Clinical efficacy and safety of Panax notoginseng saponins in treating chronic obstructive pulmonary disease with blood hypercoagulability: A meta-analysis of randomized controlled trials.

BACKGROUND: Panax notoginseng saponins (PNS) are the primary active components of an ancient Chinese herb Panax notoginseng. Hypercoagulable state of blood (HCS) is an independent risk factor and a cause of death in chronic obstructive pulmonary disease (COPD). Several vivo studies have demonstrated the use of PNS preparations for treating COPD with HCS. PURPOSE: This study aimed to systematically evaluate the clinical efficacy and safety of PNS preparations in treating COPD with HCS. STUDY DESIGN: Meta-analysis of the randomized controlled trials (RCTs) was conducted to review data. METHODS: RCTs on the treatment of COPD with HCS and PNS preparations were searched from PubMed, Cochrane Library, Embase, Web of Science, Chinese National Knowledge Infrastructure, Vip Information Database, Wanfang data, and Chinese Biomedical Literature Database. Relevant data were extracted from the included studies and methodological quality evaluation was performed. R language (version 4.2.3) was applied for the meta-analysis. RESULTS: Twenty RCTs involving 1831 patients were analyzed. The results revealed that PNS preparations considerably increased the total clinical efficiency, improved forced expiratory volume in one second percent of predicted, and forced expiratory volume/forced vital capacity ratio. Further, PNS preparations improved fibrinogen, plasma d-dimer, whole blood viscosity at high cut, whole blood viscosity at low cut, and plasma viscosity levels. The results obtained for activated partial thromboplastin and prothrombin times were not statistically significant. Finally, PNS preparations increased partial pressure of oxygen and decreased carbon dioxide pressure. CONCLUSION: This is the first relatively comprehensive systematic review of the clinical efficacy and safety of PNS preparations for treating COPD with HCS. The study revealed that PNS preparations considerably improve lung function, hypoxia, and blood hypercoagulability in patients with COPD and HCS without increasing the risk of hemorrhage and has a good safety profile; therefore, it can be used as a new modulating agent and anticoagulant.

The Pollen Donor Affects Seed Development, Taste, and Flavor Quality in 'Hayward' Kiwifruit.

To investigate how different species or ploidy level of pollen donors affects the fruit quality of kiwifruit, flowers of 'Hayward' kiwifruit (a hexaploid Actinidia deliciosa cultivar, 6x) were hand-pollinated with pollen from ten different male donors. Kiwifruit plants pollinated with four distant species-M7 (2x, A. kolomikta), M8 (4x, A. arguta), M9 (4x, A. melanandra), and M10 (2x, A. eriantha)-had a low fruit-setting rate and therefore were not investigated further. Of the other six treatments, kiwifruit plants pollinated with M4 (4x, A. chinensis), M5 (6x, A. deliciosa) M6 (6x, A. deliciosa) had a larger fruit size and weight than those pollinated with M1 (2x, A. chinensis) and M2 (2x, A. chinensis). However, pollination with M1 (2x) and M2 (2x) resulted in seedless fruits, having few small and aborted seeds. Notably, these seedless fruits had higher fructose, glucose, and total sugar and lower citric acid content. This resulted in a higher sugar to acid ratio compared to fruits from plants pollinated with M3 (4x, A. chinensis), M4 (4x), M5 (6x), and M6 (6x). Most volatile compounds increased in the M1 (2x)- and M2 (2x)-pollinated fruit. A combination of principal component analysis (PCA), electronic tongue, and electronic nose suggested that the different pollen donors significantly affected the kiwifruit's overall taste and volatiles. Specifically, two diploid donors had the most positive contribution. This was in agreement with the findings from the sensory evaluation. In conclusion, the present study showed that the pollen donor affected the seed development, taste, and flavor quality of 'Hayward' kiwifruit. This provides useful information for improving the fruit quality and breeding of seedless kiwifruit.

Innovative ochre processing and tool use in China 40,000 years ago.

Homo sapiens was present in northern Asia by around 40,000 years ago, having replaced archaic populations across Eurasia after episodes of earlier population expansions and interbreeding1-4. Cultural adaptations of the last Neanderthals, the Denisovans and the incoming populations of H. sapiens into Asia remain unknown1,5-7. Here we describe Xiamabei, a well-preserved, approximately 40,000-year-old archaeological site in northern China, which includes the earliest known ochre-processing feature in east Asia, a distinctive miniaturized lithic assemblage with bladelet-like tools bearing traces of hafting, and a bone tool. The cultural assembly of traits at Xiamabei is unique for Eastern Asia and does not correspond with those found at other archaeological site assemblages inhabited by archaic populations or those generally associated with the expansion of H. sapiens, such as the Initial Upper Palaeolithic8-10. The record of northern Asia supports a process of technological innovations and cultural diversification emerging in a period of hominin hybridization and admixture2,3,6,11.

Efficacy of Cigu Xiaozhi pill on non-alcoholic steatohepatitis-associated lipoapoptosis through stress-activated c-Jun N-terminal kinase signalling pathway.

OBJECTIVE: To investigate the efficacy of Cigu Xiaozhi pill (, CGXZ) on non-alcoholic steatohepatitis (NASH)-associated lipoapoptosis through the stress-activated c-Jun N-terminal kinase (JNK)/ stress-activated protein kinase signalling pathway. METHODS: Sixty male Sprague-Dawley rats were randomly divided into the following groups (10rats each): blank control, model, low-dose CGXZ, medium-dose CGXZ, high-dose CGXZ, and positive control (treated with SP600125, a JNK inhibitor). The NASH model was established and the histomorphological characteristics of haematoxylin and eosin-stained liver tissues were examined under a light microscope. Cell apoptosis in liver tissues was assessed via terminal deoxynucleotidyl transferase dUTP nick-end labelling assay. In addition, the mRNA and protein expression levels of p-JNK, p-c-Jun, caspase-8, Fas, and Fas-L were determined via fluorescence-based quantitative real-time PCR, immunohistochemical and Western blot assays. RESULTS: Histopathological examination of the liver showed that the model rats had moderate-to-severe steatosis with infiltration of inflammatory cells as well as significantly higher expression levels of the p-JNK, p-c-Jun, caspase-8, Fas, and Fas-L proteins, compared with those in the blank control group (P < 0.01). Hepatic lobules of the rats in the treatment groups showed significantly reduced vacuolar degeneration and steatosis as well as alleviated inflammatory cell infiltration. The high and medium-dose CGXZ groups exhibited significantly lower mRNA and protein expression levels of p-JNK, p-c-Jun, caspase-8, Fas, and Fas-L, compared with those in the model group (P < 0.05 or P < 0.01). CONCLUSION: CGXZ pill inhibited the onset of hepatocyte apoptosis by regulating the expression of p-JNK, p-c-Jun, caspase-8, Fas, and Fas-L, thereby exerting therapeutic effects against NASH.

Ellagic Acid Inhibits Trichophyton rubrum Growth via Affecting Ergosterol Biosynthesis and Apoptotic Induction.

BACKGROUND: Trichophyton rubrum, among other dermatophytes, is a major causative agent for superficial dermatomycoses like onychomycosis and tinea pedis, especially among pediatric and geriatric populations. Ellagic acid (EA) and shikonin (SK) have been reported to have many bioactivities, including antifungal activity. However, the mechanism of EA and SK on Trichophyton rubrum has not yet been reported. OBJECTIVES: The purposes of this study were to evaluate the antifungal activities of EA and SK against Trichophyton rubrum and to illuminate the underlying action mechanisms. METHODS: The effect of EA (64, 128, and 256 µg/mL) and SK (8, 4, and 2 µg/mL) on Trichophyton rubrum was investigated with different doses via detecting cell viability, ultrastructure with using a scanning electron microscope (SEM), cell apoptosis and necrosis by using the flow cytometry instrument technique (FCIT), and the ergosterol biosynthesis pathway-related fungal cell membrane key gene expressions in vitro. RESULTS: SEM detection revealed that the T. rubrum cell surface was shrivelled, folded, and showed deformation and expansion, visible surface peeling, and broken hyphae, and cell contents overflowed after being treated with EA and SK; the cell apoptosis rate was significantly increased in dose-dependent manner after T. rubrum was treated with EA and SK; the qPCR results showed that mRNA expression of MEP4 and SUB1 was downregulated in EA- and SK-treated groups. CONCLUSIONS: Overall, our results revealed the underlying antifungal mechanism of EA and SK, which may be related to the destruction of the fungal cell membrane and inhibition of C14 demethylase and the catalytic rate of squalene cyclooxidase in the ergosterol biosynthesis pathway via downregulation of MEP4 and SUB1, suggesting that EA and SK have the potential to be developed further as a natural antifungal agent for clinical use.

Aqueous Extract of Whitmania Pigra Whitman Alleviates Thrombus Burden Via Sirtuin 1/NF-κB Pathway.

BACKGROUND: Whitmania pigra Whitman (W pigra), a traditional Chinese medicine, has functions of breaking stagnant and eliminating blood stasis. The aim of this study was to investigate the underlying mechanism of W pigra against deep vein thrombosis (DVT). METHODS: A rat model of DVT induced by inferior vena cava stenosis was successfully established. Rats were administered vehicle (saline solution, p.o.), three doses of W pigra aqueous extract (34.7, 104.2, or 312.5 mg crude W pigra/kg, p.o.), heparin (200 U/kg, i.v.), or clopidogrel (25 mg/kg, p.o.) once daily for 2 d. Thrombus weight and histopathological changes were examined. Blood samples were collected to determine blood cell counts, blood viscosity, blood coagulation, blood fibrinolysis, serum levels of interleukin-1ß, and tumor necrosis factor-α. Protein expressions of Sirtuin1 (SIRT1), acetylated p65 (Ace-p65), and phosphorylated p65 (p-p65) were determined by Western blot. Furthermore, SIRT1-specific inhibitor EX527 was applied to confirm the role of SIRT1 in the antithrombotic effect of W pigra. RESULTS: W pigra significantly decreased thrombus weight. W pigra had no effects on blood cell counts, whole blood viscosity, blood coagulation, blood fibrinolysis. However, it reduced tissue factor protein expression in the vein wall and thrombus. Moreover, it sharply increased SIRT1 protein expression and decreased leukocytes recruitment in the thrombus and vein wall, serum levels of interleukin-1ß and tumor necrosis factor-α, and protein expressions of Ace-p65 and p-p65. Furthermore, the antithrombotic effect of W pigra was significantly abolished by EX527. CONCLUSIONS: Aqueous extract of W pigra effectively reduced DVT burden by inhibiting inflammation via SIRT1/nuclear factor-kappa B signaling pathway.

[Comparative study on anti-inflammatory and immunomodulation of different Isatidis Radix strains growing in Gansu Province].

OBJECTIVE: To investigate anti-inflammatory and immunomodulation effects of different ecotype from Isatidis Radix growing in Gansu province. METHODS: Mice were randomly divided into 6 groups (n=11)and used the auricular swelling and paw edema to observe the anti-inflammatory effects of Isatidis Radix; Mice were randomly divided into 7 groups (n=11) and through the gasbag synovitis model to observe the anti-inflammatory effects of Isatidis Radix; Mice were randomly divided into 6 groups (n=11), the immunosuppressed model were established by injection of cyclophosphamide (CTX) to study the effects of Isatidis Radix on index of thymus, blood routine and cytokines. RESULTS: Gansu different ecotype from Isatidis Radix could reduce the swelling of the mice auricle, paw edema and total protein, leukotriene B4(LTB4)and malonaldehyde(MDA) in airbag synovitis exudates, and upgrade serum levels of superoxide dismutase (SOD); Degrade the tumor necrosis factor-α (TNF-α) and upgrade the index of thymus, the number of red and white corpuscles, the level of interferon-γ (IFN-γ), interleukin-4 (IL-4) (P<0.05, 0.01) of mice immunosuppressed model; Above the research of anti-inflammatory and immunomodulation, there were no significant differences between Isatidis Radix of Gansu different ecotype and tetraploid. CONCLUSIONS: Different ecotype of Isatidis Radix has obvious functions in anti-inflammatory and immunomodulation, but there are no significant differences between Gansu different ecotype and tetraploid.

Arabidopsis VAC14 Is Critical for Pollen Development through Mediating Vacuolar Organization.

Pollen viability depends on dynamic vacuolar changes during pollen development involving increases and decreases of vacuolar volume through water and osmolite accumulation and vacuolar fission. Mutations in FAB1A to FAB1D, the genes encoding phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2]-converting kinases, are male gametophyte lethal in Arabidopsis (Arabidopsis thaliana) due to defective vacuolar fission after pollen mitosis I, suggesting a key role of the phospholipid in dynamic vacuolar organization. However, other genetic components that regulate the production of PI(3,5)P2 and its involvement in pollen germination and tube growth are unknown. Here, we identified and characterized Arabidopsis VAC14, a homolog of the yeast and metazoan VAC14s that are crucial for the production of PI(3,5)P2VAC14 is constitutively expressed and highly present in developing pollen. Loss of function of VAC14 was male gametophyte lethal due to defective pollen development. Ultrastructural studies showed that vacuolar fission after pollen mitosis I was compromised in vac14 mutant microspores, which led to pollen abortion. We further showed that inhibiting the production of PI(3,5)P2 or exogenous application of PI(3,5)P2 mimicked or rescued the pollen developmental defect of the vac14 mutant, respectively. Genetic interference and pharmacological approaches suggested a role of PI(3,5)P2 in pollen germination and tube growth. Our results provide insights into the function of VAC14 and, by inference, that of PI(3,5)P2 in plant cells.

The lithic assemblages of Donggutuo, Nihewan basin: Knapping skills of early pleistocene hominins in North China.

Donggutuo (DGT) is one of the richest archaeological localities in the Nihewan Basin of North China, thereby providing key information about the technological behaviours of early hominins in eastern Asia. Although DGT has been subject of multiple excavations and technological studies over the past several decades, few detailed studies on the lithic assemblages have been published. Here we summarize and describe the DGT lithic assemblages, examining stone tool reduction methods and technological skills. DGT dates to ca. 1.1 Ma, close to the onset of the mid-Pleistocene climate transition (MPT), indicating that occupations at DGT coincided with increased environmental instability. During this time interval, the DGT knappers began to apply innovative flaking methods, using free hand hard hammer percussion (FHHP) to manufacture pre-determined core shapes, small flakes and finely retouched tools, while occasionally using the bipolar technique, in contrast to the earlier and nearby Nihewan site of Xiaochangliang (XCL). Evidence for some degree of planning and predetermination in lithic reduction at DGT parallels technological developments in African Oldowan sites, suggesting that innovations in early industries may be situational, sometimes corresponding with adaptations to changes in environments and local conditions.

Enhanced phosphorus removal in intermittently aerated constructed wetlands filled with various construction wastes.

Phosphorus (P) loss by various pathways in constructed wetlands (CWs) is often variable. The effects of intermittent aeration and different construction waste substrates (gravel, red brick, fly-ash brick) on P processing using six batch-operated vertical flow constructed wetlands (VFCWs) were studied for decentralized domestic wastewater treatment. Average removal of total phosphorus (TP) in three aerated CWs was markedly higher (21.06, 24.83, and 27.02 mg m-2 day-1, respectively) than non-aerated CWs (10.64, 18.16, and 25.09 mg m-2 day-1, respectively). Fly-ash brick offered superior TP removal efficiency in both aerated and non-aerated batch-operated VFCWs, suggesting its promising application for P removal in CWs. Aeration greatly promoted plant growth and thusly increased plant uptake of P by 0.57-1.45 times. Substance storage was still the main P sink accounting for 23.92-59.47% of TP removal. Other process including microbial uptake was revealed to be a very important P removal pathway (accounting for 14.86-34.84%). The contribution of microbial uptake was also indicated by microbial analysis. Long-term results suggested that the contribution of microbial P uptake could be always ignored and underestimated in most CWs. A combination of intermittent aeration and suitable substrates is effective to intensify P transformation in CWs.

Reactive oxygen species mediate tapetal programmed cell death in tobacco and tomato.

BACKGROUND: Hybrid vigor is highly valued in the agricultural industry. Male sterility is an important trait for crop breeding. Pollen development is under strict control of both gametophytic and sporophytic factors, and defects in this process can result in male sterility. Both in the dicot Arabidopsis and in the moncot rice, proper timing of programmed cell death (PCD) in the tapetum ensures pollen development. Dynamic ROS levels have been reported to control tapetal PCD, and thus pollen development, in Arabidopsis and rice. However, it was unclear whether it is evolutionarily conserved, as only those two distantly related species were studied. RESULTS: Here, we performed histological analyses of anther development of two economically important dicot species, tobacco and tomato. We identified the same ROS amplitude during anther development in these two species and found that dynamic ROS levels correlate with the initiation and progression of tapetal PCD. We further showed that manipulating ROS levels during anther development severely impaired pollen development, resulting in partial male sterility. Finally, real-time quantitative PCR showed that several tobacco and tomato RBOHs, encoding NADPH oxidases, are preferentially expressed in anthers. CONCLUSION: This study demonstrated evolutionarily conserved ROS amplitude during anther development by examining two commercially important crop species in the Solanaceae. Manipulating ROS amplitude through genetic interference of RBOHs therefore may provide a practical way to generate male sterile plants.

The Effect of Butin on the Vitiligo Mouse Model Induced by Hydroquinone.

Vernonia anthelmintica (L.) Willd has been traditionally used in the treatment of vitiligo in Uyghur medicine. This study used butin, the main component of V. anthelmintica, to study the influence on hydroquinone-induced vitiligo in mice. The animals were randomly divided into six groups: control, model, 8-methoxypsoralen (8-MOP, 4.25 mg/kg), and butin (0.425, 4.25, and 42.5 mg/kg) groups. The number of melanin-containing hair follicles, basal layer melanocytes, melanin-containing epidermal cells, the expression of tyrosinase (TYR) and tyrosinase-related protein-1 (TRP-1), the malondialdehyde (MDA), and cholinesterase (CHE) activity in serum were measured. Our results indicated that compared with the model group, the melanin-containing hair follicles, the expression of TYR and TRP-1 increased, the activity of CHE decreased after treatment with 8-MOP and all doses of butin (p < 0.05, p < 0.01), the basal layer melanocytes and melanin-containing epidermal cells increased significantly after treatment with butin 4.25 and 42.5 mg/kg (p < 0.05, p < 0.01), and the MDA activity decreased after using butin 4.25 and 42.5 mg/kg and 8-MOP (p < 0.05, p < 0.01). Our results support the use of butin on vitiligo, and its possible mechanisms may be related to increase the TYR and TRP-1 protein expression and decrease the activity of MDA and CHE in hydroquinone-induced vitiligo model in mice. Copyright © 2017 John Wiley & Sons, Ltd.

Timosaponin B-II Ameliorates Palmitate-Induced Insulin Resistance and Inflammation via IRS-1/PI3K/Akt and IKK/NF-[Formula: see text]B Pathways.

This study aimed to investigate the effect of timosaponin B-II (TB-II) on palmitate (PA)-induced insulin resistance and inflammation in HepG2 cells, and probe the potential mechanisms. TB-II, a main ingredient of the traditional Chinese medicine Anemarrhena asphodeloides Bunge, notably ameliorated PA-induced insulin resistance and inflammation, and significantly improved cell viability, decreased PA-induced production of tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]) and interleukin-6 (IL-6) levels. Further, TB-II treatment notably decreased malondialdehyde (MDA) and lactate dehydrogenase (LDH) levels, and improved superoxide dismutase (SOD) and nitric oxide (NO). TB-II also reduced HepG2 cells apoptosis. Insulin receptor substrate-1 (IRS1)/phosphatidylinositol 3-kinase (PI3K)/Akt and inhibitor of nuclear factor [Formula: see text]-B kinase (IKK)/NF-[Formula: see text]B pathways-related proteins, and IKK[Formula: see text], p65 phosphorylation, serine phosphorylation of insulin receptor substrate-1 (IRS-1) at S307, tyrosine phosphorylation of IRS-1, and Akt activation were determined by Western blot. Compared to model group, TB-II significantly downregulated the expression of p-NF-[Formula: see text]Bp65, p-IKK[Formula: see text], p-IRS-1, p-PI3K and p-Akt. TB-II is a promising potential agent for the management of palmitate-induced insulin resistance and inflammation, which might be via IR/IRS-1/PI3K/Akt and IKK/NF-[Formula: see text]B pathways.

Pharmacokinetics of acteoside following single dose intragastric and intravenous administrations in dogs.

Acteoside (verbascoside), a phenylethanoid glycoside widely distributed in various plants, has been shown to have potential activity against Alzheimer's disease, attracting great attentions recently. The present study was designed to develop a selective and sensitive LC-MS/MS method for the determination of acteoside in biological samples and carry our a pharmacokinetic (PK) study in beagle dogs. The PK parameters were calculated using non-compartmental models. Following a single-dose oral administration, acteoside was rapidly absorbed and eliminated, with Tmax being between 30 to 45 min and terminal half-life being about 90 min. The areas under the time-concentration curve (AUC) were 47.28 ± 8.74, 87.86 ± 13.33, and 183.14 ± 28.69 mg · min · L(-1) for oral administration of 10, 20, and 40 mg · kg(-1), respectively, demonstrating that the exposure of acteoside proportionally increased with the dose level. The absolute bioavailability of acteoside was around 4%. For all the PK parameters, there were large variations between individual dogs. In conclusion, the pharmacokinetic characteristics observed in the present study can be of great value to help better understand the pharmacological properties of acteoside and to improve the outcome of its clinical use.

The Mechanism of Memory Enhancement of Acteoside (Verbascoside) in the Senescent Mouse Model Induced by a Combination of D-gal and AlCl3.

Acteoside (verbsacoside), one of the main active phenylethanoid glycosides from Cistanche deserticola, is known to have antioxidant and neuroprotective activity, and herbs containing it are used to enhance memory. However, there is relatively little direct experimental evidence to support the use of acteoside in Alzheimer's disease (AD). The purpose of this study was to elucidate the effects of acteoside in improving learning and memory, using a mouse model of senescence induced by a combination of d-galactose and AlCl3 , and investigate its potential mechanisms compared with the positive controls vitamin E and piracetam. Acteoside was administered intragastrically at doses of 30, 60 and 120 mg/kg/day for 30 days after AD was induced. Memory function was evaluated using a step-down test. The number of neuron was analysed by haematoxylin and eosin staining and the number of Nissl bodies by Nissl staining. The expression of caspase-3 protein in hippocampus was detected by immunohistochemistry and western blot. Nitric oxide and total nitric oxide synthase level in hippocampus were also assessed. Our results showed that the latency of step down was shortened in AD model mice and the number of errors decreased after treatment with all doses of acteoside. Neurons and Nissl bodies in the hippocampus were increased significantly with higher doses (60 and 120 mg/kg/day) of acteoside. The content of nitric oxide, the activity of nitric oxide synthase and the expression of caspase-3 protein were decreased by 120 mg/kg/day acteoside compared with that of the AD model group. Our results support the results obtained previously using the Morris maze test in the same mouse model of senescence, and the use of traditional medicinal herbs containing acteoside for neuroprotection and memory loss.

Memory Enhancement of Acteoside (Verbascoside) in a Senescent Mice Model Induced by a Combination of D-gal and AlCl3.

Acteoside, also known as verbascoside or orobanchin, is a common compound found in many important medicinal plants including the Chinese herb Cistanche deserticola Y. C. Ma, which is used for its neuroprotective and memory enhancement properties. We have investigated the effects of acteoside using a senescent mouse model induced by a combination of chronic intraperitoneal administration of d-gal (60 mg/kg/day) and oral administration AlCl3 (5 mg/kg/day) once daily for 90 days. After 60 days, acteoside (30, 60, and 120 mg/kg/day) was orally administered once daily for 30 days. The memory enhancing effects of acteoside were evaluated using the Morris water maze test. The results showed that 30-120 mg/kg/day of acteoside reduced the escape latency in finding the platform, and increased the number of crossings of the platform. A 30-120 mg/kg/day of acteoside increased significantly the expression of nerve growth factor and tropomycin receptor kinase A mRNA and protein in the hippocampus, measured using real-time RT-PCR, immunohistochemical analysis, and western blotting. These results support the use of C. deserticola for memory enhancement and indicate that the effects of acteoside are induced via promotion of nerve growth factor and tropomycin receptor kinase A expression.

Pharmacokinetics of acteoside following single dose intragastric and intravenous administrations in dogs / 中国天然药物

Acteoside (verbascoside), a phenylethanoid glycoside widely distributed in various plants, has been shown to have potential activity against Alzheimer's disease, attracting great attentions recently. The present study was designed to develop a selective and sensitive LC-MS/MS method for the determination of acteoside in biological samples and carry our a pharmacokinetic (PK) study in beagle dogs. The PK parameters were calculated using non-compartmental models. Following a single-dose oral administration, acteoside was rapidly absorbed and eliminated, with Tmax being between 30 to 45 min and terminal half-life being about 90 min. The areas under the time-concentration curve (AUC) were 47.28 ± 8.74, 87.86 ± 13.33, and 183.14 ± 28.69 mg · min · L(-1) for oral administration of 10, 20, and 40 mg · kg(-1), respectively, demonstrating that the exposure of acteoside proportionally increased with the dose level. The absolute bioavailability of acteoside was around 4%. For all the PK parameters, there were large variations between individual dogs. In conclusion, the pharmacokinetic characteristics observed in the present study can be of great value to help better understand the pharmacological properties of acteoside and to improve the outcome of its clinical use.

The effects of galangin on a mouse model of vitiligo induced by hydroquinone.

Galangin, the main active component of Alpinia officinarum Hance, was tested in a mouse model of vitiligo induced in C57BL/6 mice by the topical application of 2 mL of 2.5% hydroquinone daily to shaved areas (2 × 2 cm) of dorsal skin for 60 days. Thirty days after the final application of hydroquinone, galangin (0.425, and 4.25 mg/kg) was administered orally for 30 days. The hair colour darkened when it grew back after treatment, and histological analysis showed that the number of melanin-containing hair follicles had increased after treatment with all doses of galangin groups and 8-methoxypsoralen (8-MOP, the positive control) compared with the untreated vitiligo group (p < 0.05). The number of skin basal layer melanocytes and melanin-containing epidermal cells had also increased significantly with the application of 4.25 mg/kg of galangin. The concentration of tyrosinase (TYR) in serum was found to have increased, whereas the content of malondialdehyde and the activity of cholinesterase had decreased after treatment with all doses of galangin and 8-MOP, compared with control (p < 0.05). The expression of TYR protein in treated areas of skin also increased with the application of 4.25 mg/kg galangin and 8-MOP. In conclusion, the results showed that galangin was able to improve vitiligo induced by hydroquinone in mice, with the activity related to concentrations of TYR, expression of TYR protein, activity of malondialdehyde and content of cholinesterase. Galangin may therefore be a potential candidate for the treatment of vitiligo, subject to further investigation.

The effect of glutamine therapy on outcomes in critically ill patients: a meta-analysis of randomized controlled trials.

INTRODUCTION: Glutamine supplementation is supposed to reduce mortality and nosocomial infections in critically ill patients. However, the recently published reducing deaths due to oxidative stress (REDOX) trials did not provide evidence supporting this. This study investigated the impact of glutamine-supplemented nutrition on the outcomes of critically ill patients using a meta-analysis. METHODS: We searched for and gathered data from the Cochrane Central Register of Controlled Trials, MEDLINE, Elsevier, Web of Science and ClinicalTrials.gov databases reporting the effects of glutamine supplementation on outcomes in critically ill patients. We produced subgroup analyses of the trials according to specific patient populations, modes of nutrition and glutamine dosages. RESULTS: Among 823 related articles, eighteen Randomized Controlled Trials (RCTs) met all inclusion criteria. Mortality events among 3,383 patients were reported in 17 RCTs. Mortality showed no significant difference between glutamine group and control group. In the high dosage subgroup (above 0.5 g/kg/d), the mortality rate in the glutamine group was significantly higher than that of the control group (relative risk (RR) 1.18; 95% confidence interval (CI), 1.02 to 1.38; P = 0.03). In 15 trials, which included a total of 2,862 patients, glutamine supplementation reportedly affected the incidence of nosocomial infections in the critically ill patients observed. The incidence of nosocomial infections in the glutamine group was significantly lower than that of the control group (RR 0.85; 95% CI, 0.74 to 0.97; P = 0.02). In the surgical ICU subgroup, glutamine supplementation statistically reduced the rate of nosocomial infections (RR 0.70; 95% CI, 0.52 to 0.94; P = 0.04). In the parental nutrition subgroup, glutamine supplementation statistically reduced the rate of nosocomial infections (RR 0.83; 95% CI, 0.70 to 0.98; P = 0.03). The length of hospital stay was reported in 14 trials, in which a total of 2,777 patients were enrolled; however, the patient length of stay was not affected by glutamine supplementation. CONCLUSIONS: Glutamine supplementation conferred no overall mortality and length of hospital stay benefit in critically ill patients. However, this therapy reduced nosocomial infections among critically ill patients, which differed according to patient populations, modes of nutrition and glutamine dosages.

[Study on protective effect of acteoside on cellular model of Alzheimer's disease induced by okadaic acid].

OBJECTIVE: To investigate the effect of acteoside on SK-N-SH nerve cell injury induced by okadaic acid (OA). METHOD: SK-N-SH nerve cells were processed with 20 nmol * L OA to establish the Alzheimer's disease (AD) cellular model, and 5, 10, 20 mg . L-1 acteoside was used to antagonize against its effect. Cell morphology was observed under inverted microscope. The cell survival rate was detected with MTT, and the LDH release rate was measured by enzyme label kit. Western blot was applied to determine the expression of phosphorylation tau proteins in nerve cells. RESULT: The acteoside could significantly improve SK-N-SH cell morphology, enhance the cell survival rate, decrease the cell LDH release rate and the expression of phosphorylated tau proteins at p-Ser 199/202 and p-Ser 404 sites, up-regulated the expression of at non-phosphorylated tau proteins at Ser 202 site and Ser 404 sites. CONCLUSION: Acteoside has significant protective effect on nerve cell injury induced by OA.