A diarylheptanoid phytoestrogen from Curcuma comosa, 1,7-diphenyl-4,6-heptadien-3-ol, accelerates human osteoblast proliferation and differentiation

Abstract

Curcuma comosa Roxb. is ginger-family plant used to relieve menopausal symptoms. Previous work showed that C. comosa extracts protect mice from ovariectomy-induced osteopenia with minimal effects on reproductive organs, and identified the diarylheptanoid (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (DPHD) as the major active component of C. comosa rhizomes. At 1–10 μM, DPHD increased differentiation in transformed mouse osteoblasts, but the effect of DPHD on normal bone cells was unknown. We examined the concentration dependency and mechanism of action of DPHD relative to 17β-estradiol in nontransformed human osteoblasts (h-OB). The h-OB were 10–100 fold more sensitive to DPHD than transformed osteoblasts: DPHD increased h-OB proliferation at 10 nM and, at 100 nM, activated MAP kinase signaling within 30 minutes. In long-term differentiation assays, responses of h-OB to DPHD were significant at 10 nM, and optimal response in most cases was at 100 nM. At 7–21 days, DPHD accelerated osteoblast differentiation, indicated by alkaline phosphatase activity and osteoblast-specific mRNA production. Effects of DPHD were eliminated by the estrogen receptor antagonist ICI182780. During differentiation, DPHD promoted early expression of osteoblast transcription factors, RUNX2 and osterix. Subsequently, DPHD accelerated production of bone structural genes, including COL1A1 and osteocalcin comparably to 17β-estradiol. In h-OB, DPHD increased the osteoprotegerin to RANKL ratio and supported mineralization more efficiently than 10 nM 17β-estradiol. We conclude that DPHD promotes human osteoblast function in vitro effectively at nanomolar concentrations, making it a promising compound to protect bone in menopausal women.

Sphingosine‐1‐Phosphate Modulates the Effect of Estrogen in Human Osteoblasts

“…Previously, we reported that E2 promotes osteoblast proliferation via activating the MAP kinase activity. (18) In this study, we investigated the effect of S1P on the MAP kinase activity in osteoblast precursors (h-MSC) and osteoblasts (hOB). S1P-stimulated phospho-AKT and phospho-ERK at 15 minutes in h-MSC are shown on Fig.…”

Protective Effects of a Diarylheptanoid from Curcuma comosa Against Hydrogen Peroxide-Induced Astroglial Cell Death

“…In other experimental models, ASPP 049 has been shown to exert anti-inflammatory action and beneficial effects on bone density and cholesterol levels acting via estrogen receptors. [14,16,21]. Astroglial cell death induced by H 2 O 2 was found to be accompanied by elevation of intracellular ROS indicating the presence of oxidative damage.…”

Adrenocorticotropic hormone and 1,25-dihydroxyvitamin D3 enhance human osteogenesis in vitro by synergistically accelerating the expression of bone-specific genes

“…This is well documented in contexts including estrogen and synthetic estrogen receptor modifier response of human osteoblasts. 35 In regard to this, when studied in vivo , modification of the rate of osteoblast differentiation is largely masked, with bone appearing to develop and mineralize normally, but with differences in the rate of bone formation under some circumstances, and differences in the susceptibility of bone to regional necrosis 36 when survival signals including VEGF 1 are compromised. In this regard, sensitization of osteoblast VEGF production to ACTH by 1,25(OH) 2 D deserves further study and might be useful in clinical trials in contexts including glucocorticoid treatment where osteonecrosis is commonly seen.…”