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Exploring molecular mechanism of bone-forming capacity of Eurycoma longifolia: Evidence of enhanced expression of bone-related biomarkers.

ABSTRACT: 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-?1 (TGF-?1) 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 ?g/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.

SUBMITTER: Thu HE

PROVIDER: S-EPMC6314246 | biostudies-other | 2018 Oct - Dec

REPOSITORIES: biostudies-other

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Exploring molecular mechanism of bone-forming capacity of Eurycoma longifolia: Evidence of enhanced expression of bone-related biomarkers.

Thu Hnin Ei HE Mohamed Isa Naina IN Hussain Zahid Z Shuid Ahmad Nazrun AN

Journal of Ayurveda and integrative medicine 20171113 4

<h4>Background</h4>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.<h4>Objective(s)</h4>The present study was aimed to investigate the mechanism of bone-forming capacity of EL using MC3T3-E1 as an in vitro osteoblastic m ...[more]

PMID: 29146110

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Project description:ObjectiveTo explore the mechanisms that mediate the anti-inflammatory activity of Eurycoma longifolia.MethodsKunming mouse models of xylene-induced ear swelling and lipopolysaccharide (LPS)-induced acute pneumonia were used to compare the anti- inflammatory activities of aqueous and ethanol extracts of Eurycoma longifolia. UPLC-Q-TOF-MS/MS was used to identify the chemical composition in the ethanol extract of Eurycoma longifolia, based on which the potential antiinflammatory targets of Eurycoma longifolia were screened using the databases including SwissADME, SwissTargetPrediction, and Genecards. The String database was used to generate the protein-protein interaction (PPI) network, and Cytoscape was used for network topology analysis and screening the core targets. The enrichment of the core targets was analyzed using Metascape database, the core components and targets were docked with Autodock software, and the docking results were visualized using Pymol software. In a RAW264.7 cell model of LPS-induced inflammation, the Griess reagent was used to measure NO level, and Western blotting was performed to detect the expression levels of MAPK1, JAK2, and STAT3 proteins to verify the anti- inflammatory mechanism of Eurycoma longifolia.ResultsThe ethanol extract (75%) of Eurycoma longifolia (ELE) was the active site, which contained a total of 37 chemical components. These chemical compounds and diseases had 541 targets, involving the JAK/STAT3, cAMP and other signaling pathways. Twelve indicator components were identified, which all showed good results of molecular docking with two core targets involved in the signaling pathways. In the cell validation experiment, treatment of the cells with low-, medium-, and high-dose ELE significantly reduced NO release in the cells, and ELE at the medium dose significantly decreased the cellular expressions of JAK2 and STAT3.ConclusionThe anti-inflammatory activity of Eurycoma longifolia is attributed primarily to its active ingredients bitter lignin and alkaloids, which may regulate the JAK/STAT3 signaling pathway by targeting JAK2 and STAT3.

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Exploring molecular mechanism of bone-forming capacity of Eurycoma longifolia: Evidence of enhanced expression of bone-related biomarkers.

Publications

Exploring molecular mechanism of bone-forming capacity of Eurycoma longifolia: Evidence of enhanced expression of bone-related biomarkers.

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