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.

Effect of esophagus distention on urinary bladder function in rats.

AIMS: Micturition process is a spinobulbospinal reflex that is affected by the viscero-visceral interactions due to convergent inputs into spinal and/or supraspinal centers controlling that reflex. Although interaction between bladder and other pelvic organs, such as colon, are well studied, the viscero-visceral interaction between urinary bladder and internal organs in other regions are rarely studied. METHODS: In the present study, continuous filling cystometry recordings, in male rats, were used to investigate the effects of mechanical stimulation of distal-esophagus (distention), as well as, electrical stimulation of abdominal branches of the vagus nerve on urinary bladder micturition cycles. RESULTS: Distal esophagus distention and electrical stimulation of the vagus nerve significantly increased the micturition frequency through decreasing the time of the storage phase of the micturition cycle. However, bilateral cervical vagotomy eliminated the effects of distal esophagus distention and electrical stimulation of vagus nerve on micturition cycles. CONCLUSIONS: The results of this study indicate that there is a viscero-visceral interaction between esophagus and urinary bladder, which is mediated through vagal afferents. Understanding the properties of the viscero-visceral interactions affecting the urinary bladder will help in the diagnosis and management of micturition problems.

Short-term synaptic plasticity at the main and vomeronasal olfactory receptor to mitral cell synapse in frog.

Synaptic responses resulting from stimulation of the main olfactory and vomeronasal (VN) nerves were measured in main and accessory olfactory bulb (AOB) of frog, Rana pipiens, to test the hypothesis that properties of these synapses would reflect the distinct differences in the time course of odour delivery to each of these olfactory structures. Paired-pulse depression dominated responses to repetitive stimulation of the main olfactory nerve for interstimulus intervals (ISI) up to several seconds. Inhibition of voltage-gated Ca(2+) channels by GABAb receptors contributes significantly to this inhibition of transmitter release, particularly for ISI > 0.5 s. In contrast, the monosynaptic connection between VN sensory neurons and mitral cells in the AOB showed enhancement with pairs or short trains of stimuli for ISI of 0.5 to > 10 s. A small inhibitory effect of GABAb receptors on presynaptic Ca(2+) influx and release was only evident when a large proportion of the VN axons were stimulated simultaneously but even with inhibition present an overall enhancement of release was observed. Increasing the number of conditioning stimuli from one to five increased residual [Ca(2+)] and enhancement but a direct correlation between residual [Ca(2+)] and either the magnitude or the time course of enhancement was not observed. Enhanced transmitter release from VN afferent terminals results in effective integration of sustained low-frequency activity, which may play a role in the detection of low-intensity odourant stimuli by the VN system.