Analgesic effect of the flavonoid herbacetin in nociception animal models.

OBJECTIVE: This study aimed to assess the antinociceptive activity of herbacetin using chemically and thermally induced nociception in a mouse model. MATERIALS AND METHODS: The antinociceptive effects of various herbacetin doses (50, 100, 150, and 200 µg/kg) were assessed in mice using the acetic acid-induced writhing test, hot plate test, and formalin-induced paw-licking assay. The effects were compared to those of mice treated with acetylsalicylic acid or morphine in the presence or absence of naloxone (an opioid receptor antagonist). Capsaicin- and glutamate-induced paw-licking tests were also used to evaluate the involvement of the vanilloid and glutamatergic systems, respectively. Pro-inflammatory mediators: Interleukin-1-beta (IL-1ß), Tumour Necrosis Factor alpha (TNF-α), Interferon-gamma (IFN-γ), and Nitric Oxide (NO) were also assessed. RESULTS: Herbacetin produced significant dose-dependent inhibition of nociceptive behavior in the acetic acid-induced writhing test, showing 65% inhibition at a dose of 200 µg/kg. Herbacetin also caused a significant increase in the latency period in response to the hot plate test (70% at 200 µg/kg), and significantly inhibited both the neurogenic and inflammatory phases in the formalin-induced paw-licking test. Naloxone significantly reverses the effect of herbacetin in both the hot plate and formalin-induced paw-licking test. Moreover, herbacetin significantly inhibited the neurogenic nociception induced by intraplantar injections of capsaicin and glutamate (75% and 48%, respectively, at a dose of 200 µg/kg). Pro-inflammatory cytokines IL-1ß, TNF-α, IFN-γ, and NO in the serum of mice were assessed. These cytokines were significantly inhibited by herbacetin (100 and 200  µg/kg). Thus, herbacetin exhibited peripheral and central antinociception through the modulation of vanilloid receptors, opioid receptors, and the glutamatergic system. CONCLUSIONS: Herbacetin possesses antinociceptive activity in adult mice that is mediated through both central and peripheral pathways.

Effects of orally administered Thymus vulgaris leaves on memory, anxiety, depression, and sleep quality in university students: a randomized controlled trial.

OBJECTIVE: The aim of this study was to evaluate the effects of orally administering Thymus vulgaris leaves on memory performance, anxiety, depression, and sleep quality in a sample of university students. PATIENTS AND METHODS: This randomized controlled trial included 106 students who were randomly assigned to one of two groups. The first group received 500 mg of Thymus vulgaris leaves twice daily, while the second group received a placebo. The intervention period lasted for one month. The participants' memory performance (both prospective and retrospective), levels of anxiety and depression, and sleep quality were assessed using the Prospective and Retrospective Memory Questionnaire (PRMQ), Hospital Anxiety and Depression Scale (HADS), and Pittsburgh Sleep Quality Inventory (PSQI) at the beginning of the study and after one month. RESULTS: The findings revealed significant reductions in the scores of all scales and subscales, with the exception of the sleep latency and sleep duration components of the Pittsburgh Sleep Quality Inventory, among the group that received Thymus vulgaris leaves in comparison to the control group. CONCLUSIONS: Thymus vulgaris leaves, a traditional food source, demonstrate potential for enhancing both prospective and retrospective memory, alleviating anxiety and depression, and improving sleep quality in university students.

Exploring the therapeutic potential of fisetin: a comprehensive study on its anti-nociceptive and anti-inflammatory effects.

OBJECTIVE: This study's primary objective was to explore and validate the pain-relieving and inflammation-reducing properties of fisetin, a flavonoid known for its antioxidant benefits, using different mouse models. MATERIALS AND METHODS: We assessed fisetin's pain-relieving effects using mouse models exposed to both heat-induced and chemical-induced pain. The inflammation-reducing capacity of fisetin was evaluated using the carrageenan-triggered paw swelling test, focusing on the influx of leukocytes in the peritoneal space. The air pouch test was utilized to determine fisetin's ability to counteract proinflammatory cytokines. The performance of fisetin, when paired with opioid blockers, was analyzed, and juxtaposed with results from conventional medicines. The muscle-relaxing potential of fisetin was assessed through the open field assessment. RESULTS: Fisetin consistently demonstrated marked anti-inflammatory actions across various models. It also proved to be effective in reducing pain in the pain-induced models. When combined with opioid blockers, fisetin's effects were on par with those of traditional medications. Noteworthily, fisetin displayed muscle-relaxing properties in the open-field assessment. CONCLUSIONS: The compiled data showcases fisetin as a powerful anti-inflammatory agent with significant pain-relieving capacities, positioning it as a promising contender for pain treatment modalities.

The association between fingolimod and mental health outcomes in a cohort of Multiple Sclerosis patients with stress.

OBJECTIVE: The primary objective was to study the association between fingolimod and the frequency of depression, anxiety, and insomnia symptoms among a cohort of Multiple Sclerosis (MS) patients with stress. The secondary objective was to examine the association between patient characteristics and these psychiatric symptoms. PATIENTS AND METHODS: Patients with MS and stress were recruited according to the Arabic version of the Perceived Stress Scale (PSS). Psychiatric outcomes were measured by validated scales. Logistic regression was used to estimate adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Data from 324 participants were analyzed. RESULTS: Fingolimod was associated with a significantly lower adjusted odds ratio for depression (aOR 0.58, 95% CI 0.35-0.97, p<0.05) but less associated with anxiety (aOR 0.63, 95% CI 0.35-1.01, p=0.05) and insomnia (aOR 0.88, 95% CI 0.52-1.51, p=0.64). CONCLUSIONS: Close monitoring of mental health is required for patients with MS using disease-modifying therapies.

Oxidative stress and inflammation in COVID-19: potential application OF GLP-1 receptor agonists.

COVID-19 is a global pandemic with devastating economic and public health impacts, which is particularly associated with increased incidence of respiratory and cardiovascular disease together with inflammation and oxidative stress as essential underlying features. Glucagon-Like Peptide-1 (GLP-1) receptor agonists are now routinely used for the clinical management of type 2 diabetes due to their established glucose-dependent insulinotropic actions. However, these agents also display a variety of pleiotropic functions, including the promotion of anti-inflammatory and antioxidant responses, highlighting likely therapeutic applications beyond glycemic control. Given that COVID-19 is particularly linked with adverse modulation of inflammatory and oxidative signaling, which are known to be impacted by GLP-1 receptor activation, it seems logical that GLP-1 receptor agonists may be beneficial for the clinical management of patients with SARS-CoV-2 infection. In this review, we discuss the specific role of inflammation and oxidative stress associated with COVID-19, including underlying pathogenic mechanisms, as the basis for the potential therapeutic application of GLP-1 receptor agonists to combat both acute and chronic complications of this devastating disease.

Phylogenetic analysis and genetic similarities of Phyllidia spp. by comparing the nucleotide sequence of 16S rRNA and cytochrome c genes.

Phyllidiid nudibranchs are brightly colored gastropod molluscs, frequently encountered in coral reefs of the tropical Indo-Pacific. This study aimed to identify the phylogenetic similarities among the Phyllidia spp. The phylogenetic similarities among all the available Phyllidia spp. were studied by comparing the nucleotide sequence of 16s rRNA and cytochrome c genes (cox I). Sequences were retrieved from NCBI databases and aligned by using Geneious software. A phylogenetic tree was constructed for the retrieved sequences of Phyllidia spp. by using the neighbor-joining method on MEGA software and the pairwise distances were also calculated. The similarities among nucleotide sequences of 16s rRNA showed that the P. elegans, and P. haegeli had the highest similarities (99.92%) and the lowest similarities (99.14%) among P. haegeli and P. picta. While nucleotide sequences of cox I showed the highest similarities (99.90%) between P. elegans and P. ocellata, and the P. varicosa had the lowest similarities 99.74% with P. koehleri and P. larryi. The molecular phylogenetic analysis based on mitochondrial marker indicated a close relation between P. elegans and P. alyta in both cox I and 16s rRNA phylogenetic tree. The phylogenetic tree of 16s rRNA gene shows the P. ocellata is closely related to the clade of species P. exquisita. The available phylogenetic analysis could be useful in further studies of Phyllidiidae within Nudibranchia.

Progesterone inhibitory role on gastrointestinal motility.

Progesterone is a steroidal hormone that is produced from the corpus luteum of the ovaries and from the placenta. The main function of progesterone is to promote the secretory differentiation in the endometrium of the uterus and to maintain pregnancy by inhibiting uterine contractions throughout pregnancy. Progesterone performs its actions by activating the classical progesterone nuclear receptors that affect gene transcription and by the non-classical activation of cell surface membrane receptors that accounts for the rapid actions of progesterone. Besides the reproductive roles of progesterone, it exerts functions in many tissues and systems such as the nervous system, the bone, the vascular system, and the gastrointestinal (GI) tract. This review will summarize the recent literature that investigated the role of progesterone in GI tract motility. Most literature indicates that progesterone exerts an inhibitory role on gut smooth muscle cells in part by elevating nitric oxide synthesis which induces relaxation in smooth muscle. Moreover, progesterone inhibits the signaling pathways that lead to contraction such as Rho kinase inhibition. These data serve as a quick resource for the future directions of progesterone research that could lead to better understanding and more effective treatment of gender-related GI tract motility disorders.

Risk of pre-eclampsia in women taking metformin: a systematic review and meta-analysis.

AIMS: To perform meta-analyses of studies evaluating the risk of pre-eclampsia in high-risk insulin-resistant women taking metformin prior to, or during pregnancy. METHODS: A search was conducted of the Medline, EMBASE, Web of Science and Scopus databases. Both randomized controlled trials and prospective observational cohort studies of metformin treatment vs. placebo/control or insulin either prior to or during pregnancy were selected. The main outcome measure was the incidence of pre-eclampsia in each treatment group. RESULTS: Overall, in five randomized controlled trials comparing metformin treatment (n = 611) with placebo/control (n = 609), no difference in the risk of pre-eclampsia was found [combined/pooled risk ratio (RR), 0.86 (95% CI 0.33-2.26); P = 0.76; I2  = 66%]. Meta-analysis of four cohort studies again showed no significant effect [RR, 1.21 (95% CI 0.56-2.61); P = 0.62; I2  = 30%]. A meta-analysis of eight randomized controlled trials comparing metformin (n = 838) with insulin (n = 836), however, showed a reduced risk of pre-eclampsia with metformin [RR, 0.68 (95% CI 0.48-0.95); P = 0.02; I2  = 0%]. No heterogeneity was present in the metformin vs. insulin analysis of randomized controlled trials, whereas high levels of heterogeneity were present in studies comparing metformin with placebo/control. Pre-eclampsia was a secondary outcome in most of the studies. The mean weight gain from time of enrolment to delivery was lower in the metformin group (P = 0.05, metformin vs. placebo; P = 0.004, metformin vs. insulin). CONCLUSIONS: In studies randomizing pregnant women to glucose-lowering therapy, metformin was associated with lower gestational weight gain and a lower risk of pre-eclampsia compared with insulin.