Oral administration of kaempferol inhibits bone loss in rat model of ovariectomy-induced osteopenia

Nowak, Beata; Matuszewska, Agnieszka; Nikodem, Anna; Filipiak, Jarosław; Landwójtowicz, Marcin; Sadanowicz, Ewa; Jędrzejuk, Diana; Rzeszutko, Marta; Zduniak, Krzysztof; Piasecki, Tomasz; Dziewiszek, Wojciech; Merwid-Ląd, Anna; Trocha, Małgorzata; Sozański, Tomasz; Kwiatkowska, J; Bolanowski, Marek; Szeląg, Adam

doi:10.1016/j.pharep.2017.05.002

Cited by 38 publications

(22 citation statements)

References 29 publications

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“…From the in vivo assessment of bone microarchitecture, the present study verified that the bone mass parameters (BMD, BV/TV, Tb.N and Tb.Th) were significantly elevated, and the parameters of osteoporosis (SMI and Tb.Sp) reduced in OVX rats treated with Kae compared with OVX group rats. These changes in bone morphology induced by Kae in OVX rats are similar to those found in previously published research (26,27). However, the concentration of Kae used in the in vivo experiment of the present study was higher than that of previous studies (26,27).…”

Section: Discussionsupporting

confidence: 91%

“…These changes in bone morphology induced by Kae in OVX rats are similar to those found in previously published research (26,27). However, the concentration of Kae used in the in vivo experiment of the present study was higher than that of previous studies (26,27). The similarity of the results may be associated with differences in delivery time or the vehicle solution used in the present study.…”

Section: Discussionsupporting

confidence: 91%

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Kaempferol promotes bone formation in part via the mTOR signaling pathway

Zhao

et al. 2019

Mol Med Report

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Previous research indicates that kaempferol (Kae) promotes osteogenesis, but its underlying mechanism of action remains unclear. The present study hypothesized that the osteogenic effects of Kae were mediated through mammalian target of rapamycin (mTor). To validate this hypothesis, bone marrow mesenchymal stem cells (BMScs) from ovariectomized (oVX) rats were differentiated into osteoblasts. The bone mineral density and bone microarchitecture of the oVX rats was measured in vivo, while osteogenesis was evaluated in vitro via alizarin red S staining and alkaline phosphatase activity measurements in cultured BMScs. The levels of phosphorylated eukaryotic translation initiation factor 4e-binding protein 1 (p-4e/BP1) and phosphorylated ribosomal protein S6 kinase B1 (p-S6K), and the expression of runt-related transcription factor 2 and Osterix, were concurrently quantified by western blot analysis. The data suggested that Kae prevented oVX-induced osteoporosis in rats by promoting osteoblastogenesis. Furthermore, treatment with Kae in rat BMScs enhanced mineralization, elevated alP activity, increased the expression levels of runx-2 and osterix and increased the levels of p-S6K and decreased the levels of p-4e/BP1 and, consistent with its ability to promote osteoblast differentiation. in contrast, treatment with rapamycin, an mTor inhibitor, produced the opposite phenotype. Taken together, these data suggested that the protective effects of Kae in BMScs and in the oVX rat model resulted from the induction of osteogenesis via mTor signaling, or at least partially via the regulation of downstream effectors of the mTor pathway.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 91%

Kaempferol promotes bone formation in part via the mTOR signaling pathway

Zhao

et al. 2019

Mol Med Report

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“…A recent study demonstrated that oral administration of kaempferol (5 mg/kg) for 8 weeks increased femoral bone mineral density (BMD) and Young’s modulus of elasticity but decreased osteocalcin (OCN) and RANKL in OVX rats. Histologically, the OVX rats receiving kaempferol had higher bone volume/total volume (BV/TV), trabecular bone area (B.Ar), trabecular bone perimeter (B.Pm) and bone surface/total volume (BS/TV) relative to the negative control animals 22. Kaempferitrin, another name for kaempferol-3,7-dirhamnoside, at the dose of 8 or 16 mg/kg had been shown to increase BMD, bone mineral content (BMC), tissue mineral content, tissue mineral density, bone volume fraction, trabecular number (Tb.N), connectivity density (Conn.D) and decrease trabecular separation (Tb.Sp) in the OVX rats.…”

Section: In Vivo Studies On the Effects Of Kaempferol On Bonementioning

confidence: 99%

“…Kaempferitrin also influenced the levels of bone formation and resorption markers, whereby a higher level of ALP, as well as lower levels of cathepsin K and tartrate-resistant acid phosphatase (TRAP), were observed after the treatment 23Table 1In Vivo Studies On The Bone-Protecting Properties Of KaempferolAnimal StrainExperimental GroupsOutcomesReferenceNewborn Sprague–Dawley ratsControlKaempferol (5 μM, injected into the top of the periosteum of the parietal bone)Compared to normal group, treatment with kaempferol: ↑ BSP, OSX and Runx-2↑ bone area and number of osteoblasts↑ osteoblast differentiationYang et al20 (2010)Female Sprague–Dawley rats (n=10/group)ShamOVXOVX + kaempferol (5 mg/kg, oral)Compared to OVX group, treatment with kaempferol: ↑ BMD in total femur, femoral neck, proximal tibia, total vertebra and L3 vertebra↑ compressive energy for L3 vertebra and ↓ ALP↑ mineralization and ↓ adipogenesis in bone marrow cellsTrivedi et al21 (2008)Female Wistar rats (n=8/group)ShamOVXOVX + kaempferol (5 mg/kg, oral)Compared to OVX group, treatment with kaempferol: ↑ BMD and Young’s modulus↓ OCN and RANKL↑ BV/TV, B.Ar, B.Pm and BS/TVNowak et al22 (2017)Female Sprague–Dawley rats (n=8/group)ShamOVXOVX + estradiol valerate (1 mg/kg, oral)OVX + kaempferitrin (8 mg/kg, oral)OVX + kaempferitrin (16 mg/kg, oral)Compared to OVX group, treatment with kaempferitrin: ↑ BMD, BMC, tissue mineral content, tissue mineral density, bone volume fraction, Tb.N, Conn.D and ↓ Tb.Sp↑ ALP, ↓ cathepsin K and TRAPMa et al23 (2015)Female Sprague–Dawley rats (n=10/group)NormalMethylprednisolone (5 mg/kg, s.c.)Methylprednisolone (5 mg/kg, s.c.) + kaempferol (5 mg/kg, oral)Methylprednisolone (5 mg/kg, s.c.) + human 1–34 PTH (5 μg/kg, 5 times/week, s.c.)Compared to methylprednisolone-treated group, treatment with kaempferol: ↑ BV/TV, BS/TV, Tb.N, Conn.D, ↓ Tb.Sp and SMI of proximal tibial metaphyseal region↑ Cs.Th, MMI, B.Pm and T.Pm of tibial diaphyseal region↑ BMD of femur and tibia↑ BFR, MAR and MS of femur diaphysis↑ energy to failure and stiffness of femur diaphysis↑ P1NP and ↓ CTX-1 in serum↑ ...…”

Section: In Vivo Studies On the Effects Of Kaempferol On Bonementioning

confidence: 99%

<p>The Osteoprotective Effects Of Kaempferol: The Evidence From In Vivo And In Vitro Studies</p>

Wong

Chin

2019

DDDT

126

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Kaempferol is a dietary bioflavonoid ubiquitously found in various types of plant. It possesses a wide range of medicinal properties suggesting its potential clinical utility that requires further investigation. The present review intends to highlight the efficacy of kaempferol and its molecular mechanisms of action in regulating bone metabolism. Many reports have acknowledged the bone-protecting property of kaempferol and kaempferol-containing plants using in vitro and in vivo experimental models. Kaempferol supplementation showed bone-sparing effects in newborn rats, glucocorticoid-induced and ovariectomy-induced osteoporotic models as well as bone fracture models. It achieves the bone-protective effects by inhibiting adipogenesis, inflammation, oxidative stress, osteoclastic autophagy and osteoblastic apoptosis while activating osteoblastic autophagy. The anti-osteoporotic effects of kaempferol are mediated through regulation of estrogen receptor, bone morphogenetic protein-2 (BMP-2), nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) signaling pathways. In summary, kaempferol exhibits beneficial effects on skeleton, thus is potentially effective for the prophylaxis and treatment of osteoporosis.

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“…Quercetin can also directly or indirectly down-regulate the expression of RANKL, inhibit osteoclast differentiation, reduce bone resorption, and stimulate osteoblast activity through estrogen signaling pathway and ERK signaling pathway [31]. Kaempferol has also been shown to have bone protective effects on ovariectomized rats [32], possibly through estrogen receptor, MAPK, NF-κB and other signaling pathways [33]. Luteolin can prevent bone loss after osteoporosis by inhibiting osteoclast differentiation.…”

Section: Key Active Ingredient Of Zytlf For Anti-pmopmentioning

confidence: 99%

Exploration of the mechanism of Ziyin Tongluo Formula on preventing and treating postmenopausal osteoporosis based on the network pharmacology and molecular docking

Chen

Yang

Sun

et al. 2020

Preprint

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Background: Postmenopausal osteoporosis (PMOP) is a global chronic and metabolic bone disease, which poses huge challenges to individuals and society. Ziyin Tongluo Formula (ZYTLF) has been proved effective in the treatment of PMOP. However, the material basis and mechanism of ZYLTF against PMOP have not been thoroughly elucidated.Methods: Online databases were used to identify the active ingredients of ZYTLF and corresponding putative targets. Genes associated with PMOP were mined, and then mapped with the putative targets to obtain overlapping genes. Multiple networks were constructed and analyzed, from which the key genes were selected. The key genes were imported to the DAVID database to performs GO and KEGG pathway enrichment analysis. Finally, AutoDock Tools and other software were used for molecular docking of core compounds and key proteins. Results: Ninety-two active compounds of ZYTLF corresponded to 243 targets, with 129 target genes interacting with PMOP, and 50 key genes were selected. Network analysis showed the top 5 active ingredients including quercetin, kaempferol, luteolin, scutellarein, and formononetin., and the top 50 key genes such as VEGFA, MAPK8, AKT1, TNF, ESR1. Enrichment analysis uncovered two significant types of KEGG pathways in PMOP, hormone-related signaling pathways (estrogen , prolactin, and thyroid hormone signaling pathway) and inflammation-related pathways (TNF, PI3K-Akt, and MAPK signaling pathway). Moreover, molecular docking analysis verified that the main active compounds were tightly bound to the core proteins, further confirming the anti-PMOP effects. Conclusions: Based on network pharmacology and molecular docking technology, this study initially revealed the mechanisms of ZYTLF on PMOP, which involves multiple targets and multiple pathways.

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Oral administration of kaempferol inhibits bone loss in rat model of ovariectomy-induced osteopenia

Abstract: Kaempferol has a beneficial influence on estrogen-deficiency-induced disturbances of bone structure in rats.

Cited by 38 publications

References 29 publications

Kaempferol promotes bone formation in part via the mTOR signaling pathway

Kaempferol promotes bone formation in part via the mTOR signaling pathway

<p>The Osteoprotective Effects Of Kaempferol: The Evidence From In Vivo And In Vitro Studies</p>

Exploration of the mechanism of Ziyin Tongluo Formula on preventing and treating postmenopausal osteoporosis based on the network pharmacology and molecular docking

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