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Fulltext Differential responses to blood pressure and oxidative stress in streptozotocin-induced diabetic Wistar-Kyoto rats and spontaneously hypertensive rats: effects of antioxidant (honey) treatment

Erejuwa OO, Sulaiman SA, Wahab MS, Sirajudeen KN, Salleh MS, Gurtu S

Int J Mol Sci, 2011;12(3):1888-907.
PMID: 21673929 DOI: 10.3390/ijms12031888

Oxidative stress is implicated in the pathogenesis and/or complications of hypertension and/or diabetes mellitus. A combination of these disorders increases the risk of developing cardiovascular events. This study investigated the effects of streptozotocin (60 mg/kg; ip)-induced diabetes on blood pressure, oxidative stress and effects of honey on these parameters in the kidneys of streptozotocin-induced diabetic Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Diabetic WKY and SHR were randomized into four groups and received distilled water (0.5 mL) and honey (1.0 g/kg) orally once daily for three weeks. Control SHR had reduced malondialdehyde (MDA) and increased systolic blood pressure (SBP), catalase (CAT) activity, and total antioxidant status (TAS). SBP, activities of glutathione peroxidase (GPx) and glutathione reductase (GR) were elevated while TAS was reduced in diabetic WKY. In contrast, SBP, TAS, activities of GPx and GR were reduced in diabetic SHR. Antioxidant (honey) treatment further reduced SBP in diabetic SHR but not in diabetic WKY. It also increased TAS, GSH, reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, activities of GPx and GR in diabetic SHR. These data suggest that differences in types, severity, and complications of diseases as well as strains may influence responses to blood pressure and oxidative stress.
Fulltext Effects of honey and its mechanisms of action on the development and progression of cancer

Erejuwa OO, Sulaiman SA, Wahab MS

Molecules, 2014;19(2):2497-522.
PMID: 24566317 DOI: 10.3390/molecules19022497

Honey is a natural product known for its varied biological or pharmacological activities-ranging from anti-inflammatory, antioxidant, antibacterial, antihypertensive to hypoglycemic effects. This review article focuses on the role of honey in modulating the development and progression of tumors or cancers. It reviews available evidence (some of which is very recent) with regards to the antimetastatic, antiproliferative and anticancer effects of honey in various forms of cancer. These effects of honey have been thoroughly investigated in certain cancers such as breast, liver and colorectal cancer cell lines. In contrast, limited but promising data are available for other forms of cancers including prostate, bladder, endometrial, kidney, skin, cervical, oral and bone cancer cells. The article also underscores the various possible mechanisms by which honey may inhibit growth and proliferation of tumors or cancers. These include regulation of cell cycle, activation of mitochondrial pathway, induction of mitochondrial outer membrane permeabilization, induction of apoptosis, modulation of oxidative stress, amelioration of inflammation, modulation of insulin signaling and inhibition of angiogenesis. Honey is highly cytotoxic against tumor or cancer cells while it is non-cytotoxic to normal cells. The data indicate that honey can inhibit carcinogenesis by modulating the molecular processes of initiation, promotion, and progression stages. Thus, it may serve as a potential and promising anticancer agent which warrants further experimental and clinical studies.
Fulltext Evidence in support of potential applications of lipid peroxidation products in cancer treatment

Erejuwa OO, Sulaiman SA, Ab Wahab MS

Oxid Med Cell Longev, 2013;2013:931251.
PMID: 24369491 DOI: 10.1155/2013/931251

Cancer cells generate reactive oxygen species (ROS) resulting from mitochondrial dysfunction, stimulation of oncogenes, abnormal metabolism, and aggravated inflammatory activities. Available evidence also suggests that cancer cells depend on intrinsic ROS level for proliferation and survival. Both physiological and pathophysiological roles have been ascribed to ROS which cause lipid peroxidation. In spite of their injurious effects, the ROS and the resulting lipid peroxidation products could be beneficial in cancer treatment. This review presents research findings suggesting that ROS and the resulting lipid peroxidation products could be utilized to inhibit cancer growth or induce cancer cell death. It also underscores the potential of lipid peroxidation products to potentiate the antitumor effect of other anticancer agents. The review also highlights evidence demonstrating other potential applications of lipid peroxidation products in cancer treatment. These include the prospect of lipid peroxidation products as a diagnostic tool to predict the chances of cancer recurrence, to monitor treatment progress or how well cancer patients respond to therapy. Further and detailed research is required on how best to successfully, effectively, and selectively target cancer cells in humans using lipid peroxidation products. This may prove to be an important strategy to complement current treatment regimens for cancer patients.
Inappropriate prescribing in hospitalised Australian elderly as determined by the STOPP criteria

Wahab MS, Nyfort-Hansen K, Kowalski SR

Int J Clin Pharm, 2012 Dec;34(6):855-62.
PMID: 22864867 DOI: 10.1007/s11096-012-9681-8

BACKGROUND: The elderly population is increasing worldwide. Due to age-related physiological changes that affect the pharmacokinetics and pharmacodynamics of drugs, the elderly are predisposed to adverse drug reactions. Prescribing of potentially inappropriate medications (PIMs) has been found to be prevalent among the elderly and PIM use has been associated with hospitalisations and mortality.
OBJECTIVES: This study aims to identify the prevalence and nature of pre-admission inappropriate prescribing by using the STOPP (screening tool of older people's prescriptions) criteria amongst a sample of hospitalised elderly inpatients in South Australia.
SETTING: Medical, surgical and rehabilitation wards of a public teaching hospital in Adelaide, South Australia.
MAIN OUTCOME MEASURE: Pre-admission prevalence of PIM.
METHOD: Medication management plans of 100 patients of ≥65 years old were prospectively studied to determine the prevalence of pre-admission PIM use. Sixty-five criteria of STOPP were applied to identify PIMs.
RESULTS: The total number of pre-admission medications screened during the study period was 949; the median number of medicines per patient was nine (range 2-28). Overall the STOPP criteria identified 138 PIMs in 60 % of patients. The most frequently encountered PIM was opiates prescribed in patients with recurrent falls (12.3 %), followed by benzodiazepines in fallers (10.1 %) and proton pump inhibitors when prescribed for peptic ulcer disease for long-term at maximum doses (9.4 %). The number of medications were found to have a positive correlation with pre-admission PIM use (r(s) = 0.49, P < 0.01).
CONCLUSIONS: Pre-admission PIM use is highly prevalent among the studied population. Strategies to reduce PIM use should be undertaken by physicians and pharmacists. The use of the STOPP criteria in clinical practice to reduce prescriptions of inappropriate medications requires further investigation.
Fulltext Oligosaccharides might contribute to the antidiabetic effect of honey: a review of the literature

Erejuwa OO, Sulaiman SA, Wahab MS

Molecules, 2011 Dec 28;17(1):248-66.
PMID: 22205091 DOI: 10.3390/molecules17010248

Evidence shows that honey improves glycemic control in diabetes mellitus. Besides its hypoglycemic effect, studies indicate that honey ameliorates lipid abnormalities in rats and humans with diabetes. The majority of these studies do not examine the mechanisms by which honey ameliorates glycemic and/or lipid derangements. The gut microbiota is now recognized for its ability to increase energy harvest from the diet and alter lipid metabolism of the host. Recently available data implicate a causal role of these gut microbes in the pathophysiology of obesity, insulin resistance, and diabetes mellitus. In this review, we present some of the latest findings linking gut microbiota to pathogenesis of obesity, insulin resistance, and diabetes mellitus. The review also underlines data that demonstrate the beneficial effects of oligosaccharides on various abnormalities commonly associated with these disorders. Based on the similarities of some of these findings with those of honey, together with the evidence that honey contains oligosaccharides, we hypothesize that oligosaccharides present in honey might contribute to the antidiabetic and other health-related beneficial effects of honey. We anticipate that the possibility of oligosaccharides in honey contributing to the antidiabetic and other health-related effects of honey will stimulate a renewed research interest in this field.
Flux model development and synthesis optimization for an enhanced GO embedded nanocomposite membrane through FFD and RSM approach

Abdul Wahab MS, Abd Rahman S, Abu Samah R

Heliyon, 2020 Nov;6(11):e05610.
PMID: 33305039 DOI: 10.1016/j.heliyon.2020.e05610

A two-level full factorial design was used to analyze several factors involved in PSF-GO-Pebax thin film nanocomposite membranes development. Permeate flux was chosen as a single response for four possible factors: Pebax selective layer concentration, amount of GO load to Pebax selective layer, Pebax-GO selective layer thickness, and amount of GO load to PSF substrate. The study is aimed at factors interaction and contribution towards the highest permeation flux via FFD and RSM approach. R2 obtained from the ANOVA is 0.9937 with Pebax concentration as the highest contributing factor. Pebax concentration-amount of GO load to PSF substrate is the only interaction contributing to the highest flux. A regression analysis concluded the study with model development and an optimized condition for the membrane design.
Fulltext Adulterated Traditional-Herbal Medicinal Products and Its Safety Signals in Malaysia

Ariffin SH, A Wahab I, Hassan Y, Abd Wahab MS

Drug Healthc Patient Saf, 2021;13:133-140.
PMID: 34135639 DOI: 10.2147/DHPS.S305953

BACKGROUND: Usage of traditional-herbal medicines (THM) for various illnesses has been increased around the world, so does the adulteration of these products with hazardous compounds. There are limited Malaysian data that have been published on the characteristics trend and adverse events associated with adulterated THM products.
AIM: This study described characteristics of adulterated THM products in Malaysia and aimed to quantify THM products' safety signals of adverse reactions (ARs).
METHODS: THM products that were seized by Pharmacy Enforcement Division between 2008 and 2014 were extracted and analysed for 59,440 THM products. Of these, only 6452 THM products with complete information were included in the final analyses. Safety signalling tools were used to measure AR signals from AR reports obtained from the National Pharmaceutical Regulatory Agency Adverse Drug Reaction Database.
RESULTS: More than half of adulterated THM products originated from countries outside of Malaysia, with the majority were from Indonesia. The most common claimed indication of adulterated THM products was for pain and fever relief, while steroids were the most common adulterant. AR signals were generated for cough and cold products for respiratory and thoracic disorders, weight-loss products for cardiac disorders, and women's health products for reproductive and breast disorders.
CONCLUSION: Health authorities from various fields can work collaboratively by implementing strategic actions that include the use of safety signalling tools to curb the increasing number of adulterated THM products in the Malaysian market.
Fulltext Honey: a novel antioxidant

Erejuwa OO, Sulaiman SA, Ab Wahab MS

Molecules, 2012 Apr 12;17(4):4400-23.
PMID: 22499188 DOI: 10.3390/molecules17044400

The global prevalence of chronic diseases such as diabetes mellitus, hypertension, atherosclerosis, cancer and Alzheimer's disease is on the rise. These diseases, which constitute the major causes of death globally, are associated with oxidative stress. Oxidative stress is defined as an "imbalance between oxidants and antioxidants in favor of the oxidants, potentially leading to damage". Individuals with chronic diseases are more susceptible to oxidative stress and damage because they have elevated levels of oxidants and/or reduced antioxidants. This, therefore, necessitates supplementation with antioxidants so as to delay, prevent or remove oxidative damage. Honey is a natural substance with many medicinal effects such as antibacterial, hepatoprotective, hypoglycemic, reproductive, antihypertensive and antioxidant effects. This review presents findings that indicate honey may ameliorate oxidative stress in the gastrointestinal tract (GIT), liver, pancreas, kidney, reproductive organs and plasma/serum. Besides, the review highlights data that demonstrate the synergistic antioxidant effect of honey and antidiabetic drugs in the pancreas, kidney and serum of diabetic rats. These data suggest that honey, administered alone or in combination with conventional therapy, might be a novel antioxidant in the management of chronic diseases commonly associated with oxidative stress. In view of the fact that the majority of these data emanate from animal studies, there is an urgent need to investigate this antioxidant effect of honey in human subjects with chronic or degenerative diseases.
Fulltext Fructose might contribute to the hypoglycemic effect of honey

Erejuwa OO, Sulaiman SA, Wahab MS

Molecules, 2012 Feb 15;17(2):1900-15.
PMID: 22337138 DOI: 10.3390/molecules17021900

Honey is a natural substance with many medicinal properties, including antibacterial, hepatoprotective, hypoglycemic, antioxidant and antihypertensive effects. It reduces hyperglycemia in diabetic rats and humans. However, the mechanism(s) of its hypoglycemic effect remain(s) unknown. Honey comprises many constituents, making it difficult to ascertain which component(s) contribute(s) to its hypoglycemic effect. Nevertheless, available evidence indicates that honey consists of predominantly fructose and glucose. The objective of this review is to summarize findings which indicate that fructose exerts a hypoglycemic effect. The data show that glucose and fructose exert a synergistic effect in the gastrointestinal tract and pancreas. This synergistic effect might enhance intestinal fructose absorption and/or stimulate insulin secretion. The results indicate that fructose enhances hepatic glucose uptake and glycogen synthesis and storage via activation of hepatic glucokinase and glycogen synthase, respectively. The data also demonstrate the beneficial effects of fructose on glycemic control, glucose- and appetite-regulating hormones, body weight, food intake, oxidation of carbohydrate and energy expenditure. In view of the similarities of these effects of fructose with those of honey, the evidence may support the role of fructose in honey in mediating the hypoglycemic effect of honey.
Fulltext Modulation of gut microbiota in the management of metabolic disorders: the prospects and challenges

Erejuwa OO, Sulaiman SA, Ab Wahab MS

Int J Mol Sci, 2014 Mar 07;15(3):4158-88.
PMID: 24608927 DOI: 10.3390/ijms15034158

The gut microbiota plays a number of important roles including digestion, metabolism, extraction of nutrients, synthesis of vitamins, prevention against pathogen colonization, and modulation of the immune system. Alterations or changes in composition and biodiversity of the gut microbiota have been associated with many gastrointestinal tract (GIT) disorders such as inflammatory bowel disease and colon cancer. Recent evidence suggests that altered composition and diversity of gut microbiota may play a role in the increased prevalence of metabolic diseases. This review article has two main objectives. First, it underscores approaches (such as probiotics, prebiotics, antimicrobial agents, bariatric surgery, and weight loss strategies) and their prospects in modulating the gut microbiota in the management of metabolic diseases. Second, it highlights some of the current challenges and discusses areas of future research as it relates to the gut microbiota and metabolic diseases. The prospect of modulating the gut microbiota seems promising. However, considering that research investigating the role of gut microbiota in metabolic diseases is still in its infancy, more rigorous and well-designed in vitro, animal and clinical studies are needed.
Fulltext Honey--a novel antidiabetic agent

Erejuwa OO, Sulaiman SA, Wahab MS

Int J Biol Sci, 2012;8(6):913-34.
PMID: 22811614 DOI: 10.7150/ijbs.3697

Diabetes mellitus remains a burden worldwide in spite of the availability of numerous antidiabetic drugs. Honey is a natural substance produced by bees from nectar. Several evidence-based health benefits have been ascribed to honey in the recent years. In this review article, we highlight findings which demonstrate the beneficial or potential effects of honey in the gastrointestinal tract (GIT), on the gut microbiota, in the liver, in the pancreas and how these effects could improve glycemic control and metabolic derangements. In healthy subjects or patients with impaired glucose tolerance or diabetes mellitus, various studies revealed that honey reduced blood glucose or was more tolerable than most common sugars or sweeteners. Pre-clinical studies provided more convincing evidence in support of honey as a potential antidiabetic agent than clinical studies did. The not-too-impressive clinical data could mainly be attributed to poor study designs or due to the fact that the clinical studies were preliminary. Based on the key constituents of honey, the possible mechanisms of action of antidiabetic effect of honey are proposed. The paper also highlights the potential impacts and future perspectives on the use of honey as an antidiabetic agent. It makes recommendations for further clinical studies on the potential antidiabetic effect of honey. This review provides insight on the potential use of honey, especially as a complementary agent, in the management of diabetes mellitus. Hence, it is very important to have well-designed, randomized controlled clinical trials that investigate the reproducibility (or otherwise) of these experimental data in diabetic human subjects.
The relevance of educating doctors, pharmacists and older patients about potentially inappropriate medications

Abd Wahab MS

Int J Clin Pharm, 2015 Dec;37(6):971-4.
PMID: 26415737 DOI: 10.1007/s11096-015-0203-3

Providing appropriate pharmacotherapy to older people can be difficult since older people are more at risk of developing adverse drug reactions due to age-related physiological changes. The use of potentially inappropriate medications (PIMs) among older people is common throughout the globe, and is a cause for concern due to their clinical, humanistic and economic implications. Nevertheless, it appears that doctors and pharmacists have limited knowledge regarding PIMs. Moreover, uninformed older patients may use PIMs without considering their potential negative consequences. There is a need, therefore, to educate doctors, pharmacists and older patients about PIMs. Geriatric pharmacotherapy education with an emphasis on appropriate prescribing, and PIMs, should be included in the medical and pharmacy teachings at the undergraduate, postgraduate and continuing education levels. Moreover, older patients should be informed about PIMs and the possible risks that they may pose.

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