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Article ; Online: Histamine H3 receptor antagonists - Roles in neurological and endocrine diseases and diabetes mellitus.

Abdulrazzaq, Yousef M / Bastaki, Salim M A / Adeghate, Ernest

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

2022 Volume 150, Page(s) 112947

Abstract: Human histamine H3 receptor (H3R) was initially described in the brain of rat in 1983 and cloned in 1999. It can be found in the human brain and functions as a regulator of histamine synthesis and release. H3 receptors are predominantly resident in the ... ...

Abstract	Human histamine H3 receptor (H3R) was initially described in the brain of rat in 1983 and cloned in 1999. It can be found in the human brain and functions as a regulator of histamine synthesis and release. H3 receptors are predominantly resident in the presynaptic region of neurons containing histamine, where they modulate the synthesis and release of histamine (autoreceptor) or other neurotransmitters such as dopamine, norepinephrine, gamma-aminobutyric acid (GABA), glutamate, acetylcholine and serotonin (all heteroreceptors). The human histamine H3 receptor has twenty isoforms of which eight are functional. H3 receptor expression is seen in the cerebral cortex, neurons of the basal ganglia and hippocampus, which are important for process of cognition, sleep and homoeostatic regulation. In addition, histamine H3R antagonists stimulate insulin release, through inducing the release of acetylcholine and cause significant reduction in total body weight and triglycerides in obese subjects by causing a feeling of satiety in the hypothalamus. The ability of histamine H3R antagonist to reduce diabetes-induced hyperglycaemia is comparable to that of metformin. It is reasonable therefore, to claim that H3 receptor antagonists may play an important role in the therapy of disorders of cognition, the ability to sleep, oxidative stress, inflammation and anomaly of glucose homoeostasis. A large number of H3R antagonists are being developed by pharmaceutical companies and university research centres. As examples of these new drugs, this review will discuss a number of drugs, including the first histamine H3R receptor antagonist produced.
MeSH term(s)	Acetylcholine ; Animals ; Diabetes Mellitus ; Histamine ; Histamine Antagonists/pharmacology ; Histamine H3 Antagonists/pharmacology ; Histamine H3 Antagonists/therapeutic use ; Humans ; Rats ; Receptors, Histamine H3/metabolism
Chemical Substances	Histamine Antagonists ; Histamine H3 Antagonists ; Receptors, Histamine H3 ; Histamine (820484N8I3) ; Acetylcholine (N9YNS0M02X)
Language	English
Publishing date	2022-04-19
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	392415-4
ISSN	1950-6007 ; 0753-3322 ; 0300-0893
ISSN (online)	1950-6007
ISSN	0753-3322 ; 0300-0893
DOI	10.1016/j.biopha.2022.112947
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Article ; Online: Lycopodium Mitigates Oxidative Stress and Inflammation in the Colonic Mucosa of Acetic Acid-Induced Colitis in Rats.

Bastaki, Salim M A / Amir, Naheed / Adeghate, Ernest / Ojha, Shreesh

Molecules (Basel, Switzerland)

2022 Volume 27, Issue 9

Abstract: Inflammatory bowel diseases (IBDs) such as ulcerative colitis (UC) and Crohn's disease (CD) are diseases of the gastrointestinal system involving genetic and environmental factors attributed to oxidative stress and inflammation. Targeting oxidative ... ...

Abstract	Inflammatory bowel diseases (IBDs) such as ulcerative colitis (UC) and Crohn's disease (CD) are diseases of the gastrointestinal system involving genetic and environmental factors attributed to oxidative stress and inflammation. Targeting oxidative stress and inflammation by novel dietary compounds of natural origin convincingly appears to be one of the important therapeutic strategies to keep the disease in remission. As there is no permanent cure for IBD except for chronic long-term treatment or surgery, it is therefore imperative to investigate plant-based agents that are receiving attention for their therapeutic benefits to overcome the debilitating clinical conditions of IBD. Lycopodium (LYCO), a plant of tropical and subtropical origin and known by numerous names such as ground pine, club moss, or devil's claw, has been popularly used for centuries in traditional medicine including Chinese and Indian medicines. In the present study, the effect of LYCO has been investigated in an acetic acid (AA)-induced colitis model in Wistar rats. LYCO was orally administered at the dose of 50 mg/kg/day either 3 days before or 30 min after the induction of IBD and continued for 7 days by intrarectal administration of AA. The changes in body weight and macroscopic and microscopic analysis of the colon of rats of different experimental groups were observed on days 0, 2, 4, and 7. The levels of myeloperoxidase (MPO), reduced glutathione (GSH), and malondialdehyde (MDA) were measured. AA caused a significant reduction in body weight and increased macroscopic and microscopic ulcer scores along with a significant decline in antioxidant enzymes, superoxide dismutase (SOD), and catalase and antioxidant substrate, glutathione (GSH). There was a concomitant increased formation of malondialdehyde (MDA), a marker of lipid peroxidation, and raised myeloperoxidase (MPO) activity, a marker of neutrophil activation. Treatment with LYCO significantly improved IBD-induced reduction in body weight, improved histology, inhibited MDA formation, and restored antioxidants along with reduced MPO activity. AA also caused the release of proinflammatory cytokines such as interleukin-1β (IL-1β) and interleukin-23 (IL-23). Furthermore, AA also increased the levels of calprotectin, a protein released by neutrophils under inflammatory conditions of the gastrointestinal tract. LYCO treatment significantly reduced the release of calprotectin and proinflammatory cytokines. The results demonstrate that LYCO treatment has the potential to improve disease activity by inhibiting oxidative stress, lipid peroxidation, and inflammation along with histological preservation of colonic tissues.
MeSH term(s)	Acetic Acid/metabolism ; Animals ; Anti-Inflammatory Agents/therapeutic use ; Antioxidants/metabolism ; Body Weight ; Colitis/chemically induced ; Colitis/drug therapy ; Colitis/metabolism ; Colitis, Ulcerative/chemically induced ; Colitis, Ulcerative/drug therapy ; Colitis, Ulcerative/metabolism ; Cytokines/metabolism ; Glutathione/metabolism ; Inflammation/metabolism ; Inflammatory Bowel Diseases/pathology ; Intestinal Mucosa/metabolism ; Leukocyte L1 Antigen Complex/metabolism ; Leukocyte L1 Antigen Complex/pharmacology ; Leukocyte L1 Antigen Complex/therapeutic use ; Lycopodium ; Malondialdehyde/metabolism ; Oxidative Stress ; Peroxidase/metabolism ; Rats ; Rats, Wistar
Chemical Substances	Anti-Inflammatory Agents ; Antioxidants ; Cytokines ; Leukocyte L1 Antigen Complex ; Malondialdehyde (4Y8F71G49Q) ; Peroxidase (EC 1.11.1.7) ; Glutathione (GAN16C9B8O) ; Acetic Acid (Q40Q9N063P)
Language	English
Publishing date	2022-04-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules27092774
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Article ; Online: Nerolidol, a sesquiterpene, attenuates oxidative stress and inflammation in acetic acid-induced colitis in rats.

Bastaki, Salim M A / Amir, Naheed / Adeghate, Ernest / Ojha, Shreesh

Molecular and cellular biochemistry

2021 Volume 476, Issue 9, Page(s) 3497–3512

Abstract: Targeting oxidative stress and inflammation by novel dietary compounds of natural origin convincingly appears to be one of the most important therapeutic strategies to keep inflammatory bowel diseases (IBD) such as ulcerative colitis disease in remission. ...

Abstract	Targeting oxidative stress and inflammation by novel dietary compounds of natural origin convincingly appears to be one of the most important therapeutic strategies to keep inflammatory bowel diseases (IBD) such as ulcerative colitis disease in remission. It is imperative to investigate naturally occuring plant-derived dietary phytochemicals that are receiving attention for their therapeutic benefits to overcome the debilitating conditions of IBD. In the present study, the effect of nerolidol (NRD), a monocyclic sesquiterpene found in German Chamomile tea, was investigated in acetic acid-induced colitis model in Wistar rats. NRD was orally administered at a dose of 50 mg/kg/day either for 3 days before or 30 min after induction of IBD for 7 days, after intrarectal administration of acetic acid. The body weight, macroscopic, and microscopic analyses of the colon in different experimental groups were observed on days 0, 2, 4, and 7. Acetic acid caused significant reduction in body weight and induced macroscopic and microscopic ulcer along with a significant decline of antioxidants, concomitant to increased malondialdehyde (MDA), a marker of lipid peroxidation, and myeloperoxidase (MPO) activity, a marker of neutrophil activation. Treatment with NRD significantly improved IBD-induced reduction in body weight, improved histology, inhibited MDA formation, and restored antioxidants along with reduced MPO activity. Acetic acid also induced the release of pro-inflammatory cytokines and increased calprotectin, released by neutrophils under inflammatory conditions. NRD treatment significantly reduced calprotectin and pro-inflammatory cytokines. NRD treatment showed potential to improve disease activity and inhibit oxidative stress, lipid peroxidation, and inflammation along with histological preservation of the colon tissues.
MeSH term(s)	Acetic Acid/toxicity ; Animals ; Anti-Bacterial Agents/toxicity ; Anti-Inflammatory Agents/pharmacology ; Antioxidants/pharmacology ; Colitis/chemically induced ; Colitis/drug therapy ; Colitis/metabolism ; Colitis/pathology ; Cytokines/metabolism ; Glutathione/metabolism ; Inflammation/etiology ; Inflammation/metabolism ; Inflammation/pathology ; Inflammation/prevention & control ; Lipid Peroxidation ; Male ; Oxidative Stress/drug effects ; Rats ; Rats, Wistar ; Sesquiterpenes/pharmacology
Chemical Substances	Anti-Bacterial Agents ; Anti-Inflammatory Agents ; Antioxidants ; Cytokines ; Sesquiterpenes ; Glutathione (GAN16C9B8O) ; Acetic Acid (Q40Q9N063P) ; nerolidol (QR6IP857S6)
Language	English
Publishing date	2021-05-17
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	184833-1
ISSN	1573-4919 ; 0300-8177
ISSN (online)	1573-4919
ISSN	0300-8177
DOI	10.1007/s11010-021-04094-5
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Article ; Online: Chemical constituents and medicinal properties of Allium species.

Bastaki, Salim M A / Ojha, Shreesh / Kalasz, Huba / Adeghate, E

Molecular and cellular biochemistry

2021 Volume 476, Issue 12, Page(s) 4301–4321

Abstract: Allium species, belonging to Alliaceae family, are among the oldest cultivated vegetables used as food. Garlic, onions, leeks and chives, which belong to this family, have been reported to have medicinal properties. The Allium species constituents have ... ...

Abstract	Allium species, belonging to Alliaceae family, are among the oldest cultivated vegetables used as food. Garlic, onions, leeks and chives, which belong to this family, have been reported to have medicinal properties. The Allium species constituents have been shown to have antibacterial and antioxidant activities, and, in addition, other biological properties. These activities are related to their rich organosulfur compounds. These organosulfur compounds are believed to prevent the development of cancer, cardiovascular, neurological, diabetes, liver diseases as well as allergy and arthritis. There have also been reports on toxicities of these compounds. The major active compounds of Allium species includes, diallyl disulfide, diallyl trisulfide, diallyl sulfide, dipropyl disulfide, dipropyl trisulfide, 1-propenylpropyl disulfide, allyl methyl disulfide and dimethyl disulfide. The aim of this review is to focus on a variety of experimental and clinical reports on the effectiveness, toxicities and possible mechanisms of actions of the active compounds of garlic, onions, leek and chives.
MeSH term(s)	Allium/chemistry ; Allium/metabolism ; Animals ; Anti-Infective Agents/chemistry ; Anti-Infective Agents/pharmacology ; Antioxidants/chemistry ; Antioxidants/pharmacology ; Cardiovascular Diseases/drug therapy ; Cardiovascular Diseases/metabolism ; Cardiovascular Diseases/pathology ; Diabetes Mellitus/drug therapy ; Diabetes Mellitus/metabolism ; Diabetes Mellitus/pathology ; Humans ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Neoplasms/pathology ; Nervous System Diseases/drug therapy ; Nervous System Diseases/metabolism ; Nervous System Diseases/pathology ; Plants, Medicinal/chemistry ; Plants, Medicinal/metabolism
Chemical Substances	Anti-Infective Agents ; Antioxidants
Language	English
Publishing date	2021-08-21
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	184833-1
ISSN	1573-4919 ; 0300-8177
ISSN (online)	1573-4919
ISSN	0300-8177
DOI	10.1007/s11010-021-04213-2
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Article ; Online: Health Benefits, Pharmacological Effects, Molecular Mechanisms, and Therapeutic Potential of α-Bisabolol.

Eddin, Lujain Bader / Jha, Niraj Kumar / Goyal, Sameer N / Agrawal, Yogeeta O / Subramanya, Sandeep B / Bastaki, Salim M A / Ojha, Shreesh

Nutrients

2022 Volume 14, Issue 7

Abstract: α-Bisabolol is one of the important monocyclic sesquiterpenes, derived naturally from essential oils of many edible and ornamental plants. It was first obtained ... ...

Abstract	α-Bisabolol is one of the important monocyclic sesquiterpenes, derived naturally from essential oils of many edible and ornamental plants. It was first obtained from
MeSH term(s)	Animals ; Matricaria/metabolism ; Monocyclic Sesquiterpenes ; Oils, Volatile/pharmacology ; Plant Extracts/pharmacology ; Sesquiterpenes/metabolism ; Sesquiterpenes/pharmacology
Chemical Substances	Monocyclic Sesquiterpenes ; Oils, Volatile ; Plant Extracts ; Sesquiterpenes ; bisabolol (24WE03BX2T)
Language	English
Publishing date	2022-03-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu14071370
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Article ; Online: Effect of Aspirin and ibuprofen either alone or in combination on gastric mucosa and bleeding time and on serum prostaglandin E

Bastaki, Salim M A / Padol, Ireneusz T / Amir, Naheed / Hunt, Richard H

Molecular and cellular biochemistry

2018 Volume 438, Issue 1-2, Page(s) 25–34

Abstract: There is much evidence that a combination of ibuprofen (IBU) and Aspirin (ASA) can antagonize the irreversible inhibition of platelet function. This study was designed to investigate the degree of gastric damage, bleeding time (BT) and fluctuations in ... ...

Abstract	There is much evidence that a combination of ibuprofen (IBU) and Aspirin (ASA) can antagonize the irreversible inhibition of platelet function. This study was designed to investigate the degree of gastric damage, bleeding time (BT) and fluctuations in the serum levels of prostaglandin E
MeSH term(s)	Anesthesia ; Animals ; Aspirin/adverse effects ; Aspirin/pharmacokinetics ; Bleeding Time ; Dinoprostone/blood ; Female ; Gastric Mucosa/metabolism ; Gastric Mucosa/pathology ; Ibuprofen/adverse effects ; Ibuprofen/pharmacology ; Male ; Rats ; Rats, Wistar ; Stomach Ulcer/blood ; Stomach Ulcer/chemically induced ; Stomach Ulcer/pathology ; Thromboxane A2/blood
Chemical Substances	Thromboxane A2 (57576-52-0) ; Dinoprostone (K7Q1JQR04M) ; Aspirin (R16CO5Y76E) ; Ibuprofen (WK2XYI10QM)
Language	English
Publishing date	2018-01
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	184833-1
ISSN	1573-4919 ; 0300-8177
ISSN (online)	1573-4919
ISSN	0300-8177
DOI	10.1007/s11010-017-3110-1
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Article: Influence of the Novel Histamine H3 Receptor Antagonist/Inverse Agonist M39 on Gastroprotection and PGE2 Production Induced by (

Bastaki, Salim M A / Amir, Naheed / Więcek, Małgorzata / Kieć-Kononowicz, Katarzyna / Sadek, Bassem

Frontiers in pharmacology

2019 Volume 10, Page(s) 966

Abstract: The role of histamine H3 receptors (H3Rs) in the regulation of gastroprotection and production of prostaglandin E2 (PGE2) as well as somatostatin remains contradictory. Therefore, the effects of the H3R antagonist/inverse agonist M39 ... ...

Abstract	The role of histamine H3 receptors (H3Rs) in the regulation of gastroprotection and production of prostaglandin E2 (PGE2) as well as somatostatin remains contradictory. Therefore, the effects of the H3R antagonist/inverse agonist M39 on
Language	English
Publishing date	2019-09-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2019.00966
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Article ; Online: Effect of turmeric on colon histology, body weight, ulcer, IL-23, MPO and glutathione in acetic-acid-induced inflammatory bowel disease in rats.

Bastaki, Salim M A / Al Ahmed, Mohammed Majed / Al Zaabi, Ahmed / Amir, Naheed / Adeghate, Ernest

BMC complementary and alternative medicine

2016 Volume 16, Page(s) 72

Abstract: Background: This study investigates the protective effects of turmeric (Curcuma longa, CL) on acetic acid-induced colitis in rats.: Method: Inflammatory bowel disease (IBD) was induced in male Wistar rats by intra-rectal administration of 1 ml of 4% ... ...

Abstract	Background: This study investigates the protective effects of turmeric (Curcuma longa, CL) on acetic acid-induced colitis in rats. Method: Inflammatory bowel disease (IBD) was induced in male Wistar rats by intra-rectal administration of 1 ml of 4% acetic acid at 8 cm proximal to the anus for 30 s. Curcuma longa (CL) powder, (1, 10, or 100 mg/kg/day) was administered for either 3 days before or after IBD for 7 days. The body weight, macroscopic and microscopic analysis of the colon of CL-treated IBD rats and that of control rats (no IBD, no CL) were performed on 0 day, 2, 4 and 7th day. Myeloperoxidase (MPO), IL-23 and glutathione levels in control, untreated and treated rats were measured by ELISA. Results: CL significantly (P < 0.05) improved IBD-induced reduction in mean body weight and mean macroscopic ulcer score. Administration of CL also significantly (P < 0.01) reduced the mean microscopic ulcer score when compared to untreated IBD control. Intake of CL by rats resulted in a significant (P < 0.05) increase in the mean serum glutathione level compared to untreated control. CL reduced both MPO and IL-23 levels in the colonic mucosa of the rat. Conclusion: CL improved body weight gain, mean macroscopic and microscopic ulcer scores in the colon of rats suffering from acetic acid-induced IBD. CL reduced both MPO and IL-23 in the mucosa of the colon. The increase in the mean serum glutathione level may help in the reduction of oxidative stress associated with IBD.
MeSH term(s)	Acetic Acid ; Animals ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use ; Antioxidants/pharmacology ; Antioxidants/therapeutic use ; Body Weight/drug effects ; Colitis, Ulcerative/chemically induced ; Colitis, Ulcerative/drug therapy ; Colitis, Ulcerative/metabolism ; Colitis, Ulcerative/pathology ; Colon/drug effects ; Colon/metabolism ; Colon/pathology ; Curcuma ; Glutathione/metabolism ; Inflammatory Bowel Diseases/drug therapy ; Inflammatory Bowel Diseases/metabolism ; Inflammatory Bowel Diseases/pathology ; Interleukin-23/blood ; Intestinal Mucosa/drug effects ; Intestinal Mucosa/metabolism ; Intestinal Mucosa/pathology ; Male ; Oxidative Stress/drug effects ; Peroxidase/blood ; Phytotherapy ; Plant Extracts/pharmacology ; Plant Extracts/therapeutic use ; Rats, Wistar ; Ulcer
Chemical Substances	Anti-Inflammatory Agents ; Antioxidants ; Interleukin-23 ; Plant Extracts ; Peroxidase (EC 1.11.1.7) ; Glutathione (GAN16C9B8O) ; Acetic Acid (Q40Q9N063P)
Language	English
Publishing date	2016-02-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2050429-9
ISSN	1472-6882 ; 1472-6882
ISSN (online)	1472-6882
ISSN	1472-6882
DOI	10.1186/s12906-016-1057-5
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Article: Effect of turmeric on colon histology, body weight, ulcer, IL-23, MPO and glutathione in acetic-acid-induced inflammatory bowel disease in rats

Bastaki, Salim M. A / Mohammed Majed Al Ahmed / Ahmed Al Zaabi / Naheed Amir / Ernest Adeghate

BMC complementary and alternative medicine. 2016 Dec., v. 16, no. 1

2016

Abstract: BACKGROUND: This study investigates the protective effects of turmeric (Curcuma longa, CL) on acetic acid-induced colitis in rats. METHOD: Inflammatory bowel disease (IBD) was induced in male Wistar rats by intra-rectal administration of 1Â ml of 4Â % ... ...

Abstract	BACKGROUND: This study investigates the protective effects of turmeric (Curcuma longa, CL) on acetic acid-induced colitis in rats. METHOD: Inflammatory bowel disease (IBD) was induced in male Wistar rats by intra-rectal administration of 1Â ml of 4Â % acetic acid at 8Â cm proximal to the anus for 30Â s. Curcuma longa (CL) powder, (1, 10, or 100Â mg/kg/day) was administered for either 3Â days before or after IBD for 7Â days. The body weight, macroscopic and microscopic analysis of the colon of CL-treated IBD rats and that of control rats (no IBD, no CL) were performed on 0Â day, 2, 4 and 7thÂ day. Myeloperoxidase (MPO), IL-23 and glutathione levels in control, untreated and treated rats were measured by ELISA. RESULTS: CL significantly (Pâ<â0.05) improved IBD-induced reduction in mean body weight and mean macroscopic ulcer score. Administration of CL also significantly (Pâ<â0.01) reduced the mean microscopic ulcer score when compared to untreated IBD control. Intake of CL by rats resulted in a significant (Pâ<â0.05) increase in the mean serum glutathione level compared to untreated control. CL reduced both MPO and IL-23 levels in the colonic mucosa of the rat. CONCLUSION: CL improved body weight gain, mean macroscopic and microscopic ulcer scores in the colon of rats suffering from acetic acid-induced IBD. CL reduced both MPO and IL-23 in the mucosa of the colon. The increase in the mean serum glutathione level may help in the reduction of oxidative stress associated with IBD.
Keywords	Curcuma longa ; acetic acid ; alternative medicine ; anus ; blood serum ; body weight changes ; colitis ; colon ; enzyme-linked immunosorbent assay ; glutathione ; histology ; interleukin-23 ; males ; mucosa ; myeloperoxidase ; oxidative stress ; protective effect ; rats ; turmeric
Language	English
Dates of publication	2016-12
Size	p. 72.
Publishing place	BioMed Central
Document type	Article
ZDB-ID	2050429-9
ISSN	1472-6882
ISSN	1472-6882
DOI	10.1186/s12906-016-1057-5
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Genetic polymorphisms of cytochrome P450-1A2 (CYP1A2) among Emiratis.

Al-Ahmad, Mohammad M / Amir, Naheed / Dhanasekaran, Subramanian / John, Anne / Abdulrazzaq, Yousef M / Ali, Bassam R / Bastaki, Salim M A

PloS one

2017 Volume 12, Issue 9, Page(s) e0183424

Abstract: Cytochrome P450 1A2 (CYP1A2) is one of the CYP450 mixed-function oxidase system that is of clinical importance due to the large number of drug interactions associated with its induction and inhibition. In addition, significant inter-individual ... ...

Abstract	Cytochrome P450 1A2 (CYP1A2) is one of the CYP450 mixed-function oxidase system that is of clinical importance due to the large number of drug interactions associated with its induction and inhibition. In addition, significant inter-individual differences in the elimination of drugs metabolized by CYP1A2 enzyme have been observed which are largely due to the highly polymorphic nature of CYP1A2 gene. However, there are limited studies on CYP1A2 phenotypes and CYP1A2 genotypes among Emiratis and thus this study was carried out to fill this gap. Five hundred and seventy six non-smoker Emirati subjects were asked to consume a soft drink containing caffeine (a non-toxic and reliable probe for predicting CYP1A2 phenotype) and then provide a buccal swab along with a spot urine sample. Taq-Man Real Time PCR was used to determine the CYP1A2 genotype of each individual. Phenotyping was carried out by analyzing the caffeine metabolites using High Performance Liquid Chromatography (HPLC) analysis. We found that 1.4%, 16.3% and 82.3% of the Emirati subjects were slow, intermediate and rapid CYP1A2 metabolizers, respectively. In addition, we found that 1.4% of the subjects were homozygote for derived alleles while 16.1% were heterozygote and 82.5% were homozygote for the ancestral allele. The genotype frequency of the ancestral allele, CYP1A21A/1A, is the highest in this population, followed by CYP1A2 1A/1C and CYP1A2 1A/1K genotypes, with frequencies of 0.825, 0.102 and 0.058, respectively. The degree of phenotype/genotype concordance was equal to 81.6%. The CYP1A21C/1C and CYP1A23/3 genotypes showed significantly the lowest enzyme phenotypic activity. The frequency of slow activity CYP1A2 enzyme alleles is very low among Emiratis which correlates with the presence of low frequencies of derived alleles in CYP1A2 gene.
MeSH term(s)	Adolescent ; Adult ; Caffeine/metabolism ; Cytochrome P-450 CYP1A2/genetics ; Female ; Genotype ; Haplotypes ; Humans ; Male ; Middle Aged ; Phenotype ; Polymorphism, Single Nucleotide ; United Arab Emirates ; Young Adult
Chemical Substances	Caffeine (3G6A5W338E) ; CYP1A2 protein, human (EC 1.14.14.1) ; Cytochrome P-450 CYP1A2 (EC 1.14.14.1)
Language	English
Publishing date	2017
Publishing country	United States
Document type	Journal Article
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0183424
Database	MEDical Literature Analysis and Retrieval System OnLINE

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