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Fulltext Lifestyle indices of body composition and obesity risk and prevalence among multi-ethnic adolescents in Malaysia

Zulfarina MS, Sharif R, Mokhtar SA, Shuid AN, Naina-Mohamed I

Front Pediatr, 2022;10:899014.
PMID: 36389377 DOI: 10.3389/fped.2022.899014

The prevalence of childhood obesity in Malaysia has doubled in less than a decade. Moreover, being overweight and obese have been associated with immediate and later comorbidities, thus emphasizing the need to prevent obesity from an early age. This cross-sectional study involved 923 multi-ethnic Malaysian adolescents aged between 15 and 17 years old. Body composition was estimated using bioelectrical impedance analysis. Body mass index (BMI) classification was based on the World Health Organization (WHO) growth reference and the International Obesity Task Force (IOTF) cut-off. Meanwhile, the Child Growth Foundation (CGF) body fat reference was used to classify adolescents' adiposity. Lifestyle indices including physical activity, sedentary behavior, supplement intake, smoking and alcohol status were assessed via questionnaires. A high prevalence of overweight/obesity among the adolescents was observed according to the CGF (26%), followed by that of the WHO (24%) and then the IOTF (23%) cut-off, with high concordance values between each pair. After adjustment, a significant association was found between physical activity (PAQ score) and lean mass (p = 0.027). No lifestyle determinant was found to be a significant predictor of fat percentage. A high sedentary level increased the likelihood of obesity (OR 3.0, p
Quality of energy intake in Malaysian adolescents: prevalence, characteristics, determinants and impact of implausible reporters

Zulfarina MS, Sharif R, Sharkawi AM, Mokhtar SA, Shuid AN, Naina-Mohamed I

Public Health Nutr, 2023 Jan;26(1):122-131.
PMID: 35321764 DOI: 10.1017/S1368980022000726

OBJECTIVE: Misreporting of energy intake (EI) in nutritional epidemiology is common and even severe among adolescents. Thus, the current study aims to examine the presence, bias and impact introduced by implausible reporters.
DESIGN: Cross-sectional.
SETTING: Central and eastern regions of Peninsular Malaysia.
PARTICIPANTS: A stratified random sampling was employed to select 917 secondary school-going adolescents (aged 15-17 years).
RESULTS: The prevalence of under-reporters was 17·4 %, while no over-reporters were identified. Under-reporters had higher body composition and lower dietary intakes (except for vitamin C, Cr and Fl) compared with plausible reporters (P < 0·05). Adolescents with overweight and obesity had a higher odds of under-reporting compared with under-/normal weight adolescents (P < 0·001). In model 3, the highest regression coefficient (R2 = 0·404, P < 0·001) was obtained after adjusting for reporting status.
CONCLUSIONS: Overweight and obese adolescents were more likely to under-report their food intake and consequently affect nutrient intakes estimates. Future analyses that include nutrient intake data should adjust for reporting status so that the impact of misreporting on study outcomes can be conceded and consequently improve the accuracy of dietary-related results.
Fulltext Machine learning-based integrated identification of predictive combined diagnostic biomarkers for endometriosis

Zhang H, Zhang H, Yang H, Shuid AN, Sandai D, Chen X

Front Genet, 2023;14:1290036.
PMID: 38098472 DOI: 10.3389/fgene.2023.1290036

Background: Endometriosis (EM) is a common gynecological condition in women of reproductive age, with diverse causes and a not yet fully understood pathogenesis. Traditional diagnostics rely on single diagnostic biomarkers and does not integrate a variety of different biomarkers. This study introduces multiple machine learning techniques, enhancing the accuracy of predictive models. A novel diagnostic approach that combines various biomarkers provides a new clinical perspective for improving the diagnostic efficiency of endometriosis, holding significant potential for clinical application. Methods: In this study, GSE51981 was used as a test set, and 11 machine learning algorithms (Lasso, Stepglm, glmBoost, Support Vector Machine, Ridge, Enet, plsRglm, Random Forest, LDA, XGBoost, and NaiveBayes) were employed to construct 113 predictive models for endometriosis. The optimal model was determined based on the AUC values derived from various algorithms. These genes were then evaluated using nine machine learning algorithms (Random Forest, SVM, Gradient Boosting Machine, LASSO, XGB, NNET, Generalized Linear Model, KNN, and Decision Tree) to assess significance scores and identify diagnostic genes for each algorithm. The diagnostic value of these genes was further validated in external datasets from GSE7305, GSE11691, and GSE120103. Results: Analysis of the GSE51981 dataset revealed 62 DEGs. The Stepglm [Both] and plsRglm algorithms identified 30 genes with the most potential using the AUC evaluation. Subsequently, nine machine learning algorithms were applied to select diagnostic genes, leading to the identification of five key diagnostic genes using the LASSO algorithm. The ADAT1 gene exhibited the best single-gene predictive performance, with an AUC of 0.785. A combination of genes (FOS, EPHX1, DLGAP5, PCSK5, and ADAT1) achieves an AUC of 0.836 in the test dataset. Moreover, these genes consistently exhibited an AUC exceeding 0.78 in all validation datasets, demonstrating superior predictive performance. Furthermore, correlation analysis with immune infiltration strengthened their predictive value by demonstrating the close relationship of the diagnostic genes with immune infiltrating cells. Conclusion: A combination of biomarkers consisting of FOS, EPHX1, DLGAP5, PCSK5, and ADAT1 can serve as a diagnostic tool for endometriosis, enhancing diagnostic efficiency. The association of these genes with immune infiltrating cells reveals their potential role in the pathogenesis of endometriosis, providing new insights for early detection and treatment.
Protective effects of Tualang honey on bone structure in experimental postmenopausal rats

Zaid SS, Sulaiman SA, Othman NH, Soelaiman IN, Shuid AN, Mohamad N, et al.

Clinics (Sao Paulo), 2012 Jul;67(7):779-84.
PMID: 22892923

OBJECTIVE: The objective of this study was to evaluate the effects of Tualang honey on trabecular structure and compare these effects with those of calcium supplementation in ovariectomized rats.
METHODS: Forty female, Sprague-Dawley rats were randomly divided into five groups (n =8): four controls and one test arm. The control arm comprised a baseline control, sham-operated control, ovariectomized control, and ovariectomized calcium-treated rats (receiving 1% calcium in drinking water ad libitum). The test arm was composed of ovariectomized, Tualang honey-treated rats (received 0.2 g/kg body weight of Tualang honey). Both the sham-operated control and ovariectomized control groups received vehicle treatment (deionized water), and the baseline control group was sacrificed without treatment.
RESULTS: All rats were orally gavaged daily for six weeks after day one post-surgery. The bone structural analysis of rats in the test arm group showed a significant increase in the bone volume per tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular number (Tb.N) and a significant decrease in inter-trabecular space (Tb.Sp) compared with the ovariectomized control group. The trabecular thickness (Tb.Th) in the test arm group was significantly higher compared with the ovariectomized-calcium treated group, and the inter-trabecular space (Tb.Sp) in the test arm group was significantly narrower compared with the ovariectomized-calcium treated group.
CONCLUSION: In conclusion, ovariectomized rats that received Tualang honey showed more improvements in trabecular bone structure than the rats that received calcium.
Fulltext The Molecular Mechanism of Vitamin E as a Bone-Protecting Agent: A Review on Current Evidence

Wong SK, Mohamad NV, Ibrahim N', Chin KY, Shuid AN, Ima-Nirwana S

Int J Mol Sci, 2019 Mar 22;20(6).
PMID: 30909398 DOI: 10.3390/ijms20061453

Bone remodelling is a tightly-coordinated and lifelong process of replacing old damaged bone with newly-synthesized healthy bone. In the bone remodelling cycle, bone resorption is coupled with bone formation to maintain the bone volume and microarchitecture. This process is a result of communication between bone cells (osteoclasts, osteoblasts, and osteocytes) with paracrine and endocrine regulators, such as cytokines, reactive oxygen species, growth factors, and hormones. The essential signalling pathways responsible for osteoclastic bone resorption and osteoblastic bone formation include the receptor activator of nuclear factor kappa-B (RANK)/receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG), Wnt/β-catenin, and oxidative stress signalling. The imbalance between bone formation and degradation, in favour of resorption, leads to the occurrence of osteoporosis. Intriguingly, vitamin E has been extensively reported for its anti-osteoporotic properties using various male and female animal models. Thus, understanding the underlying cellular and molecular mechanisms contributing to the skeletal action of vitamin E is vital to promote its use as a potential bone-protecting agent. This review aims to summarize the current evidence elucidating the molecular actions of vitamin E in regulating the bone remodelling cycle.
The use of selective estrogen receptor modulators on bone health in men

Wong SK, Mohamad NV, Jayusman PA, Shuid AN, Ima-Nirwana S, Chin KY

Aging Male, 2019 Jun;22(2):89-101.
PMID: 29508640 DOI: 10.1080/13685538.2018.1448058

Selective estrogen receptor modulators (SERMs) represent a class of drugs that act as agonist or antagonist for estrogen receptor in a tissue-specific manner. The SERMs drugs are initially used for the prevention and treatment of osteoporosis in postmenopausal women. Bone health in prostate cancer patients has become a significant concern, whereby patients undergo androgen deprivation therapy is often associated with deleterious effects on bone. Previous preclinical and epidemiological findings showed that estrogens play a dominant role in improving bone health as compared to testosterone in men. Therefore, this evidence-based review aims to assess the available evidence derived from animal and human studies on the effects of SERMs on the male skeletal system. The effects of SERMs on bone mineral density (BMD)/content (BMC), bone histomorphometry, bone turnover, bone strength and fracture risk have been summarized in this review.
Eurycoma longifolia as a potential alternative to testosterone for the treatment of osteoporosis: Exploring time-mannered proliferative, differentiative and morphogenic modulation in osteoblasts

Thu HE, Mohamed IN, Hussain Z, Shuid AN

J Ethnopharmacol, 2017 Jan 04;195:143-158.
PMID: 27818256 DOI: 10.1016/j.jep.2016.10.085

ETHNOPHARMACOLOGICAL RELEVANCE: Eurycoma longifolia (EL) has been well-studied traditionally as a chief ingredient of many polyherbal formulations for the management of male osteoporosis. It has also been well-recognised to protect against bone calcium loss in orchidectomised rats.
AIM OF THE STUDY: To evaluate the effects of EL on the time-mannered sequential proliferative, differentiative, and morphogenic modulation in osteoblasts compared with testosterone.
MATERIALS AND METHODS: Cell proliferation was analysed using MTS assay and phase contrast microscopy. Osteogenic differentiation of MC3T3-E1 cells was assessed through a series of characteristic assays which include crystal violet staining, alkaline phosphatase (ALP) activity and Van Gieson staining. Taken together, the bone mineralization of extra cellular matrix (ECM) was estimated using alizarin red s (ARS) staining, von kossa staining, scanning electron microscopic (SEM) and energy dispersive x-ray (EDX) analysis.
RESULTS: The cell proliferation data clearly revealed the efficiency of EL particularly at a dose of 25µg/mL, in improving the growth of MC3T3-E1 cells compared with the untreated cells. Data also showed the prominence of EL in significantly promoting ALP activity throughout the entire duration of treatment compared with the testosterone-treated cells. The osteogenic differentiation potential of EL was further explored by analysing mineralization data which revealed that the calcified nodule formation (calcium deposition) and phosphate deposition was more pronounced in cells treated with 25µg/mL concentration of EL at various time points compared with the untreated and testosterone treated cells. The scanning electron microscopic (SEM) analysis also revealed highest globular masses of mineral deposits (identified as white colour crystals) in the ECM of cultured cells treated with 25µg/mL concentration of EL.
CONCLUSION: Compared to testosterone, greater potential of EL in promoting the proliferation and osteogenic differentiation of MC3T3-E1 cells provides an in vitro basis for the prevention of male osteoporosis. Thus, we anticipate that EL can be considered as an alternative approach to testosterone replacement therapy (TRT) for the treatment of male osteoporosis.
Eurycoma longifolia, A Potential Phytomedicine for the Treatment of Cancer: Evidence of p53-mediated Apoptosis in Cancerous Cells

Thu HE, Hussain Z, Mohamed IN, Shuid AN

Curr Drug Targets, 2018;19(10):1109-1126.
PMID: 28721818 DOI: 10.2174/1389450118666170718151913

BACKGROUND: Eurycoma longifolia is a well-documented herbal medicine that has gained widespread recognition due to its versatile pharmacological activities including anticancer, antimalarial, antimicrobial, antioxidant, aphrodisiac, anti-inflammatory, anxiolytic, anti-diabetic, antirheumatism and anti-ulcer. Plethora of in vitro and in vivo studies evidenced their excellent antiproliferative and anticancer efficacy against various types of human cancers.
OBJECTIVE: This review was aimed to critically analyze the therapeutic viability and anticancer efficacy of Eurycoma longifolia in the treatment of cancer and also to propose its molecular and translational mechanism of cytotoxicity against cancerous cells.
RESULTS: Among a range of medicinally active compounds isolated from various parts (roots, stem, bark and leaves) of Eurycoma longifolia, 16 compounds have shown promising anti-proliferative and anticancer efficacies. Eurycomanone, one of the most active medicinal compounds of Eurycoma longifolia, displayed a strong dose-dependent anticancer efficacy against lung carcinoma (A-549 cells) and breast cancer (MCF-7 cells); however, showed moderate efficacy against gastric (MGC-803 cells) and intestinal carcinomas (HT-29 cells). The prime mode of cytotoxicity of Eurycoma longifolia and its medicinal compounds is the induction of apoptosis (programmed cell death) via the up-regulation of the expression of p53 (tumor suppressor protein) and pro-apoptotic protein (Bax) and downregulation of the expression of anti-apoptotic protein (Bcl-2). A remarkable alleviation in the mRNA expression of various cancer-associated biomarkers including heterogeneous nuclear ribonucleoprotein (hnRNP), prohibitin (PHB), annexin-1 (ANX1) and endoplasmic reticulum protein-28 (ERp28) has also been evidenced.
CONCLUSION: Eurycoma longifolia and its medicinal constituents exhibit promising anticancer efficacy and thus can be considered as potential complementary therapy for the treatment of various types of human cancers.
Eurycoma Longifolia as a potential adoptogen of male sexual health: a systematic review on clinical studies

Thu HE, Mohamed IN, Hussain Z, Jayusman PA, Shuid AN

Chin J Nat Med, 2017 Jan;15(1):71-80.
PMID: 28259255 DOI: 10.1016/S1875-5364(17)30010-9

Eurycoma longifolia (EL) has been well recognized as a booster of male sexual health. Over the past few decades, numerous in vivo animal studies and human clinical trials have been conducted across the globe to explore the promising role of EL in managing various male sexual disorders, which include erectile dysfunction, male infertility, low libido, and downregulated testosterone levels. The aim of the present review is to analyze and summarize the literature on human clinical trials which revealed the clinical significance and therapeutic feasibility of EL in improving male sexual health. This systematic review is focused on the following databases: Medline, Wiley Online Library, BioMed Central, Hindawi, Web of Knowledge, PubMed Central and Google Scholar, using search terms such as "Eurycoma longifolia", "EL", "Tongkat Ali", "male sexual health", "sexual infertility", "erectile dysfunction", "male libido", and "testosterone levels". Notably, only human clinical studies published between 2000 and 2014 were selected and thoroughly reviewed for relevant citations. Out of 150 articles, 11 met the inclusion criteria. The majority of articles included were randomized placebo-controlled trials, multiple cohort studies, or pilot trials. All these studies demonstrated considerable effects of EL on male sexual health disorders. Among them, 7 studies revealed remarkable association between the use of EL and the efficacy in the treatment of male sexual disorders, and remaining 4 studies failed to demonstrate sufficient effects on male sexual health. In summary, there is convincing evidence for the prominence of EL in improving the male sexual health. The review also substantiates the use of current methodology in the development of novel and more rationale natural herbal medicines for the management of male sexual disorders.
Fulltext Eurycoma longifolia, a promising suppressor of RANKL-induced differentiation and activation of osteoclasts: An in vitro mechanistic evaluation

Thu HE, Hussain Z, Mohamed IN, Shuid AN

J Ayurveda Integr Med, 2018 08 16;10(2):102-110.
PMID: 30120052 DOI: 10.1016/j.jaim.2017.07.014

BACKGROUND: Eurycoma longifolia (E. longifolia) has gained remarkable recognition due to its promising efficacy of stimulating bone formation in androgen-deficient osteoporosis. Numerous in vivo studies have explored the effects of E. longifolia on osteoporosis; however, the in vitro cellular mechanism was not discovered yet.
OBJECTIVES: The present study was aimed to investigate the effect of E. longifolia on the proliferation, differentiation and maturation of osteoclasts and the translational mechanism of inhibition of osteoclastogenesis using RAW 264.7 cells as an in vitro osteoclastic model.
MATERIALS AND METHODS: Having assessed cytotoxicity, the cell viability, cell proliferation rate and osteoclastic differentiation capacity of E. longifolia was investigated by evaluating the tartrate-resistant acid phosphatase (TRAP) activity in receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclasts. Taken together, the time-mannered expression of osteoclast-related protein biomarkers such as matrix metallopeptidase-9 (MMP-9), cathepsin-K, TRAP, nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), superoxide (free radicals) generation and superoxide dismutase activity were also measured to comprehend the mechanism of osteoclastogenesis.
RESULTS: E. longifolia did not show significant effects on cytotoxicity and cell proliferation of RAW 264.7 cells; however, a significant inhibition of cells differentiation and maturation of osteoclasts was observed. Moreover, a significant down-regulation of RANKL-induced TRAP activity and expression of MMP-9, cathepsin-K, TRAP, NFATc1 and generation of superoxide and enhanced superoxide dismutase activity was observed in E. longifolia treated cell cultures.
CONCLUSION: We anticipated that E. longifolia that enhances bone regeneration on the one hand and suppresses osteoclast's maturation on the other hand may have great therapeutic value in treating osteoporosis and other bone-erosive diseases such as rheumatoid arthritis and metastasis associated with bone loss.
Fulltext Dihydrotestosterone, a robust promoter of osteoblastic proliferation and differentiation: understanding of time-mannered and dose-dependent control of bone forming cells

Thu HE, Mohamed IN, Hussain Z, Shuid AN

Iran J Basic Med Sci, 2017 Aug;20(8):894-904.
PMID: 29085581 DOI: 10.22038/IJBMS.2017.9111

OBJECTIVES: The present study was aimed to evaluate the time-mannered and dose-dependent effects of 5α-dihydrotestosterone (5α-DHT) on the proliferation and differentiation of bone forming cells using MC3T3-E1 cells.
MATERIALS AND METHODS: Cell proliferation was analyzed using MTS and phase contrast microscopic assays. Osteogenic differentiation was assessed through a series of in vitro experiments including crystal violet staining, alkaline phosphatase (ALP) activity, and Van Gieson (VG) staining. Taken together, the efficiency of bone mineralization was examined by using alizarin red s (ARS) staining, Von Kossa staining, scanning electron microscopy (SEM) and energy dispersive x-ray (EDX) analysis.
RESULTS: The resulting data revealed that 5α-DHT exhibits promising potential particularly at a dose of 0.1 ng/ml, in promoting the growth of MC3T3-E1 cells compared to the control group (CN). Moreover, a significantly higher ALP activity was evident in the experimental group treated with 5α-DHT compared to the CN group at various time intervals. MC3T3-E1 cells treated with 5α-DHT also expressed a remarkably higher collagen deposition and mineralization (calcium and phosphate contents) compared to the CN group at various time intervals.
CONCLUSION: Conclusively, we suggest that 5α-DHT exhibits outstanding potential of promoting proliferation and differentiation in osteoblasts which could be the in vitro basis for the efficacy of 5α-DHT in the treatment of androgen-deficient male osteoporosis.
Fulltext Exploring molecular mechanism of bone-forming capacity of Eurycoma longifolia: Evidence of enhanced expression of bone-related biomarkers

Thu HE, Mohamed IN, Hussain Z, Shuid AN

J Ayurveda Integr Med, 2017 11 13;9(4):272-280.
PMID: 29146110 DOI: 10.1016/j.jaim.2017.04.005

BACKGROUND: Among the numerous well-documented medicinal herbs, Eurycoma longifolia (EL) has gained remarkable recognition due to its promising efficacy of stimulating bone formation in androgen-deficient osteoporosis. Though numerous animal studies have explored the bone-forming capacity of EL, the exact mechanism was yet to be explored.
OBJECTIVE(S): The present study was aimed to investigate the mechanism of bone-forming capacity of EL using MC3T3-E1 as an in vitro osteoblastic model.
MATERIALS AND METHODS: The cell differentiation capacity of EL was investigated by evaluating cell growth, alkaline phosphatase (ALP) activity, collagen deposition and mineralization. Taken together, time-mannered expression of bone-related mediators which include bone morphogenic protein-2 (BMP-2), ALP, runt-related transcription factor-2 (Runx-2), osteocalcin (OCN), type I collagen, osteopontin (OPN), transforming growth factor-β1 (TGF-β1) and androgen receptor (AR) were measured to comprehend bone-forming mechanism of EL.
RESULTS: Results demonstrated a superior cell differentiation efficacy of EL (particularly at a dose of 25 μg/mL) that was evidenced by dramatically increased cell growth, higher ALP activity, collagen deposition and mineralization compared to the testosterone. Results analysis of the bone-related protein biomarkers indicated that the expression of these mediators was well-regulated in EL-treated cell cultures compared to the control groups. These findings revealed potential molecular mechanism of EL for the prevention and treatment of male osteoporosis.
CONCLUSION: The resulting data suggested that EL exhibited superior efficacy in stimulating bone formation via up-regulating the expression of various mitogenic proteins and thus can be considered as a potential natural alternative therapy for the treatment of osteoporosis.
Recent Advances in Antibacterial, Antiprotozoal and Antifungal Trends of Eurycoma longifolia: A Review of Therapeutic Implications and Future Prospects

Thu HE, Hussain Z, Mohamed IN, Shuid AN

Curr Drug Targets, 2018;19(14):1657-1671.
PMID: 29468964 DOI: 10.2174/1389450119666180219123815

BACKGROUND: Eurycoma longifolia (E. longifolia) has gained widespread recognition due to its versatile pharmacological activities including aphrodisiac, anticancer, antimicrobial, antioxidant, anti-inflammatory, anxiolytic, anti-diabetic, ergogenic, insecticidal, anti-rheumatism, bone protection, and anti-ulcer effects.
OBJECTIVE: This review was aimed to critically overview the literature and summarizes the antibacterial, antiprotozoal, and antifungal trends of E. longifolia and its medicinally active components.
RESULTS: Besides its well-documented safety, efficacy, and tolerability, a plethora of in vitro, in vivo, and human clinical studies has evidenced the antimicrobial efficacy of E. longifolia and its bioactive constituents. Phytochemical screening of various types of extracts (methanolic, ethyl acetate, and nbutanolic) from different parts (roots, stem, and leaves) of E. longifolia displayed a dose-dependent antibacterial, antiprotozoal, and antifungal responses. Comparative analysis revealed that the root extract of E. longifolia exhibited the highest antimicrobial efficacy compared to other parts of the plant. Bioactivity-guided fractionation identified that among all of the medicinal compounds isolated/ extracted from different parts of E. longifolia, eurycomanone displayed the strongest antibacterial, antiprotozoal and antifungal activities.
CONCLUSION: Based on the critical analysis of the literature, we identified that E. longifolia exhibits promising antibacterial, antiprotozoal, and antifungal efficacies against various pathogenic microbes and thus can be considered as a potential complementary and alternative antimicrobial therapy.
Fulltext Effects of Eurycoma longifolia on Testosterone Level and Bone Structure in an Aged Orchidectomised Rat Model

Tajul Ariff AS, Soelaiman IN, Pramanik J, Shuid AN

Evid Based Complement Alternat Med, 2012;2012:818072.
PMID: 22966245 DOI: 10.1155/2012/818072

Testosterone replacement is the choice of treatment in androgen-deficient osteoporosis. However, long-term use of testosterone is potentially carcinogenic. Eurycoma longifolia (EL) has been reported to enhance testosterone level and prevent bone calcium loss but there is a paucity of research regarding its effect on the bone structural parameters. This study was conducted to explore the bone structural changes following EL treatment in normal and androgen-deficient osteoporosis rat model. Thirty-six male Sprague-Dawley rats aged 12 months were divided into normal control, normal rat supplemented with EL, sham-operated, orchidectomised-control, orchidectomised with testosterone replacement, and orchidectomised with EL supplementation groups. Testosterone serum was measured both before and after the completion of the treatment. After 6 weeks of the treatment, the femora were processed for bone histomorphometry. Testosterone replacement was able to raise the testosterone level and restore the bone volume of orchidectomised rats. EL supplementation failed to emulate both these testosterone actions. The inability of EL to do so may be related to the absence of testes in the androgen deficient osteoporosis model for EL to stimulate testosterone production.
Fulltext Palm tocotrienol supplementation enhanced bone formation in oestrogen-deficient rats

Soelaiman IN, Ming W, Abu Bakar R, Hashnan NA, Mohd Ali H, Mohamed N, et al.

Int J Endocrinol, 2012;2012:532862.
PMID: 23150728 DOI: 10.1155/2012/532862

Postmenopausal osteoporosis is the commonest cause of osteoporosis. It is associated with increased free radical activity induced by the oestrogen-deficient state. Therefore, supplementation with palm-oil-derived tocotrienols, a potent antioxidant, should be able to prevent this bone loss. Our earlier studies have shown that tocotrienol was able to prevent and even reverse osteoporosis due to various factors, including oestrogen deficiency. In this study we compared the effects of supplementation with palm tocotrienol mixture or calcium on bone biomarkers and bone formation rate in ovariectomised (oestrogen-deficient) female rats. Our results showed that palm tocotrienols significantly increased bone formation in oestrogen-deficient rats, seen by increased double-labeled surface (dLS/Bs), reduced single-labeled surface (sLS/BS), increased mineralizing surface (MS/BS), increased mineral apposition rate (MAR), and an overall increase in bone formation rate (BFR/BS). These effects were not seen in the group supplemented with calcium. However, no significant changes were seen in the serum levels of the bone biomarkers, osteocalcin, and cross-linked C-telopeptide of type I collagen, CTX. In conclusion, palm tocotrienol is more effective than calcium in preventing oestrogen-deficient bone loss. Further studies are needed to determine the potential of tocotrienol as an antiosteoporotic agent.
Fulltext Use of medicinal plants and natural products for treatment of osteoporosis and its complications

Soelaiman IN, Das S, Shuid AN, Mo H, Mohamed N

Evid Based Complement Alternat Med, 2013;2013:764701.
PMID: 23476703 DOI: 10.1155/2013/764701
Editorial: novel agents in the treatment of osteoporosis and its complications

Shuid AN, Soelaiman IN, Das S

Curr Drug Targets, 2013 Dec;14(13):1523.
PMID: 24266612
Novel agents in the treatment of osteoporosis

Shuid AN, Ima Nirwana S, Das S

Curr Drug Targets, 2013 Dec;14(14):1631.
PMID: 24383964
Drug delivery systems for prevention and treatment of osteoporotic fracture

Shuid AN, Ibrahim N', Mohd Amin MC, Mohamed IN

Curr Drug Targets, 2013 Dec;14(13):1558-64.
PMID: 24200294

Anti-osteoporotic drugs are available for treatment of osteoporosis and for preventing osteoporosis complications especially fractures. Most of the current anti-osteoporotic drugs are administered orally or parenterally to target the osteoporosis-affected bones. However, bone is a peripheral organ with limited blood supply. Therefore, the drugs delivered are exposed to various physicochemical and biological factors which affect the bioavailability of the drugs. In preclinical research, the dose of a potential anti-osteoporotic agent used in animal model may be too high for human application when administered via the conventional route of administration. The current anti-osteoporotic drugs need to be administered at higher doses to account for pharmacological interactions. However, this will expose the patients to adverse effects such as the cancer risks of postmenopausal women who took estrogen replacement therapy. There is also problem with patient compliance as anti-osteoporotic drugs may have to be taken for prolonged duration. The current deliveries of drugs need to be improved to overcome these problems. This review discussed several potential drug delivery systems which are able to contain the anti-osteoporosis drugs and release them slowly to the targeted bone. Among them are various carriers, polymers and microsponges, which may not only increase drug efficacy but also reduce adverse effects. The delivery systems allow the drugs to be administered locally at the targeted bone for longer duration, therefore reducing drug frequency and improving patient's compliance. It is hoped that these delivery systems may be applicable for the treatment of osteoporosis in the future to keep tab of the rising osteoporotic fracture incidence.
Pomegranate use to attenuate bone loss in major musculoskeletal diseases: an evidence-based review

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.

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