A study integrated metabolomics and network pharmacology to investigate the effects of Shicao in alleviating acute liver injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Shicao is the aerial part of Achillea alpina L., a common herb found mainly in Europe, Asia, and North America. Traditional Chinese medicine has a history of thousands of years and is widely used to treat various diseases. AIM OF STUDY: To explore the hepatoprotective effects of Shicao on CCl4-induced acute liver injury. METHODS: A rat model of acute liver injury was established and liver function indices were assessed to evaluate the protective effect of Shicao on the liver. Untargeted metabolomics of the serum and liver tissues was conducted using UPLC-Q-TOF/MS to identify differential metabolites related to acute liver injury. A network of metabolite-reaction-enzyme-gene constituents was constructed using network pharmacology. Hub targets and key components of the effect of Shicao on acute liver injury were screened from the network. RESULTS: Compared to the model group, Shicao improved the degree of liver damage through the assessment of the liver index, ALT and AST levels, and hepatic pathology slices, demonstrating its hepatoprotective effect against acute liver injury in rats. 10 and 38 differential metabolites involved in acute liver injury were identified in serum and liver tissues, respectively. Most of these were regulated or restored following treatment with Shicao, which mainly consisted of bile acids, lipids, and nucleotides such as taurocholic acid, LysoPC (17:0), and adenosine diphosphate ribose. Through the network of metabolite-reaction-enzyme-gene-constituents, 10 key components and 5 hub genes, along with 7 crucial differential metabolites, were mainly involved in glycerophospholipid metabolism, purine metabolism, biosynthesis of unsaturated fatty acids, and primary bile acid biosynthesis, which may play important roles in the prevention of acute liver injury by Shicao. CONCLUSION: This study revealed that Shicao had protective effects against CCl4-induced liver injury in rats. It was speculated that the ingredients of Shicao might be closely related to the hub targets, thereby regulating the levels of key metabolites, affecting inflammatory response and oxidative stress and attenuate the liver injury consequently. This study provides a basis for further investigation of its therapeutic potential and the mechanism of action.

Immune pathway activation in neurons triggers neural damage after stroke.

Ischemic brain injury is a severe medical condition with high incidences in elderly people without effective treatment for the resulting neural damages. Using a unilateral mouse stroke model, we analyze single-cell transcriptomes of ipsilateral and contralateral cortical penumbra regions to objectively reveal molecular events with single-cell resolution at 4 h and 1, 3, and 7 days post-injury. Here, we report that neurons are among the first cells that sense the lack of blood supplies by elevated expression of CCAAT/enhancer-binding protein ß (C/EBPß). To our surprise, the canonical inflammatory cytokine gene targets for C/EBPß, including interleukin-1ß (IL-1ß) and tumor necrosis factor α (TNF-α), are subsequently induced also in neuronal cells. Neuronal-specific silencing of C/EBPß or IL-1ß and TNF-α substantially alleviates downstream inflammatory injury responses and is profoundly neural protective. Taken together, our findings reveal a neuronal inflammatory mechanism underlying early pathological triggers of ischemic brain injury.

Astragaloside IV-mediated inhibition of oxidative stress by upregulation of ghrelin in type 2 diabetes-induced cognitive impairment.

This study is to observe the upregulation effect of astragaloside IV on ghrelin in diabetic cognitive impairment (DCI) rats and to investigate the pathway in prevention and treatment by reducing oxidative stress. The DCI model was induced with streptozotocin (STZ) in conjunction with a high-fat and high-sugar diet and divided into three groups: model, low-dose (40 mg/kg), and high-dose (80 mg/kg) astragaloside IV. After 30 days of gavage, the learning and memory abilities of rats, as well as their body weight and blood glucose levels, were tested using the Morris water maze and then detection of insulin resistance, SOD activity, and serum MDA levels. The whole brain of rats was sampled for hematoxylin-eosin and Nissl staining to observe pathological changes in the hippocampal CA1 region. Immunohistochemistry was used to detect ghrelin expression in the hippocampal CA1 region. A Western blot was used to determine changes in GHS-R1α/AMPK/PGC-1α/UCP2. RT-qPCR was used to determine the levels of ghrelin mRNA. Astragaloside IV reduced nerve damage, increased superoxide dismutase (SOD) activity, decreased MDA levels, and improved insulin resistance. Ghrelin levels and expression increased in serum and hippocampal tissues, and ghrelin mRNA levels increased in rat stomach tissues. According to Western blot, it increased the expression of the ghrelin receptor GHS-R1α and upregulated the mitochondrial function associated-protein AMPK-PGC-1α-UCP2. Astragaloside IV increases ghrelin expression in the brain to reduce oxidative stress and delay diabetes-induced cognitive impairment. It may be related to the promotion of ghrelin mRNA levels.

Effect of a carbohydrate-rich beverage on rate of cesarean delivery in primigravidae with epidural labor analgesia: a multicenter randomized trial.

BACKGROUND: Labor represents a period of significant physical activity. Inefficient energy supply may delay labor process and even lead to cesarean delivery. Herein we investigated whether ingestion of a carbohydrate-rich beverage could reduce cesarean delivery in laboring women with epidural analgesia. METHODS: This multicenter randomized trial was conducted in obstetrician-led maternity units of nine tertiary hospitals in China. Primigravidae with single term cephalic pregnancy who were preparing for vaginal birth under epidural analgesia were randomized to intake a carbohydrate-rich beverage or commercially available low-carbohydrate beverages during labor. The primary outcome was the rate of cesarean delivery. Secondary outcomes included maternal feeling of hunger, assessed with an 11-point scale where 0 indicated no hunger and 10 the most severe hunger, and maternal and neonatal blood glucose after childbirth. RESULTS: Between 17 January 2018 and 20 July 2018, 2008 women were enrolled and randomized, 1953 were included in the intention-to-treat analysis. The rate of cesarean delivery did not differ between the two groups (11.3% [111/982] with carbohydrate-rich beverage vs. 10.9% [106/971] with low-carbohydrate beverages; relative risk 1.04, 95% CI 0.81 to 1.33; p = 0.79). Women in the carbohydrate-rich beverage group had lower subjective hunger score (median 3 [interquartile range 2 to 5] vs. 4 [2 to 6]; median difference - 1; 95% CI - 1 to 0; p < 0.01); their neonates had less hypoglycemia (1.0% [10/968] vs. 2.3% [22/956]; relative risk 0.45; 95% CI 0.21 to 0.94; p = 0.03) when compared with those in the low-carbohydrate beverage group. They also had higher rates of maternal hyperglycemia (6.9% [67/965] vs. 1.9% [18/953]; p < 0.01) and neonatal hyperglycemia (9.2% [89/968] vs. 5.8% [55/956]; p < 0.01), but none required special treatment. CONCLUSIONS: For laboring primigravidae with epidural analgesia, ingestion of a carbohydrate-rich beverage compared with low-carbohydrate beverages did not reduce cesarean delivery, but relieved maternal hunger and reduced neonatal hypoglycemia at the expense of increased hyperglycemia of both mothers and neonates. Optimal rate of carbohydrate supplementation remains to be determined. TRIAL REGISTRATION: www.chictr.org.cn ; identifier: ChiCTR-IOR-17011994 ; registered on 14 July 2017.

Retraction notice to "Neuroprotective effect of Liuwei Dihuang decoction on cognition deficits of diabetic encephalopathy in streptozotocin-induced diabetic rat" [J. Ethnopharmacol. 150 (2013) 371-381].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. The authors have plagiarized/duplicated part of a paper that appeared in Neurosci Lett, 549 (2013) 63-68, (https://doi.org/10.1016/j.neulet.2013.06.002). Several images in the Journal of Ethnopharmacology paper; 3A, 3B, 4A, 4B correspond to figures; 2A, 2B, 3A and 3B respectively as published in Neuroscience Letters. One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.

1,3-Benzodioxole-based fibrate derivatives as potential hypolipidemic and hepatoprotective agents.

A series of target compounds 1,3-benzodioxole-based fibrate derivatives were designed and synthesized. All the target compounds were preliminarily evaluated by hyperlipidemia mice induced by Triton WR-1339, in which compound 12 displayed a greater anti-hyperlipidemia activity than other compounds as well as positive drug fenofibrate (FF). 12 showed a significant reduction of plasma lipids, such as triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterin (LDL-C), in high fat diet (HFD) induced hyperlipidemic mice. In addition, hepatic transaminases (AST and ALT) were ameliorated after administration of 12, in particular the AST, and the histopathological examination showed that 12 improved the hepatic lipid accumulation. The expression of PPAR-α involved in lipids metabolism was up-regulated in the liver tissues of 12-treated group. Other significant activity such as antioxidant, and anti-inflammation was confirmed and reinforced the effects of 12 as a potential hypolipidemia and hepatoprotective agent.

Clinical efficacy and safety of modified Sijunzi decoction for the treatment of ulcerative colitis: A protocol for a systematic review and meta-analysis.

BACKGROUND: Ulcerative colitis (UC) is a chronic non-specific intestinal inflammatory disease with unknown etiology. In recent years, the global incidence has been increasing. Sijunzi decoction (SJZD) is a traditional Chinese medicine that has been used for treatment of other diseases in previous studies as it has no side effects and it has a pharmacological effect in gastrointestinal function, immune system, ulcers, and tissue repair. METHODS: PubMed, Embase, Cochrane Library, GeenMedical, China National Knowledge Infrastructure, Chinese Sci-tech Journals full-text Database, Chinese Biomedical Database, and Chinese Science Citation Database were searched to screen the related literatures of "ulcerative colitis" and "Jiawei Sijunzi decoction". The research data extracted from above studies was analyzed by Review Manager 5.3 and Stata14.2 software. RESULTS: This systematic review and meta-analysis will evaluate the efficacy and safety of Jiawei SJZD in the treatment of UC and provide effective evidence for clinical use. CONCLUSION: In this study, the published evidence of modified SJZD in the treatment of UC was systematically summarized and evaluated, so that it can be better applied in clinic. INPLASY REGISTRATION NUMBER: INPLASY2020100102.

3,4-Dihydroxyphenethyl nitrate with nitric oxide releasing, antioxidant, hypoglycemic and hypolipidemic effects.

Nitric oxide (NO) dysfunction, oxidative stress, and dyslipidemia are main risk factors associated with the pathophysiology of diabetic complications. In this study, 3,4-dihydroxyphenethyl nitrate (HT-ONO2) was designed, synthesized and evaluated, which incorporated hydroxytyrosol (HT) and nitrate. HT-ONO2 significantly exhibited hypoglycemic activity after oral administration to diabetic mice induced by streptozocin (STZ). HT-ONO2 also potently decreased plasma triglyceride (TG), total cholesterol (TC) in hyperlipidemia mice induced by Triton WR 1339. Meanwhile, HT-ONO2 displayed NO-releasing and antioxidant activity both in diabetic and hyperlipidemia mice and in vitro. Moreover, HT-ONO2 shown definite vasodilation and α-glucosidase inhibition activity in vitro. The results suggested that the hybrid hydroxytyrosol-based nitrate with NO supplement, antioxidant, hypoglycemia and hypolipidemia provided a potential multi-target agent to ameliorate the diabetes mellitus and its complications.

Clathrin-dependent endocytosis predominantly mediates protein absorption by fat body from the hemolymph in Bombyx mori.

During insect larval-pupal metamorphosis, proteins in the hemolymph are absorbed by the fat body for the maintenance of intracellular homeostasis; however, the type of proteins and how these proteins are internalized into the fat body are unclear. In Bombyx mori, the developmental profiles of total proteins in the hemolymph and fat body showed that hemolymph-decreased protein bands (55-100 kDa) were in accordance with those protein bands that increased in the fat body. Inhibition of clathrin-dependent endocytosis predominantly blocked the transportation of 55-100 kDa proteins from the hemolymph into the fat body, which was further verified by RNA interference treatment of Bmclathrin. Six hexamerins were shown to comprise ∼90% of the total identified proteins in both the hemolymph and fat body by mass spectrum (MS) analysis. In addition, hemolymph-specific proteins were mainly involved in material transportation, while fat body-specific proteins particularly participated in metabolism. In this paper, four hexamerins were found for the first time, and potential proteins absorbed by the fat body from the hemolymph through clathrin-dependent endocytosis were identified. This study sheds light on the protein absorption mechanism during insect metamorphosis.

Design and Synthesis of Novel Thiazolo[5,4-d]pyrimidine Derivatives as Potential Angiogenesis Inhibitors.

Vascular endothelial growth factor receptor-2 (VEGFR-2) plays an important role in both vasculogenesis and angiogenesis. Inhibition of VEGFR-2 has been demonstrated as a key method against tumor-associated angiogenesis. Thiazolopyrimidine is an important analog of the purine ring, and we choose the thiazolopyrimidine scaffold as the mother nucleus. Two series of thiazolo[5,4-d]pyrimidine derivatives were synthesized and evaluated for their antiproliferative activity. In HUVEC inhibition assay, compounds 3l (=1-(5-{[2-(4-chlorophenyl)-5-methyl[1,3]thiazolo[5,4-d]pyrimidin-7-yl]amino}pyridin-2-yl)-3-(3,4-dimethylphenyl)urea) and 3m (=1-(5-{[2-(4-chlorophenyl)-5-methyl[1,3]thiazolo[5,4-d]pyrimidin-7-yl]amino}pyridin-2-yl)-3-(4-methoxyphenyl)urea) exhibited the most potent inhibitory effect (IC50 =1.65 and 3.52 µm, respectively). Compound 3l also showed the best potency against VEGFR-2 at 50 µm (98.5 %). These results suggest that further investigation of compound 3l might provide potential angiogenesis inhibitors.

Phenyl and Diaryl Ureas with Thiazolo[5,4-d]pyrimidine Scaffold as Angiogenesis Inhibitors: Design, Synthesis and Biological Evaluation.

Angiogenesis is crucial for tumor growth and inhibition of angiogenesis has been regarded as a promising approach for cancer therapy. Vascular endothelial growth factor receptor-2 (VEGFR-2) is an important factor in angiogenesis. In this work, a novel series of thiazolo[5,4-d]pyrimidine derivatives inhibiting angiogenesis were rationally designed and synthesized. Their inhibitory activities against human umbilical vein endothelial cells (HUVEC) were investigated in vitro. 1-(4-Fluorophenyl)-3-{4-[(5-methyl-2-phenyl[1,3]thiazolo[5,4-d]pyrimidin-7-yl)amino]phenyl}urea (19b) and 1-(3-Fluorophenyl)-3-{4-[(5-methyl-2-phenyl[1,3]thiazolo[5,4-d]pyrimidin-7-yl)amino]phenyl}urea (19g) exhibited the most potent inhibitory effect on HUVEC proliferation (IC50 =12.8 and 5.3 µm, respectively). Compound 19g could inhibit the migration of human umbilical vein endothelial cells. These results support the further investigation of these compounds as potent anticancer agents.

Pyrimidinylacetamide-based 2-pyridylureas as Angiogenesis Inhibitors: Design, Synthesis and Biological Evaluation.

BACKGROUND: VEGFR-2 inhibitors have been widely used in the treatment of cancer. In our continued efforts to search for potent and novel VEGFR-2 inhibitors as antitumor agents, we have identified a series of ureas and amides bearing a oxazolopyrimidine scaffold. AIM OF THE STUDY: To discover more potent VEGFR-2 inhibitors with stronger binding affinity and better physical and chemical properties. METHODS: 23 pyrimidinylacetamide-based ureas were designed and synthesized. Replacement of oxazolopyrimidine with a pyrimidinylacetamide generated a series of novel VEGFR-2 inhibitors. RESULTS AND CONCLUSIONS: In HUVEC inhibition assay, the most potent compound (compound 16) possessed an IC50 value of 0.43 µM. Compound 16 also inhibited the migration and capillary like tube formation of HUVECs with inhibition rate at 22% (1 µM) and 17.5% (0.8 µM) respectively. These results support the further investigation of compound 16 as a potential anti-cancer agent.

Diarylureas and Diarylamides with Oxazolo[5,4-d]pyrimidine Scaffold as Angiogenesis Inhibitors.

A series of oxazolopyrimidine-based ureas and amides were designed, synthesized, and biologically evaluated for their antiproliferative and antiangiogenic activities. These compounds were identified to exhibit inhibitory activities against human umbilical vein endothelial cells (HUVEC) in vitro. Among these compounds, compound 22 effectively inhibited the migration and capillary-like tube formation of human umbilical vein endothelial cells. It also exhibited a concentration-dependent inhibition on capillary sprouting from the rat aorta rings. Preliminary mechanistic studies revealed that compound 22 suppressed protein kinases activation, by decreasing PI3K and ERK 1/2 phosphorylation. These results support the further investigation of this class of compounds as potential anticancer agents.

Margin evaluation of translational and rotational set-up errors in intensity modulated radiotherapy for cervical cancer.

A clinical target volume (CTV) to planning target volume (PTV) margin recipes was routinely used to ensure dose was actually delivered to target for all (most) patients. Currently used margin recipes were associated with only translational set-up errors in radiotherapy. However, when set-up errors extended to six-degree (6D) scope (three translational and three rotational set-up errors), margin recipe should be re-evaluated. The purpose of this study was to investigate dosimetric changes of targets (both CTV and PTV) coverage when 6D set-up errors were introduced and testify the practicability of currently used margin recipe in radiotherapy. A total number of 105 cone beam computer tomography scans for ten patients with cervical cancer were derived prior to treatment delivery and 6D set-up errors were acquired with image registration tools. Target coverage was evaluated retrospectively for 6D set-up errors introduced plan with 6 mm CTV to PTV margin. Target coverage of PTV showed significant decreases (3.3 %) in set-up errors introduced plans compared with original plans. But CTV coverage was not susceptible to these set-up errors. A tendency of coverage decrease for PTV along with distance away from treatment was testified, from -0.2 to -6.2 %. However, CTV seems changed less, from -0.2 to -0.8 %. The result indicate that a CTV to PTV margin of 6 mm was sufficient to take into account 6D set-up errors for most patients with cervical cancer. Future research suggests a smaller margin to further improve both tumor coverage and organs at risk sparing.

Curcumin inhibits advanced glycation end product-induced oxidative stress and inflammatory responses in endothelial cell damage via trapping methylglyoxal.

Methylglyoxal (MGO)-induced carbonyl stress and pro-inflammatory responses have been suggested to contribute to endothelial dysfunction. Curcumin (Cur), a polyphenolic compound from Curcuma longa L., may protect endothelial cells against carbonyl stress-induced damage by trapping dicarbonyl compounds such as MGO. However, Cur-MGO adducts have not been studied in depth to date and it remains to be known whether Cur-MGO adducts are able to attenuate endothelial damage by trapping MGO. In the present study, 1,2-diaminobenzene was reacted with MGO to ensure the reliability of the reaction system. Cur was demonstrated to trap MGO at a 1:1 ratio to form adducts 1, 2 and 3 within 720 min. The structures of these adducts were identified by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry. The kinetic curves of Cur (10(-7), 10(-6) and 10(-5) M) were measured from 0-168 h by fluorescent intensity. Cur significantly inhibited the formation of advanced glycation end products (AGEs). The differences in oxidative damage and the levels of pro-inflammatory cytokines following MGO + HSA or Cur-MGO treatment were investigated in human umbilical vein endothelial cells (HUVECs). Exposure of HUVECs to the Cur-MGO reaction adducts significantly reduced the intracellular ROS levels and improved cell viability compared with MGO alone. Furthermore, there was a significant reduction in the expression levels of transforming growth factor-ß1 and intercellular adhesion molecule(-1) following treatment with Cur-MGO adducts compared with MGO alone. These results provide further evidence that the trapping of MGO by Cur inhibits the formation of AGEs. The current study indicates that the protective effect of Cur on carbonyl stress and pro-inflammatory responses in endothelial damage occurs via the trapping of MGO.

A Combination of Genetic Algorithm and Particle Swarm Optimization for Vehicle Routing Problem with Time Windows.

A combination of genetic algorithm and particle swarm optimization (PSO) for vehicle routing problems with time windows (VRPTW) is proposed in this paper. The improvements of the proposed algorithm include: using the particle real number encoding method to decode the route to alleviate the computation burden, applying a linear decreasing function based on the number of the iterations to provide balance between global and local exploration abilities, and integrating with the crossover operator of genetic algorithm to avoid the premature convergence and the local minimum. The experimental results show that the proposed algorithm is not only more efficient and competitive with other published results but can also obtain more optimal solutions for solving the VRPTW issue. One new well-known solution for this benchmark problem is also outlined in the following.

Shikonin inhibits the cell viability, adhesion, invasion and migration of the human gastric cancer cell line MGC-803 via the Toll-like receptor 2/nuclear factor-kappa B pathway.

OBJECTIVES: Shikonin is an active naphthoquinone pigment isolated from the root of Lithospermum erythrorhizon. This study was designed to explore the inhibition of Shikonin on cell viability, adhesion, migration and invasion ability of gastric cancer (GC) and its possible mechanism. METHODS: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed for cell viability and adhesion ability of MGC-803 cells. Cell scratch repair experiments were conducted for the determination of migration ability while transwell assay for cell invasion ability. Western blot analysis and real-time polymerase chain reaction assay were used for the detection of protein and mRNA expressions. KEY FINDINGS: Fifty per cent inhibitory concentration of Shikonin on MGC-803 cells was 1.854 µm. Shikonin (1 µm) inhibited significantly the adhesion, invasion and migratory ability of MGC-803 cells. Interestingly, Shikonin in the presence or absence of anti-Toll-like receptor 2 (TLR2) antibody (2 µg) and nuclear factor-kappa B (NF-κB) inhibitor MG-132 (10 µm) could decrease these ability of MGC-803 cells markedly, as well as the expression levels of matrix metalloproteinases (MMP)-2, MMP-7, TLR2 and p65 NF-κB. In addition, the co-incubation of Shikonin and anti-TLR2/MG-132 has a significant stronger activity than anti-TLR2 or MG-132 alone. CONCLUSIONS: The results indicated that Shikonin could suppress the cell viability, adhesion, invasion and migratory ability of MGC-803 cells through TLR2- or NF-κB-mediated pathway. Our findings provide novel information for the treatment of Shikonin on GC.

Blockade of emodin on amyloid-ß 25-35-induced neurotoxicity in AßPP/PS1 mice and PC12 cells through activation of the class III phosphatidylinositol 3-kinase/Beclin-1/B-cell lymphoma 2 pathway.

Autophagy plays an important role in the pathogenesis of Alzheimer's disease. In the present study, the blockade mechanism of emodin on amyloid-ß 25-35-induced neurotoxicity was explored. Cell viability of PC12 cells was evaluated by the MTT assay and neuro damage by the lactate dehydrogenase leakage assay. Gene silencing by small interfering RNA, cDNA constructs and transfection, as well as Western blot were performed to assess protein expression levels. AßPP/PS1 mice were administered orally with emodin (50 mg/kg/day), and LC3-II positive cells in their brain cortex sections were detected by immunohistochemical staining. Emodin could significantly inhibit the LC3-I/LC3-II conversion ratio and cell viability while decreasing the lactate dehydrogenase level in AßPP/PS1 mice and PC12 cells. LC3II positive cells in the cortex were decreased significantly by the treatment with both emodin and 3-methyladenine. Furthermore, emodin and 3-methyladenine could increase B-cell lymphoma 2 while decreasing Beclin-1 and hVps34 expressions, which were induced by amyloid-ß 25-35. Small interfering gene silencing Beclin-1 and B-cell lymphoma 2 confirmed this signaling pathway. We also found that the phosphatidylinositol 3-kinase inhibitor LY294002 could block LC3-I/LC3-II conversion and increase B-cell lymphoma 2 while decreasing hVps34 and Beclin-1 expressions. The results suggest that the blockade of emodin on amyloid-ß 25-35-induced autophagy may occur via the activation of the class III phosphatidylinositol 3-kinase/Beclin-1/B-cell lymphoma 2 pathway. Our results provide confirmatory evidence for the application of emodin in the prevention and treatment of Alzheimer's disease.

Tectorigenin inhibits the inflammation of LPS-induced acute lung injury in mice.

AIM: In a previous study, the anti-inflammatory effects of tectorigenin were disclosed. In this study, the anti-inflammatory effects of tectorigenin on acute lung injury using a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model were investigated METHOD: The cell-count in the bronchoalveolar lavage fluid (BALF) was measured. The animal lung edema degree was evaluated by the wet/dry weight (W/D) ratio. The superoxidase dismutase (SOD) activity and myeloperoxidase (MPO) activity was assayed using SOD and MPO kits, respectively. The levels of inflammatory mediators, including tumor necrosis factor-α (TNF-α), IL-1ß, and IL-6 were assayed using an enzyme-linked immunosorbent assay method. Pathological changes of lung tissues were observed through HE staining. The inflammatory signal pathway related protein nuclear factor NF-κB p65 mRNA expression was measured by real-time PCR, and the protein level of NF-κB p65 was measured using Western blotting analysis. RESULTS: The data showed that treatment with the tectorigenin markedly attenuated the inflammatory cell numbers in the BALF, decreased nuclear factor NF-κB p65 mRNA level and protein level in the lungs, and improved SOD activity and inhibited MPO activity. Histological studies showed that tectorigenin substantially inhibited LPS-induced neutrophils in lung tissue compared with the model group. CONCLUSION: The results indicated that tectorigenin had a protective effect on LPS-induced ALI in mice.

Qifu-Yin attenuates AGEs-induced Alzheimer-like pathophysiological changes through the RAGE/NF-κB pathway.

Qifu-Yin (QFY), a widely used formula of traditional Chinese medicine (TCM) derived from "Jingyue Quanshu", is one of the most commonly used TCM prescriptions for the clinical treatment of Alzheimer disease. The role of advanced glycation end products (AGEs) and its receptor RAGE have attracted increasing attention as the pivotal role of Aß has been questioned. The present study was designed to test the neuroprotective effects of QFY, and the possible mechanism in AGE-induced Alzheimer model rats. After injection of AGE in the CA3 area of the hippocampus, QFY (8.6, 4.3, and 2.15 g·kg(-1)), and a positive control drug donepezil (2 mg·kg(-1)) were administrated through gastric intubation to rats once daily for thirty consecutive days. Another positive control group was the AGE + anti-RAGE group, which was simultaneously injected with anti-RAGE antibody before AGE treatment. The control group, sham-operated group, as well as the AGE + anti-RAGE group received saline at the same dosage. The Morris water maze test and the step-down passive avoidance test were conducted to evaluate the cognitive function of the rats. The expression of RAGE and NF-κB were assayed by immunohistochemical staining. The levels of Aß, TNF-α, and IL-1ß in the hippocampus were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that QFY could significantly attenuate the memory impairment induced by AGE, decrease the expressions of RAGE and NF-κB, and reduce the levels of Aß, TNF-α, and IL-1ß in the hippocampus in a dose-dependent manner. Also, the blockage of RAGE could significantly reduce the impairments caused by AGEs. In conclusion, QFY could attenuate AGEs-induced, Alzheimer-like pathophysiological changes. These neuroprotective effects might be related to the RAGE/NF-κB pathway and its anti-inflammatory activity.