Table 2: Antiosteoporotic compounds isolated from medicinal plants.

CompoundPharmacological activityreference

IcariinSee Section 3.1.1[2326]
GenisteinSee Section 3.1.2[29]
Daidzeinprevent bone loss in ovariectomized rats and orchidectomized rats;
inhibit osteoclastic differentiation and bone resorption by increasing the activity of mature osteoblasts via ERβ, regulating RUNX 2/Cbfα1 production, and stimulating the secretion osteoprotegerin.
[31, 32]
Kaempferolincrease ALP activity in cultured human MG-63 osteoblasts through ERK and ER pathway;
prevent antimycin A-induced cell damage in mitochondrial membrane potential dissipation, complex IV inactivation, ROS production through activation of PI3K (phosphoinositide 3-kinase), Akt (protein kinase B), CREB (cAMP-response element-binding protein) in MC3T3-E1.
Quercetinreverse the decreased biomechanical quality and the impaired microarchitecture of the femurs in diabetic rats through improving antioxidant capacity;
inhibit osteoclastic differentiation and bone resorption via inducing apoptosis and involving NF- B and AP-1.
[73, 74]
Naringinprotect against retinoic acid-induced osteoporosis and improve bone quality in rats;
perturb osteoclast formation and bone resorption by inhibiting RANK-mediated NF- B and ERK signaling;
induce bone morphogenetic protein-2 expression via PI3K, Akt, c-Fos/c-Jun and AP-1 pathway in osteoblasts;
prevent hydrogen peroxide-induced dysfunction in osteoblastic MC3T3-E1 cells.
Hesperidinprotect bone loss in OVX rats, improve BMD and femoral load in intact rats[78]
Linarinprotect osteoblasts against hydrogen peroxide-induced osteoblastic dysfunction, exert antiresorptive actions via the reduction of RANKL and oxidative damage[79]
Bavachalconeinhibit osteoclastogenesis by interfering with the ERK and Akt signaling pathways and the induction of c-Fos and NFATc1.[36]
Rutininhibit ovariectomy—induced trabecular bone loss in rats by slowing down resorption and increasing osteoblastic activity.[80]
(+)-Catechinenhance cell survival, alkaline phosphatase activity, decrease bone-resorbing cytokines (TNF-α and IL-6) production and apoptosis in osteoblasts.[81]
Nobiletinprevent bone loss in ovariectomized rats;
suppress formation and bone resorption of osteoclast induced by interleukin-1;
suppress the expression of cyclooxygenase-2, NF-κB-dependent transcription, and prostaglandin E production in osteoblasts.
Luteolinincrease bone mineral density and bone mineral content of trabecular and cortical bones in the femur of OVX rats;
inhibit the differentiation of both bone marrow mononuclear cells and RAW 264.7 cells into osteoclasts and the bone resorptive activity of osteoclasts.
Baicaleininhibit the differentiation and bone resorptive activity of osteoclasts by inhibiting RANKL-induced activation of signaling molecules (Akt, ERK/MAP kinase and NF- B) and mRNA expression of osteoclast-associated genes TRAP, matrix metalloproteinase 9 and c-Src, c-Fos, Fra-2 and NFATc1.[84]
Baicalinpromote osteoblastic differentiation via Wnt/β-catenin signaling and enhance the mRNA expression of osteoprotegerin[85]
Xanthohumolupregulate ALP activity and expression of osteogenic marker genes by activation of RUNX2 via mechanisms related to the p38 MAPK and ERK signaling pathway[86]
Psoralenpromote osteoblast differentiation by up-regulation of expressions of osteoblast-specific marker through the activation of BMP signaling[35]
Ostholeprevent bone loss and improve bone microarchitecture, histomorphometric parameters, and biomechanical properties in OVX rats;
stimulate osteoblast proliferation and differentiation through β-catenin/BMP signaling.
Honokiolincrease cell growth, alkaline phosphatase activity, collagen synthesis, mineralization, glutathione content, and osteoprotegerin release in the osteoblast;
decrease the production of TNF-α, IL-6, and RANKL in the presence of antimycin A;
stimulate osteoblastogenesis by suppressing NF-κB activation.
[88, 89]
Isotaxiresinolimprove bone mineral content, bone mineral density, and bone strength indexes in OVX control rats;
slightly increase bone formation and significantly inhibit bone resorption
Magnololcause a significant elevation of cell growth, alkaline phosphatase activity, collagen synthesis, mineralization, and glutathione content in osteoblast;
decrease the production of osteoclast differentiation inducing factors such as RANKL, TNF-α, and IL-6 in the presence of antimycin A
Resveratrolprevent osteoporosis induced by cyclosporin A;
inhibit the differentiation and bone resorbing activity of osteoclasts through inhibition of ROS production;
promote the formation of osteoblasts by induction of bone morphogenetic protein-2 through Src kinase-dependent estrogen receptor activation;
promote osteogenesis of human mesenchymal stem cells by upregulating RUNX2 gene expression via the SIRT1/FOXO3A axis.
Curcuminimprove bone microarchitecture and mineral density in APP/PS1 transgenic mice;
improve bone strength and biochemical marker in ovariectomized mature rat model;
inhibit OVX-induced bone loss by reducing osteoclastogenesis through increasing antioxidant activity and impairing RANKL signaling.
Tea polyphenols (including epigallocatechin-3-gallate, epigallocatechin epi-catechin epicatechin-3-gallate)attenuate trabecular and cortical bone loss through increasing bone formation while suppressing bone resorption due to its antioxidant capacity;
inhibit the formation and differentiation of osteoclasts via inhibition of matrix metalloproteinases.
[99, 100]
decrease bone resorption, the number of multinucleated osteoclasts, and the activity TRAP and cathepsin K of osteoclast;
induce the apoptosis of osteoclasts through improving the ratio of OPG and RANKL in osteoblasts, interfering with the JNK and NF-κB signal pathway, and reducing the expression of calcitonin receptor and carbonic anhydrase/II in osteoclasts.
Harmineprevent bone loss in ovariectomized osteoporosis model mice;
inhibit osteoclast formation and bone resorption via downregulation of c-Fos and NFATc1 induced by RANKL.
Coptisineinhibit RANKL-induced NF- B phosphorylation in osteoclast precursors;
suppress the formation, differentiation and bone resorption of osteoclast through regulation of RANKL and OPG gene expression in osteoblastic cells
Palmatineinhibit osteoclast formation and bone resorption in the co-culture system with mouse bone marrow cells (BMC) and osteoblasts;
induce disruption of actin ring formation in mature osteoclasts with an impact on cell viability
Berberineprevent bone loss in SAMP6 senile osteoporosis model and ovariectomized rats;
inhibit formation and differentiation of osteoclast;
promote osteoblast differentiation through activation of Runx2 by p38 MAPK.
[104, 105]
Other compounds
Curculigosideinhibit bone loss in ovariectomized mice;
promote the proliferation and differentiation of osteoblast;
prevent hydrogen peroxide-induced dysfunction and oxidative damage in calvarial osteoblasts;
inhibit the formation, differentiation and bone resorption of osteoclast.
[106, 107]
Asperosaponin VIinduce osteoblast maturation and differentiation, and bone formation via increasing BMP-2 synthesis and activating p38 and ERK1/2 pathway[108]
Limonoid 7-oxo-deacetoxygedunin inhibit RANKL-induced osteoclastogenesis by suppressing activation of the NF- B and MAPK pathways[109]
Zerumboneabolish RANKL-induced NF- B activation, inhibit osteoclastogenesis, and suppress human breast cancer—induced bone loss in athymic nude mice[110]
Costunolide stimulate the growth and differentiation of osteoblastic MC3T3-E1 cells, which may be associated with ER, PI3K, PKC, and MAPK signaling pathway[111]
Lycopenereduce oxidative stress and the levels of bone turnover markers in postmenopausal women;
stimulate proliferation and alkaline phosphatase activity of osteoblasts;
inhibit osteoclasts formation and bone resorption activity.
[112, 113]
Tanshinone IIAinhibit osteoclast differentiation and bone resorption through disruption of the actin ring by inhibiting c-Fos and NFATc1 expression.[49, 50]
Salvianic acid Aprevent bone loss from long-term administration of prednisone in rats;
protect bone from glucocorticoid—induced bone marrow impairment by stimulating osteogenesis and depressing adipogenesis in bone marrow stromal cells.
Salvianolic acid Bprevent glucocorticoid—induced cancellous bone loss and decrease adipogenesis;
stimulate bone marrow stromal cell differentiation to osteoblast and increase osteoblast activities;
decrease glucocorticoid—induced associated adipogenic differentiation through regulating the mRNA expression of PPAR-γ, Runx2, Dickkopf-1 and β-catenin in MSC
Alisol-Bprevent bone loss in mice;
inhibit osteoclastogenesis by inhibiting the phosphorylation of JNK, and expression of NFATc1 and c-Fos;
suppresses 2-methylene-19-nor-(20S)-1α, 25(OH)2D3—induced hypercalcemia as resulting from the inhibition of osteoclastogenesis
Maslinic acidsuppress osteoclastogenesis and prevent ovariectomy-induced bone loss by regulating RANKL-mediated NF- B and MAPK signaling pathway[115]