The Effect of Grape Seed Extract on the Alveolar, Jaw, and Skeletal Bone Remodeling: A Scoping Review

Abstract Herbal medicine has an important part in promoting and maintaining human health. One of them was grape seed extract (GSE). Various potentials of GSE in human health have been explored, and its potential for maintaining bone health is promising. Some initial research has provided evidence that the GSE was able to affect bone remodeling (bone resorption and bone formation). This scoping review analyzed and discussed all the reports on the effect of GSE on bone healing and bone remodeling in animals in the alveolar bone, jaw bone, and skeletal bone. The further purpose is to give an opportunity to research and development of supplementation of GSE for humans. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines were used to compose this scoping review through database on Scopus, PubMed, Science Direct, Web of Science, Embase, and manual search until December 2022. The inclusion criteria were a study that analyzed the effect of supplementation GSE on all bones. All included study was in vivo study with supplementation of GSE. The supplementation of GSE affects the alveolar bone, jaw bones, and skeletal bone by promoting bone formation and inhibiting bone resorption by suppressing inflammation, apoptosis pathways, and osteoclastogenesis. It not only supports bone remodeling in bone inflammation, osteonecrosis, osteoporosis, and arthritis but also the GSE increases bone health by increasing the density and mineral deposition in trabecula and cortical bone. The supplementation of GSE supports bone remodeling by interfering with the inflammation process and bone formation not only by preventing bone resorption but also by maintaining bone density.

[1]  M. Zadurska,et al.  Bone Remodeling during Orthodontic Movement of Lower Incisors—Narrative Review , 2022, International journal of environmental research and public health.

[2]  F. Naeini,et al.  The effect of grape products on liver enzymes: A systematic review and meta‐analysis of randomized controlled trials , 2022, Phytotherapy research : PTR.

[3]  Yongjia Wu,et al.  Runx2 and Nell-1 in dental follicle progenitor cells regulate bone remodeling and tooth eruption , 2022, Stem Cell Research & Therapy.

[4]  R. Gan,et al.  Bioactive Compounds, Health Benefits and Food Applications of Grape , 2022, Foods.

[5]  D. He,et al.  Neural regulation of alveolar bone remodeling and periodontal ligament metabolism during orthodontic tooth movement in response to therapeutic loading. , 2022, Journal of the World federation of orthodontists.

[6]  R. Rigual,et al.  Molecular Mechanisms Involved in Hypoxia-Induced Alterations in Bone Remodeling , 2022, International journal of molecular sciences.

[7]  Dong Ding,et al.  Dihydroartemisinin attenuates osteoclast formation and bone resorption via inhibiting the NF-κB, MAPK and NFATc1 signaling pathways and alleviates osteoarthritis , 2021, International journal of molecular medicine.

[8]  E. Sadeghi,et al.  The Effect of Grape (Vitis vinifera) Seed Extract Supplementation on Flow-Mediated Dilation, Blood Pressure, and Heart Rate: A Systematic Review and Meta-Analysis of Controlled Trials with Duration- and Dose-Response Analysis. , 2021, Pharmacological research.

[9]  Zohaib Khurshid,et al.  Literature search strategies in dental education and research , 2021, Journal of Taibah University Medical Sciences.

[10]  Y. Li,et al.  Biomechanical and biological responses of periodontium in orthodontic tooth movement: up-date in a new decade , 2021, International journal of oral science.

[11]  R. Amani,et al.  The effect of grape seed extract supplementation on oxidative stress and inflammation: A systematic review and meta‐analysis of controlled trials , 2021, International journal of clinical practice.

[12]  M. Prodanov,et al.  Pre-Treatment with Grape Seed Extract Reduces Inflammatory Response and Oxidative Stress Induced by Helicobacter pylori Infection in Human Gastric Epithelial Cells , 2021, Antioxidants.

[13]  G. Horgan,et al.  Efficacy of Bilberry and Grape Seed Extract Supplement Interventions to Improve Glucose and Cholesterol Metabolism and Blood Pressure in Different Populations—A Systematic Review of the Literature , 2021, Nutrients.

[14]  Omid Asbaghi,et al.  Effects of grape products on inflammation and oxidative stress: A systematic review and meta‐analysis of randomized controlled trials , 2021, Phytotherapy research : PTR.

[15]  Yin Yuan,et al.  Hypoxia inhibits RANKL-induced ferritinophagy and protects osteoclasts from ferroptosis. , 2021, Free radical biology & medicine.

[16]  T. Yoneda,et al.  Dmrt2 promotes transition of endochondral bone formation by linking Sox9 and Runx2 , 2021, Communications biology.

[17]  S. Eick,et al.  Salivary Pellicle Modification with Grape-seed Extract: In Vitro Study on the Effect on Bacterial Adhesion and Biofilm Formation. , 2021, Oral health & preventive dentistry.

[18]  A. Adámková,et al.  Health Effects of Grape Seed and Skin Extracts and Their Influence on Biochemical Markers , 2020, Molecules.

[19]  Ju-Young Kim,et al.  Grape Seed Proanthocyanidin Extract Prevents Bone Loss via Regulation of Osteoclast Differentiation, Apoptosis, and Proliferation , 2020, Nutrients.

[20]  Ş. Suciu,et al.  Grape Seed Extract Reduces the Degree of Atherosclerosis in Ligature-Induced Periodontitis in Rats – An Experimental Study , 2020, Journal of medicine and life.

[21]  Yuan Tian,et al.  Epithelium-specific Runx2 Knockout Mice Display Junctional Epithelium and Alveolar Bone Defects. , 2020, Oral diseases.

[22]  M. Hosseinzadeh,et al.  The effect of grape products containing polyphenols on C-reactive protein levels: a systematic review and meta-analysis of randomised controlled trials , 2020, British Journal of Nutrition.

[23]  A. Iraji,et al.  The protective effects of grape seed oil on induced osteoarthritis of the knee in male rat models , 2020, Journal of Orthopaedic Surgery and Research.

[24]  M. Greenblatt,et al.  Osteoblast-Osteoclast Communication and Bone Homeostasis , 2020, Cells.

[25]  H. Kitaura,et al.  Osteocyte-Related Cytokines Regulate Osteoclast Formation and Bone Resorption , 2020, International journal of molecular sciences.

[26]  Yi-Han Chen,et al.  Proanthocyanidins: Components, Pharmacokinetics and Biomedical Properties. , 2020, The American journal of Chinese medicine.

[27]  Taichi Tenkumo,et al.  Proanthocyanidin-rich grape seed extract improves bone loss, bone healing, and implant osseointegration in ovariectomized animals , 2020, Scientific Reports.

[28]  Zhixin Wu,et al.  GSH attenuates RANKL-induced osteoclast formation in vitro and LPS-induced bone loss in vivo. , 2020, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[29]  M. Aydın,et al.  Effect of Grape Seed Extract on Bone Formation in The Expanded Inter-premaxillary Suture , 2020 .

[30]  F. Ji,et al.  Inhibition of long non-coding RNA TSIX accelerates tibia fraction healing via binding and positively regulating the SOX6 expression. , 2020, European review for medical and pharmacological sciences.

[31]  Fernando Soveral D'aviz,et al.  Antibacterial Efficacy of the Grape Seed Extract as an Irrigant for Root Canal Preparation , 2020, European endodontic journal.

[32]  B. Larijani,et al.  Effects of grape seed extract on dyslipidaemia: a systematic review and dose–response meta-analysis of randomised controlled trials , 2020, British Journal of Nutrition.

[33]  Peng Yun,et al.  Effects of Grape Seed Proanthocyanidin Extract on Obesity , 2020, Obesity Facts.

[34]  C. Bladé,et al.  The effects of Vitis vinifera L. phenolic compounds on a blood-brain barrier culture model: Expression of leptin receptors and protection against cytokine-induced damage. , 2020, Journal of ethnopharmacology.

[35]  Ž. Reiner,et al.  The effects of grape seed extract on glycemic control, serum lipoproteins, inflammation, and body weight: A systematic review and meta‐analysis of randomized controlled trials , 2019, Phytotherapy research : PTR.

[36]  A. Almulla,et al.  Effect of Black Grape Seed Extract (Vitis vinifera) on Biofilm Formation of Methicillin-Resistant Staphylococcus aureus and Staphylococcus haemolyticus , 2019, Current Microbiology.

[37]  Nicole M Delimont,et al.  Prevention of dental caries by grape seed extract supplementation: A systematic review , 2019, Nutrition and health.

[38]  N. Miyasaka,et al.  Effects of Grape Seed Proanthocyanidin Extract on Vascular Endothelial Function in Participants with Prehypertension: A Randomized, Double-Blind, Placebo-Controlled Study , 2019, Nutrients.

[39]  Yi Tang,et al.  HIF‐1α facilitates osteocyte‐mediated osteoclastogenesis by activating JAK2/STAT3 pathway in vitro , 2019, Journal of cellular physiology.

[40]  A. Alhasyimi,et al.  Postorthodontic Relapse Prevention by Administration of Grape Seed ( Vitis vinifera ) Extract Containing Cyanidine in Rats , 2019, European Journal of Dentistry.

[41]  V. Verardo,et al.  Grape Seeds Proanthocyanidins: An Overview of In Vivo Bioactivity in Animal Models , 2019, Nutrients.

[42]  S. Dey,et al.  Grape seed extract: having a potential health benefits , 2019, Journal of Food Science and Technology.

[43]  S. Muallem,et al.  Homer2 and Homer3 modulate RANKL-induced NFATc1 signaling in osteoclastogenesis and bone metabolism. , 2019, The Journal of endocrinology.

[44]  Weiguo Zou,et al.  STAT3 controls osteoclast differentiation and bone homeostasis by regulating NFATc1 transcription , 2019, The Journal of Biological Chemistry.

[45]  E. Yilmaz,et al.  Grape seed extract supplement increases bone callus formation and mechanical strength: an animal study , 2019, Journal of Orthopaedic Surgery and Research.

[46]  Z. Ouyang,et al.  Proanthocyanidins inhibit osteoclast formation and function by inhibiting the NF-κB and JNK signaling pathways during osteoporosis treatment. , 2019, Biochemical and biophysical research communications.

[47]  N. Oršolić,et al.  The Beneficial Effect of Proanthocyanidins and Icariin on Biochemical Markers of Bone Turnover in Rats , 2018, International journal of molecular sciences.

[48]  H. Toker,et al.  Morphometric and histopathological evaluation of the effect of grape seed proanthocyanidin on alveolar bone loss in experimental diabetes and periodontitis , 2018, Journal of periodontal research.

[49]  N. Hasona,et al.  The impact of grape proanthocyanidin extract on dexamethasone-induced osteoporosis and electrolyte imbalance , 2018, Comparative Clinical Pathology.

[50]  Hongxia Zhang,et al.  Phytochemical Constituents, Health Benefits, and Industrial Applications of Grape Seeds: A Mini-Review , 2017, Antioxidants.

[51]  J. Lozano-Sánchez,et al.  Cocoa and Grape Seed Byproducts as a Source of Antioxidant and Anti-Inflammatory Proanthocyanidins , 2017, International journal of molecular sciences.

[52]  J. Serrano,et al.  Antioxidant effects of proanthocyanidin-rich natural extracts from grape seed and cupuassu on gastrointestinal mucosa. , 2016, Journal of the science of food and agriculture.

[53]  L. Tao,et al.  Aconine inhibits RANKL-induced osteoclast differentiation in RAW264.7 cells by suppressing NF-κB and NFATc1 activation and DC-STAMP expression , 2015, Acta Pharmacologica Sinica.

[54]  L. Mei,et al.  LRP4 in neuromuscular junction and bone development and diseases. , 2015, Bone.

[55]  Oluwadamilola O Olaku,et al.  The Role of Grape Seed Extract in the Treatment of Chemo/Radiotherapy Induced Toxicity: A Systematic Review of Preclinical Studies , 2015, Nutrition and cancer.

[56]  J. Ling,et al.  The preventive effect of grape seed extract on artificial enamel caries progression in a microbial biofilm-induced caries model. , 2014, Journal of dentistry.

[57]  F. Elmalı,et al.  Effect of Grape Seed Extract Upon Plasma Oxidative Status and Alveolar Bone, in Ligature Induced Periodontitis , 2013 .

[58]  Z. Lee,et al.  Grape-Seed Proanthocyanidin Extract as Suppressors of Bone Destruction in Inflammatory Autoimmune Arthritis , 2012, PloS one.

[59]  M. Valenti,et al.  Transcription Factor Runx2 and its Application to Bone Tissue Engineering , 2012, Stem Cell Reviews and Reports.

[60]  Jun Yu Li,et al.  Genetic variants in the SOX6 gene are associated with bone mineral density in both Caucasian and Chinese populations , 2012, Osteoporosis International.

[61]  Y. Joo,et al.  Grape seed proanthocyanidin extract ameliorates monosodium iodoacetate-induced osteoarthritis , 2011, Experimental & Molecular Medicine.

[62]  Xin Fu,et al.  Synergistic inhibition of endochondral bone formation by silencing Hif1α and Runx2 in trauma-induced heterotopic ossification. , 2011, Molecular therapy : the journal of the American Society of Gene Therapy.

[63]  H. Feringa,et al.  The effect of grape seed extract on cardiovascular risk markers: a meta-analysis of randomized controlled trials. , 2011, Journal of the American Dietetic Association.

[64]  N. Hettiarachchy,et al.  Green tea and grape seed extracts — Potential applications in food safety and quality , 2011 .

[65]  Sung-Hwan Park,et al.  Grape seed proanthocyanidin extract (GSPE) attenuates collagen-induced arthritis. , 2009, Immunology letters.

[66]  M. Cheng,et al.  Effects of grape seed proanthocyanidins extracts on AGEs and expression of bone morphogenetic protein-7 in diabetic rats. , 2008, Journal of nephrology.

[67]  M. Saito,et al.  Beneficial effects of grape seed extract on malondialdehyde-modified LDL. , 2007, Journal of nutritional science and vitaminology.

[68]  R. Dziak,et al.  Alveolar bone osteoblast differentiation and Runx2/Cbfa1 expression. , 2006, Archives of oral biology.

[69]  I. Tofani,et al.  Mechanical assessment of effects of grape seed proanthocyanidins extract on tibial bone diaphysis in rats. , 2005, Journal of musculoskeletal & neuronal interactions.

[70]  I. Tofani,et al.  Grape seed proanthocyanidins extract promotes bone formation in rat's mandibular condyle. , 2005, European journal of oral sciences.

[71]  I. Tofani,et al.  Effects of grape seed proanthocyanidins extract on rat mandibular condyle. , 2004, Journal of musculoskeletal & neuronal interactions.

[72]  I. Tofani,et al.  Mechanical evaluation of effect of grape seed proanthocyanidins extract on debilitated mandibles in rats. , 2004, Dental materials journal.

[73]  L. Norris,et al.  90-day oral toxicity study of a grape seed extract (IH636) in rats. , 2002, Journal of agricultural and food chemistry.

[74]  V. Lefebvre,et al.  Accelerated Up‐Regulation of L‐Sox5, Sox6, and Sox9 by BMP‐2 Gene Transfer During Murine Fracture Healing * , 2001, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[75]  C. Mortellaro,et al.  Clinical efficacy of grape seed extract as an adjuvant to scaling and root planing in treatment of periodontal pockets. , 2021, Journal of biological regulators and homeostatic agents.

[76]  Ş. Suciu,et al.  The effects of a grape seed extract on ligature induced – periodontitis in rats – an experimental study , 2021 .

[77]  M. M. Hassanane,et al.  Grape Seed Extract Alone or Combined with Atropine in Treatment of Malathion Induced Neuro- and Genotoxicity. , 2018, Journal of Nanoscience and Nanotechnology.

[78]  S. R.,et al.  Matrix metalloproteinase-13: A special focus on its regulation by signaling cascades and microRNAs in bone. , 2018, International Journal of Biological Macromolecules.

[79]  Wenchao Bi,et al.  Beneficial effect of grape seed proanthocyanidin extract in rabbits with steroid-induced osteonecrosis via protecting against oxidative stress and apoptosis , 2015, Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association.

[80]  I. Tofani,et al.  Mechanical evaluation of debilitated tibia diaphysis in rats during the growth period-Combination therapy with high-calcium diet and grape seed proanthocyanidin extract-:—Combination therapy with high-calcium diet and grape seed proanthocyanidin extract— , 2005 .

[81]  Jun Mitsui,et al.  Effect of grape seed proanthocyanidins extract on alteration of mechanical properties of metaphysis tibia bone in rats fed a low-calcium diet , 2005 .

[82]  I. Tofani,et al.  Beneficial effects of grape seed proanthocyanidins extract on formation of tibia bone in low-calcium feeding rats , 2004 .

[83]  I. Tofani,et al.  Effects of grape seed proanthocyanidins extract on mandibles in developing rats. , 2004, Oral diseases.