A Scoping Review of the Skeletal Effects of Naringenin

Overview

Journal Nutrients

Date 2022 Nov 26

PMID 36432535

Authors

Muhamed Lahtif Nor Muhamad

Sophia Ogechi Ekeuku

Sok-Kuan Wong

Kok-Yong Chin

Affiliations

Soon will be listed here.

Abstract

Background: Osteoporosis is caused by the deterioration of bone density and microstructure, resulting in increased fracture risk. It transpires due to an imbalanced skeletal remodelling process favouring bone resorption. Various natural compounds can positively influence the skeletal remodelling process, of which naringenin is a candidate. Naringenin is an anti-inflammatory and antioxidant compound found in citrus fruits and grapefruit. This systematic review aims to present an overview of the available evidence on the skeletal protective effects of naringenin.

Method: A systematic literature search was conducted using the PubMed and Scopus databases in August 2022. Original research articles using cells, animals, or humans to investigate the bone protective effects of naringenin were included.

Results: Sixteen eligible articles were included in this review. The existing evidence suggested that naringenin enhanced osteoblastogenesis and bone formation through BMP-2/p38MAPK/Runx2/Osx, SDF-1/CXCR4, and PI3K/Akt/-Fos/-Jun/AP-1 signalling pathways. Naringenin also inhibited osteoclastogenesis and bone resorption by inhibiting inflammation and the RANKL pathway.

Conclusions: Naringenin enhances bone formation while suppressing bone resorption, thus achieving its skeletal protective effects. It could be incorporated into the diet through fruit intake or supplements to prevent bone loss.

Citing Articles

Epigenetic Mechanisms in Osteoporosis: Exploring the Power of mA RNA Modification.

Tian S, Song Y, Guo L, Zhao H, Bai M, Miao M J Cell Mol Med. 2025; 29(1):e70344.

PMID: 39779466 PMC: 11710941. DOI: 10.1111/jcmm.70344.

Osteoporosis: Causes, Mechanisms, Treatment and Prevention: Role of Dietary Compounds.

Stromsnes K, Martinez Fajardo C, Soto-Rodriguez S, Kajander E, Lupu R, Pozo-Rodriguez M Pharmaceuticals (Basel). 2025; 17(12.

PMID: 39770539 PMC: 11679375. DOI: 10.3390/ph17121697.

Mechanistic Exploration of Roxb. in Osteoarthritis: Insights from Network Pharmacology, Molecular Docking, and In Vitro Validation.

Ilyas S, Baek C, Manan A, Choi Y, Jo H, Lee D Pharmaceuticals (Basel). 2024; 17(10).

PMID: 39458926 PMC: 11510151. DOI: 10.3390/ph17101285.

Crebanine mitigates glucocorticoid-induced osteonecrosis of the femoral head by restoring bone remodelling homeostasis via attenuating oxidative stress.

Dong S, Ge J, Meng Q, Yuan T, Wang Y, Li Y J Cell Mol Med. 2024; 28(16):e70044.

PMID: 39205463 PMC: 11358393. DOI: 10.1111/jcmm.70044.

Association between systemic inflammatory response index and bone turnover markers in Chinese patients with osteoporotic fractures: a retrospective cross-sectional study.

Zhou P, Lu K, Li C, Xu M, Ye Y, Shan H Front Med (Lausanne). 2024; 11:1404152.

PMID: 39055700 PMC: 11269153. DOI: 10.3389/fmed.2024.1404152.

References

Xiao G, Gopalakrishnan R, Jiang D, Reith E, Benson M, Franceschi R . Bone morphogenetic proteins, extracellular matrix, and mitogen-activated protein kinase signaling pathways are required for osteoblast-specific gene expression and differentiation in MC3T3-E1 cells. J Bone Miner Res. 2002; 17(1):101-10. DOI: 10.1359/jbmr.2002.17.1.101. View

Wei M, Yang Z, Li P, Zhang Y, Sse W . Anti-osteoporosis activity of naringin in the retinoic acid-induced osteoporosis model. Am J Chin Med. 2007; 35(4):663-7. DOI: 10.1142/S0192415X07005156. View

Bhia M, Motallebi M, Abadi B, Zarepour A, Pereira-Silva M, Saremnejad F . Naringenin Nano-Delivery Systems and Their Therapeutic Applications. Pharmaceutics. 2021; 13(2). PMC: 7926828. DOI: 10.3390/pharmaceutics13020291. View

Yao J, Ma S, Feng W, Wei Y, Lu H, Zhong G . Tanshinone IIA protects against polyethylene particle-induced osteolysis response in a mouse calvarial model. Int J Clin Exp Pathol. 2020; 11(9):4461-4471. PMC: 6962947. View

Xu J, Chen Y, Liu Y, Zhang J, Kang Q, Ho K . Effect of SDF-1/Cxcr4 Signaling Antagonist AMD3100 on Bone Mineralization in Distraction Osteogenesis. Calcif Tissue Int. 2017; 100(6):641-652. DOI: 10.1007/s00223-017-0249-4. View

Yang L, Ma S, Zhou S, Chen W, Yuan M, Yin Y . Preparation and characterization of inclusion complexes of naringenin with β-cyclodextrin or its derivative. Carbohydr Polym. 2013; 98(1):861-9. DOI: 10.1016/j.carbpol.2013.07.010. View

Swarnkar G, Sharan K, Siddiqui J, Mishra J, Khan K, Khan M . A naturally occurring naringenin derivative exerts potent bone anabolic effects by mimicking oestrogen action on osteoblasts. Br J Pharmacol. 2011; 165(5):1526-42. PMC: 3372735. DOI: 10.1111/j.1476-5381.2011.01637.x. View

Baber R, Panay N, Fenton A . 2016 IMS Recommendations on women's midlife health and menopause hormone therapy. Climacteric. 2016; 19(2):109-50. DOI: 10.3109/13697137.2015.1129166. View

Shulman M, Cohen M, Soto-Gutierrez A, Yagi H, Wang H, Goldwasser J . Enhancement of naringenin bioavailability by complexation with hydroxypropyl-β-cyclodextrin. [corrected]. PLoS One. 2011; 6(4):e18033. PMC: 3071816. DOI: 10.1371/journal.pone.0018033. View

10.

Cosman F, de Beur S, LeBoff M, Lewiecki E, Tanner B, Randall S . Clinician's Guide to Prevention and Treatment of Osteoporosis. Osteoporos Int. 2014; 25(10):2359-81. PMC: 4176573. DOI: 10.1007/s00198-014-2794-2. View

11.

La V, Tanabe S, Grenier D . Naringenin inhibits human osteoclastogenesis and osteoclastic bone resorption. J Periodontal Res. 2008; 44(2):193-8. DOI: 10.1111/j.1600-0765.2008.01107.x. View

12.

Takayanagi H, Kim S, Koga T, Nishina H, Isshiki M, Yoshida H . Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Dev Cell. 2002; 3(6):889-901. DOI: 10.1016/s1534-5807(02)00369-6. View

13.

Luan J, Cui Y, Zhang Y, Zhou X, Zhang G, Han J . Effect of CXCR4 inhibitor AMD3100 on alkaline phosphatase activity and mineralization in osteoblastic MC3T3-E1 cells. Biosci Trends. 2012; 6(2):63-9. View

14.

Mun S, Park P, Park-Min K . The M-CSF receptor in osteoclasts and beyond. Exp Mol Med. 2020; 52(8):1239-1254. PMC: 8080670. DOI: 10.1038/s12276-020-0484-z. View

15.

Bali V, Ali M, Ali J . Nanocarrier for the enhanced bioavailability of a cardiovascular agent: in vitro, pharmacodynamic, pharmacokinetic and stability assessment. Int J Pharm. 2010; 403(1-2):46-56. DOI: 10.1016/j.ijpharm.2010.10.018. View

16.

Chung T, Li S, Lin C, Tsai S . Antinociceptive and anti-inflammatory effects of the citrus flavanone naringenin. Tzu Chi Med J. 2019; 31(2):81-85. PMC: 6450145. DOI: 10.4103/tcmj.tcmj_103_18. View

17.

Wang Y, Bai S, Cheng Q, Zeng Y, Xu X, Guan G . Naringenin promotes SDF-1/CXCR4 signaling pathway in BMSCs osteogenic differentiation. Folia Histochem Cytobiol. 2021; 59(1):66-73. DOI: 10.5603/FHC.a2021.0008. View

18.

Kumar R, Abraham A . PVP- coated naringenin nanoparticles for biomedical applications - In vivo toxicological evaluations. Chem Biol Interact. 2016; 257:110-8. DOI: 10.1016/j.cbi.2016.07.012. View

19.

Kaczmarczyk-Sedlak I, Wojnar W, Zych M, Ozimina-Kaminska E, Bonka A . EFFECT OF DIETARY FLAVONOID NARINGENIN ON BONES IN RATS WITH OVARIECTOMY-INDUCED OSTEOPOROSIS. Acta Pol Pharm. 2018; 73(4):1073-1081. View

20.

Tanaka Y, Nakayamada S, Okada Y . Osteoblasts and osteoclasts in bone remodeling and inflammation. Curr Drug Targets Inflamm Allergy. 2005; 4(3):325-8. DOI: 10.2174/1568010054022015. View