Uric acid-lowering effect of harpagoside and its protective effect against hyperuricemia-induced renal injury in mice.

Hyperuricemia (HUA) is caused by increased synthesis and/or insufficient excretion of uric acid (UA). Long-lasting HUA may lead to a number of diseases including gout and kidney injury. Harpagoside (Harp) is a bioactive compound with potent anti-inflammatory activity from the roots of Scrophularia ningpoensis. Nevertheless, its potential effect on HUA was not reported. The anti-HUA and nephroprotective effects of Harp on HUA mice were assessed by biochemical and histological analysis. The proteins responsible for UA production and transportation were investigated to figure out its anti-HUA mechanism, while proteins related to NF-κB/NLRP3 pathway were evaluated to reveal its nephroprotective mechanism. The safety was evaluated by testing its effect on body weight and organ coefficients. The results showed that Harp significantly reduced the SUA level and protected the kidney against HUA-induced injury but had no negative effect on safety. Mechanistically, Harp significantly reduced UA production by acting as inhibitors of xanthine oxidase (XOD) and adenosine deaminase (ADA) and decreased UA excretion by acting as activators of ABCG2, OAT1 and inhibitors of GLUT9 and URAT1. Moreover, Harp markedly reduced infiltration of inflammatory cells and down-regulated expressions of TNF-α, NF-κB, NLRP3 and IL-1ß in the kidney. Harp was a promising anti-HUA agent.

Isolation and identification of hemostatic steroidal glycosides from Ypsilandra thibetica.

The phytoconstituents of the fraction with hemostatic activity of the 70% aqueous ethanol extract of Ypsilandra thibetica Franch. were investigated. As a result, fourteen previously unreported spirostanol saponins, ypsilandrosides Z1-Z14, and nine known analogues were isolated and characterized by MS, NMR, and chemical methods. Among them, ypsilandrosides Z1-Z4 (1-4) have a rare 12-O-ß-d-glucopyranosyl group, while ypsilandrosides Z5-Z8 (5-8) possess a rare double bond between C-4 and C-5, and a hydroxyl or carbonyl located at the C-6. All isolates were further tested for their hemostatic activity. The results suggested that five spirostanol tetraglycosides show favorable inducing platelet aggregation activities. Among them, ypsilandroside G (16) displayed significant inducing platelet aggregation activity with an EC50 value of 57.17 µM. Furthermore, the preliminary structure-activity relationship of these spirostanol glycosides' hemostatic activity was discussed.

A retrospective observational study of the treatment with polymyxin B for liver transplantation recipients infected by multidrug-resistant gram-negative bacteria.

WHAT IS KNOWN AND OBJECTIVE: Only a few studies about polymyxin B (PMB) against multidrug-resistant gram-negative bacteria (MDR GNB) infection were conducted in liver transplantation recipients (LTRs). The purpose of this study was to investigate the efficacy and safety of PMB in the treatment of MDR-GNB in liver transplant recipients and to determine the risk factors affecting clinical cure and 30-day all-cause mortality. METHODS: Data of LTRs receiving PMB from January 2016 to February 2020 were collected. Clinical cure and 30-day all-cause mortality were the main efficacy outcomes, while the incidence of nephrotoxicity, neurotoxicity, and hyperpigmentation of PMB was the main safety outcome. RESULTS AND DISCUSSION: Data of 42 LTRs were included. Clinical cure with PMB was observed in 27 recipients (64.3%), and the 30-day all-cause mortality rate was 31.0% (13/42). The incidence of acute kidney injury (AKI), neurotoxicity, and hyperpigmentation was 57.1% (16/28), 4.8% (2/42), and 16.7% (7/42), respectively. Logistic regression analysis showed that Acute Physiology and Chronic Health Evaluation (APACHE) II score (OR, 1.203; 95% CI, 1.016-1.423, p = 0.032) was an independent risk factor for 30-day all-cause mortality, whereas renal replacement therapy (OR, 0.128; 95% CI, 0.019-0.860, p = 0.034) was an independent risk factor for clinical cure with PMB. WHAT IS NEW AND CONCLUSIONS: This is the first study to evaluate the application of PMB in LTRs. If there were no better therapeutic options left for LTRs other than PMB, it can be used against MDR GNB infection in LTRs. We should closely observe adverse events or reactions, and adjust the dose based on the balance of efficacy and safety.

Heat shock protein B8 promotes proliferation and migration in lung adenocarcinoma A549 cells by maintaining mitochondrial function.

Heat shock protein B8 (HSPB8) impacts on tumor proliferation and migration of malignancy. However, the role of HSPB8 in lung adenocarcinoma (LUAC) remains unclear. The aim of this study, therefore, was to clarify whether HSPB8 could bring benefits to proliferation and migration of LUAC and its underlying mechanisms. The expression of HSPB8 was first evaluated by immunohistochemistry in 35 LUAC samples. Then, A549 lung adenocarcinoma cells were transfected with pcDNA-HSPB8 or si-HSPB8 to induce HSPB8 overexpression and silence. Cellular activity was evaluated with a Cell Counting Kit-8 (CCK-8) assay. Cell proliferation and migration were observed by EdU assay and scratch assay. Mitochondria-specific reactive oxygen species (mtROS) and membrane potential were measured using MitoSOX Red probe and JC-1 staining. Superoxide dismutase (SOD) activities and malondialdehyde (MDA) level were measured using commercial kits, respectively. HSPB8 protein, mitochondrial fusion protein MFN2 and mitochondrial fission protein p-Drp1/Drp1 were measured using western blot. Compared with the normal tissues, the expression of HSPB8 protein was higher in LUAC tissues and upregulation of HSPB8 protein was related to tumor size and tumor location. Furthermore, HSPB8 overexpression aggravated cell proliferation and migration of A549 cells. Mechanistically, HSPB8 suppressed mitochondrial impairment, leading to promoting the progress of A549 lung adenocarcinoma cells. These data demonstrate that HSPB8 plays an important role in progression of LUAC and may be a new target to treat LUAC.

Potential Target Genes in the Development of Atrial Fibrillation: A Comprehensive Bioinformatics Analysis.

BACKGROUND Atrial fibrillation (AF) is the most prevalent arrhythmia worldwide. Although it is not life-threatening, the accompanying rapid and irregular ventricular rate can lead to hemodynamic deterioration and obvious symptoms, especially the risk of cerebrovascular embolism. Our study aimed to identify novel and promising genes that could explain the underlying mechanism of AF development. MATERIAL AND METHODS Expression profiles GSE41177, GSE79768, and GSE14975 were acquired from the Gene Expression Omnibus Database. R software was used for identifying differentially expressed genes (DEGs), and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were subsequently performed. A protein-protein interaction network was constructed in Cytoscape software. Next, a least absolute shrinkage and selection operator (LASSO) model was constructed and receiver-operating characteristic curve analysis was conducted to assess the specificity and sensitivity of the key genes. RESULTS We obtained 204 DEGs from the datasets. The DEGs were mostly involved in immune response and cell communication. The primary pathways of the DEGs were related to the course or maintenance of autoimmune and chronic inflammatory diseases. The top 20 hub genes (high scores in cytoHubba) were selected in the PPI network. Finally, we identified 6 key genes (FCGR3B, CLEC10A, FPR2, IGSF6, S100A9, and S100A12) via the LASSO model. CONCLUSIONS We present 6 target genes that are potentially involved in the molecular mechanisms of AF development. In addition, these genes are likely to serve as potential therapeutic targets.

Piracetam ameliorated oxygen and glucose deprivation-induced injury in rat cortical neurons via inhibition of oxidative stress, excitatory amino acids release and P53/Bax.

Our previous work has demonstrated that piracetam inhibited the decrease in amino acid content induced by chronic hypoperfusion, ameliorated the dysfunction of learning and memory in a hypoperfusion rat model, down-regulated P53, and BAX protein, facilitated the synaptic plasticity, and may be helpful in the treatment of vascular dementia. To explore the precise mechanism, the present study further evaluated effects of piracetam on Oxygen and glucose deprivation (OGD)-induced neuronal damage in rat primary cortical cells. The addition of piracetam to the cultured cells 12 h before OGD for 4 h significantly reduced neuronal damage as determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and lactate dehydrogenase release experiments. Piracetam also lowered the levels of malondialdehyde, nitrogen monoxidum, and xanthine oxidase which was increased in the OGD cells, and enhanced the activities of superoxide dismutase and glutathione peroxidase, which were decreased in the OGD cells. We also demonstrated that piracetam could decrease glutamate and aspartate release when cortical cells were subjected to OGD. Furthermore, Western blot study demonstrated that piracetam attenuated the increased expression of P53 and BAX protein in OGD cells. These observations demonstrated that piracetam reduced OGD-induced neuronal damage by inhibiting the oxidative stress and decreasing excitatory amino acids release and lowering P53/Bax protein expression in OGD cells.

Protoberberine isoquinoline alkaloids from Arcangelisia gusanlung.

HPLC-DAD-directed isolation and purification of the methanol extract of stems of Arcangelisia gusanlung H. S. Lo. led to the isolation of a new protoberberine alkaloid, gusanlung E (1), along with fourteen known derivatives 2-15, seven of which were obtained from the genus Arcangelisia for the first time. The structures and absolute stereochemistry of these compounds were elucidated on the basis of spectroscopic analyses, including 1D and 2D NMR, mass spectrometry, and CD analyses. Gusanlung E (1) expressed weak cytotoxic activity against the SGC 7901 cell line with an IC50 value of 85.1 µM.

Withanolides from the active extract of Physalis angulate and their anti-hepatic fibrosis effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Physalis angulata L., a traditional Chinese medicine called "Kuzhi" in China, was used traditionally to treat liver diseases (eg. icterus, hepatitis) as well as malaria, asthma, and rheumatism. AIM OF THE STUDY: Our study aimed to investigate the withanolides with anti-hepatic fibrosis effect from P. angulate. MATERIALS AND METHODS: Withanolides were obtained from the EtOH extract of P. angulate by bioassay-molecular networking analysis-guided isolation using column chromatography and normal/reversed-phase semipreparative HPLC. The structures of new withanolides were elucidated by combinations of spectroscopic techniques with NMR and ECD calculations. MTT cell viability assay, AO/EB staining method, cell wound healing assay, ELISA and Western blot experiments were employed to evaluate the anti-hepatic fibrosis activity and to uncover related mechanism. Molecular docking analysis and cellular thermal shift assay were used to evaluate and verify the interaction between the active withanolides and their potential targets. RESULTS: Eight unreported withanolides, withagulides A-H (1-8), along with twenty-eight known ones were obtained from P. angulate. Withanolides 6, 9, 10, 24, 27, and 29-32 showed marked anti-hepatic fibrosis effect with COL1A1 expression inhibition above 50 %. Physalin F (9), the main component in the active fraction, significantly decreased the TGF ß1-stimulated expressions of collagen I and α-SMA in LX-2 cells. Mechanism study revealed that physalin F exerted its anti-hepatic fibrosis effect via the PI3K/AKT/mTOR signaling pathway. CONCLUSION: This study suggested that withanolides were an important class of natural products with marked anti-hepatic fibrosis effect. The main withanolide physalin F might be a promising candidate for hepatic fibrosis treatment. The work provided experimental foundation for the use of P. angulate to treat hepatic fibrosis.

[Age-specific detection rates of colorectal neoplasms by colonoscopic screening in high-incidence rural area].

OBJECTIVE: To compare the age-specific detection rates of colorectal neoplasms by colonoscopic screening among high-risk population in rural area and to provide evidence for determining the initial age in the colorectal cancer screening. METHODS: The age-specific detection rates of colorectal cancers and adenomas, and the proportion of detected cases in each age group after screening by the optimized sequential colorectal cancer screening program in Jiashan County, Zhejiang Province, were analyzed. RESULTS: Mass screening with the optimized sequential colorectal cancer screening program in Jiashan was conducted and 8867 colonoscopic examinations were performed. A total of 1811 individuals with at least one colorectal neoplastic lesion were found. Among them, there were 92 (1.04%) colorectal cancer patients, 1164 (13.13%) patients with at least one adenoma and 377 (4.25%) patients with at least one advanced adenoma. The detection rate of colorectal neoplastic lesions for the age group 40 - 44 was considerably lower than that in the age group 45 - 49. Hypothetically, to increase the initial age to 45-years for the optimized sequential colorectal cancer screening program would yield a 7.84% increase in the detection rate of total colorectal neoplastic lesions, 13.46% increase in the detection rate of colorectal cancer, 8.76% increase in the detection rate of adenoma, 12.24% increase in the detection rate of advanced adenoma and 19.64% lower in the cost of initial screening, 13.30% lower in the cost of colonoscopic screening. CONCLUSIONS: Among the high-risk population aged 40 to 74, the detection rates of colorectal cancer and adenoma are increasing with the increase of age, the detection rates of colorectal cancer and adenoma as well as proportion of detected cases in the 40 - 44 age group are considerably lower. To increase the initial age to 45 for colorectal cancer screening in rural area of China is reasonable.

The dichloromethane extract of Callicarpa longissima rich in diterpenoid phenols exerts anti-inflammatory effect via inhibiting the TLR4/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Callicarpa longissima is a typical Yao ethnomedicine that has been used to treat arthritis in China. Our previous study found that the dichloromethane extract (DCME) of C. longissima showed anti-inflammatory activity in vitro. However, the anti-inflammatory mechanism and detailed chemical composition of DCME remain unclear, which lead to the original interest of this study. AIM OF THE STUDY: The study aimed to evaluate the anti-inflammatory properties of the DCME from C. longissima and further explore the accurate chemical components responsible for this active extract. MATERIALS AND METHODS: The anti-inflammatory activity of DCME in vivo was tested with carrageenan-induced mice paw edema model. Its anti-inflammatory mechanism was explored with LPS-stimulated RAW264.7 macrophages model. The compounds in DCME were isolated by repeated column chromatography and their structures were identified on the basis of nuclear magnetic resonance spectroscopy. The anti-inflammatory activities of the isolates in vitro were also tested by suppressing releases of inflammatory mediators (NO, IL-6 and TNF-α) in RAW264.7 macrophages model. In addition, the molecular docking analysis, which evaluated the potential interaction between the compounds and Toll-like receptor 4 (TLR4) and nuclear factor κB (NF-κB), was performed. RESULTS: DCME effectively alleviated the mice paw edema induced by carrageenan. In LPS-stimulated RAW264.7 cells, DCME significantly decreased the production of interleukin (IL)-6 and tumor necrosis factor α (TNF-α) via inhibiting their mRNA transcription, down-regulated the expression of TLR4 and myeloid differentiation factor 88, inhibited the phosphorylation of alpha inhibitor of NF-κB (IκBα), NF-κB p65, and degradation of IκBα. Twelve diterpenoid phenols were identified from DCME, and they not only showed different inhibitory effects on the production of NO, IL-6 and TNF-α in LPS-stimulated RAW264.7 cells, but also could bind to TLR4 and NF-κB as analyzed by molecular docking. CONCLUSIONS: Taken together, DCME from C. longissima could inhibit inflammatory response both in vitro and in vivo, which is mainly attributed to the synergistic effect of abundant diterpenoid phenols through inhibiting the TLR4/NF-κB signaling pathway, and might be a promising agent for the treatment of inflammatory diseases.

Evaluating the effectiveness and safety of acupuncture on serum uric acid in asymptomatic hyperuricemia population: a randomized controlled clinical trial study protocol.

Background: The clinical dangers of asymptomatic hyperuricemia to human health have become increasingly prominent over the past 20 years. Previous studies have shown the potential benefits of acupuncture on uric acid levels in the body. However, definitive evidence is lacking. Our objective is to evaluate the efficacy and safety of acupuncture on serum uric acid (SUA) in individuals with asymptomatic hyperuricemia. Methods: This is a randomized, single-blind, sham-controlled trial. A total of 180 eligible patients with asymptomatic hyperuricemia will be recruited at three hospitals in China. Patients will be randomly assigned in a 1:1 ratio to receive 16 sessions of manual acupuncture or sham acupuncture for 8 weeks. Patients will be followed up for 12 weeks. The primary outcome will be the change in SUA levels at week 8 after randomization. Secondary outcomes will include dynamic changes in SUA levels, efficacy rates, proportion of gout flare, body weight, and acute medication intake. The MGH Acupuncture Sensation Scale and adverse events related to acupuncture will be measured after each treatment. A blinding assessment will be performed on patients who receive at least one session of acupuncture. Data analyses will be performed on a full analysis set and a per-protocol set. Ethics and dissemination: Ethics approval has been obtained from the Clinical Trial Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology (approval no. 2021-S135). Written informed consent will be obtained from enrolled patients. The findings will be disseminated in a peer-reviewed journal. Clinical trial registration: ClinicalTrials.gov identifier, NCT05406830.

Parisvaniosides A-E, five new steroidal saponins from Paris vaniotii.

The species of Paris genus is a prolific source of structurally diverse steroidal saponins responsible for multivarious biological properties. The first phytochemical investigation on the steroidal saponin constituents from the rhizomes of Paris vaniotii Lévl. led to the discovery and structural characterization of four new spirostanol saponins, named parisvaniosides A-D (1-4), and one new furostanol glycoside, named parisvanioside E (5), along with eleven known analogues (6-16). Their structures were unambiguously established on the basis of extensive spectroscopic analysis and comparison with the reported spectroscopic data. Compound 1 is a rare spirostanol saponin sharing with a C-9/C-11 double bond and a peroxy group located between C-5 and C-8 of the aglycone, whereas 3 and 4 are unusual C-27 steroidal sapoins with hydroxyl/methoxyl at both C-5 and C-6. Furthermore, 5 is the first furostanol saponin with a unique aglycone featuring two trisubstituted double bonds in ring B. All isolated saponins were evaluated for their anti-inflammatory effects on a lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production model in RAW 264.7 macrophages.

Steroidal saponin components and their cancer cell cytotoxicity from Paris rugosa.

The chemical components and availability of Paris rugosa were investigated for the first time, using a UPLC-MS/MS-based molecular networking strategy and phytochemical research. Ultimately, eleven undescribed steroidal saponins, parisrugosides A-K, and ten known analogs were identified. Their structures were confirmed using comprehensive spectroscopic data and chemical methods. The aglycones of parisrugosides A-D are first spirostanes with an epoxy group at C-5/C-6, a hydroxy group at C-7, and a double bond at C-8/C-9 or C-8/C-14. Parisrugosides G and H possess an undescribed spirostane aglycone with two double bonds located at C-5/C-6 and C-8/C-9, which are conjugated with a carbonyl group at C-7. The isolates were evaluated for their cytotoxicity against five human cancer cell lines (human HL-60 leukemia, A549 lung, MCF-7 breast, SMMC-7721 liver, and SW480 colon solid cancer cell lines). Parisyunnanoside D, kingianoside K, and dichotomin displayed significant cytotoxicity against these cancer lines, with IC50 values ranging from 0.50 to 19.58 µM.

Ypsilandrosides U-Y, five new steroidal saponins from Ypsilandra thibetica.

Phytochemical reinvestigation on the whole plants of Ypsilandra thibetica obtained four new spirostanol glycosides, named ypsilandrosides U-X (1-4), and one new cholestanol glycoside, named ypsilandroside Y (5). Their structures have been established by extensive spectroscopic data and chemical methods. Among them, compound 4 is a rare spirostanol glycoside which possesses a novel 5(6 → 7) abeo-steroidal aglycone, while compound 1 is a first spirostanol bisdesmoside attached to C-3 and C-12, respectively, isolated from the genus Ypsilandra. The induced platelet aggregation activity of the isolates was tested.

Parisfargosides A-E, five new cholestane glycosides from the rhizomes of Paris fargesii.

Five new cholestane glycosides, named parisfargosides A-E (1-5), were isolated from the rhizomes of Paris fargesii. Their structures were elucidated on the basis of UV, HR-ESI-MS, 1D and 2D NMR data as well as chemical methods. The structures of all compounds contained α, ß-unsaturated ketone unit. Compounds 3-5 possessed a 16,23-cyclocholest skeleton with 6/6/6/5/5 condensed ring, and the absolute configurations of C-16 and C-23 were confirmed according to ROESY spectra with pyridine­d5 and DMSO­d6 as solvents. In addition, the platelet aggregation activity and cytotoxic activity against five human cancer cell lines (HL-60, A549, SMMC-7721, MDA-MB-231, and SW480) of compounds 1-5 were evaluated.

Bioinformatics analysis of candidate genes and potential therapeutic drugs targeting adipose tissue in obesity.

Obesity is a complex medical condition that affects multiple organs in the body. However, the underlying mechanisms of obesity, as well as its treatment, are largely unexplored. The focus of this research was to use bioinformatics to discover possible treatment targets for obesity. To begin, the GSE133099 database was used to identify 364 differentially expressed genes (DEGs). Then, DEGs were subjected to tissue-specific analyses and enrichment analyses, followed by the creation of a protein-protein interaction (PPI) network and generation of a drug-gene interaction database to screen key genes and potential future drugs targeting obesity. Findings have illustrated that the tissue-specific expression of neurologic markers varied significantly (34.7%, 52/150). Among these genes, Lep, ApoE, Fyn, and FN1 were the key genes observed in the adipocyte samples from obese patients relative to the controls. Furthermore, nine potential therapeutic drugs (dasatinib, ocriplasmin, risperidone, gemfibrozil, ritonavir, fluvastatin, pravastatin, warfarin, atorvastatin) that target the key genes were also screened and selected. To conclude the key genes discovered (Lep, ApoE, Fyn, and FN1), as well as 9 candidate drugs, could be used as therapeutic targets in treating obesity.

Electroacupuncture Reduces Visceral Pain Via Cannabinoid CB2 Receptors in a Mouse Model of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) results in chronic abdominal pain in patients due to the presence of inflammatory responses in the colon. Electroacupuncture (EA) is effective in alleviating visceral pain and colonic inflammation associated with IBD. Cannabinoid CB2 receptor agonists also reduce colonic inflammation in a mouse model of IBD. However, whether EA reduces visceral pain and colonic inflammation via the CB2 receptor remains unknown. Here, we determined the mechanism of the antinociceptive effect of EA in a mouse model of IBD induced by rectal perfusion of 2,4,6-trinitrobenzenesulfonic acid solution (TNBS). EA or sham EA was performed at the bilateral Dachangshu (BL25) point for seven consecutive days. The von Frey and colorectal distension tests were performed to measure mechanical referred pain and visceral pain. Western blotting and immunohistochemistry assays were carried out to determine the expression of IL-1ß and iNOS and activation of macrophages in the colon tissues. We found that EA, but not sham EA, attenuated visceral hypersensitivity and promoted activation of CB2 receptors, which in turn inhibited macrophage activation and the expression of IL-1ß and iNOS. The effects of EA were blocked by AM630, a specific CB2 receptor antagonist, and by CB2 receptor knockout. Our findings suggest that EA attenuates mechanical allodynia and visceral hypersensitivity associated with IBD by activating CB2 receptors and subsequent inhibition of macrophage activation and expression of IL-1ß and iNOS.

Electroacupuncture Reduces Anxiety Associated With Inflammatory Bowel Disease By Acting on Cannabinoid CB1 Receptors in the Ventral Hippocampus in Mice.

The therapeutic effects of electroacupuncture (EA) on the comorbidity of visceral pain and anxiety in patients with inflammatory bowel disease (IBD) is well known. It has been known that the ventral hippocampus (vHPC) and the cannabinoid type 1 receptors (CB1R) are involved in regulating anxiety and pain. Therefore, in this study, we determined whether EA reduces visceral pain and IBD-induced anxiety via CB1R in the vHPC. We found that EA alleviated visceral hyperalgesia and anxiety in TNBS-treated IBD mice. EA reversed over-expression of CB1R in IBD mice and decreased the percentage of CB1R-expressed GABAergic neurons in the vHPC. Ablating CB1R of GABAergic neurons in the vHPC alleviated anxiety in TNBS-treated mice and mimicked the anxiolytic effect of EA. While ablating CB1R in glutamatergic neurons in the vHPC induced severe anxiety in wild type mice and inhibited the anxiolytic effect of EA. However, ablating CB1R in either GABAergic or glutamatergic neurons in the vHPC did not alter visceral pain. In conclusion, we found CB1R in both GABAergic neurons and glutamatergic neurons are involved in the inhibitory effect of EA on anxiety but not visceral pain in IBD mice. EA may exert anxiolytic effect via downregulating CB1R in GABAergic neurons and activating CB1R in glutamatergic neurons in the vHPC, thus reducing the release of glutamate and inhibiting the anxiety circuit related to vHPC. Thus, our study provides new information about the cellular and molecular mechanisms of the therapeutic effect of EA on anxiety induced by IBD.

Gusanlungionosides A-D, potential tyrosinase inhibitors from Arcangelisia gusanlung.

Four new megastigmane glycosides, named gusanlungionosides A-D (1-4), together with 10 known compounds (5-14), were isolated from the stems of Arcangelisia gusanlung. The structures and absolute configurations of 1-4 were elucidated by comprehensive analysis of their NMR and CD data. Compounds 1-4 exhibited strong inhibitory effects not only on the mushroom tyrosinase activity in vitro but also on melanogenesis in cells.

[Activity of macrolides and fluoroquinolones against intracellular Legionella pneumophila].

OBJECTIVE: To evaluate the activity of macrolides and fluoroquinolones against Legionella pneumophila by intracellular susceptibility testing. METHODS: Minimum inhibitory concentration (MIC) was determined by standard agar dilution test according to the CLSI. For intracellular assays, legionella pneumonia was used to infect human monocytic cell line THP-1. Erythromycin, azithromycin, levofloxacin and moxifloxacin at 1 × MIC, 4 × MIC, 8 × MIC were added following phagocytosis. Number of viable bacteria was enumerated at 24 h on BCYE (buffered charcoal yeast extract) agar in duplicates using standard plate count method. The result was expressed as percentage inhibition. Mann-Whitney U test was used to determine the significant differences in mean percentage inhibition between agents. RESULTS: Percentage inhibition at 24 h were as follows: Erythromycin 1 × MIC (50.18 ± 27.29)%, 4 × MIC (79.48 ± 20.08)%, 8 × MIC (91.46 ± 8.70)%; Azithromycin 1 × MIC (66.77 ± 26.18)%, 4 × MIC (91.73 ± 8.72)%, 8 × MIC (97.10 ± 3.37)%; Levofloxacin 1 × MIC (99.84 ± 0.25)%, 4 × MIC (99.99 ± 0.02)%, 8 × MIC (99.99 ± 0.01)%; Moxifloxacin 1 × MIC (99.90 ± 0.10)%, 4 × MIC (99.99 ± 0.03)%, 8 × MIC (99.99 ± 0.03)%. The fluoroquinolones showed greater inhibitory activity than macrolides against legionella pneumophila(u = 1.0, 2.0, 5.0, P < 0.05). Levofloxacin and moxifloxacin had the same intracellular activity against legionella pneumophila (u = 190, 183, 217, P > 0.05). Azithromycin was more effective than erythromycin in inhibiting intracellular legionella pneumophila (u = 132, 125, 128, P < 0.05). CONCLUSIONS: The fluoroquinolones were more active than macrolides against legionella pneumophila. The intracellular activity of levofloxacin against legionella pneumophila appeared to be similar to moxifloxacin. Azithromycin was demonstrated to have superior activity against legionella pneumophila compared with erythromycin.