Phytochemical Compounds Involved in the Bone Regeneration Process and Their Innovative Administration: A Systematic Review

Hanga-Farcaș, Alina; Miere, Florina; Filip, Gabriela Adriana; Clichici, Simona; Fritea, Luminița; Vlaia, Lavinia; Marian, Eleonora; Pallag, Annamária; Jurca, Tünde; Filip, S.; Mureşan, Mariana

doi:10.20944/preprints202304.0484.v1

2023

DOI: 10.20944/preprints202304.0484.v1

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Phytochemical Compounds Involved in the Bone Regeneration Process and Their Innovative Administration: A Systematic Review

Alina Hanga-Farcaș¹,

Florina Miere²,

Gabriela Adriana Filip³

et al.

Abstract: Bone metabolism is a complex process which is influenced by the activity of bone cells (e.g., osteocytes, osteoblasts, osteoclasts), the effect of some specific biomarkers (e.g., parathyroid hormone, vitamin D, alkaline phosphatase, osteocalcin, osteopontin, osteoportegerin, osterix, RANKL, Runx2) and the characteristic signaling pathways (e.g., RANKL/RANK, Wnt/β, Notch, BMP, SMAD). Some phytochemical compounds such as flavonoids, tannins, polyphenols, anthocyanins, terpenoids, polysaccharides, alkalo… Show more

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Cited by 3 publications

References 99 publications

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The Effects of Polyphenols on Bone Metabolism in Postmenopausal Women: Systematic Review and Meta-Analysis of Randomized Control Trials

Salvio,

Ciarloni,

Gianfelice

et al. 2023

Antioxidants

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Osteoporosis is a condition favored by the postmenopausal decline in estrogen levels and worsened by oxidative stress (OS). Polyphenols are natural compounds abundantly found in fruits and vegetables, and they exert antioxidant and hormonal effects that could be useful in osteoporosis prevention, as suggested by epidemiological studies showing a lower incidence of fractures in individuals consuming polyphenol-rich diets. The aim of our meta-analysis is to evaluate the effects of polyphenols on bone mineral density (BMD, primary endpoint) and bone turnover markers (BTMs, secondary endpoint) in postmenopausal women. Twenty-one randomized control trials (RCTs) were included in our analysis after in-depth search on PubMed, EMBASE, and Scopus databases. We found that supplementation with polyphenols for 3–36 months exerted no statically significant effects on BMD measured at lumbar spine (sMD: 0.21, 95% CI [−0.08 to 0.51], p = 0.16), femoral neck (sMD: 0.16, 95% CI [−0.23 to 0.55], p = 0.42), total hip (sMD: 0.05, 95% CI [−0.14 to 0.24], p = 0.61), and whole body (sMD: −0.12, 95% CI [−0.42 to 0.17], p = 0.41). Subgroup analysis based on treatment duration showed no statistical significance, but a significant effect on lumbar BMD emerged when studies with duration of 24 months or greater were analyzed separately. On the other hand, we found a significantly slight increase in bone-specific alkaline phosphatase (BALP) levels (sMD: 1.27, 95% CI [1.13 to 1.42], p < 0.0001) and a decrease in pyridinoline (PD) levels (sMD: −0.58, 95% CI [−0.77 to −0.39], p < 0.0001). High heterogeneity among studies and unclear risk of bias in one third of the included studies emerged. A subgroup analysis showed similar effects for different duration of treatment and models of dual-energy X-ray absorptiometry (DXA) scanner. More robust evidence is needed before recommending the prescription of polyphenols in clinical practice.

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The Effects of Polyphenols on Bone Metabolism in Postmenopausal Women: Systematic Review and Meta-Analysis of Randomized Control Trials

Salvio,

Ciarloni,

Gianfelice

et al. 2023

Antioxidants

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The Influence of Juglans regia L. Extract and Ellagic Acid on Oxidative Stress, Inflammation, and Bone Regeneration Biomarkers

Hanga-Farcas,

Fritea,

Filip

et al. 2024

IJMS

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Bone regeneration is a highly dynamic and complex process that involves hematopoietic stem cells and mesenchymal cells, collagen fibers, non-collagenous proteins and biomolecules from extracellular matrices, and different cytokines and immune cells, as well as growth factors and hormones. Some phytochemicals due to antioxidant and anti-inflammatory effects can modulate the bone signaling pathways and improve bone healing and thus can be a good candidate for osteoregeneration. The aim of this study was to analyze the impact of Juglans regia L. extract compared to ellagic acid on bone neoformation in rats. The animals with a 5 mm calvaria defect were divided into four groups (n = 10): group 1 was treated with ellagic acid 1% (EA), group 2 was treated with Juglans regia L. extract 10% (JR), group 3 was treated with a biphasic mix of hydroxyapatite and tricalcium phosphate (Ceraform), and group 4 was treated with vehicle inert gel with carboxymethylcellulose (CMC). After 3 weeks of treatment, blood samples were collected for oxidative stress and inflammation assessment. Additionally, the receptor activator of nuclear factor kappa-Β ligand (RANKL) and hydroxyproline levels were quantified in blood. The skull samples were analyzed by scanning electron microscopy in order to detect the modifications in the four groups. The results suggested that JR extract had relevant anti-oxidant effect and bone protective activity and generated the accumulation of Ca and P, demonstrating the potential therapeutic abilities in bone regeneration.

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Use of Plant Extracts in Polymeric Scaffolds in the Regeneration of Mandibular Injuries

de Oliveira,

Maia,

Massimino

et al. 2024

Pharmaceutics

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Severe loss of bone mass may require grafting, and, among the alternatives available, there are natural biomaterials that can act as scaffolds for the cell growth necessary for tissue regeneration. Collagen and elastin polymers are a good alternative due to their biomimetic properties of bone tissue, and their characteristics can be improved with the addition of polysaccharides such as chitosan and bioactive compounds such as jatoba resin and pomegranate extract due to their antigenic actions. The aim of this experimental protocol was to evaluate bone neoformation in experimentally made defects in the mandible of rats using polymeric scaffolds with plant extracts added. Thirty rats were divided into group 1, with a mandibular defect filled with a clot from the lesion and no graft implant (G1-C, n = 10); group 2, filled with collagen/chitosan/jatoba resin scaffolds (G2-CCJ, n = 10); and group 3, with collagen/nanohydroxyapatite/elastin/pomegranate extract scaffolds (G3-CHER, n = 10). Six weeks after surgery, the animals were euthanized and samples from the surgical areas were submitted to macroscopic, radiological, histological, and morphometric analysis of the mandibular lesion repair process. The results showed no inflammatory infiltrates in the surgical area, indicating good acceptance of the scaffolds in the microenvironment of the host area. In the control group (G1), there was a predominance of reactive connective tissue, while in the grafted groups (G2 and G3), there was bone formation from the margins of the lesion, but it was still insufficient for total bone repair of the defect within the experimental period standardized in this study. The histomorphometric analysis showed that the mean percentage of bone volume formed in the surgical area of groups G1, G2, and G3 was 17.17 ± 2.68, 27.45 ± 1.65, and 34.07 ± 0.64 (mean ± standard deviation), respectively. It can be concluded that these scaffolds with plant extracts added can be a viable alternative for bone repair, as they are easily manipulated, have a low production cost, and stimulate the formation of new bone by osteoconduction.

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Phytochemical Compounds Involved in the Bone Regeneration Process and Their Innovative Administration: A Systematic Review

Cited by 3 publications

References 99 publications

The Effects of Polyphenols on Bone Metabolism in Postmenopausal Women: Systematic Review and Meta-Analysis of Randomized Control Trials

The Effects of Polyphenols on Bone Metabolism in Postmenopausal Women: Systematic Review and Meta-Analysis of Randomized Control Trials

The Influence of Juglans regia L. Extract and Ellagic Acid on Oxidative Stress, Inflammation, and Bone Regeneration Biomarkers

Use of Plant Extracts in Polymeric Scaffolds in the Regeneration of Mandibular Injuries

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