Research Progress of Icariin in the Treatment of Osteoporosis

Abstract

Abstract: Osteoporosis is a chronic disease characterized by bone loss and structural damage of bone tissue. It has a high incidence rate in middle-aged and elderly people, especially in postmenopausal women. The disease seriously threatens the physical and mental health of patients and brings heavy burden to their families. Because of its side effects and high price, the use of drugs for the treatment of osteoporosis has been affected. Epimedium, a traditional Chinese medicine, is safe to use and easy to obtain. It is widely used in the treatment of orthopedic diseases. Previous studies have confirmed that icariin, the main component of epimedium, has a good application prospect in the treatment of osteoporosis. It can promote the proliferation and differentiation of osteoblasts and BMSCs by up regulating the expression of osteogenic markers ALP, RUNX2, BMP-2, etc., and achieve bone regeneration and bone formation. In this process, Wnt/ β- Catenin, OPG/RANK/RANKL and other signaling pathways play an important role. Based on this, this article reviews the effect and possible mechanism of icariin on osteoporosis.

Key words: icariin, osteoporosis, osteogenic markers, Wnt/β-catenin signaling pathway, OPG/RANK/RANKL signaling pathway

CLC Number:

ZHU Yuan-chao, QIN Hao-tian, LIU Su, CHEN Yi-xiao, ZHANG Geng, LIAO Shuai, WENG Jian, YU Fei, ZENG Hui. Research Progress of Icariin in the Treatment of Osteoporosis[J]. ZHONGHUA YANGSHENG BAOJIAN, 2023, 41(4): 58-62.

References

[1] NOH J Y, YANG Y, JUNG H.Molecular Mechanisms and Emerging Therapeutics for Osteoporosis[J]. Int J Mol Sci,2020,21(20):7623.
[2] ASPRAY T J, HILL T R.Osteoporosis and the Ageing Skeleton[J]. Subcell Biochem,2019,91:453-476.
[3] ZHAO X L, FENG Y X, PENG Y.Prevention and Treatment of Osteoporosis with Chinese Herbal Medicines[J]. Chinese Herbal Medicines, 2012,4(4):265-270.
[4] 严红梅,张振海,孙娥,等.中药治疗骨质疏松症的研究进展[J].中草药,2014,45(8):1174-1178.
[5] 裴利宽,郭宝林.近10年淫羊藿药材及饮片研究进展[J].中国中药杂志,2007(6):466-471.
[6] 傅淑平,杨丽,洪浩,等.淫羊藿苷促SD大鼠骨髓间充质干细胞骨向分化作用的实验研究[J].中国中西医结合杂志,2015,35(7):839-846.
[7] LIANG W, LIN M, LI X, et al.Icariin promotes bone formation via the BMP-2/Smad4 signal transduction pathway in the hFOB 1.19 human osteoblastic cell line[J]. Int J Mol Med,2012,30(4):889-895.
[8] LI M, ZHANG N D, WANG Y, et al.Coordinate regulatory osteogenesis effects of icariin, timosaponin B II and ferulic acid from traditional Chinese medicine formulas on UMR-106 osteoblastic cells and osteoblasts in neonatal rat calvaria cultures[J]. J Ethnopharmacol,2016,185:120-131.
[9] YANG J, LIU Y, HE L, et al.Icariin conjugated hyaluronic acid/collagen hydrogel for osteochondral interface restoration[J]. Acta Biomater, 2018,74:156-167.
[10] SUN X, WEI J, LYU J, et al.Bone-targeting drug delivery system of biomineral-binding liposomes loaded with icariin enhances the treatment for osteoporosis[J]. J Nanobiotechnology,2019,17(1):10.
[11] SONG Y, MA A, NING J, et al.Loading icariin on titanium surfaces by phase-transited lysozyme priming and layer-by-layer self-assembly of hyaluronic acid/chitosan to improve surface osteogenesis ability[J]. Int J Nanomedicine,2018,13:6751-6767.
[12] HUANG X, WANG X, ZHANG Y, et al.Absorption and utilisation of epimedin C and icariin from Epimedii herba, and the regulatory mechanism via the BMP2/ Runx2 signalling pathway[J]. Biomed Pharmacother. 2019,118:109345.
[13] YUE J, YU H, LIU P, et al.Preliminary study of icariin indicating prevention of steroid-induced osteonecrosis of femoral head by regulating abnormal expression of miRNA-335 and protecting the functions of bone microvascular endothelial cells in rats[J]. Gene,2021,766:145128.
[14] JING X, DU T, CHEN K, et al.Icariin protects against iron overload-induced bone loss via suppressing oxidative stress[J]. J Cell Physiol, 2019,234(7):10123-10137.
[15] SUN J B, WANG Z, AN W J.Protection of Icariin Against Hydrogen Peroxide-Induced MC3T3-E1 Cell Oxidative Damage[J]. Orthop Surg, 2021,13(2):632-640.
[16] CHOI S, NOH S H, LIM C O, et al.Icariin-Functionalized Nanodiamonds to Enhance Osteogenic Capacity In Vitro[J]. Nanomaterials (Basel), 2020,10(10):2071.
[17] ZHAO R, BU W, CHEN Y.Icariin Treatment Enhanced the Skeletal Response to Exercise in Estrogen-Deficient Rats[J]. Int J Environ Res Public Health,2019,16(19):3779.
[18] YANG Y, NIAN H, TANG X, et al.Effects of the combined Herba Epimedii and Fructus Ligustri Lucidi on bone turnover and TGF-β1/Smads pathway in GIOP rats[J]. JOURNAL OF ETHNOPHARMACOLOGY, 2017,201:91-99.
[19] HUANG Z, WEI H, WANG X, et al.Icariin promotes osteogenic differentiation of BMSCs by upregulating BMAL1 expression via BMP signaling[J]. Mol Med Rep,2020,21(3):1590-1596.
[20] LI M, ZHANG C, MAO Y, et al.A Cell-Engineered Small Intestinal Submucosa-Based Bone Mimetic Construct for Bone Regeneration[J]. Tissue Eng Part A,2018,24(13-14):1099-1111.
[21] ZHANG X, LIN X, LIU T, et al.Osteogenic Enhancement Between Icariin and Bone Morphogenetic Protein 2: A Potential Osteogenic Compound for Bone Tissue Engineering[J]. Front Pharmacol,2019,10:201.
[22] LIAN F, ZHAO C, QU J, et al.Icariin attenuates titanium particle-induced inhibition of osteogenic differentiation and matrix mineralization via miR-21-5p[J]. Cell Biol Int,2018,42(8):931-939.
[23] WANG Y, WANG R, ZHANG F.Icariin promotes the proliferation and differentiation of osteoblasts from the rat mandible by the Wnt/β-catenin signalling pathway[J]. Mol Med Rep,2018,18(3):3445-3450.
[24] LIU Y, HUANG L, HAO B, et al.Use of an Osteoblast Overload Damage Model to Probe the Effect of Icariin on the Proliferation, Differentiation and Mineralization of MC3T3-E1 Cells through the Wnt/β-Catenin Signalling Pathway[J]. Cell Physiol Biochem,2017,41(4):1605-1615.
[25] BREATHWAITE E, WEAVER J, ODANGA J, et al.3D Bioprinted Osteogenic Tissue Models for In Vitro Drug Screening[J]. Molecules, 2020,25(15):3442.
[26] WEI Q, HE M, CHEN M, et al.Icariin stimulates osteogenic differentiation of rat bone marrow stromal stem cells by increasing TAZ expression[J]. Biomed Pharmacother,2017,91:581-589.
[27] WEI Q, WANG B, HU H, et al.Icaritin promotes the osteogenesis of bone marrow mesenchymal stem cells via the regulation of sclerostin expression[J]. Int J Mol Med,2020,45(3):816-824.
[28] HU J, MAO Z, HE S, et al.Icariin protects against glucocorticoid induced osteoporosis, increases the expression of the bone enhancer DEC1 and modulates the PI3K/Akt/GSK3β/β-catenin integrated signaling pathway[J]. Biochem Pharmacol,2017,136:109-121.
[29] XU Y, JIANG Y, JIA B, et al.Icariin stimulates osteogenesis and suppresses adipogenesis of human bone mesenchymal stem cells via miR-23a-mediated activation of the Wnt/β-catenin signaling pathway[J]. Phytomedicine,2021,85:153485.
[30] XIE Y, SUN W, YAN F, et al.Icariin-loaded porous scaffolds for bone regeneration through the regulation of the coupling process of osteogenesis and osteoclastic activity[J]. Int J Nanomedicine,2019,14:6019-6033.
[31] SUN K, MEI W, MO S, et al.Lead exposure inhibits osteoblastic differentiation and inactivates the canonical Wnt signal and recovery by icaritin in MC3T3-E1 subclone 14 cells[J]. Chem Biol Interact, 2019,303:7-13.
[32] ZHANG X Y, CHEN Y P, ZHANG C, et al.Icariin Accelerates Fracture Healing via Activation of the WNT1/β-catenin Osteogenic Signaling Pathway[J]. Curr Pharm Biotechnol,2020,21(15):1645-1653.
[33] XIE L, LIU N, XIAO Y, et al.In Vitro and In Vivo Osteogenesis Induced by Icariin and Bone Morphogenetic Protein-2: A Dynamic Observation[J]. Front Pharmacol,2020,11:1058.
[34] HE J, FENG X, WANG J, et al.Icariin prevents bone loss by inhibiting bone resorption and stabilizing bone biological apatite in a hindlimb suspension rodent model[J]. ACTA PHARMACOLOGICA SINICA,2018,39(11):1760-1767.
[35] QI S, HE J, ZHENG H, et al.Icariin Prevents Diabetes-Induced Bone Loss in Rats by Reducing Blood Glucose and Suppressing Bone Turnover[J]. Molecules (Basel, Switzerland),2019,24(10):1871.
[36] SUN L J, LI C, WEN X H, et al.Icariin Stimulates hFOB 1.19 Osteoblast Proliferation and Differentiation via OPG/RANKL Mediated by the Estrogen Receptor[J]. Curr Pharm Biotechnol,2021,22(1):168-175.
[37] ZHANG Y, HAN B, WEI Y, et al.Icariin Promotes Fracture Healing in Ovariectomized Rats[J]. Med Sci Monit,2020,26:e924554.
[38] LONG Z, WU J, XIANG W, et al.Exploring the Mechanism of Icariin in Osteoporosis Based on a Network Pharmacology Strategy[J]. Med Sci Monit, 2020,26:e924699.