Experimental Study on the Role of 5-Ht2 Serotonin Receptors in the Mechanism of Anti-Inflammatory and Antihyperalgesic Action of Antidepressant Fluoxetine

ABSTRACT INTRODUCTION: Fluoxetine is an antidepressant that has anti-inflammatory and antihyperalgesic effects in experimental models of pain and inflammation. The AIM of the present study was to determine the role of 5-HT2 receptors in the mechanism of anti-inflammatory and antihyperalgesic action of fluoxetine after single and repeated administration of the drug. MATERIALS AND METHODS: 40 male Wistar rats were randomly divided in five groups (n = 8) treated for 14 days with saline (control), diclofenac (positive control), fluoxetine, cyproheptadine (5-HT2 antagonist), and fluoxetine + cyproheptadine, respectively. We used the experimental model of inflammation induced by intraplantar injection of carrageenan and nociceptive test with mechanical pressure on the inflamed hind paw. RESULTS: Single and repeated administration of fluoxetine showed that it had significant anti-inflammatory and antihyperalgesic effects when compared with the control (p < 0.05). Cyproheptadine did not change significantly the anti-inflammatory effect of fluoxetine in the first 4 hours, after a single administration. At 24 hours the combination did not differ statistically when compared with the control. Cyproheptadin did not change significantly the anti-inflammatory effect of fluoxetine after repeated administration. After prolonged treatment the group that received fluoxetine + cyproheptadine showed a statistically significant increase in paw pressure to withdraw the hind paw compared with that treated with fluoxetine alone (p < 0.05). CONCLUSIONS: Fluoxetine has anti-inflammatory and antihyperalgesic effects in the carrageenan model of inflammation. 5-HT2 receptor mediated its anti-inflammatory effect in single dose treated animals. Spinal 5-HT2 receptors are involved in the antihyperalgesic effect of fluoxetine after repeated administration

Download Full-text

Anti-inflammatory Effect of Picrorhiza kurroa in Experimental Models of Inflammation

Planta Medica ◽

10.1055/s-0042-106304 ◽

2016 ◽

Vol 82 (16) ◽

pp. 1403-1409 ◽

Cited By ~ 13

Author(s):

Rohit Kumar ◽

Yogendra Gupta ◽

Surender Singh ◽

Arun Raj

Keyword(s):

Experimental Models ◽

Picrorhiza Kurroa ◽

Anti Inflammatory ◽

Inflammatory Effect

Download Full-text

Neuroactive steroids, their metabolites, and neuroinflammation

Journal of Molecular Endocrinology ◽

10.1530/jme-12-0127 ◽

2012 ◽

Vol 49 (3) ◽

pp. R125-R134 ◽

Cited By ~ 49

Author(s):

Silvia Giatti ◽

Mariaserena Boraso ◽

Roberto Cosimo Melcangi ◽

Barbara Viviani

Keyword(s):

Nervous System ◽

Biomedical Research ◽

Experimental Models ◽

Neuroactive Steroids ◽

Steroid Metabolism ◽

Neuroactive Steroid ◽

Neuroprotective Strategy ◽

Testosterone Metabolites ◽

Inflammatory Effect

Neuroinflammation represents a common feature of many neurodegenerative diseases implicated both in their onset and progression. Neuroactive steroids act as physiological regulators and protective agents in the nervous system. Therefore, the attention of biomedical research has been recently addressed in evaluating whether neuroactive steroids, such as progestagens, androgens, and estrogens may also affect neuroinflammatory pathways. Observations so far obtained suggest a general anti-inflammatory effect with a beneficial relapse on several neurodegenerative experimental models, thus confirming the potentiality of a neuroprotective strategy based on neuroactive steroids. In this scenario, neuroactive steroid metabolism and the sophisticated machinery involved in their signaling are becoming especially attractive. In particular, because metabolism of neuroactive steroids as well as expression of their receptors is affected during the course of neurodegenerative events, a crucial role of progesterone and testosterone metabolites in modulating neuroinflammation and neurodegeneration may be proposed. In the present review, we will address this issue, providing evidence supporting the hypothesis that the efficacy of neuroactive steroids could be improved through the use of their metabolites.

Download Full-text

Multiple Disruptions of Glial-Neuronal Networks in Epileptogenesis That Follows Prolonged Febrile Seizures

Frontiers in Neurology ◽

10.3389/fneur.2021.615802 ◽

2021 ◽

Vol 12 ◽

Author(s):

Gary P. Brennan ◽

Megan M. Garcia-Curran ◽

Katelin P. Patterson ◽

Renhao Luo ◽

Tallie Z. Baram

Keyword(s):

Neuronal Networks ◽

Day Treatment ◽

High Mobility ◽

Febrile Seizures ◽

Experimental Models ◽

Normal Brain ◽

Molecular Signaling ◽

Rat Pups ◽

Anti Inflammatory

Background and Rationale: Bi-directional neuronal-glial communication is a critical mediator of normal brain function and is disrupted in the epileptic brain. The potential role of aberrant microglia and astrocyte function during epileptogenesis is important because the mediators involved provide tangible targets for intervention and prevention of epilepsy. Glial activation is intrinsically involved in the generation of childhood febrile seizures (FS), and prolonged FS (febrile status epilepticus, FSE) antecede a proportion of adult temporal lobe epilepsy (TLE). Because TLE is often refractory to treatment and accompanied by significant memory and emotional difficulties, we probed the role of disruptions of glial-neuronal networks in the epileptogenesis that follows experimental FSE (eFSE).Methods: We performed a multi-pronged examination of neuronal-glia communication and the resulting activation of molecular signaling cascades in these cell types following eFSE in immature mice and rats. Specifically, we examined pathways involving cytokines, microRNAs, high mobility group B-1 (HMGB1) and the prostaglandin E2 signaling. We aimed to block epileptogenesis using network-specific interventions as well as via a global anti-inflammatory approach using dexamethasone.Results: (A) eFSE elicited a strong inflammatory response with rapid and sustained upregulation of pro-inflammatory cytokines. (B) Within minutes of the end of the eFSE, HMGB1 translocated from neuronal nuclei to dendrites, en route to the extracellular space and glial Toll-like receptors. Administration of an HMGB1 blocker to eFSE rat pups did not decrease expression of downstream inflammatory cascades and led to unacceptable side effects. (C) Prolonged seizure-like activity caused overall microRNA-124 (miR-124) levels to plunge in hippocampus and release of this microRNA from neurons via extra-cellular vesicles. (D) Within hours of eFSE, structural astrocyte and microglia activation was associated not only with cytokine production, but also with activation of the PGE2 cascade. However, administration of TG6-10-1, a blocker of the PGE2 receptor EP2 had little effect on spike-series provoked by eFSE. (E) In contrast to the failure of selective interventions, a 3-day treatment of eFSE–experiencing rat pups with the broad anti-inflammatory drug dexamethasone attenuated eFSE-provoked pro-epileptogenic EEG changes.Conclusions: eFSE, a provoker of TLE-like epilepsy in rodents leads to multiple and rapid disruptions of interconnected glial-neuronal networks, with a likely important role in epileptogenesis. The intricate, cell-specific and homeostatic interplays among these networks constitute a serious challenge to effective selective interventions that aim to prevent epilepsy. In contrast, a broad suppression of glial-neuronal dysfunction holds promise for mitigating FSE-induced hyperexcitability and epileptogenesis in experimental models and in humans.

Download Full-text

The Role of Simvastatin in the Therapeutic Approach of Rheumatoid Arthritis

Autoimmune Diseases ◽

10.1155/2013/326258 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Lucia Cojocaru ◽

Andrei Constantin Rusali ◽

Cristina Şuţa ◽

Anca Mihaela Rădulescu ◽

Maria Şuţa ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Cardiovascular Disease ◽

Active Rheumatoid Arthritis ◽

Therapeutic Potential ◽

Efficacy And Safety ◽

Good Safety Profile ◽

Study Support ◽

Anti Inflammatory ◽

Inflammatory Effect

The pleiotropic effects of statins, especially the anti-inflammatory and immunomodulatory ones, indicate that their therapeutic potential might extend beyond cholesterol lowering and cardiovascular disease to other inflammatory disorders such as rheumatoid arthritis. Therefore, we undertook a prospective cohort study to evaluate the efficacy and safety of simvastatin used for inflammation control in patients with rheumatoid arthritis. One hundred patients with active rheumatoid arthritis divided into two equal groups (the study one who received 20 mg/day of simvastatin in addition to prior DMARDs and the control one) were followed up over six months during three study visits. The results of the study support the fact that simvastatin at a dose of 20 mg/day has a low anti-inflammatory effect in patients with rheumatoid arthritis with a good safety profile.

Download Full-text

Machaerium hirtum (Vell.) Stellfeld Alleviates Acute Pain and Inflammation: Potential Mechanisms of Action

Biomolecules ◽

10.3390/biom10040590 ◽

2020 ◽

Vol 10 (4) ◽

pp. 590 ◽

Cited By ~ 2

Author(s):

Juliana Agostinho Lopes ◽

Vinícius Peixoto Rodrigues ◽

Marcelo Marucci Pereira Tangerina ◽

Lucia Regina Machado da Rocha ◽

Catarine Massucato Nishijima ◽

...

Keyword(s):

Transient Receptor Potential ◽

Antinociceptive Effect ◽

Folk Medicine ◽

Receptor Potential ◽

Experimental Models ◽

Transient Receptor Potential Channels ◽

Anti Inflammatory ◽

Potential Channels ◽

Inflammatory Effect

Machaerium hirtum (Vell.) Stellfeld (Fabaceae) known in Brazil as “jacaranda de espinho” or “espinheira santa nativa” is a medicinal plant commonly used in folk medicine to treat ulcers, cough and diarrhea. This study aimed to investigate the anti-inflammatory and antinociceptive effects of hydroalcoholic extracts from M. hirtum twig (HEMh) using in vivo experimental models of nociception through the involvement of transient receptor potential channels, acid-sensing ion channel (ASIC), nitrergic, opioidergic, glutamatergic, and supraspinal pathways. Our results revealed an antinociceptive effect of HEMh mediated by the opioidergic, l-arginine-nitric oxide and glutamate systems, as well as by interactions with TRPA1/ASIC channels. The anti-inflammatory effect of HEMh evaluated with a xylene-induced ear edema and by the involvement of arachidonic acid and prostaglandin E2 (PGE2) showed involvement of the COX pathway, based on observed decreases in PGE2 levels. A phytochemical investigation of the HEMh led to the isolation of α-amyrin, β-amyrin, allantoin, apigenin-7-methoxy-6-C-β-d-glucopyranoside, and apigenin-6-C-β-d-glucopyranosyl-8-C-β-d-xylopyranoside. In conclusion, the acute oral administration of HEMh inhibits the nociceptive behavioral response in animals through the nitrergic, opioid, glutamatergic pathways, and by inhibition of the TRPA1 and ASIC channels, without causing locomotor dysfunction. In addition, its anti-inflammatory effect is associated with the COX pathway and decreased PGE2 levels.

Download Full-text