Archiv für Experimentelle Pathologie und Pharmakologie (N-S ARCH PHARMACOL )

Publisher: Springer Verlag

Journal description

Naunyn-Schmiedeberg's Archives of Pharmacology was founded in 1873 as "Archiv für experimentelle Pathologie und Pharmakologie" by B. Naunyn O. Schmiedeberg E. Klebs. In cooperation with colleagues it was edited by L. Krehl W. Straub W. Heubner and others; from Vol. 208 No. 2 on edited in cooperation with the Deutsche Pharmakologische Gesellschaft. Vols. 1-158 (1930) Leipzig F.C.W. Vogel Vols. 159-196 (1940) Berlin F.C.W. Vogel; from Vol. 197 on Berlin Springer. Vols. 110 to 253 "Naunyn-Schmiedebergs Archiv für experimentelle Pathologie und Pharmakologie"; from Vol. 254 (1966) to 263 "Naunyn-Schmiedebergs Archiv für Pharmakologie und experimentelle Pathologie"; from Vol. 264 (1969) to 271 "Naunyn-Schmiedebergs Archiv für Pharmakologie"; from Vol. 272 (1972) "Naunyn-Schmiedeberg's Archives of Pharmacology". As of Vol. 343 (1991) edited on behalf of the Deutsche Gesellschaft für Pharmakologie und Toxikologie; from Vol. 349 (1994) Deutsche Gesellschaft für experimentelle und klinische Pharmakologie und Toxikologie e.V.

Current impact factor: 2.36

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2013 / 2014 Impact Factor 2.36
2012 Impact Factor 2.147
2011 Impact Factor 2.647
2010 Impact Factor 2.5
2009 Impact Factor 2.631
2008 Impact Factor 2.83
2007 Impact Factor 2.161
2006 Impact Factor 2.779
2005 Impact Factor 2.098
2004 Impact Factor 1.963
2003 Impact Factor 2.101
2002 Impact Factor 2.566
2001 Impact Factor 2.472
2000 Impact Factor 2.869
1999 Impact Factor 2.414
1998 Impact Factor 2.2
1997 Impact Factor 2.492
1996 Impact Factor 2.679
1995 Impact Factor 3.04
1994 Impact Factor 2.813
1993 Impact Factor 3
1992 Impact Factor 3.227

Impact factor over time

Impact factor
Year

Additional details

5-year impact 2.23
Cited half-life 0.00
Immediacy index 0.53
Eigenfactor 0.01
Article influence 0.62
Website Naunyn-Schmiedeberg's Archives of Pharmacology website
Other titles Naunyn-Schmiedeberg's archives of pharmacology (Online), Archives of pharmacology
ISSN 0028-1298
OCLC 43450808
Material type Document, Periodical, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Springer Verlag

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • Author's pre-print on pre-print servers such as arXiv.org
    • Author's post-print on author's personal website immediately
    • Author's post-print on any open access repository after 12 months after publication
    • Publisher's version/PDF cannot be used
    • Published source must be acknowledged
    • Must link to publisher version
    • Set phrase to accompany link to published version (see policy)
    • Articles in some journals can be made Open Access on payment of additional charge
  • Classification
    ​ green

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: TRPM8 has been implicated in pain and migraine based on dorsal root- and trigeminal ganglion-enriched expression, upregulation in preclinical models of pain, knockout mouse studies, and human genetics. Here, we evaluated the therapeutic potential in pain of AMG2850 ((R)-8-(4-(trifluoromethyl)phenyl)-N-((S)-1,1,1-trifluoropropan-2-yl)-5,6-dihydro-1,7-naphthyridine-7(8H)-carboxamide), a small molecule antagonist of TRPM8 by in vitro and in vivo characterization. AMG2850 is potent in vitro at rat TRPM8 (IC90 against icilin activation of 204 ± 28 nM), highly selective (>100-fold IC90 over TRPV1 and TRPA1 channels), and orally bioavailable (F po > 40 %). When tested in a skin-nerve preparation, AMG2850 blocked menthol-induced action potentials but not mechanical activation in C fibers. AMG2850 exhibited significant target coverage in vivo in a TRPM8-mediated icilin-induced wet-dog shake (WDS) model in rats (at 10 mg/kg p.o.). However, AMG2850 did not produce a significant therapeutic effect in rat models of inflammatory mechanical hypersensitivity or neuropathic tactile allodynia at doses up to 100 mg/kg. The lack of efficacy suggests that either TRPM8 does not play a role in mediating pain in these models or that a higher level of target coverage is required. The potential of TRPM8 antagonists as migraine therapeutics is yet to be determined.
    Archiv für Experimentelle Pathologie und Pharmakologie 02/2015;
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    ABSTRACT: This theme issue of Naunyn-Schmiedeberg’s Archives of Pharmacology contains six review articles covering recent advances in our understanding of the potential pharmacological roles of different transient receptor potential (TRP) ion channel subtypes that can be targeted for the therapeutic use. Numerous review articles and several book chapters in recent years have extensively covered the advances in modulation of TRPV1, founding member of TRP family. The intended purpose of this theme issue was to summarize the knowledge about other less studied TRP subtypes. For comparison, as of early January 2015, SciFinder identifies 8814 publications for TRPV1, but only 2410 for TRPA1, 1759 for TRPV4, and 1608 publications for TRPM8.Transient receptor potential melastatin 8 (TRPM8) can be activated by cold temperatures (8-25 °C) and cooling agents such as menthol and icilin. Several studies with TRPM8 knockout mice demonstrated significant deficiencies to cold responses including cold allodynia. ...
    Archiv für Experimentelle Pathologie und Pharmakologie 02/2015;
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    ABSTRACT: Sesquiterpene lactones (SLs) are plant-derived compounds that are abundant in plants of the Asteraceae family and posses a broad spectrum of biological activities, ranging from anti-inflammatory, phytotoxic, antibacterial, and antifungal to cytotoxic/anticancer. In recent years, anticancer properties of these compounds and molecular mechanisms of their action have been studied extensively on numerous cell lines and also on experimental animals. SLs have been shown to disrupt cellular redox balance and induce oxidative stress in cancer cells. Oxidative stress is associated with increased production of reactive oxygen species (ROS) which in turn can promote many aspects of cancer development and progression. On the other hand, ROS, which initiate apoptosis via the mitochondrial-dependent pathway, can also be used to kill cancer cells, if they can be generated in cancer. One of the most important regulators of the redox equilibrium in the cells is reduced glutathione (GSH). In cancer cells, GSH levels are higher than in normal cells. Therefore, SL can induce apoptosis of cancer cells by decreasing intracellular GSH levels. The use of SL which can affect intracellular redox signaling pathways can be considered an interesting approach for cancer treatment. In this review, we give a brief description of the mechanisms and pathways involved in oxidative stress-induced anticancer activity of SL.
    Archiv für Experimentelle Pathologie und Pharmakologie 02/2015;
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    ABSTRACT: Our previous study has shown that mangiferin (MGF), a glucosylxanthone from Mangifera indica, exerts gastrointestinal prokinetic action involving a cholinergic mechanism. Postoperative ileus (POI) is a temporary disturbance in gastrointestinal motility following surgery, and intestinal inflammatory response plays a critical role in the pathogenesis of POI. The present study investigated to know whether MGF having anti-inflammatory and prokinetic actions can ameliorate the intestinal inflammation and impaired gastrointestinal transit seen in the mouse model of POI. Experimental POI was induced in adult male Swiss mice by standardized small intestinal manipulation (IM). Twenty-four hours later, gastrointestinal transit was assessed by charcoal transport. MGF was administered orally 1 h before the measurement of GIT. To evaluate the inflammatory response, plasma levels of proinflammatory cytokines TNF-α, IL-1β, IL-6, and chemokine MCP-1, and the myeloperoxidase activity, nitrate/nitrite level, and histological changes of ileum were determined in mice treated or not with MGF. Experimental POI in mice was characterized by decreased gastrointestinal transit and marked intestinal and systemic inflammatory response. MGF treatment led to recovery of the delayed intestinal transit induced by IM. MGF in ileum significantly inhibited the myeloperoxidase activity, a marker of neutrophil infiltration, and nitrate/nitrite level and reduced the plasma levels of TNF-α, IL-1β, IL-6, and MCP-1 as well. MGF treatment ameliorates the intestinal inflammatory response and the impaired gastrointestinal motility in the mouse model of POI.
    Archiv für Experimentelle Pathologie und Pharmakologie 02/2015;
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    ABSTRACT: The transient receptor potential ankyrin 1 (TRPA1) channel is a nonselective cation channel belonging to the superfamily of transient receptor potential (TRP) channels. It is predominantly expressed in sensory neurons and serves as an irritant sensor for a plethora of electrophilic compounds. Recent studies suggest that TRPA1 is involved in pain, itch, and respiratory diseases, and TRPA1 antagonists have been actively pursued as therapeutic agents. Here, we review the recent progress, unsettled issues, and challenges in TRPA1 research and drug discovery.
    Archiv für Experimentelle Pathologie und Pharmakologie 02/2015;
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    ABSTRACT: Nitrate tolerance is an important problem in the treatment of ischemic heart diseases. The present study investigated whether or not a soluble guanylyl cyclase (sGC) activator can be used as a coronary vasodilator under nitrate-tolerant conditions. Helically cut strips of endothelium-denuded monkey and canine coronary arteries were suspended in organ chambers for isometric tension recording. Nitrate tolerance was induced by a 1-h treatment with nitroglycerin (0.1 mM) followed by 1-h washout of the agent. Control strips were not exposed previously to nitroglycerin, but otherwise were treated identically. The relaxant response to nitroglycerin was dramatically impaired by previous exposure to the drug for 1 h in either monkey or canine coronary arteries, indicating the development of nitrate tolerance. In contrast, development of nitrate tolerance did not affect the relaxant potency and efficacy of the sGC activator BAY 60-2770 in either the monkey or canine coronary arteries. These findings suggest that it may be possible to use sGC activators as substitute drugs for nitroglycerin if tolerance is developed during the treatment of ischemic heart diseases.
    Archiv für Experimentelle Pathologie und Pharmakologie 01/2015;
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    ABSTRACT: Cough is currently the most common reason for patients to visit a primary care physician in the UK, yet it remains an unmet medical need. Current therapies have limited efficacy or have potentially dangerous side effects. Under normal circumstances, cough is a protective reflex to clear the lungs of harmful particles; however, in disease, cough can become excessive, dramatically impacting patients’ lives. In many cases, this condition is linked to inflammatory diseases such as asthma and chronic obstructive pulmonary disease (COPD), but can also be refractory to treatment and idiopathic in nature. Therefore, there is an urgent need to develop therapies, and targeting the sensory afferent arm of the reflex which initiates the cough reflex may uncover novel therapeutic targets. The cough reflex is initiated following activation of ion channels present on vagal sensory afferents. These ion channels include the transient receptor potential (TRP) family of cation-selective ion channels which act as cellular sensors and respond to changes in the external environment. Many direct activators of TRP channels, including arachidonic acid derivatives, a lowered airway pH, changes in temperature, and altered airway osmolarity are present in the diseased airway where responses to challenge agents which activate airway sensory nerve activity are known to be enhanced. Furthermore, the expression of some TRP channels is increased in airway disease. Together, this makes them promising targets for the treatment of chronic cough. This review will cover the current understanding of the role of the TRP family of ion channels in the activation of airway sensory nerves and cough, focusing on four members, transient receptor potential vanilloid (TRPV) 1, transient receptor potential ankyrin (TRPA) 1, TRPV4, and transient receptor potential melastatin (TRPM) 8 as these represent the channels where most information has been gathered with relevance to the airways. We will describe recent data and highlight the possible therapeutic utility of specific TRP channel antagonists as antitussives in the clinic.
    Archiv für Experimentelle Pathologie und Pharmakologie 01/2015;
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    ABSTRACT: Though anti-metastatic function of non-metastatic 2 (NME2) has been implicated in multiple cancers, mechanisms of metastases control by NME2 are not clearly understood. Recent observations indicating the involvement of telomerase, the ribonucleoprotein required for telomere synthesis, in metastatic outcome are interesting. Notably, though the role of telomerase dysfunction in tumorigenesis is relatively well studied, involvement in metastasis progression is poorly understood. Recent findings demonstrate NME2 presence at telomere ends, association with telomerase, and NME2's role in inhibition of telomerase activity in cancer cells. These present a novel opportunity to investigate mechanisms underlying NME2-mediated metastasis suppression.
    Archiv für Experimentelle Pathologie und Pharmakologie 12/2014;
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    ABSTRACT: Recent studies suggest the importance of combined treatment of glycogen synthase kinase-3β (GSK-3β) and histone deacetylase (HDAC) inhibition in various in vitro and in vivo models of neurological diseases. Lithium chloride (LiCl) and valproate (VPA), two well-known mood stabilizers, have been reported to act through GSK-3β and HDAC inhibition, respectively. The present study was designed to investigate the potential of low-dose combination of LiCl and VPA in intracerebroventricular streptozotocin (ICV-STZ)-induced cognitive deficits in rats. STZ was injected twice (3 mg/kg ICV) on alternate days (day 1 and day 3) in rats. The ICV-STZ-treated rats received LiCl (60 mg/kg, i.p.), VPA (200 mg/kg, i.p.), and combination of both LiCl (60 mg/kg, i.p.) and VPA (200 mg/kg, i.p.) drugs for a period of 3 weeks. The ICV-STZ administration results in significant memory impairment, elevated oxidative-nitrosative stress, and reduced brain-derived neurotrophic factor (BDNF) levels. Using a battery of behavioral and biochemical tests, we observed that co-treatment of both drugs showed synergistic effect in improving the spatial learning and memory impairment as well as significantly attenuated the oxidative stress markers in STZ-treated rats as compared to either drug alone. Moreover, the combination of both drugs reversed the hyperinsulinemic brain condition and improved the BDNF levels in STZ-treated rats. Based upon these results, it could be suggested that a low-dose combination of LiCl and VPA produces synergistic and more consistent neuroprotective effects in ICV-STZ-induced cognitive deficits in rats.
    Archiv für Experimentelle Pathologie und Pharmakologie 12/2014;
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    ABSTRACT: Biomechanical factors play a critical role in regulating the physiology as well as the pathology of multiple joint tissues and have been implicated in the pathogenesis of osteoarthritis. Therefore, the mechanisms by which cells sense and respond to mechanical signals may provide novel targets for the development of disease-modifying osteoarthritis drugs (DMOADs). Transient receptor potential vanilloid 4 (TRPV4) is a Ca(2+)-permeable cation channel that serves as a sensor of mechanical or osmotic signals in several musculoskeletal tissues, including cartilage, bone, and synovium. The importance of TRPV4 in joint homeostasis is apparent in patients harboring TRPV4 mutations, which result in the development of a spectrum of skeletal dysplasias and arthropathies. In addition, the genetic knockout of Trpv4 results in the development of osteoarthritis and decreased osteoclast function. In engineered cartilage replacements, chemical activation of TRPV4 can reproduce many of the anabolic effects of mechanical loading to accelerate tissue growth and regeneration. Overall, TRPV4 plays a key role in transducing mechanical, pain, and inflammatory signals within joint tissues and thus is an attractive therapeutic target to modulate the effects of joint diseases. In pathological conditions in the joint, when the delicate balance of TRPV4 activity is altered, a variety of different tools could be utilized to directly or indirectly target TRPV4 activity.
    Archiv für Experimentelle Pathologie und Pharmakologie 12/2014;
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    ABSTRACT: Sepsis is characterized by a severe production of reactive oxygen species (ROS) and other radical species with consequent oxidative stress. S-allyl cysteine (SAC) is a water-soluble organosulfur component present in garlic which is a potent antioxidant and free radical scavenger. In the present study, the purpose was to explore the anti-inflammatory, antioxidant, and anti-apoptotic actions of SAC on lipopolysaccharide (LPS)-induced sepsis in rats. Thirty-two male Wistar rats were separated into 4 groups. These were control, SAC control, sepsis, and sepsis + SAC-induced groups. Sepsis was induced by administration of LPS (5 mg/kg) into 2 groups. SAC (50 mg/kg) was given orally to SAC control and SAC treatment groups per 12 h during 2 days after intraperitoneal LPS injection. Serum AST, ALT, ALP, and hsCRP levels and liver and lung MPO, NO, and DNA fragmentation levels were evaluated. In sepsis group, elevated levels of ALT, AST, ALP, and hsCRP were observed. The abnormal increases were decreased in sepsis + SAC group compared to sepsis group. In lung tissue, MPO and NO levels were increased in sepsis group compared to the control group. MPO activity and NO levels were decreased by SAC application in sepsis + SAC group compared with sepsis group. In liver tissue, DNA fragmentation was significantly higher in sepsis group than that in the control group. In contrast, a decreased level of DNA fragmentation was noted in sepsis + SAC group when compared with the sepsis group. In conclusion, SAC ameliorates LPS-induced indicators of liver damage and suppresses the discharge of NO and MPO in lung tissue via its antioxidant properties.
    Archiv für Experimentelle Pathologie und Pharmakologie 12/2014;
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    ABSTRACT: The cyclic pyrimidine nucleotides cytidine 3',5'-cyclic monophosphate (cCMP) and uridine 3',5'-cyclic monophosphate (cUMP) have been unequivocally identified in mammalian cells using the most advanced mass spectrometry methods. On October 10, 2014, leading experts in the field met at the Hannover Medical School, Hannover, Germany, to discuss the latest findings in this emerging field of research. Generators, effectors, biological functions, inactivation mechanisms, and model systems for cCMP and cUMP were discussed. Pseudomonas aeruginosa nucleotidyl cyclase toxin ExoY, effectively producing cUMP, was a central topic of the meeting. cCMP and cUMP fulfill the criteria for second messengers. Future research directions in the field will include the identification of specific effector proteins of cCMP and cUMP, new cCMP- and cUMP-generating bacterial toxins, the analysis of new model organisms such as the zebra fish, and elucidation of the function of other noncanonical cyclic nucleotides such as inosine 3',5'-cyclic monophosphate (cIMP).
    Archiv für Experimentelle Pathologie und Pharmakologie 12/2014;
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    ABSTRACT: Baicalin, a flavonoid isolated from Scutellaria baicalensis, is known to have multiple biological functions. Recent studies have demonstrated that baicalin treatment increases alkaline phosphatase activity (ALP) and osteoprotegerin secretion by osteoblasts. Furthermore, baicalin induces the differentiation of cultured osteoblasts via the activation of the Wnt/β-catenin signaling pathway. In this study, we evaluated the hair growth-promoting effects of baicalin in human follicular dermal papilla (DP) cells. A reporter assay and Western blotting were used to assess the effect of baicalin on β-catenin signaling in DP cells. ALP activity and messenger RNA (mRNA) expression were examined by ALP staining and real-time polymerase chain reaction (PCR), respectively. Growth factor expression levels were also evaluated using real-time PCR. Finally, the effect of baicalin on hair growth in vivo was examined by topical application of baicalin on the shaved dorsal skin of C57BL/6 mice. Our results indicate that baicalin activates Wnt/β-catenin signaling in a dose-dependent manner in human DP cells. ALP mRNA expression and activity were significantly induced in the presence of baicalin. In addition, treatment with baicalin induced the mRNA expression of growth factors, such as insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF). Moreover, compared to vehicle treatment, baicalin treatment induced an earlier conversion from telogen to anagen. Our results strongly suggest that baicalin promotes hair growth by regulating the activity of DP cells.
    Archiv für Experimentelle Pathologie und Pharmakologie 12/2014;
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    ABSTRACT: The recent resolution of G-protein-coupled receptor (GPCR) structures in complex with Na(+) bound to an allosteric modulatory site has renewed interest of the regulation of GPCRs by ions. Here, we summarise key data on ion modulation of GPCRs, obtained in pharmacological, crystallographic, mutagenesis and molecular modelling studies. We show that ion modulation is a highly complex process, involving not only cations but also, rather neglected until now, anions. Pharmacotherapeutic and toxicological aspects are discussed. We provide a mathematical framework for the analysis of ion effects. Finally, we discuss open questions in the field and future research directions. Most importantly, the in vivo relevance of the modulation of GPCR function by monovalent ions must be clarified.
    Archiv für Experimentelle Pathologie und Pharmakologie 11/2014;
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    ABSTRACT: Arterial hypertension is a considerable side effect that accompanies the clinical use of immunosuppressant drugs such as cyclosporine (CSA). In addition to promoting graft rejection, uncontrolled hypertension is a major risk factor for atherosclerosis, left ventricular hypertrophy, heart failure, and premature death. Most, if not all, reports that reviewed the hypertensive effect of CSA and underlying mechanisms focused on the roles of peripheral vasoactive machinaries, perhaps because of the limited capacity of CSA to diffuse to brain tissues and the lack of any appreciable effect for centrally administered CSA on blood pressure (BP) or central sympathetic outflow. This review focuses primarily on evidence that supports a modulatory role for central neural pathways, as go-between afferent and efferent sympathetic circuits, in the elicitation of the hypertensive action of CSA. Other areas covered briefly in the review include (1) an outline of peripheral mechanisms that contribute to the hypertensive action of CSA, and (2) comparisons of the BP effects of CSA and other calcineurin-dependent (tacrolimus) and independent (sirolimus) immunosuppressants. The knowledge of these mechanisms, central and peripheral, may permit the identification of new therapeutic strategies against CSA hypertension.
    Archiv für Experimentelle Pathologie und Pharmakologie 11/2014;
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    ABSTRACT: NADPH oxidase-derived reactive oxygen species are important for various cellular functions, including proliferation. Endothelial cells predominantly express the Nox4 isoform of NADPH oxidase, but it is not entirely clear how it is regulated. In this study, we investigated the signalling pathways involved in transforming growth factor-β1 (TGF-β1)-induced Nox4 expression and the proliferation of human microvascular endothelial cells (HMECs). TGF-β1 stimulated Nox4 messenger RNA and protein expression in HMECs. TGF-β1-induced Nox4 also increased hydrogen peroxide production, which was inhibited by diphenyleneiodonium and EUK134. The acute treatment of HMECs with TGF-β1 enhanced the phosphorylation of Smad2 and extracellular signal-regulated kinase (ERK) 1/2, without affecting p38MAPK, Akt, or Jun N-terminal kinase 1/2 (JNK1/2) pathways. Further, inhibition of Smad2 signalling using an inhibitor of activin receptor-linked kinase 5 SB431542 reduced TGF-β1-induced Nox4 expression, while inhibition of ERK1/2 with the inhibitor of mitogen-activated protein kinase kinase 1/2 U0126 decreased both basal and TGF-β1-induced Nox4 expression. Inhibition of ERK1/2 phosphorylation with U0126 did not affect Smad2 phosphorylation. Finally, TGF-β1 enhanced endothelial cell proliferation, which was reduced by U0126 but not by SB431542. These findings suggest that the non-canonical pathway ERK1/2 regulates Nox4 expression and may be involved in TGF-β1-induced proliferation of endothelial cells, which is vital during angiogenesis and vascular development.
    Archiv für Experimentelle Pathologie und Pharmakologie 11/2014;
  • Archiv für Experimentelle Pathologie und Pharmakologie 11/2014;
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    ABSTRACT: Lupeol, a dietary triterpene, present in many fruits and medicinal plants, has been reported to possess many pharmacological properties including anti-cancer activities both in vitro and in vivo. However, the precise mechanism involved remains largely unknown. The present study is conducted to investigate the anti-cancer activity and the underlying mechanisms of lupeol on human pancreatic cancer proliferating cell nuclear antigen 1 (PCNA-1) cells in vitro and in vivo. Lupeol significantly inhibited the proliferation of the cells in dose- and time-dependent manners and induced apoptosis as well as cell cycle arrest in G0/G1 phase by upregulating P21 and P27 and downregulating cyclin D1. The expression of apoptosis-related proteins in cells was evaluated by western blot analysis, and we found that lupeol induced cell apoptosis by decreasing the levels of p-AKT and p-ERK. In addition, pretreatment with a specific PI3K/AKT activator (IGF-1) significantly neutralized the pro-apoptotic activity of lupeol in PCNA-1 cells, demonstrating the important role of AKT in this process. More importantly, our in vivo studies showed that administration of lupeol decreased tumor growth in a dose-dependent manner. Immunohistochemistry analysis demonstrated the downregulation of p-AKT and p-ERK in tumor tissues following lupeol treatment, consistent with the in vitro results. Therefore, these findings indicate that lupeol can inhibit cell proliferation and induce apoptosis as well as cell cycle arrest of PCNA-1 cells and might offer a therapeutic potential advantage for human pancreatic cancer chemoprevention or chemotherapy.
    Archiv für Experimentelle Pathologie und Pharmakologie 11/2014;
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    ABSTRACT: Acute itch (pruritus) is unpleasant and acts as an alerting mechanism for removing irritants. However, severe chronic itch is debilitating and impairs the quality of life. Rapid progress has been made in recent years in our understanding of the fundamental neurobiology of itch. Notably, several temperature-sensitive transient receptor potential (thermo-TRP) ion channels have emerged as critical players in many types of itch, in addition to pain. They serve as markers that define the itch neural pathway. Thermo-TRP ion channels are thus becoming attractive targets for developing effective anti-pruritic therapies.
    Archiv für Experimentelle Pathologie und Pharmakologie 11/2014;
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    ABSTRACT: The purpose of the present study was to evaluate the gastroprotective and healing effects of the methanolic extract of the seed of the papaya Carica papaya L. (MECP) in rats. Models of acute gastric ulcer induction by ethanol and indomethacin and of chronic ulcer by acetic acid were used. The gastric juice and mucus parameters were evaluated using the pylorus ligation model, and the involvement of sulfhydryl compounds (GSH) and nitric oxide in the gastroprotective effect was analyzed using the ethanol model. The toxicity was assessed through toxicity tests. No signs of toxicity were observed when the rats received a single dose of 2000 mg/kg of extract. The MECP in doses of 125, 250, and 500 mg/kg significantly reduced the gastric lesion with 56, 76, and 82 % inhibition, respectively, and a dose of 30 mg/kg lansoprazole showed 79 % inhibition in the ethanol model. MECP (125, 250, 500 mg/kg) and cimetidine (200 mg/kg) reduced the gastric lesion in the indomethacin model, with 62, 67, 81, and 85 % inhibition, respectively. The MECP (500 mg/kg) and cimetidine (200 mg/kg) treatments showed a reduction in ulcerative symptoms induced by acetic acid by 84 and 73 %, respectively. The antiulcerogenic activity seems to involve GSH because the inhibition dropped from 72 to 13 % in the presence of a GSH inhibitor. Moreover, the MECP showed systemic action, increasing the mucus production and decreasing gastric acidity. Treatments with MECP induce gastroprotection without signs of toxicity. This effect seems to involve sulfhydryl compounds, increased mucus, and reduced gastric acidity.
    Archiv für Experimentelle Pathologie und Pharmakologie 11/2014;