Bibliometric Analysis of Meningiomas from 2001 to 2023: Focus on the Top 100 Most Cited Papers.

OBJECTIVE: The aim was to conduct a comprehensive bibliometric analysis of meningioma research, focusing on publication trends, top authors, universities, countries, and thematic analysis of keywords. METHODS: From Scopus databases, first we analyzed 23180 papers (or 19,824 articles and 3,356 reviews) published between 2001 and 2023. Second, we selected the top 100 most cited papers and descriptively analyzed on Vosviewer and R Studio (bibliometrix/biblioshiny). RESULTS: For both sets, we highlighted the annual publication trends and the impact of top-cited papers. We identified leading authors, universities, and countries contributing significantly to the field. Keywords analysis categorized research themes across all papers. Specific focus was given to the top 100 most cited documents in meningioma. Details about the annual number of papers, mean citations per year, and the citable years are provided. The top authors are presented by number of publications, citations, h-index, g-index and m-index. Co-words analysis was performed and the main focus of the 100 most cited papers are presented in more than 20 categories CONCLUSION: Our findings may provide insights into the evolution of meningioma research and its scholarly impact. The analysis underscores the pivotal contributions of top authors and institutions, outlines thematic research trends, and highlights areas of significant interest and growth in the field. Our study may contribute to understanding the landscape of meningioma research, guiding future research directions and collaborations.

A systematic literature review of natural products for male sexual dysfunction.

This study systematically reviewed the scientific literature on natural remedies for male sexual dysfunction (MSD), including conditions like erectile dysfunction, premature ejaculation, and reduced libido. Limited scientific evidence exists regarding the efficacy and safety of these natural products. To ensure an objective assessment, the study used the Scopus database, followed the PRISMA guidelines, and employed a comprehensive search strategy involving relevant vital concepts, controlled vocabularies, and specific inclusion/exclusion criteria. The analysis included 1504 documents from 624 journals, spanning from 1967 to 2023. The literature showed an annual growth rate of 2.46%, with an average document age of 10.2 years and an average of 23.54 citations per document. India had the highest publication count (319), followed by the United States (164). Conceptual Mapping categorized themes into basic, motor, niche, emerging, and declining categories, including nitric oxide, oxidative stress, phytotherapy, herbal medicine, Asparagus racemosus, and dopamine. This mapping provided a holistic understanding of the field, identified research gaps, and guided the development of new interventions or treatment strategies for MSD. Trend topics include molecular coupling, Ashwagandha, phytochemistry, phosphodiesterase-5, and arginase. The study findings will assist healthcare professionals in making informed decisions when recommending or advising patients about the use of these remedies.

Risk of acute coronary syndrome and relationship with the use of khat and tobacco products in the Jazan region, Saudi Arabia: A prospective case-control study.

INTRODUCTION: Previous studies have identified several risk factors for acute coronary syndrome (ACS). This study was intended to examine the potential risk of ACS associated with khat and tobacco use. METHODS: A case-control study of 344 people (172 cases and 172 controls) was conducted at Prince Mohammed Bin Nasser Hospital in Jazan, Saudi Arabia, from April to September 2019. The cases and controls were matched for age (±5 years) and gender. Data were analyzed using descriptive, inferential, and modeling analyses. We utilized the adjusted odds ratio (AOR) to express the results. RESULTS: The prevalence of ever khat chewing among all study participants was 29.1%, significantly higher for the cases with ACS than for the control group (43.6% vs 14.5%, p<0.001). Cigarette smokers accounted for 33.4% of the study participants, and 22.1% were ACS cases, which is a significantly higher percentage than the control group. The prevalence of smokeless tobacco was 20.3% among ACS cases and 14.5% among controls, with no statistically significant differences (p>0.05). In the final model, tobacco use was more likely to be reported among cases with myocardial infarction (MI) (AOR=4.58; 95% CI: 1.01-4.73, p<0.05) as was khat chewing (AOR=3.4; 95% CI: 1.55-7.46, p<0.05), after controlling for other traditional risk factors. CONCLUSIONS: Khat chewing was reported more by those who reported ACS. ACS cases were more likely to be frequent khat users with chewing sessions of five or more days per week. Regular tobacco use was also reported in those who reported ACS, and this increases with the amount of tobacco used. Implementing early intervention strategies can help mitigate the impact of khat chewing and smoking on the development of ACS.

The Neurosurgical Research Progress of 98 Low and Lower Middle-Income Countries from 1928 to 2024.

OBJECTIVE: The aim of the present study was to analyze the trends of neurosurgical research in low and lower middle-income countries (LLMICs). METHODS: The data was retrieved from Scopus database and 82 neurosurgical journals were analyzed. RESULTS: Initially the global research scholarly output (n = 195,658) was explored and later papers originating solely from LLMICs, without international collaboration with advance countries (n = 8408) were analyzed. The per decade number of publications (from 1920 to May 2024), top ten authors, universities, countries and sources of all (global) countries, and 98 LLMICs is provided. Eighty countries have published less than 50 papers. Even more striking, 68, 55, 38, and 36 LLMICs countries have produced less than 20, 10, 5, and 3 papers, respectively. The keywords analysis was performed to present the main focus of 8408 publications. The top 1000 most cited documents were also identified, and later relevant scientometrics details were provided. The top countries dynamic and most prolific authors (on the basis of number of publications, total citations, h-index, g-index, and m-index) in the top 1000 cited documents (from LLMICs) are highlighted. CONCLUSIONS: The findings suggest that neurosurgical research in LLMICs is low, which could be attributed to several factors including limited funding, inadequate infrastructure, and insufficient training opportunities.

Bibliometric Analysis of Machine Learning Applications in Ischemia Research.

OBJECTIVE: The objective of this study is to conduct a comprehensive bibliometric analysis to elucidate the landscape of machine learning applications in ischemia research. METHODS: The analysis can be divided in three sections: part 1 scrutinizes articles and reviews with "ischemia" in their titles, while part 2 further narrows the focus to publications containing both "ischemia" and "machine learning" in their titles. Additionally, part 3 delves into the examination of the top 50 most cited papers, exploring their thematic focus and co-word dynamics. RESULTS: The findings reveal a significant increase in publications over the years, with notable trends identified through detailed analysis. The growth in publication counts over time, the leading contributors, institutions, geographical distribution of research output and journals are numerically presented for part 1 and part 2. For the top 50 most cited papers the dynamics of co-words, which offer a nuanced understanding of thematic trends and emerging concepts, are presented. Based on the number of citations the top 10 authors were selected, and later for each, total number of publications, h-index, g-index and m-index are provided. Additionally, figures depicting the co-authorship network among authors, departments, and countries involved in the top 50 cited papers may enrich our comprehension of collaborative networks in ischemia research. CONCLUSION: This comprehensive bibliometric analysis provides valuable insights into the evolving landscape of machine learning applications in ischemia research.

Tuberculosis research advances and future trends: A bibliometric knowledge mapping approach.

The Gulf Cooperation Council (GCC) countries are more vulnerable to many transmissible diseases, including tuberculosis (TB). This study is to identify the scientific publications related to TB in the GCC countries using topic modeling and co-word analysis. A bibliometric analytic study. The R-package, VOSviewer software, IBM SPPS, and Scopus Analytics were used to analyze performance, hotspots, knowledge structure, thematic evolution, trend topics, and inter-gulf and international cooperation on TB in the past 30 years (1993-2022). A total of 1999 publications associated with research on GCC-TB were published. The annual growth rate of documents was 7.76%. Saudi Arabia is the most highly published, followed by the United Arab Emirates, Kuwait, Qatar, Oman, and Bahrain. The most-cited GC country is Kingdom Saudi Arabia, followed by Kuwait. One hundred sixty research institutions contributed to the dissemination of TB-related knowledge in the GCC, where the highest publishing organizations were King Saud University (Kingdom Saudi Arabia; n = 518). The number of publications related to TB is high in GCC Countries. The current tendencies indicated that GCC scholars are increasingly focused on deep learning, chest X-ray, molecular docking, comorbid covid-19, risk factors, and Mycobacterium bovis.

Cancer research in the United Arab Emirates from birth to present: A bibliometric analysis.

Background: Accumulating evidence indicates that the incidence of cancer is increasing in the United Arab Emirates (UAE). This analysis aimed to determine the current cancer research output in the UAE to guide future national research. Methods: The Scopus database was searched for cancer-related bibliographic data from the UAE. The number of publications, citation analysis, co-authorship of the author, institution, and country, keyword co-occurrence, and reference co-citations were analyzed using the R-studio bibliometrics package and VOSviewer software. Results: A total of 1678 journal articles were retrieved from 1981 to 2022. Cancer research in the UAE (UCR) is increasing at a rate of 14.64% (R-squared = 0.75; F = 46.477; P<0.001). The UAE had a 0.06% participation rate in terms of the number of original articles. The rate of international co-authorship is 40.23%. The U.S.A., U.K., Egypt, Saudi Arabia, India, and Canada had more than 100 co-authored documents from 156 countries that collaborated with the U.A.E. Conclusions: Compared to other nations, the UAE has fewer publications on cancer, although the number is growing. The current report provides an up-to-date and in-depth summary of the trends in UCR. This project is an excellent place for researchers interested in conducting data-mapping work in this field.

Synthesis, molecular docking, and in vivo antidiabetic evaluation of new benzylidene-2,4-thiazolidinediones as partial PPAR-γ agonists.

Peroxisome proliferator-activated receptor-γ (PPAR-γ) partial agonists or antagonists, also termed as selective PPAR-γ modulators, are more beneficial than full agonists because they can avoid the adverse effects associated with PPAR-γ full agonists, such as weight gain and congestive heart disorders, while retaining the antidiabetic efficiency. In this study, we designed and synthesized new benzylidene-thiazolidine-2,4-diones while keeping the acidic thiazolidinedione (TZD) ring at the center, which is in contrast with the typical pharmacophore of PPAR-γ agonists. Five compounds (5a-e) were designed and synthesized in moderate to good yields and were characterized using spectral techniques. The in vivo antidiabetic efficacy of the synthesized compounds was assessed on streptozotocin-induced diabetic mice using standard protocols, and their effect on weight gain was also studied. Molecular docking and molecular dynamics (MD) simulation studies were performed to investigate the binding interactions of the title compounds with the PPAR-γ receptor and to establish their binding mechanism. Antidiabetic activity results revealed that compounds 5d and 5e possess promising antidiabetic activity comparable with the standard drug rosiglitazone. No compound showed considerable effect on the body weight of animals after 21 days of administration, and the findings showed statistical difference (p < 0.05 to p < 0.0001) among the diabetic control and standard drug rosiglitazone groups. In molecular docking study, compounds 5c and 5d exhibited higher binding energies (- 10.1 and - 10.0 kcal/mol, respectively) than the native ligand, non-thiazolidinedione PPAR-γ partial agonist (nTZDpa) (- 9.8 kcal/mol). MD simulation further authenticated the stability of compound 5c-PPAR-γ complex over the 150 ns duration. The RMSD, RMSF, rGyr, SASA, and binding interactions of compound 5c-PPAR-γ complex were comparable to those of native ligand nTZDpa-PPAR-γ complex, suggesting that the title compounds have the potential to be developed as partial PPAR-γ agonists.

Psychotropic Medication Adherence and Its Associated Factors Among Schizophrenia Patients: Exploring the Consistency of Adherence Scales.

Background and objective Non-adherence to psychotropic medication can aggravate an individual's illness, diminish treatment efficacy, or make patients less responsive to future therapeutic interventions. There are several scales available to measure non-adherence to medications. In this study, we aimed to measure psychotropic medication adherence and its associated factors among schizophrenic outpatients in Saudi Arabia. Methodology A cross-sectional study was conducted with a view to measuring psychotropic medication adherence and its associated factors. The Medication Adherence Rating Scale (MARS) and the Drug Attitude Inventory-10 (DAI-10) were translated into Arabic, and their internal consistency was measured. The adjusted odds ratios (AOR) were calculated using logistic regression in the IBM SPSS Statistics software version 23 (IBM Corp., Armonk, NY). Results Spearman's rho correlation indicated a negative association between DAI-10 and MARS scores (r = -0.579; p<0.05). The Arabic version of MARS was more reliable than DAI-10, as evidenced by Cronbach's alpha value. Of note, 60.20% (n = 59) of the sample demonstrated high adherence levels. The adherence level based on MARS scoring remained unaffected (p>0.05) in terms of gender, age, employment, marital status, educational level, income level, and duration of sickness. These results were obtained by using the multivariate logistic regression model; 89% of respondents reported not using psychiatric drugs given by someone else, despite the adherence rate not affecting this number. Conclusion The rate of non-adherence to psychotropic treatment was found to be high in our cohort. Hence, it is imperative to develop comprehensive intervention methods targeting the causes of non-adherence to psychiatric medication.

Comprehensive analysis of research related to rehabilitation and COVID-19, hotspots, mapping, thematic evolution, trending topics, and future directions.

BACKGROUND: This study conducted a comprehensive analysis of research pertaining to the intersection of rehabilitation and COVID-19 (COV-REH). The main aim of this study is to analyze the thematic progression and hotspots, detect emerging topics, and suggest possible future research directions in the COV-REH. METHODS: Appropriate keywords were selected based on the Medical Subject Headings (MeSH) PubMed database and the Scopus database were used to retrieve a total of 3746 original studies conducted in the English language. The data extraction was performed on June 30, 2023. VOSviewer and Bibliometrix utilize CVS and BibTex files to facilitate the performance analysis and generate visual maps. The performance indicators reported for the research components of the COV-REH were compiled using the Scopus Analytics tool. RESULTS: From 2003 to 2023, 3470 authors from 160 organizations in 119 countries generated 3764 original research documents, with an annual growth of 53.73%. 1467 sources identified these scholarly works. Vitacca, M. (Italy), Harvard University (USA), and the USA published the most articles. This study included 54.1% of medical scholars. Telerehabilitation, exercise, quality of life, case reports, anxiety, and pulmonary rehabilitation were the primary themes of the COV-REH. One component of "telerehabilitation" is now the cardiac rehabilitation cluster. The trending topics in COV-REH are "symptoms," "protocol," and "community-based rehabilitation". CONCLUSIONS: This study proposed several significant research directions based on the current thematic map and its evolution. Given that COV-REH investigations have been determined to be multidisciplinary, this study contributes conceptually to several fields and has wide-ranging implications for practitioners and policymakers.

Diabetes mellitus research in Saudi Arabia: A bibliometric study (2010-2021).

Diabetes Mellitus (DM) causes global exhaustion, consumes economic resources, and has several risk factors. The bibliometric studies re-evaluate the research efforts on this illness using mathematical and statistical tools to indicate current research and future trends. This study examines KSA's DM research during 2010-2021. Data were acquired from Scopus and analyzed using VOSviewer and MS Excel. Several characteristics were examined to measure the quantity and quality of KSA-related DM articles. In total, 1,919 journal and conference papers were published. DM research included researchers from multidisciplinary sectors. Thirty-seven percent of them have ten or more scientific publications. Al-Daghri, N.M. (King Saud University) leads the pack. In total, 757 (39.44%) research projects got funding from 159 sources within and outside KSA. Memish, Z.A. is the most cited author. The Saudi Medical Journal has the most citations (1214). Al-Daghri, N.M. (KSU) collaborates the most. One hundred forty-one nations aided KSA's diabetes research. Egypt's High Institute of Public Health has the most scientific collaboration with KSA. Authors' and all Keywords analyses indicated a rich knowledge structure. Diabetes Care Journal has the most cocitations with 2,220 and a total link strength of 19,283, followed by The New England Journal of Medicine. The study results will be helpful to stakeholders to understand better the trends and performance of diabetes-related regional research, which will be beneficial.

Broccoli: A Multi-Faceted Vegetable for Health: An In-Depth Review of Its Nutritional Attributes, Antimicrobial Abilities, and Anti-inflammatory Properties.

Broccoli, Brassica oleracea var. italica, has recently gained considerable attention due to its remarkable nutritional composition and numerous health benefits. In this review, the nutritional aspects of broccoli are examined, highlighting its rich nutrient content and essential bioactive compounds. The cruciferous vegetable broccoli is a rich source of several important nutrients, including fiber, vitamins (A, C, and K), minerals (calcium, potassium, and iron), and antioxidants. It has also been shown to contain bioactive compounds such as glucosinolates, sulforaphane, and indole-3-carbinol, all of which have been shown to have significant health-promoting effects. These chemicals are known to have potent antioxidant, anti-inflammatory, and anticancer effects. This review article aims to comprehensively examine the diverse spectrum of nutrients contained in broccoli and explore its medicinal potential to promote human health.

Cinnamon Oil Alleviates Acetaminophen-Induced Uterine Toxicity in Rats by Abrogation of Oxidative Stress, Apoptosis, and Inflammation.

Paracetamol, or acetaminophen (APAP), is one of the first-line medications that is used for fever and pain. However, APAP can induce uterine toxicity when overused. The mode of action of APAP toxicity is due to the production of free radicals. The main goal of our study is to determine uterine toxicity from APAP overdose and the antioxidative activity of cinnamon oil (CO) in female rats. The effect of different doses of CO (50-200 mg/kg b.w.) was assessed in the uterus toxicity induced by APAP. Additionally, the imbalance in oxidative parameters, interleukins, and caspases was evaluated for the protective effects of CO. A single dose of APAP (2 g/kg b.w.) resulted in uterus toxicity, indicated by a significant increase in the level of lipid peroxidation (LPO), inflammatory interleukins cytokines (IL-1 and 6), expression of caspases 3 and 9, and a marked change in uterus tissue architecture evaluated by histopathology. Co-treatment of CO resulted in a significant amelioration of all the parameters such as LPO, interleukins IL-1ß, IL-6, caspases 3 and 9 expression, and distortion of tissue architecture in a dose-dependent manner. Therefore, we can conclude that APAP-induced uterine injury due to oxidative stress can be restored by co-treatment with cinnamon oil (CO).

Knowledge, attitudes, and practices (KAP) during the malaria elimination phase: A household-based cross-sectional survey.

Malaria is a major health problem in Southwestern Saudi Arabia. This study aimed to measure the level of community understanding of malaria transmission, protection, and treatment. A questionnaire-based cross-sectional study enrolled 1070 participants from 2 districts with different malaria prevalence rates in Jazan Province. The response rate was 97.27%. Of the 1070 total; 754 (70.5%) had heard about malaria. Sixty-seven percentage know that fever was the main symptom. Approximately 59.8% did not know that stagnant water is one of the most important locations for mosquito breeding. Nevertheless, we found that 50% of the participants knew that mosquitoes bite at night and 96.9% confirmed that mosquitoes did not bite during the day. The most effective sources of information were distributed leaflets (41.8%) and video awareness (31.9%). The most significant factors affecting participants knowledge were gender, residence, family members, income, and education (P < .05). Knowledge levels were satisfactory in this study, and the majority of participants exhibited adequate attitudes and practices related to malaria prevention. However, knowledge differences were observed with regard to the place of residence. Greater emphasis should be directed towards education programs in malaria-endemic areas to ensure complete eradication of malaria.

Neuroprotective Effects of Nano-Curcumin against Cypermethrin Associated Oxidative Stress and Up-Regulation of Apoptotic and Inflammatory Gene Expression in Rat Brains.

Cypermethrin (CPM) is the most toxic synthetic pyrethroid that has established neurotoxicity through oxidative stress and neurochemical agitation in experimental rats. The toxic effects are supposed to be mediated by modifying the sodium channels, reducing Na-K ATPase, acetylcholine esterase (AchE), and monoamine oxidase (MAO). The use of curcumin nanoparticles (NC) that have potent antioxidant, anti-inflammatory and antiapoptotic properties with improved bioavailability attenuates neurotoxicity in rat brains. To test this hypothesis, animals were divided into five groups, each having six animals. Group-I control received vehicle only, while Group-II was treated with 50 mg/kg CPM. Group-III and Group-IV received both CPM and NC 2.5 mg/kg and 5 mg/kg, respectively. Group-V received 5 mg of NC alone. The CPM and NC were given by oral route. Afterwards, brain antioxidant status was measured by assessing lipid peroxidation (LPO), 4-HNE, glutathione reduced (GSH), antioxidant enzyme catalase, and superoxide dismutase (SOD) along with neurotoxicity markers Na-K ATPase, AchE, and MAO. Inflammation and apoptosis indices were estimated by ELISA, qRT-PCR, and immunohistochemistry, while morphologic changes were examined by histopathology. Observations from the study confirmed CPM-induced neurotoxicity by altering Na-K ATPase, AchE, and MAO, and by decreasing the activity of antioxidant enzymes and GSH. Oxidative stress marker LPO and the level of inflammatory interleukins IL-6, IL-1ß, and TNF-α were notably high, and elevated expressions of Bax, NF-kB, and caspase-3 and -9 were reported in CPM group. However, NC treatment against CPM offers protection by improving antioxidant status and lowering LPO, inflammation, and apoptosis. The neurotoxicity marker's enzyme successfully attenuated after NC treatment. Therefore, this study supports the administration of NC effectively ameliorated CPM-induced neurotoxicity in experimental rats.

Hepatoprotective Effect of Curcumin Nano-Lipid Carrier against Cypermethrin Toxicity by Countering the Oxidative, Inflammatory, and Apoptotic Changes in Wistar Rats.

This study investigated the potential hepatoprotective activity of curcumin-incorporated nano-lipid carrier (Cur-NLC) against cypermethrin (Cyp) toxicity in adult Wistar male rats. All animals in groups III, IV, V, and VI were subjected to Cyp (50 mg/kg) toxicity for 15 days. Three different doses of Cur-NLC (1, 2.5, and 5 mg/kg/day) were administered orally for 10 days. The toxic effects were evaluated considering the increases in serum hepatic biomarkers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein and albumin, and lipid peroxidation (LPO), as well as a decrease in antioxidative activity (reduced glutathione (GSH), superoxide dismutase (SOD), and catalase) and the upregulation of inflammatory cytokines (IL-1ß, IL-6, and TNF-α). Immunohistochemistry studies of proteins (NF-κB, Apaf-1, 4-HNE, and Bax) showed enhanced expression, and histopathological examination revealed architectural changes in liver cells, indicating liver toxicity in animals. Toxicity was determined by quantitative and qualitative determinations of DNA fragmentation, which show massive apoptosis with Cyp treatment. The administration of Cur-NLC significantly ameliorates all changes caused by Cyp, such as a decrease in the levels of serum liver markers, an increase in antioxidative parameters, a decrease in expression of inflammatory cytokines (IL-1ß, IL-6, TNF-α, and NF-κB), and apoptosis (caspases-3, 9, Apaf-1, 4-HNE, and Bax), according to calorimetric and immunohistochemistry studies. The smear-like pattern of DNA is ameliorated similarly to the control at a high dose of Cur-NLC. Furthermore, all histopathological changes were reduced to a level close to the control. In conclusion, Cur-NLC could be a potent nutraceutical that exhibits a hepatoprotective effect against Cyp-induced hepatotoxicity in rats.

Spectral Analysis and Antiulcer Potential of Lactuca sativa through the Amelioration of Proinflammatory Cytokines and Apoptosis Markers.

The objective of this study was to characterize the bioactive ingredients and antiulcer effects of Lactuca sativa leaves. Several bioactive chemicals were found in the cold methanolic extract of Lactuca sativa leaves after gas chromatography-mass spectrometry (GC-MS) research: 9,12-octadecadienoic acid (Z,Z)-, cyclononasiloxane, octadecamethyl-, n-hexadecanoic acid, Hexadecanoic acid, 2-hydroxy-1-(hydroxymethyl)ethyl, octadecanoic acid, 2-hydroxy-1-(hydroxymethyl)ethyl ester, 9-octadecenamide, (Z)-, hexadecanoic acid, stigmasterol, benzothiazole, ethyl iso-allocholate, and octacosane. Distinct fingerprint regions in GCMS indicated the existence of bioactive compounds. The leaf powder of Lactuca sativa (LPL) demonstrated substantial antiulcer properties at 400 mg/kg, which was almost equivalent to the standard drug at 20 mg/kg. The cytokine network was efficiently regulated by reducing the production of proinflammatory cytokines such as IL-1ß, IL-6, and TNF-α. The levels of caspase-3 and caspase-9 were also considerably lowered at p < 0.05 significant level.

Study of influence of Catha edulis (Khat) chewing on oral pharmacokinetics of irbesartan in rats using a newly developed HPLC-UV method.

Khat consumers might use a number of drugs for underlying conditions; however the potential drug-herb interaction between khat and other drugs including Irbesartan (IRB) is unknown. The present study was conducted to evaluate the effects of khat chewing on pharmacokinetic profile of IRB, a commonly available antihypertensive agent. The pharmacokinetic profile of orally administered IRB (15.5 mg/kg) with and without pre-administration of khat (12.4 mg/kg) were determined in Sprague-Dawley rats. IRB was estimated in rat plasma samples using a newly developed HPLC method. The chromatographic separation of the drug and internal standard (IS) was performed on a C-18 column (Raptor C-18, 100 mm × 4.6 mm id.; 5 µm) using a mobile phase consisting of 10 mM ammonium acetate buffer (pH 4.0) and acetonitrile in a ratio 60:40 v/v. Acceptable linearity for IRB was recorded at 1 - 12 µg/mL concentration range (R2 > 0.99). Intra-day and inter-day precision (%RSD = 0.44% - 3.27% and 0.39-1.98% respectively) and accuracy (% recovery = 98.3 - 104.3%) in rat plasma was within the acceptable limit according to USFDA guidelines. The AUC0-t was found to be significantly increased in IRB-khat co-administered rats as compared to rats receiving IRB only; whereas, the Tmax (0.5 h) value remained unchanged. Results of this study revealed that the IRB level considerably increased in rat plasma upon co-administration of khat. This might be due to the inhibition of CYP2D9 by khat which is the principal cytochrome P450 isoform responsible for IRB metabolism.

p-Trifluoromethyl- and p-pentafluorothio-substituted curcuminoids of the 2,6-di[(E)-benzylidene)]cycloalkanone type: Syntheses and activities against Leishmania major and Toxoplasma gondii parasites.

A series of the title curcuminoids with structural variance in the heteroatom of the cycloalkanone and the p-substituents of the phenyl rings were tested for their activities against Leishmania major and Toxoplasma gondii parasites. The majority of them showed high activities against both parasite forms with EC50 values in the sub-micromolar concentration range. Bis(p-pentafluorothio)-substituted 3,5-di[(E)-benzylidene]piperidin-4-one 1b was not just noticeable antiparasitic, but also exhibited a considerable selectivity for L. major promastigotes over normal Vero cells. While derivatives differing only in the p-phenyl substituents being CF3 or SF5 showed similar antiparasitic activities, the cyclic ketone hub was more decisive both for the anti-parasitic activities and the selectivities for the parasites vs. normal cells. QSAR calculations confirmed the observed structure-activity relations and suggested structural variations for a further improvement of the antiparasitic activity. Docking studies based on DFT calculations revealed L. major pteridine reductase 1 as a likely molecular target protein of the title compounds.