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  1. Fulltext Wound Healing Properties of Selected Natural Products
    Ibrahim N', Wong SK, Mohamed IN, Mohamed N, Chin KY, Ima-Nirwana S, et al.
    Int J Environ Res Public Health, 2018 10 25;15(11).
    PMID: 30366427 DOI: 10.3390/ijerph15112360
    Wound healing is a complex process of recovering the forms and functions of injured tissues. The process is tightly regulated by multiple growth factors and cytokines released at the wound site. Any alterations that disrupt the healing processes would worsen the tissue damage and prolong repair process. Various conditions may contribute to impaired wound healing, including infections, underlying diseases and medications. Numerous studies on the potential of natural products with anti-inflammatory, antioxidant, antibacterial and pro-collagen synthesis properties as wound healing agents have been performed. Their medicinal properties can be contributed by the content of bioactive phytochemical constituents such as alkaloids, essential oils, flavonoids, tannins, saponins, and phenolic compounds in the natural products. This review highlights the in vitro, in vivo and clinical studies on wound healing promotions by the selected natural products and the mechanisms involved.
  2. Fulltext Methods of the Dehydration Process and Its Effect on the Physicochemical Properties of Stingless Bee Honey: A Review
    Ikhsan LN, Chin KY, Ahmad F
    Molecules, 2022 Oct 25;27(21).
    PMID: 36364068 DOI: 10.3390/molecules27217243
    Stingless bee honey (SLBH) has a high moisture content, making it more prone to fermentation and leading to honey spoilage. Dehydration of SLBH after harvest is needed to reduce the moisture content. This review compiles the available data on the dehydration methods for SLBH and their effect on its physicochemical properties. This review discovered the dehydration process of vacuum drying at 60 °C and 5% moisture setting, freeze-drying at −54 °C and 5% moisture setting for 24 h, and using a food dehydrator at 55 °C for 18 h could extract >80% water content in SLBH. As a result, these methods could decrease moisture content to <17% and water activity to <0.6. These will prevent the fermentation process and microorganism growth. The hydroxymethylfurfural (HMF) contents remain within the permissible standard of <40 mg/kg. The total phenolic content increased after dehydration by these methods. Therefore, dehydration of SLBH is recommended to increase its benefits.
  3. Fulltext Augmentation of the Female Reproductive System Using Honey: A Mini Systematic Review
    Ismail NH, Ibrahim SF, Jaffar FHF, Mokhtar MH, Chin KY, Osman K
    Molecules, 2021 Jan 27;26(3).
    PMID: 33513715 DOI: 10.3390/molecules26030649
    Phytochemical contents of honey are presumed to be beneficial to the female reproductive system (FRS). However, the biological effects of honey supplementation (HS) in vivo on the FRS remain unclear. This review aims to investigate the current literature on the effects of HS on the FRS, particularly on the sex hormone profile and reproductive organs (uterus and vagina). A systematic literature search using Scopus, MEDLINE via Ovid and Cochrane Library databases was conducted. Records were screened and identified for preclinical and clinical studies addressing the effects of HS on the FRS. Data on populations, interventions, outcomes and methodological quality were extracted. Studies were synthesised using tables and written summaries. Of the 198 identified records, six fulfilled the inclusion criteria. All six records were used for data extraction: two experimental studies using rats as the model organism and four human clinical studies of honey on female reproductive health. HS elevated the progesterone levels, restrained body weight increase, prevented uterine and vaginal atrophies in ovariectomised rats, attenuated symptoms of candidiasis and improved oxidative status in patients. Current evidence shows that short-term HS following surgical or physiological menopause exerts an oestrogenic, antioxidant and anti-inflammatory effect on the FRS. However, insufficient long-term studies preclude any definitive conclusions.
  4. Fulltext Adverse Effects of Wi-Fi Radiation on Male Reproductive System: A Systematic Review
    Jaffar FHF, Osman K, Ismail NH, Chin KY, Ibrahim SF
    Tohoku J. Exp. Med., 2019 07;248(3):169-179.
    PMID: 31353326 DOI: 10.1620/tjem.248.169
    Extensive use of Wi-Fi has contributed to radiofrequency electromagnetic radiation (RF-EMR) pollution in environment. Various studies have been conducted to evaluate the effect of RF-EMR emitted by Wi-Fi transmitter on male reproduction health. However, there are conflicting findings between studies. Thus, this review aims to elucidate the possible effects of 2.45 GHz Wi-Fi exposure on both animal and human male reproductive system. A computerized database search performed through MEDLINE via Ovid and PUBMED with the following set of keywords: 'Wi-Fi or WiFi or wireless fidelity or Wi-Fi router or WiFi router or electromagnetic or radiofrequency radiation' AND 'sperm or spermatozoa or spermatogenesis or semen or seminal plasma or testes or testis or testosterone or male reproduction' had returned 526 articles. Only 17 studies conformed to pre-set inclusion criterion. Additional records identified through Google Scholar and reviewed article further revealed six eligible articles. A total of 23 articles were used for data extraction, including 15 studies on rats, three studies on mice, and five studies on human health. Sperm count, motility and DNA integrity were the most affected parameters when exposed to RF-EMR emitted by Wi-Fi transmitter. Unfortunately, sperm viability and morphology were inconclusive. Structural and/or physiological analyses of the testes showed degenerative changes, reduced testosterone level, increased apoptotic cells, and DNA damage. These effects were mainly due to the elevation of testicular temperature and oxidative stress activity. In conclusion, exposure towards 2.45 GHz RF-EMR emitted by Wi-Fi transmitter is hazardous on the male reproductive system.
  5. Fulltext Knowledge, Attitude and Practice Related to Vitamin D and Its Relationship with Vitamin D Status among Malay Female Office Workers
    Jamil NA, Shahudin NN, Abdul Aziz NS, Jia Qi C, Wan Aminuddin WAA, Mat Ludin AF, et al.
    Int J Environ Res Public Health, 2019 11 27;16(23).
    PMID: 31783521 DOI: 10.3390/ijerph16234735
    This study assessed knowledge, attitude and practice (KAP) related to vitamin D and its relationship with vitamin D status among Malay female office workers. A total of 147 women aged between 20 and 55 years were recruited from a university in Kuala Lumpur. They answered questionnaires related to KAP on vitamin D, sun exposure, dietary vitamin D intake and physical activity. Serum 25-hydroxyvitamin D (25OHD) was analysed using an enzyme-linked immunoassay. Nearly half (45%) of the subjects had good knowledge but moderate attitude (76%) and practice (84%) towards sunlight exposure and dietary vitamin D intake. Median serum 25OHD was 34.1 nmol/L with the majority (91%) had vitamin D insufficiency (25OHD < 50 nmol/L). Knowledge was weakly associated with attitude (r = 0.29, p < 0.001) but no association was found between knowledge and practice (r = 0.08, p = 0.355) nor attitude and practice (r = -0.001, p = 0.994). Serum 25OHD was positively associated with sunlight exposure (r = 0.22, p = 0.008) and dietary vitamin D intake (r = 0.37, p < 0.001). It can be implied that this group is at increased risk of low bone health status, which highlights the needs of public health campaigns to improve their vitamin D status.
  6. Fulltext Skeletal microenvironment system utilising bovine bone scaffold co-cultured with human osteoblasts and osteoclast-like cells
    Jolly JJ, Mohd Fozi NF, Chin KY, Wong SK, Chua KH, Alias E, et al.
    Exp Ther Med, 2021 Jul;22(1):680.
    PMID: 33986845 DOI: 10.3892/etm.2021.10112
    A three-dimensional ex vivo bone cell culture system mimicking the skeletal system is useful for bone tissue engineering and as drug discovery platforms. The present study aimed to establish a three-dimensional skeletal culture system using native bovine bone scaffolds and human bone cells. Bovine bone scaffolds were cultured with human foetal osteoblasts 1.19 and human peripheral blood mononuclear cells for 21 days under standard culture conditions. The following groups were established: Decalcified unseeded bone scaffold (DUBS) as baseline control, decalcified seeded bone scaffold (DSBS) to mimic osteoporosis condition and undecalcified seeded bone scaffold to mimic normal condition. The scaffold's porosity and cell attachment on the scaffolds were determined using scanning electron microscopy. Histological evaluation was used to examine changes in trabecular bone structure. Dual-energy X-ray absorptiometry analysis was performed to determine the bone mineral density (BMD) and bone mineral content (BMC) of the scaffolds. A compression test was performed to examine the total biomechanical strength of the scaffolds. The trabecular thickness and number increased, while the trabecular separationwas reduced slightly in DSBS than in DUBS (P>0.05). The BMD and BMC increased significantly (P<0.05), while the compressive strength only increased slightly in DSBS than in DUBS (P>0.05). In conclusion, the ex vivo skeletal microenvironment comprising native bovine bone scaffolds seeded with bone cells is structurally, functionally and mechanically comparable with natural bone. This system may be used as a platform to understand bone physiology and screen for potential drug candidates.
  7. Optimization of the Static Human Osteoblast/Osteoclast Co-culture System
    Jolly JJ, Chin KY, Farhana MFN, Alias E, Chua KH, Hasan WNW, et al.
    Iran J Med Sci, 2018 Mar;43(2):208-213.
    PMID: 29749990
    Osteoblasts (OBs) and osteoclasts (OCs) are 2 major groups of bone cells. Their cell-to-cell interactions are important to ensure the continuity of the bone-remodeling process. Therefore, the present study was carried out to optimize an OB/OC co-culture system utilizing the human OB cell line hFOB 1.19 and OCs extracted from peripheral blood mononuclear cells (PBMNCs). It was a 2-step procedure, involving the optimization of the OB culture and the co-culture of the OBs with PBMNCs at an optimum ratio. Firstly, pre-OBs were cultured to 90% confluency and the time required for differentiation was determined. OB differentiation was determined using the van Gieson staining to detect the presence of collagen and Alizarin Red for calcium. Secondly, OBs and OCs were co-cultured at the ratios of 1 OC: 1 OB, 1 OC: 4 OBs, 2 OCs: 1 OB, and 1 OC: 2 OBs. Tartrate-resistant acid phosphatase (TRAP) staining was used to detect the differentiation of the OCs. The results showed that collagen was present on day 1, whereas calcium was detected as early as day 3. Based on the result of TRAP staining, 1 OC: 2 OBs was taken as the most appropriate ratio. No macrophage colony-stimulating factor and receptor activator of the nuclear factor-κB ligand were added because they were provided by the OBs. In conclusion, these optimization processes are vital as they ensure the exact time point and ratio of the OB/OC co-culture in order to produce a reliable and reproducible co-culture system.
  8. Fulltext Protective Effects of Selected Botanical Agents on Bone
    Jolly JJ, Chin KY, Alias E, Chua KH, Soelaiman IN
    Int J Environ Res Public Health, 2018 05 11;15(5).
    PMID: 29751644 DOI: 10.3390/ijerph15050963
    Osteoporosis is a serious health problem affecting more than 200 million elderly people worldwide. The early symptoms of this disease are hardly detectable. It causes progressive bone loss, which ultimately renders the patients susceptible to fractures. Osteoporosis must be prevented because the associated fragility fractures result in high morbidity, mortality, and healthcare costs. Many plants used in herbal medicine contain bioactive compounds possessing skeletal protective effects. This paper explores the anti-osteoporotic properties of selected herbal plants, including their actions on osteoblasts (bone forming cells), osteoclasts (bone resorbing cells), and bone remodelling. Some of the herbal plant families included in this review are Berberidaceae, Fabaceae, Arecaceae, Labiatae, Simaroubaceaea, and Myrsinaceae. Their active constituents, mechanisms of action, and pharmaceutical applications were discussed. The literature shows that very few herbal plants have undergone human clinical trials to evaluate their pharmacological effects on bone to date. Therefore, more intensive research should be performed on these plants to validate their anti-osteoporotic properties so that they can complement the currently available conventional drugs in the battle against osteoporosis.
  9. Fulltext A Review of Potential Beneficial Effects of Honey on Bone Health
    Kamaruzzaman MA, Chin KY, Mohd Ramli ES
    Evid Based Complement Alternat Med, 2019;2019:8543618.
    PMID: 31641368 DOI: 10.1155/2019/8543618
    Bone remodelling is a complex and tightly regulated process. Disruption of bone remodelling skewing towards resorption will cause osteoporosis and increase the risk of fragility fracture. Honey is a natural product containing various bioactive ingredients with health benefits, especially polyphenols. Therefore, honey may be a novel dietary supplement to prevent osteoporosis. This review aims to summarize the current evidence on the effects of honey on bone health. The evidence reported so far indicates a skeletal-beneficial effect of honey in animal models of osteoporosis. However, the number of studies on humans is limited. Honey can protect the bone via its antioxidant and anti-inflammatory properties, primarily through its polyphenol content that acts upon several signalling pathways, leading to bone anabolic and antiresorptive effects. In conclusion, honey is a potential functional food for bone health, but the dose and the bioactive contents of honey need to be verified prior to its application in humans.
  10. Fulltext Effects of tocotrienols supplementation on markers of inflammation and oxidative stress: A systematic review and meta-analysis of randomized controlled trials
    Khor BH, Tiong HC, Tan SC, Wong SK, Chin KY, Karupaiah T, et al.
    PLoS One, 2021;16(7):e0255205.
    PMID: 34297765 DOI: 10.1371/journal.pone.0255205
    Studies investigating the effects of tocotrienols on inflammation and oxidative stress have yielded inconsistent results. This systematic review and meta-analysis aimed to evaluate the effects of tocotrienols supplementation on inflammatory and oxidative stress biomarkers. We searched PubMed, Scopus, and Cochrane Central Register of Controlled Trials from inception until 13 July 2020 to identify randomized controlled trials supplementing tocotrienols and reporting circulating inflammatory or oxidative stress outcomes. Weighted mean difference (WMD) and corresponding 95% confidence interval (CI) were determined by pooling eligible studies. Nineteen studies were included for qualitative analysis, and 13 studies were included for the meta-analyses. A significant reduction in C-reactive protein levels (WMD: -0.52 mg/L, 95% CI: -0.73, -0.32, p < 0.001) following tocotrienols supplementation was observed, but this finding was attributed to a single study using δ-tocotrienols, not mixed tocotrienols. There were no effects on interleukin-6 (WMD: 0.03 pg/mL, 95% CI: -1.51, 1.58, p = 0.966), tumor necrosis factor-alpha (WMD: -0.28 pg/mL, 95% CI: -1.24, 0.68, p = 0.571), and malondialdehyde (WMD: -0.42 μmol/L, 95% CI: -1.05, 0.21, p = 0.189). A subgroup analysis suggested that tocotrienols at 400 mg/day might reduce malondialdehyde levels (WMD: -0.90 μmol/L, 95% CI: -1.20, -0.59, p < 0.001). Future well-designed studies are warranted to confirm the effects of tocotrienols on inflammatory and oxidative stress biomarkers, particularly on different types and dosages of supplementation. PROSPERO registration number: CRD42020198241.
  11. Deleterious Biological Effects of Endocrine Disruptors: An Insight into Human Health Risks
    Lawati AA, Hashmi LA, Aswami HA, Hadhrami AA, Chin KY, Das S, et al.
    Endocr Metab Immune Disord Drug Targets, 2024 Jan 30.
    PMID: 38299284 DOI: 10.2174/0118715303279298231228074222
    Endocrine-disrupting chemicals (EDCs) are environmental pollutants. Since EDCs are present in various consumer products, contamination of human beings is very common. EDCs have deleterious effects on various systems of the body, especially the endocrine and reproductive systems. EDCs interfere with the synthesis, metabolism, binding, or cellular responses of natural estrogens and alter various pathways. Biological samples such as blood, saliva, milk, placental tissue, and hair are frequently used for biomonitoring and the detection of EDCs. Early detection and intervention may help in preventing congenital anomalies and birth defects. The common methods for determining the presence of EDCs in body fluids include gas chromatography, high-performance liquid chromatography, and mass spectrometry. Understanding the health effects and dangers of EDC is important, given their widespread use. This mini-review aims to summarize the adverse biological effects of several important classes of EDCs and highlights future perspectives for appropriate control.
  12. Comparing the performance of body mass index, waist circumference and waist-to-height ratio in predicting Malaysians with excess adiposity
    Low NY, Chan CY, Subramaniam S, Chin KY, Ima Nirwana S, Muhammad N, et al.
    Ann Hum Biol, 2022 Dec;49(7-8):299-304.
    PMID: 36373795 DOI: 10.1080/03014460.2022.2147585
    BACKGROUND: Body mass index (BMI) is a widely used surrogate tool to screen for obesity/adiposity, but it cannot differentiate between lean and fat mass. Thus, alternative tools to detect excess adiposity should be identified.

    AIM: This study aimed to compare the performance of BMI, waist circumference (WC) and waist-to-height ratio (WtHR) in predicting Malaysians with excess body fat defined by dual-energy X-ray absorptiometry (DXA).

    SUBJECTS AND METHODS: A total of 399 men and women aged ≥40 years were recruited from Klang Valley, Malaysia. The body composition of the subjects, including body fat percentage, was measured by DXA. The weight, height, WC and WHtR of the subjects were also determined.

    RESULTS: BMI [sensitivity = 55.7%, specificity = 86.1%, area under curve (AUC) = 0.709] and WC (sensitivity = 62.7%, specificity = 90.3%, AUC = 0.765) performed moderately in predicting excess adiposity. Their performance and sensitivity improved with lower cut-off values. The performance of WHtR (sensitivity = 96.6%, specificity = 36.1, AUC = 0.664) was optimal at the standard cut-off value and no modification was required.

    CONCLUSION: The performance of WC in identifying excess adiposity was greater than BMI and WHtR based on AUC values. Modification of cut-off values for BMI and WC could improve their performance and should be considered by healthcare providers in screening individuals with excess adiposity.

  13. On the critical importance of meticulous data extraction for meta-analysis of genetic association study
    Low TY, Chin KY, Tan SC
    Arch Physiol Biochem, 2023 Dec;129(4):1007-1008.
    PMID: 33689514 DOI: 10.1080/13813455.2021.1890132
  14. Fulltext Therapeutic potential of annatto tocotrienol with self-emulsifying drug delivery system in a rat model of postmenopausal bone loss
    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 
  15. Fulltext Are Oxidative Stress and Inflammation Mediators of Bone Loss Due to Estrogen Deficiency? A Review of Current Evidence
    Mohamad NV, Ima-Nirwana S, Chin KY
    Endocr Metab Immune Disord Drug Targets, 2020;20(9):1478-1487.
    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.
  16. A concise review of testosterone and bone health
    Mohamad NV, Soelaiman IN, Chin KY
    Clin Interv Aging, 2016;11:1317-1324.
    PMID: 27703340
    Osteoporosis is a condition causing significant morbidity and mortality in the elderly population worldwide. Age-related testosterone deficiency is the most important factor of bone loss in elderly men. Androgen can influence bone health by binding to androgen receptors directly or to estrogen receptors (ERs) indirectly via aromatization to estrogen. This review summarized the direct and indirect effects of androgens on bone derived from in vitro, in vivo, and human studies. Cellular studies showed that androgen stimulated the proliferation of preosteoblasts and differentiation of osteoblasts. The converted estrogen suppressed osteoclast formation and resorption activity by blocking the receptor activator of nuclear factor k-B ligand pathway. In animal studies, activation of androgen and ERα, but not ERβ, was shown to be important in acquisition and maintenance of bone mass. Human epidemiological studies demonstrated a significant relationship between estrogen and testosterone in bone mineral density and fracture risk, but the relative significance between the two remained debatable. Human experimental studies showed that estrogen was needed in suppressing bone resorption, but both androgen and estrogen were indispensable for bone formation. As a conclusion, maintaining optimal level of androgen is essential in preventing osteoporosis and its complications in elderly men.
  17. Effects of tocotrienol from Bixa orellana (annatto) on bone histomorphometry in a male osteoporosis model induced by buserelin
    Mohamad NV, Soelaiman IN, Chin KY
    Biomed Pharmacother, 2018 Jul;103:453-462.
    PMID: 29674281 DOI: 10.1016/j.biopha.2018.04.083
    INTRODUCTION: Osteoporosis is a debilitating skeletal side effect of androgen deprivation therapy based on gonadotropin-releasing hormone (GnRH) agonist in men. Tocotrienol from Bixa orellana (annatto) has been demonstrated to offer protection against osteoporosis by exerting anabolic effects on bone. Thus, it may prevent osteoporosis among GnRH agonist users.

    OBJECTIVE: This study aimed to determine the effectiveness of annatto-tocotrienol on the bone turnover markers and bone histomorphometry in a model of male osteoporosis induced by buserelin (a GnRH agonist).

    METHODS: Forty-six three-months-old male Sprague-Dawley rats (three months old; 300-350 g) were randomly divided into six groups. The baseline control group (n = 6) was sacrificed at the onset of the study. The normal control group (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/day daily. The calcium control (n = 8) received 1% calcium in drinking water and subcutaneous buserelin injection 75 μg/kg/day. The remaining rats were treated with two different treatments, i.e., (1) oral annatto tocotrienol at 60 mg/kg/day plus subcutaneous buserelin injection 75 μg/kg/day (n = 8); (2) oral annatto tocotrienol at 100 mg/kg/day plus subcutaneous buserelin injection 75 μg/kg/day (n = 8). The rats were injected with calcein twice before being sacrificed to label the bones. The rats were euthanized, and their blood and right femur were harvested at the end of the treatment for bone turnover markers and bone histomorphometry examination.

    RESULTS: Both serum osteocalcin and C-telopeptide of type 1 collagen were not significantly different between treated groups and buserelin control (P > 0.05). The buserelin control group had a significantly lower bone volume and higher eroded surface compared with the normal control group (P 

  18. Fulltext Effect of tocotrienol from Bixa orellana (annatto) on bone microstructure, calcium content, and biomechanical strength in a model of male osteoporosis induced by buserelin
    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.

  19. The relationship between circulating testosterone and inflammatory cytokines in men
    Mohamad NV, Wong SK, Wan Hasan WN, Jolly JJ, Nur-Farhana MF, Ima-Nirwana S, et al.
    Aging Male, 2019 Jun;22(2):129-140.
    PMID: 29925283 DOI: 10.1080/13685538.2018.1482487
    Testosterone is the predominant gonadal androgen in men. Low testosterone levels are found to be associated with an increased in metabolic risk and systematic inflammation. Since adipose tissue is a source of inflammatory cytokines, testosterone may regulate inflammation by acting on adipose tissue. This review aimed to explore the role of testosterone in inflammation and its mechanism of action. Both animal studies and human studies showed that (1) testosterone deficiency was associated with an increase in pro-inflammatory cytokines; (2) testosterone substitution reduced pro-inflammatory cytokines. The suppression of inflammation by testosterone were observed in patients with coronary artery disease, prostate cancer and diabetes mellitus through the increase in anti-inflammatory cytokines (IL-10) and the decrease in pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α). Despite these, some studies also reported a non-significant relationship. In conclusion, testosterone may possess anti-inflammatory properties but its magnitude is debatable. More evidence is needed to validate the use of testosterone as a marker and in the management of chronic inflammatory diseases.
  20. The effects of gonadotropin-releasing hormone agonist (buserelin) and orchidectomy on bone turnover markers and histomorphometry in rats
    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 
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