraction (Bx2) exhibited a moderate action.

Inhibition of xanthine oxidase by liquiritigenin and isoliquiritigenin isolated from Sinofranchetia chinensis.

The methanol extract of the stem of Sinofranchetia inhibited the activity of xanthine oxidase in vitro. Bioassay-guided purification led to the isolation ofliquiritigenin and isoliquiritigenin as the main xanthine oxidase inhibitors. This inhibition of enzyme activity was found to be dose dependent, with an IC50 value of approximately 49.3 microM for liquiritigenin and 55.8 microM for isoliquiritigenin. Lineweaver-Burk transformation of the inhibition data indicated that the inhibition was of a mixed type for both liquiritigenin and isoliquiritigenin. For liquiritigenin, the Ki and K(I) were determined to be 14.0 microM and 151.6 microM, respectively. For isoliquiritigenin, the Ki and K(I) were determined to be 17.4 microM and 81.9 microM, respectively. These results suggest that these natural products could be used to treat conditions where the inhibition of xanthine oxidase is warranted.

In vitro inhibition of rat monoamine oxidase by liquiritigenin and isoliquiritigenin isolated from Sinofranchetia chinensis.

AIM: To study the inhibition of liquiritigenin (1) and isoliquiritigenin (2) isolated from Sinofranchetia chinensis on rat monoamine oxidase A and B (MAO A and B). METHODS: Rat brain mitochondrial fraction, prepared by differential centrifugation, was utilized as a source of MAO activity. MAO activity was determined radiochemically with [14C]5-hydroxytryptamine (5-HT) and [14C]beta-phenylethylamine (beta-PEA) used as MAO A or B specific radiolabled substrates, respectively. The Ki and KI values were obtained from Lineweaver-Burk plot using linear regression analysis. RESULTS: Liquiritigenin and isoliquiritigenin were found to be inhibitory against both MAO A and B in a dose-dependent manner. IC50 (95% of confidence limits) of liquiritigenin and isoliquiritigenin were 32 (26-36) and 13.9 (12.8-15.6) mumol/L for the inhibition of MAO A, and 104.6 (89.0-118.9) and 47.2 (39.5-54.5) mumol/L for that of MAO B, respectively. Lineweaver-Burk transformation of the MAO A inhibition data indicated that the inhibition was non-competitive for both liquiritigenin and isoliquiritigenin whereas their inhibition of MAO B was of mixed type. Regarding MAO A inhibition, the Ki values of liquiritigenin and isoliquiritigenin were 31.5 mumol/L and 14.3 mumol/L, respectively. As to the inhibition of MAO B, the Ki and KI data for liquiritigenin were 164.7 and 15.2 mumol/L, and those for isoliquiritigenin were 62.2 and 9.3 mumol/L, respectively. CONCLUSION: Liquiritigenin and isoliquiritigen inhibited the activity of MAO A and B in rat brain mitochondria, and the latter was more active than the former.