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SUMMARY: Angiogenesis, a process by which new blood vessels are generated from pre-existing ones, is significantly compromised in tumor development, given that due to the nutritional need of tumor cells, pro-angiogenic signals will be generated to promote this process and thus receive the oxygen and nutrients necessary for its development, in addition to being a key escape route for tumor spread. Although there is currently an increase in the number of studies of various anti-angiogenic therapies that help reduce tumor progression, it is necessary to conduct a review of existing studies of therapeutic alternatives to demonstrate their importance.
La angiogénesis, proceso por el cual se generan nuevos vasos sanguíneos a partir de otros preexistentes, se encuentra comprometida de forma importante en el desarrollo tumoral, dado que por necesidad nutritiva de las células tumorales se generarán señales pro angiogénicas para promover este proceso y así recibir el oxígeno y los nutrientes necesarios para su desarrollo, además de ser una ruta de escape clave para la diseminación tumoral. Si bien, actualmente existe un aumento en la cantidad de estudios de diversas terapias anti angiogénicas que ayudan a reducir el avance tumoral, es necesario realizar una revisión de los estudios existentes de alternativas terapéuticas para demostrar su importancia.
Subject(s)
Humans , Angiogenesis Inhibitors/therapeutic use , Celecoxib/therapeutic use , Neoplasms/drug therapy , Neovascularization, Pathologic/drug therapy , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Cyclooxygenase 2 Inhibitors , Neoplasms/pathology , Antineoplastic Agents/therapeutic useABSTRACT
ABSTRACT BACKGROUND AND OBJECTIVES: The objective of this study was to assess the bioequivalence between two 200 mg celecoxib hard capsule formulations administered to healthy male and female participants under fasting conditions with the aim of providing an alternative pharmaceutical product to the reference drug, Celebra®. METHODS: A randomized, open label, single dose, 2x2 crossover trial was conducted with 60 adult healthy subjects under fasting conditions comparing single doses of two celecoxib hard capsules formulation. Pharmacokinetic parameters were calculated following the determination of drugs concentrations in human plasma using a validated liquid chromatography with a tandem mass spectrometer detector method (LC-MS/MS). RESULTS: Statistical analysis provided geometric mean of test/reference ratio, confidence intervals, intra-subject variation coefficient and power of the test to the pharmacokinetic parameters Cmax, AUC0-t, and AUC0-∞. Confidence intervals for the geometric mean (90% CI) of the test/reference drugs for celecoxib were 98.26 to 122.75% for Cmax, 100.27% to 110.78% for AUC0-t, and 96.87% to 110.29% for AUC0-∞. The power of the test found was 95.09% for Cmax, 100.00% for AUC0-t, and 99.99% for AUC0-∞. CONCLUSION: The formulations met the Brazilian standards for interchangeability, as the confidence intervals for Cmax and AUC0-t ratios are within the range of 80% to 125%, thus meeting the requirements of the legislation during market registration. The researched product was approved by the regulatory authorities and became a commercially competitive option to the reference product for the Brazilian population.
RESUMO JUSTIFICATIVA E OBJETIVOS: O objetivo deste estudo foi avaliar a bioequivalência entre duas formulações de cápsulas duras de celecoxibe de 200 mg administradas a participantes saudáveis do sexo masculino e feminino em condições de jejum com o objetivo de fornecer um produto farmacêutico alternativo ao fármaco de referência, Celebra®. MÉTODOS: Estudo randomizado, aberto, de dose única e cruzado 2x2. Foi conduzido com 60 indivíduos adultos saudáveis em condições de jejum, comparando doses únicas de duas formulações de cápsulas duras de celecoxibe. Os parâmetros farmacocinéticos foram calculados após a determinação das concentrações dos fármacos no plasma humano usando uma cromatografia líquida validada com um método detector de espectrômetro de massa em tandem (LC-MS/MS). RESULTADOS: A análise estatística forneceu a média geométrica da razão teste/referência, os intervalos de confiança, o coeficiente de variação intra-sujeito e o poder do teste para os parâmetros farmacocinéticos Cmáx, AUC0-t e AUC0-∞. Os intervalos de confiança para a média geométrica (IC 90%) dos fármacos teste/referência para o celecoxibe foram 98,26 a 122,75% para Cmáx, 100,27% a 110,78% para AUC0-t e 96,87% a 110,29% para AUC0-∞. O poder do teste encontrado foi de 95,09% para Cmáx, 100,00% para AUC0-t e 99,99% para AUC0-∞. CONCLUSÃO: As formulações atenderam aos padrões brasileiros de intercambialidade, pois os intervalos de confiança para as razões Cmáx e AUC0-t estão dentro da faixa de 80% a 125%, atendendo, assim, às exigências da legislação para o registro no mercado. O produto pesquisado foi aprovado pelas autoridades regulatórias e tornou-se uma opção comercialmente competitiva ao produto de referência para a população brasileira.
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ObjectiveTo observe the glucose-lowering， insulin resistance-improving， and anti-inflammatory effects of flavonoids from mulberry leaves （FML） and explore their underlying mechanism. MethodMale db/db mice aged 6-7 weeks were randomly divided into a model group， a high-dose FML group （1.00 g·kg·d-1）， and a low-dose FML group （0.50 g·kg-1·d-1）. C57BL mice of the same age were assigned to the normal group. After six weeks of intervention， fasting blood glucose （FBG）， serum fasting insulin levels （Fins）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， free fatty acid （FFA）， blood creatinine （SCr）， blood urea nitrogen （BUN）， and aspartate aminotransferase （AST） levels were measured， and the homeostasis model assessment of insulin resistance （HOMA-IR） was calculated. Superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， and catalase activities in the liver were measured. Morphological changes in the liver were assessed by hematoxylin-eosin （HE） staining. The protein expression of cyclooxygenase-2 （COX-2）， inducible nitric oxide synthase （iNOS）， and nuclear factor-κB （NF-κB） in the liver was detected by Western blot. ResultCompared with the model group， the high-dose and low-dose FML groups showed significant reductions in FBG， Fins， HOMA-IR， IL-6， TNF-α， and FFA levels （P<0.05， P<0.01）， and increased levels of SOD， GSH-Px， and catalase in the liver （P<0.05， P<0.01）. HE staining of the liver in the FML groups showed improved arrangement of hepatocytes， reduced inflammatory cell infiltration， and alleviated cellular steatosis compared with the model group. The protein expression of COX-2， iNOS， and NF-κB in the liver significantly decreased in the FML groups as compared with that in the model group （P<0.05， P<0.01）. ConclusionFML have glucose-lowering and insulin resistance-improving effect， which may be attributed to their regulation of the NF-κB pathway in the liver of diabetic mice， leading to the suppression of the release of COX-2， iNOS， and inflammatory cytokines， thereby improving the inflammatory state.
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ObjectiveTo explore the underlying mechanism of Tripterygium wilfordii polyglycoside tablets （TWPT） in the prevention and treatment of kidney injury in diabetic nephropathy （DN） through the nuclear factor of activated T-cells 2（NFAT2）/cyclooxygenase-2（COX-2） pathway. MethodForty-two male SD rats of SPF grade were selected and randomly divided into a normal group （n=8） and an experimental group （n=34） after one week of adaptive feeding. The rats in the normal group were fed conventionally. The DN model was established in rats of the experimental group by intraperitoneal injection of streptozotocin （STZ） following one week of feeding on a high-fat and high-glucose diet. After the death and failure cases during modeling were eliminated， the remaining 24 model rats were randomly divided into model group， valsartan （8.33 mg·kg-1·d-1） group， and TWPT （5 mg·kg-1·d-1） group. Rats in normal group and model group were given equal amounts of normal saline by gavage. After six weeks， body weight was measured and urine samples were collected. Blood samples were collected from the abdominal aorta， and then the rats were sacrificed for sampling. Biochemical indicators， such as serum blood urea nitrogen （BUN）， serum creatinine （SCr）， alanine aminotransferase （ALT）， blood lipid， blood glucose， and 24-hour urine total protein （24 h UTP）， were determined. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the pathology of the kidney. Enzyme-linked immunosorbent assay （ELISA） was used to detect NFAT2 and COX-2 expression levels in the serum. Western blot and Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）were adopted to detect NFAT2， COX-2 protein and mRNA expression in kidney tissues， respectively. ResultCompared with the normal group， the model group showed elevated 24 h UTP， BUN， SCr， CHO， TG， and FBG， increased serum NFAT2 and COX-2 production and expression （P<0.01）， and elevated protein and mRNA expression of NFAT2 and COX-2 in kidney tissues （P<0.01）. In addition， the pathology of the kidney showed enlarged glomeruli， mild proliferation of mesangial cells， and widened mesangial stroma. Compared with the model group， the TWPT group showed decreased 24 h UTP， BUN， SCr， CHO， TG， and FBG （P<0.05，P<0.01）， basically normal glomerular morphology， decreased expression of serum NFAT2 and COX-2 （P<0.01）， and down-regulated protein and mRNA expression of NFAT2 and COX-2 in kidney tissues （P<0.01）. ConclusionTWPT can alleviate 24 h UTP in DN model rats， protect renal function， and improve renal pathology， and its mechanism of action may be related to the down-regulation of NFAT2/COX-2 expression in the serum and kidney tissues.
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OBJECTIVE@#To observe the effects of moxibustion at "Baihui" (GV 20) and "Dazhui" (GV 14) at different time points on the serum level of β-endorphin (β-EP), substance P (SP) and expression of interleukin-1β (IL-1β) and cyclooxygenase-2 (COX-2) protein in brainstem in rats with migraine, and to explore the effect and mechanism of moxibustion in preventing and treating migraine.@*METHODS@#Forty male SD rats were randomly divided into a blank group, a model group, a prevention+treatment (PT) group and a treatment group, 10 rats in each group. Except the blank group, the rats in the remaining groups were injected with nitroglycerin subcutaneously to prepare migraine model. The rats in the PT group were treated with moxibustion 7 days before modeling (once a day) and 30 min after modeling, while the rats in the treatment group were treated with moxibustion 30 min after modeling. The "Baihui" (GV 20) and "Dazhui" (GV 14) were taken for 30 minutes each time. The behavioral scores in each group were observed before and after modeling. After intervention, ELISA method was used to detect the serum level of β-EP and SP; the immunohistochemistry method was used to detect the number of positive cells of IL-1β in brainstem; the Western blot method was used to detect the expression of COX-2 protein in brainstem.@*RESULTS@#Compared with the blank group, the behavioral scores in the model group were increased 0-30 min, 60-90 min and 90-120 min after modeling (P<0.01); compared with the model group, in the treatment group and the PT group, the behavioral scores were decreased 60-90 min and 90-120 min after modeling (P<0.01). Compared with the blank group, in the model group, the serum level of β-EP was decreased (P<0.01), while the serum level of SP, the number of positive cells of IL-1β in brainstem and the expression of COX-2 protein were increased (P<0.01). Compared with the model group, in the PT group and and the treatment group, the serum level of β-EP was increased (P<0.01), while the serum level of SP, the number of positive cells of IL-1β and the expression of COX-2 protein in brainstem were decreased (P<0.01, P<0.05). Compared with the treatment group, in the PT group, the serum level of β-EP was increased and COX-2 protein expression was decreased (P<0.05).@*CONCLUSION@#Moxibustion could effectively relieve migraine. The mechanism may be related to reduce the serum level of SP, IL-1β and COX-2 protein expression in brainstem, and increase the serum level of β-EP, and the optimal effect is observed in the PT group.
Subject(s)
Rats , Male , Animals , Moxibustion , Rats, Sprague-Dawley , Cyclooxygenase 2 , beta-Endorphin , Substance P , Interleukin-1beta , Migraine Disorders , Brain StemABSTRACT
Hepatotoxicity is a common drug adverse effect and gentamycin has been linked to hepatotoxic adverse reactions. Folklore and ethnobotanical studies indicate Eugenia uniflora L is used in the treatment of gastrointestinal ailments and has exhibited diverse biological activities. We investigated the hepatoprotective potential of this plant in treating gentamycin-induced hepatoxicity and compared the effect with Celebrex a COX2 selective inhibitor. Twenty-eight male adult Wistar rats average of 225g were used for the study and randomised into groups as described: normal control( normal saline), negative control: Gentamycin (40mg/kg. i.p), positive control; Gentamycin (40mg/kg. i.p) +5mg/kg Celebrex. Extract low dose: Gentamycin (40mg/kg i.p)+(50mg/kg) Eugenia uniflora L. leaves, intermediate-dose: Gentamycin (40mg/kg i.p) +100mg/kg Eugenia uniflora L leaves, high dose : Gentamycin (40mg/kg, i.p)+ (200mg/kg, ) of Eugenia uniflora L leaves. Our findings indicate that the body weight was unaffected throughout the experiment, as clearly demonstrated by the lack of significant variability (p<0.05). Hepatotoxicity was confirmed by dose-dependent alteration in Liver marker enzymes, including AST, ALT, and ALP. Eugenia uniflora L leaves were able to ameliorate the levels of these liver enzymes to a normal level. Liver tissue revealed a dose-dependent curative effect with Eugenia uniflora L compared to the COX2 inhibitor (Celebrex) treatment. Consequently, we hereby report, for the first time, that an aqueous extract of Eugenia uniflora L leaves confers hepatoprotection against gentamycin-induced hepatoxicity in Wistar rats.
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Nimesulide, a nonsteroidal anti-inflammatory drug (NSAID), has been used as an effective treatment regimen for patients aged >12 years for fever, acute pain, acute tendinitis, osteoarthritis and dysmenorrhea. It is reported to be a superior antipyretic and anti-inflammatory drug than paracetamol and aspirin, respectively, and is equal to any of the NSAIDs alone in terms of analgesia. This paper reviews the current scenario of nimesulide in adult patients, concerning clinical evidence, use in special population and expert opinion. Overall, in comparison to other NSAIDs, including coxibs, nimesulide has a promising overall efficacy, safety and tolerability profile, as well as a satisfactory benefit/risk evaluation.
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Background: Nimesulide shows preferential inhibition for the cyclooxygenase-2 (COX-2) enzyme, which blocks the formation of prostaglandins critical in pain and inflammatory pathways. Few studies in the past have reported rare and unpredictable hepatic effects with nimesulide. The present study aimed to evaluate the efficacy and safety of nimesulide/paracetamol (100 mg + 325 mg) fixed-dose combination twice a day for 2 weeks in the management of acute pain in Indian population. Materials and methods: This was a multicenter study, performed on 500 patients, by 24 experienced physicians across India. The primary outcome assessed clinical safety at 2 weeks for mild/serious adverse effects (AEs), change in liver function tests (LFTs), serum bilirubin and alkaline phosphatase levels. The secondary outcomes assessed the clinical effectiveness in reduction of pain at rest and at movement. Results: Analysis of LFT at 2 weeks showed a slight increase (mean change) in the aspartate transaminase {-0.73 [95% confidence interval (CI) -1.54, 0.09; p = 0.081]}, alanine transaminase [-1.73 (95% CI -2.82, -0.64; p = 0.002)], serum bilirubin [-0.02 (95% CI -0.04, -0.001; p = 0.018)] and alkaline phosphatase levels [-1.92 (95% CI -5.84, 2; p = 0.336), not exceeding the normal range. Only one in 500 patients reported AEs. The numerical rating scale (NRS) scores for intensity of pain at rest and at movement at 2 weeks, ?7 days and >7 days were 68.38%, 68.44% and 68.39%; and 65.43%, 64.60% and 66.02%, respectively. An improvement of 96.6% was observed in patient global assessment scale (GAS) and 97.2% in physician GAS. Conclusion: Nimesulide/paracetamol combination was safe, effective and well-tolerated in acute pain conditions and did not lead to clinically significant changes in liver parameters indicating hepatic safety.
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Gastric issues that accompany the use of NSAIDs (Non-steroid anti-inflammatory drugs) are always a serious global concern. The inhibition of the Cycloxygenase enzyme (COX) limits the prostaglandin synthesis and thereby facilitates the control of pains, inflammation etc. But this creates gastric issues due to the reduction of mucin formation in the stomach. The present work was performed to create a modification in the structure of NSAID drug Diflunisal, to reduce the gastric effect of acidic moiety in the structure and elevate the overall biological properties. The drug Tromethamine, a base used in acidosis treatment was substituted to reduce the acidic issues. The heterocyclic compound pyrrole was substituted to elevate the properties. Neutral, salt, amide and ester combinations of Tromethamine-Diflunisal were designed, optimized and docked to the crystal structures of COX-1 (PDB ID: 6Y3C) and COX-2 (PDB ID: 5IKR) enzymes, using PyRx software. The combinations with lower COX-1 and COX-2 binding energies relative to Diflunisal were noted. It was analysed if the combinations of Diflunisal, Tromethamine and pyrrole lowers drug-properties or induce toxicities. Pyrrole substitution at position R4 was not found favourable for COX binding. Among the favourable combinations, DF19 is the Diflunisal-Pyrrole-Tromethamine combination, equally favourable for binding to COX targets.
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Gastric issues that accompany the use of NSAIDs (Non-steroid anti-inflammatory drugs) are always a serious global concern. The inhibition of the Cycloxygenase enzyme (COX) limits the prostaglandin synthesis and thereby facilitates the control of pains, inflammation etc. But this creates gastric issues due to the reduction of mucin formation in the stomach. The present work was performed to create a modification in the structure of NSAID drug Diflunisal, to reduce the gastric effect of acidic moiety in the structure and elevate the overall biological properties. The drug Tromethamine, a base used in acidosis treatment was substituted to reduce the acidic issues. The heterocyclic compound pyrrole was substituted to elevate the properties. Neutral, salt, amide and ester combinations of Tromethamine-Diflunisal were designed, optimized and docked to the crystal structures of COX-1 (PDB ID: 6Y3C) and COX-2 (PDB ID: 5IKR) enzymes, using PyRx software. The combinations with lower COX-1 and COX-2 binding energies relative to Diflunisal were noted. It was analysed if the combinations of Diflunisal, Tromethamine and pyrrole lowers drug-properties or induce toxicities. Pyrrole substitution at position R4 was not found favourable for COX binding. Among the favourable combinations, DF19 is the Diflunisal-Pyrrole-Tromethamine combination, equally favourable for binding to COX targets.
ABSTRACT
Gastric issues that accompany the use of NSAIDs (Non-steroid anti-inflammatory drugs) are always a serious global concern. The inhibition of the Cycloxygenase enzyme (COX) limits the prostaglandin synthesis and thereby facilitates the control of pains, inflammation etc. But this creates gastric issues due to the reduction of mucin formation in the stomach. The present work was performed to create a modification in the structure of NSAID drug Diflunisal, to reduce the gastric effect of acidic moiety in the structure and elevate the overall biological properties. The drug Tromethamine, a base used in acidosis treatment was substituted to reduce the acidic issues. The heterocyclic compound pyrrole was substituted to elevate the properties. Neutral, salt, amide and ester combinations of Tromethamine-Diflunisal were designed, optimized and docked to the crystal structures of COX-1 (PDB ID: 6Y3C) and COX-2 (PDB ID: 5IKR) enzymes, using PyRx software. The combinations with lower COX-1 and COX-2 binding energies relative to Diflunisal were noted. It was analysed if the combinations of Diflunisal, Tromethamine and pyrrole lowers drug-properties or induce toxicities. Pyrrole substitution at position R4 was not found favourable for COX binding. Among the favourable combinations, DF19 is the Diflunisal-Pyrrole-Tromethamine combination, equally favourable for binding to COX targets.
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Despite being one of the most common gynecological issues faced by women of reproductive age, dysmenorrhea largely remains an ignored, underdiagnosed and untreated condition. It continues to be a public health issue and has a significant impact on the quality of life of the affected women in terms of inability to lead routine activities, absenteeism from academic activities or work and reduced social activities. Currently, existing evidence correlates and implicates the excessive synthesis of prostaglandins with the menstrual pain. Hence, treatment approaches that can inhibit prostaglandins' production or already formed prostaglandins can provide relief in dysmenorrhea. In this review, the impact of dysmenorrhea on the quality of life of women, the role of prostaglandins in the pathogenesis of dysmenorrhea, and how nonsteroidal anti-inflammatory drugs (NSAIDs) like mefenamic acid can be safe and effective in managing dysmenorrhea are discussed.
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BACKGROUND: Colorectal cancer (CRC) is the fourth most common cancer in Nigeria, and it affects mostly persons in their middle age. In a bid to gain some insight into the molecular characteristics of CRC in our environment, we set out to investigate the expression of COX-2 and HER-2 among Nigerian subjects. OBJECTIVES: To evaluate the expression of COX-2 and HER2 and determine their correlation with clinicopathologic parameters in surgically resected histologically diagnosed cases of colorectal cancer. METHODS: Fifty-three paraffin-embedded tissue blocks of colorectal resections and corresponding patient information were retrieved from the archives of the Anatomic and Molecular Pathology Department of Lagos University Teaching Hospital.A 4-micron slide section was obtained from each specimen and immunohistochemistry for COX-2 and HER-2 expression was performed. RESULTS: Mean age of cases was 53.9years with an almost equal M:F ratio of 1.12:1. Half of the cases were moderately differentiated adenocarcinoma and 17% were high grade tumors.Eighty three percent of the tumours showed positive cytoplasmic COX-2 expression and extremely low membranous HER-2 positivity was observed in 2%. There was no significant correlation between COX-2 expression and age, gender, tumour location, tumour size, depth of invasion or lymph node status.However, COX-2 expression revealed a significant correlation with tumour grade (p= 0.013). CONCLUSION: This study detects a high COX-2 and low HER2 expression in colorectal cancer using immunohistochemistry,suggesting a possible role for COX-2 in CRC pathogenesis.This report should trigger further investigations of both markers vis-à-vis the management of CRC in our environment. WAJM 2022; 39(11): 11341140.
Subject(s)
Humans , Colorectal Neoplasms , Neoplasm, Residual , Immunohistochemistry , Adenocarcinoma , Genes, erbB-2 , Cyclooxygenase 2 InhibitorsABSTRACT
Objective:To investigate CK19 and COX-2 expression in papillary thyroid carcinoma (PTC) and their relationship with clinicopathologic parameters.Methods:Retrospective study of 120 consecutive patients with PTC who underwent resection from May. 2017 to Dec. 2020 was conducted. The expression of CK19 and COX-2 in 120 pieces of primary PTC tissue and 30 pieces of adjacent carcinoma tissue were detected by EliVision TM plus two-step immunohistochemical method. The relationship between the expression of CK19 and COX-2 and the clinicopathologic parameters including patient age, TI-RADS classification, TNM staging, carcinomatous infiltration, lymph node metastasis was studied. The analysis was performed using SPSS 22.0 software. The numerical data were presented as numbers and percentages, and chi-test ( χ2 test) and Pearson’s correlation were used to analyze the difference and association between two groups. P<0.05 was considered statistically significant. Results:The positive immunostaining of CK19 and COX-2 were mainly localized in the cytoplasm. The positive rates of CK19 and COX-2 were 87.50% (105/120) and 72.50% (87/120) in cancer tissues and 10.00% (3/30) and 3.33% (1/30) in paracancerous tissues, respectively, with statistically significant differences (both P<0.05 by χ2 test) . In the groups with patients aged <45 years versus ≥45 years, the CK19 positive rates were 88.16% (67/76) and 86.36% (38/44) , and the COX-2 positive rates were 69.74% (53/76) and 77.27% (34/44) , respectively. In the groups of TI-RADS (grade 4 and 5) versus grade 6, the CK19 positive rates were 85.26% (81/95) and 96.00% (24/25) , and the COX-2 positive rates were 69.47% (66/95) and 84.00% (21/25) , respectively, with no statistically significant differences between the two groups (both P>0.05) . In the groups of TNM (stage T1 and T2) versus stage T3, the CK19 positive rates were 82.28% (65/79) and 97.56% (40/41) , and the COX-2 positive rates were 65.82% (52/79) and 85.36% (35/41) , respectively. In the groups with versus without cancer infiltration, the CK19 positive rates were 94.44% (68/72) and 77.08% (37/48) , and the COX-2 positive rates were 83.33% (60/72) and 56.25% (27/48) , respectively. In the groups with versus without lymph node metastasis, the CK19 positive rates were 95.59% (65/68) and 76.92% (40/52) , and the COX-2 positive rates were 83.82% (57/68) and 57.69% (30/52) , respectively, and the differences between the above groups were statistically significant (all P<0.05 by χ2 test) . The co-positive and co-negative expression rates of CK19 and COX-2 in 120 patients were 70.83% (85/120) and 10.83% (13/120) , respectively, with a positive correlation ( r=0.45, P<0.05 by Pearson’s correlation) . Conclusions:The positive rates of CK19 and COX-2 expressions are not related to patient’s age or TI-RADS classification, but closely related to TNM stage, cancer invasion and lymph node metastasis. The up-regulation of both CK19 and COX-2 expressions predicts higher tumor stage, more aggressive invasion and more prone to lymph node metastasis.
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Cyclooxygenases play a vital role in inflammation and are responsible for the production of prostaglandins. Two cyclooxygenases are described, the constitutive cyclooxygenase-1 and the inducible cyclooxygenase-2, for which the target inhibitors are the non-steroidal anti-inflammatory drugs (NSAIDs). Prostaglandins are a class of lipid compounds that mediate acute and chronic inflammation. NSAIDs are the most frequent choices for treatment of inflammation. Nevertheless, currently used anti-inflammatory drugs have become associated with a variety of adverse effects which lead to diminished output even market withdrawal. Recently, more studies have been carried out on searching novel selective COX-2 inhibitors with safety profiles. In this review, we highlight the various structural classes of organic and natural scaffolds with efficient COX-2 inhibitory activity reported during 2011-2021. It will be valuable for pharmaceutical scientists to read up on the current chemicals to pave the way for subsequent research.
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Objective:To evaluate the anti-inflammatory potential of aqueous extract of Pterocarpus santalinus L.f. heartwood using molecular docking and in vivo experiment. Methods:An aqueous extract of Pterocarpus santalinus heartwood was prepared using a Soxhlet apparatus. Phytocompounds in the extract were tentatively identified using high-resolution mass spectrometry. Molecular docking experiments were carried out to evaluate the binding affinity of selected compounds, phloridzin to cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), prostaglandin E synthase-1 (PGES-1) and 5-lipoxygenase (5-LOX). Anti-inflammatory potential was evaluated by carageenan induced paw edema model in rats. Results:The presence of major component phloridzin along with quercetin, parthenin, ginkgolide B, picrotoxinin, usnic acid, octopine, and epigallocatechin was detected in the extract. Molecular docking study showed that phloridzin inhibited COX-1, COX-2, PGES-1 and 5-LOX with more affinity than ibuprofen and paracetamol. Pterocarpus santalinus heartwood extract at 200 and 400 mg/kg BW showed significant reduction in carageenan-induced hind paw edema in a dose-dependent manner, but the effect was slow when compared with the standard ibuprofen (30 mg/kg p.o.). Conclusions:The study indicated that after clinical trials, the aqueous extract of Pterocarpus santalinus heartwood can be effectively used in phytotherapy to treat inflammation.
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Xiaoer-Feire-Kechuan (XFK) is an 11-herb Chinese medicine formula to treat cough and pulmonary inflammation.The complicated composition rendered its chemical analysis and effective-component elucidation.In this study,we combined quantitative analysis and bioactivity test to reveal the anti-inflammatory constituents of XFK.First,UPLC-DAD and UHPLC/Q-Orbitrap-MS methods were estab-lished and validated to quantify 35 analytes (covering 9 out of 11 herbs) in different XFK formulations.Parallel reaction monitoring mode built in Q-Orbitrap-MS was used to improve the sensitivity and selectivity.Then,anti-inflammatory activities of the 35 analytes were analyzed using in vitro COX-2 inhibition assay.Finally,major analytes forsythosides H,I,A (8-10),and baicalin (15) (total contents varied from 21.79 to 91.20 mg/dose in different formulations) with significant activities (inhibitory rate ≥ 80％) were proposed as the anti-inflammatory constituents of XFK.The present study provided an effective strategy to discover effective constituents of multi-herb formulas.
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Background: Cyclea peltata is one of the herbs mentioned in ancient scriptures of Ayurveda and is used indifferent types of Ayurvedic gritham preparations. Moreover, in traditional/tribal medicine C. peltata isused as digestive, anti-inflammatory, diuretic and to treat jaundice, digestive disorders, etc.Objective: Activity guided fractionation of C. peltata and in correlation with the levels of bioactivecompound tetrandrine.Materials and methods: Preliminary phytochemical screening, estimation of total alkaloid content,preparation of different extracts of C. peltata (crude extract CP, hexane extract HCP, chloroform extractCCP, methanol extract MCP, alkaloid fraction ACP). In vitro anti-inflammatory studies using RAW264.7 cells and in vitro antioxidant assays of the different extracts of C. peltata. HPTLC estimation oftetrandrine (TET) was carried out using solvent system toluene: ethyl acetate: diethylamine (7.2: 2: 0.8)and isolation of TET from ACP.Results: Preliminary phytochemical studies of C. peltata showed the presence of alkaloid content in allextracts. Whereas, saponins, steroids and terpenoids were detected in CP and CCP. ACP and TET showedsignificant in vitro anti-inflammatory and antioxidant activity when compared to other extracts. ACP andTET (100 mg/ml) treatment significantly inhibited the mRNA expression of iNOS, COX-2, TNF-a in LPStreated RAW 264.7 cells. HPTLC estimation of bioactive compound tetrandrine was highest in ACP228.4 mg/mg followed by CP-29.62 mg/mg, CCP-23.46 mg/mg, MCP-18.82 mg/mg and HCP-1.25 mg/mg. TEThas been isolated from ACP.Conclusion: The results of the present in vitro assays revealed that the alkaloid fraction (ACP) is the mostactive fraction when compared to other extracts and has a positive correlation with the levels of bioactivecompound tetrandrine.
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Abstract Aim: To investigate the consequences of chronic eccentric exercise in histopathology, inflammatory, and myogenic regulatory factors response in gastrocnemius muscle of X-chromosome-linked muscular dystrophy (mdx) mice. Method: Male mdx and control mice (C57BL/10 lineage) were distributed in the following groups: Sedentary Control (SC), Trained Control (TC), Sedentary Mdx (S-Mdx), and Trained Mdx (T-Mdx). Trained animals were subjected to downhill running for 7 weeks. Gastrocnemius was submitted to histopathological analysis and immunoexpression of Cyclooxygenase-2 (COX-2) and myogenic regulatory factors (myoD and myogenin). Results: The exercise influenced inflammation response as demonstrated by the increased COX-2 immunoexpression in T-Mdx. Interestingly, Myogenic regulatory factors revealed that the lack of dystrophin has not been influenced myoD and the increase of myogenin occurred due to exercise and was not aggravated by the absence of dystrophin. Conclusion: In conclusion, an eccentric exercise in gastrocnemius of mdx mice was characterized by an intense inflammatory process without myogenic response. These findings suggest that special attention should be given to inflammatory aspects related to COX-2 associated with a decrease of myoD expression, as biomarkers in motor rehabilitation programs.
Subject(s)
Animals , Mice , Exercise , Myogenin , Cyclooxygenase 2 Inhibitors , Muscular DystrophiesABSTRACT
Sepsis is an infection-induced systemic inflammatory syndrome. The immune response in sepsis is characterized by the activation of both proinflammatory and anti-inflammatory pathways. When sepsis occurs, the expression and activity of many inflammatory cytokines are markedly affected. Xenobiotic receptors are chemical-sensing transcription factors that play essential roles in the transcriptional regulation of drug-metabolizing enzymes (DMEs). Xenobiotic receptors mediate the functional crosstalk between sepsis and drug metabolism because the inflammatory cytokines released during sepsis can affect the expression and activity of xenobiotic receptors and thus impact the expression and activity of DMEs. Xenobiotic receptors in turn may affect the clinical outcomes of sepsis. This review focuses on the sepsis-induced inflammatory response and xenobiotic receptors such as pregnane X receptor (PXR), aryl hydrocarbon receptor (AHR), glucocorticoid receptor (GR), and constitutive androstane receptor (CAR), DMEs such as CYP1A, CYP2B6, CYP2C9, and CYP3A4, and drug transporters such as p-glycoprotein (P-gp), and multidrug resistance-associated protein (MRPs) that are affected by sepsis. Understanding the xenobiotic receptor-mediated effect of sepsis on drug metabolism will help to improve the safe use of drugs in sepsis patients and the development of new xenobiotic receptor-based therapeutic strategies for sepsis.