共查询到20条相似文献，搜索用时 46 毫秒
1.
The aim of this study was to evaluate fosinopril‐induced changes in hemodynamic parameters and tactile allodynia in a rat model of diabetes. Diabetes was induced by streptozotocin (STZ; 50 mg/kg, i.p.) in male Wistar rats. STZ produced hyperglycemia, weight loss, polydipsia, polyphagia, and polyuria as well as long‐term arterial hypotension, bradycardia, and tactile allodynia at 10–12 weeks. Daily administration of the angiotensin converting enzyme inhibitor, fosinopril (25 mg/kg, p.o., for 11 weeks) partially reduced the loss of body weight, decreased hyperglycemia, and systolic blood pressure in diabetic rats. Likewise, systemic administration of fosinopril prevented the development and maintenance of tactile allodynia in STZ‐induced diabetic rats. These data suggest that fosinopril may have a role in the pharmacotherapy of diabetic neuropathic pain. Drug Dev Res 76 : 442–449, 2015. © 2015 Wiley Periodicals, Inc. 相似文献
2.
Rhodiola rosea L. (Crassulaceae) is used for enhancing physical and mental performance. Recent studies demonstrated that R. rosea had anti‐inflammatory activity in animal models, for example, carrageenan‐ and nystatin‐induced edema in rats, possibly by inhibiting phospholipase A 2 and cyclooxygenases‐1 and ‐2. In addition, R. rosea had antinociceptive activity in thermal and chemical pain tests as well as mechanical hyperalgesia. The purpose of the present study was to assess the antihyperalgesic effect of an ethanol extract of Rhodiola rosea ( R. rosea) in a diabetic rat model. Rats were administered a single dose of s treptozotocin (STZ; 50 mg/kg, i.p.) and hyperalgesia was evaluated four weeks later. Formalin‐evoked (0.5%) flinching was increased in diabetic rats compared with nondiabetic controls Systemic (1–100 mg/kg, i.p.) and local (0.1–10 mg/paw into the dorsal surface of the right hind paw) administration of R. rosea ethanol extract dose‐dependently reduced formalin‐induced hyperalgesia in diabetic rats. The antihyperalgesic effect of R. rosea was compared with gabapentin. These results suggest that R. rosea ethanol extract may have potential as a treatment for diabetic hyperalgesia. Drug Dev Res 77 : 29–36, 2016. © 2016 Wiley Periodicals, Inc. 相似文献
3.
The aim of this study was to elucidate the antioxidant effects of Caralluma tuberculata (C. tuberculata) in streptozotocin (STZ)‐induced diabetic rats. Diabetes was induced in male Wistar rats with an intraperitoneal injection of STZ at dose of 60 mg/kg body weight. Three days after diabetes induction, powdered aerial part of plant at doses of 100 and 200 mg/kg body weight were gavaged orally for a period of 45 days. The diabetes significantly decreased the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and level of total thiol in liver, kidney, and heart of animals ( P < 0.05). In contrast, a significant increase in the levels of protein carbonyl was observed in diabetic rats compared with control animals ( P < 0.05). Oral treatment of diabetic rats with C. tuberculata showed ameliorative effects on blood glucose and markers of oxidative stress in a dose‐dependent manner. Altered levels of all oxidative stress parameters in tissues of diabetic rats reverted back to those normal animals after the treatment with dose of 200 mg/kg /day of plant materials. It seems that the appropriate dose of C. tuberculata has both antihyperglycemic and antioxidant activities in STZ‐induced diabetic rats. Therefore, it can have preventive properties on oxidative stress‐induced diabetic complications. Drug Dev Res 76 : 40–47, 2015 相似文献
4.
The aim of the present study was to evaluate the neuroprotective benefits of rhGLP‐1 in diabetic rats subjected to acute cerebral ischemia/reperfusion injury induced by middle cerebral artery occlusion/reperfusion (MCAO/R). Streptozotocin (STZ)‐induced diabetic rats were pretreated with rhGLP‐1 (10, 20, or 40 μg/kg ip, tid) for 14 days. During this time, body weight and fasting blood glucose levels were assessed. Rats were then subjected to MCAO 90 min/R 24 h. At 2 and 24 h of reperfusion, rats were evaluated for neurological deficits and blood samples were collected to analyze markers of brain injury. Rats were then sacrificed to assess the infarction volume. rhGLP‐1 pretreatment lowered blood glucose levels, improved neurological scores, attenuated infarct volumes, and reduced the blood levels of S100 calcium‐binding protein B (S100B), neuron‐specific enolase (NSE), and myelin basic protein (MBP). rhGLP‐1 has neuroprotective benefits in diabetic rats with cerebral ischemia/reperfusion injury and could potentially be used as a prophylatic neuroprotectant in diabetic patients at high risk of ischemic stroke. Drug Dev Res 77 : 124–133, 2016. © 2016 Wiley Periodicals, Inc. 相似文献
5.
The majority of studies on vildagliptin and pioglitazone have focused on their combination in glycemic control. The aim of the present study was to investigate their effects in combination on (i) hyperglycemia‐induced oxidative stress and inflammation and (ii) on organs involved in the pathophysiology of diabetes, pancreas, kidney and liver. Type 2 diabetes was induced using low‐dose streptozotocin in male Wistar rats. Diabetic rats were treated for 4 weeks, with vildagliptin (10 mg/kg/day), pioglitazone (10 mg/kg/day) and their combination. Diabetic rats showed elevated fasting serum glucose, fasting serum insulin, serum transaminases together with a deleterious lipid profile and elevated serum creatinine and urea concentrations. Serum levels of the inflammatory markers tumor necrosis factor‐α (TNF‐α) and nitrite/nitrate were also elevated compared to normal rats. Oxidative stress was manifested by lowered hepatic reduced glutathione (GSH) and increased malondialdehyde (MDA) levels. Pancreatic sections from diabetic rats showed degenerated islets with poorly maintained architecture that was prevented by drug treatment. Pioglitazone was generally more effective than vildagliptin in the studied parameters except for the lipid profile where the effect of both drugs was comparable and for the liver enzymes and renal parameters where vildagliptin was more effective. The combination of vildagliptin and pioglitazone produced superior effects than either drug alone. Drug Dev Res 77 : 251–257, 2016. © 2016 Wiley Periodicals, Inc. 相似文献
6.
Sanguinarine, an alkaloid isolated from the root of Sanguinaria canadensis and other plants of the Papaveraceae family, selectively induces apoptotic cell death in a variety of human cancer cells, but its mechanism of action requires further elaboration. The present study investigated the pro‐apoptotic effects of sanguinarine in human oral squamous cell carcinoma KB cells. Sanguinarine treatment increased DR5/TRAILR2 (death receptor 5/TRAIL receptor 2) expression and enhanced the activation of caspase‐8 and cleavage of its substrate, Bid. Sanguinarine also induced the mitochondrial translocation of pro‐apoptotic Bax, mitochondrial dysfunction, cytochrome c release to the cytosol, and activation of caspase‐9 and ‐3. However, a pan‐caspase inhibitor, z‐VAD‐fmk, reversed the growth inhibition and apoptosis induced by sanguinarine. Sanguinarine also suppressed the phosphorylation of phosphoinositide 3‐kinase (PI3K) and Akt in KB cells, while co‐treatment of cells with sanguinarine and a PI3K inhibitor revealed synergistic apoptotic effects. However, pharmacological inhibition of AMP‐activated protein kinase and mitogen‐activated protein kinases did not reduce or enhance sanguinarine‐induced growth inhibition and apoptosis. Collectively, these findings indicate that the pro‐apoptotic effects of sanguinarine in KB cells may be regulated by a caspase‐dependent cascade via activation of both intrinsic and extrinsic signaling pathways and inactivation of PI3K/Akt signaling. Drug Dev Res 77 : 227–240, 2016. © 2016 Wiley Periodicals, Inc. 相似文献
7.
Resveratrol (trans‐3,5,4′‐trihydroxystilbene) is a nutritional supplement with anti‐inflammatory properties. The present study investigated the long‐term anti‐inflammatory property of resveratrol in the retinas of type 2 diabetic rats. Male Wistar rats were divided into four groups: normal control, diabetic control, resveratrol‐treated normal rats and resveratrol‐treated diabetic rats. Type 2 diabetes was induced by a single dose injection of streptozotocin (50 mg/kg; i.p.) 15 min after the administration of nicotinamide (110 mg/kg; i.p.) in 12‐h fasted rats (the streptozotocin–nicotinamide type 2 diabetic model). Oral resveratrol administration (5 mg/kg per day for 4 months) significantly improved glucose tolerance, and alleviated hyperglycemia and weight loss in diabetic rats. Furthermore, resveratrol administration significantly decreased the elevated levels of nuclear factor‐ κB activity, and mRNA expression, tumour necrosis factor alpha level and apoptotic cells in the retinas of the diabetic rats. Furthermore, resveratrol did not significantly affect plasma insulin levels. Long‐term resveratrol administration has beneficial anti‐inflammatory properties in a rat model of diabetes. However, whether resveratrol exerts its effects directly or through reducing blood glucose levels requires further investigation. 相似文献
8.
Baicalein is one of the main bioactive flavonoids found in the roots of Scutellaria baicalensis Georgi. Here, we report that baicalein‐induced growth inhibition was associated with the induction of apoptosis in human lung carcinoma A549 cells. Baicalein stimulated the expression of DR5, FasL, and FADD, and activated caspase‐8 by reducing the levels of FLIPs (FLICE‐inhibitory proteins). The apoptotic cell death was also connected with an activation of caspase‐9 and ?3, and cleavage of poly(ADP‐ribose) polymerase; however, a blockage of caspase activation abolished baicalein‐induced apoptotic potentials. Additionally, baicalein caused a mitochondrial membrane potential (MMP), the truncation of Bid, and the translocation of pro‐apoptotic Bax to the mitochondria, thereby inducing the release of cytochrome c into the cytosol. In turn, baicalein increased the generation of reactive oxygen species (ROS); however, an ROS scavenger, N‐acetylcysteine, notably attenuated baicalein‐mediated loss of MMP and activation of caspases. Furthermore, baicalein activated the AMP‐activated protein kinase (AMPK) signaling pathway. Consequently, baicalein‐triggered cell death was attenuated by an AMPK inhibitor, but increased by an AMPK activator, compound C. Overall, the results suggest that the apoptotic activity of baicalein may be associated with caspase‐dependent cascade through the activation of both intrinsic and extrinsic signaling pathways connected with ROS generation and AMPK activation. Drug Dev Res 77 : 73–86, 2016. © 2016 Wiley Periodicals, Inc. 相似文献
9.
Isorhanmetin (ISH) exhibits a wide range of biological properties including anticancer, anti‐oxidant and anti‐inflammatory activities. However, the pharmacological properties of isorhamnetin ‐3 ‐O‐glucuronide (IG), a glycoside derivative of ISH, have not been extensively examined. The objective of this study was to examine the anti‐inflammatory properties of IG and its underlying mechanism in lipopolysaccharide (LPS)‐challenged RAW264.7 macrophage cells in comparison with its aglycone, ISH. IG suppressed LPS‐induced extracellular secretion of the proinflammatory mediators, nitric oxide (NO) and PGE 2, and proinflammatory protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2. IG also increased expression of heme oxygenase‐1 (HO‐1). IG attenuated LPS‐induced activation of c‐Jun N‐terminal kinase (JNK) and p38 in a concentration‐dependent manner with negligible suppression of extracellular signal‐regulated kinases (ERK) phosphorylation. In conclusion, this study demonstrates that IG exerts anti‐inflammatory activity by increasing HO‐1 expression and by suppressing JNK and p38 signaling pathways in LPS‐challenged RAW264.7 macrophage cells. Drug Dev Res 77 : 143–151, 2016. © 2016 Wiley Periodicals, Inc. 相似文献
10.
Osteoarthritis (OA) is characterized by a loss of articular cartilage accompanied with inflammation of synovium. β‐Ecdysterone (Ecd), a major component of several Chinese herbal medicines, e.g., Achyranthes bidentata BL., has been used for the prevention and treatment of OA. Ecd is an estrogen analog and is likely to have similar pharmacological effects including the effect of protective chondrocytes. This study investigated the effects of Ecd on interleukin‐1β (IL‐1β)‐induced apoptosis and inflammation in rat chondrocytes. Ecd protected chondrocytes from IL‐1β‐induced injury by inhibiting expression of Bax, p53 phosphorylation, and promoting expression of Bcl‐x L. Simultaneously, Ecd reduced caspase 3 activity. IL‐1β‐induced inflammation and matrix degration were also prevented by Ecd via down‐regulation of matrix metalloproteinases MMP 3, MMP 9, and cyclooxygenase‐2 expression. Additionally, Ecd inhibited Nuclear Factor Kappa B (NF‐κB) p65 phosphorylation, IκBα degradation, and phosphorylation in IL‐1β‐induced rat chondrocytes. These results suggested Ecd exerted anti‐apoptosis and anti‐inflammation in IL‐1β‐induced rat chondrocytes, which might be related to NF‐κB signal pathway. 相似文献
11.
Krameria cytisoides is used for the treatment of inflammation, stomach pain, and gastric ulcers. The active ingredient from this plant is a peroxide, kramecyne (KACY) which has anti‐inflammatory effects. The aim of the present study was to evaluate the anti‐inflammatory activities of KACY in lipopolysaccharide (LPS)‐induced systemic chronic inflammation in mice for 60 days, using dexamethasone (DEX) as the positive control, vehicle (the LPS group) as the negative control and the control group (mice without inflammation). KACY did not affect survival, body weight or relative organ weight in mice but it: decreased nitric oxide (NO) production by 68%; prostaglandin E 2 (PGE 2) by 67%; increased release of anti‐inflammatory cytokine IL‐10 (2.0‐fold), and reduced production of the proinflammatory cytokines, IL‐6 (2.0‐fold), IL‐1β (2.4‐fold), and TNF‐α (2.0‐fold). Furthermore, the gastroprotective effects of KACY in mice were evaluated in an ethanol‐induced gastric ulcer model. The results showed that KACY at 50 and 100 mg/kg exerted gastroprotective effects with similar activity to 50 mg/kg ranitidine. In gastric tissues, KACY decreased the level of malondialdehyde (MDA) but increased the catalase (CAT) activity. KACY have potential for the treatment of chronic inflammatory diseases due its similar activity to that of DEX. It also has gastroprotective effects. Drug Dev Res 76 : 185–193, 2015. © 2015 Wiley Periodicals, Inc. 相似文献
12.
| Preclinical Research & Development | Angelicin is a furocoumarin derived from Psoralea corylifolia L. fruit that has anti‐inflammatory and anti‐tumor activity. In the present study, the effect of angelicin in enhancing tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL)‐induced apoptotic cell death was studied in Caki (renal carcinoma) cells. Angelicin alone and TRAIL alone had no effect on apoptosis, but in combination these compounds markedly induced apoptosis in the cancer cell lines while not inducing apoptosis in normal cells. The combination treatment induced accumulation of the sub‐G1 population, DNA fragmentation, and activated caspase 3 activity in Caki cells, induced down‐regulation of c‐FLIP expression post‐translationally, and over‐expression of c‐FLIP markedly blocked apoptosis induced by combined treatment with angelicin plus TRAIL. This study provides evidence that angelicin might be a TRAIL sensitizer. 相似文献
13.
Vanillic acid (VA) is a dihydroxybenzoic acid derivative widely used as a flavoring agent. It has chemopreventive effects on experimentally‐induced carcinogenesis and in ulcerative colitis. The object of the present study was to investigate the effects of VA, alone and in combination with methylprednisolone (MP), on cationic bovine serum albumin (cBSA induced immune‐complex glomerulonephritis in female BALB/c mice. Pre‐immunization was carried out with cBSA in BALB/c mice and repeated (cBSA, 13 mg/kg, 3 times/week, i.v.) for 6 weeks to induce glomerulonephritis which was confirmed by the presence of severe proteinuria. The effect of VA (50, 100, and 200 mg/kg, p.o.) and its combination with MP (12.5 mg/kg, p.o.) was assessed in the nephrotic disease model. Treatment with VA decreased inflammatory nephrotic injury as evidenced by decreased proteinuria, serum creatinine, blood urea nitrogen, serum IgG1 and TNF‐α levels. Co‐administration of VA with MP showed an improvement in the immunohistochemistry of glomerular nephrin and podocin. The present results indicate that VA has a nephroprotective effect in the management of autoimmune nephritis. Drug Dev Res 77 : 171–179, 2016. © 2016 Wiley Periodicals, Inc. 相似文献
14.
The aim of this study was to evaluate the anti‐cancer effects of lipopolysaccharide binding protein (LBP) analogs derived from the marine resource Paralichthy olivaceus on MKN‐28 gastric cancer cells. Five LBP analogs were used: ofLBP1N, ofLBP2A, ofLBP4N, ofLBP5A, and ofLBP6A. ofLBP6A induced cell death of MKN‐28 cells at a concentration of 40 μM. While the anti‐proliferation effects ofLBP6A showed on MKN‐28 cells at concentration of 40 μM, it did not affect non‐cancerous HEK‐293 cells at the same concentration. The mechanism study showed that ofLBP6A lead to the inhibition of cell proliferation by apoptosis along with morphological changes. The phosphorylation of Fas associated death domain (FADD) as well as the expressions of cleaved caspase‐8, ?7, and ?3 were increased by ofLBP6A treatment. Increased the expression level of cleaved caspase‐3 was confirmed by immunofluorescence staining. The expressions of Bid, Bax, and cytochrome C were also increased by the treatment. However, the expressions of cellular FLICE (FADD‐like IL‐1β‐converting enzyme)‐inhibitory protein (FLIP), Bcl‐XL, and Bcl‐2 were decreased by ofLBP6A treatment. The results of this study were the first to demonstrate the apoptotic anti‐cancer effects of ofLBP6A, derived from P. olivavaceus on gastric cancer cells. Drug Dev Res 77 : 94–102, 2016. © 2016 Wiley Periodicals, Inc. 相似文献
16.
The aim of the present study was to analyze the antihyperalgesic and antiallodynic interaction between the non‐selective cholecystokinin (CCK) antagonist receptor, proglumide, and the selective cyclooxygenase‐2 inhibitor, celecoxib in streptozotocin (STZ)‐induced diabetic rats. Hyperalgesia was evaluated in the formalin test and tactile allodynia using von Frey filaments. Isobolographic analyses were employed to define the nature of the compound interactions, using a fixed dose ratio (0.5:0.5). Proglumide (20–160 mg/kg) and celecoxib (0.3–30 mg/kg) in these fixed dose ratio combinations induced dose‐dependent antihyperalgesia and an antiallodynic effect in diabetic rats. ED 40 values were calculated for the treatments and an isobologram was constructed. Theoretical ED 40 values for combination proglumide–celecoxib estimated from the isobolograms for antihyperalgesic and antiallodynic activity (30.50 ± 1.90 mg/kg and 45.81 ± 4.55 mg/kg, respectively) were obtained, while experimental ED 40 values for this antihyperalgesic and antiallodynic combined effect (13.83 ± 0.65 mg/kg and 17.74 ± 3.57 mg/kg; respectively) were significantly different. Coadministration of proglumide–celecoxib showed an interaction index value of 0.45 ± 0.03 for the antihyperalgesic effect and 0.39 ± 0.08 for the antiallodynic activity, indicating a synergistic interaction. These data suggest that proglumide and celecoxib can interact synergistically to reduce hyperalgesic and allodynic behaviors in diabetic neuropathy. This combination could be useful to treat neuropathic pain in diabetic patients. Drug Dev Res 78 : 116–123, 2017. ©2017 Wiley Periodicals, Inc. 相似文献
17.
The aim of this study was to evaluate the efficacy of multiple applications of S(+)‐flurbiprofen plaster (SFPP), a novel Nonsteroidal anti‐inflammatory drug (NSAID) patch, for the alleviation of inflammatory pain and edema in rat adjuvant‐induced arthritis (AIA) model as compared to other NSAID patches. The AIA model was induced by the injection of Mycobacterium butyricum and rats were treated with a patch (1.0 cm × 0.88 cm) containing each NSAID (SFP, ketoprofen, loxoprofen, diclofenac, felbinac, flurbiprofen, or indomethacin) applied to the paw for 6 h per day for 5 days. The pain threshold was evaluated using a flexion test of the ankle joint, and the inflamed paw edema was evaluated using a plethysmometer. cyclooxygenase (COX)?1 and COX‐2 inhibition was evaluated using human recombinant proteins. Multiple applications of SFPP exerted a significant analgesic effect from the first day of application as compared to the other NSAID patches. In terms of paw edema, SFPP decreased edema from the second day after application, Multiple applications of SFPP were superior to those of other NSAID patches, in terms of the analgesic effect with multiple applications. These results suggest that SFPP may be a beneficial patch for providing analgesic and anti‐inflammatory effects clinically. Drug Dev Res 77 : 206–211, 2016. © 2016 The Authors Drug Development Research Published by Wiley Periodicals, Inc. 相似文献
18.
The objective of this study was to evaluate the pharmacological antihyperalgesic interaction between N‐palmitoylethanolamide (PEA) and acetaminophen in diabetic rats using the formalin paw test. Streptozotocin (STZ)‐induced diabetic rats received subcutaneous injections in the paw of PEA alone (1–100 μg/paw) or acetaminophen alone (3–300 μg/paw) 15 min before formalin (0.5%) injection. The results revealed concentration‐dependent responses produced by PEA (EC 50 = 7.19 ± 0.7 μg/paw) and acetaminophen (EC 50 = 57.9 ± 1.9 μg/paw). Isobolographic analysis was used to evaluate the pharmacological interaction between the PEA + acetaminophen using the EC 50 value and a fixed 1:1 ratio combination. The isobologram demonstrated that the combination investigated in this study produced a synergistic interaction; the experimental value (EC 50= 23.64 ± 1.9 μg/paw) was significantly smaller than those that resulted from theoretical calculations (EC 50 = 32.56 μg/paw). These results provide evidence that PEA in combination with acetaminophen could be useful for pain therapy in neuropathic diabetic patients. Drug Dev Res 76 : 228–234, 2015. © 2015 Wiley Periodicals, Inc. 相似文献
19.
The development of new genomic technologies has led to an exponential increase in the number of biomarkers for drug safety and efficacy. Pharmacogenomics has the potential to impact clinically relevant outcomes in drug dosing, efficacy, toxicity, and prediction of adverse drug reactions (ADRs). Genotype‐based prescribing is anticipated to improve the overall efficacy rates and minimize ADRs, making personalized medicine a reality. Genome‐wide association studies have been increasingly applied to pharmacogenetics. Severe ADRs are a major issue for drug therapy because they can cause serious disorders and can be life threatening. For severe ADRs, significant associations have been reported for drug‐induced liver injury, statin‐induced myopathy, increased risk of hemorrhagic complications of anticoagulant use, drug‐induced torsade de pointes, drug‐induced long QT, and severe cutaneous ADRs. This review summarizes the current position concerning the clinical and pharmacoepidemiological relevance of pharmacogenetic biomarkers in ADR prediction and prevention, with an emphasis on genetic risk factors and biomarkers for three specific severe ADRs. 相似文献
20.
The anti‐inflammatory and analgesic activities of a polyphenol‐rich fraction (TMEF) obtained from Terminalia muelleri Benth. were measured. The analgesic activity of TMEF was tested using acetic acid‐induced writhing and hot plate models in mice. The anti‐inflammatory activity was assessed using carrageenan‐induced paw edema model by measuring PGE 2, TNF‐α, IL‐1β, and IL‐6 plasma levels as well as the paw thickness. TMEF was tested at doses of 100, 200, and 400 mg/kg p.o. and diclofenac sodium was used as a standard (100 mg/kg) in all experiments. The group treated with 400 mg/kg of TMEF showed a greater inhibition in the number of writhes (by 63%) than the standard‐treated group (61%). Pretreatment with TMEF increased the analgesic effect in hot plate test in a dose‐dependent manner with a maximum effect after 120 min. TMEF pretreatment alos reduced the edema thickness by 48, 53, and 62% at the tested doses, respectively. TMEF administration inhibited the carrageenan‐induced elevations in PGE 2 (by 34, 43, and 47%), TNF‐α (18, 28, and 41%), IL‐1β (14, 22, and 29%), and IL‐6 (26, 31, and 46%). Four phenolic compounds were isolated from Terminalia muelleri for the first time. Drug Dev Res 78 : 146‐154, 2017. © 2017 Wiley Periodicals, Inc. 相似文献
|
下载免费PDF全文