Comparative anti-osteoporotic properties of the leaves and roots of Marantodes pumilum var. alata in postmenopausal rat model.
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ABSTRACT:
SUBMITTER: Giaze TR
PROVIDER: S-EPMC6702132 | biostudies-literature | 2019 Oct
REPOSITORIES: biostudies-literature
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Comparative anti-osteoporotic properties of the leaves and roots of <i>Marantodes pumilum var. alata</i> in postmenopausal rat model.
Giaze Tijjani Rabiu TR Shuid Ahmad Nazrun AN Soelaiman Ima Nirwana IN Muhammad Norliza N Jamal Jamia Azdina JA Fauzi Mh Busra MB Mohamed Norazlina N
Journal of traditional and complementary medicine 20190104 4
<h4>Background</h4><i>Marantodes pumilum</i> var. <i>alata</i> (<i>MPva</i>), popularly known as Kacip Fatimah, is widely used to maintain female reproductive health, facilitate post-partum recovery and manage symptoms of menopause and osteoporosis in South-East Asia. This study aims to further evaluate the osteoprotective potential of <i>MPva</i> in view of reports of its bone-protective properties in postmenopausal condition.<h4>Methods</h4>Thirty female Sprague-Dawley rats were sorted into 5 ...[more]
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Project description:Phytoestrogens have attracted considerable attention for their potential in the prevention of postmenopausal osteoporosis. Recently, a phytoestrogen-rich herbal plant, Marantodes pumilum var. alata (Blume) Kuntze was reported to protect against bone loss in ovariectomized rat. However, the bioactive compound responsible for these effects and the underlying mechanism were not known. Through bioassay-guided isolation, demethylbelamcandaquinone B (Dmcq B) was isolated and identified from Marantodes pumilum var. alata leaf extract. In terms of its bone anabolic effects, Dmcq B was at par with 17β-estradiol (E2), in promoting the proliferation, differentiation and mineralization of osteoblast cells. Dmcq-B increased early differentiation markers, collagen content and enzymatic ALP activity. It was demonstrated to regulate BMP2 signaling pathway which further activated the transcription factor, osterix. Subsequently, Dmcq B was able to increase the osteocalcin expression which promoted matrix mineralization as evidenced by the increase in calcium deposition. Dmcq B also reduced the protein level of receptor activator of NF-κβ ligand (RANKL) and promoted osteoprotegerin (OPG) protein expression by osteoblast cells, therefore hastening bone formation rate by decreasing RANKL/OPG ratio. Moreover, Dmcq B was able to increase ER expression, postulating its phytoestrogen property. As the conclusion, Dmcq B is the active compound isolated from Marantodes pumilum var. alata leaves, regulating osteoanabolic activities potentially through the BMP2 and ER signaling pathways.
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Project description:Background:Marantodes pumilum is traditionally used for dysentery, gonorrhea, and sickness in the bones. Previous studies revealed its antibacterial and xanthine oxidase inhibitory activities. Objective:To evaluate the inhibitory effects of three M. pumilum varieties on the secretion of lipopolysaccharide (LPS)- and monosodium urate crystal (MSU)-induced cytokines and plasma prostaglandin E2 (PGE2) in vitro. Materials and Methods:The leaves and roots of M. pumilum var. alata (MPA), M. pumilum var. pumila (MPP), and M. pumilum var. lanceolata (MPL) were successively extracted with dichloromethane (DCM), methanol, and water. Human peripheral blood mononuclear cells and ELISA technique were used for the cytokine assay, whereas human plasma and radioimmunoassay technique were used in the PGE2 assay. Flavonoids content was determined using a reversed-phase high-performance liquid chromatography. Results:DCM extract of MPL roots showed the highest inhibition of LPS-stimulated cytokine secretion with IC50 values of 29.87, 7.62, 5.84, 25.33, and 5.40 ?g/mL for interleukin (IL)-1?, IL-1?, IL-6, IL-8, and tumor necrosis factor (TNF)-?, respectively; while that of plasma PGE2 secretion was given by DCM extract of MPP roots (IC50 31.10 ?g/mL). Similarly, the DCM extract of MPL roots demonstrated the highest inhibition against MSU-stimulated IL-1?, IL-1?, IL-6, IL-8, TNF-?, and PGE2 secretion with IC50 values of 11.2, 8.92, 12.29, 49.51, 9.60, and 31.58 ?g/mL, respectively. Apigenin in DCM extracts of MPL (0.051 mg/g) and MPP (0.064 mg/g) roots could be responsible for the strong inhibitory activity against IL-1?, IL-6, TNF-?, and PGE2. Conclusion:The results suggested that DCM extracts of MPL and MPP roots are potential anti-inflammatory agents by inhibiting the secretion of LPS- and MSU-stimulated pro-inflammatory cytokines and PGE2. SUMMARY:Amongst 18 tested extracts, DCM extracts of MPL and MPP roots remarkably inhibited LPS- and MSU-stimulated pro-inflammatory cytokines and PGE2 secretionPhytochemical analysis was performed for the active extracts using RP-HPLC systemThe presence of flavonoids particularly apigenin could be responsible for the anti-inflammatory activity. Abbreviations used: BSA: Bovine serum albumin, COX-2: Cyclooxygenase-2, CPM: Count per minute, DAMP: Danger-associated molecular pattern, DCM: Dichloromethane, DMSO: Dimethyl sulfoxide, ELISA: Enzyme-linked immunosorbent assay, FBS: Fetal bovine serum, H2O: Water, HEPES: 4-(2-Hydroxyethyl)piperazine-1-ethanesulfonic acid, HMC-1: Human mast cell-1, HMGB1: High-mobility group box 1, ICAM: Intercellular adhesion molecule, IFN: Interferon, IgG: Immunoglobulin G, IKK: IkB kinase, IL: Interleukin, iNOS: Inducible nitric oxide synthase, LPS: Lipopolysaccharide, MeOH: Methanol, MPA: Marantodes pumilum var. alata, MPL: Marantodes pumilum var. lanceolata, MPP: Marantodes pumilum var. pumila, MSU: Monosodium urate, MTT: Methylthiazole tetrazolium, NF-?B: Nuclear factor-kappa B, NLR: NOD-like receptor, NLRP3: NLR family pyrin domain containing protein 3, NO: Nitric oxide, NOD: Nucleotide-binding oligomerization domain, NSAID: Nonsteroidal anti-inflammatory drug, PAMP: Pathogen-associated molecular pattern, PBMC: Peripheral blood mononuclear cell, PBS: Phosphate buffered saline, PGE2: Prostaglandin E2, PMACI: Phorbol-12-myristate 13-acetate and calcium ionosphere A23187, PRR: Pathogen recognition receptor, PTFE: Polytetrafluoroethylene, RIA: Radioimmunoassay, RIG: Retinoic acid-inducible gene I, RLR: RIG I-like receptor, RP-HPLC: Reversed-phase high-performance liquid chromatography, RPMI-1640: Roswell Park Memorial Institute-1640, TLR: Toll-like receptor, TNF: Tumor necrosis factor, VCAM: Vascular cell adhesion molecule.
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