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. 2013 Jul;37(3):261-8.
doi: 10.5142/jgr.2013.37.261.

Ginseng Saponins and the Treatment of Osteoporosis: Mini Literature Review

Free PMC article

Ginseng Saponins and the Treatment of Osteoporosis: Mini Literature Review

Muhammad Hanif Siddiqi et al. J Ginseng Res. .
Free PMC article


The ginseng plant (Panax ginseng Meyer) has a large number of active ingredients including steroidal saponins with a dammarane skeleton as well as protopanaxadiol and protopanaxatriol, commonly known as ginsenosides, which have antioxidant, anticancer, antidiabetic, anti-adipocyte, and sexual enhancing effects. Though several discoveries have demonstrated that ginseng saponins (ginsenosides) as the most important therapeutic agent for the treatment of osteoporosis, yet the molecular mechanism of its active metabolites is unknown. In this review, we summarize the evidence supporting the therapeutic properties of ginsenosides both in vivo and in vitro, with an emphasis on the different molecular agents comprising receptor activator of nuclear factor kappa-B ligand, receptor activator of nuclear factor kappa-B, and matrix metallopeptidase-9, as well as the bone morphogenetic protein-2 and Smad signaling pathways.

Keywords: Bone morphogenetic protein-2; Ginsenosides; Osteoporosis; Panax ginseng; Receptor activator of nuclear factor kappa-B ligand.


Fig. 1.
Fig. 1.. Osteoclastogenesis. Proposed model of a ginsenoside inhibiting the binding of receptor activator of nuclear factor kappa-B ligand (RANKL) to receptor activator of nuclear factor kappa-B (RANK) and melatonin receptor type 1A, matrix metallopeptidase (MMP) by binding with RANK or RANKL. This decreases the response of RANKL, reduces the induction of MMP-9, and blocks the RANKL, RANK signaling pathway. RANKL binds to RANK, so tumor necrosis factor-receptor-associated factor-6 (TRAF6) binds to RANK and plays a key role in osteoclast differentiation by regulating and activating downstream signaling pathways, such as the nuclear factor-kappa B (NF-κB) pathway, the inhibitor of NF-κB kinase (INK) pathway, the c-Jun N-terminal kinase (JNK) pathway and the p38 pathway. These pathways ultimately prop up osteoclast differentiation and bone resorption by stimulating different transcriptional factors such as activator protein-1 (AP1) and NF-κB pathways. It is not clear how these factors are activated by TRAF6 and cause bone resorption by activating osteoclast specific markers, such as tartrate-resistant acid phosphatase (TRAP), cathepsin (CTSK), β3 integrin and calcitonin receptors (CTR). MMPs, and in particular MMP-9, are responsible for bone resorption, which is extremely articulated in osteoclasts, are stimulated by the action of RANKL signaling pathways and influence osteoclast differentiation and bone resorption . C-K, compound K; PNS, Panax notoginseng saponins; OPG, osteoprotegerin; NIK, NF-kappa-B-inducing kinase; MEK, mitogen-activated protein kinase kinase; AMPK, AMP-activated protein kinase; IKK, inhibitor of nuclear factor kappa-B kinase; PKD, protein kinase D; NFAT, nuclear factor of activated T-cell.
Fig. 2.
Fig. 2.. Osteoblastogenesis. Upon the binding of bone morphogenetic protein 2 (BMP-2) to transmembrane proteins such as bone morphogenetic protein receptor II, it phosphorylate type I receptor, and hence activates the Smad complex (Smad 1, 4, 5, and 8) signaling pathways -, which can help in the activation of osteoblast specific transcriptional regulation genes such as osteocalcin (OCN), collagen type I (Col-I), osteonectin (ON), osterix (OSX), and bone sialoprotein (BSP). Recently it has been suggested that retinoblastoma binding protein 1 (RBP1) may be the co-activator of Runx2 ,. cAMP, cyclic adenosine monophosphate; PNS, Panax notoginseng saponins; AMPK, AMP-activated protein kinase; PKD, protein kinase D; Runx2, runt-related transcription factor 2; ALP, alkaline phosphatase; BSP, bone sialoprotein.

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