Enzymatic Activity Of Cyclooxygenase-2 Research Articles

Aspirin in a new role in human body

In 1897, German chemist Felix Hoffman synthesized acetylsalicylic acid, known as aspirin, which revolutionized its widespread modern use for pain relief. Aspirin acts as an inhibitor of cyclooxygenase-1 (COX-1) and has a modifying effect on the enzymatic activity of cyclooxygenase-2 (COX-2). It inhibits the production of prostaglandins, crucial for various physiological processes, and has been linked to a reduced risk of pre-eclampsia and preterm delivery before 34 weeks of pregnancy. However, aspirin's COX-1 inhibition is irreversible and long-lasting, requiring new enzymes to replace those acetylated. Low-dose aspirin has been reported to increase bone mineral density (BMD) in elderly individuals, coinciding with the growing prevalence of osteoporosis. However, a definitive connection between the use of low-dose aspirin and BMD remains elusive. A study examined the relationship between low-dose aspirin use and BMD in adults aged 50 to 80. A higher BMD in the femur, intertrochanter, and L1 regions compared to those who do not use aspirin was reported. However, the abstract acknowledges limitations and emphasizes the need for future research, including randomized controlled trials, to establish a causal relationship between low-dose aspirin use and enhanced bone density.

Anti-inflammatory Activity and Cyclooxygenase-2 Inhibitory effect of Peperomia pellucida (L.) Kunth Extract

Inflammation is an adaptive response underlying a wide variety of physiological and pathological processes mediated by the Cyclooxygenase (COX) enzyme. Cyclooxygenase-2 (COX-2) is an important enzyme that catalyzes the production of prostaglandins from arachidonic acid and has a crucial role in various pathologies including inflammation, neurological disorders, and cancer. The selective suppression of COX-2 over COX-1 is thought to be a useful approach for treating inflammation. Peperomia pellucida (L.)Kunth has been traditionally used as an anti-inflammatory and antioxidant, thus giving scope for anti-inflammatory studies. Since the action of Ethanol extract of Peperomia pellucida (EEPp) on COX-2 has not been previously described, in this study, we further investigated the effect of Cyclooxygenase-2 inhibitory effects spectrophotometrically in ELISA readers and evaluated of anti-inflammatory activity in the carrageenan-induced rat paw edema model. The edema volume was measured using a plethysmometer. The results showed that the EEPp (100, 200, and 400mg/kg BW) had significant anti-inflammatory activity and the EEPp demonstrated a COX-2 Inhibitory effect. The percentage of COX-2 inhibition was 10.87%, 47.04%, 56%, and the percentage of inhibition of paw edema was 34.93%, 46.61%, and 64.04%, respectively. These findings suggest that Peperomia pellucida extracts possess promising and remarkable anti-inflammatory activity, which is directed against the enzymatic activity of COX-2.

Vitex trifolia as Cyclooxygenase-2 Inhibitors in Anti-Inflammatory Drug Discovery

Inflammation is involved in several stages of diseases such as cardiovascular diseases, asthma, diabetes, neurodegenerative diseases, or cancer. Cyclooxygenase-2 (COX-2) is an important enzyme that catalyzes the production of prostaglandins from arachidonic acid and has an important role in various inflammatory-related pathologies. The selective suppression of COX-2 over COX-1 is thought to be a useful approach for treating inflammation. Vitex trifolia is traditionally used for various inflammatory ailments, thus giving scope for anti-inflammatory studies. Since the action of Ethanol extract of Vitex trifolia (EEVT) on COX-2 has not been previously described. In this study, we further investigated the effect of Cyclooxygenase-2 inhibitory effects spectrophotometrically in ELISA readers and evaluated anti-inflammatory activity in the carrageenan-induced rat paw edema model. The edema volume was measured using a plethysmometer. The results showed that the EEVt (200, 400, and 800 mg/kg BW) had significant anti-inflammatory activity and the EEVt demonstrated a COX-2 Inhibitory effect. The percentage of COX-2 inhibition was 8,04%, 20,74%, 21,92%, and the percentage of inhibition of paw edema was 39,56%, 45,60%, and 40,56%, respectively. These findings suggest that Vitex trifolia leaves extracts to possess promising and remarkable anti-inflammatory activity, which is directed against the enzymatic activity of COX-2.

Dietary magnesium ions block the effects of nutrient deficiency on inducing the formation of LC3B autophagosomes and disrupting the proteolysis of autolysosomes to degrade β-amyloid protein by activating cyclooloxygenase-2 at tyrosine 385

• As an important mineral nutrient, Mg 2+ inhibits the activity of COX-2 via mTORC1. • By nutrient deprivation, COX-2 activation induces formation of LC3B autophagosomes. • Mg 2+ disrupts the formation of LC3B autophagosomes via deactivating the COX-2. • COX-2 disturbs hydrolysis of Aβ via suppressing activity of UCH-L1 in lysosomes. • Tyr 385 is critical for the activity of COX-2 in cognitive decline of AD. Nutrient deficiency has been recently suggested to be associated with the deposition of β-amyloid protein (Aβ) during the course of Alzheimer’s disease (AD) development and progression. We thereby aimed to reveal the roles of a deficiency in important mineral nutrient, magnesium ions (Mg 2+ ), in the deposition of Aβ via autophagy mechanisms. Specifically, we report here that Mg 2+ functions as a critical enhancer of the formation of the mammalian target of rapamycin complex 1 (mTORC1) by inhibiting the expression and enzymatic activity of cyclooxygenase-2 (COX-2), which is responsible for inducing autophagosome formation, as indicated by the microtubule-associated protein 1 light chain 3 beta (LC3B) puncta. Although autophagosome generation was strongly induced in COX-2 Tg mice, COX-2 overexpression facilitated Aβ deposition by disrupting the proteolytic function of autolysosomes through an ubiquitin carboxy terminal hydrolase L1 (UCH-L1)-depressing mechanism. More interestingly, COX-2 mutation at Tyr 385 restores the activity of UCH-L1, which results in Aβ degradation and improvements in the cognitive decline of APP/PS1 Tg mice.

Cyclooxygenase-2 mediates puerarin to inhibit the invasion and metastasis of lung cancer A549 cells

Background: The mechanisms by which puerarin prevents and treats lung cancer remain largely unknown. We aimed to study the roles of puerarin in the invasion and metastasis of lung cancer A549 cells based on cyclooxygenase-2 (COX-2). Methods: The effects of different concentrations of puerarin on the proliferation of A549 cells were evaluated. The in vitro and in vivo effects of puerarin on the invasion and metastasis of A549 cells were assessed by Transwell assay and an animal model of tumor lung metastasis respectively. The influence of puerarin on COX-2 in A549 cells was also analyzed in terms of enzymatic activity and tissue level to explore the role of COX-2 in the inhibitory effects of puerarin on cell invasion and metastasis. Results: Puerarin inhibited the proliferation of A549 cells in time- and dose-dependent manners. Compared with the control group, more cells in the puerarin treatment groups were arrested in the G0/G1 phase, but the proportion of S phase cells decreased. Puerarin blocked the cell cycle dose-dependently. After 24 h of culture with 200 μg/mL puerarin, significantly fewer cells penetrated the basement membrane of Transwell chambers than those in the control group, and the MMP-2/TIMP-2 levels in PUE200, PUE400 and PUE800 groups significantly dropped. For the animal experiments, the puerarin treatment groups had significantly fewer and smaller tumors with pulmonary metastasis than those of the control group. After 24 h of culture with puerarin, like the indomethacin (IN) group, PUE200, PUE400 and PUE800 groups had significantly lower enzymatic activity of COX-2 than that of the control group, but the puerarin treatment groups had similar results. The IN group had lower COX-2 protein expression than that of the control group, but the puerarin treatment groups had similar expressions to that of the control group, indicating that COX-2 protein expression was hardly affected by puerarin in A549 cells. Similar to the IN group, the puerarin treatment groups had significantly lower PGE2 levels than that of the control group (P Conclusions: Puerarin inhibited the enzymatic activity of COX-2 in A549 cells and its expression in tumor tissues with pulmonary metastasis. MMP-2/TIMP-2 may be one of the mechanisms by which puerarin inhibits the invasion of A549 cells.

Induction of heme oxygenase-1 attenuates lipopolysaccharide-induced cyclooxygenase-2 expression in mouse brain endothelial cells

BackgroundProstaglandin E2 (PGE2), an arachidonic acid metabolite converted by cyclooxygenase-2 (COX-2), plays important roles in the regulation of endothelial functions in response to bacterial infection. The enzymatic activity of COX-2 can be down-regulated by heme oxygenase-1 (HO-1) induction. However, the mechanisms underlying HO-1 modulating COX-2 protein expression are not known.ObjectiveThe aim of the present study was to investigate whether the up-regulation of HO-1 regulates COX-2 expression induced by lipopolysaccharide (LPS), an endotoxin produced by Gram negative bacteria, in mouse brain endothelial cells (bEnd.3)MethodsCultured bEnd.3 cells were used to investigate LPS-induced COX-2 expression and PGE2 production. Cobalt protoporphyrin IX (CoPP, an HO-1 inducer), infection with a recombinant adenovirus carried with HO-1 gene (Adv-HO-1), or zinc protoporphyrin (ZnPP, an HO-1 inhibitor) was used to stimulate HO-1 induction or inhibit HO-1 activity. The expressions of COX-2 and HO-1 were evaluated by western blotting. PGE2 levels were detected by an enzyme-linked immunoassay. Hemoglobin (a chelator of carbon monoxide, CO, one of metabolites of HO-1) and CO-RM2 (a CO releasing molecule) were used to investigate the mechanisms of HO-1 regulating COX-2 expression.ResultsWe found that LPS-induced COX-2 expression and PGE2 production were mediated through NF-κB (p65) via activation of Toll-like receptor 4 (TLR4). LPS-induced COX-2 expression was inhibited by HO-1 induction by pretreatment with CoPP or infection with Adv-HO-1. This inhibitory effect of HO-1 was reversed by pretreatment with either ZnPP or hemoglobin. Pretreatment with CO-RM2 also inhibited TLR4/MyD88 complex formation, NF-κB (p65) activation, COX-2 expression, and PGE2 production induced by LPS.ConclusionsWe show here a novel inhibition of HO-1 on LPS-induced COX-2/PGE2 production in bEnd.3. Our results reinforce the emerging role of cerebral endothelium-derived HO-1 as a protector against cerebral vascular inflammation triggered by bacterial infection.

In vitro anti-inflammatory effects of arctigenin, a lignan from Arctium lappa L., through inhibition on iNOS pathway

Ethnopharmacological relevance Arctigenin, a bioactive constituent from dried seeds of Arctium lappa L . (Compositae) which has been widely used as a Traditional Chinese Medicine for dispelling wind and heat included in Chinese Pharmacophere, was found to exhibit anti-inflammatory activities but its molecular mechanism remains unknown yet. Aim of the study To investigate the anti-inflammatory mechanism of arctigenin. Materials and methods Cultured macrophage RAW 264.7 cells and THP-1 cells were used for the experiments. Griess assay was used to evaluate the inhibitory effect of arctigenin on the overproduction of nitric oxide (NO). ELISA was used to determine the level of pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). The inhibitory effect on the enzymatic activity of cyclooxygenase-2 (COX-2) was tested by colorimetric method. Western blot was used to detect the expression of inducible nitric oxide synthase (iNOS) and COX-2. Results Arctigenin suppressed lipopolysaccharide (LPS)-stimulated NO production and pro-inflammatory cytokines secretion, including TNF-α and IL-6 in a dose-dependent manner. Arctigenin also strongly inhibited the expression of iNOS and iNOS enzymatic activity, whereas the expression of COX-2 and COX-2 enzymatic activity were not affected by arctigenin. Conclusions These results indicated that potent inhibition on NO, TNF-α and IL-6, but not COX-2 expression and COX-2 activity, might constitute the anti-inflammatory mechanism of arctigenin. Arctigenin suppressed the overproduction of NO through down-regulation of iNOS expression and iNOS enzymatic activity in LPS-stimulated macrophage.

Cryptotanshinone inhibits cyclooxygenase-2 enzyme activity but not its expression

Cyclooxygenase-2 (COX-2) is a key enzyme that catalyzes the biosynthesis of prostaglandins from arachidonic acid and plays a critical role in some pathologies including inflammation, neurodegenerative diseases and cancer. Cryptotanshinone is a major constituent of tanshinones, which are extracted from the medicinal herb Salvia miltiorrhiza Bunge, and has well-documented antioxidative and anti-inflammatory effects. This study confirmed the remarkable anti-inflammatory effect of cryptotanshinone in the carrageenan-induced rat paw edema model. Since the action of cryptotanshinone on COX-2 has not been previously described, in the present study, we further examined the effect of cryptotanshinone on cyclooxygenase activity in the exogenous arachidonic acid-stimulated insect sf-9 cells, which highly express human COX-2 or human COX-1, and on cyclooxygenases expression in human U937 promonocytes stimulated by lipopolysaccharide (LPS) plus phorbolmyristate acetate (PMA). Cryptotanshinone reduced prostaglandin E 2 synthesis and reactive oxygen species generation catalyzed by COX-2, without influencing COX-1 activity in cloned sf-9 cells. In PMA plus LPS-stimulated U937 cells, cryptotanshinone had negligible effects on the expression of COX-1 and COX-2, at either a mRNA or protein level. These results demonstrate that the anti-inflammatory effect of cryptotanshinone is directed against enzymatic activity of COX-2, not against the transcription or translation of the enzyme.

COX-2 inhibition as a tool to treat and prevent colorectal cancer

The cyclooxygenase-2 (COX-2) enzyme has a fundamental role in the carcinogenesis of colorectal cancer. The anticarcinogenic mechanisms of NSAIDs are not completely understood and appear to be only partially dependent on inhibition tumoral COX-2. Moreover, the mechanisms of NSAIDs depend on the concentration. In experimental setting, at low levels NSAIDs downregulate the COX-2 gene in colorectal cancer cells , whereas at clinical relevant concentrations the production of prostaglandin E2 by enzymatic activity of COX-2 is diminished resulting in inhibition of the tumor angiogenesis . At higher levels NSAIDs and especially some selective COX-2 inhibitors are capable of COX-2 independent effects, such as apoptosis induction of tumor cells. In animal models, NSAIDs administration results in inhibition of angiogenesis and proliferation, induction apoptosis and prevention of metastasis . In clinical setting, NSAIDs and selective COX-2 inhibitors have the capacity to prevent the development of colorectal adenomas . We have summarized data regarding the role of COX-2 in CRC and discuss the multiple targets of NSAIDs in their anticarcinogenic action. However, the translation of these anticarcinogenic effects of NSAIDs to its clinical application as adjuvant therapy in CRC is hampered by a lack of randomized clinical trials with long-term follow-up.

Inhibition of cyclooxygenase-2, but not cyclooxygenase-1, reduces prostaglandin E 2 secretion from diabetic rat retinas

Up-regulation of cyclooxygenase-2 occurs in retinal cells during the early onset of diabetic retinopathy. Under these conditions, prostaglandin production is elevated, which in turn leads to an increased expression of vascular endothelial growth factor (VEGF)—a growth factor implicated in vascular leakage and neovascularization. In this ex vivo study, we tested whether cyclooxygenase-1 or cyclooxygenase-2 is responsible for diabetes-induced secretion of prostaglandin E 2 from isolated rat retinas. Celecoxib, a selective cyclooxygenase-2 inhibitor, significantly inhibited prostaglandin E 2 secretion, whereas SC560 [5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole], a selective cyclooxygenase-1 inhibitor, had no inhibitory effect. These results suggests that the enzymatic activity of cyclooxygenase-2, but not cyclooxygenase-1, results in prostaglandin E 2 secretion under diabetic conditions.