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Application of Natural Products in Prevention of Bone Related Diseases
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Application of Natural Products in Prevention of Bone Related Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (20 January 2025) | Viewed by 7744

Special Issue Editors

Dr. Eunkuk Park

E-Mail Website
Guest Editor
Department of Medical Genetics, Ajou University School of Medicine, Suwon 16499, Republic of Korea
Interests: osteoporosis; osteoarthritis; obesity; woman's menopause; cognitive impairment; phytomedicine; natural compounds; animal study
Dr. Seon-Yong Jeong

E-Mail Website
Guest Editor
Department of Medical Genetics, College of Medicine, Ajou University, Suwon, Republic of Korea
Interests: hergbal medicine; obesity; osteoporosis; menopausal symptoms; genetics and genomics; osteoarthritis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The application of natural products for the prevention of bone-related diseases has recently gained significant attention. Natural products such as food sources, herbs, and plants contain various vitamins, minerals, and other bioactive compounds that have been reported to have beneficial effects on bone health.

A multitude of studies have suggested the potential benefits of natural products for the prevention of bone loss and improvement of bone density. These natural products exert their effects by modulating bone remodeling processes, ameliorating oxidative stress and inflammation, and augmenting the bioavailability of essential minerals, such as calcium and magnesium.

Moreover, natural products have been proposed as a promising alternative or adjunctive therapy to conventional treatments for bone-related diseases. In contrast to synthetic drugs, natural products have exhibited a favorable safety profile, with fewer adverse effects reported. Furthermore, natural products exhibit the potential to provide additional benefits beyond bone health, including anti-menopausal, anti-osteoarthritic, and anti-cancer effects. These advantages can be attributed to the presence of various bioactive compounds in natural sources that can modulate several signaling pathways and cellular processes involved in these diseases.

In summary, the utilization of natural products for the prevention of bone-related diseases holds great promise and may significantly enhance the quality of life for individuals afflicted with or at risk of these conditions. Nevertheless, additional investigations are required to gain a comprehensive understanding of their underlying mechanisms of action and optimize their clinical application.

Dr. Eunkuk Park
Dr. Seon-Yong Jeong
Guest Editors

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Keywords

  • osteoporosis
  • natural products
  • functional food
  • clinical application
  • menopause
  • osteoarthritis
  • bone-related diseases
  • alternative therapy
 

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Published Papers (5 papers)

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18 pages, 7328 KiB  
Article
Arcyriaflavin A Alleviates Osteoporosis by Suppressing RANKL-Induced Osteoclastogenesis
by Mengbo Zhu, Mingwei Xu, Damien Bertheloot, Victoria C. Brom, Alexander Sieberath, Jochen Salber, Kristian Welle, Christof Burger, Dieter C. Wirtz, Shaowei Wang and Frank A. Schildberg
Int. J. Mol. Sci. 2025, 26(5), 2141; https://doi.org/10.3390/ijms26052141 - 27 Feb 2025
Viewed by 650
Abstract
Osteoclasts (OCs) are important therapeutic targets in the treatment of osteoporosis. The aim of this study was to explore a novel therapeutic approach for osteoporosis using Arcyriaflavin A (ArcyA), a natural compound derived from the marine invertebrate Eudistoma sp. We systematically evaluated the [...] Read more.
Osteoclasts (OCs) are important therapeutic targets in the treatment of osteoporosis. The aim of this study was to explore a novel therapeutic approach for osteoporosis using Arcyriaflavin A (ArcyA), a natural compound derived from the marine invertebrate Eudistoma sp. We systematically evaluated the effects of ArcyA on OC differentiation and function in mouse models using molecular biology assays, cellular function analyses and in vivo animal experiments. We also evaluated the efficacy of ArcyA in human cells. The TRAP staining results provide the first clear evidence of the drug’s inhibitory effect, whereby the administration of ArcyA led to a significant reduction in TRAP-positive cells compared to the control group at concentrations that were non-toxic to bone marrow macrophages. Meanwhile, a significant reduction in the number of multinucleated giant cells with more than ten nuclei was observed. Furthermore, similar TRAP staining results were reproduced in human OCs, suggesting that ArcyA has the same effect on OCs derived from human PBMCs. At the molecular level, ArcyA treatment resulted in the downregulation of genes relevant to OC differentiation (NFATc1, cFos and TNFrsf11α), fusion and survival (DCstamp and ATP6v0d2) and resorption function (CTSK, MMP9, integrin β3 and ACP5). A western blot analysis of the corresponding proteins (NFATc1, cFos, CTSK and integrin β3) further confirmed the PCR results. Furthermore, ArcyA-treated OCs produced significantly fewer resorption pits, indicating suppressed bone resorption activity. Consistent with this, in vivo experiments using an ovariectomy (OVX)-induced osteoporosis mouse model showed that ArcyA treatment significantly alleviated bone loss. Mice in the treatment groups had higher BV/TV values, and this therapeutic effect was enhanced in a dose-dependent manner. In addition, our research also showed that IκB could be a potential target for the inhibitory effect of ArcyA. In conclusion, these findings suggest that ArcyA has significant therapeutic potential for the treatment of osteoporosis by inhibiting osteoclastogenesis and bone resorption. Further studies are warranted to explore its clinical applications. Full article
(This article belongs to the Special Issue Application of Natural Products in Prevention of Bone Related Diseases)
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18 pages, 6179 KiB  
Article
Porcine-Derived Chondroitin Sulfate Sodium Alleviates Osteoarthritis in HTB-94 Cells and MIA-Induced SD Rat Models
by Hyelim Kim, Jinhee Kim, Seong-Hoo Park, Jinhak Kim, Yuri Gwon, Minhee Lee and Soo-Jeung Park
Int. J. Mol. Sci. 2025, 26(2), 521; https://doi.org/10.3390/ijms26020521 - 9 Jan 2025
Viewed by 1007
Abstract
Osteoarthritis (OA) is a chronic disease characterized by cartilage degradation, leading to bone friction, inflammation, stiffness, pain, and reduced mobility. This study investigates the therapeutic effects of porcine-derived chondroitin sulfate sodium (CS) on OA symptoms at both cellular and animal levels. In vitro [...] Read more.
Osteoarthritis (OA) is a chronic disease characterized by cartilage degradation, leading to bone friction, inflammation, stiffness, pain, and reduced mobility. This study investigates the therapeutic effects of porcine-derived chondroitin sulfate sodium (CS) on OA symptoms at both cellular and animal levels. In vitro study, HTB-94 chondrocytes were treated with inflammatory stimuli and CS (10, 50, 100, and 200 μg/mL) to assess the release of inflammatory mediators and the expression of genes and proteins related to cartilage synthesis and degradation. In vivo study, an MIA-induced OA rat model was used, and CS (62, 124, and 248 mg/kg b.w.) was orally administered for 4 weeks. Key parameters, such as exercise capacity, micro-CT, histological evaluation of joint tissues, serum inflammatory markers, and the expression of mRNA and proteins (inflammatory, cartilage synthesis and degradation, and apoptosis markers), were analyzed. Porcine-derived CS significantly reduced PGE2, NO, and extracellular matrix degradation marker (COMP and CTX-II) levels and increased the expression of cartilage synthesis-related genes and proteins in both HTB-94 cells and the MIA-induced rats. Additionally, CS modulated cartilage degradation pathways and notably inhibited apoptosis in vivo. The effects of porcine CS were comparable to the NSAID ibuprofen, demonstrating its potential as an anti-inflammatory and chondroprotective agent for OA management and dietary supplementation. Full article
(This article belongs to the Special Issue Application of Natural Products in Prevention of Bone Related Diseases)
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15 pages, 2603 KiB  
Article
Water Extract of Angelica dahurica Inhibits Osteoclast Differentiation and Bone Loss
by Dong Ryun Gu, Hyun Yang, Seong Cheol Kim, Youn-Hwan Hwang and Hyunil Ha
Int. J. Mol. Sci. 2023, 24(19), 14715; https://doi.org/10.3390/ijms241914715 - 28 Sep 2023
Cited by 2 | Viewed by 1545
Abstract
Angelica dahurica radix has a long history of traditional use in China and Korea for treating headaches, cold-damp pain and skin diseases. Despite various pharmacological studies on A. dahurica, its impact on bones remains unclear. Hence, this study investigated the inhibitory effect [...] Read more.
Angelica dahurica radix has a long history of traditional use in China and Korea for treating headaches, cold-damp pain and skin diseases. Despite various pharmacological studies on A. dahurica, its impact on bones remains unclear. Hence, this study investigated the inhibitory effect of A. dahurica’s radix water extract (WEAD) on osteoclast differentiation. In vitro experiments showed that WEAD effectively suppresses osteoclast differentiation. Treatment of an osteoclast precursor with WEAD significantly suppressed the expression of nuclear factor of activated T-cells 1 (NFATc1), essential transcription factor for osteoclastogenesis, while increasing the expression of negative regulators, interferon regulatory factor 8 (Irf8) and v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MafB). Consistent with the in vitro findings, the oral administration of WEAD (100 and 300 mg/kg/day) to mice subjected to surgical ovariectomy for a duration of six weeks alleviated bone loss, while also mitigating weight gain and liver fat accumulation. In addition, we also identified phytochemicals present in WEAD, known to regulate osteoclastogenesis and/or bone loss. These results suggest the potential use of WEAD for treating various bone disorders caused by excessive bone resorption. Full article
(This article belongs to the Special Issue Application of Natural Products in Prevention of Bone Related Diseases)
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15 pages, 4235 KiB  
Article
Extract of Artemisia dracunculus L. Modulates Osteoblast Proliferation and Mineralization
by Matthew C. Scott, Aleah Bourgeois, Yongmei Yu, David H. Burk, Brenda J. Smith and Z. Elizabeth Floyd
Int. J. Mol. Sci. 2023, 24(17), 13423; https://doi.org/10.3390/ijms241713423 - 30 Aug 2023
Cited by 5 | Viewed by 1716
Abstract
Thiazolidinediones (TZD) significantly improve insulin sensitivity via action on adipocytes. Unfortunately, TZDs also degrade bone by inhibiting osteoblasts. An extract of Artemisia dracunculus L., termed PMI5011, improves blood glucose and insulin sensitivity via skeletal muscle, rather than fat, and may therefore spare bone. [...] Read more.
Thiazolidinediones (TZD) significantly improve insulin sensitivity via action on adipocytes. Unfortunately, TZDs also degrade bone by inhibiting osteoblasts. An extract of Artemisia dracunculus L., termed PMI5011, improves blood glucose and insulin sensitivity via skeletal muscle, rather than fat, and may therefore spare bone. Here, we examine the effects of PMI5011 and an identified active compound within PMI5011 (2′,4′-dihydroxy-4-methoxydihydrochalcone, DMC-2) on pre-osteoblasts. We hypothesized that PMI5011 and DMC-2 will not inhibit osteogenesis. To test our hypothesis, MC3T3-E1 cells were induced in osteogenic media with and without PMI5011 or DMC-2. Cell lysates were probed for osteogenic gene expression and protein content and were stained for osteogenic endpoints. Neither compound had an effect on early stain outcomes for alkaline phosphatase or collagen. Contrary to our hypothesis, PMI5011 at 30 µg/mL significantly increases osteogenic gene expression as early as day 1. Further, osteogenic proteins and cell culture mineralization trend higher for PMI5011-treated wells. Treatment with DMC-2 at 1 µg/mL similarly increased osteogenic gene expression and significantly increased mineralization, although protein content did not trend higher. Our data suggest that PMI5011 and DMC-2 have the potential to promote bone health via improved osteoblast maturation and activity. Full article
(This article belongs to the Special Issue Application of Natural Products in Prevention of Bone Related Diseases)
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11 pages, 2276 KiB  
Brief Report
Vitamin D Attenuates Fibrotic Properties of Fibrous Dysplasia-Derived Cells for the Transit towards Osteocytic Phenotype
by Ha-Young Kim, Jung-Hee Shim, Baek-Kyu Kim and Chan-Yeong Heo
Int. J. Mol. Sci. 2024, 25(9), 4954; https://doi.org/10.3390/ijms25094954 - 1 May 2024
Viewed by 1851
Abstract
Fibrous dysplasia (FD) poses a therapeutic challenge due to the dysregulated extracellular matrix (ECM) accumulation within affected bone tissues. In this study, we investigate the therapeutic potential of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in managing FD by examining its effects on [...] Read more.
Fibrous dysplasia (FD) poses a therapeutic challenge due to the dysregulated extracellular matrix (ECM) accumulation within affected bone tissues. In this study, we investigate the therapeutic potential of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in managing FD by examining its effects on FD-derived cells in vitro. Our findings demonstrate that 1,25(OH)2D3 treatment attenuates the pro-fibrotic phenotype of FD-derived cells by suppressing the expression of key pro-fibrotic markers and inhibiting cell proliferation and migration. Moreover, 1,25(OH)2D3 enhances mineralization by attenuating pre-osteoblastic cellular hyperactivity and promoting maturation towards an osteocytic phenotype. These results offer valuable insights into potential treatments for FD, highlighting the role of 1,25(OH)2D3 in modulating the pathological properties of FD-derived cells. Full article
(This article belongs to the Special Issue Application of Natural Products in Prevention of Bone Related Diseases)
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