Zoheir A. Damanhouri

A review on therapeutic potential of Nigella sativa: A miracle herb

Nigella sativa (N. sativa) (Family Ranunculaceae) is a widely used medicinal plant throughout the world. It is very popular in various traditional systems of medicine like Unani and Tibb, Ayurveda and Siddha. Seeds and oil have a long history of folklore usage in various systems of medicines and food. The seeds of N. sativa have been widely used in the treatment of different diseases and ailments. In Islamic literature, it is considered as one of the greatest forms of healing medicine. It has been recommended for using on regular basis in Tibb-e-Nabwi (Prophetic Medicine). It has been widely used as antihypertensive, liver tonics, diuretics, digestive, anti-diarrheal, appetite stimulant, analgesics, anti-bacterial and in skin disorders. Extensive studies on N. sativa have been carried out by various researchers and a wide spectrum of its pharmacological actions have been explored which may include antidiabetic, anticancer, immunomodulator, analgesic, antimicrobial, anti-inflammatory, spasmolytic, bronchodilator, hepato-protective, renal protective, gastro-protective, antioxidant properties, etc. Due to its miraculous power of healing, N. sativa has got the place among the top ranked evidence based herbal medicines. This is also revealed that most of the therapeutic properties of this plant are due to the presence of thymoquinone which is major bioactive component of the essential oil. The present review is an effort to provide a detailed survey of the literature on scientific researches of pharmacognostical characteristics, chemical composition and pharmacological activities of the seeds of this plant.

Aged garlic extract protects against doxorubicin-induced cardiotoxicity in rats.

Clinical uses of doxorubicin (DOX), a highly active anticancer agent, are limited by its severe cardiotoxic side effects associated with increased oxidative stress and apoptosis. In this study we investigated whether aged garlic has protective effects against doxorubicin-induced free radical production and cardiotoxicity in male rats. A single dose of doxorubicin (25mg/kg) caused increased both serum cardiac enzymes LDH and CPK activities and a significant increase malonyldialdehyde (MDA) in plasma. However, pretreatment of rats with aged garlic extract (250 mg/kg) for 27 days before doxorubicin therapy, reduced the activity of both enzymes, and significantly decreased of MDA production in plasma. Total antioxidant activity was increased after aged garlic extract administration. Histopathological examination of heart tissue showed that DOX treatment resulted in alteration of cardiac tissue structure in the form of peri arterial fibrosis and apoptotic changes in cardiomyocytes. Pretreatment with aged garlic extract for 27 days ameliorated the effect of DOX administration on cardiac tissue; cardiomyocytes looked more or less similar to those of control. However, still vascular dilatation, mild congestion and interstitial edemas were observed. Our results suggest that aged garlic extract is potentially protective against doxorubicin-induced cardiotoxicity.

Modulation of doxorubicin cytotoxicity by resveratrol in a human breast cancer cell line

BackgroundBreast cancer is the most common cancer in the Arab world and it ranked first among Saudi females. Doxorubicin (DOX), an anthracycline antibiotic is one of the most effective anticancer agents used to treat breast cancer. chronic cardiotoxicity is a major limiting factor of the use of doxorubicin. Therefore, our study was designed to assess the role of a natural product resveratrol (RSVL) on sensitization of human breast cancer cells (MCF-7) to the action of DOX in an attempt to minimize doxorubicin effective dose and thereby its side effects.MethodsHuman breast cancer cell line MCF-7, was used in this study. Cytotoxic activity of DOX was determined using (sulforhodamine) SRB method. Apoptotic cells were quantified after treatment by annexin V-FITC- propidium iodide (PI) double staining using flow-cytometer. Cell cycle disturbance and doxorubicin uptake were determined after RSVL or DOX treatment.ResultsTreatment of MCF-7 cells with 15 μg/ml RSVL either simultaneously or 24 h before DOX increased the cytotoxicity of DOX, with IC50 were 0.056 and 0.035 μg/ml, respectively compared to DOX alone IC50 (0.417 μg/ml). Moreover, flow cytometric analysis of the MCF-7 cells treated simultaneously with DOX (0.5 μg/ml) and RSVL showed enhanced arrest of the cells in G0 (80%). On the other hand, when RSVL is given 24 h before DOX although there was more increased in the cytotoxic effect of DOX against the growth of the cells, however, there was decreased in percentage arrest of cells in G0, less inhibition of DOX-induced apoptosis and reduced DOX cellular uptake into the cells.ConclusionRSVL treatment increased the cytotoxic activity of DOX against the growth of human breast cancer cells when given either simultaneously or 24 h before DOX.

Mechanisms of Cardioprotective Effect of Aged Garlic Extract Against Doxorubicin-Induced Cardiotoxicity

Aged garlic has been extensively studied and has been shown to have a number of medicinal properties, including immunomodulatory, hepatoprotective, antimutagenic, anticarcinogenic, and antioxidant effects. The objective of this study was to investigate the mechanisms of the cardioprotective effect of aged garlic extract (AGE), a widely used herbal medicine with potent antioxidant activity, against doxorubicin-induced cardiotoxicity. Moreover, the study investigated if the cardioprotective effect of AGE might be at the expense of the antitumor effect of the anticancer drug doxorubicin (DOX). Primary cultured neonatal rat cardiac myocytes were treated with DOX, AGE, and their combination for 24 hours. DOX increased p53 and caspase 3 activity–induced apoptotic cell death, whereas AGE pretreatment suppressed the action of DOX. AGE pretreatment did not interfere with the cytotoxic activity of DOX, but it increased the DOX uptake into tumor cells and increased the long term survivors of tumor-bearing mice from 30% to 70%. In conclusion, DOX impairs viability of cardiac myocytes, at least partially by activating the p53-mediated apoptotic signaling. AGE can effectively and extensively counteract this action of DOX and may potentially protect the heart from severe toxicity of DOX. At the same time, AGE did not interfere with antitumor activity of DOX.

A new gender-specific model for skin autofluorescence risk stratification.

Advanced glycation endproducts (AGEs) are believed to play a significant role in the pathophysiology of a variety of diseases including diabetes and cardiovascular diseases. Non-invasive skin autofluorescence (SAF) measurement serves as a proxy for tissue accumulation of AGEs. We assessed reference SAF and skin reflectance (SR) values in a Saudi population (n = 1,999) and evaluated the existing risk stratification scale. The mean SAF of the study cohort was 2.06 (SD = 0.57) arbitrary units (AU), which is considerably higher than the values reported for other populations. We show a previously unreported and significant difference in SAF values between men and women, with median (range) values of 1.77 AU (0.79–4.84 AU) and 2.20 AU (0.75–4.59 AU) respectively (p-value « 0.01). Age, presence of diabetes and BMI were the most influential variables in determining SAF values in men, whilst in female participants, SR was also highly correlated with SAF. Diabetes, hypertension and obesity all showed strong association with SAF, particularly when gender differences were taken into account. We propose an adjusted, gender-specific disease risk stratification scheme for Middle Eastern populations. SAF is a potentially valuable clinical screening tool for cardiovascular risk assessment but risk scores should take gender and ethnicity into consideration for accurate diagnosis.

Anticonvulsant activity of ethanol extracts of Vetiveria zizanioides roots in experimental mice

 Abstract Context: Vetiveria zizanioides Linn. (Gramineae), an aromatic plant commonly known as vetiver, is traditionally used for various ailments. Ethanol and aqueous extract of this plant found extensive use in Indian folklore medicine and used in treatment of a wide range of disorders including seizure. However, the anticonvulsant activity of this plant has not been studied. Objective: To evaluate anticonvulsant activity of ethanol extract of V. zizanioides (EEVZ) in experimental mice. Materials and methods: Anticonvulsant activity of EEVZ was determined by maximal electroshock stimulation (MES) and pentylenetetrazole (PTZ) in mice for 8 d experimental protocol. The extract at a dose of 100, 200 and 400 mg/kg body weight was administered once by oral route. Results: LD50 value of EEVZ in mice was found at a dose of 600 mg/kg body weight. EEVZ at a dose of 400 mg/kg significantly (p < 0.001) reduced flexion (l5.98 to 3.73 s), extension (13.73 to 0.96 s), clonus (14.07 to 4.93 s), stupor (6.29 to 1.22 s) in the MES model. Further, it increases onset of clonic (88.25 to 708.32 s/30 min) and tonic (139.52 to 1126.39 s/30 min) in the PTZ model. In the PTZ model, 33% normal control and 83% EEVZ (100 mg/kg) animals were alive, while 100% protection was achieved in standard drug phenobarbital (20 mg/kg), EEVZ (200 mg/kg) and EEVZ (400 mg/kg) animals. Discussion and conclusion: Findings demonstrate that V. zizanioides shows significant anticonvulsant activity in mice.

Anxiolytic potential of ursolic acid derivative-a stearoyl glucoside isolated from Lantana camara L.(verbanaceae)

OBJECTIVE To investigate the anxiolytic activity of newly isolated compound by our lab called ursolic acid stearoyl glucoside (UASG) from the leaves of Lantana camara (L. camara). METHODS Column chromatography was used to isolate UASG. Anxiolytic potential was experimentally proved and demonstrated through Elevated plus-maze, Open field and light and dark test. RESULTS The UASG showed marked increased in time spent (%) and number of frequent movements made by animals in open arm of elevated plus-maze apparatus. In light and dark model, UASG produced marked increase in time spent by animal, number of crossing and reduced duration of immobility in light box. CONCLUSIONS UASG showed significant increase in number of rearing, assisted rearing and number of square crossed in open field established test model. UASG showed its anxiolytic effect in dose dependent manner.

Metabolic Phenotype of Obesity in a Saudi Population

Metabolic phenotyping of obese populations can shed light on understanding environmental interactions underpinning obesogenesis. Obesity and its comorbidities are a major health and socioeconomic concern globally and are highly prevalent in the Middle East. We employed nuclear magnetic resonance spectroscopy to characterize the metabolic signature of urine and blood plasma for a cohort of obese (n = 50) compared to non-obese (n = 48) Saudi participants. The urinary metabolic phenotype of obesity was characterized by higher concentrations of N-acetyl glycoprotein fragments, bile acids, lysine, and methylamines and lower concentrations of tricarboxylic acid cycle intermediates, glycine, and gut microbial metabolites. The plasma metabolic phenotype of obesity was dominated by sugars, branched chain amino acids, and lipids, particularly unsaturated lipids, with lower levels of plasma phosphorylcholine and HDL. Serum hepatic enzymes, triglycerides, and cholesterol mapped to specific metabolic phenotypes, potentially indicating the dysregulation of multiple distinct obesity-related pathways. Differences between urine and plasma phenotypes of obesity for this Saudi population and that reported for Caucasian individuals indicate population disparities in pathways relating to ketogenesis (more apparent in the Saudi obese population), dysregulated liver function, and the gut microbiome. Mapping population-specific metabolic perturbations may hold promise in establishing population differences relevant to disease risk and stratification of individuals with respect to discovery of new therapeutic targets.

Development of response surface methodology for optimization of extraction parameters and quantitative estimation of embelin from Embelia ribes Burm by high performance liquid chromatography

Background: Embelia ribes Burm is widely used medicinal plant for the treatment of different types of disorders in the Indian traditional systems of medicine. Objective: The present work was aimed to optimize the extraction parameters of embelin from E. ribes fruits and also to quantify embelin content in different extracts of the plant. Materials and Methods: Optimization of extraction parameters such as solvent: drug ratio, temperature and time were carried out by response surface methodology (RSM). Quantitative estimation of embelin in different extracts of E. ribes fruits was done through high performance liquid chromatography. Results: The optimal conditions determined for extraction of embelin through RSM were; extraction time (27.50 min), extraction temperature 45°C and solvent: drug ratio (8:1). Under the optimized conditions, the embelin yield (32.71%) was equitable to the expected yield (31.07%, P > 0.05). These results showed that the developed model is satisfactory and suitable for the extraction process of embelin. The analysis of variance showed a high goodness of model fit and the accomplishment of the RSM method for improving embelin extraction from the fruits of E. ribes. Conclusion: It is concluded that this may be a useful method for the extraction and quantitative estimation of embelin from the fruits of E. ribes.

Comparison of cytochrome P-450 content and conjugative enzymes in livers of camels (Camelus dromedarius), guinea-pigs (Cavia porcellus) and rats (Rattus norvegicus)

The activities of the conjugative enzymes, glutathione S-transferase and UDP-glucuronyl-transferase, have been measured in vitro in the livers of camels, guinea-pigs and rats. Some sex differences were observed in the levels of these conjugative enzymes. In rats and guinea-pigs, females had higher UDP-glucuronyltransferase activity than males. In camels, females had higher glutathione S-transferase activity than males. In these species, the cytochrome P-450 isozymes observed between the 50,000 and 60,000 mol. wt regions have been separated and characterized by SDS-polyacrylamide gel electrophoresis. Camels showed lower levels of all types of cytochrome P-450 isozymes, while guinea-pigs showed higher levels of most of these isozymes. In general, camels seemed to have the lowest drug-metabolizing enzyme activity when compared to rats and guinea-pigs.