Zaki Tubesha

Universiti Putra Malaysia

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Maznah Ismail

Universiti Malaysia Perlis

Mustapha Umar Imam

Usmanu Danfodiyo University

Hairuszah Ithnin

Universiti Putra Malaysia

Mohd Idris Shah Ismail

Universiti Putra Malaysia

Abdul Rahman Omar

Universiti Putra Malaysia

Khalaf S. Al-Delaimy

University of Jordan

Zuki Abu Bakar

Universiti Putra Malaysia

Shahid Iqbal

University of Education

Rozi Mahmud

Universiti Putra Malaysia

Cooperative Institutions

Universiti Putra Malaysia

Bioscience (China)

University of Baghdad

John Wiley & Sons (United States)

University of Peshawar

Serdang Hospital

National Cancer Council Malaysia

Okayama University

Tun Hussein Onn University of Malaysia

Usmanu Danfodiyo University

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Characterization and chemical stability studies for thymoquinone-rich fraction (TQRF) nanoemulsion prepared by high pressure homogenizer

PharmaNutrition (2014)

Zaki Tubesha Mohd Idris Shah Ismail

Thymoquinone

Homogenizer

Fraction (chemistry)

Characterization

10.1016/j.phanu.2013.11.105

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Citations (4)

Effects of hydrolytic conditions on recovery of antioxidants from methanolic extracts of Nigella sativa seeds

Journal of Medicinal Plants Research (2011)

Zaki Tubesha Shahid Iqbal Maznah Ismail

Nigella sativa (NS) has health promoting beneficial properties including antioxidant activity. In this study, the impact of acid and alkaline hydrolysis conditions on phenolic (TPC), flavonoid (TFC) contents and antioxidant activity of methanolic extracts from N. sativa (NS) seeds powder is evaluated. Total phenolic and flavonoid contents were evaluated according to Folin-Ciocalteu procedure and aluminium chloride colorimetric assays, respectively. The TPC extracts varied from 67 to 73 mg/100 g NS powder, expressed as Gallic acid equivalents (GAE), while TFC concentrations varied from 96 to 113 mg rutin equivalents (RE)/100 g NS powder. Positive correlations were found between TPC and TFC in NS hydrolyzates and their1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity (r2 = 0.975 and 0.978, respectively). The alkaline hydrolyzed extract (BHE) showed the highest TPC and TFC (730 µg GAE and1130 µg RE/g NS powder, respectively) as well as the highest antioxidant activity (DPPH• =167±0.133 mg TEAC /100 g dry NS, ABTS•+=112 ± 0.023 mg TEAC /100 g dry NS and FRAP=28 ± 0.159 mg GAE/100 g dry NS) compared to acid hydrolyzed (AHE) and non-hydrolyzed extracts (NHE). Non-hydrolyzed extracts showed the lowest TPC and TFC content (670 µg GAE and 960 µg RE/g NS powder, respectively) through the assays (p < 0.05). Findings of the study reveal that hydrolysis has profound effects on recovery of antioxidants from NS extracts. Overall, BHE has the highest antioxidant activity compared to AHE or NHE. Key words: Nigella sativa, methanolic extracts, hydrolysis, total phenolic content, total flavonoid content, antioxidant activity.

Nigella sativa

ABTS

10.5897/jmpr.9000526

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Citations (11)

Study on the Potential Toxicity of a Thymoquinone-Rich Fraction Nanoemulsion in Sprague Dawley Rats

Molecules (2013)

Zaki Tubesha Mustapha Umar Imam Rozi Mahmud Maznah Ismail

Toxicological studies constitute an essential part of the effort in developing an herbal medicine into a drug product. A newly developed thymoquinone-rich fraction nanoemulsion (TQRFNE) has been prepared using a high pressure homogenizer. The purpose of this study was to investigate the potential acute toxicity of this nanoemulsion in Sprague Dawley rats. The acute toxicity studies were conducted as per the OECD guidelines 425, allowing for the use of test dose limit of 20 mL TQRFNE (containing 44.5 mg TQ)/kg. TQRFNE and distilled water (DW) as a control were administered orally to both sexes of rats on Day 0 and observed for 14 days. All the animals appeared normal, and healthy throughout the study. There was no observed mortality or any signs of toxicity during the experimental period. The effects of the TQRFNE and DW groups on general behavior, body weight, food and water consumption, relative organ weight, hematology, histopathology, and clinical biochemistry were measured. All the parameters measured were unaffected as compared to the control (DW) group. The administration of 20 mL TQRFNE /kg was not toxic after an acute exposure.

Thymoquinone

Distilled water

Histopathology

10.3390/molecules18077460

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Citations (51)

Effects of Germinated Brown Rice and Its Bioactive Compounds on the Expression of the Peroxisome Proliferator-Activated Receptor Gamma Gene

Nutrients (2013)

Mustapha Umar Imam Maznah Ismail Hairuszah Ithnin Zaki Tubesha Abdul Rahman Omar

Dysregulated metabolism is implicated in obesity and other disease conditions like type 2 diabetes mellitus and cardiovascular diseases, which are linked to abnormalities of peroxisome proliferator-activated receptor gamma (PPARγ). PPARγ has been the focus of much research aimed at managing these diseases. Also, germinated brown rice (GBR) is known to possess antidiabetic, antiobesity and hypocholesterolemic effects. We hypothesized that GBR bioactive compounds may mediate some of the improvements in metabolic indices through PPARγ modulation. Cultured HEP-G2 cells were treated with 50 ppm and 100 ppm of extracts from GBR (GABA, ASG and oryzanol) after determination of cell viabilities using MTT assays. Results showed that all extracts upregulated the expression of the PPARγ. However, combination of all three extracts showed downregulation of the gene, suggesting that, in combination, the effects of these bioactives differ from their individual effects likely mediated through competitive inhibition of the gene. Upregulation of the gene may have therapeutic potential in diabetes mellitus and cardiovascular diseases, while its downregulation likely contributes to GBR’s antiobesity effects. These potentials are worth studying further.

10.3390/nu5020468

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Citations (25)

Development, characterization and anti-diabetic properties of thymoquinone rich fraction nanoemulsion obtained from black cumin

Zaki Tubesha

For thousands of years, natural products have played important roles throughout the world in preventing and treating human diseases. Black cumin (Nigella sativa L.) and its bioactive constituents, thymoquinone (TQ), have been used for various health benefits such as antidiabetic, antitumor, antihypertensive, antioxidative and antibacterial agents. Type 2 diabetes mellitus (T2DM) which accounts for over 90 % of diabetes cases is currently a major chronic disease affecting about 6 % of the global population. Therefore, discovering new therapies is vital for management of T2DM. Although TQ and thymoquinone rich fraction (TQRF) are known to be powerful antioxidants and have hypoglycemic properties, their administration in vivo remains problematic partly due to their low bioavailability. Lipid nanoemulsions from some medicinal plant oils such as TQRF or from hydrophobic bioactives such as TQ are attractive candidates for improving solubility and bioavailability of the oils and their bioactives. Therefore, the aim of the present study was to develop, characterize, and investigate antidiabetic properties of TQRF nanoemulsion (TQRFNE) and TQ nanoemulsion (TQNE). Conventional emulsions from TQRF (TQRFCE) and from TQ (TQCE) were also prepared for comparison. TQRF extracted from N. sativa using supercritical fluid extraction (SFE) contained 4.45 % TQ and was used to develop TQRFNE and TQRFCE. To develop TQNE and TQCE, Triolein (TR) was used as a carrier of commercially acquired TQ based on the concentration of TQ in TQRF. Conventional emulsions were prepared first by mixing 5 % lipid phase (TQRF or TR which contains calculated amount of TQ) with 95 % aqueous phase (2 % Tween-80, and 93 % distilled water) at room temperature using Ultra-Turrax mixer (13000 rpm / 3 min). Nanoemulsions were produced by passing the conventional emulsions through high pressure Homogenizer (800 bars and five homogenization cycles). In the characterization study, the changes in particle size, zeta potential,polydispersity index, refractive index, and chemical stability (loss of TQ during storage) of all emulsions were investigated over a period of 6 months at three different storage temperatures (4, 25, and 40 ˚C). At the end of characterization period, all nanoemulsions displayed good physical and chemical stability; there was no phase separation or any sign of instability of all nanoemulsion samples. In the antioxidant study, all emulsion samples were tested for antioxidant activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH•), 2,2-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS•+), and β-carotene bleaching (BCB) assays using UV- visible spectrophotometer, and hydroxyl radical scavenging activity by electron spin resonance (ESR) spectrometer. Antioxidant activities of all nanoemulsions were slightly lower compared to conventional emulsions. In addition, acute toxicity of TQRFNE, and TQNE was studied using Sprague–Dawley rats. All the parameters measured were unaffected as compared to the negative control group (administered with distilled water). Further study was done to investigate the antidiabetic properties of the emulsions using T2DM animal model. Rats treated with TQRFNE and TQNE (10 ml/kg bw) exhibited a significant (P < 0.05) reduction in plasma total cholesterol levels (43 and 58 %), triglyceride (45 and 59 %), and fasting plasma glucose (42.1 and 54.9 %), respectively, compared to diabetic rats (DC group). However, TQRFCE and TQCE (10 ml/kg bw) also exhibited a significant (P < 0.05) reduction in plasma total cholesterol levels (56 and 69 %), triglyceride (57 and 67 %), and fasting plasma glucose (58 and 54.2 %), respectively, compared to DC group. For the liver and kidney function tests, the concentration of Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Aspartate aminotransferase (AST), Urea (URE), and Creatinine (CREA) were also measured to test any toxic effect on all tested groups. All tested parameters were also significantly lower compared to DC group. For the gene expression study, genes related to glucose metabolism (FBP1), cholesterol metabolism (LDL-R) and antioxidants (SOD1) were evaluated in this study. Treatment with TQRFNE showed antihyperglycemic,hypocholesterolemic and antioxidant effects, partly through regulation of above mentioned genes. Taken together, our finding showed that TQRFNE as a novel nanocarrier has the potential to produce better metabolic outcomes in T2DM. In addition, the findings also suggest that TQRFNE may be better than metformin in management of T2DM, and that it potentially could improve the wellbeing of diabetics through better control of metabolic indices, and likely fewer side effects.

Thymoquinone

Nigella sativa

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Rennin‐like milk coagulant enzyme produced by a local isolate of Mucor

International Journal of Dairy Technology (2003)

Zaki Tubesha Khalaf S. Al-Delaimy

Among 20 isolates of Mucor isolated from various environments in Jordan and found to produce a rennin‐like acid protease, known as Mucor rennin‐like enzyme (MRE), Mucor J20 was found to produce the highest level of MRE. The optimum incubation conditions for enzyme production in a fortified wheat bran mixture using solid‐state fermentation were 3–4 days at 30°C. The highest MRE activity (185–200 rennin units or RU) was produced in a medium containing wheat bran and lentil straw (1 : 1 w/w) moistened with whey, and incubated in clay pots at 30°C for 4 days. A slightly lower activity value (178 RU) was found when using a mineral salt solution or distilled water instead of whey, or when using wheat bran alone with whey. At pH 4, the MRE retained its complete activity (100%) for 6 weeks at 5°C and 10°C, and for 3 and 2 weeks at 20°C and 30°C, respectively. After heating at 60°C for 10 min, the enzyme lost its activity at all pH levels used (pH 2–8). The crude extract of MRE was successfully applied in the manufacture of a cheese curd.

Distilled water

Solid-State Fermentation

10.1046/j.1471-0307.2003.00113.x

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Citations (37)

Characterization and Stability Evaluation of Thymoquinone Nanoemulsions Prepared by High‐Pressure Homogenization

Journal of Nanomaterials (2013)

Zaki Tubesha Zuki Abu Bakar Maznah Ismail

Despite the pharmacological properties of thymoquinone (TQ), its administration in vivo remains problematic partly due to its poor water solubility, leading to low absorptivity and bioavailability. Hence, the objective of this study is to prepare, characterize, and evaluate the stability of TQ nanoemulsion (TQNE). Conventional emulsion from TQ (TQCE) and empty nano‐ and conventional emulsions from Triolein (TRNE and TRCE) are also produced for comparison purposes. The oil‐in‐water nanoemulsions of TQ and Triolein were produced by high‐pressure homogenization. Emulsions were characterized physically by droplet size, polydispersity index, zeta potential, and refractive index. The changes of these parameters in TQNE samples stored for 6 months at 4 and 25°C were not statistically significant ( P < 0.05). In addition, the initial particle sizes of TQNE and TRNE were 119.6 and 119.5 nm, respectively. Stability studies were also performed for the period of 6 months. At the end of the experiment, the percent of remaining TQ in TQNE at 4, 25, and 40°C was 90.6, 89.1, and 87.4 % respectively. Slower degradation of TQ indicated the chemical stability of TQ in TQNE samples. These results indicated that TQNE is stable over a period of 6 months.

Thymoquinone

Homogenization

Characterization

10.1155/2013/453290

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Citations (34)