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  1. Nor Muhamad ML, Ekeuku SO, Wong SK, Chin KY
    Nutrients, 2022 Nov 16;14(22).
    PMID: 36432535 DOI: 10.3390/nu14224851
    BACKGROUND: Osteoporosis is caused by the deterioration of bone density and microstructure, resulting in increased fracture risk. It transpires due to an imbalanced skeletal remodelling process favouring bone resorption. Various natural compounds can positively influence the skeletal remodelling process, of which naringenin is a candidate. Naringenin is an anti-inflammatory and antioxidant compound found in citrus fruits and grapefruit. This systematic review aims to present an overview of the available evidence on the skeletal protective effects of naringenin.

    METHOD: A systematic literature search was conducted using the PubMed and Scopus databases in August 2022. Original research articles using cells, animals, or humans to investigate the bone protective effects of naringenin were included.

    RESULTS: Sixteen eligible articles were included in this review. The existing evidence suggested that naringenin enhanced osteoblastogenesis and bone formation through BMP-2/p38MAPK/Runx2/Osx, SDF-1/CXCR4, and PI3K/Akt/c-Fos/c-Jun/AP-1 signalling pathways. Naringenin also inhibited osteoclastogenesis and bone resorption by inhibiting inflammation and the RANKL pathway.

    CONCLUSIONS: Naringenin enhances bone formation while suppressing bone resorption, thus achieving its skeletal protective effects. It could be incorporated into the diet through fruit intake or supplements to prevent bone loss.

  2. Ekeuku SO, Nor Muhamad ML, Aminuddin AA, Ahmad F, Wong SK, Mark-Lee WF, et al.
    Biomed Pharmacother, 2024 Jan;170:115998.
    PMID: 38091638 DOI: 10.1016/j.biopha.2023.115998
    Postmenopausal women are susceptible to osteoporosis and osteoarthritis. Tocotrienol, a bone-protective nutraceutical, is reported to prevent osteoarthritis in male rats. However, its efficacy on joint health in oestrogen deficiency has not been validated. Besides, data on the use of emulsification systems in enhancing bioavailability and protective effects of tocotrienol are limited. Ovariectomised adult female Sprague-Dawley rats (3 months old) were treated with refined olive oil, emulsified (EPT, 100 mg/kg/day with 25% vitamin E content), non-emulsified palm tocotrienol (NEPT, 100 mg/kg/day with 50% vitamin E content) and calcium carbonate (1% w/v in drinking water) plus glucosamine sulphate (250 mg/kg/day) for 10 weeks. Osteoarthritis was induced with monosodium iodoacetate four weeks after ovariectomy. Baseline control was sacrificed upon receipt, while the sham group was not ovariectomised and treated with refined olive oil. EPT and NEPT prevented femoral metaphyseal and subchondral bone volume decline caused by ovariectomy. EPT decreased subchondral trabecular separation compared to the negative control. EPT preserved stiffness and Young's Modulus at the femoral mid-shaft of the rats. Circulating RANKL was reduced post-treatment in the EPT group. Joint width was reduced in all the treatment groups vs the negative control. The EPT group's grip strength was significantly improved over the negative control and NEPT group. EPT also preserved cartilage histology based on several Mankin's subscores. EPT performed as effectively as NEPT in preventing osteoporosis and osteoarthritis in ovariectomised rats despite containing less vitamin E content. This study justifies clinical trials for the use of EPT in postmenopausal women with both conditions.
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