Displaying publications 1 - 20 of 87 in total

  1. Effendy NM, Shuid AN
    Nutrients, 2014 Aug;6(8):3288-302.
    PMID: 25195641 DOI: 10.3390/nu6083288
    Postmenopausal osteoporosis can be associated with oxidative stress and deterioration of antioxidant enzymes. It is mainly treated with estrogen replacement therapy (ERT). Although effective, ERT may cause adverse effects such as breast cancer and pulmonary embolism. Labisia pumila var. alata (LP), a herb used traditionally for women's health was found to protect against estrogen-deficient osteoporosis. An extensive study was conducted in a postmenopausal osteoporosis rat model using several LP doses and duration of treatments to determine if anti-oxidative mechanisms were involved in its bone protective effects. Ninety-six female Sprague-Dawley rats were randomly divided into six groups; baseline group (BL), sham-operated (Sham), ovariectomised control (OVXC), ovariectomised (OVX) and given 64.5 μg/kg of Premarin (ERT), ovariectomised and given 20 mg/kg of LP (LP20) and ovariectomised and given 100 mg/kg of LP (LP100). The groups were further subdivided to receive their respective treatments via daily oral gavages for three, six or nine weeks of treatment periods. Following euthanization, the femora were dissected out for bone oxidative measurements which include superoxide dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA) levels.
  2. Shuid AN, Mohamed IN
    Curr Drug Targets, 2013 Dec;14(13):1565-78.
    PMID: 24200293
    This review explores the effects of pomegranate on the pathogenesis of bone loss in osteoporosis, osteoarthritis and rheumatoid arthritis. A systematic review of the literature was conducted to identify the relevant studies on pomegranate and osteoporosis/osteoarthritis/rheumatoid arthritis. A comprehensive search was conducted in Medline and CINAHL for relevant studies published between the years 1946 to 2012. The main inclusion criteria were research articles published in English, studies had to report the association or effect of pomegranate and these bone and joint diseases: osteoporosis, osteoarthritis or rheumatoid arthritis. The literature search identified 35 potentially relevant articles, whereby 8 met the inclusion criteria. Two animal studies, two combinations of animal and in vitro studies, three in vitro studies and one human study were included in this review. All the studies reported positive effects of pomegranate extract or juice on osteoporosis, osteoarthritis and rheumatoid arthritis. This evidence-based review highlighted the potential of pomegranate extract being used for treating bone loss in osteoporosis, osteoarthritis and rheumatoid arthritis. Further studies are required to identify the active ingredients and molecular mechanisms before controlled human observational studies are conducted to provide stronger evidence.
  3. Shuid AN, Ima Nirwana S, Das S
    Curr Drug Targets, 2013 Dec;14(14):1631.
    PMID: 24383964
  4. Rufus P, Mohamed N, Shuid AN
    Curr Drug Targets, 2013 Dec;14(14):1689-93.
    PMID: 24354584
    Osteoporosis is a metabolic bone disorder that affects both men and women worldwide. It causes low bone mass and therefore increases bone susceptibility to fracture when bone undergoes a minor trauma. Lack of estrogen is the principal cause of osteoporosis. Estrogen, calcium, calcitonin, vitamin D and several antioxidants help in the prevention of osteoporosis. In order to effectively treat osteoporosis, there has been an extended research on the biological activities of traditional medicines since synthetic medicines possess several side effects that reduce their efficacy. Therefore, there is a need to develop new treatment alternatives for osteoporosis. This review centres on the scientific researches carried out on the evaluation of Chinese traditional medicines in the treatment of osteoporosis. Various plants like Achyranthes bidentata, Davallia formosana, polygonatum sibiricum, Cibotium barometz, Er-Zhi-Wan, Curculigo orchioides and a combined treatment of Hachimi-jio-gan (Ba-Wei-Di-Huang-Wan) with alendronate proved active in preventing post-menopausal osteoporosis.
  5. Abdul Jalil MA, Shuid AN, Muhammad N
    Curr Drug Targets, 2013 Dec;14(14):1651-8.
    PMID: 24354586
    With improvements in living standards and healthcare, life expectancy has been increasing dramatically in most parts of the world. These situations lead to the increase in the reported cases of geriatrics-related diseases such as hypogonadal osteoporosis with skeletal fracture being the ultimate outcome, which eventually causes significant morbidity and mortality. The deficient gonadal hormones, which are the main cause of hypogonadal osteoporosis, could be substituted with hormone replacement therapy to hinder bone loss. However, the artificial hormonal therapy has been linked to grievous conditions such as breast and prostate cancers. In view of the various adverse effects associated with conventional treatment, many researchers are now focusing on finding alternative remedies from nature. This article explores the possibilities of certain medicinal plants native to Malaysia that possess androgenic and antioxidant properties to potentially be used in the treatment of fracture due to osteoporosis in ageing people.
  6. Ibrahim N', Mohamed N, Shuid AN
    Curr Drug Targets, 2013 Dec;14(13):1524-32.
    PMID: 23876090
    Fracture healing is a process of recovering injured bone tissue forms and functions. Osteoporosis can delay the healing process, which contributes to personal suffering and loss of activities. Osteoporosis patients tend to lose bone mass at the metaphyseal region which require treatment to increase bone mass. Postmenopausal osteoporosis is the most common osteoporosis that occurs in women which subsequently resulted in fractures even under slight trauma. Estrogen Replacement Therapy (ERT), the recommended therapy for postmenopausal osteoporosis, is associated with higher risk of breast cancer, ovarian cancer and cardiovascular diseases. As osteoporotic fractures are becoming a public health issue, alternative treatment is now being thoroughly explored. The potential agent is statins, the HMG-CoA reductase inhibitor which is widely used for hypercholesterolemia treatment. Statins have been found to increase bone mass by stimulation of Bone morphogenetic protein-2 (BMP-2) expression and Vascular Endothelial Growth Factor (VEGF) production. However, these bone forming effects were achieved at very high systemic doses. Therefore, studies on locally applied statins are required to further explore the ability of statins to stimulate bone formation at acceptable doses for better fracture healing. This review highlights the animal and clinical studies on fracture healing promotions by statins and the mechanisms involved.
  7. Effendy NM, Khamis MF, Shuid AN
    Curr Drug Targets, 2013 Dec;14(13):1542-51.
    PMID: 24010967
    Bone quality assessment is important in assessments of potential agents for the prevention and treatment of osteoporosis. Bone density, microarchitecture and strength are important determinants in osteoporotic study which are widely studied using Dual-Energy X-ray Absorptiometry (DXA), histomorphometry and radiological imaging techniques. In recent years, high resolution micro-CT has become feasible for in vitro or in vivo evaluation of bone architecture. Three-dimensional images of micro-CT reflected high correlations with the conventional histomorphometry and DXA. In comparison to other imaging techniques, micro-CT is the most effective tool in detecting early bone changes for fracture prediction and assessments of potential anti-osteoporotic agents. It is crucial to define an ideal setting with safe radiation doses and appropriate methods for image reconstruction and segmentation to obtain high resolution images. Micro-CT evaluation provides a better insight of bone structure as well as non-metric parameters such as connectivity density, structural model index (SMI) and degree of anisotropy (DA). This non- invasive imaging technique is also equipped with finite element analysis for evaluation of bone biomechanical strength. Micro-CT allows a compressive understanding of the relationships between bone density, microarchitecture and strength which is fundamental to development of pharmacological interventions.
  8. Ramli R, Khamis MF, Shuid AN
    PMID: 22952556 DOI: 10.1155/2012/501858
    Recent studies suggested that Eurycoma longifolia, a herbal plant, may have the potential to treat osteoporosis in elderly male. This study aimed to determine the effects of Eurycoma longifolia supplementation on the trabecular bone microarchitecture of orchidectomised rats (androgen-deficient osteoporosis model). Forty-eight-aged (10-12 months old) Sprague Dawley rats were divided into six groups of sham-operated (SHAM), orchidectomised control (ORX), orchidectomised + 7 mg/rat testosterone enanthate (TEN) and orchidectomised + Eurycoma longifolia 30 mg/kg (EL30), orchidectomised + Eurycoma longifolia 60 mg/kg (EL60), orchidectomised + Eurycoma longifolia 90 mg/kg (EL90). Rats were euthanized following six weeks of treatment. The left femora were used to measure the trabecular bone microarchitecture using micro-CT. Orchidectomy significantly decreased connectivity density, trabecular bone volume, and trabecular number compared to the SHAM group. Testosterone replacement reversed all the orchidectomy-induced changes in the micro-CT parameters. EL at 30 and 60 mg/kg rat worsened the trabecular bone connectivity density and trabecular separation parameters of orchidectomised rats. EL at 90 mg/kg rat preserved the bone volume. High dose of EL (90 mg/kg) may have potential in preserving the bone microarchitecture of orchidectomised rats, but lower doses may further worsen the osteoporotic changes.
  9. Abd Jalil MA, Shuid AN, Muhammad N
    PMID: 22973405 DOI: 10.1155/2012/714512
    Popularly known as "the silent disease" since early symptoms are usually absent, osteoporosis causes progressive bone loss, which renders the bones susceptible to fractures. Bone fracture healing is a complex process consisting of four overlapping phases-hematoma formation, inflammation, repair, and remodeling. The traditional use of natural products in bone fractures means that phytochemicals can be developed as potential therapy for reducing fracture healing period. Located closely near the equator, Malaysia has one of the world's largest rainforests, which are homes to exotic herbs and medicinal plants. Eurycoma longifolia (Tongkat Ali), Labisia pumila (Kacip Fatimah), and Piper sarmentosum (Kaduk) are some examples of the popular ethnic herbs, which have been used in the Malay traditional medicine. This paper focuses on the use of natural products for treating fracture as a result of osteoporosis and expediting its healing.
  10. Abd Manan N, Mohamed N, Shuid AN
    PMID: 22956976 DOI: 10.1155/2012/680834
    Oxidative stress and apoptosis can disrupt the bone formation activity of osteoblasts which can lead to osteoporosis. This study was conducted to investigate the effects of γ-tocotrienol on lipid peroxidation, antioxidant enzymes activities, and apoptosis of osteoblast exposed to hydrogen peroxide (H(2)O(2)). Osteoblasts were treated with 1, 10, and 100 μM of γ-tocotrienol for 24 hours before being exposed to 490 μM (IC(50)) H(2)O(2) for 2 hours. Results showed that γ-tocotrienol prevented the malondialdehyde (MDA) elevation induced by H(2)O(2) in a dose-dependent manner. As for the antioxidant enzymes assays, all doses of γ-tocotrienol were able to prevent the reduction in SOD and CAT activities, but only the dose of 1 μM of GTT was able to prevent the reduction in GPx. As for the apoptosis assays, γ-tocotrienol was able to reduce apoptosis at the dose of 1 and 10 μM. However, the dose of 100 μM of γ-tocotrienol induced an even higher apoptosis than H(2)O(2). In conclusion, low doses of γ-tocotrienol offered protection for osteoblasts against H(2)O(2) toxicity, but itself caused toxicity at the high doses.
  11. Ei Thu H, Hussain Z, Shuid AN
    Curr Drug Targets, 2018;19(8):865-876.
    PMID: 27894237 DOI: 10.2174/1389450117666161125174625
    Psychotic disorders are recognized as severe mental disorders that rigorously affect patient's personality, critical thinking, and perceptional ability. High prevalence, global dissemination and limitations of conventional pharmacological approaches compel a significant burden to the patient, medical professionals and the healthcare system. To date, numerous orally administered therapies are available for the management of depressive disorders, schizophrenia, anxiety, bipolar disorders and autism spectrum problems. However, poor water solubility, erratic oral absorption, extensive first-pass metabolism, low oral bioavailability and short half-lives are the major factors which limit the pharmaceutical significance and therapeutic feasibility of these agents. In recent decades, nanotechnology-based delivery systems have gained remarkable attention of the researchers to mitigate the pharmaceutical issues related to the antipsychotic therapies and to optimize their oral drug delivery, therapeutic outcomes, and patient compliance. Therefore, the present review was aimed to summarize the available in vitro and in vivo evidences signifying the pharmaceutical importance of the advanced delivery systems in improving the aqueous solubility, transmembrane permeability, oral bioavailability and therapeutic outcome of the antipsychotic agents.
  12. Effendy NM, Khamis MF, Shuid AN
    J Xray Sci Technol, 2016 Oct 21.
    PMID: 27768005
    Labisia pumila (LP) is a popular herb used by women over the past few decades. This herb has shown potentials as an alternative agent for treatment and prevention of postmenopausal osteoporosis. It was observed in previous studies that supplementation to ovariectomized rats were associated with increased bone antioxidative enzymes and reduced lipid peroxidation activity. It had also improved bone formation markers in ovariectomized rats. This study aimed to evaluate the effects of giving different forms of LP extracts on the trabecular bone microarchitecture of ovariectomised rats.
  13. Jayusman PA, Mohamed IN, Shuid AN
    Int J Endocrinol Metab, 2018 Jul;16(3):e64038.
    PMID: 30197659 DOI: 10.5812/ijem.64038
    Background: Gonadotropin releasing hormone (GnRH) antagonists may cause chemical castration in males by suppressing the pituitary-gonadal axis, hence reducing testosterone level. There are limited data on the effects of degarelix, a newer series of potent and long acting GnRH antagonist on bone.

    Objectives: The current study aimed at determining the effects of degarelix on bone turnover, bone densitometry, and bone mechanical strength in male rats.

    Methods: Eighteen male Sprague-Dawley rats were randomly divided into sham (SHAM), orchidectomized (ORX), and degarelix-induced (DGX) groups. Chemical castration was performed by subcutaneous degarelix injection (2 mg/kg) at the scapular region. The rats were scanned for baseline bone mineral area (BMA), bone mineral content (BMC), and bone mineral density (BMD) using dual-energy x-ray absorptiometry (DXA). Following six weeks of experimental period, BMA, BMC, and BMD were measured again with DXA and blood was collected for testosterone and bone biomarkers (osteocalcin and C-terminal of type I collagen crosslink (CTX-1)) measurements. The rats were euthanized and femora were dissected for bone biomechanical strength analysis.

    Results: Bilateral orchidectomy and degarelix administration significantly lowered serum testosterone level, decreased whole body BMC, femoral BMA, femoral BMC, and femoral BMD (P < 0.05) compared with the SHAM group. However, no significant changes were observed in bone biochemical markers and bone mechanical strength in all experimental groups.

    Conclusions: In conclusion, degarelix administration had comparable effects on bone as bilateral orchidectomy. Administration of degarelix provides an alternative method of inducing testosterone deficient-osteopenia in male rats without need for removing the testes.

  14. Mehrbod P, Harun MS, Shuid AN, Omar AR
    Methods Mol Biol, 2015;1282:241-50.
    PMID: 25720485 DOI: 10.1007/978-1-4939-2438-7_20
    Feline infectious peritonitis (FIP) is a lethal systemic disease caused by FIP virus (FIPV). There are no effective vaccines or treatment available, and the virus virulence determinants and pathogenesis are not fully understood. Here, we describe the sequencing of RNA extracted from Crandell Rees Feline Kidney (CRFK) cells infected with FIPV using the Illumina next-generation sequencing approach. Bioinformatics analysis, based on Felis catus 2X annotated shotgun reference genome, using CLC bio Genome Workbench is used to map both control and infected cells. Kal's Z test statistical analysis is used to analyze the differentially expressed genes from the infected CRFK cells. In addition, RT-qPCR analysis is used for further transcriptional profiling of selected genes in infected CRFK cells and Peripheral Blood Mononuclear Cells (PBMCs) from healthy and FIP-diagnosed cats.
  15. Effendy NM, Khamis MF, Soelaiman IN, Shuid AN
    J Xray Sci Technol, 2014;22(4):503-18.
    PMID: 25080117 DOI: 10.3233/XST-140441
    Postmenopausal osteoporosis is best treated and prevented by estrogen replacement therapy (ERT). Although effective, ERT may cause breast cancer, uterine cancer and cardiovascular problems. Labisia pumila var. alata (LP), a herb with phytoestrogenic, antioxidative and anti-inflammatory effects has potential as an ERT alternative.
  16. Ibrahim N', Mohamad S, Mohamed N, Shuid AN
    Curr Drug Targets, 2013 Dec;14(14):1642-50.
    PMID: 24350807
    Osteoporosis may cause bone fracture even under slight trauma. Osteoporotic fracture has become a major public health problem but until today, the treatments available are not satisfactory. Many pre-clinical testings on animals were done to find new agents that can be sourced from natural products and synthetic drugs for osteoporotic fracture healing. Animal models are more appropriate for fracture healing study than human subject due to several reasons including the ethical issues involved. The bones of rodents are similar to human in term of their morphological change and response to therapy. Small rodents such as rats and mice are suitable animal models for fracture healing studies as they have a similar bone remodeling system to human. To date, there is no specific guideline to carry out fracture healing studies in animal models for the evaluation of new agents. This paper highlights the protocols of various fracture and fixation methods for experimental osteoporotic fracture healing using rodent models.
  17. Muhammad N, Luke DA, Shuid AN, Mohamed N, Soelaiman IN
    Clinics (Sao Paulo), 2013 Oct;68(10):1338-43.
    PMID: 24212841 DOI: 10.6061/clinics/2013(10)08
    OBJECTIVE: Accelerated bone loss that occurs in postmenopausal women has been linked to oxidative stress and increased free radicals. We propose the use of antioxidants to prevent and reverse postmenopausal osteoporosis. This study aimed to examine the effects of tocotrienol, a vitamin E analog, on bone loss due to estrogen deficiency. Our previous study showed that tocotrienol increased the trabecular bone volume and trabecular number in ovariectomized rats. In the current study, we investigated the effects of tocotrienol supplementation on various biochemical parameters in a postmenopausal osteoporosis rat model.
    MATERIALS AND METHODS: A total of 32 female Wistar rats were randomly divided into four groups. The baseline group was sacrificed at the start of the study, and another group was sham operated. The remaining rats were ovariectomized and either given olive oil as a vehicle or treated with tocotrienol at a dose of 60 mg/kg body weight. After four weeks of treatment, blood was withdrawn for the measurement of interleukin-1 (IL1) and interleukin-6 (IL6) (bone resorbing cytokines), serum osteocalcin (a bone formation marker) and pyridinoline (a bone resorption marker).
    RESULTS: Tocotrienol supplementation in ovariectomized rats significantly reduced the levels of osteocalcin, IL1 and IL6. However, it did not alter the serum pyridinoline level.
    CONCLUSION: Tocotrienol prevented osteoporotic bone loss by reducing the high bone turnover rate associated with estrogen deficiency. Therefore, tocotrienol has the potential to be used as an anti-osteoporotic agent in postmenopausal women.
  18. Mohd Fozi NF, Mazlan M, Shuid AN, Isa Naina M
    Curr Drug Targets, 2013 Dec;14(14):1659-66.
    PMID: 24093748
    Osteoporosis is a progressive disease of the skeleton characterised by bone fragility due to a reduction in bone mass and possibly to alteration in bone architecture that lead to a propensity to fracture with minimum trauma. Most osteoporotic fractures occur at locations rich in trabecular or cancellous bone and usually related to post menopausal women. Recently, silymarin received attention due to its alternative beneficial effect on bone formation. It is a mixture of flavonoids with powerful antioxidant properties. This review focuses on the use of milk thistle or silymarin for the treatment of osteoporosis that may be related to fracture bone. Silymarin shows potent antioxidant herb that may modulate multiple genes in favour of helping to build bone and prevent bone loss. In the mouse fracture healing model, silymarin supplementation improved tibial healing with elevated BMD and serum levels of ALP and osteocalcin. Silymarin also demonstrated clear estrogenic antiosteoporotic effects in bone structure. Silymarin appears to play a crucial role to prevent bone loss and might regulate osteogenesis and may be beneficial for fracture healing. If silymarin is considered for the use of post menopausal women, it may be used for the treatment of osteoporosis. It would be of great benefit to postmenopausal women to develop an oestrogen antagonist that is as potent and efficacious as oestrogen in preventing bone loss without the major side effect associated with HRT.
  19. Muhammad N, Luke DA, Shuid AN, Mohamed N, Soelaiman IN
    PMID: 23118785 DOI: 10.1155/2012/161527
    Postmenopausal osteoporotic bone loss occurs mainly due to cessation of ovarian function, a condition associated with increased free radicals. Vitamin E, a lipid-soluble vitamin, is a potent antioxidant which can scavenge free radicals in the body. In this study, we investigated the effects of alpha-tocopherol and pure tocotrienol on bone microarchitecture and cellular parameters in ovariectomized rats. Three-month-old female Wistar rats were randomly divided into ovariectomized control, sham-operated, and ovariectomized rats treated with either alpha-tocopherol or tocotrienol. Their femurs were taken at the end of the four-week study period for bone histomorphometric analysis. Ovariectomy causes bone loss in the control group as shown by reduction in both trabecular volume (BV/TV) and trabecular number (Tb.N) and an increase in trabecular separation (Tb.S). The increase in osteoclast surface (Oc.S) and osteoblast surface (Ob.S) in ovariectomy indicates an increase in bone turnover rate. Treatment with either alpha-tocopherol or tocotrienol prevents the reduction in BV/TV and Tb.N as well as the increase in Tb.S, while reducing the Oc.S and increasing the Ob.S. In conclusion, the two forms of vitamin E were able to prevent bone loss due to ovariectomy. Both tocotrienol and alpha-tocopherol exert similar effects in preserving bone microarchitecture in estrogen-deficient rat model.
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