Displaying publications 21 - 40 of 101 in total

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  1. Ima-Nirwana S, Merican Z, Jamaluddin M, Viswanathan P, Khalid BA
    Asia Pac J Clin Nutr, 1996 Jun;5(2):100-4.
    PMID: 24394519
    The atherogenic potential of soybean oil (Sb) and palm oil (PO) was compared by measuring lipid profile, lipid peroxidation (LP) and activity of the antioxidant enzyme glutathione peroxidase (GSHPx) in rat sera and liver and heart homogenates. Male Rattus norwegicus rats were fed a basal diet, or basal diet fortified with 20% weight/ weight Sb or PO for 4 or 9 months. There was no difference in high density lipoprotein cholesterol:low density lipoprotein cholesterol ratio between the two groups, but triglyceride concentrations were higher in the PO fed rats compared to the Sb fed rats, although the difference diminished after 9 months. No differences in serum LP and GSHPx activity were seen between the two groups. In the liver and heart, LP was lower in PO after 4 months feeding, but the reverse was seen after 9 months. Liver and heart GSHPx activity was higher in the PO group after both treatment periods. In conclusion, both PO and Sb fed rats appeared comparable in their lipid profile, but the PO food had a temporary beneficial effect on the LP process in liver and heart. GSHPx activity however did not correlate well with LP in liver and heart, suggesting involvement of other antioxidants.
  2. Ima-Nirwana S, Jamaludin M, Khalid BA, Merican Z, Baharom S
    Asia Pac J Clin Nutr, 1995 Jun;4(2):244-8.
    PMID: 24394332
    The effects of castration with/ without testosterone replacement in male rats, and ovarectomy with oestrogen replacement in female rats, on serum lipids were studied. Simultaneous feeding with diets fortified with 20% weight/ weight (w/ w) soybean oil (Sb) or palm oil (P0) were done to determine the influence of these oils on serum lipids in castrated and sex hormone replaced rats. Two month old male and female Rattus norwegicus rats were given the above treatment for 4 months, and their sera assayed for lipid profile. Castration increased HDL-cholesterol (HDLchol) and total cholesterol (Tchol) concentrations. Testosterone or oestrogen replacement in male and female rats respectively increased HDLchol and decreased LDL-cholesterol (LDLchol) concentrations. Testosterone replacement also decreased Tchol concentration back to noncastrated levels, and reduced serum triglycerides (TG) to lower than non-castrated levels. Addition of Sb or P0 to the diet increased the LDLchol in the testosterone or oestrogen replaced male and female rats, but there was no difference between the two groups. P0 raised serum TG of the testosterone replaced group compared to control and Sb groups. In conclusion, testosterone and oestrogen were found to have favourable effects on serum lipids. Sb and P0 did not differ in their effects on lipoprotein cholesterol and Tchol, but P0 raised serum TG as compared to Sb.
  3. Hafiz A, Ima-Nirwana S, Chin KY
    J Taibah Univ Med Sci, 2018 Oct;13(5):491-495.
    PMID: 31435368 DOI: 10.1016/j.jtumed.2018.01.004
    Objectives: Physicians are known to experience a high level of stress due to the profession itself, as well as due to factors related to the workplace, patient care, and work-life balance. Owing to the nature of public and private hospitals in Malaysia, physicians working in different settings are expected to have different levels of stress. However, there is no study to validate this assumption. The present study aimed to compare stress levels between physicians working in public and private hospitals in the state of Johor, Malaysia.

    Methods: Participants were selected via stratified sampling. Participants completed an online questionnaire comprising demographic details and the Health Professional Stress Inventory. Scores on each domain and the aggregate scores were compared between physicians in public and private hospitals using a univariate analysis adjusted for potential confounders.

    Results: The overall stress level between physicians in public and private hospitals was similar. However, physicians in private hospitals experienced a higher stress level related to patient care responsibilities and professional uncertainty as compared to those in public hospitals.

    Conclusion: Physicians from private hospitals experience stress in different aspects of their profession as compared to physicians in public hospitals, especially with reference to patient care and career uncertainty. Measures should be taken to relieve the stress of physicians and thus improve their wellbeing.

  4. Wong SK, Chin KY, Ima-Nirwana S
    Int J Med Sci, 2020;17(11):1625-1638.
    PMID: 32669965 DOI: 10.7150/ijms.47103
    Oxidative stress and inflammation are two interlinked events that exist simultaneously in metabolic syndrome (MetS) and its related complications. These pathophysiological processes can be easily triggered by each other. This review summarizes the current evidence from animal and human studies on the effects of vitamin C in managing MetS. In vivo studies showed promising effects of vitamin C, but most of the interventions used were in combination with other compounds. The direct effects of vitamin C remain to be elucidated. In humans, the current state of evidence revealed that lower vitamin C intake and circulating concentration were found in MetS subjects. A negative relationship was observed between vitamin C intake / concentration and the risk of MetS. Oral supplementation of vitamin C also improved MetS conditions. It has been postulated that the positive outcomes of vitamin C may be in part mediated through its anti-oxidative and anti-inflammatory properties. These observations suggest the importance of MetS patients to have an adequate intake of vitamin C through food, beverages or supplements in order to maintain its concentration in the systemic circulation and potentially reverse MetS.
  5. Wong SK, Chin KY, Ima-Nirwana S
    Int J Mol Sci, 2020 Sep 03;21(17).
    PMID: 32899435 DOI: 10.3390/ijms21176448
    Quercetin is a flavonoid abundantly found in fruits and vegetables. It possesses a wide spectrum of biological activities, thus suggesting a role in disease prevention and health promotion. The present review aimed to uncover the bone-sparing effects of quercetin and its mechanism of action. Animal studies have found that the action of quercetin on bone is largely protective, with a small number of studies reporting negative outcomes. Quercetin was shown to inhibit RANKL-mediated osteoclastogenesis, osteoblast apoptosis, oxidative stress and inflammatory response while promoting osteogenesis, angiogenesis, antioxidant expression, adipocyte apoptosis and osteoclast apoptosis. The possible underlying mechanisms involved are regulation of Wnt, NF-κB, Nrf2, SMAD-dependent, and intrinsic and extrinsic apoptotic pathways. On the other hand, quercetin was shown to exert complex and competing actions on the MAPK signalling pathway to orchestrate bone metabolism, resulting in both stimulatory and inhibitory effects on bone in parallel. The overall interaction is believed to result in a positive effect on bone. Considering the important contributions of quercetin in regulating bone homeostasis, it may be considered an economical and promising agent for improving bone health. The documented preclinical findings await further validation from human clinical trials.
  6. Wong SK, Chin KY, Ima-Nirwana S
    Curr Drug Targets, 2019;20(12):1264-1280.
    PMID: 30961493 DOI: 10.2174/1389450120666190405172524
    Metabolic Syndrome (MetS) involves a cluster of five conditions, i.e. obesity, hyperglycaemia, hypertension, hypertriglyceridemia and low High-Density Lipoprotein (HDL) cholesterol. All components of MetS share an underlying chronic inflammatory aetiology, manifested by increased levels of pro-inflammatory cytokines. The pathogenic role of inflammation in the development of MetS suggested that toll-like receptor (TLR) activation may trigger MetS. This review summarises the supporting evidence on the interactions between MetS and TLR activation, bridged by the elevation of TLR ligands during MetS. The regulatory circuits mediated by TLR activation, which modulates signal propagation, leading to the state of chronic inflammation, are also discussed. Taken together, TLR activation could be the molecular basis in the development of MetS-induced inflammation.
  7. Wong SK, Ima-Nirwana S, Chin KY
    Bosn J Basic Med Sci, 2020 Nov 02;20(4):423-429.
    PMID: 32156247 DOI: 10.17305/bjbms.2020.4664
    Telomeres are repetitive DNA sequences located at the end of chromosomes that serve as a protective barrier against chromosomal deterioration during cell division. Approximately 50-200 base pairs of nucleotides are lost per cell division, and new repetitive nucleotides are added by the enzyme telomerase, allowing telomere maintenance. Telomere shortening has been proposed as an indicator for biological aging, but its relationship with age-related osteoporosis is ambiguous. We summarize the current evidence on the relationship between telomere length and bone health in experimental and epidemiological studies, which serve as a scientific reference for the development of novel diagnostic markers of osteoporosis or novel therapeutics targeting telomere and telomerase of bone cells to treat osteoporosis.
  8. Mohamad NV, Ima-Nirwana S, Chin KY
    Biomed Pharmacother, 2021 May;137:111368.
    PMID: 33582449 DOI: 10.1016/j.biopha.2021.111368
    Tocotrienol has been shown to prevent bone loss in animal models of postmenopausal osteoporosis, but the low oral bioavailability might limit its use. A self-emulsifying drug delivery system (SEDDS) could increase the bioavailability of tocotrienol. However, evidence of this system in improving the skeletal effects of tocotrienol is scanty. This study aims to evaluate the therapeutic efficacy of annatto tocotrienol with SEDDS in a rat model of postmenopausal bone loss. Ten-month-old female Sprague Dawley rats were randomized into six groups. The baseline group was euthanatized at the onset of the study. Four other groups underwent ovariectomy to induce estrogen deficiency. The sham underwent similar surgery procedure, but their ovaries were retained. Eight weeks after surgery, the ovariectomized rats received one of the four different regimens orally daily: (a) SEDDS, (b) annatto tocotrienol [60 mg/kg body weight (b.w.)] without SEDDS, (c) annatto-tocotrienol (60 mg/kg b.w.) with SEDDS, (d) raloxifene (1 mg/kg b.w.). After eight weeks of treatment, blood was collected for the measurement of delta-tocotrienol level and oxidative stress markers. The rats were euthanized and their bones were harvested for the evaluation of the bone microstructure, calcium content and strength. Circulating delta-tocotrienol level was significantly higher in rats receiving annatto tocotrienol with SEDDS compared to the group receiving unformulated annatto-tocotrienol (p 
  9. Mohamad NV, Ima-Nirwana S, Chin KY
    PMID: 32496996 DOI: 10.2174/1871530320666200604160614
    Osteoporosis is one of the major health issues associated with menopause-related estrogen deficiency. Various reports suggest that the hormonal changes related to menopausal transition may lead to the derangement of redox homeostasis and ultimately oxidative stress. Estrogen deficiency and oxidative stress may enhance the expression of genes involved in inflammation. All these factors may contribute, in synergy, to the development of postmenopausal osteoporosis. Previous studies suggest that estrogen may act as an antioxidant to protect the bone against oxidative stress, and as an antiinflammatory agent in suppressing pro-inflammatory and pro-osteoclastic cytokines. Thus, the focus of the current review is to examine the relationship between estrogen deficiency, oxidative stress and inflammation, and the impacts of these phenomena on skeletal health in postmenopausal women.
  10. Mohamad NV, Ima-Nirwana S, Chin KY
    Drug Des Devel Ther, 2018;12:555-564.
    PMID: 29588572 DOI: 10.2147/DDDT.S158410
    Background: Patients receiving androgen deprivation therapy experience secondary hypogonadism, associated bone loss, and increased fracture risk. It has been shown that tocotrienol from Bixa orellana (annatto) prevents skeletal microstructural changes in rats experiencing primary hypogonadism. However, its potential in preventing bone loss due to androgen deprivation therapy has not been tested. This study aimed to evaluate the skeletal protective effects of annatto tocotrienol using a buserelin-induced osteoporotic rat model.

    Methods: Forty-six male Sprague Dawley rats aged 3 months were randomized into six groups. The baseline control (n=6) was sacrificed at the onset of the study. The normal control (n=8) received corn oil (the vehicle of tocotrienol) orally daily and normal saline (the vehicle of buserelin) subcutaneously daily. The buserelin control (n=8) received corn oil orally daily and subcutaneous buserelin injection (75 µg/kg) daily. The calcium control (n=8) was supplemented with 1% calcium in drinking water and daily subcutaneous buserelin injection (75 µg/kg). The remaining rats were given daily oral annatto tocotrienol at 60 mg/kg (n=8) or 100 mg/kg (n=8) plus daily subcutaneous buserelin injection (75 µg/kg) (n=8). At the end of the experiment, the rats were euthanized and their blood, tibia, and femur were harvested. Structural changes of the tibial trabecular and cortical bone were examined using X-ray micro-computed tomography. Femoral bone calcium content and biomechanical strength were also evaluated.

    Results: Annatto tocotrienol at 60 and 100 mg/kg significantly prevented the deterioration of trabecular bone and cortical thickness in buserelin-treated rats (P<0.05). Both doses of annatto tocotrienol also improved femoral biomechanical strength and bone calcium content in buserelin-treated rats (P<0.05). The effects of annatto tocotrienol were comparable to calcium supplementation.

    Conclusion: Annatto tocotrienol supplementation is effective in preventing degeneration of the bone induced by buserelin. Therefore, it is a potential antiosteoporotic agent for men receiving androgen deprivation therapy.

  11. Wong SK, Chin KY, Ima-Nirwana S
    Drug Des Devel Ther, 2019;13:3497-3514.
    PMID: 31631974 DOI: 10.2147/DDDT.S227738
    Kaempferol is a dietary bioflavonoid ubiquitously found in various types of plant. It possesses a wide range of medicinal properties suggesting its potential clinical utility that requires further investigation. The present review intends to highlight the efficacy of kaempferol and its molecular mechanisms of action in regulating bone metabolism. Many reports have acknowledged the bone-protecting property of kaempferol and kaempferol-containing plants using in vitro and in vivo experimental models. Kaempferol supplementation showed bone-sparing effects in newborn rats, glucocorticoid-induced and ovariectomy-induced osteoporotic models as well as bone fracture models. It achieves the bone-protective effects by inhibiting adipogenesis, inflammation, oxidative stress, osteoclastic autophagy and osteoblastic apoptosis while activating osteoblastic autophagy. The anti-osteoporotic effects of kaempferol are mediated through regulation of estrogen receptor, bone morphogenetic protein-2 (BMP-2), nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) signaling pathways. In summary, kaempferol exhibits beneficial effects on skeleton, thus is potentially effective for the prophylaxis and treatment of osteoporosis.
  12. Wong SK, Chin KY, Ima-Nirwana S
    Phytomedicine, 2020 Jul 15;73:152892.
    PMID: 30902523 DOI: 10.1016/j.phymed.2019.152892
    BACKGROUND: Musculoskeletal disorders are a group of disorders that affect the joints, bones, and muscles, causing long-term disability. Berberine, an isoquinoline alkaloid, has been previously established to exhibit beneficial properties in preventing various diseases, including musculoskeletal disorders.

    PURPOSE: This review article aims to recapitulate the therapeutic potential of berberine and its mechanism of action in treating musculoskeletal disorders.

    METHODS: A wide range of literature illustrating the effects of berberine in ameliorating musculoskeletal disorders was retrieved from online electronic databases (PubMed and Medline) and reviewed.

    RESULTS: Berberine may potentially retard the progression of osteoporosis, osteoarthritis and rheumatoid arthritis. Limited studies reported the effects of berberine in suppressing the proliferation of osteosarcoma cells. These beneficial properties of berberine are mediated in part through its ability to target multiple signaling pathways, including PKA, p38 MAPK, Wnt/β-catenin, AMPK, RANK/RANKL/OPG, PI3K/Akt, NFAT, NF-κB, Hedgehog, and oxidative stress signaling. In addition, berberine exhibited anti-apoptotic, anti-inflammatory, and immunosuppressive properties.

    CONCLUSION: The current evidence indicates that berberine may be effective in preventing musculoskeletal disorders. However, findings from in vitro and in vivo investigations await further validation from human clinical trial.

  13. Wong SK, Chin KY, Ima-Nirwana S
    Front Pharmacol, 2020;11:430.
    PMID: 32317977 DOI: 10.3389/fphar.2020.00430
    Lithium, the lightest natural-occurring alkali metal with an atomic number of three, stabilizes the mood to prevent episodes of acute manic and depression. Multiple lines of evidence point to lithium as an anti-suicidal, anti-viral, anti-cancer, immunomodulatory, neuroprotective and osteoprotective agent. This review article provides a comprehensive review of studies investigating the bone-enhancing effects of lithium and its possible underlying molecular mechanisms. Most of the animal experimental studies reported the beneficial effects of lithium in defective bones but not in healthy bones. In humans, the effects of lithium on bones remain heterogeneous. Mechanistically, lithium promotes osteoblastic activities by activating canonical Wingless (Wnt)/beta (β)-catenin, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and bone morphogenetic protein-2 (BMP-2) transduction pathways but suppresses osteoclastic activities by inhibiting the receptor activator of nuclear factor-kappa B (RANK)/receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) system, nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and calcium signaling cascades. In conclusion, lithium confers protection to the skeleton but its clinical utility awaits further validation from human clinical trials.
  14. Mohamad NV, Ima-Nirwana S, Chin KY
    Aging Male, 2020 Dec;23(5):327-334.
    PMID: 29495911 DOI: 10.1080/13685538.2018.1446075
    This study aimed to compare the skeletal effect between GnRH agonist therapy and orchidectomy in male rats assessed using serum turnover markers and bone histomorphometry. Three-month-old male Sprague-Dawley rats (n = 46) were divided into three experimental arms, baseline, buserelin, and orchidectomy. In the buserelin arm, the rats received a daily subcutaneous injection of either normal saline or buserelin acetate at 25 µg/kg or 75 µg/kg. In the orchidectomy arm, the rats were either sham-operated or orchidectomized. The rats were euthanized after the three-month treatment. Blood was collected for the evaluation of bone turnover markers. Femurs were harvested for bone histomorphometry examination. A significant increase in serum C-telopeptide of type 1 collagen was observed in the orchidectomized group compared with the sham group (p 
  15. Mohamad NV, Ima-Nirwana S, Chin KY
    PMID: 33327926 DOI: 10.2174/1871530321666201216164410
    Prolonged treatment with Gonadotropin-Releasing Hormone (GnRH) agonists is known to induce bone loss among prostate cancer patients. However, evidence on the skeletal effects of GnRH antagonists is relatively less well-known. This review aims to examine the effects of GnRH antagonists on bone health. GnRH antagonists are an effective treatment for hormone-dependent conditions, such as advanced prostate cancer and endometriosis. They induce a competitive and reversible GnRH-receptor blockage, thereby suppressing the release of gonadotropins and sex hormones. The sex hormone ablation results in undesirable side effects, including accelerated bone loss. In animal studies, treatment with GnRH antagonists is reported to cause deterioration of bone microstructure. Human clinical trials revealed significant bone loss at the spine, hip and femur in patients treated with GnRH antagonists. Thus, osteoporosis and the resultant fragility fractures pose a significant impact on health and quality of life of GnRH antagonist users. Thus, early preventive measures of bone loss are critical in preventing fractures and its associated morbidity in these patients.
  16. Mohamad NV, Ima-Nirwana S, Chin KY
    Int J Med Sci, 2021;18(16):3665-3673.
    PMID: 34790038 DOI: 10.7150/ijms.64045
    Menopause is the leading cause of osteoporosis for elderly women due to imbalanced bone remodelling in the absence of oestrogen. The ability of tocotrienol in reversing established bone loss due to oestrogen deficiency remains unclear despite the plenitude of evidence showcasing its preventive effects. This study aimed to investigate the effects of self-emulsified annatto tocotrienol (SEAT) on bone histomorphometry and remodelling in ovariectomised rats. Female Sprague Dawley rats (n=36) were randomly assigned into baseline, sham, ovariectomised (OVX) control, OVX-treated with annatto tocotrienol (AT) (60 mg/kg), SEAT (60 mg/kg) and raloxifene (1 mg/kg). Daily treatment given through oral gavage was started two months after castration. The rats were euthanised after eight weeks of treatment. Blood was collected for bone biomarkers. Femur and lumbar bones were collected for histomorphometry and remodelling markers. The results showed that AT and SEAT improved osteoblast numbers and trabecular mineralisation rate (p<0.05 vs untreated OVX). AT also decreased skeletal sclerostin expression in OVX rats (p<0.05 vs untreated OVX). Similar effects were observed in the raloxifene-treated group. Only SEAT significantly increased bone formation rate and reduced RANKL/OPG ratio (p<0.05 vs untreated OVX). However, no changes in osteoclast-related parameters were observed among the groups (p>0.05). In conclusion, SEAT exerts potential skeletal anabolic properties by increasing bone formation, suppressing sclerostin expression and reducing RANKL/OPG ratio in rats with oestrogen deficiency.
  17. Wong SK, Chin KY, Ima-Nirwana S
    Drug Des Devel Ther, 2021;15:4615-4632.
    PMID: 34785890 DOI: 10.2147/DDDT.S331027
    Andrographolide is the major compound found in the medicinal plant, Andrographis paniculata (Burm.f.) Nees, which accounts for its medicinal properties. Both the plant extract and compound have been reported to exhibit potential cardiovascular activities. This review summarises related studies describing the biological activities and target mechanisms of A. paniculata and andrographolide in vivo and in vitro. The current evidence unambiguously indicated the protective effects provided by A. paniculata and andrographolide administration against myocardial injury. The intervention ameliorates the symptoms of myocardial injury by interfering with the inductive phase of a) inflammatory response mediated by nuclear factor-kappa B (NF-κB), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) signalling molecules; b) oxidative stress via activation of nuclear factor erythroid 2-related factor (Nrf-2) and reduction of enzymes responsible for generating reactive oxygen and nitrogen species; c) intrinsic and extrinsic mechanisms in apoptosis regulated by upstream insulin-like growth factor-1 receptor (IGF-1R) and peroxisome proliferator-activated receptor-alpha (PPAR-α); d) profibrotic growth factors thus reducing cardiac fibrosis, improving endothelial function and fibrinolytic function. In conclusion, A. paniculata and andrographolide possess therapeutic potential in the management of myocardial injury, which requires further validation in human clinical trials.
  18. Mohamad NV, Ima-Nirwana S, Chin KY
    Curr Drug Targets, 2018;19(8):898-906.
    PMID: 28914204 DOI: 10.2174/1389450118666170913162739
    Cognitive function and testosterone level of men decline concurrently with age. Low testosterone levels are associated with higher risk of Alzheimer's disease and mild cognitive impairment in men. There are continuous debates on whether this relationship is casual. This paper aims to summarize the current evidence on the association between testosterone level and cognitive function in elderly men. The presence of testosterone, androgen receptor and its responsive genes indicates that testosterone has biological functions in the central nervous system. The ability of the body to convert testosterone into estrogen suggests that part of the actions of testosterone could be mediated by estrogen. Observational studies generally showed that low endogenous testosterone levels were associated with poor cognitive performance in healthy elderly men. Testosterone substitution exerted positive effects on certain cognitive domains in normal and hypogonadal elderly men. In conclusion, testosterone may influence cognitive function in elderly men and its substitution may be considered in men with cognitive impairment and testosterone deficiency.
  19. Wong SK, Chin KY, Ima-Nirwana S
    Curr Drug Targets, 2018;19(8):888-897.
    PMID: 28914205 DOI: 10.2174/1389450118666170913161030
    Depression is a common psychiatric disorder that decreases the quality of life and increases the mortality of patients. It incurs significant healthcare costs if left untreated. Even though intervention with antidepressants can reduce depressive symptoms, side effects are often an issue and relapse is very common. Vitamin D, commonly known as the sunshine vitamin, is an essential fat-soluble vitamin for the absorption of calcium to prevent rickets (children) and osteomalacia (adults). Evidence on a possible relationship between vitamin D deficiency and depression is growing. In this review, the authors summarized the evidence on the association between vitamin D status and depression in human observational studies, followed by clinical trials to evaluate the effects of vitamin D supplementation in treating depression. In conclusion, vitamin D deficiency may be associated with an increased risk or severity of depression. Supplementation of vitamin D may confer protection for depressed patients.
  20. Wong SK, Chin KY, Ima-Nirwana S
    PMID: 31505801 DOI: 10.3390/ijerph16183313
    A positive association between metabolic syndrome (MetS) and osteoporosis has been demonstrated in previous animal studies. The mechanisms of MetS in orchestrating the bone remodelling process have traditionally focused on the interactions between mature osteoblasts and osteoclasts, while the role of osteocytes is unexplored. Our earlier studies demonstrated the bone-promoting effects of tocotrienol using a rat model of osteoporosis induced by MetS. This study aimed to investigate the expression of osteocyte-derived peptides in the bone of rats with MetS-induced osteoporosis treated with tocotrienol. Age-matched male Wistar rats (12-week-old; n = 42) were divided into seven experimental groups. Two groups served as the baseline and normal group, respectively. The other five groups were fed with a high-carbohydrate high-fat (HCHF) diet to induce MetS. The five groups of HCHF animals were treated with tocopherol-stripped corn oil (vehicle), annatto tocotrienol (60 and 100 mg/kg), and palm tocotrienol (60 and 100 mg/kg) starting from week 8. At the end of the study, the rats were sacrificed and their right tibias were harvested. Protein was extracted from the metaphyseal region of the proximal right tibia and levels of bone peptides, including osteoprotegerin (OPG), soluble receptor activator of nuclear factor-kappa B ligand (sRANKL), sclerostin (SOST), Dickkopf-related protein 1 (DKK-1), fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH), were measured. The vehicle-treated animals displayed higher levels of sRANKL, SOST, DKK-1, FGF-23, and PTH as compared to the normal animals. Oral supplementation of annatto and palm tocotrienol (60 and 100 mg/kg) reduced the levels of sRANKL and FGF-23 in the HCHF animals. Only 100 mg/kg annatto and palm tocotrienol lowered SOST and DKK-1 levels in the HCHF animals. In conclusion, tocotrienol exerts potential skeletal-promoting benefit by modulating the levels of osteocytes-derived bone-related peptides.
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