Phenolics Isolated from Aframomum meleguta Enhance Proliferation and Ossification Markers in Bone Cells

Abstract

Osteoporosis is a serious health problem characterized by decreased bone mineral density and deterioration of bone microarchitecture. Current antiosteoporotic agents exhibit a wide range of adverse effects; meanwhile, phytochemicals are effective and safer alternatives. In the current work, nine compounds belonging to hydroxyphenylalkane and diarylheptanoid groups were isolated from Aframomum meleguea seeds and identified as 6-gingerol (1), 6-paradol (2), 8-dehydrogingerdione (3), 8-gingerol (4), dihydro-6-paradol (5), dihydrogingerenone A (6), dihydrogingerenone C (7), 1,7-bis(3,4-dihydroxy-5-methoxyphenyl)heptane-3,5-diyl diacetate (8), and 1-(3,4-dihydroxy-5-methoxyphenyl)-7-(3,4-dihydroxyphenyl)heptane-3,5-diyl diacetate (9). The structures of isolated compounds were established by NMR and mass spectral data, in addition to referring to literature data. Exposure of MCF-7, MG-63, and SAOS-2 cells to subcytotoxic concentrations of the compounds under investigation resulted in accelerated proliferation. Among them, paradol was selected for further detailed biochemical analysis in SAOS-2 cells. DNA flowcytometric analysis of cell cycle distribution revealed that paradol did not induce any significant change in the proliferation index of SAOS-2 cells. Assessment of osteogenic gene expression revealed that paradol enhanced the expression of osteocyte and osteoblast-related genes and inhibited osteoclast and RUNX suppressor genes. Biochemically, paradol enhanced alkaline phosphatase activity and vitamin D content and decreased the osteoporotic marker acid phosphatase. In conclusion, paradol, which is a major constituents of A. melegueta seeds, exhibited potent proliferative and ossification characteristics in bone cells.

Rutin Isolated from Chrozophora tinctoria Enhances Bone Cell Proliferation and Ossification Markers

“…The five tested gene markers of osteoblast activity were augmented by 2.1- to 4.0-folds after the application of E 2 ( Figure 3(b) ). Compared to our previous work on paradol [ 27 ], rutin significantly increased HYOU1 but not SOST. Further, rutin could significantly enhance expression of the osteoblast marker CD44 while paradol failed to exert a similar effect.…”

“…The lowered expression of HES1 and TWIST1 (RUNX suppressors) by rutin supports its osteogenic effects. All these data are in alignment with our previous publication on paradol [ 27 ]. However, rutin showed superior activities with regard to suppressing CALCR expression.…”

“…When studying the proliferating cell fraction balance in SAOS-2 cells, rutin significantly decreased the proliferation index; on the other hand, treatment with E 2 did not alter their proliferation index ( Figure 2(e) ). In a previous study in our laboratory, paradol showed no influence on the proliferation index of SAOS-2 cells [ 27 ]. Our current data are in alignment with our studies on SAOS-2 cells where 1 μ M rutin was found to decrease the doubling time.…”

“…There is an immense need for the development of novel drugs to treat osteoporosis which are devoid of potentially life-threatening side effects, namely, stroke and carcinogenesis [ 8 , 26 ]. We have previously found that the phenolic compound paradol, isolated from Aframomum meleguea seeds, showed proliferative effects in bone cells [ 27 ]. Flavonoids have been shown by numerous studies to prevent bone loss [ 12 , 28 – 31 ].…”

“…The cytotoxicity of these compounds was studied using the SRB viability assay in various estrogenic cell lines, namely, MCF-7, SAOS-2, and MG-63 cells. We have previously used these cell lines to study the effects of paradol on A. meleguea seeds, where we noted an accelerated proliferation [ 27 ]. In the present study, when looking at the effects on MCF-7 cells, the compounds showed a maximum of 20% alteration in the viability of cells, after being applied to the compounds for 72 h in 10 μ M concentrations.…”