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  1. Zainal Z, Abdul Rahim A, Khaza'ai H, Chang SK
    Int J Mol Sci, 2019 Apr 10;20(7).
    PMID: 30974772 DOI: 10.3390/ijms20071764
    Synthetic therapeutic drugs for asthma, a chronic airway inflammation characterised by strong eosinophil, mast cell, and lymphocyte infiltration, mucus hyper-production, and airway hyper-responsiveness, exhibit numerous side effects. Alternatively, the high antioxidant potential of palm oil phytonutrients, including vitamin E (tocotrienol-rich fractions; TRF) and carotene, may be beneficial for alleviating asthma. Here, we determined the therapeutic efficacy of TRF, carotene, and dexamethasone in ovalbumin-challenged allergic asthma in Brown Norway rats. Asthmatic symptoms fully developed within 8 days after the second sensitization, and were preserved throughout the time course via intranasal ovalbumin re-challenge. Asthmatic rats were then orally administered 30 mg/kg body weight TRF or carotene. TRF-treated animals exhibited reduced inflammatory cells in bronchial alveolar lavage fluid. TRF- and carotene-treated rats exhibited notable white blood cell reduction comparable to that from dexamethasone. TRF- and carotene-treatment also downregulated pro-inflammatory markers (IL-β, IL-6, TNF-α), coincident with anti-inflammatory marker IL-4 and IL-13 upregulation. Treatment significantly reduced asthmatic rat plasma CRP and IgE, signifying improved systemic inflammation. Asthmatic lung histology displayed severe edema and inflammatory cell infiltration in the bronchial wall, whereas treated animals retained healthy, normal-appearing lungs. The phytonutrients tocotrienol and carotene thus exhibit potential benefits for consumption as nutritional adjuncts in asthmatic disease.
    Matched MeSH terms: Carotenoids/pharmacology*
  2. Dauqan E, Sani HA, Abdullah A, Kasim ZM
    Pak J Biol Sci, 2011 Mar 15;14(6):399-403.
    PMID: 21902064
    The objective of the study was to evaluate the effect of four different vegetable oils [red palm olein (RPO), palm olein (PO), corn oil (CO), coconut oil (COC)] on antioxidant enzymes activity of rat liver. Sixty six Sprague Dawley male rats which were randomly divided into eleven groups of 6 rats per group and were treated with 15% of RPO, PO, CO and COC for 4 and 8 weeks. Rats in the control group were given normal rat pellet only while in treated groups, 15% of additional different vegetable oils were given. After 4 weeks of treatment the catalase (CAT) activity results showed that there was no significance difference (p > or = 0.05) between the control group and treated groups while after 8 weeks of treatment showed that there was no significant different (p > or = 0.05) between control group and RPO group but the treated rat liver with PO, CO and COC groups were the lowest and it were significantly lower (> or = 0.05) than control group. For superoxide dismutase (SOD) there was no significance difference (p > or = 0.05) between the control group and treated groups of vegetable oils after 4 and 8 weeks of treatment. Thus the study indicated that there was no significant (p > or = 0.05) effect on antioxidant enzyme (superoxide dismutase) but there was significant effect (p > or = 0.05) on catalase in rat liver.
    Matched MeSH terms: Carotenoids/pharmacology
  3. Ng JH, Nesaretnam K, Reimann K, Lai LC
    Int J Cancer, 2000 Oct 1;88(1):135-8.
    PMID: 10962451
    Oestrogen is important in the development of breast cancer. Oestrogen receptor positive breast cancers are associated with a better prognosis than oestrogen-receptor negative breast cancers since they are more responsive to hormonal treatment. Oestrone sulphate acts as a huge reservoir for oestrogens in the breast. It is converted to the potent oestrogen, oestradiol (E(2)) by the enzymes oestrone sulphatase and oestradiol-17beta hydroxysteroid dehydrogenase (E(2)DH). Retinoic acid and carotenoids have been shown to have chemopreventive activity against some cancers. The aim of our study was to determine and compare the effects of retinoic acid and palm oil carotenoids on growth of and oestrone sulphatase and E(2)DH activities in the oestrogen receptor positive, MCF-7 and oestrogen receptor negative, MDA-MB-231 breast cancer cell lines. Retinoic acid and carotenoids inhibited MCF-7 cell growth but had no effect on MDA-MB-231 cell growth. Both retinoic acid and carotenoids stimulated oestrone sulphatase activity in the MCF-7 cell line. E(1) to E(2) conversion was inhibited by 10(-7) M carotenoids but was stimulated at 10(-6) M in the MCF-7 cell line. Retinoic acid had no effect on E(1) to E(2) conversion at 10(-7) M but stimulated E(1) to E(2) conversion at 10(-6) M. Retinoic acid and carotenoids had no effect on E(2) to E(1) conversion in the MCF-7 cell line. Retinoic acid stimulated E(1) to E(2) conversion in the MDA-MB-231 cell line but had no effect on oestrone sulphatase activity or E(2) to E(1) conversion in this cell line. Both oestrone sulphatase and E(2)DH activity were not affected by carotenoids in the MDA-MB-231 cell line. In conclusion, retinoic acid and carotenoids may prevent the development of hormone-dependent breast cancers since they inhibit the growth of the MCF-7 cell line.
    Matched MeSH terms: Carotenoids/pharmacology*
  4. Nesaretnam K, Sies H
    Antioxid Redox Signal, 2006 10 13;8(11-12):2175-7.
    PMID: 17034360
    The 6(th) COSTAM/SFRR (ASEAN/Malaysia) workshop, "Micronutrients, Oxidative Stress, and the Environment," was held from June 29 to July 2 at Holiday Inn Damai Beach Resort in Kuching, Sarawak. Two hundred twenty participants from 17 countries presented recent advances on natural antioxidants in the area of oxidative stress and molecular aspects of nutrition. Natural products and research are an important program in academic institutions and are experiencing unprecedented interest and growth by the scientific community and public health authorities. Progress is being driven by better understanding of the molecular mechanisms of the relation between oxidative stress and micronutrient action. The gathering of scientists from around the world was fruitful, and we hope that future work will be developed by the formal and informal interactions that took place in this beautiful tropical setting.
    Matched MeSH terms: Carotenoids/pharmacology
  5. Chin KY, Abdul-Majeed S, Fozi NF, Ima-Nirwana S
    Nutrients, 2014 Nov;6(11):4974-83.
    PMID: 25389899 DOI: 10.3390/nu6114974
    This study aimed to evaluate the effects of annatto tocotrienol on indices of bone static histomorphometry in orchidectomized rats. Forty male rats were randomized into baseline (BL), sham (SH), orchidectomized (ORX), annatto tocotrienol-treated (AnTT) and testosterone enanthate-treated (TE) groups. The BL group was sacrificed upon receipt. All rats except the SH group underwent bilateral orchidectomy. Annatto tocotrienol at 60 mg/kg body weight was administered orally daily to the AnTT group for eight weeks. Testosterone enanthate at 7 mg/kg body weight was administered intramuscularly once weekly for eight weeks to the TE group. The rat femurs were collected for static histomorphometric analysis upon necropsy. The results indicated that the ORX group had significantly higher osteoclast surface and eroded surface, and significantly lower osteoblast surface, osteoid surface and osteoid volume compared to the SH group (p < 0.05). Annatto tocotrienol and testosterone enanthate intervention prevented all these changes (p < 0.05). The efficacy of annatto tocotrienol was on par with testosterone enanthate. In conclusion, annatto tocotrienol at 60 mg/kg can prevent the imbalance in bone remodeling caused by increased osteoclast and bone resorption, and decreased osteoblast and bone formation. This serves as a basis for the application of annatto tocotrienol in hypogonadal men as an antiosteoporotic agent.
    Matched MeSH terms: Carotenoids/pharmacology*
  6. Chin KY, Ima-Nirwana S
    Clin Interv Aging, 2014;9:1247-59.
    PMID: 25120355 DOI: 10.2147/CIA.S67016
    BACKGROUND: Previous animal models have demonstrated that tocotrienol is a potential treatment for postmenopausal osteoporosis. This study evaluated the antiosteoporotic effects of annatto-derived tocotrienol (AnTT) using a testosterone-deficient osteoporotic rat model.
    METHODS: Forty rats were divided randomly into baseline, sham, orchidectomized, AnTT, and testosterone groups. The baseline group was euthanized without undergoing any surgical treatment or intervention. The remaining groups underwent orchidectomy, with the exception of the sham group. AnTT 60 mg/kg/day was given orally to the AnTT group, while the testosterone group received testosterone enanthate 7 mg/kg per week intramuscularly for 8 weeks. Structural changes in trabecular bone at the proximal tibia were examined using microcomputed tomography. Structural and dynamic changes at the distal femur were examined using histomorphometric methods. Serum osteocalcin and C-terminal of type 1 collagen crosslinks were measured. Bone-related gene expression in the distal femur was examined.
    RESULTS: There were significant degenerative changes in structural indices in the orchidectomized group (P<0.05), but no significant changes in dynamic indices, bone remodeling markers, or gene expression (P>0.05) when compared with the sham group. The AnTT group showed significant improvement in structural indices at the femur (P<0.05) and significantly increased expression of bone formation genes (P<0.05). Testosterone was more effective than AnTT in preventing degeneration of bone structural indices in the femur and tibia (P<0.05).
    CONCLUSION: AnTT supplementation improves bone health in testosterone-deficient rats by enhancing bone formation. Its potential should be evaluated further by varying the dosage and treatment duration.
    KEYWORDS: bone remodeling; osteoporosis; testosterone; tocotrienol
    Matched MeSH terms: Carotenoids/pharmacology*
  7. Wong JY, Matanjun P, Ooi YB, Chia KF
    Int J Food Sci Nutr, 2013 Aug;64(5):621-31.
    PMID: 23368987 DOI: 10.3109/09637486.2013.763910
    This study was carried out to characterize phenolic compounds, carotenoids, vitamins and the antioxidant activity of selected wild edible plants. Plant extracts were purified, and phenolic compounds comprising 11 phenolic acids (hydroxybenzoic acid and hydrocinnamic acid) and 33 flavonoids (including catechin, glycosides and aglycones) were analysed using High Performance Liquid Chromatography - Diode Array Detector (HPLC-DAD). Furthermore, the contents of ascorbic acid and tocopherol ((α and γ tocopherol) and carotenoids (lutein and β-carotene) were also determined. The major phenolics identified consisted of glycosides of flavones (apigenin and luteolin) and flavonols (kaempferol and quercetin). Among the phenolic acids identified after hydrolysis, coumaric acid was the predominant phenolic acid in all the extracts of wild plants. Ascorbic acid [53.8 mg/100 g fresh weight (FW)] and β-carotene (656.5 mg/100 g FW) showed the highest content in the leaf of Heckeria umbellatum. In conclusion, the leaves of H. umbellatum, Aniseia martinicensis and Gonostegia hirta have excellent potential in the future to emerge as functional ingredients.
    Matched MeSH terms: Carotenoids/pharmacology*
  8. 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 

    Matched MeSH terms: Carotenoids/pharmacology
  9. Wan Hasan WN, Chin KY, Abd Ghafar N, Soelaiman IN
    Drug Des Devel Ther, 2020;14:969-976.
    PMID: 32184566 DOI: 10.2147/DDDT.S224941
    Purpose: Annatto-derived tocotrienol (AnTT) has been shown to improve bone formation in animal models of osteoporosis and promote differentiation of pre-osteoblastic cells. However, the mechanism of action of AnTT in achieving these effects is unclear. This study aims to investigate the mechanism of action of AnTT on MC3T3-E1 pre-osteoblasts via the mevalonate pathway.

    Methods: Murine pre-osteoblastic cells, MC3T3-E1, were cultured with the density of 1 × 104 cells/mL and treated with 4 concentrations of AnTT (0.001-1 µg/mL). Expression of HMG-CoA reductase (HMGR) gene was carried out using qPCR after treatment with AnTT for 21 days. RhoA activation and bone morphogenetic protein-2 (BMP-2) were measured using immunoassay after 9 and 15 days of AnTT treatment. Lovastatin was used as the positive control. Mineralized nodules were detected using Von Kossa staining after 21 days of AnTT treatment.

    Results: The results showed that HMGR was up-regulated in the lovastatin group on day 9 and 21 compared to the control. Lovastatin also inhibited RhoA activation (day 9 and 15) and increased BMP-2 protein (day 15). On the other hand, AnTT at 0.001 μg/mL (day 3) and 0.1 μg/mL (day 21) significantly down-regulated HMGR gene expression compared to the control. On day 21, HMGR gene expression was significantly reduced in all groups compared to day 15. AnTT at 0.1 μg/mL significantly decreased RhoA activation on day 9 compared to the control. AnTT at 1 μg/mL significantly increased BMP-2 protein on day 15 compared to the control (P<0.05). Mineralized calcium nodules were more abundant in AnTT treated groups compared to the control on day 21.

    Conclusion: AnTT suppresses the mevalonate pathway by downregulating HMGR gene expression and inhibiting RhoA activation, leading to increased BMP-2 protein in MC3T3-E1 cells. This explains the stimulating effects of AnTT on osteoblast mineralization.

    Matched MeSH terms: Carotenoids/pharmacology*
  10. Nesaretnam K, Jin Lim E, Reimann K, Lai LC
    Toxicology, 2000 Oct 26;151(1-3):117-26.
    PMID: 11074306
    Breast cancer is the most common cancer in women worldwide. The growth of breast cancer cells is either hormone-dependent or hormone-independent. Both types are represented in vitro by the estrogen-receptor positive (ER+) MCF-7 and the estrogen-receptor negative (ER-) MDA-MB-231 cell lines, respectively. The pS2 gene is an estrogen-regulated gene and serves as a marker for the ER+ tumours. Carotenoids are pigments with anti-cancer properties besides having pro-vitamin A, antioxidant and free-radical quenching effects. This study was designed firstly, to compare the effect of palm oil carotene concentrate with retinoic acid on the growth of the ER+ MCF-7 and the ER- MDA-MB-231 cells; and secondly to evaluate the effect of the palm oil carotene concentrate on the regulation of pS2 mRNA. The growth experiments were performed with monolayer cells seeded in phenol red free RPMI 1640 culture media and subsequently treated with varying concentrations of either retinoic acid or palm oil carotenoids. The cell numbers were determined at the start of each experiment and then at successive time intervals. The results showed that the palm oil carotene concentrate caused dose-dependent inhibition of estradiol-stimulated growth of MCF-7 cells but did not affect the proliferation of MDA-MB-231 cells. Retinoic acid caused similar, albeit more potent effects, as significant inhibition was observed at lower concentrations than the palm oil carotenoids. In the pS2 gene expression experiment, cell monolayers were treated with the carotene concentrate (10(-6) M), either with or without supplemented estradiol (10(-8) M), and subsequently the RNA was extracted. Northern blotting was performed and the regulation of pS2 mRNA determined using a 32P-labelled pS2 cDNA probe. The results showed that the palm oil carotene concentrate did not affect the expression of pS2 mRNA and are therefore independent of the estrogen-regulated pathway.
    Matched MeSH terms: Carotenoids/pharmacology*
  11. Chin KY, Gengatharan D, Mohd Nasru FS, Khairussam RA, Ern SL, Aminuddin SA, et al.
    Nutrients, 2016 Dec 14;8(12).
    PMID: 27983628
    Osteoporosis reduces the skeletal strength and increases the risk for fracture. It is an underdiagnosed disease in men. Annatto tocotrienol has been shown to improve bone structural indices and increase expression of bone formation genes in orchidectomized rats. This study aimed to evaluate the effects of annatto tocotrienol on biomechanical strength and calcium content of the bone in orchidectomized rats. Thirty three-month-old male Sprague-Dawley rats were randomly assigned to five groups. The baseline control (BC) group was sacrificed at the onset of the study. The sham-operated group (SHAM) received olive oil (the vehicle of tocotrienol) orally daily and peanut oil (the vehicle of testosterone) intramuscularly weekly. The remaining rats were orchidectomized and treated with three different regimens, i.e., (1) daily oral olive oil plus weekly intramuscular peanut oil injection; (2) daily oral annatto tocotrienol at 60 mg/kg plus weekly intramuscular peanut oil injection; (3) daily oral olive oil plus weekly intramuscular testosterone enanthate injection at 7 mg/kg. Blood, femur and tibia of the rats were harvested at the end of the two-month treatment period for the evaluation of serum total calcium and inorganic phosphate levels, bone biomechanical strength test and bone calcium content. Annatto-tocotrienol treatment improved serum calcium level and tibial calcium content (p < 0.05) but it did not affect femoral biomechanical strength (p > 0.05). In conclusion, annatto-tocotrienol at 60 mg/kg augments bone calcium level by preventing calcium mobilization into the circulation. A longer treatment period is needed for annatto tocotrienol to exert its effects on bone strength.
    Matched MeSH terms: Carotenoids/pharmacology*
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