Band 36, Heft 4

Oxy+ is a natural source of arthrospira found in nature, used as a dietary supplement and manufactured in Aruba for lifefactors. Arthrospira contains good quality of proteins, sulfated polysaccharides, γ-linoleic acid, along with an array of carotene and phytopigments, vitamins, and minerals which are reported to be antioxidant, immunomodulator, antihyperglycemic, antidyslipidemic, cardioprotective, hepatoprotective, antiviral, anticancerous, antihypertensive, anti-inflammatory, analgesic, neuroprotective and renoprotective activities. Several studies have shown arthrospira, and active ingredients of it revealed various pharmacological activities. It can be used for the management of various ailments such as diabetes, dyslipidemia, obesity, hypertension, cancer, arthritis, osteoarthritis, autoimmune disorders, etc. This review attempts to explore the hidden benefits of Oxy+ (arthrospira).

Objectives Glucosamine, chondroitin and diacerein are natural compounds commonly used in treating osteoarthritis. Their concomitant intake may trigger drug–natural product interactions. Cytochrome P450 (CYP) has been implicated in such interactions. Cytochrome P450 2D6 (CYP2D6) is a major hepatic CYP involved in metabolism of 25% of the clinical drugs. This study aimed to investigate the inhibitory effect of these antiarthritic compounds on CYP2D6. Methods CYP2D6 was heterologously expressed in Escherichia coli . CYP2D6–antiarthritic compound interactions were studied using in vitro enzyme kinetics assay and molecular docking. Results The high-performance liquid chromatography (HPLC)-based dextromethorphan O -demethylase assay was established as CYP2D6 marker. All glucosamines and chondroitins weakly inhibited CYP2D6 (IC 50 values >300 µM). Diacerein exhibited moderate inhibition with IC 50 and K i values of 34.99 and 38.27 µM, respectively. Its major metabolite, rhein displayed stronger inhibition potencies (IC 50 =26.22 μM and K i =32.27 μM). Both compounds exhibited mixed-mode of inhibition. In silico molecular dockings further supported data from the in vitro study. From in vitro – in vivo extrapolation, rhein presented an area under the plasma concentration-time curve (AUC) ratio of 1.5, indicating low potential to cause in vivo inhibition. Conclusions Glucosamine, chondroitin and diacerein unlikely cause clinical interaction with the drug substrates of CYP2D6. Rhein, exhibits only low potential to cause in vivo inhibition.

Objectives Majoon-e-Seer Alvi Khan, a compound Unani formulation, has been indicated in disease conditions simulating dyslipidemia. The present study was done to substantiate the efficacy of Majoon-e-Seer Alvi Khan (MSAK) in dyslipidaemia on scientific parameters. Methods A randomized, single-blind, Standard controlled, clinical trial was carried out on 40 patients of dyslipidemia who were randomly allocated into test (n=30) and control (n=10) groups. The test drug, MSAK , and control drug, tablet Atorvastatin was given to the respective group for 60 days along with lifestyle modification. Results The test drug significantly alleviated the symptoms of subjective parameters (p<0.05). There was a statistically significant reduction in lipid profile of the patients in the test group (p<0.05) than control drug treatment. Conclusions The study evidenced that Majoon-e-Seer Alvi Khan is potentially effective and safe in the treatment of dyslipidemia. However, a multicentre study with a robust study design is required to generalize the results.

Objectives Alcohol and medication use are increasingly prevalent in the older population. Concurrent use of alcohol and alcohol-interactive (AI) medication can lead to significant adverse consequences. Methods Three reference works were used to create an explicit list of drug substances for which information about the interaction with alcohol was available in at least one of them. Additional information was extracted from the Summary of Product Characteristics (SPC). The first aim was to generate a list of 256 substances with standardized advice regarding the concurrent use of each drug with alcohol. The second aim was to observe the prevalence of potential drug–alcohol-interactions. The list was applied to a database containing information about alcohol and medication use of 1,016 community-dwelling older patients (≥70 years) with polypharmacy. Results About half of the sample population reported to consume alcohol at least once a week. Around 22% were classified as frequent drinkers (5–7 days/week) and 11% as heavier drinkers (>7 units/week). Ninety-three percent alcohol consumers in our sample took at least one chronic drug that potentially interacts with alcohol and 42% used at least one chronic drug for which alcohol use is considered contraindicated. Conclusions We developed an explicit list of potentially drug–alcohol-interactions in older adults, with standardized handling advice. We observed that prevalence of potential drug–alcohol-interactions is substantial in community-dwelling older patients with polypharmacy.

Objectives Pharmacogenomics (PGx) testing optimizes pharmacotherapy and reduces interindividual variation in drug responses. However, it is still not implemented in clinical practice in the West Bank of Palestine (WBP). The aim of this study was to determine the need for PGx education and testing among physicians from different specialties in WBP. Methods This study used a cross-sectional survey that was administered to 381 physicians from different cities in WBP. The questionnaire consisted of 27 closed-ended questions that evaluate the exposure and attitude toward PGx education, the role of PGx testing in clinical practice, and the capabilities of physicians in PGx testing. Results It was found that exposure to PGx education is low, with most of the respondents (81.1%) answering that PGx was not an integral part of their medical education. The majority (>90%) of the participants agreed that PGx should be included in the medical school curriculum. It was also found that 58.5% of the participants agreed that PGx testing is relevant to their current clinical practice. In addition, most of the participant physicians (>60%) think that they are currently not capable of prescribing and making decisions for pharmacotherapy based on PGx testing. Conclusions It is concluded that there is a high need for PGx education and implementation in clinical practice in WBP. We recommend adding PGx courses to the curricula of medical schools and going forward with the implementation of PGx testing in clinical practice in WBP.

Objectives Khat ( Catha edulis ) is a stimulant plant, and it is abusive to induce euphoria, alertness and activity. Concomitant use of medications and khat chewing predisposes to the appearance of drug interactions result in treatment failure or toxicity. This study determined the changes in the urinary inorganic profile in adult healthy males who are chewing khat compared with non-khat chewer males. Methods A total of 40 adult non-smoker healthy males (20 khat chewer and 20 non-khat chewer) aged 24–30 years were selected. Khat chewer samples were positive for cathinone and cathine and negative for other drug of abuse, while non-khat chewer samples were negative for drug of abuse include cathinone and cathine. Samples were selected according to their results in immunoassay and gas chromatography mass spectrometry (GCMS) analysis. Cathine and cathinone were confirmed using liquid chromatography mass spectrometry (LC-MSMS) analysis. Inorganic profile includes titanium (Ti), cobalt (Co), copper (Cu), zinc (Zn), cadmium (Cd), and lead (Pb) were determined by using inductively coupled plasma-mass spectrometry (ICP-MS). Results The levels of Ti, Co, Zn, Cd, and Pb in urine were significantly higher among the khat chewer group compared with non-khat chewer. Ti, Cd, Co, Pb and Zn urine levels were 0.5-, 1.5-, 1.15-, 5-, and 8.2-fold higher in the khat chewer group compared to non-khat chewer, respectively. Conclusions We suggested that continuous khat chewing has a long term effect on metabolic pathway of therapeutic drugs that result in toxicity or failure of therapy.

Objectives This work was designed to compare the sensitizing effects of epigenetic modifiers on cancer cells vs. that of glucocorticoids. Also, to evaluate their effects on genes involved in epigenetic changes and drug metabolism. Methods Hepatoma cells (HepG2) were treated with the anticancer drug (Taxol), with a histone deacetylase inhibitor (Trichostatin A [TSA]), DNA methyltransferase inhibitor (5-Aza-dC) or dexamethasone (DEX). Cytotoxicity was assessed by MTT assay and the apoptosis was determined by Annexin V-FITC. The expression levels of HDAC1 , HDAC3 , Dnmt1 , Dnmt3α, CYP1A2, CYP3A4, CYP2B6, CYP2C19 and CYP2D6 were monitored by qRT-PCR. Results TSA, synergistically enhanced cells sensitivity with the anticancer effect of Taxol more than 5-Aza-dC and DEX. This was evidenced by the relative decrease in IC 50 in cells cotreated with Taxol + TSA, Taxol + 5-Aza-dC or Taxol + DEX. Apoptosis was induced in 51.2, 16.9 and 41.3% of cells, respectively. In presence of Taxol, TSA induced four-fold increase in the expression of HDAC1 and downregulated Dnmt1&3α genes . CYP2D6 demonstrated progressive expression (up to 28-fold) with the increasing number of drugs. Moreover, the isoform overexpressed in cells treated with TSA + Taxol > DEX + Taxol > 5-Aza-dC + Taxol (6.4, 4.6 and 2.99, respectively). The investigated genes were clustered in two distinct subsets, where no coregulation was observed between HDAC1 and HDAC3. However, tight pairwise correlation-based cluster was seen between ( CYP3A4/Dnmt3α and CYP2D6/CYP2C19). Conclusions The data reflects the sensitizing effect of acetylation modification by TSA on the responsiveness of hepatoma cells to anticancer therapy. The effect of histone deacetylase inhibition was more than hypomethylation and glucocorticoid effects. TSA exerts its role through its modulatory role on epigenetics and drugs metabolizing genes. Other modifiers (5-Aza-dC and DEX), however may adopt different mechanisms.

Objectives Ocimum gratissimum L. is used in traditional medicine for the treatment of bacterial infections and anaemia. This study was designed to evaluate the effect of O. gratissimum leaf extract on phenylhydrazine (PHZ)-induced anaemia and toxicity in rats. Methods The experimental rats were divided into five groups (A–E) (n=6/sex/group). Each rat in groups B–E was intraperitoneally administered 50 mg/kg of PHZ for two consecutive days. Group A (normal control) did not receive any PHZ, group B (negative control), group C received orally 5 mg/kg ferrous sulphate whereas groups D and E received 200 and 400 mg/kg O. gratissimum leaf extract respectively, for 14 days. Results Red blood cell count, packed cell volume, haemoglobin concentration and high-density lipoprotein increased significantly (p<0.05) whereas low-density lipoprotein and very-low-density lipoprotein decreased in extract-treated groups when compared to the negative control. O. gratissimum (400 mg/kg extract) and standard drug (5 mg/kg ferrous sulphate) significantly (p<0.05) reduced the levels of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. Conclusions The results of this study indicate that O. gratissimum leaf extract has a restorative effect on the phenylhydrazine-induced metabolic distortions in the blood, liver, and kidney, and therefore could be used therapeutically as an anti-anaemic tonic.

Objectives Hyperinsulinemia increases the risk factor of diabetes and infertility at a manifold. Lactobacillus plantarum has several medical significances with limited reports. Hence, this study assessed the effect of L. plantarum on sexual-reproductive functions and distribution of insulin receptors in the hypothalamic-pituitary-testicular axis of hyperinsulinemic mice. Methods Forty male adult mice were divided into five groups as follows: control, high-fat diet (HFD) + streptozotocin (STZ), therapeutic, co-administration group type 1 (CO-AD) and probiotics. They were either simultaneously exposed to an HFD and L. plantarum treatment for 28 days with a dose of STZ injection to induce hyperinsulinemia on day 28 or treated with L. plantarum for 14 days, and following induction of hyperinsulinemia. Mice were subjected to a sexual behavioural test and thereafter sacrificed under euthanasia condition. Blood, brain and testes were collected for biochemical and immunohistochemical assays. Results Treatment with L. plantarum ameliorated reproductive hormones activity disruption, sexual behavioural defects, antioxidant imbalance, insulin dysregulation and lipid metabolism dysfunction following exposure to HFD + STZ when compared to the hyperinsulinemic untreated mice. Conclusions Taken together, data from this study reveal that L. plantarum abrogated hyperinsulinemia-induced male sexual and reproductive deficits by modulating antioxidant status, lipid metabolism and insulin signalling in the hypothalamic-pituitary-testicular axis of mice.

Objectives Ashtanga Ghrita (AG), an Indian traditional formulation, has been used to promote neuropharmacological activities. AG is made up of clarified cow butter (ghee) and eight different herbs. Methods To test whether scopolamine (SCP)-induced dementia and brain oxidative stress can be counteracted by AG, rats were separated into five groups (n=6/group): group one control, group two SCP (1 mg/kg b.w., i.p.) treated and group three to five were co-treated with different doses of AG (1.25, 2.5 and 5 g/kg b.w., orally) and SCP. After the treatment regimen, behavioral (Y-maze test) and brain biochemical changes were measured in all groups. Results Microbial load and heavy metals were found within permissible limits. Results from attenuated total reflection Fourier-transform infrared spectroscopy demonstrated the complexation/interaction of herbal phytoconstituents with the functional groups of Ghrita. Preliminary phytochemical analysis of AG exhibited the occurrence of flavonoids, phenolics, glycosides, steroids, triterpenes, tannins, and amino acids. Findings of the experimental study exhibited that AG significantly protected the rats from SCP-induced behavioral dysfunction and brain biochemical alterations. Conclusions This study demonstrates that AG protects the brain from SCP-induced dementia by promoting brain antioxidant activity and thus could be a promising drug for the treatment of neurodegenerative disease.