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OBJECTIVE: Isorhamnetin, a naturally occurring flavonoid compound, holds paramount importance as a primary constituent within several medicinal plants, exhibiting profound pharmacological significance. The aim of this study is to investigate the pain-relieving attributes of isorhamnetin in murine models through both formalin-induced pain and diabetic neuropathy scenarios. MATERIALS AND METHODS: To achieve our objective, isorhamnetin was orally administered to mice at varying dosage levels (10 to 100 mg/ kg). Pain-related behaviors were assessed using the formalin test during its secondary phase. Additionally, the potential pain-alleviating effect of isorhamnetin was evaluated in a diabetic neuropathy model induced by streptozotocin. Additionally, we carried out advanced interventions using naloxone, which is a well-known antagonist of opioid receptors, yohimbine, which blocks a2-adrenergic receptors, and methy-sergide, which inhibits serotonergic receptors, during the formalin test. RESULTS: The oral intake of isorhamne-tin showed a decrease in behaviors associated with pain that was proportional to the dose observed during the second phase of the formalin test when induced by formalin. In the diabetic neuropathy model, isorhamnetin administration effectively reversed the reduced pain threshold observed. Notably, naloxone, the opioid receptor antagonist, effectively counteracted the pain-relieving effect produced by isorhamne-tin in the formalin test, whereas yohimbine and methysergide did not yield similar outcomes. Isorhamnetin also led to a reduction in elevated spinal cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) levels triggered by formalin, with this effect reversed by pre-treatment with naloxone. The compound also suppressed heightened spinal phosphory-lated CREB (p-CREB) levels caused by diabetic neuropathy. CONCLUSIONS: This research determined that isorhamnetin has notable abilities to relieve pain in models of formalin-induced pain and diabetic neuropathy. The pain-relieving mechanism of isorhamnetin in the formalin-induced pain model seems to be connected to the activation of spinal opioid receptors and the adjustment of CrEb protein amounts. This insight improves our knowledge of how isorhamnetin could be used therapeutically to treat pain conditions stemming from formalin-induced pain and diabetic neuropathy. [ABSTRACT FROM AUTHOR]

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-1β), 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-1β, 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. [ABSTRACT FROM AUTHOR]

Objectives: Nanosuspensions are increasingly recognized as a valuable technology for enhancing poorly water-soluble drugs' solubility and dissolution rate, thereby improving their bioavailability. In this study, we employed ultrasonic-assisted precipitation to fabricate nanosuspensions of indomethacin (IND), utilizing Soluplus ® (Sol) as a stabilizing agent. Our objectives were driven by hypotheses centered on optimizing formulation variables and developing predictive models for optimal IND formulations., Significance: This research highlights the Box-Behnken design (BBD) as a powerful tool that optimizes the properties of IND nanosuspensions, thus significantly enhancing their dissolution rate., Methods: The impacts of the independent variables on the mean particle size (MPS), polydispersity index (PDI), and zeta potential (ZP) were investigated using BBD. The optimized nanosuspension was freeze-dried with 3% trehalose to produce a dry nanosuspension (DNS). The DNS was characterized by SEM, DSC, XRPD, solubility, and dissolution., Results: The IND: Sol ratio and sonication power significantly affected the MPS and ZP of the nanosuspensions. The optimized formulation showed MPS, PDI, and ZP of 144.77 ± 6.68 nm, 0.26 ± 0.08, and -24.6 ± 1.90 mV, respectively. The DNS exhibited spherical particle morphology. The DSC and XRPD confirmed the amorphous state of IND with enhanced solubility and dissolution of IND. DNS showed a 3.7-fold increase in drug release in the first 15 min compared with raw IND., Conclusions: This study demonstrated the critical role of BBD in accurately predicting the values of independent variables essential for formulating optimal nanosuspensions. These formulations possess specific properties that can be effectively integrated into various dosage forms tailored for different routes of administration.

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-1β, 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., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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-1β, 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., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: In today's competitive job market, pharmacists must have a well-crafted curriculum vitae (CV), cover letter, and personal statement. However, non-native English speakers may face challenges in crafting effective job application documents. Jordan is one such country where English is a second language for many, and little is known about the CV/job application writing skills of Jordanian pharmacists. Therefore, this study examined Jordanian pharmacists' ability to write job applications cover letters, and personal statements in English and investigated the association between several demographics and professional variables and the readability index of cover letters and personal statements., Methods: This study aimed to investigate Jordanian pharmacists' ability to write job applications cover letters, and personal statements in English and evaluate the readability of their personal statements and cover letters. The data were blindly and independently reviewed by two researchers. The readability of the cover letters and personal statements was assessed using an online calculator that assigns a readability index score. A readability score of 7-12 was considered "target", while scores above 12 or below 7 were considered "complicated" or "simple", respectively. The relationship between readability index scores and other variables was analyzed using the chi-square test with a statistical significance level of 0.05., Results: The study recruited 592 pharmacists. Most applicants, specifically 62.3%, were female, and 60.0% of them graduated more than six months before submitting their job applications. While 78.2% of the applications included a personal statement, only 34.8% included a cover letter, and 27.2% provided both. Of the 206 cover letters written in English, 43.2% were tailored, and 80.6% were structured. The study also found that the provision of an official photo was associated with providing a cover letter (P < 0.001, Phi(φ) = 0.14) while providing a structured cover letter was associated with including a personal statement (P < 0.001, Phi (φ) = 0.24). Only 102 cover letters and 65 personal statements had readability index scores within the target range., Conclusion: In this study, most Jordanian pharmacists undervalue the importance of cover letters and personal statements and lack job application writing skills. The study also highlighted the need for improved pharmacists' English proficiency to write effective job application documents in Jordan., (© 2023. The Author(s).)

Objective: To evaluate the role of a clinical pharmacist in improving knowledge and outcomes among isotretinoin users., Methods: Patients were randomly assigned to an intervention group (received education about isotretinoin by a clinical pharmacist in addition to the physician) and a control group (received routine education by the physician), then followed for three months. Patients' knowledge about isotretinoin optimal use, and side effects and their management and other outcomes were measured in both groups at baseline and at follow up after three months using a validated questionnaire., Results: Two-hundred and three patients completed the study; 103 were in the intervention group and 100 in the control group. The knowledge improvement between baseline score and follow-up score was greater in the intervention group (mean = 2.835 ± 1.329) compared to the control group (mean = 0.530 ± 0.784) with mean differences = -2.30495, P < 0.001., Conclusion: Implementing clinical pharmacy services in dermatology clinics can positively increase patients' level of knowledge about isotretinoin, which could reduce the severity of its side effects. Therefore, improving patients' quality of life, and improvement in acne., Practice Implications: Implementing clinical pharmacist services to patients using isotretinoin is feasible in an outpatient setting. Clinical pharmacist counseling and education improve the medication knowledge among patients who use isotretinoin., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Enhancing adherence to medication has the potential to improve clinical outcomes and decrease healthcare cost. The role of clinical pharmacist-led education on adherence to short-term antibiotic has never been investigated in Jordan. This study aimed to evaluate the impact of an educational intervention on antibiotic short-term adherence and to assess the antibiotic utilization pattern. A prospective, single blinded, randomized controlled study was conducted in a tertiary referral hospital in Jordan. Adult patients diagnosed with acute infection and prescribed a short-term antibiotic course (< 30 day) were included in the study. Recruited patients were randomly allocated into control and intervention groups. Pharmaceutical education about the correct use of antibiotic/s was provided to the intervention group. The results showed that penicillins were the most prescribed antibiotics (38.7%) followed by fluoroquinolones (23.9%) and cephalosporines (20.9%). Patients in the intervention group were more likely to be adherent to the prescribed antibiotics compared to control group (OR = 1.445, 95CI% = 1.029-2.030, p = 0.033). Employed patients, less frequent administration of antibiotic, and searching information related to the prescribed antibiotics were factors associated with better adherence to short-term antibiotic (p<0.05). The most common reasons for non-adherence were feeling better and forgetfulness to take medication. These findings highlighted that pharmacist-led educational intervention significantly enhance adherence to prescribed short-term antibiotics which is a major drive to control antibiotic resistance. Initiatives should be adopted to include patient education as a regular element in the medication dispensing process. Clinical trial registration: The trial is registered at ClinicalTrials.gov (identifier: NCT05293977)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Almomani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

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., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Alrosan et al.)

Immunophilins are a family of proteins encompassing FK506-binding proteins (FKBPs) and cyclophilins (Cyps). FKBPs and Cyps exert peptidyl-prolyl cis-trans isomerase (PPIase) activity, which facilitates diverse protein folding assembly, or disassembly. In addition, they bind to immunosuppressant medications where FKBPs bind to tacrolimus (FK506) and rapamycin, whereas cyclophilins bind to cyclosporin. Some large immunophilins have domains other than PPIase referred to as tetratricopeptide (TPR) domain, which is involved in heat shock protein 90 (Hsp90) and heat shock protein 70 (Hsp 70) chaperone interaction. The TPR domain confers immunophilins' pleotropic actions to mediate various physiological and biochemical processes. So far, immunophilins have been implicated to play an important role in pathophysiology of inflammation, cancer and neurodegenerative disorders. However, their importance in the development of fibrosis has not yet been elucidated. In this review we focus on the pivotal functional and mechanistic roles of different immunophilins in fibrosis establishment affecting various organs. The vast majority of the studies reported that cyclophilin A, FKBP12 and FKBP10 likely induce organ fibrosis through the calcineurin or TGF-β pathways. FKBP51 demonstrated a role in myelofibrosis development through calcineurin-dependant pathway, STAT5 or NF-κB pathways. Inhibition of these specific immunophilins has been shown to decrease the extent of fibrosis suggesting that immunophilins could be a novel promising therapeutic target to prevent or reverse fibrosis., (© 2022. The Author(s).)

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.

Aim: This study aimed to identify the perspective knowledge, attitudes, and barriers of community pharmacists in promoting breast cancer health., Methods: An internet-based self-administrated questionnaire was distributed using social media groups to the community pharmacists in Jordan., Results: A 76.7% of the pharmacists had insufficient knowledge score of breast cancer and 92.7% had positive attitude. Access to breast cancer educational materials was the major barrier to pharmacists. A significant association was found between pharmacists' knowledge and breast cancer educational materials being given to patients (p < 0.001)., Conclusion: Despite the low breast cancer knowledge score and stated barriers that could prevent actualizing community pharmacists' role, they had positive attitude toward educating patients about breast cancer health., Competing Interests: The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed, (© 2023 Muna Oqal.)

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.

Background: Isorhamnetin is a flavonoid that is found in medical plants. Several studies showed that isorhamnetin has anti-inflammatory and anti-obesity effects. This study aims to investigate the anti-diabetic effects of isorhamnetin in a high-fat diet and Streptozotocin-(HFD/STZ)-induced mice model of type 2 diabetes. Materials and Methods: Mice were fed with HFD followed by two consecutive low doses of STZ (40 mg/kg). HFD/STZ diabetic mice were treated orally with isorhamnetin (10 mg/kg) or (200 mg/kg) metformin for 10 days before sacrificing the mice and collecting plasma and soleus muscle for further analysis. Results: Isorhamnetin reduced the elevated levels of serum glucose compared to the vehicle control group (p < 0.001). Isorhamnetin abrogated the increase in serum insulin in the treated diabetic group compared to the vehicle control mice (p < 0.001). The homeostasis model assessment of insulin resistance (HOMA-IR) was decreased in diabetic mice treated with isorhamnetin compared to the vehicle controls. Fasting glucose level was significantly lower in diabetic mice treated with isorhamnetin during the intraperitoneal glucose tolerance test (IPGTT) (p < 0.001). The skeletal muscle protein contents of GLUT4 and p-AMPK-α were upregulated following treatment with isorhamnetin (p > 0.01). LDL, triglyceride, and cholesterol were reduced in diabetic mice treated with isorhamnetin compared to vehicle control (p < 0.001). Isorhamnetin reduced MDA, and IL-6 levels (p < 0.001), increased GSH levels (p < 0.001), and reduced GSSG levels (p < 0.05) in diabetic mice compared to vehicle control. Conclusions: Isorhamnetin ameliorates insulin resistance, oxidative stress, and inflammation. Isorhamnetin could represent a promising therapeutic agent to treat T2D.

Background: Ceratonia siliqua L. (Leguminosae) has neuroprotective, mutagenic, hypotensive, anti-bacterial, hypoglycaemic, and anti-inflammatory effects through extracts from its leaves. Therefore, the aim of this study is to assess the anti-nociceptive activity of ethanol extracts of Ceratonia siliqua leaves ., Methods: Ethanol extract of Ceratonia siliqua leaves were studied using well-established animal models of inflammation and pain. A hot plate latency assay (55 °C) was used to assess the analgesic effect of 10, 31.6, 100, and 316 mg/kg doses of ethanol extracts in addition to paw licking time in early and late phase using a formalin-induced paw licking assay test. Paw oedema induction using carrageenan and cotton pellet granuloma assays were used to assess the anti-inflammatory effect of 10, 31.6, 100, and 316 mg/kg doses of ethanol extract., Results: The ethanol extract of Ceratonia siliqua leaves reduces paw licking time in early and late phase after formalin injection. The same effect was also observed when the hotplate test was performed. Ethanol extract of Ceratonia siliqua leaves caused dose dependent inhibition in paw oedema after the injection of carrageenan and cotton pellet granuloma in mice. These effects were not antagonized when opioid receptors were blocked by naloxone (5 mg/kg). The preliminary phytochemical analysis of the ethanol extract of Ceratonia siliqua leaves showed the presence of tannins, alkaloids, flavonoids and terpenoids., Conclusion: The present data indicate that ethanol extract of Ceratonia siliqua leaves might possess anti-inflammatory and anti-nociception properties and should be considered for further therapeutic research., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Aims: Pharmacists in all clinical settings are recognized drug experts and integral educators of biosimilar medicines. Therefore, the objective of this study was to assess pharmacists' knowledge, predictors of knowledge, and views toward biosimilar medicines in Jordan., Methods: A cross-sectional study was conducted in Jordan during October-December 2020. An Internet-based self-administrated questionnaire on knowledge and views was distributed using social media groups to the pharmacists among different areas in Jordan. A descriptive and univariate analysis was 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 536 responses were received, 502 of which were completed (93.7% response rate). A total of 52.6% of the pharmacists were knowledgeable about biosimilar medicines and the mean of knowledge level was 6.47 ± 1.62 (range 2-10). Multivariate analysis identified that respondents who had heard about biosimilars before (OR = 1.942, 95% CI = 1.231-3.063, p < 0.05) was more likely to be knowledgeable. Respondents who had not taken the course or the postgraduating training course about biosimilars that were less likely to be knowledgeable (OR = 0.548, 95% CI = 0.357-0.839, p < 0.05). A positive response was noted in pharmacist's view regarding the implementation of biosimilar medicines in healthcare setting, biosimilar medicine prescription related to decreased costs, self-study about biosimilar medicine, and incorporating biosimilar education program at the pharmacy school curriculum universities level., Conclusions: Pharmacists' views and knowledge vary regarding the particularities and key issues on biosimilar medicines in Jordan. Incorporating biosimilar course in pharmacy school curriculum could improve their acceptance for future pharmacy jobs., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Muna Oqal et al.)

Background: Sodium/glucose cotransporter 2 (SGLT2) inhibitors are a new class of oral anti-diabetic drugs which improve glycaemic control in type 2 diabetes mellitus (T2DM) by preventing the kidney from reabsorbing glucose back to blood. Community pharmacists have long-term relationships with most of their chronic patients, so they play a key role in care for people with diabetes. Therefore, the objective of this study was to assess pharmacists' knowledge and practice towards SGLT2 inhibitors. Methods : A cross-sectional study was conducted to meet the study objectives. A convenience sample of 348 community pharmacists in Jordan was recruited. knowledge and practice were assessed using a self-administered questionnaire created for the purpose of this study. Results : A total of 400 community pharmacists were reached, of whom 348 answered the survey (response rate 87%). The results indicated that SGLT2 inhibitors knowledge score among community pharmacists in Jordan was 6.61 (out of 12). Factors like age, gender, location of the pharmacy, years of pharmacists' experience had no effect on knowledge score; however, pharmacists who attended training courses on diabetes had higher knowledge scores. Additionally, pharmacists' dispensing practice toward SGLT2 inhibitors had insufficient knowledge, such as lack of knowledge about the superiority of SGLT2 inhibitors over other anti-diabetics and inability to give the best advice to patients. Conclusions : Our findings reflect a moderate knowledge among community pharmacists about SGLT2 inhibitors which may negatively affect the patients' outcome; thus, continuous education for the pharmacists is essential., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 Alqudah A et al.)

Objective: This study was conducted to study the anxiety scores among undergraduate university students in Jordan during COVID-19 pandemic and to assess the relationship between quarantine and shifting to distance learning resulted from the governmental strict isolation measures and severity of anxiety among students., Methods: A cross-sectional design was conducted to meet the study objectives. A convenience sample of 736 undergraduate university students in Jordan was recruited, and anxiety was assessed using the Hamilton Anxiety Scale., Results: The results indicated that anxiety score was 22.76 and 40.6% of the participant experienced moderate to severe anxiety, whereas 23.5% experienced mild to moderate anxiety and 35.9% experienced mild anxiety. Factors like suffering from chronic illnesses, having chronic medications, grade point average, shifting to distance learning, quarantine during the pandemic, study duties, the newly developed evaluation methods and the experience of students towards the use of anti-anxiety drugs and herbs had significantly increased the anxiety scores., Conclusion: Our findings indicate that quarantine and shifting to distance learning during COVID-19 pandemic have negatively affected the anxiety scores of the university students which should be taken in consideration by the policymakers in Jordan in order to support this vulnerable group., (© 2021 John Wiley & Sons Ltd.)