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Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

Exploring Effects and Mechanism of Ingredients of Herba Epimedii on Osteogenesis and Osteoclastogenesis In Vitro

Author(s): Lei Song, Yating Zhou, Lin Qu, Dongyu Wang, Xinyue Diao, Xiaoying Zhang, Yuxia Zhai, Yue Zhang, Yingli Yu and Kun Zhou*

Volume 27, Issue 19, 2024

Published on: 07 November, 2023

Page: [2824 - 2837] Pages: 14

DOI: 10.2174/0113862073243559231023065934

Price: $65

Abstract

Background: Herba Epimedii, a commonly used traditional herb, has been proven effective in ameliorating osteoporosis. However, the active ingredients and potential mechanism need further exploration.

Objective: To screen active ingredients of Herba Epimedii with the effect of ameliorating osteoporosis and to explore their potential mechanisms.

Methods: TCMSP and Swiss Target Prediction were applied to collect the ingredients of Herba Epimedii and their targets. UniProt, GeneCards, TTD, DisGeNET, and OMIM were adopted to search osteoporosis-related genes. STRING and DAVID were used to perform enrichment analysis. Effects of screened ingredients were evaluated on MC3T3-E1 cells and RAW264.7 cells, respectively.

Results: Eleven ingredients were screened by Network Pharmacology. They exerted a promoting effect on MC3T3-E1 cells (10-9-10-5 M). The ingredients didn’t significantly affect ALP activity and osteoblastogenesis-related genes. Baohuoside 1, Sagittatoside B, Chlorogenic acid, Cryptochlorogenic acid, and Neochlorogenic acid significantly increased calcium depositions. The ingredients didn’t exhibit a dose-dependent inhibition or promotion on RAW264.7 cells. Baohuoside 1, Sagittatoside B, Neochlorogenic acid, Cryptochlorogenic acid, Icariin, Epimedin A, Chlorogenic acid, Sagittatoside A, and Epimedin C suppressed the level of TRACP. Baohuoside 1, Sagittatoside B, Cryptochlorogenic acid, Neochlorogenic acid, Chlorogenic acid, Sagittatoside A, and Icariin decreased the number of multinucleated osteoclastic cells. Baohuoside 1, Sagittatoside B, and Cryptochlorogenic acid could significantly inhibit MMP-9 expression.

Conclusion: Neochlorogenic acid, Sagittatoside B, Chlorogenic acid, and Cryptochlorogenic acid promoted MC3T3-E1 differentiation, among which Neochlorogenic acid showed significant promotion in viability, mineralization, and OPN expression. Baohuoside 1, Sagittatoside B, Cryptochlorogenic acid, Neochlorogenic acid, Chlorogenic acid, and Icariin inhibited RAW264.7 differentiation, among which Baohuoside 1 showed significant inhibition on TRACP, multinucleated osteoclastic cells number and MPP-9 expression. The mechanism might relate to the FoxO signaling pathway, MAPK signaling pathway, and TNF signaling pathway.

Keywords: Osteoporosis, osteoblasts, osteoclasts, network pharmacology, herba, epimedin, osteogenesis.

Graphical Abstract
[1]
Noh, J.Y.; Yang, Y.; Jung, H. Molecular mechanisms and emerging therapeutics for osteoporosis. Int. J. Mol. Sci., 2020, 21(20), 7623.
[http://dx.doi.org/10.3390/ijms21207623] [PMID: 33076329]
[2]
Johnell, O.; Kanis, J.A. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos. Int., 2006, 17(12), 1726-1733.
[http://dx.doi.org/10.1007/s00198-006-0172-4] [PMID: 16983459]
[3]
Jeremiah, M.P.; Unwin, B.K.; Greenawald, M.H.; Casiano, V.E. Diagnosis and management of osteoporosis. Am. Fam. Physician, 2015, 92(4), 261-268.
[PMID: 26280231]
[4]
Cosman, F.; de Beur, S.J.; LeBoff, M.S.; Lewiecki, E.M.; Tanner, B.; Randall, S.; Lindsay, R. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos. Int., 2014, 25(10), 2359-2381.
[http://dx.doi.org/10.1007/s00198-014-2794-2] [PMID: 25182228]
[5]
Wu, L.; Ling, Z.; Feng, X.; Mao, C.; Xu, Z. Herb medicines against osteoporosis: Active compounds & relevant biological mechanisms. Curr. Top. Med. Chem., 2017, 17(15), 1670-1691.
[http://dx.doi.org/10.2174/1568026617666161116141033] [PMID: 27848901]
[6]
Wang, L.; Li, Y.; Guo, Y.; Ma, R.; Fu, M.; Niu, J.; Gao, S.; Zhang, D. Herba epimedii: An ancient chinese herbal medicine in the prevention and treatment of osteoporosis. Curr. Pharm. Des., 2015, 22(3), 328-349.
[http://dx.doi.org/10.2174/1381612822666151112145907] [PMID: 26561074]
[7]
Indran, I.R.; Liang, R.L.Z.; Min, T.E.; Yong, E.L. Preclinical studies and clinical evaluation of compounds from the genus Epimedium for osteoporosis and bone health. Pharmacol. Ther., 2016, 162, 188-205.
[http://dx.doi.org/10.1016/j.pharmthera.2016.01.015] [PMID: 26820757]
[8]
Wu, H.; Lien, E.J.; Lien, L.L. Chemical and pharmacological investigations of Epimedium species: A survey. Prog. Drug Res., 2003, 60, 1-57.
[http://dx.doi.org/10.1007/978-3-0348-8012-1_1] [PMID: 12790338]
[9]
Li, S.; Fan, T.P.; Jia, W.; Lu, A.; Zhang, W. Network pharmacology in traditional chinese medicine. Evid. Based Complement. Alternat. Med., 2014, 2014, 138460.
[PMID: 24707305]
[10]
Li, S.; Zhang, B. Traditional Chinese medicine network pharmacology: theory, methodology and application. Chin. J. Nat. Med., 2013, 11(2), 110-120.
[http://dx.doi.org/10.1016/S1875-5364(13)60037-0] [PMID: 23787177]
[11]
Gao, Y.; Patil, S.; Jia, J. The development of molecular biology of osteoporosis. Int. J. Mol. Sci., 2021, 22(15), 8182.
[http://dx.doi.org/10.3390/ijms22158182] [PMID: 34360948]
[12]
Kim, B.; Lee, K.Y.; Park, B. Icariin abrogates osteoclast formation through the regulation of the RANKL-mediated TRAF6/NF-κB/ERK signaling pathway in Raw264.7 cells. Phytomedicine, 2018, 51, 181-190.
[http://dx.doi.org/10.1016/j.phymed.2018.06.020] [PMID: 30466615]
[13]
Kong, L.; Smith, W.; Hao, D. Overview of RAW264.7 for osteoclastogensis study: Phenotype and stimuli. J. Cell. Mol. Med., 2019, 23(5), 3077-3087.
[http://dx.doi.org/10.1111/jcmm.14277] [PMID: 30892789]
[14]
Zhai, Y.K.; Guo, X.; Pan, Y.L.; Niu, Y.B.; Li, C.R.; Wu, X.L.; Mel, Q.B. A systematic review of the efficacy and pharmacological profile of Herba Epimedii in osteoporosis therapy. Pharmazie, 2013, 68(9), 713-722.
[PMID: 24147339]
[15]
Luo, T.; Lu, Y.; Yan, S.; Xiao, X.; Rong, X.; Guo, J. Network pharmacology in research of chinese medicine formula: Methodology, application and prospective. Chin. J. Integr. Med., 2020, 26(1), 72-80.
[http://dx.doi.org/10.1007/s11655-019-3064-0] [PMID: 30941682]
[16]
Shen, P.; Guo, B.L.; Gong, Y.; Hong, D.Y.Q.; Hong, Y.; Yong, E.L. Taxonomic, genetic, chemical and estrogenic characteristics of Epimedium species. Phytochemistry, 2007, 68(10), 1448-1458.
[http://dx.doi.org/10.1016/j.phytochem.2007.03.001] [PMID: 17434191]
[17]
Li, H.; Xiao, Z.; Quarles, L.D.; Li, W. Osteoporosis: Mechanism, molecular target and current status on drug development. Curr. Med. Chem., 2021, 28(8), 1489-1507.
[http://dx.doi.org/10.2174/1875533XMTA1hNTIy2] [PMID: 32223730]
[18]
Chatakun, P.; Núñez-Toldrà, R.; Díaz López, E.J.; Gil-Recio, C.; Martínez-Sarrà, E.; Hernández-Alfaro, F.; Ferrés-Padró, E.; Giner-Tarrida, L.; Atari, M. The effect of five proteins on stem cells used for osteoblast differentiation and proliferation: a current review of the literature. Cell. Mol. Life Sci., 2014, 71(1), 113-142.
[http://dx.doi.org/10.1007/s00018-013-1326-0] [PMID: 23568025]
[19]
Reddi, S.; Shanmugam, V.P.; Tanedjeu, K.S.; Kapila, S.; Kapila, R. Effect of buffalo casein-derived novel bioactive peptides on osteoblast differentiation. Eur. J. Nutr., 2018, 57(2), 593-605.
[http://dx.doi.org/10.1007/s00394-016-1346-2] [PMID: 27868152]
[20]
Junrui, P.; Bingyun, L.; Yanhui, G.; Xu, J.; Darko, G.M.; Dianjun, S. Relationship between fluoride exposure and osteoclast markers during RANKL-induced osteoclast differentiation. Environ. Toxicol. Pharmacol., 2016, 46, 241-245.
[http://dx.doi.org/10.1016/j.etap.2016.08.001] [PMID: 27500448]
[21]
Tortelli, F.; Pujic, N.; Liu, Y.; Laroche, N.; Vico, L.; Cancedda, R. Osteoblast and osteoclast differentiation in an in vitro three-dimensional model of bone. Tissue Eng. Part A, 2009, 15(9), 2373-2383.
[http://dx.doi.org/10.1089/ten.tea.2008.0501] [PMID: 19292676]
[22]
Zheng, X.; Zhang, Y.; Guo, S.; Zhang, W.; Wang, J.; Lin, Y. Dynamic expression of matrix metalloproteinases 2, 9 and 13 in ovariectomy-induced osteoporosis rats. Exp. Ther. Med., 2018, 16(3), 1807-1813.
[http://dx.doi.org/10.3892/etm.2018.6356] [PMID: 30186405]
[23]
Ma, X.; Su, P.; Yin, C.; Lin, X.; Wang, X.; Gao, Y.; Patil, S.; War, A.R.; Qadir, A.; Tian, Y.; Qian, A. The roles of FoxO transcription factors in regulation of bone cells function. Int. J. Mol. Sci., 2020, 21(3), 692.
[http://dx.doi.org/10.3390/ijms21030692] [PMID: 31973091]
[24]
Wu, J.; Cai, P.; Lu, Z.; Zhang, Z.; He, X.; Zhu, B.; Zheng, L.; Zhao, J. Identification of potential specific biomarkers and key signaling pathways between osteogenic and adipogenic differentiation of hBMSCs for osteoporosis therapy. J. Orthop. Surg. Res., 2020, 15(1), 437.
[http://dx.doi.org/10.1186/s13018-020-01965-3] [PMID: 32967719]
[25]
Xiao, L.; Zhong, M.; Huang, Y.; Zhu, J.; Tang, W.; Li, D.; Shi, J.; Lu, A.; Yang, H.; Geng, D.; Li, H.; Wang, Z. Puerarin alleviates osteoporosis in the ovariectomy-induced mice by suppressing osteoclastogenesis via inhibition of TRAF6/ROS-dependent MAPK/NF-κB signaling pathways. Aging, 2020, 12(21), 21706-21729.
[http://dx.doi.org/10.18632/aging.103976] [PMID: 33176281]
[26]
He, G.; Ma, R. Overview of molecular mechanisms involved in herbal compounds for inhibiting osteoclastogenesis from macrophage linage RAW264.7. Curr. Stem Cell Res. Ther., 2020, 15(7), 570-578.
[http://dx.doi.org/10.2174/1574888X14666190703144917] [PMID: 31269885]
[27]
Kitaura, H.; Marahleh, A.; Ohori, F.; Noguchi, T.; Shen, W.R.; Qi, J.; Nara, Y.; Pramusita, A.; Kinjo, R.; Mizoguchi, I. Osteocyte-Related cytokines regulate osteoclast formation and bone resorption. Int. J. Mol. Sci., 2020, 21(14), 5169.
[http://dx.doi.org/10.3390/ijms21145169] [PMID: 32708317]
[28]
Gu, H.; Huang, Z.; Chen, G.; Zhou, K.; Zhang, Y.; Chen, J.; Xu, J.; Yin, X. Network and pathway-based analyses of genes associated with osteoporosis. Medicine, 2020, 99(8), e19120.
[http://dx.doi.org/10.1097/MD.0000000000019120] [PMID: 32080087]
[29]
Liu, M.M.; Dong, R.; Hua, Z.; Lv, N.N.; Ma, Y.; Huang, G.C.; Cheng, J.; Xu, H.Y. Therapeutic potential of Liuwei Dihuang pill against KDM7A and Wnt/β-catenin signaling pathway in diabetic nephropathy-related osteoporosis. Biosci. Rep., 2020, 40(9), BSR20201778.
[http://dx.doi.org/10.1042/BSR20201778] [PMID: 32914833]
[30]
Karthik, V.; Guntur, A.R. Energy metabolism of osteocytes. Curr. Osteoporos. Rep., 2021, 19(4), 444-451.
[http://dx.doi.org/10.1007/s11914-021-00688-6] [PMID: 34117625]
[31]
Song, L.; Bi, Y.; Zhang, P.; Yuan, X.; Liu, Y.; Zhang, Y.; Huang, J.; Zhou, K. Optimization of the time window of interest in ovariectomized imprinting control region mice for antiosteoporosis research. BioMed Res. Int., 2017, 2017, 1-10.
[http://dx.doi.org/10.1155/2017/8417814] [PMID: 29119115]
[32]
Yousefzadeh, N.; Kashfi, K.; Jeddi, S.; Ghasemi, A. Ovariectomized rat model of osteoporosis: A practical guide. EXCLI J., 2020, 19, 89-107.
[PMID: 32038119]

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