Abstract Objectives Cyclic nucleotides play a pivotal role in the establishment of synaptic plasticity which in turn facilitates the memory processes. Dysregulation of cyclic nucleotides due to increased phosphodiesterase (PDE) activity has been implicated in various neurodegenerative diseases. In this study, we investigated the potential effects of Papaverine (PAP), a PDE10A inhibitor, on cognitive dysfunction induced by chronic REM sleep deprivation in a mouse model. Methods The modified multiple platform method (MMPM) was used for the induction of chronic REM sleep deprivation. Morris water maze was used to access the cognitive functions, while cAMP level was quantified by ELISA technique. Through Western blot analysis, we evaluated the expression of PDE10A, amyloid beta, CREB, BDNF, NR2A, NR2B, Beclin-1, LC3B, and synaptic proteins. Results Administration of PAP ameliorated learning and memory deficits in mice subjected to chronic REM sleep deprivation. PAP increased cAMP and PSD-95, Synapsin, SAP97, pCREB, BDNF levels and decreased NR2A, and NR2B expression, along with the restoration of basal autophagy (Beclin-1, LC3B) in the hippocampal region of chronic REM sleep deprived mice. Increased cAMP and autophagy proteins are probably linked to the decrease in PDE10A and amyloid beta expression, respectively. Conclusions This study evidences that papaverine, a non-narcotic opium alkaloid and PDE10A inhibitor, can alleviate learning and memory impairments induced by chronic REM sleep deprivation.

Papaverine (PV) has been previously identified as a promising candidate in SARS-CoV-2 repurposing screens. In this study, we further investigated both its antiviral and immunomodulatory properties. PV displayed antiviral efficacy against SARS-CoV-2 and influenza A viruses H1N1 and H5N1 in single infection as well as in co-infection. We demonstrated PV's activity against various SARS-CoV-2 variants and identified its action at the post-entry stage of the viral life cycle. Notably, treatment of air-liquid interface (ALI) cultures of primary bronchial epithelial cells with PV significantly inhibited SARS-CoV-2 levels. Additionally, PV was found to attenuate interferon (IFN) signaling independently of viral infection. Mechanistically, PV decreased the activation of the IFN-stimulated response element following stimulation with all three IFN types by suppressing STAT1 and STAT2 phosphorylation and nuclear translocation. Furthermore, the combination of PV with approved COVID-19 therapeutics molnupiravir and remdesivir demonstrated synergistic effects. Given its immunomodulatory effects and clinical availability, PV shows promising potential as a component for combination therapy against COVID-19.

Fractional flow reserve (FFR) is considered the standard for assessment of the physiological significance of coronary artery stenosis. Intracoronary papaverine (PAP) is the most potent vasodilator used for the achievement of maximal hyperemia. However, its use can provoke ventricular tachycardia (VT) due to excessive QT prolongation. We evaluated the clinical efficacy and safety of the administration of PAP after nicorandil (NIC), a potassium channel opener that prevents VT, for optimal FFR measurement.A total of 127 patients with 178 stenoses were enrolled. The FFR values were measured using NIC (NIC-FFR) and PAP (PAP-FFR). We administered PAP following NIC (NIC-PAP). Changes in the FFR and electrogram parameters (baseline versus NIC versus PAP) were assessed and the incidence of arrhythmias after PAP was evaluated. In addition, we analyzed another 41 patients with 51 stenoses by assessing the FFR using PAP before NIC (PAP-NIC). After propensity score matching, the electrogram parameters between 2 groups were compared.The mean PAP-FFR was significantly lower than the mean NIC-FFR (0.82 ± 0.11 versus 0.81 ± 0.11, P < 0.05). The mean baseline-QTc, NIC-QTc, and PAP-QTc values were 425 ± 37 ms1/2, 424 ± 41 ms1/2, and 483 ± 54 ms1/2, respectively. VT occurred in only 1 patient (0.6%). Although PAP induced QTc prolongation (P < 0.05), the PAP-QTc duration was significantly shorter in NIC-PAP compared to PAP-NIC (P < 0.05).The administration of PAP with NIC may induce sufficient hyperemia and prevent fatal arrhythmia through reductions in the PAP-induced QTc prolongation during FFR measurement.

ABSTRACT In this work, we present a fast, simple and selective method for the extraction/preconcentration and determination of five opium alkaloids. This method is based on the combination of dispersive solid phase extraction with magnetic molecularly imprinted polymers (MMIP) and determination via high performance liquid chromatography. The surface modified Fe3O4 nanoparticles were synthesised in-situ, from a co-precipitation method by addition of a mixture of the methacrylic acid and ammonia to a mixture of Fe2+/Fe3+ under nitrogen atmosphere. MMIP was prepared from surface modified nanoparticles in the presence of ethylene glycol dimethyl acrylate as cross-linker and azobisisobutyronitrile as initiator and template molecule under reflux in acetonitrile. MMIPs for five natural occurring opium alkaloids, including morphine (MO), codeine (CO), thebaine (TE), noscapine (NO) and papaverine (PA) were prepared in the same manner. Structural characterisation and elucidation of both synthesised nanoprticles were performed by Fourier transform-infrared spectroscopy, scanning electron microscopy. X-ray diffraction and vibrating sample magnetometry. A precise chromatographic method was developed and coupled with extraction with MMIP nanoparticles for simultaneous preconcentration and determination of above-mentioned alkaloids in underground water samples. The limit of detection obtained 0.007, 0.007, 0.004, 0.003, 0.003 mg L−1 for MO, CO, TE, NO and PA, respectively and recoveries were about 97–102%. Linear dynamic range and relative standard deviation were 0.03–100 mg L−1 and less than 1.5% for each analyte.

Microglial priming is the process of microglial proliferation and activation in response to neurodegeneration and abnormal protein accumulation. Priming makes microglia susceptible to secondary inflammatory stimuli and causes exaggerated inflammatory responses. In the present study, we established a microglial priming model in mice by administering a single injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 20 mg/kg). MPTP induced microglial activation without dopaminergic degeneration; however, subsequent treatment with a sub-toxic dose of lipopolysaccharides (LPS) induced an amplified inflammatory response and caused nigrostriatal dopaminergic degeneration. These pathological and inflammatory changes, including microglial activation and dopaminergic cell loss in the substantia nigra (SN) area were reversed by papaverine (PAP) administration. In addition, MPTP/LPS enhanced interleukin-1β (IL-1β) expression and processing via nod-like receptor protein 3 (NLRP3) inflammasome activation in the SN region of mice. However, PAP treatment suppressed inflammasome activation and subsequent IL-1β maturation. Moreover, PAP inhibited nuclear factor-κB (NF-κB) and enhanced cAMP-response element binding protein (CREB) activity in the SN of MPTP/LPS mice. These results suggest that PAP inhibits the activation of NLRP3 inflammasome by modulating NF-κB and CREB signaling pathways, which results in reduced microglial activation and neuronal cell death. Thus, PAP may be a potential candidate for the treatment of Parkinsons’s disease, which is aggravated by systemic inflammation.

Phosphodiesterase-10A (PDE10A) hydrolyse the secondary messengers cGMP and cAMP, two molecules playing important roles in neurodevelopment and brain functions. PDE10A is associated to progression of neurodegenerative diseases like Alzheimer's, Parkinson's, Huntington's diseases, and a critical role in cognitive functions. The present study was undertaken to determine the possible neuroprotective effects and the associated mechanism of papaverine (PAP), a PDE10A isoenzyme inhibitor, against quinolinic acid (QUIN)-induced excitotoxicity using human primary cortical neurons. Cytotoxicity potential of PAP was analysed using MTS assay. Reactive oxygen species (ROS) and mitochondrial membrane potential were measured by DCF-DA and JC10 staining, respectively. Caspase 3/7 and cAMP levels were measured using ELISA kits. Effect of PAP on the CREB, BNDF and synaptic proteins such as SAP-97, synaptophysin, synapsin-I, and PSD-95 expression was analysed by Western blot. Pre-treatment with PAP increased intracellular cAMP and nicotinamide adenine dinucleotide (NAD+) levels, restored mitochondrial membrane potential (ΔΨm), and decreased ROS and caspase 3/7 content in QUIN exposed neurons. PAP up-regulated CREB and BDNF, and synaptic protein expression. In summary, these data indicate that PDE10A is involved in QUIN-mediated synaptotoxicity and its inhibition elicit neuroprotection by reducing the oxidative stress and protecting synaptic proteins via up-regulation of cAMP signalling cascade.

The use of chilled semen has gained increasing interest in canine reproductive services. The addition of phosphodiesterase (PDE) inhibitors that increase the intracellular cyclic adenosine monophosphate levels may improve sperm motility. The purpose of this study was to examine the quality of sperm under the effect of the specific PDE-10 inhibitor (papaverine) added after storage for 1, 2, and 3 days at 5 °C. The ejaculates were obtained from 5 healthy Beagle dogs by digital manipulation. After collection, ejaculates were pooled, extended and cooled at 5 °C during 3 days. Sperm parameters were tested 30 min after the addition of different papaverine (PA) concentrations: 0, 5, 10 and 20 µM. Sperm motility (CASA), viability (PI/FITC-PNA) and capacitation status (chlortetracycline assay) were evaluated. The results showed that the addition of PA has no effect on sperm samples at day 0. However, concentrations of 5 and 10 µM increased (p < .05) sperm motility kinetics and viability significantly compared to the control at day 1, day 2 and day 3 of cooling. The addition of 20 μM PA decreased (p < .05) sperm quality parameters significantly and increased the percentage of capacitated/acrosome-reacted spermatozoa. In conclusion, the addition of 5 and 10 μM PA concentrations after cooled storage improved canine sperm quality.

Papaverine inhibits α-synuclein aggregation by modulating neuroinflammation and matrix metalloproteinase-3 expression in the subacute MPTP/P mouse model of Parkinson’s disease

Pluripotent anti-inflammatory immunomodulatory effects of papaverine against cerebral ischemic-reperfusion injury

A novel lab-on-chip integrated microfluidic device for solid-phase extraction (SPE) and spectrophotometric detection of morphine (MOR), codeine (COD), and papaverine (PAP) was developed. The extracted analytes were analyzed with a miniature UV-Vis spectrophotometer. The SPE adsorptive phase composed of polyurethane/polyaniline (PU/PANI) nanofibers was fabricated by electrospinning and in situ oxidative polymerization techniques. The sorbent was characterized by Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). The main factors of extraction such as desorption conditions, pH, salt effect, and extraction time were investigated. The partial least square (PLS) regression was applied to improve the quantification of analytes. The linear dynamic ranges (LDRs) for MOR, COD, and PAP were 4-240, 4-210, and 1-150 ng mL-1, respectively. Finally, the proposed method was successfully applied for the determination of MOR, COD, and PAP in human urine samples and the extraction recoveries were obtained in the range of 66.7-85.0% with RSDs < 8.3%.

Objective To explore the anatomic basis of the thinning of the free posterior tibial artery perforator flaps and the clinical effect of repairing wound on hand or foot due to trauma. Methods From November, 2016 to December, 2017, 10 cases of lower extremity cadaver specimens perfused with red ralex were dissected, which were perfused through the amputated femoral artery. Five of them were left and the rest were right. All cases were males. The number, diameter, branches and distribution of the perforator was observed. From September, 2012 to September, 2017, there were 13 cases of clinical application, which were 5 cases of hand wound and 8 cases of foot wound. The size of the wound was 3.0 cm × 2.0 cm to 6.0 cm × 4.0 cm, and the flap area was 3.5 cm × 2.2 cm to 6.5 cm × 4.5 cm. The repairing procedure was suitable for the wound associated with tendon, bone, joint capsule exposure. Results The number of posterior tibial artery perforating branches that more than 0.50 mm in diameter was 4 to 6, and the mean diameter was (0.87±0.26) mm. The perforating branch penetrated into the fat layer and was divided into 3 layers of vascular network: deep fat vascular network, superficial fat vascular network and subdermal vascular network. The perforating branch was located according to the positional relationship from deep to shallow, and vessel diameter become smaller step by step. The perforating branch trunk gave off branches to the deep vascular network, and the superficial vascular network had the same origin or shared with the deep blood vessels. The subdermal vascular network issued from the superficial vascular network or directly from the perforating branch trunk. There was no or few communicating branch between the deep vascular network and superficial ones, besides the vessel pedicle. So trimming deep fat layer will not affect the blood supply of superficial vascular network and neither will affect the flap blood supply. Most of the deep fat tissue was trimmed in 13 cases. The superficial and subdermal fat vascular network was preserved, and the same to the trunk and branches of the pedicle. All the flaps survived. Of which, 1 appeared arterial crisis on the 2nd day after operation, and relieved by the local injection of papaverine. There was 1 case of venous crisis on the 3rd day, and improved by stitches, local release of congestion. Followed-up time was ranged from 2 to 12 months. All flaps were soft with good blood supply and good appearance, and did not need a second thinning surgery. Flaps restored the protective feeling 6 months later. Conclusion The microdissection of perforator flap of posterior tibial artery provides a theoretical basis for the perforator flap thinning, and the thinning of perforator flap is a good method to repair the appearance and function of the wound after foot and hand injuries. Key words: Posterior tibial artery perforator flap; Applied anatomy; Wound; Repair; Microsurgical operation

Planar polyamide 6 nanofibrous membrane was for the first time used in direct coupling of supported liquid membrane (SLM) extraction to CE analysis. Disposable microextraction device with the nanofibrous membrane was preassembled and stored for immediate use. The membrane in the device was impregnated with 1 µL of 1-ethyl-2-nitrobenzene and the device was subsequently filled with 10 µL of acceptor solution (10 mM HCl) and 15 µL of donor solution (sample). The device was in-line coupled to CE system for selective extraction and direct injection, separation and quantification of model basic drugs (nortriptyline, haloperidol, loperamide and papaverine) from standard saline solutions (150mM NaCl) and from undiluted human body fluids (urine and blood plasma). Compared to standard polypropylene supporting material, the nanofibrous membrane demonstrated superior characteristics in terms of lower consumption of organic solvents, constant volumes of operational solutions, full transparency and possibility to preassemble the devices. Extraction parameters were better or comparable for the nanofibrous vs. the polypropylene membrane and the hyphenated SLM-CE method with the nanofibrous membrane was characterized by good repeatability (RSD ≤ 11.3%), linearity (r2 ≥ 0.9953; 0.5-20mg/L), sensitivity (LOD ≤ 0.4mg/L) and transfer (27-126%) of the basic drugs.

Objective To compare the survival rate, incidence of vascular crisis, adverse drug reactions and average in-hospital time of the traditional and modified treatment groups after digit replantation. Methods From January 2015 to January 2016, 923 cases (1 225 fingers) of digit replantation were treated with modified postoperative protocol. Only papaverine (72 hours), low molecular heparin (5 days) and prophylactic antibiotics (72 hours) were used. Fluid was replenished with crystal only, except for patients with serious blood loss, who might need concentrated red blood cell or cryofresh plasma. The patients were advised to stay in bed for absolutely 3 days. From January 2012 to January 2013, 785 cases (915 fingers) of digit replantation were treated with traditional protocol, in addition to the use of papaverine and low molecular heparin, including low molecular dextran or hydroxyethyl starch and anisodamine hydrochloride. After operation the patients were advised to stay in bed for absolutely 7 days. The results of the two groups were compared statistically including the survival rate, incidence of vascular crisis, adverse drug reactions and average in-hospital time. Results The survival rate of digit replantation was 92.13% in traditional group and 92.07% in modified group. There was no statistical difference between the two groups. Similarly, the incidence of vascular crisis was 14.09% in traditional group and 15.18% in modified group. There was no statistical difference between the two groups. However, the incidence of adverse drug reactions was 15.7% in traditional group and 2.2% in modified group. There was a significant difference between the two groups (P<0.01). The average in-hospital time was (10.23±3.21) days in traditional group and (8.34±2.75) days in modified group. The difference between the two groups was statistically significant (P<0.05). Conclusion The modified postoperative protocol for digit replantation can shorten the in-hospital time, reduce the medicine related complications, and had no effect on the survival rate of digit replantation. Thus it is worthy of clinical promotion. Key words: Replantation; Case-control studies; Treatment protocol; Anticoagulation

Objective To research the surgical procedure and clinical effects of proper digital artery island flaps of adjacent digit for repair of finger soft tissue defects and reconstruction of blood circulation. Methods From March 2010 to May 2015, 21 cases of finger soft tissue defects were treated with proper digital artery island flaps of adjacent digit. The artery or nerve defect ranged from 1.5 to 4.0 cm. The skin and soft tissue defects area ranged from 1.5 cm×1.0 cm to 4.0 cm×2.0 cm. During the operation, proper digital artery and its island flaps were obtained from adjacent side margin of adjacent digit, and transferred to repair skin and soft tissue defects and reconstruct blood circulation simultaneously. The nerve defect was bridged by forearm or foot dorsal cutaneous nerve graft. Results Vasospasm occurred in 2 cases during intraoperative dissection, which was relieved after local application of papaverine and hot warm saline. Vascular crisis occurred in one case 2 hours after the operation, which was relieved by operative exploration. The rest flaps survived uneventfully. The follow-up period ranged from 6 to 48 months with the average being 18 months. The appearance and texture of the flaps were good. Partial protective sensations were restored. The original appearance and function of the injured finger were recovered. No dysfunction occurred in donor fingers. According to the functional evaluation standards issued by Hand Surgery Society of the Chinese Medical Association, the results were excellent in 13 cases, good in 6 cases, fair in 2 cases. Conclusion Application of proper digital artery island flaps of adjacent digit for repair of finger soft tissue defects and reconstruction of blood circulation not only has the clinical effect of flow-through flap, but also has the advantages of simplicity, safety and reliability, which is worth promoting. Key words: Finger injuries; Surgical flaps; Flow-through flaps; Transfer repair

As part of a research programme to establish an analytical method for the simultaneous detection of the five major opium alkaloids in poppy seeds by liquid chromatography–electrospray ionization–mass spectrometry (LC-ESI-MS) it was discovered that the inclusion of thebaine produced two peaks for the same compound. This was in contrast to the effective simultaneous detection, by LC-ESI-MS, of morphine, codeine, papaverine and noscapine. The presence of these two peaks for thebaine was investigated using nuclear magnetic resonance spectroscopy with deuterated solvents to emulate the mobile phase conditions experienced. It was found that the presence of 80%, or higher ratios of, water caused two epimeric forms of thebaine to be formed; this explained the presence of two peaks on the chromatogram. In contrast, when a lower water content was used with 1% acetic acid, one stable form of thebaine could be analysed and resulted in a single peak visible in the subsequent chromatography.

Objective To investigate the curative effect and safety of continuous pulse injection of urokinase for the treatment of arteriovenous internal fistula thrombosis. Methods During the period from Jan. 2011 to Dec. 2014, 40 patients with arteriovenous internal fistula thrombosis were collected. They were randomly assigned to the improved group (continuous pulse urokinase injection) and control group (traditional urokinase application) according to the table of random digit. Thrombin time, prothrombin time, D-dimer, fibrinogen, hemoglobin, platelet, lipid and colored doppler ultrasonography of arteriovenous internal fistula before thrombolysis were recorded. All the patients used the 18 G venous indwelling needles. In the improved group, continuous pulse injection of urokinase (200 000 units) was performed. The same dose of urokinase were injected by micro-pump at the speed of 20 000 U/min in the control group. After that all the patients still received micro-pump injection of 300 000 units urokinase at the speed of 20 000 U/min, subcutaneous injection of low molecular heparin (4 000 U), intravenous injection of papaverine (30 mg), oral administration of aspirin (150 mg) for 3 days, respectively. We recorded the internal fistula recanalization, vital signs, bleeding, and the dose of urokinase every hour. The end points of our study were internal fistula recanalization, severe bleeding and pulmonary thromboembolism. The treatment could be repeated during the three days after admission. We compared the time and incidence of recanalization, dose of urokinase, incidence of bleeding and pulmonary thromboembolism between two groups. Results A total of 28 cases (93.33%) showed successful results in (30.33±27.23)hours an average, with (20 000±12 000)units urokinase in the improved group. Whereas, 22 cases (75.86%) showed successful results in an average of (50.15±22.18)hours, with (25 000±18 000)units urokinase in the control group. There was significant difference in the time and incidence of recanalization, dose of urokinase between two groups (P 0.05). Conclusions Compared to traditional urokinase application, continuous pulse urokinase injection achieves higher recanalization rate, shorter recanalization time, and less dose of urokinase. It does not increase the risk of bleeding as well. For the treatment of arteriovenous internal fistula thrombosis, continuous pulse urokinase injection is an effective and safe way, with great clinical value. Key words: Urinary plasminogen activator/TU; Injections, jet; Arteriovenous fistula/CO/DT; Thrombosis/CO/DT; Thrombolytic therapy

A sensitive electrochemical method for the determination of papaverine (PAP) by using Mg-Al layered double hydroxide graphene oxide (LDH-GO) and multiwall carbon nanotubes (MWCNT) immobilized on carbon paste electrode (CPE) has been introduced. Electrochemical behavior of PAP as an antispasmodic was investigated on modified CPE by cyclic voltammetry, differential pulse voltammetry, electrochemical impedance spectroscopy, and double step chronoamperometry techniques. Due to the remarkable electrochemical behavior of MWCNT and the high chemical activity of LDH-GO, CNT/LDH-GO/CPE anodic peak current of PAP enhances compared with CNT/CPE and LDH-GO/CPE. The surface morphology of the electrode was studied by the field emission scanning electron microscopy technique. The effect of experimental parameters, such as pH and scan rate on voltammetric response of PAP, was investigated. Maximum current was observed in phosphate buffer pH = 9.0. The electrode reaction followed a diffusion-controlled pathway. The wide dynamic range of concentration (0.10-100 μmol L <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-1</sup> ) with a detection limit of 0.04 μmol L <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-1</sup> was obtained for PAP under optimized conditions. This electrode displayed proper reproducibility, stability, and anti-interference. Low cost, easy preparation, high sensitivity, and good selectivity have made the modified electrode suitable for the determination of PAP in urine and plasma matrixes.

Objective To observe the effect of drug combinations on the blood flow after reduction of the testicular torsion in rabbits. Methods From October 2014 to June 2015, 36 male rabbits(weighing 1.8-2.4 kg, 10-14 months of age) were randomly divided into experimental group and control group, 18 in each group.Produced by surgical testicular torsion model (720°counterclockwise rotation of the left side testicle), every rabbit was accepted surgery reset after 9 hours and found all twisted testicles were dark.After fomentation with warm salt water, all the testicles were observed no significant improvement in colors, and no fresh blood flow after opening tunica albuginea, then all the testicles were retained and fixed.Low molecular dextran(5 ml/kg, ear marginal vein injection, 1/d), papaverine(1.5 mg/kg, intramuscular, 3/d) and low molecular weight heparin sodium(200 IU/kg, subcutaneous, 1/d) were applied to promote testicular revascularization for 5 days in experimental group, and penicillin (40 000 U/kg, intramuscular, 1/d) for 7 days.Control group was only given penicillin(40 000 U/kg, intramuscular, 1/d) to prevent wound infection.Then Color Doppler ultrasound was used to observe the testicular blood flow siganals that were divided into 0, 1, 2, 3 classes.Class 2 and class 3 could be considered as testicular survival.After each scrotum was opened, according to color, texture of testicle and whether the fresh blood flowing out when tunica albuginea was opened, to determine whether the testicle was alive.The testicle was ruddy, flexible, and fresh blood was observed, which could prove testicular survival. Results In experimental group, the testicular blood flow siganals: 0 class 4 cases, 1 class 3 cases, 2 class 4 cases, 3 class 7 cases.In control group, the testicular blood flow siganals: 0 class 9 cases, 1 class 2 cases, 2 class 4 cases, 3 class 3 cases.Surgical exploration found 11 cases of testicular survival in experimental group and 7 cases in control group, which was significantly difference (P<0.05). Conclusions The combined application of low molecular dextran, papaverine, low molecular weight heparin sodium can promote the recovery of testicular blood after reduction of testicular torsion, and improve testicular survival rate. Key words: Testicular torsion; Low molecular dextran; Papaverine; Low molecular weight heparin sodium; Testicular survival

ObjectiveTo investigate the effects of papaverine (PAP) on lipopolysaccharide (LPS)-induced microglial activation and its possible mechanisms.Materials and methodsBV2 microglial cells were first pretreated with PAP (0, 0.4, 2, 10, and 50 μg/mL) and then received LPS stimulation. Transcription and production of proinflammatory factors (IL1β, TNFα, iNOS, and COX-2) were used to evaluate microglial activation. The transcriptional changes undergone by M1/M2a/M2b markers were used to evaluate phenotype transformation of BV2 cells. Immunofluorescent staining and Western blot were used to detect the location and expression of P65 and p-IKK in the presence or absence of PAP pretreatment.ResultsPretreatment with PAP significantly inhibited the expression of IL1β and TNFα, and suppressed the transcription of M1/M2b markers Il1rn, Socs3, Nos2 and Ptgs2, but upregulated the transcription of M2a markers (Arg1 and Mrc1) in a dose-dependent manner. In addition, PAP pretreatment significantly decreased the expression of p-IKK and inhibited the nuclear translocation of P65 after LPS stimulation.ConclusionPAP not only suppressed the LPS-induced microglial activity by inhibiting transcription/production of proinflammatory factors, but also promoted the transformation of activated BV2 cells from cytotoxic phenotypes (M1/M2b) to a neuroprotective phenotype (M2a). These effects were probably mediated by NF-κB signaling pathway. Thus, it would be a promising candidate for the treatment of neurodegenerative diseases.

179. Effect of papaverine on neurospheres