Prostaglandin Research Articles

The role of Doppler studies in predicting non-reassuring fetal heart rate monitoring following induction of labor.

The role of Doppler studies in predicting non-reassuring fetal heart rate monitoring following induction of labor.

Plasma and Fecal Bioactive Mediators in Relation to the Prevention of Atherogenesis in LDL-r-KO Mice: Insights from an African Staple Food.

Our previous study revealed a significant anti-atherosclerotic effect of Kgengwe seed powder (KSP) in low-density lipoprotein receptor knockout (LDL-r-KO) mice. The importance of various lipid and protein metabolites, including certain amino acids and fatty acids on atherogenesis has been well established. Thus, we used plasma and fecal samples from our previous study to further study the association of such metabolites with atherosclerotic lesion development. Male LDL-r-KO mice were provided with an atherogenic diet supplemented with (treated, n = 10) or without (controls, n = 10) 10% (w/w) KSP for 20 weeks. The treated group showed significantly (P < 0.05) higher plasma levels of many amino acids plus propionic acid, indoleacetic acid, pyruvic acid, beta-hydroxybutyric acid, alpha-ketoglutaric acid, trimethylamine N-oxide, LYSOC16:0, LYSOC18:0, and LYSOC18:2, as compared with those of the control group. Similarly, several oxylipins, including 15-keto prostaglandin E2, 9,10,13-trihydroxy-octadecenoic acid, 9,10-epoxy-octadecenoic acid, and 12,13-epoxy-octadecenoic acid increased by approximately 2.0 log2 folds (P < 0.05) in the plasma of the treated group. Other oxylipins, including 15,16-epoxy- octadecadieonic acid, 13-hydroxy-octadecadienoic acid, and prostaglandin E2 showed also an increased level, but to a lesser extent. Furthermore, our findings showed a significant positive correlation between plasma concentrations of prostaglandin E2 and IL-10 in the treated mice. We also observed a significant negative association between atherosclerotic lesion size and plasma levels of citrulline, lysine, alpha-ketoglutaric acid, and 15,16 epoxy-octadecadienoic acid. Additional in vitro and in vivo studies are needed to explore the mechanisms of such associations.

M-Aminophenylacetylene shortened the eggsac-carrying stages in the wolf spider through enhancing the synthesis of prostaglandins.

Spiders are important predatory enemies that control a range of insect pests in the rice ecosystem. m-Aminophenylacetylene (m-A) has been demonstrated to induce maternal care behaviors in Pardosa pseudoannulata, protecting young spiders and promoting population growth. Here the roles of m-A on other reproduction stages were evaluated by injecting m-A into virgin and postreproductive female spiders. When injected into virgin females, m-A can prolong the first pulli-carrying stage of the females after mating and breeding offsprings. In postreproductive females, m-A injection shortened the eggsac-carrying stages, especially in the second and third stages. Transcriptomic analysis showed that differentially expressed genes between the control female and m-A-injected female were enriched in the arachidonic acid (AA) metabolism pathway. Real-time quantitative PCR (qPCR) confirmed the upregulation of cyclooxygenase-II (COX-II), prostaglandin E synthase 2 (PGES2), and prostaglandin E synthase 3 (PGES3) genes involved in PGE2 (prostaglandin E2) synthesis. In a reverse validation experiment, the sequential injection of m-A followed by a COX inhibitor aspirin restored the shortened eggsac-carrying stage to normal level. The findings indicated that m-A enhanced PGs synthesis, leading to a reduced eggsac-carrying stage. The eggsac-carrying stage can be fatal when female spiders encounter their enemies, so the shortening of the stage by m-A would reduce the potential threat. These findings are significant for developing environmentally friendly control strategies.

The Molecular and Cellular Mechanisms of Endometriosis: From Basic Pathophysiology to Clinical Implications

Endometriosis is a complex gynecological disorder characterized by endometrial-like tissue growing outside the uterus, leading to chronic pain, infertility, and reduced quality of life. Its pathophysiology involves genetic, epigenetic, immune, and molecular factors. Theories such as retrograde menstruation, coelomic metaplasia, and stem cell involvement explain lesion formation. Endometrial mesenchymal stem cells (eMSCs) and epithelial progenitors (eEPs) contribute to lesion establishment by adhering to peritoneal surfaces, proliferating, and differentiating into ectopic tissue. Aberrant adhesion molecules, inflammatory cytokines, and molecular pathways like PI3K/Akt and Wnt/β-catenin drive proliferation, angiogenesis, and resistance to apoptosis. Elevated estrogen levels and progesterone resistance further promote lesion growth and immune evasion. Immune dysfunction, including altered macrophage activity and reduced natural killer (NK) cell function, contributes to inflammation and lesion persistence. Pain is linked to prostaglandin E2 (PGE2) and nerve infiltration, emphasizing the need for targeted pain management. Current therapies, such as GnRH agonists, suppress ovarian hormone production but face limitations in long-term efficacy and side effects. Integrating molecular insights into clinical practice may advance diagnostics and treatment, with emerging approaches focusing on molecular pathways, immune modulation, and hormonal regulation for more effective, personalized therapies. Future research should unravel the complex mechanisms driving endometriosis to improve patient outcomes.

DIFFERENTIAL RESPONSES TO PROSTAGLANDINS IN THE CIRCULAR AND LONGITUDINAL MUSCLE LAYERS OF THE MURINE ILEUM.

Prostaglandin E2 (PGE2) actions on intestinal motility are complex due the differential expression of the PGE2 receptors EP1-EP4. We sought to determine the actions of PGE2 on electrical pacemaker and contractile activity of the circular and longitudinal muscle layers of the murine small intestine. Intracellular microelectrode and isometric force measurements were performed to examine the effects of PGE2 receptor activation on circular and longitudinal muscle layers. In the two muscle layers PGE2 produced differential responses. In the circular muscle layer PGE2 caused dose-dependent membrane hyperpolarization and reduction in slow wave amplitude, accompanied by a decrease in the amplitude of phasic contractions. Membrane hyperpolarization and the reduction in slow wave amplitude and phasic contractions were insensitive to TTX and L-NNA, but inhibited by the KATP channel antagonist, glibenclamide. The actions of PGE2 on the circular muscle layer were mimicked by the selective EP2 and EP4 agonists ONO AE1-259 and ONO AE1-329, respectively. The actions of PGE2 were partially inhibited by the EP4 antagonist ONO AE3-208. The EP1 agonist ONO DI-004 produced little effect while the EP3 agonist ONO AE-248 caused dose-dependent membrane depolarization. In comparison, PGE2 produced increased tone and phasic contractions in the longitudinal muscle layer that was mimicked by ONO DI-004 and ONO AE-248, while EP2 and EP4 agonists had little effect on contractile activity. These data suggest that differential expression of PGE2 receptors on intestinal muscle layers can produce antagonistic actions on intestinal motility.

The Role of Prostaglandin Pathway and EP Receptors in Skin Cancer Development.

Skin cancer is the most prevalent malignancy worldwide, with nonmelanoma skin cancers (NMSC) such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) constituting most cases. Melanoma, although less common, is the most aggressive form of skin cancer and is responsible for the majority of skin cancer-related deaths. Prostaglandins, particularly prostaglandin E2 (PGE2), play a central role in the pathogenesis of skin cancer by mediating inflammation, angiogenesis, immune suppression, and tumor progression through the cyclooxygenase (COX)-PGE2 pathway. PGE2 exerts its effects via E-prostanoid (EP) receptors (EP1-EP4), which activate distinct signaling pathways that promote cell proliferation, survival, and metastasis. In melanoma, the COX-2-E2 axis is implicated in tumor-mediated immunosuppression and tumor growth. Although COX-2 inhibitors like celecoxib have shown efficacy in reducing NMSC incidence, their long-term use is limited by adverse effects. EP receptor antagonists represent a promising therapeutic alternative, offering targeted inhibition of PGE2-driven tumorigenesis with potentially fewer side effects. Emerging therapies, including combination strategies with immune checkpoint inhibitors, highlight the potential of precision medicine approaches to optimize the treatment and prevention of skin cancers, including melanoma. Further research is essential to elucidate the mechanisms of PGE2 signaling and refine therapeutic interventions targeting the COX-PGE2-receptor axis.

Enhanced Transdermal Delivery of Piroxicam via Nanocarriers, Formulation, Optimization, Characterization, Animal Studies and Randomized Double-Blind Clinical Trial.

Piroxicam is a non-steroidal anti-inflammatory drug which is used topically as an adjunctive treatment of knee osteoarthritis and as an option to control joint pain in patients suffering rheumatoid arthritis. In this study, an emulgel containing optimized nano-niosomal piroxicam was formulated and characterized in terms of mean size, polydispersity index, zeta potential, drug entrapment efficiency and capacity, release and transdermal permeation. Also, animal studies including pain level assessment, synovial prostaglandin E2 levels, knee joint swelling degree and histopathologic investigations were conducted. A randomized double-blind clinical trial was also performed to compare the analgesic effect of nano-niosomal piroxicam emulgel with piroxicam gel. The results showed optimized niosome formulation with 142 ± 7nm mean size and 0.23 ± 0.08 PDI, entrapped 99.48 ± 0.79% of added piroxicam with a sustained release pattern. Permeation studies indicated a 3.31-fold transdermal permeation of niosomal piroxicam emulgel compared with the piroxicam gel. The niosomal formulation significantly reduced knee joint swelling and prostaglandin E2 levels. The clinical trial indicated that the painkilling efficiency of the niosomal piroxicam emulgel was 37.30-fold and 3.16-fold greater compared to the placebo and the positive control groups, respectively. In conclusion, the niosomal piroxicam emulgel which may enable the drug to permeate through the skin and accumulate in synovial tissue more efficiently, showed a promising performance in lowering pain and inflammation based on the animal studies and the human clinical trial.

The Efficacy and Safety of Intravenous Prostaglandin E1 in the Management of Retinal Artery Occlusion: A Systematic Review.

To evaluate the efficacy and safety of prostaglandin E1 (PGE1) for the management of central/branch retinal artery occlusion (CRAO/BRAO). Our protocol was registered prospectively on PROSPERO (CRD42024522961). We searched 4 electronic databases [PubMed, Scopus, Web of Science, and Google Scholar] to retrieve all studies reported using PGE1 for patients with CRAO/BRAO. We conducted a Wilcoxon signed-rank test to assess the effect of PGE1 on the visual acuity (VA) of included subjects. VA change was utilized as a measure to assess the degree of VA improvement. We assessed the quality of included studies using the JBI tool. We included a total of 6 studies with a total of 21 cases. Age ranged from 45 to 97 years with a mean of 65.76 years for 10 females and 11 males. Cases with CRAO represented 85.7% and BRAO represented 14.3% of total cases. The median time from symptoms onset to treatment initiation was 7 hours. The median for the initial dose was 40 μg. Wilcoxon signed-rank test revealed significant improvement in visual acuity after intravenous PGE1 treatment (V = 231, p < 0.05). Our analysis revealed preliminary evidence suggesting that IV PGE1 may be a potentially safe and effective treatment for improving VA in patients with CRAO/BRAO. However, our evidence is limited as our review relies primarily on case reports and case series.

LGR-5 as a Biomarker in Colorectal Cancer: A Systematic Review of Clinicopathological Features and Prognostic Value

Colorectal cancer (CRC) had the third highest cancer incidence worldwide. Recent researches are targeting specific gene expression as CRC marker. Leucine rich repeat-containing G-protein coupled receptor 5 (LGR5) is one of the genes that regulate tumor metastasis and growth. The aim of this study is to explain the correlation between LGR5, clinical pathology, and prognosis of CRC. This systematic review was arranged using PRISMA for eligible cohort studies and evaluated using Newcastle-Ottawa scale. From 63 articles, 6 articles were selected as eligible articles for data extraction and evaluation. Based on the studies, LGR5 positivity was positively associated with histopathological characteristics, TNM staging, and vascular invasion. Besides, LGR5 expressions in those studies were high and could be positively detected by this marker. LGR5 regulates Wnt/β-catenin signaling pathway promotion in normal colon stem cell. Methylation of Wnt target gene promoter is potent predictor to CRC recurrence thus the expression of LGR5 can be used as CRC marker. LGR5 plays a role as pro-oncogenic factor in colorectal carcinogenesis via prostaglandin E2 and Epidermal Growth Factor signaling. LGR5 induction also could increase cancer cells chemoresistant ability. Thus, LGR5 could determine prognosis of CRC patient and were related to certain clinicopathological features and tumor progressions.

Invitro Evaluation of the Anti-Inflammatory Activity of Phloroglucinol and Alpha-lipoic acid

It was decided to test the anti-inflammatory activity of phloroglucinol and alpha-lipoic acid combined in order to evaluate the possibility of a synergistic effect in the battle against inflammation. Both the antioxidant alpha-lipoic acid and the naturally occurring phenolic compound phloroglucinol were investigated by researchers in order to ascertain whether or not they were capable of modulating inflammatory pathways and pathways in vitro. The effects of the combination on numerous inflammatory mediators, including cytokines (TNF-α, IL-1β, and IL-6), prostaglandin E2 (PGE2), and nitric oxide (NO) generation, were assessed by employing human peripheral blood mononuclear cells (PBMCs) that were cultivated. The results demonstrated that these pro-inflammatory markers were greatly reduced following the combination treatment, which may indicate that the combination treatment had a synergistic effect on reducing inflammation. Furthermore, the combination had a considerable impact on inhibiting the activation of nuclear factor-kappa B (NF-κB), which is an essential regulator of inflammation. These findings imply that the combination of phloroglucinol and alpha-lipoic acid could be a feasible therapy method for inflammatory disorders; nevertheless, additional in vivo research are required to establish the efficacy and safety of the combination.

Kirenol ameliorates endotoxin-induced acute lung injury by inhibiting the ERK and JNK phosphorylation-mediated NFκB pathway in mice.

Acute lung injury (ALI) is a pathological condition characterised by varying degrees of lung damage in patients. Kirenol exerts anti-inflammatory, immunosuppressive, and antioxidative effects. We investigated the protective effects of kirenol on lipopolysaccharide-induced ALI in mice. Pretreatment with kirenol significantly ameliorated lung oedema and neutrophil infiltration in ALI mice. Kirenol downregulated the chemokines (MIP-2) expression and the adhesion molecules (ICAM-1 and VCAM-1) secretion. Furthermore, kirenol inhibited the production of the proinflammatory mediators nitric oxide and prostaglandin (PG)E2 through the upstream factors iNOS and cyclooxygenase (COX)-2, respectively. Kirenol suppressed the IKK-IκB-NFκB pathway, which is involved in lipopolysaccharide-induced inflammation. Kirenol inhibited the lipopolysaccharide-induced phosphorylation of ERK and JNK, to a lesser extent, p38 MAPK and Akt. In conclusion, our findings suggest that kirenol exerts ameliorative effects against ALI by suppressing the production of chemokines, adhesion molecules, and proinflammatory mediators and inhibiting the IKK-IκB-NFκB pathway and its upstream factors, phosphorylated ERK and JNK.

A simple platelet biomarker is associated with symptom severity in major depressive disorder.

Previous studies have shown that the heterotrimeric G protein, Gsalpha (Gsα), is ensconced predominantly in lipid rafts in acutely depressed subjects with major depressive disorder (MDD) in contrast to healthy controls, and that effective antidepressant treatment (ADT) facilitates translocation of Gsα from lipid rafts. The measurement of Gsα via prostaglandin E1 stimulation of adenylyl cyclase (PGE1 stimulation) has been proposed as a peripheral biomarker for assessing clinical status in MDD. We examined the Gsα biomarker in a new study. PGE1 stimulation was used to assess the coupling of Gsα with platelet adenylyl cyclase in depressed subjects in active treatment and healthy controls. The Quick Inventory of Depressive Symptomatology (QIDS-C16) measured thresholds of symptom severity at two study visits spaced 2 weeks apart. QIDS-C16 scores and PGE1 stimulated responses were stable between the two study visits. The QIDS-C16 was inversely correlated with PGE1 stimulated responses at each visit (rs = -0.33, rs = -0.60, respectively). MDD subjects with mild-moderate depressive symptoms (defined by QIDS-C16 ≥ 6) had significantly lower PGE1 stimulated responses than asymptomatic MDD subjects (QIDS-C16 < 6) or healthy controls (p = 0.001 and 0.002 respectively). MDD subjects with moderate depressive symptoms (QIDS-C16 ≥ 10) had the lowest PGE1 responses of all subjects (Fisher's exact = 0.012). These results support our earlier findings that a simple, high-throughput-capable platelet assay may be a useful biomarker to assess the clinical status of depressed subjects. Larger studies are needed to evaluate the utility of this biomarker for diagnosis and treatment response.

The Kv2.2 channel mediates the inhibition of prostaglandin E2 on glucose-stimulated insulin secretion in pancreatic β-cells

Prostaglandin E2 (PGE2) is an endogenous inhibitor of glucose-stimulated insulin secretion (GSIS) and plays an important role in pancreatic β-cell dysfunction in type 2 diabetes mellitus (T2DM). This study aimed to explore the underlying mechanism by which PGE2 inhibits GSIS. Our results showed that PGE2 inhibited Kv2.2 channels via increasing PKA activity in HEK293T cells overexpressed with Kv2.2 channels. Point mutation analysis demonstrated that S448 residue was responsible for the PKA-dependent modulation of Kv2.2. Furthermore, the inhibitory effect of PGE2 on Kv2.2 was blocked by EP2/4 receptor antagonists, while mimicked by EP2/4 receptor agonists. The immune fluorescence results showed that EP1–4 receptors are expressed in both mouse and human β-cells. In INS-1(832/13) β-cells, PGE2 inhibited voltage-gated potassium currents and electrical activity through EP2/4 receptors and Kv2.2 channels. Knockdown of Kcnb2 reduced the action potential firing frequency and alleviated the inhibition of PGE2 on GSIS in INS-1(832/13) β-cells. PGE2 impaired glucose tolerance in wild-type mice but did not alter glucose tolerance in Kcnb2 knockout mice. Knockout of Kcnb2 reduced electrical activity, GSIS and abrogated the inhibition of PGE2 on GSIS in mouse islets. In conclusion, we have demonstrated that PGE2 inhibits GSIS in pancreatic β-cells through the EP2/4-Kv2.2 signaling pathway. The findings highlight the significant role of Kv2.2 channels in the regulation of β-cell repetitive firing and insulin secretion, and contribute to the understanding of the molecular basis of β-cell dysfunction in diabetes.

The Kv2.2 channel mediates the inhibition of prostaglandin E2 on glucose-stimulated insulin secretion in pancreatic β-cells.

Prostaglandin E2 (PGE2) is an endogenous inhibitor of glucose-stimulated insulin secretion (GSIS) and plays an important role in pancreatic β-cell dysfunction in type 2 diabetes mellitus (T2DM). This study aimed to explore the underlying mechanism by which PGE2 inhibits GSIS. Our results showed that PGE2 inhibited Kv2.2 channels via increasing PKA activity in HEK293T cells overexpressed with Kv2.2 channels. Point mutation analysis demonstrated that S448 residue was responsible for the PKA-dependent modulation of Kv2.2. Furthermore, the inhibitory effect of PGE2 on Kv2.2 was blocked by EP2/4 receptor antagonists, while mimicked by EP2/4 receptor agonists. The immune fluorescence results showed that EP1-4 receptors are expressed in both mouse and human β-cells. In INS-1(832/13) β-cells, PGE2 inhibited voltage-gated potassium currents and electrical activity through EP2/4 receptors and Kv2.2 channels. Knockdown of Kcnb2 reduced the action potential firing frequency and alleviated the inhibition of PGE2 on GSIS in INS-1(832/13) β-cells. PGE2 impaired glucose tolerance in wild-type mice but did not alter glucose tolerance in Kcnb2 knockout mice. Knockout of Kcnb2 reduced electrical activity, GSIS and abrogated the inhibition of PGE2 on GSIS in mouse islets. In conclusion, we have demonstrated that PGE2 inhibits GSIS in pancreatic β-cells through the EP2/4-Kv2.2 signaling pathway. The findings highlight the significant role of Kv2.2 channels in the regulation of β-cell repetitive firing and insulin secretion, and contribute to the understanding of the molecular basis of β-cell dysfunction in diabetes.

Acetylsalicylic acid aggravates anaphylaxis in a PGE2-dependent manner.

Acetylsalicylic acid (ASA) can exert proanaphylactic effects, but the extent of this phenomenon and its underlying mechanisms are undefined. Yet, low homeostatic prostaglandin E2 (PGE2) levels have been associated with anaphylaxis. In this study, we investigated whether the proanaphylactic effect of ASA is PGE2 dependent. We assessed the effect of ASA in experimental anaphylaxis models, analyzed a large dataset of patients with anaphylaxis, and performed titrated allergen challenges in ASA-treated allergic individuals. Registry data indicated an increased risk for severe anaphylaxis in patients with ASA comedication. ASA pretreatment aggravated allergen-dependent anaphylaxis in mice, whereas histamine-induced anaphylaxis remained unaffected. Exacerbation was due to reduced PGE2, as its stabilization or the use of prostanoid E receptor (EP) agonists reversed the proanaphylactic effects of ASA. EP2-, EP3-, and EP4 receptor-deficient mice revealed that each receptor individually contributed to ASA susceptibility. In patients with allergy, prior ASA intake increased skin responsiveness to allergen but not to histamine. Conversely, the responses of basophils to ex vivo FcεRI aggregation remained unaltered, indicating that ASA operated by enhancing the stimulability of mast cells in a PGE2-dependent manner. Collectively, our data reveal a central role of the PGE2 network in ASA-aggravated anaphylaxis. EP receptors could be potential targets to prevent or alter the outcome of anaphylaxis.

Development of a novel rat long-bone nonunion model and efficacy evaluation of a prostaglandin EP4 selective agonist (AKDS001) combined with iliac bone grafting.

Nonunion occurs when a fracture fails to heal permanently, often necessitating surgical intervention to stimulate the bone healing response. Current animal models of long-bone nonunion do not adequately replicate human pathological conditions. This study was intended as a preliminary investigation of a novel rat nonunion model using a two-stage surgical intervention, and to evaluate the efficacy of a selective prostaglandin E2 receptor 4 agonist (AKDS001) as a novel nonunion therapeutic agent compared with existing treatments. Initially, Sprague-Dawley rats underwent intramedullary Kirschner wire (K-wire) fixation of a femoral fracture with the interposition of a 2 mm-thick silicon disc. After three weeks, the silicon disc was removed, and the intramedullary K-wire was replaced with plate fixation while maintaining the 2 mm defect. Contrary to the control group (1) that received no treatment, the following therapeutic interventions were performed at injury sites after freshening: (2) freshening group: no grafting; (3) iliac bone (IB) group: IB grafting; (4) AKDS group: AKDS001-loaded microspheres (MS) combined with IB (0.75 mg/ml); and (5) bone morphogenetic protein (BMP) group: grafting of a BMP-2-loaded collagen sponge (10 μg; 0.10 mg/ml). After six weeks, micro-CT (μCT) and histological analysis was performed. In the control group, the radiological union rate was 0%, and histological findings showed that fracture sites comprised fibrous scar tissue, resembling the histology of human nonunion. The union rates in the freshening, IB, AKDS, and BMP groups were 16.7%, 0%, 62.5%, and 50.0%, respectively. The AKDS group demonstrated a significantly higher union rate than the IB group (p = 0.026). μCT and histological analysis indicated that the quality of newly formed bone was superior in the AKDS group than in the BMP group. We developed a novel long-bone nonunion model. The co-therapy of AKDS001-MS and IB grafting presents a promising new treatment for nonunion.

TissueGene-C induces anti-inflammatory activity and M2 macrophage polarization via activation of prostaglandin E2 signaling

TissueGene-C induces anti-inflammatory activity and M2 macrophage polarization via activation of prostaglandin E2 signaling

Inducing phospholipase A2 and cyclooxygenase-2 expression and prostaglandins' production of human dental pulp cells by activation of NOD receptor and its downstream signaling.

Inducing phospholipase A2 and cyclooxygenase-2 expression and prostaglandins' production of human dental pulp cells by activation of NOD receptor and its downstream signaling.

Molecular docking of flavonoids from Phaleria macrocarpa on the NF-kB p65, VEGFR2, Ki67, COX-2, and CXCR4 pathways in endometriosis

Context: Endometriosis is a condition marked by the presence of endometrial epithelium and stromal cells outside the uterus. Previous studies have shown that prostaglandin E2 has a role in the development of endometriosis via the action of local estrogen and estrogen receptors. Aims: To analyze the molecular docking between Phaleria macrocarpa flavonoid compounds in the NF-B, VEGF/VEGFR2, Ki67, COX-2, and CXCR4 pathways that are involved in the pathomechanism of endometriosis. Methods: Functional determination of Phaleria macrocarpa phytochemistry using PASS prediction ADMETSAR's prediction of Phaleria macrocarpa's flavonoids compounds meet the Lipinski rule criteria so that they are predicted to have drug-likeness and no toxicity. Phaleria macrocarpa flavonoids were synthesized using AutoDock Tools 1.5.7 software. AutoDock Vina v1.2.3 software was used to perform docking simulations of ligands and target proteins. The results of the docking analysis were visualized with the Discovery Studio 4.1 application. Results: For the NF-B pathway, the compounds that showed the highest affinity for interaction to occur were (±)-naringenin (target of NF-B p50/p65) and (-)-8-prenylnaringenin (the ATP-binding site in IKK). Against VEGF-A and VEGFR2, the flavonoids that exhibited the highest interaction affinity were glycitin, and (-)-8-prenylnaringenin, respectively. The compound that interacted most easily with Ki67, COX-2, or CXCR4 was (+)-catechin 7-O-beta-D-xyloside. For docking with standard drugs, we found that leuprolide acetate and dienogest showed higher affinity for NF-B p50/p65 heterodimer than flavonoids. Conclusions: The six compounds Phaleria macrocarpa have different affinities for selected pathways in endometriosis. Thus, the Phaleria macrocarpa flavonoids could be a multi-action herbal candidate for endometriosis, which can be used alone or as a complement to standard drugs.

Buprenorphine induces human fetal membrane sterile inflammation.

Buprenorphine induces human fetal membrane sterile inflammation.