Demethylbelamcandaquinone B (Dmcq B) Is the Active Compound of Marantodes pumilum var. alata (Blume) Kuntze with Osteoanabolic Activities.

Haryati Ahmad Hairi,Khairana Husain,Nor Ashila Aladdin,Noor Suhaili Mohd Sofi,Isa Naina Mohamed,Jamia Azdina Jamal,Norazlina Mohamed,Ahmad Nazrun Shuid

doi:10.3390/molecules23071686

Abstract

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.

Highlights

Bone remodeling is a dynamic process that maintains the balance between the bone formation and resorption processes
This study showed that the alata crude aqueous extract and fraction of crude aqueous extract were at par with
Our studies showed that M. pumilum var. alata crude extract and DCM fraction resembled E2 treatment, which significantly induced both ERα and ERβ protein expression

Summary

Introduction

Bone remodeling is a dynamic process that maintains the balance between the bone formation and resorption processes. The sequence starts when osteoclasts resorb old mineralized bone, followed by new bone formation and mineralisation by osteoblasts. This allows the bone to adapt to biomechanical forces, repair bone matrix microtraumas and improve bone structure from time to time [1]. Estrogen is the foremost modulator of bone remodeling. The decline in estrogen during menopause is the starting point for the disturbance of the bone remodeling cycle, which leads to acute bone loss [2]. Osteoporosis has become a public health threat, predominantly in post-menopausal

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Discussion

Conclusion