Therapeutic potential of a novel pyrazolyl-pyridine derivative in the treatment of experimental colitis.

Aim: Investigating a novel compound, DMPNP, for treating colitis in mice, a key issue in inflammatory bowel diseases (IBD). Methods: Mice with induced colitis received DMPNP (50, 100, 150 mg/kg) or sulfasalazine (SUL), evaluated via tissue assessment, Disease Activity Index (DAI), myeloperoxidase (MPO), nitric oxide (NO) levels and cytokine analysis. Results: DMPNP significantly reduced colitis symptoms, inflammation and oxidative stress at higher doses, with marked improvements in DAI, MPO, NO and cytokines, comparable to SUL results. Conclusion: DMPNP shows potent anti-inflammatory and immunomodulatory properties, indicating potential as an IBD therapeutic. Further clinical trials are suggested to validate these outcomes.

This article focuses on a study testing a new compound, DMPNP, for treating colitis, a challenging aspect of inflammatory bowel disease (IBD). The researchers aimed to determine if DMPNP could alleviate colitis symptoms and serve as an effective treatment option.The study involved mice with induced colitis symptoms, treated with different doses of DMPNP (50, 100, 150 mg/kg). For comparison, another group received sulfasalazine (SUL), a standard IBD medication. The evaluation focused on colon tissue health, disease severity through the Disease Activity Index (DAI) and levels of myeloperoxidase (MPO) and nitric oxide (NO), which are markers of inflammation and oxidative stress. Additionally, the effect of DMPNP on immune cell production and inflammatory gene expression was assessed.The results were encouraging. Mice treated with DMPNP showed significant improvements, particularly at higher doses. Symptoms like inflammation, tissue damage and ulceration in the colon reduced noticeably. The DAI scores, indicative of colitis severity, were substantially lower in the DMPNP group, suggesting reduced disease intensity. Also, decreases in MPO and NO levels indicated less oxidative stress and inflammation. The compound also mirrored sulfasalazine's effects in reducing inflammatory cell and gene production.These findings are crucial as they indicate DMPNP's potential as a new treatment for colitis and possibly other IBD forms. Its effectiveness in reducing inflammation and regulating the immune response, akin to existing treatments but possibly with different advantages, highlights its promise. The study paves the way for more in-depth research and eventual human trials to confirm DMPNP's safety and efficacy in IBD treatment.

"PTSD symptoms among patients with multiple sclerosis in Jordan during October 7th gaza war outbreak".

OBJECTIVE: Clinicians have noted that the ongoing war on Gaza has had a psychological impact on people with multiple sclerosis (PwMS) whose mental health is particularly vulnerable during times such as these. The present study sought to examine the prevalence and correlates of posttraumatic stress disorder (PTSD) symptoms among PwMS in Jordan during the Gaza war outbreak. METHODS: This was a cross-sectional study involving 171 patients (PwMS) out of 372 patients approached (46% response rate) who were being seen in the MS unit at Al Bashir Hospital, Ammann, Jordan. Inclusion criteria required that participants had been following daily news updates of the October 7 war in Gaza for the past 4 months. RESULTS: Of participants, 125 (73.1%) were female, 98 (57.3%) were on therapy for less than five years, and 30 (17.5%) reported having a relapse during the past 6 months. Significant PTSD symptoms were identified in 58.5% (100 of 171 participants). Those at higher risk were the unemployed (OR = 2.14, 95% CI = 1.13-4.07, P = 0.02), whereas patients receiving dimethyl fumarate (19.9%) were at lower risk (OR = 0.43, 95% CI = 0.19-0.94, P = 0.02). CONCLUSION: The high rate of significant PTSD symptoms among people with MS in this study underscores the need for attention by primary care providers and implementation of a comprehensive multidisciplinary approach to optimize the mental well-being of this fragile population.

Menstrual pain self-medication relates to poor mental health outcomes from Al-Zaatri refugees' camp.

Dysmenorrhea, the most common gynecological pain syndrome reported in women, is understudied in refugee communities. In addition, the association between dysmenorrhea self-medication and mental health symptoms in this population is poorly understood. We aimed to examine whether the use of dysmenorrhea analgesic self-medications and other clinical factors are associated with post-traumatic stress disorder (PTSD), depression, anxiety and insomnia severity in female war refugees residing in Zaatari Camp. This study followed a cross-sectional design and was performed on a cohort of women with predefined inclusion criteria. The severity of PTSD, depression, anxiety and insomnia were assessed using Davidson Trauma Scale, the Patient Health Questionnaire-9, the General Anxiety Disorder-7, and the Arabic version of the Insomnia Severity Index, respectively. Data were analysed from 386 participants. Using OTC paracetamol was significantly associated with higher PTSD severity (B=4.16, t= 2.43, p=0.01), and severe depression (OR=1.88, 95% CI= 1.07-3.28, p=0.03), while OTC non-steroidal anti-inflammatory drugs (NSAIDs) was significantly associated with severe insomnia (OR=1.62, 95% CI= 1.05-2.49, p= 0.02). In conclusion, self-medication with analgesics was correlated with poor mental health; close medical and psychiatric follow-up are required to supervise pain self-medication and implement non-pharmacological strategies to manage dysmenorrhea in this fragile community.

La dysménorrhée, le syndrome douloureux gynécologique le plus fréquemment signalé chez les femmes, est peu étudiée dans les communautés de réfugiés. De plus, l'association entre l'automédication de la dysménorrhée et les symptômes de santé mentale dans cette population est mal comprise. Nous avions pour objectif d'examiner si l'utilisation d'automédicaments analgésiques contre la dysménorrhée et d'autres facteurs cliniques sont associés au trouble de stress post-traumatique (SSPT), à la dépression, à l'anxiété et à la gravité de l'insomnie chez les réfugiées de guerre résidant dans le camp de Zaatari. Cette étude a suivi une conception transversale et a été réalisée sur une cohorte de femmes avec des critères d'inclusion prédéfinis. La gravité du SSPT, de la dépression, de l'anxiété et de l'insomnie a été évaluée à l'aide de l'échelle de traumatisme de Davidson, du questionnaire sur la santé du patient-9, du trouble d'anxiété général-7 et de la version arabe de l'indice de gravité de l'insomnie, respectivement. Les données ont été analysées auprès de 386 participants. L'utilisation de paracétamol en vente libre était significativement associée à une gravité plus élevée du SSPT (B = 4,16, t = 2,43, p = 0,01) et à une dépression sévère (OR = 1,88, IC à 95 % = 1,07-3,28, p = 0,03), tandis que les médicaments non stéroïdiens en vente libre les anti-inflammatoires (AINS) étaient associés de manière significative à l'insomnie sévère (OR = 1,62, IC à 95 % = 1,05-2,49, p = 0,02). En conclusion, l'automédication avec des analgésiques était corrélée à une mauvaise santé mentale ; un suivi médical et psychiatrique étroit est nécessaire pour encadrer l'automédication de la douleur et mettre en œuvre des stratégies non pharmacologiques pour prendre en charge la dysménorrhée dans cette communauté fragile.

Exploring Scopoletin's Therapeutic Efficacy in DSS-Induced Ulcerative Colitis: Insights into Inflammatory Pathways, Immune Modulation, and Microbial Dynamics.

This study aimed to investigate the therapeutic potential of scopoletin in ulcerative colitis, with a primary focus on its impact on crucial inflammatory pathways and immune responses. A male mouse model of DSS-induced colitis was employed with six distinct groups: a control group, a group subjected to DSS only, three groups treated with varying scopoletin doses, and the final group treated with dexamethasone. The investigation included an assessment of the effects of scopoletin on colitis symptoms, including alterations in body weight, Disease Activity Index (DAI), and histopathological changes in colonic tissue. Furthermore, this study scrutinized the influence of scopoletin on cytokine production, PPARγ and NF-κB expression, NLRP3 inflammasome, and the composition of intestinal bacteria. Scopoletin treatment yielded noteworthy improvements in DSS-induced colitis in mice, as evidenced by reduced weight loss and colonic shortening (p < 0.05, < 0.01, respectively). It effectively diminished TNF-α, IL-1ß, and IL-12 cytokine levels (p < 0.01, p < 0.05), attenuated NLRP3 inflammasome activation and the associated cytokine release (p < 0.05, p < 0.01), and modulated the immune response by elevating PPARγ expression while suppressing NF-κB pathway activation (p < 0.05, p < 0.01). Additionally, scopoletin induced alterations in the gut microbiota composition, augmenting beneficial Lactobacillus and Bifidobacteria while reducing E. coli (p < 0.05). It also enhanced tight junction proteins, signifying an improvement in the intestinal barrier integrity (p < 0.05, < 0.01). Scopoletin is a promising therapeutic agent for managing ulcerative colitis, showing benefits that extend beyond mere anti-inflammatory actions to encompass regulatory effects on gut microbiota and restoration of intestinal integrity.

Scopoletin mitigates maternal separation-induced anxiety-like and depression-like behaviors in male mice through modulation of the Sirt1/NF-κB pathway.

RATIONALE: Early-life maternal separation can lead to anxiety-like and depression-like behaviors in mice reared under maternal separation conditions. Scopoletin, a compound with anti-inflammatory and antidepressant properties, may offer therapeutic benefits, but its effectiveness against behaviors induced by maternal separation during adulthood remains unexplored. OBJECTIVES: This study investigates scopoletin's efficacy in alleviating anxiety-like and depression-like phenotypes in male mice subjected to early-life maternal separation. METHODS: Male C57BL/6J mice experienced daily maternal separation for 4 h from postnatal day (PND) 2 to 21. From postnatal day 61(PND 61), scopoletin was administered intraperitoneally at 20 mg/kg/day for four weeks. Behavioral and biochemical assessments were conducted at postnatal day 95 (PND 95). RESULTS: Maternally separated mice displayed marked anxiety-like and depression-like behaviors, evident in behavioral tests like the open field and elevated plus maze. These mice also showed increased immobility in the forced swimming and tail suspension tests. Biochemically, there were elevated levels of IL-1ß, IL-6, and TNF-α in the hippocampus, with a decrease in Sirt1 and upregulation in NF-κB p65 expression. Scopoletin treatment significantly mitigated these behavioral abnormalities, normalizing both anxiety-like and depression-like behaviors. Correspondingly, it reduced the levels of pro-inflammatory cytokines and reinstated the expression of Sirt1 and NF-κB p65. CONCLUSIONS: Scopoletin effectively reverses the adverse behavioral and biochemical effects induced by early-life maternal separation in male mice, suggesting its potential as a therapeutic agent for treating anxiety-like and depression-like behaviors. Modulation of neuroinflammatory pathways and the Sirt1/NF-κB signaling axis is one possible mechanism.

Mitigation of cisplatin-induced cardiotoxicity by Isorhamnetin: Mechanistic insights into oxidative stress, inflammation, and apoptosis modulation.

The flavonoid compound Isorhamnetin (IRMN) is known for its considerable pharmacological properties, which include antioxidant and anti-inflammatory effects, as well as significant protective actions on heart health. However, the potential of IRMN to guard against heart damage caused by cisplatin (CP), a common chemotherapeutic agent, and the specific mechanisms involved, remain unexplored areas. This research was designed to investigate how IRMN counters CP-induced heart toxicity. In our study, mice were orally given IRMN at 50 or 150 mg/kg/day for a week, followed by CP injections (5 mg/kg/day) on the third and sixth days. The animals were euthanized under sodium pentobarbital anesthesia (50 mg/kg, intraperitoneally) on the eighth day to collect blood and heart tissues for further examination. Our findings reveal that IRMN administration significantly reduced the heart damage and the elevation of heart injury markers such as cardiac troponin I, creatine kinase, and lactate dehydrogenase induced by CP. IRMN also effectively lowered oxidative stress markers, including reactive oxygen species and malondialdehyde, while boosting ATP production and antioxidants like superoxide dismutase, catalase, and glutathione. The compound's capability to diminish the levels of pro-inflammatory cytokines like tumor necrosis factor-alpha and interleukin-6, alongside modulating apoptosis-regulating proteins (enhancing Bcl-2 while suppressing Bax and Caspase-3 expression), further underscores its cardioprotective effect. Notably, IRMN modulated the p62-Keap1-Nrf2 signaling pathway, suggesting a mechanism through which it exerts its protective effects against CP-induced cardiac injury. These insights underscore the potential of IRMN as an effective adjunct in cancer therapy, offering a strategy to mitigate the cardiotoxic side effects of cisplatin.

Cirsimaritin Alleviates Dextran Sodium Sulfate-Induced Acute Colitis in Experimental Animals: A Therapeutic Approach for Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic disease that affects the entire digestive tract. IBD can be classified as ulcerative colitis or Crohn's disease. The key symptoms of IBD include the emergence of abscesses or pustules, pronounced abdominal discomfort, diarrhea, fistulas, and intestinal narrowing, all of which can greatly affect a patient's daily well-being. Several factors, including bacterial infections, immune response irregularities, and changes in the intestinal milieu, can contribute to the onset of IBD. The aim of this study was investigating the role of cirsimaritin in reducing the severity of colitis in animal model. To induce colitis in laboratory Swiss albino mice, a 4% dextran sulfate sodium (DSS) concoction was provided in their hydration source for a duration of six days. Before the onset of colitis, mice were treated with cirsimaritin (10 mg/kg) once daily to evaluate its potential treatment effects against DSS-induced inflammation. The results showed that 10 mg/kg of cirsimaritin decreased colitis severity (P<0.05). Moreover, cirsimaritin successfully reversed the detrimental effects induced by DSS, including weight reduction, colon truncation, tissue-related damage, increased levels of inflammatory cells in the affected region, and secretion of proinflammatory cytokines. Our findings suggest that cirsimaritin can effectively alleviate acute colitis triggered by DSS.

Are Sleep Aids Associated with the Severity of Attention Deficit Hyperactivity Disorder Symptoms in Adults Screened for Insomnia? A Cross-Sectional Study.

(1) Background: Attention Deficit Hyperactivity Disorder (ADHD)-like symptoms and insomnia are closely related. The present study examined whether the use of different sleep aids was related to severe ADHD-like symptoms in Jordanian adults screened for insomnia. (2) Methods: This cross-sectional study used predefined inclusion criteria. The severity of ADHD was assessed using the validated Arabic version of the Adult ADHD Self-Report Scale. (3) Results: Data were analyzed from 244 subjects who met the inclusion criteria for severe insomnia, of which 147 (65.3%) reported not using any sleep aid, 50 (22.3%) reported using homeopathy remedies as sleep aids, and 41 (18.3%) reported using over-the-counter antihistamines as sleep aids. Regression analysis revealed that the use of such sleep aids-namely, "homeopathy herbal remedies" and "over-the-counter antihistamines"-was not associated (p > 0.05) with ADHD-like symptoms. However, "age above 31 years old" was significantly associated (B = -3.95, t = -2.32, p = 0.002) with lower ADHD severity, while the "diagnosis with chronic diseases" was significantly associated (B = 4.15, t = 1.99, p = 0.04) with higher ADHD severity. (4) Conclusions: Sleep aids are not associated with ADHD-like symptoms in adults. More research is required to uncover the risk factors for adult ADHD, especially insomnia.

Isorhamnetin as a potential therapeutic agent for diabetes mellitus through PGK1/AKT activation.

CONTEXT: Type 2 Diabetes Mellitus (T2D) is a significant health concern worldwide, necessitating novel therapeutic approaches beyond conventional treatments. OBJECTIVE: To assess isorhamnetin's potential in improving insulin sensitivity and mitigating T2D characteristics through oxidative and glycative stress modulation. MATERIALS AND METHODS: T2D was induced in mice with a high-fat diet and streptozotocin injections. Isorhamnetin was administered at 10 mg/kg for 12 weeks. HepG2 cells were used to examine in vitro effects on stress markers and insulin sensitivity. Molecular effects on the PGK1 and AKT signalling pathway were also analyzed. RESULTS: The administration of isorhamnetin significantly impacted both in vivo and in vitro models. In HepG2 cells, oxidative and glycative stresses were markedly reduced, indicating a direct effect of isorhamnetin on cellular stress pathways, which are implicated in the deterioration of insulin sensitivity. Specifically, treated cells showed a notable decrease in markers of oxidative stress, such as malondialdehyde, and advanced glycation end products, highlighting isorhamnetin's antioxidant and antiglycative properties. In vivo, isorhamnetin-treated mice exhibited substantially lower fasting glucose levels compared to untreated T2D mice, suggesting a strong hypoglycemic effect. Moreover, these mice showed improved insulin responsiveness, evidenced by enhanced glucose tolerance and insulin tolerance tests. The molecular investigation revealed that isorhamnetin activated PGK1, leading to the activation of the AKT signalling pathway, crucial for promoting glucose uptake and reducing insulin resistance. This molecular action underscores the potential mechanism through which isorhamnetin exerts its beneficial effects in T2D management. DISCUSSION: The study underscores isorhamnetin's multifaceted role in T2D management, emphasizing its impact on oxidative and glycative stress reduction and molecular pathways critical for insulin sensitivity. CONCLUSION: Isorhamnetin presents a promising avenue for T2D treatment, offering a novel approach to enhancing insulin sensitivity and managing glucose levels through the modulation of key molecular pathways. Further research is needed to translate these findings into clinical practice.

Exploring the therapeutic potential of Anastatica hierochuntica essential oil in DSS-induced colitis.

The aim of this investigation was to explore the protective impacts and mechanisms of Anastatica hierochuntica essential oil (EOAH) against dextran sulfate sodium (DSS)-induced experimental colitis in mice. EOAH demonstrated a reduction in DSS-induced body weight decline, disease activity index (DAI), colon length reduction, colonic tissue damage, and myeloperoxidase (MPO) activity. The essential oil significantly mitigated the production of pro-inflammatory agents including TNF-α, IL-1ß, and IL-12. Further analysis revealed that EOAH's anti-inflammatory effects involved the regulation of NF-κB and PPARγ pathways, as well as the inhibition of NLRP3 activation in colitis mice. Notably, EOAH treatment elevated the levels of beneficial commensal bacteria such as Lactobacillus and Bifidobacteria, while reducing Escherichia coli levels in the mice's feces. In addition, EOAH restored the expression of occludin and ZO-1 proteins in colonic tissues affected by ulcerative colitis (UC). These findings indicate that supplementing with EOAH might offer a novel therapeutic approach for UC prevention.

Exploring the Roles of Vitamins C and D and Etifoxine in Combination with Citalopram in Depression/Anxiety Model: A Focus on ICAM-1, SIRT1 and Nitric Oxide.

The study of intercellular adhesion molecule-1 (ICAM-1) and SIRT1, a member of the sirtuin family with nitric oxide (NO), is emerging in depression and anxiety. As with all antidepressants, the efficacy is delayed and inconsistent. Ascorbic acid (AA) and vitamin D (D) showed antidepressant properties, while etifoxine (Etx), a GABAA agonist, alleviates anxiety symptoms. The present study aimed to investigate the potential augmentation of citalopram using AA, D and Etx and related the antidepressant effect to brain and serum ICAM-1, SIRT1 and NO in an animal model. BALB/c mice were divided into naive, control, citalopram, citalopram + etx, citalopram + AA, citalopram + D and citalopram + etx + AA + D for 7 days. On the 8th day, the mice were restrained for 8 h, followed by a forced swim test and marble burying test before scarification. Whole-brain and serum expression of ICAM-1, Sirt1 and NO were determined. Citalopram's antidepressant and sedative effects were potentiated by ascorbic acid, vitamin D and etifoxine alone and in combination (p < 0.05), as shown by the decreased floating time and rearing frequency. Brain NO increased significantly (p < 0.05) in depression and anxiety and was associated with an ICAM-1 increase versus naive (p < 0.05) and a Sirt1 decrease (p < 0.05) versus naive. Both ICAM-1 and Sirt1 were modulated by antidepressants through a non-NO-dependent pathway. Serum NO expression was unrelated to serum ICAM-1 and Sirt1. Brain ICAM-1, Sirt1 and NO are implicated in depression and are modulated by antidepressants.

Unraveling the potential of vitamins C and D as adjuvants in depression treatment with escitalopram in an LPS animal model.

Depression is linked with oxidative stress and inflammation, where key players include nitric oxide (NO), nuclear factor erythroid 2-related factor 2 (Nrf2), Brain-Derived Neurotrophic Factor (BDNF), and Heme Oxidase-1 (HO-1). Augmenting the efficacy of antidepressants represents a compelling avenue of exploration. We explored the potential of vitamins C and D as adjuncts to escitalopram (Esc) in a lipopolysaccharide (LPS)-induced depression model focusing on the aforementioned biomarkers. Male Swiss albino mice were stratified into distinct groups: control, LPS, LPS + Esc, LPS + Esc + Vit C, LPS + Esc + Vit D, and LPS + Esc + Vit C + Vit D. After a 7-day treatment period, a single LPS dose (2 mg/kg), was administered, followed by comprehensive assessments of behavior and biochemical parameters. Notably, a statistically significant (p < 0.05) alleviation of depressive symptoms was discerned in the Esc + Vit C + Vit D group versus the LPS group, albeit with concomitant pronounced sedation evident in all LPS-treated groups (p < 0.05). Within the cortex, LPS reduced (p < 0.05) the expression levels of NOx, Nrf2, BDNF, and HO-1, with only HO-1 being reinstated to baseline in the LPS + Esc + Vit D and the LPS + Esc + Vit C + Vit D groups. Conversely, the hippocampal NOx, Nrf2, and HO-1 levels remained unaltered following LPS administration. Notably, the combination of Esc, Vit C, and Vit D effectively restored hippocampal BDNF levels, which had been diminished by Esc alone. In conclusion, vitamins C and D enhance the therapeutic effects of escitalopram through a mechanism independent of Nrf2. These findings underscore the imperative need for in-depth investigations.

Amino acid profiles: exploring their diagnostic and pathophysiological significance in hypertension.

Hypertension, a major contributor to cardiovascular morbidity, is closely linked to amino acid metabolism. Amino acids, particularly branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs), may play pivotal roles in the pathogenesis and potential management of hypertension. This review investigated the relationships between amino acid profiles, specifically BCAAs and AAAs, and hypertension, and examined their potential as diagnostic and therapeutic targets. An in-depth analysis was conducted on studies highlighting the associations of specific amino acids such as arginine, glycine, proline, glutamine, and the BCAAs and AAAs with hypertension. BCAAs and AAAs, alongside other amino acids like arginine, glycine, and proline, showed significant correlations with hypertension. These amino acids influence multiple pathways including nitric oxide synthesis, vascular remodeling, and neurotransmitter production, among others. Distinct amino acid profiles were discerned between hypertensive and non-hypertensive individuals. Amino acid profiling, particularly the levels of BCAAs and AAAs, offers promising avenues in the diagnostic and therapeutic strategies for hypertension. Future studies are crucial to confirm these findings and to delineate amino acid-based interventions for hypertension treatment.

Unraveling the Potential of Isorhamnetin as an Adjuvant in Depression Treatment with Escitalopram.

Oxidative stress and inflammation are implicated in depression. While selective serotonin reuptake inhibitors (SSRIs) like escitalopram are commonly prescribed as first-line treatments, their inconsistent efficacy and delayed onset of action necessitates the exploration of adjunctive therapies. Isorhamnetin, a flavonol, has shown antioxidant and anti-inflammatory properties that makes exploring its antidepressant effect attractive. This study aims to investigate the adjuvant potential of isorhamnetin in combination with escitalopram to enhance its antidepressant efficacy in a lipopolysaccharide (LPS)-induced depression model using Swiss albino mice. Behavioral paradigms, such as the forced swim test and open field test, were employed to assess depressive symptoms, locomotion, and sedation. Additionally, enzyme-linked immunosorbent assays were utilized to measure Nrf2, BDNF, HO-1, NO, and IL-6 levels in the prefrontal cortex and hippocampus. The results demonstrate that isorhamnetin significantly improves the antidepressant response of escitalopram, as evidenced by reduced floating time in the forced swim test. Moreover, isorhamnetin enhanced antidepressant effects of escitalopram and effectively restored depleted levels of Nrf2, BDNF, and HO-1 in the cortex caused by LPS-induced depression. Isorhamnetin shows promise in enhancing the efficacy of conventional antidepressant therapy through antioxidant and anti-inflammatory effects.

Vitamins C and D Exhibit Similar Antidepressant Effects to Escitalopram Mediated by NOx and FKBPL in a Stress-Induced Mice Model.

The aim of this study was to investigate the potential antidepressant and anxiolytic effects of vitamin C and vitamin D in a stress-induced mouse model of depression, while also exploring the association between these effects and the levels of circulating NOx, periostin, and FKBPL. Our findings revealed that both vitamin C and vitamin D exhibited comparable antidepressant effects to escitalopram, a commonly used antidepressant, without demonstrating any anxiolytic effects. The antidepressant properties of vitamin C and vitamin D were linked to the normalization of Nox and FKBPL levels, while the levels of periostin showed no significant correlation. These results are consistent with previous research, indicating that the antidepressant effects of vitamin C and vitamin D may be attributed to their antioxidant and anti-inflammatory properties, as well as their modulation of neurotransmission and norepinephrine release. Additionally, our study uncovered elevated levels of periostin in stress-induced depression, which were only restored to normal levels by escitalopram, suggesting a potential role for periostin in mood disorders. Furthermore, FKBPL and NOx levels were increased in stress-induced depression and normalized by treatment with vitamin C, vitamin D, and escitalopram, indicating their involvement in the stress response and gene expression regulation. However, it is important to acknowledge certain limitations of our research, such as the use of a single depression induction model and limited dosing regimens. Future investigations should focus on examining these markers in specific brain regions, such as the hippocampus and prefrontal cortex, to gain a more comprehensive understanding of their potential implications for depression. Overall, our findings suggest that vitamin C, vitamin D, and escitalopram may possess antidepressant properties mediated by NOx and FKBPL levels, while emphasizing the potential significance of periostin in the context of depression.

Lysionotin exerts antinociceptive effects in various models of nociception induction.

Background: Lysionotin, a natural flavonoid extracted from Lysionotus pauciflorus Maxim (Gesneriaceae), has several pharmacological effects including anti-bacterial, anti-hypertensive and anti-inflammatory effects. However, its analgesic effect has not been investigated. This study aimed to assess the antinociceptive activity of lysionotin using chemically and thermally induced nociception in a mouse model. Methods: The antinociceptive effects of various lysionotin 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. Results: Lysionotin produced significant dose-dependent inhibition of nociceptive behavior in the acetic acid-induced writhing test, showing 60% inhibition at a dose of 200 µg/kg. Lysionotin also caused a significant increase in the latency period in response to the hot plate test (76.4% 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 lysionotin in both hot plate test and formalin-induced paw licking test. Moreover, lysionotin significantly inhibited the neurogenic nociception induced by intraplantar injections of glutamate and capsaicin (57% and 67.2%, respectively at a dose of 200 µg/kg). Thus, lysionotin exhibited peripheral and central antinociception through the modulation of vanilloid receptors, opioid receptors, and the glutamatergic system. Conclusion: Lysionotin possesses antinociceptive activity on adult mice that is mediated through both central and peripheral pathways.

The Emerging Importance of Cirsimaritin in Type 2 Diabetes Treatment.

Cirsimaritin is a dimethoxy flavon that has different biological activities such as antiproliferative, antimicrobial, and antioxidant activities. This study aims to investigate the anti-diabetic effects of cirsimaritin in a high-fat diet and streptozotocin-(HFD/STZ)-induced rat model of type 2 diabetes mellitus (T2D). Rats were fed HFD, followed by a single low dose of STZ (40 mg/kg). HFD/STZ diabetic rats were treated orally with cirsimaritin (50 mg/kg) or metformin (200 mg/kg) for 10 days before terminating the experiment and collecting plasma, soleus muscle, adipose tissue, and liver for further downstream analysis. Cirsimaritin reduced the elevated levels of serum glucose in diabetic rats compared to the vehicle control group (p < 0.001). Cirsimaritin abrogated the increase in serum insulin in the treated diabetic group compared to the vehicle control rats (p < 0.01). The homeostasis model assessment of insulin resistance (HOMA-IR) was decreased in the diabetic rats treated with cirsimaritin compared to the vehicle controls. The skeletal muscle and adipose tissue protein contents of GLUT4 (p < 0.01 and p < 0.05, respectively) and pAMPK-α1 (p < 0.05) were upregulated following treatment with cirsimaritin. Cirsimaritin was able to upregulate GLUT2 and AMPK protein expression in the liver (p < 0.01, <0.05, respectively). LDL, triglyceride, and cholesterol were reduced in diabetic rats treated with cirsimaritin compared to the vehicle controls (p < 0.001). Cirsimaritin reduced MDA, and IL-6 levels (p < 0.001), increased GSH levels (p < 0.001), and reduced GSSG levels (p < 0.001) in diabetic rats compared to the vehicle control. Cirsimaritin could represent a promising therapeutic agent to treat T2D.

Factors Associated with Psychotropic Medications Literacy among Community Pharmacists.

Background and objectives: Community pharmacists play an important role in ensuring the patient's adherence to medications, thus achieving therapeutic outcomes. The present study had two aims: to measure the extent of knowledge that community pharmacists had about psychotropic medications and to determine the factors associated with higher knowledge scores. Methods: A cross-sectional design was employed, using a structured online questionnaire. The study instrument assessed demographics, general practice characteristics related to psychotropics and a battery of factual questions that assessed the knowledge of pharmacists about psychotropic medications using closed-ended responses. A total knowledge score consisting of the sum of correct responses was calculated; the passing score was 75%. A total of 676 pharmacists completed the survey. Results: Only 20% passed the threshold score (75%) for the factual knowledge questions, and only (11.0%) were very comfortable with their knowledge of psychotropic agents. A total of 49.0% of the respondents felt that they had been adequately trained to counsel patients on psychotropic agents. According to the regression model, pharmacists who reported higher knowledge were more experienced (0.63, (0.26-1.0), p < 0.001), reported studying the topic in the pharmacy school (0.77 (0.27-1.26), p = 0.002) holding a Doctor of Pharmacy (Pharm D) degree (0.24 (0.05-0.43), p = 0.01), and reported a higher perceived knowledge (0.29 (0.01-0.38), p = 0.038). Conclusion: Community pharmacists reported poor knowledge of psychotropic medications, and continuous medical and professional education programs are mandatory.

Evaluation of the antinociceptive effect of valerian and hops combination in experimental animal models: Involvement of the opioid system.

Pain is a common undertreated worldwide complaint. The need to explore the antinociceptive potential of alternative herbal products is essential. Although used as a mild sedative, limited evidence focused on the potential antinociceptive effect of valerian and hops combination. The present study was carried out to evaluate the in vivo anti-nociceptive effect of the valerian-hops combination to justify its use as an effective and safe analgesic agent. Anti-nociceptive effects of valerian-hops combination (50, 100, and 200 mg/kg) were assessed in swiss albino mice for performing the acetic acid-induced writhing test, the paw licking test using formalin, the paw licking test using glutamate, and the tail immersion test. The effects were compared to those of diclofenac or morphine in the presence or absence of the opioid receptor antagonist naloxone. Valerian-hops" extract of 100 and 200 mg/kg demonstrated a significant reduction in the number of writhing episodes induced by acetic acid compared to the control (p < 0.05), a significant reduction in the licking number at doses of 100 and 200 mg/kg in the late phase formalin-induced paw licking, significantly reduced the number of lickings after glutamate injection compared to control (p < 0.05). And significantly increased pain reaction after 60 and 90 min of tail immersion test, this effect was opposed by naloxone treatment. The valerian-hops combination produced a significant antinociceptive effect that involved the opioid system. Further studies are required to fully uncover the underlying active constituents and their mechanisms.

New Treatment for Type 2 Diabetes Mellitus Using a Novel Bipyrazole Compound.

2',3,3,5'-Tetramethyl-4'-nitro-2'H-1,3'-bipyrazole (TMNB) is a novel bipyrazole compound with unknown therapeutic potential in diabetes mellitus. This study aims to investigate the anti-diabetic effects of TMNB in a high-fat diet and streptozotocin-(HFD/STZ)-induced rat model of type 2 diabetes mellitus (T2D). Rats were fed HFD, followed by a single low dose of STZ (40 mg/kg). HFD/STZ diabetic rats were treated orally with TMNB (10 mg/kg) or (200 mg/kg) metformin for 10 days before terminating the experiment and collecting plasma, soleus muscle, adipose tissue, and liver for further downstream analysis. TMNB reduced the elevated levels of serum glucose in diabetic rats compared to the vehicle control group (p < 0.001). TMNB abrogated the increase in serum insulin in the treated diabetic group compared to the vehicle control rats (p < 0.001). The homeostasis model assessment of insulin resistance (HOMA-IR) was decreased in the diabetic rats treated with TMNB compared to the vehicle controls. The skeletal muscle and adipose tissue protein contents of GLUT4 and AMPK were upregulated following treatment with TMNB (p < 0.001, < 0.01, respectively). TMNB was able to upregulate GLUT2 and AMPK protein expression in liver (p < 0.001, < 0.001, respectively). LDL, triglyceride, and cholesterol were reduced in diabetic rats treated with TMNB compared to the vehicle controls (p < 0.001, 0.01, respectively). TMNB reduced MDA and IL-6 levels (p < 0.001), and increased GSH level (p < 0.05) in diabetic rats compared to the vehicle controls. Conclusion: TMNB ameliorates insulin resistance, oxidative stress, and inflammation in a T2D model. TMNB could represent a promising therapeutic agent to treat T2D.