Expressed sequence tag analysis of khat (Catha edulis) provides a putative molecular biochemical basis for the biosynthesis of phenylpropylamino alkaloids.
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ABSTRACT:
SUBMITTER: Hagel JM
PROVIDER: S-EPMC3229120 | biostudies-literature | 2011 Oct
REPOSITORIES: biostudies-literature
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Expressed sequence tag analysis of khat (Catha edulis) provides a putative molecular biochemical basis for the biosynthesis of phenylpropylamino alkaloids.
Hagel Jillian M JM Krizevski Raz R Kilpatrick Korey K Sitrit Yaron Y Marsolais Frédéric F Lewinsohn Efraim E Facchini Peter J PJ
Genetics and molecular biology 20111001 4
Khat (Catha edulis Forsk.) is a flowering perennial shrub cultivated for its neurostimulant properties resulting mainly from the occurrence of (S)-cathinone in young leaves. The biosynthesis of (S)-cathinone and the related phenylpropylamino alkaloids (1S,2S)-cathine and (1R,2S)-norephedrine is not well characterized in plants. We prepared a cDNA library from young khat leaves and sequenced 4,896 random clones, generating an expressed sequence tag (EST) library of 3,293 unigenes. Putative functi ...[more]
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Project description:Catha edulis Forsk. (Khat) is traditionally used for treating various disorders. Nevertheless there are no reports of any scientific assessment of its psychopharmacological properties.Therefore, the current study was designed to evaluate the antidepressant-like activity of Khat ethanolic extract using established animal models of depression and stress.Ninety healthy male albino mice were used in this study. Forced swim, tail suspension and head poking tests were utilized to evaluate the antidepressant-like activity of the ethanolic extract of Khat (100, 200 and 400 mg/kg, i.p.) and escitalopram (standard drug) which were administered 30 min prior to the tests. Phytochemical analysis of the standardized extract was conducted using liquid chromatography-mass spectroscopy (LC-MS).A significant decrease in the head-dipping behavior was noticed after administration of 100, 200 and 400 mg/kg of Khat extract. Moreover, the extract significantly decreased the immobility time in tail suspension and forced swim tests. The presence of cathinone and cathine were detected in the extract using LC-MS.The current results suggest that the extract of Khat leaves has acute antidepressant properties and may have sedative effects.Antidepressant-like activity of Khat established in vivoThe extract decreased the immobility time in tail suspension and forced swim testsLiquid chromatography-mass spectroscopy data revealed the presence of cathinone and cathine in Khat extract. Abbreviations used: LC-MS: Liquid chromatography-mass spectroscopy; NIST: National institute of standard technology; SSRI: Serotonin reuptake inhibitors; FST: Forced swim test; TST: Tail suspension test.
| S-EPMC5538179 | biostudies-other
Project description:BackgroundKhat is amphetamine-like substance commonly consumed by students when they wish to study for long hours especially during examination periods. Khat consumption is associated with increased rates of cardiovascular problems, stroke, myocardial infarction, cardiomyopathy, periodontal disease, gastritis, poor oral hygiene, psychosis, decreased quality of life, and poor academic performance.MethodsPubMed, EMBASE, and SCOPUS were systematically searched without restriction by publication status. Publications were screened according to predefined inclusion criteria. Twenty-five articles were included. Random effect model was used to calculate weighted prevalence, odds ratio (OR) and corresponding 95% confidence interval (CI). We assessed the risk of publication bias by using funnel plot and Eggers's regression tests.ResultsThe pooled prevalence of current khat use among university students was 14.16% (95% CI; 11.87-16.81). The pooled prevalence of current khat use was highest in Saudi Arabia 18.85% and it was 13.59% in Ethiopia and 13.04% in Yemen. In addition, the current pooled prevalence of khat use was higher in men at 19.26% than in women 6.41%. Regarding lifetime khat use, in this study, the pooled prevalence of lifetime khat use was 27.31%. The lifetime prevalence was higher in men at 31.47% than in women 11.79%. Moreover, the lifetime prevalence of khat use was 43.27% in Yemen, 37.32% in Saudi Arabia, and 24.82% in Ethiopia. We found significantly increased odds of current (OR 3.59; 95%CI 2.01-6.41) as well as lifetime (OR 3.48; 95%CI 2.09-5.78) khat chewing in men as compared to women.ConclusionThe pooled prevalence of current and lifetime khat consumption was 14.16 and 27.31%, respectively. Both the current and lifetime prevalence of khat use was higher in men than in women. In addition, both the current and lifetime prevalence estimates of khat consumption were low in Ethiopia than in Saudi Arabia. Moreover, the odds of both current and lifetime khat consumption were higher in male students than in female students. Programmes that specifically aim at increasing awareness and that most motivate reduced khat consumption among university students were recommended.
| S-EPMC6360776 | biostudies-literature
Project description:Cellulose fibers (C40 and C80) were extracted from khat (Catha edulis) waste (KW) with chlorine-free process using 40% formic acid/40% acetic acid (C40), and 80% formic acid/80% acetic acid (C80) at the pretreatment stage, followed by further delignification and bleaching stages. Cellulose nanocrystals (CNCs40 and CNCs80) were then isolated from C40 and C80 with sulfuric acid hydrolysis, respectively. Thus, the current study aims to isolate cellulose fibers and CNCs from KW as alternative source. The KW, cellulose fibers, and CNCs were investigated for yield, chemical composition, functionality, crystallinity, morphology, and thermal stability. CNCs were also evaluated for colloidal stability, particle size, and their influence on in vitro diclofenac sodium release from gel formulations preliminarily. The FTIR spectra analysis showed the removal of most hemicellulose and lignin from the cellulose fibers. The XRD results indicated that chemical pretreatments and acid hydrolysis significantly increased the crystallinity of cellulose fibers and CNCs. The cellulose fibers and CNCs exhibited Cellulose Iβ crystalline lattice. TEM analysis revealed formation of needle-shaped nanoscale rods (length: 101.55-162.96 nm; aspect ratio: 12.84-22.73). The hydrodynamic size, polydispersity index, and zeta potential of the CNCS ranged from 222.8-362.8 nm; 0.297-0.461, and -45.7 to -75.3 mV, respectively. CNCs40 exhibited superior properties to CNCs80 in terms of aspect ratio, and colloidal and thermal stability. Gel formulations containing high proportion of CNCs sustained diclofenac sodium release (< 50%/cm2) over 12 h. This study suggests that cellulose fibers and nanocrystals can be successfully obtained from abundant and unexploited source, KW for value-added industrial applications.
| S-EPMC7872298 | biostudies-literature
Project description:BackgroundKhat (Catha edulis Forsk) leaves are chewed by people in certain regions of East Africa and the Middle East for their stimulating amphetamine-like effects. The purpose of this scoping review is to systematically map the current in vitro publications that investigated the toxicological potential effects of khat on cultured human or animal cells in terms of cellular viability and activity.MethodsA comprehensive electronic database search was undertaken up to December 2020 without starting date or language restrictions in accordance with the PRISMA extension for scoping review guideline and methodological quality evaluation based on the guidelines for reporting pre-clinical in vitro studies on dental materials. All in vitro studies that investigated the effect of khat plant extract (Catha Edulis) on the cultured human or animal cells were included.ResultsThe initial search yielded 599 articles and 16 articles were finally selected to be included. The treatment of cells with khat produced different degrees of cellular changes, including decreased cellular survival, induction of apoptosis, increased ROS production, alteration of cell phenotype, and of arrest cell cycle. In this contest, khat-exposed cells expressed higher levels of pro-apoptotic protein Bax and lower levels of anti-apoptotic Bcl-2, up-regulated p38, p53, p16, and p21 proteins, as well as premature expression of differentiation markers.ConclusionBased on the current scoping review, khat induced apoptosis and cytotoxicity in cultured human cells, including oral cells.
| S-EPMC8646973 | biostudies-literature
Project description:Amphetamine analogues are produced by plants in the genus Ephedra and by khat (Catha edulis), and include the widely used decongestants and appetite suppressants (1S,2S)-pseudoephedrine and (1R,2S)-ephedrine. The production of these metabolites, which derive from L-phenylalanine, involves a multi-step pathway partially mapped out at the biochemical level using knowledge of benzoic acid metabolism established in other plants, and direct evidence using khat and Ephedra species as model systems. Despite the commercial importance of amphetamine-type alkaloids, only a single step in their biosynthesis has been elucidated at the molecular level. We have employed Illumina next-generation sequencing technology, paired with Trinity and Velvet-Oases assembly platforms, to establish data-mining frameworks for Ephedra sinica and khat plants. Sequence libraries representing a combined 200,000 unigenes were subjected to an annotation pipeline involving direct searches against public databases. Annotations included the assignment of Gene Ontology (GO) terms used to allocate unigenes to functional categories. As part of our functional genomics program aimed at novel gene discovery, the databases were mined for enzyme candidates putatively involved in alkaloid biosynthesis. Queries used for mining included enzymes with established roles in benzoic acid metabolism, as well as enzymes catalyzing reactions similar to those predicted for amphetamine alkaloid metabolism. Gene candidates were evaluated based on phylogenetic relationships, FPKM-based expression data, and mechanistic considerations. Establishment of expansive sequence resources is a critical step toward pathway characterization, a goal with both academic and industrial implications.
| S-EPMC4373857 | biostudies-literature
Project description:BackgroundUse of psychoactive drugs such as khat leaves (Catha edulis) alter moods and emotional state and lead to adverse effects on the health and social life of users. Ethiopia is a major producer and exporter of khat in east Africa and the majority of the khat comes from the eastern part of the country, however, no studies have been conducted to investigate the habit in this area. This study was conducted to assess the prevalence and predictors of khat chewing among high school students in Harar, eastern Ethiopia.MethodologyThe study was conducted among 1,890 secondary school students in Harar town in April 2010. A structured self-administered questionnaire was used for data collection. Descriptive statistics and logistic regression were performed to examine the prevalence and predictors of khat chewing.ResultThe overall prevalence of khat chewing among the sample was 24.2% (95% CI 22.2%-26.2%). About 28.5% of females and 71.5% of males had chewed khat. Older age (OR 1.31; 95% CI 1.16-1.49), male gender (OR 2.10; 95% CI 1.50-2.93), Muslim religion (OR 1.88; 95% CI 1.17-3.04), having friends who chewed khat (OR 7.93; 95% CI 5.40-11.64), and availability of someone with a similar habit in the family (OR 1.50; 95% CI 1.07-2.11) were found to be independent predictors of chewing.ConclusionA significant proportion of students chew khat. The use of khat is significantly associated with age, gender, Muslim religion, peer influence and habit of family and other relatives among students. Measures such as educational campaigns need to be instituted to create awareness among school adolescents and their parents in order to reduce the prevalence of the habit and its adverse social and health consequences.
| S-EPMC3316517 | biostudies-literature
Project description:In a one-way cross-over study, we investigated the effect of Khat, a natural amphetamine-like psychostimulant plant, on catalytic activities of five major drug-metabolizing cytochrome P450 (CYP) enzymes. After a one-week Khat abstinence, 63 Ethiopian male volunteers were phenotyped using cocktail probe drugs (caffeine, losartan, dextromethorphan, omeprazole). Phenotyping was repeated after a one-week daily use of 400?g fresh Khat leaves. Genotyping for CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A5 were done. Urinary cathinone and phenylpropanolamine, and plasma probe drugs and metabolites concentrations were quantified using LC-MS/MS. Effect of Khat on enzyme activities was evaluated by comparing caffeine/paraxanthine (CYP1A2), losartan/losartan carboxylic acid (CYP2C9), omeprazole/5-hydroxyomeprazole (CYP2C19), dextromethorphan/dextrorphan (CYP2D6) and dextromethorphan/3-methoxymorphinan (CYP3A4) metabolic ratios (MR) before and after Khat use. Wilcoxon-matched-pair-test indicated a significant increase in median CYP2D6 MR (41%, p?<?0.0001), and a marginal increase in CYP3A4 and CYP2C19 MR by Khat. Repeated measure ANOVA indicated the impact of CYP1A2 and CYP2C19 genotype on Khat-CYP enzyme interactions. The median MR increased by 35% in CYP1A2*1/*1 (p?=?0.07) and by 40% in carriers of defective CYP2C19 alleles (p?=?0.03). Urinary log cathinone/phenylpropanolamine ratios significantly correlated with CYP2D6 genotype (p?=?0.004) and CYP2D6 MR (P?=?0.025). Khat significantly inhibits CYP2D6, marginally inhibits CYP3A4, and genotype-dependently inhibit CYP2C19 and CYP1A2 enzyme activities.
| S-EPMC6109098 | biostudies-literature
Project description:BackgroundThe burden of hypertension is more devastating in low-and middle-income countries, including sub-Saharan Africa than in high-income countries. Among the modifiable risk factors, dyslipidemia and khat chewing were expanding at an alarming rate in Ethiopia but were still underestimated. Thus, this study aimed to assess heavy khat (Catha edulis) chewing and dyslipidemia as modifiable hypertensive risk factors among patients in the southwest, Ethiopia.MethodsA facility-based case-control study was conducted among 136 cases and 270 controls from May 15 to July 30, 2017. A consecutive sampling technique was used in this study. Epi data version 3.1.1 and SPSS version 21 were used for data entry and analysis. Descriptive statistics and bivariate and multivariate logistic regression analyses were performed. Both crude and adjusted odds ratios and 95% confidence intervals were reported.ResultsThe majority of the cases had a total cholesterol to high-density lipoprotein ratio of >5 (72.1%). The odds of hypertension increased among participants who had attended no formal education [AOR = 2.25, 95% CI: (1.05-4.82)], history of alcohol consumption [AOR = 5.93,95% CI:(3.11-11.30)], moderate khat chewing [AOR = 3.68, 95% CI:(1.69,8.01)], heavy khat chewing [AOR = 18.18, 95% CI: (3.56-92.89)], mild intensity physical activity [AOR = 3.01, 95% CI: (1.66-5.47)], type of oil used for food preparation [AOR = 2.81, 95% CI: (1.49-5.28)], and dyslipidemia [AOR = 6.68, 95% CI: (2.93-15.23)].ConclusionThe study showed that modifiable risk factors were the major factors associated with the development of hypertension. The findings of this study highlighted that health education is needed to focus on physical exercise, quitting excess alcohol consumption, quitting khat chewing by giving special emphasis to those who had no formal education. In addition, consideration should be given to a healthy diet free of cholesterol and unhealthy behavior.
| S-EPMC8547649 | biostudies-literature
Project description:The use of khat (Catha edulis) and alcohol during pregnancy is a serious public health problem that has been associated with a number of harmful outcomes for both the fetus and the mother's health. There has been no systematic review with meta-analysis to determine risk factors associated with khat and alcohol use among pregnant women in Ethiopia. Therefore, we aimed to determine the pooled prevalence and risk factors of khat and alcohol use during pregnancy in Ethiopia. This review has been registered in PROSPERO with protocol ID: CRD42023395115. Studies identified from PubMed, Google Scholar, the WHO African Index Medicus, the Cochrane Library, African Journal Online, and Science Direct. Articles published from January 1, 2000 to February 10, 2023 were included. We searched for articles that included any combination of the following key terms: "khat", "qat", "alcohol", "ethanol", "prevalence", "factors", "pregnant" and "Ethiopia". Two reviewers worked independently to screen studies and extract data. A funnel plot and Egger's regression test were used to test publication bias. A forest plot was used to present the pooled prevalence and odds ratio with a 95% confidence interval (CI) using the random effect model. I2 metrics were used to assess heterogeneity. The meta-analysis was carried out with Stata 14.0 software. Nine hundred sixty-two records were retrieved from different sources, and 23 studies were included in the final analysis. The pooled prevalence of khat use and alcohol drinking during pregnancy was 26.6% (95% CI 17.8, 35.5) and 31.65% (95% CI: 21.8, 41.5), respectively. Partner khat use (OR 5.9 [95% CI (2.4, 14.5)]) was associated factor for khat use during pregnancy. Low educational level (OR 2.54 [95% CI (1.8, 3.5)]), pre-pregnancy alcohol use (OR 3.5 [95% CI (2.6, 4.7)]), unplanned pregnancy (OR 2.7 [95% CI (1.8, 4.0)]), history of abortion (OR 2.3 [95% CI (1.4, 3.7)]), poor social support (OR 3.3 [95% CI (2.0, 5.3)]), and mental distress (OR 2.6 [95% CI (2.0, 3.3)]) were associated factors for alcohol drinking during pregnancy. This review indicated that the magnitude of khat and alcohol use during pregnancy in Ethiopia was high. Targeted interventions for groups of pregnant women at high risk of khat and alcohol use are urgently needed. Community-based health education interventions and point-of-sale warnings are essential to reduce the burden. Future studies should consider the influence of community-level factors on khat and alcohol use during pregnancy.
| S-EPMC10503716 | biostudies-literature
