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.

Knowledge, Attitudes, and Practices (KAP) of community pharmacists regarding antibiotic use and resistance: a cross-sectional study from the United Arab Emirates.

One of the main contributing factors of antibiotic resistance is the dispensing of antibiotics without prescription. This study investigated community pharmacists' knowledge, attitudes, and practices in relation to antibiotic dispensing and resistance in United Arab Emirates (UAE). A cross-sectional survey was conducted using validated questionnaire. (40.1%) had an overall positive KAP score. A total of (88%) respondents were aware of the illegality of dispensing antibiotics without a prescription. Only (31%) had good knowledge regarding amoxicillin dosage for upper respiratory tract infection. The primary misconduct found numerous pharmacists prescribing antibiotics without a prescription, even though they were aware that this should never be done. Pharmacists who attended events focused on antibiotic use and resistance were more likely to have good knowledge about antibiotics (Adjusted Odd Ratio (AOR): 1.673; 95%CI: 1.029-2.719; p = 0.038), more likely to have positive attitude (AOR: 1.889; 95%CI: 1.133-3.149; p = 0.015), and more likely to have good practice (AOR: 3.182; 95%CI: 1.541-6.572; p = 0.002).

Risk factors for severe dysmenorrhea in Arab women: A focus on war displacement and mental health outcomes.

Background: Dysmenorrhea is wide spread gynecological disorder among that affect the quality of life of women world wide. The current study aims to examine whether war displacement, mental health symptoms, and other clinical factors are associated with dysmenorrhea severity. Methods: This is a cross-sectional case-control study recruiting two groups: displaced Syrian women and un-displaced local Jordanian women. Demographics and clinical details were recorded. The severity of dysmenorrhea was assessed using WaLIDD scale, the PHQ-9 scale was emplyed to assess depressive symptoms, anxiety was assessed using the GAD-7 scale, and insomnia was assessed using the ISI-A scale. Predictors of severe dysmenorrhea in females using multivariate binary logistic regression. Results: Out of 808 of the total participants, 396 (49%) were Syrian displaced war refugees, 424 (42.5%) reported using paracetamol, 232 (23.2%) were using NSAIDs, and 257 (25.9%) using herbal remedies. Severe dysmenorrhea was associated with war displacement (OR = 2.14, 95% CI = 1.49-3.08, p < 0.001), not using NSAIDs (OR = 2.75, 95% CI = 1.91-3.95, p < 0.001), not using herbal remedies (OR = 2.01, 95% CI = 1.13-3.60, p = 0.01), depression (OR = 2.14, 95% CI = 1.40-3.29, p < 0.001), and insomnia (OR = 1.66, 95% CI = 1.14-2.42, p = 0.009). Conclusions: War displacement, type of analgesic, depression, and insomnia are risk factors for severe dysmenorrhea.

Targeting Cancer Hallmarks with Epigallocatechin Gallate (EGCG): Mechanistic Basis and Therapeutic Targets.

Epigallocatechin gallate (EGCG) is a catechin, which is a type of flavonoid found in high concentrations in green tea. EGCG has been studied extensively for its potential health benefits, particularly in cancer. EGCG has been found to exhibit anti-proliferative, anti-angiogenic, and pro-apoptotic effects in numerous cancer cell lines and animal models. EGCG has demonstrated the ability to interrupt various signaling pathways associated with cellular proliferation and division in different cancer types. EGCG anticancer activity is mediated by interfering with various cancer hallmarks. This article summarize and highlight the effects of EGCG on cancer hallmarks and focused on the impacts of EGCG on these cancer-related hallmarks. The studies discussed in this review enrich the understanding of EGCG's potential as a therapeutic tool against cancer, offering a substantial foundation for scientists and medical experts to advance scientific and clinical investigations regarding EGCG's possibility as a potential anticancer treatment.

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.

Factors associated with insomnia and fatigue symptoms during the outbreak of Oct.7th war on Gaza: A study from Jordan.

Objective: The Jordanian and the Palestinian communities are tightly related, hence, the current war on Gaza also has social and psychological impacts on Jordanians. Therefore, this study aims to identify the factors associated with severe insomnia and fatigue symptoms in a cohort of Jordanians during the Gaza War outbreak. Methods: This is a cross-sectional web-based questionnaire study. The Insomnia Severity Index-Arabic version (ISI-A), and the Brief Fatigue Inventory-Arabic (BFI-A) were employed, binary logistic and linear regression analyses was performed to identify predictors to severe insomnia and fatigue respectively. Data were collected between December 2023 and January 2024. Results: Data were analyzed from 477 participants, of which 315 (66 %) were females, 107 (22.4 %) reported having a family relative or a friend residing in Gaza, 365 (76.5 %) reported not using any sleep aid, 78 (16.4 %) reported using homeopathy herbal remedies for sleep, and only 52 (10.9 %) reported using over-the-counter sedating antihistamines. Severe insomnia was significantly associated with participants "younger than 30 years old" (OR = 1.81, 95 %CI = 1.22-2.66, p = 0.003), participants "using over-the-counter sedating antihistamines" (OR = 2.78, 95 % CI = 1.27-6.06, p = 0.01). Severe fatigue was significantly associated with "females" (B = 5.87, t = 2.78, p = 0.006), and "smokers" (B = 5.09, t = 2.52, p = 0.01). On the other hand, "not using sleep aids" demonstrated significantly lower odds for severe insomnia (OR = 0.41, 95 % CI = 0.24-0.68, p = 0.001), and fatigue (B = -10.84, t = -4.81, p < 0.001). Conclusions: Addressing modifiable risk factors such as smoking and sleep self-medications is essential to improve insomnia and fatigue symptoms.

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.

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 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.

Severe depressive symptoms in patients with hypertension: Are antihypertensive medications implicated?

OBJECTIVE: This study examined whether antihypertensive medications and other patient characteristics are associated with severe depressive symptoms in patients with hypertension. METHODS: Patients with a diagnosis of hypertension were recruited from the internal medicine outpatient clinics of a hospital in Amman, Jordan, into this cross-sectional study. Depression severity was assessed using the Patient Health Questionnaire-9 (PHQ-9); anxiety by the General Anxiety Disorder-7; sleep quality by the Insomnia Severity Index; and psychological stress by the Perceived Stress Scale. Multivariable binary logistic regression was used to examine the association between the different classes of antihypertensive medication and depressive symptoms. RESULTS: Of the 431 participants, 282 (65.4%) were men; 240 (55.7%) reported having type 2 diabetes; 359 (83.3%) had dyslipidemia; 142 (32.9%) were on beta-blockers; 197 (45.2%) were on ACE inhibitors or angiotensin receptor blockers; 203 (47.1%) were on metformin; and 133 (30.9%) were taking sulfonylurea. Severe depressive symptoms, indicated by scoring above the cut-off of 14 on the PHQ-9, were present in 165 (38.3%) patients. Severe depression was associated with younger age (<55 years) (OR = 3.15, 95% CI = 1.83-5.41, P < 0.001), unemployment (OR = 2.15, 95% CI = 1.15-4.00, P = 0.01), diabetes (OR = 1.81, 95% CI = 1.09-3.02, P = 0.02), severe anxiety (OR = 6.40, 95% CI = 3.64-11.28, P < 0.001), and severe insomnia (OR = 4.73, 95% CI = 2.85-7.82, P < 0.001). CONCLUSION: Severe depressive symptoms were not associated with antihypertensive medications or other drugs used by hypertensive patients. Younger age, diabetes, anxiety, and insomnia were the primary correlates of depression.

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.

Potential roles of NEDD4 and NEDD4L and their utility as therapeutic targets in high­incidence adult male cancers (Review).

The term 'cancer' refers to >100 disorders that progressively manifest over time and are characterized by uncontrolled cell division. Although malignant growth can occur in virtually any human tissue, the underlying mechanisms underlying all forms of cancer are consistent. The International Agency for Research on Cancer's annual GLOBOCAN 2020 report provided an update on the global cancer incidence and mortality. Excluding non-melanoma skin cancer, the report predicts that there will be 19.3 million new cancer cases and >10 million cancer-related fatalities in 2023. Lung, prostate, and colon cancers are the most prevalent and lethal cancers in males. It was recognized that post-translational modifications (PTMs) of proteins are necessary for almost all cellular biological processes, as well as in cancer development and metastasis to other bodily organs. Thus, PTMs have a considerable impact on how proteins behave. Various PTMs may have harmful roles by affecting the hallmarks of cancer, metabolism and the regulation of the tumor microenvironment. PTMs and genetic changes/mutations are essential in carcinogenesis and cancer development. A pivotal PTM mechanism is protein ubiquitination. Of note, the rate-limiting stage of the protein ubiquitination cascade is hypothesized to be E3-ligase-mediated ubiquitination. Numerous studies revealed that the neural precursor cell expressed developmentally downregulated protein 4 (NEDD4) E3 ligase is among the E3 ubiquitin ligases that have essential roles in cellular processes. It regulates protein degradation and substrate ubiquitination. In addition, it has been shown that NEDD4 primarily functions as an oncogene in various malignancies but can also act as a tumor suppressor in certain types of tumor. In the present review, the roles of NEDD4 as an anticancer protein in various high-incidence male malignancies and the significance of NEDD4 as a potential cancer therapeutic target are discussed. In addition, the targeting of NEDD4 as a therapeutic strategy for the treatment of human malignancies is explored.

Perspective of biopharmaceutics knowledge and practice of pharmacy personnel toward the effect of medication route and medical procedure on nullifying fasting.

Background: In Ramadan, most of the dosing schedules for the patients are changed, and to ensure patient compliance to medications and to healthy life among patients, appropriate guidelines and educations are needed. This can be achieved by pharmacy personnel in all clinical settings who are recognized as biopharmaceutical experts and integral educators of medications. Aims: This study aimed to identify the perspective knowledge of pharmacy personnel about effect of medication route and medical procedure on nullifying fasting in Ramadan and to determine the predictors of this knowledge. Methods: A cross-sectional study was conducted in Jordan during March-April 2022. An internet-based self-administrated questionnaire on knowledge, and views was distributed using social media groups to the pharmacy personnel among different geographical areas in Jordan. A descriptive and univariate analysis were performed. Binary logistic regression was conducted to determine the predictors of knowledge including all variables with p < 0.20 on univariate analysis. Results: A total of 1003 responses to the study questionnaire were collected and included in the analysis. The most common source that pharmacy personnel used to get information on medication intake and medical procedures during fasting in Ramadan was Fatwa (57.8%) followed by Islamic materials "books and brochures" (47.1%). The majority of respondents were knowledgeable about the effect of administration route of medication and medical procedures on nullifying fasting in Ramadan (greater than70%). The univariate analysis showed that more than half of respondents (56.1%) were considered knowledgeable, and the binary logistic regression analysis identified that both professional degree type and confidence of respondents to modify the patient's medication schedule as predictors for knowledge (OR = 1.791, 95% CI = 1.035-3.098, p = 0.037), (OR = 1.375, 95% CI = 1.04-1.817, p = 0.025), respectively. Conclusions: Most of pharmacy personnel in Jordan are knowledgeable in biopharmaceutics principles and practice toward effect of medication route and medical procedure on nullifying fasting, and the identified predictors for this knowledge, can provide an opportunity to improve safe and effective use of medications and medical procedures during the holy month of Ramadan.

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.