Role of Prostaglandins in Pathogenesis of Dysmenorrhea and Place of Mefenamic Acid and Dicyclomine in its Management

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.

Recent development on COX-2 inhibitors as promising anti-inflammatory agents: The past 10 years

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.

The use of cyclooxygenase-2 inhibitors in depression: a narrative review of the state of evidence

Multiple lines of evidence suggest that inflammation contribute to the pathophysiology of depression. Various studies have found that patients with major depression have higher levels of pro-inflammatory cytokines like interleukin-1, interleukin-6, tumor necrosis factor-alpha and C-reactive protein. As a consequence of above findings this narrative literature review was done to look for the role of cyclooxygenase (COX)-2 inhibitors in the patients of depression. A web based search was done using the keywords like antidepressants, anti-inflammatory treatment, celecoxib, depression, neuro inflammation in well recognized databases like PubMed, Google scholar from the year 2006 to 2019 to come out with data that matches our inclusion criteria that have been pooled and critically analyzed. Although the exact mechanism remains to become elucidated the results suggest that COX-2 have beneficial role in treatment of depression and it may be used as an adjunct to the anti-depressant treatment as it may hasten the response to current treatment without any serious side effects.

COX-2 Inhibitors in Dental Pain Management / Inhibidores de la COX-2 en el Tratamiento del Dolor Dental

ABSTRACT: Pain is a major symptom in many dental procedures. Studies show consistently that pain, including dental pain, is not effectively treated; management of pain is a critical and challenging component in dentistry. Improvement and efficacy on the treatment depends on knowing which treatments are the most effective. Knowing how well an analgesic works and its associated adverse effects is fundamental to clinical decision. The aim of this review is to provide information to the dentistry field on the treatment of dental pain specifically with COX-2 inhibitors providing a useful guide to dentist on controlling pain. Therefore, nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed analgesic agents in surgical outpatients. Major limitations of NSAIDs are their gastrointestinal (GI) adverse events (perforation, ulceration, and bleeding), impairment of hemostatic function, and renal failure (with long-term therapy). A new class of NSAIDs, COX2 selective inhibitors (Coxibs), have been developed with the aim of reducing the GI adverse events of traditional NSAIDs while maintaining their effective anti-inflammatory and analgesic properties.

RESUMEN: El dolor es un síntoma principal en muchos procedimientos dentales. Los estudios demuestran consistentemente que el dolor, incluido el dolor dental, no se trata de manera efectiva; el manejo del dolor es un componente crítico y desafiante en odontología. La mejora y la eficacia en el tratamiento depende de saber qué tratamientos son los más efectivos. Saber qué tan bien funciona un analgésico y sus efectos adversos asociados es fundamental para la decisión clínica. El objetivo de esta revisión es proporcionar información al campo de la odontología sobre el tratamiento del dolor dental específicamente con los inhibidores de la COX-2, proporcionando una guía útil para el control del dolor por parte del dentista. Por lo tanto, los fármacos antiinflamatorios no esteroideos (AINE) son los agentes analgésicos más comúnmente prescritos en pacientes ambulatorios quirúrgicos. Las principales limitaciones de los AINE son los eventos adversos gastrointestinales (perforación, ulceración y hemorragia), deterioro de la función hemostática e insuficiencia renal (con terapia a largo plazo). Una nueva clase de AINE, los inhibidores selectivos de la COX-2 (Coxibs), se han desarrollado con el objetivo de reducir los eventos adversos gastrointestinales de los AINE tradicionales mientras se mantienen sus propiedades antiinflamatorias y analgésicas efectivas.

Docking studies on xanthones of mangosteen as cox-2 inhibitors.

The prostaglandins found in most of the tissues and organs are synthesized by sequential oxidation of cyclooxygenases (COX-1 and COX-2). Prostaglandins synthesized by COX-1 are responsible for the protection of gastrointestinal tract and by COX-2 are responsible for inflammation and pain. The objective of this investigation was to characterize and determine the effect of α-mangostin, β-mangostin and γ-mangostin on COX-1 and COX-2. We have carried out the docking of α, β and γ-mangostin inhibitors into the three dimensional structure of COX-1 and COX-2 enzymes using GOLD software. The inhibitor binding positions and affinity were evaluated using GOLD scoring fitness functions. We identified that amino acid residues Leu52, Arg49, Val33 in COX-1 and Ala18, Ser23, Asp38, Cys22 in COX-2 are important for inhibitor recognition via hydrogen bonding interactions. These hydrogen bonding interactions play an important role for stability of the complex. This information can be exploited to design Mangostin based inhibitors. Our results may be helpful for further experimental investigations.

Effects of extracts, flavonoids and iridoids from Penstemon gentianoides (Plantaginaceae) on inhibition of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) in LPS-Activated RAW 264.7 macrophage cells and their antioxidant activity / Efectos de extractos, flavonoides e iridoides de Penstemon gentianoides (Plantaginaceae) sobre la inhibición de oxido nitrico sintasa inducible (iNOS), ciclooxigenasa-2 (COX-2) celulas de macrofagos murinos RAW 264.7 activadas con LPS y sus actividades antioxidantes

Penstemon gentianoides (HBK) (Kunth) Poir (Plantaginaceae) is an evergreen shrub that grows the throughout high mountains from Guatemala, Mexico and Southern states of US. Its leaves and roots have been used therapeutically for inflammation-related conditions from Aztec times, but systematic studies of its anti-inflammatory activity are lacking and no specific active components have been identified. In this study, methanol, n-hexane, CH2Cl2, ethyl acetate and methanol/water (6:4) extracts, luteolin, diosmetin, verbascoside, martynoside, pensteminoside, globularisicin and plantarenaloside isolated from this plant were evaluated by determining their inhibitory effects on the production of proinflammatory mediators in lipopolysaccharide (LPS)-activated RAW 264.7 murine macrophage cells. Ethyl acetate extract, luteolin, and diosmetin exhibited potent anti-inflammatory and antioxidant activities. The results indicated that luteolin and diosmetin suppressed the LPS induced production of nitric oxide (NO), through the down-regulation of inducible nitric oxide synthases (iNOS) and cyclo-oxygenase 2 (COX-2) protein expressions and showed a potent antioxidant activity against DPPH, TBARS and DCFH. The inhibition of enzymes and NO production by selected extracts and compounds was dose-dependent with significant effects seen at concentration as low as 50 ìM. Thus, luteolin and diosmetin may provide a potential therapeutic approach for inflammation associated disorders.

Penstemon gentianoides (HBK) (Kunth) Poir (Plantaginaceae) es un arbusto perenne que crece a lo largo de las montañas altas de Guatemala, México y los estados del sur de los EE.UU.. Sus hojas y raíces se han utilizado terapéuticamente para afecciones relacionadas con inflamación desde la época de los aztecas, pero no existen estudios sistemáticos de su actividad anti-inflamatoria y ninguno de los metabolitos activos específicos han sido identificados. En este estudio, los extractos de metanol, n-hexano, CH2Cl2, acetato de etilo y metanol/agua (6:4), junto con, luteolina, diosmetina, verbascósido, martynoside, pensteminoside, globularisicin y plantarenaloside, aislados desde esta planta se evaluaron mediante la determinación de sus efectos inhibitorios sobre la producción de mediadores proinflamatorios en macrófagos murinos activados con lipopolisacárido (LPS)-RAW 264,7. El extracto de acetato de etilo, luteolina y diosmetina exhibieron una potente actividad anti-inflamatoria y antioxidante. Los resultados indican que luteolina y diosmetina suprimen la producción de óxido nítrico (NO), a través de la regulación de óxido nítrico sintasa-inducible (iNOS) y la ciclooxigenasa-2 (COX-2) ambas expresiones de proteínas. Ademas mostró una potente actividad antioxidante contra DPPH, TBARS y DCFH. La inhibición de las enzimas y la producción de NO por los extractos seleccionados y compuestos es dependiente de la dosis con efectos significativos visto en una concentración tan baja como 50 mM. Por lo tanto, luteolina y diosmetina puede proporcionar un enfoque terapéutico potencial para transtornos asociados a los procesos de inflamación.