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Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

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

Research Article

Total Flavonoids from Rhizoma Drynariae (Gusuibu) Alleviates Diabetic Osteoporosis by Activating BMP2/Smad Signaling Pathway

Author(s): Xin Hua Fang, Guo Er Zhou and Na Lin*

Volume 26, Issue 13, 2023

Published on: 28 March, 2023

Page: [2401 - 2409] Pages: 9

DOI: 10.2174/1386207326666230223165730

Price: $65

Abstract

Introduction: Diabetic osteoporosis (DOP) is a widespread public health problem. The flavonoids of Rhizoma Drynariae (RDF) have a clear preventive and therapeutic effect on osteoporosis (OP), but it is not yet clear whether RDF has an anti-DOP and whether its mechanism is related to the activation of the BMP2/Smad signaling pathway. The current study aimed to study this effect of RDF in DOP rats and the possible involvement of the BMP2/Smad signaling pathway activation.

Methods: Following intragastric administration of RDF for 12 weeks, the body weight, blood glucose, and the bone histopathological changes detected by hematoxylin-eosin (H&E) and calcein staining were monitored, while bone parameters were regularly assessed from observations made by micro-CT. At the end of the experiment, the expression of Bmp2, Bmpr1a, Runx2, and Smad4/5 genes was detected by real-time PCR (RT-PCR). Meanwhile, western blotting or immunohistochemical staining monitored the protein expressions of BMP2, RUNX2, and SMAD5 in the bone.

Results: The results firstly indicated that RDF significantly alleviated the signs and symptoms of DOP, which manifested as improved body weight and blood glucose. As obtained from the results of histopathology and micro-CT, RDF could promote the formation of bone trabeculae and alter several the bone microstructure parameters, including an increase in the bone volume/total volume (BV/TV), connective density (Conn-Dens), and trabecular bone number (Tb.N), as well as a decrease in the trabecular spacing (Tb.Sp). The western blotting analysis and RT-PCR results also confirmed that RDF could markedly increase the mRNA expression levels of Bmp2, Bmpr1α, Smad4, Runx2, and Smad5 in the bone, as well as the corresponding protein expression levels of BMP2, RUNX2, and SMAD5. These results reveal that RDF can activate the BMP2/Smad signaling pathway, thus promoting bone remodeling in DOP rats.

Conclusion: RDF can increase bone trabeculae and bone mineral density by promoting bone formation and inhibiting bone absorption, thereby playing a role in improving DOP. This effect is related to the regulation of the BMP2/Smad signaling pathway.

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[1]
Peng, S.; Shi, S.; Tao, G.; Li, Y.; Xiao, D.; Wang, L.; He, Q.; Cai, X.; Xiao, J. JKAMP inhibits the osteogenic capacity of adipose-derived stem cells in diabetic osteoporosis by modulating the Wnt signaling pathway through intragenic DNA methylation. Stem Cell Res. Ther., 2021, 12(1), 120.
[http://dx.doi.org/10.1186/s13287-021-02163-6] [PMID: 33579371]
[2]
Albright, F.; Reifenstein, E. Bone development in diabetic children: A roentgen study. Am. J. Med., 1948, 174, 313-319.
[3]
Si, Y.; Wang, C.; Guo, Y.; Yin, H.; Ma, Y. Prevalence of osteoporosis in patients with type 2 diabetes mellitus in the Chinese mainland. Medicine, 2020, 99(16), e19762.
[http://dx.doi.org/10.1097/MD.0000000000019762] [PMID: 32311979]
[4]
Karim, L.; Bouxsein, M.L. Effect of type 2 diabetes-related non-enzymatic glycation on bone biomechanical properties. Bone, 2016, 82(1), 21-27.
[http://dx.doi.org/10.1016/j.bone.2015.07.028] [PMID: 26211993]
[5]
Stapleton, M.; Sawamoto, K.; Alméciga-Díaz, C.; Mackenzie, W.; Mason, R.; Orii, T.; Tomatsu, S. Development of bone targeting drugs. Int. J. Mol. Sci., 2017, 18(7), 1345.
[http://dx.doi.org/10.3390/ijms18071345] [PMID: 28644392]
[6]
Xuan, Y.; Wang, J.; Zhang, X.; Wang, J.; Li, J.; Liu, Q.; Lu, G.; Xiao, M.; Gao, T.; Guo, Y.; Cao, C.; Chen, O.; Wang, K.; Tang, Y.; Gu, J. Resveratrol attenuates high glucose-induced osteoblast dysfunction via AKT/GSK3β/FYN-mediated NRF2 activation. Front. Pharmacol., 2022, 13, 862618.
[http://dx.doi.org/10.3389/fphar.2022.862618] [PMID: 35677434]
[7]
Yan, C.P. Wang, X.K.; Jiang, K.; Yin, C.; Xiang, C.; Wang, Y.; Pu, C.; Chen, L.; Li, Y.L. β-ecdysterone enhanced bone regeneration through the BMP-2/SMAD/RUNX2/osterix signaling pathway. Front. Cell Dev. Biol., 2022, 10, 883228.
[http://dx.doi.org/10.3389/fcell.2022.883228] [PMID: 35669516]
[8]
Lei, S.; Su, J.; Zhang, Y.; Huang, X.; Wang, X.; Huang, M.; Li, B.; Shou, D. Benefits and mechanisms of polysaccharides from Chinese medicinal herbs for anti-osteoporosis therapy: A review. Int. J. Biol. Macromol., 2021, 193(Pt B), 1996-2005.
[http://dx.doi.org/10.1016/j.ijbiomac.2021.11.030] [PMID: 34767882]
[9]
Huang, D.; Hou, X.; Zhang, D.; Zhang, Q.; Yan, C. Two novel polysaccharides from rhizomes of Cibotium barometz promote bone formation via activating the BMP2/SMAD1 signaling pathway in MC3T3-E1 cells. Carbohydr. Polym., 2020, 231, 115732.
[http://dx.doi.org/10.1016/j.carbpol.2019.115732] [PMID: 31888819]
[10]
Lin, G.L.; Hankenson, K.D. Integration of BMP, Wnt, and notch signaling pathways in osteoblast differentiation. J. Cell. Biochem., 2011, 112(12), 3491-3501.
[http://dx.doi.org/10.1002/jcb.23287] [PMID: 21793042]
[11]
Niedermair, T.; Lukas, C.; Li, S.; Stöckl, S.; Craiovan, B.; Brochhausen, C.; Federlin, M.; Herrmann, M.; Grässel, S. Influence of extracellular vesicles isolated from osteoblasts of patients with cox-arthrosis and/or osteoporosis on metabolism and osteogenic differentiation of BMSCs. Front. Bioeng. Biotechnol., 2020, 8, 615520.
[http://dx.doi.org/10.3389/fbioe.2020.615520] [PMID: 33425878]
[12]
Xiao, Y.P.; Zeng, J.; Jiao, L.N.; Xu, X.Y. [Review for treatment effect and signaling pathway regulation of kidney-tonifying traditional Chinese medicine on osteoporosis. Zhongguo Zhongyao Zazhi, 2018, 43(1), 21-30.
[http://dx.doi.org/10.19540/j.cnki.cjcmm.20171106.002] [PMID: 29552807]
[13]
Deng, Q.; Qiao, X.W.; Li, Z.F.; Peng, R.D.; Zhang, K.D.; Luo, L.Z.; Yang, H.Y.; Yang, J. Research progress of Gusuibu (Drynariae rhizoma) and its active ingredients in the treatment of skeletal system diseases. Liaoning Zhongyiyao Daxue Xuebao, 2022, 24(7), 1-5.
[14]
Shi, X.L.; Li, C.W.; Wan, Q.Z.; Li, A.Q.; Wang, H.; Liu, K. Drynaria total flavonoids decrease cathepsin K expression in ovariectomized rats. Genet. Mol. Res., 2014, 13(2), 4311-4319.
[http://dx.doi.org/10.4238/2014.June.9.17] [PMID: 25036175]
[15]
Zhang, Y.; Jiang, J.; Shen, H.; Chai, Y.; Wei, X.; Xie, Y. Total flavonoids from Rhizoma drynariae (Gusuibu) for treating osteoporotic fractures: Implication in clinical practice. Drug Des. Devel. Ther., 2017, 11, 1881-1890.
[http://dx.doi.org/10.2147/DDDT.S139804] [PMID: 28694688]
[16]
Hao, W.; Li, N.; Mi, C.; Wang, Q.; Yu, Y. Salidroside attenuates cardiac dysfunction in a rat model of diabetes. Diabet. Med., 2022, 39(3), e14683.
[http://dx.doi.org/10.1111/dme.14683] [PMID: 34467560]
[17]
Lei, S.S.; Li, B.; Chen, Y.H.; He, X.; Wang, Y-Z.; Yu, H-H.; Zhou, F-C.; Zheng, X.; Chen, X.; Zhang, N-Y.; Su, J.; Yan, M-Q.; Lv, G-Y.; Chen, S-H. Dendrobii officinalis, a traditional Chinese edible and officinal plant, accelerates liver recovery by regulating the gut-liver axis in NAFLD mice. J. Funct. Foods, 2019, 61, 103458.
[http://dx.doi.org/10.1016/j.jff.2019.103458]
[18]
Aswamenakul, K.; Klabklai, P.; Pannengpetch, S.; Tawonsawatruk, T.; Isarankura-Na-Ayudhya, C.; Roytrakul, S.; Nantasenamat, C.; Supokawej, A. Proteomic study of in vitro osteogenic differentiation of mesenchymal stem cells in high glucose condition. Mol. Biol. Rep., 2020, 47(10), 7505-7516.
[http://dx.doi.org/10.1007/s11033-020-05811-x] [PMID: 32918125]
[19]
Wang, N.; Xu, P.; Wu, R.; Wang, X.; Wang, Y.; Shou, D.; Zhang, Y. Timosaponin BII improved osteoporosis caused by hyperglycemia through promoting autophagy of osteoblasts via suppressing the mTOR/NFκB signaling pathway. Free Radic. Biol. Med., 2021, 171, 112-123.
[http://dx.doi.org/10.1016/j.freeradbiomed.2021.05.014] [PMID: 33992678]
[20]
Wang, N.; Xu, P.; Wang, X.; Yao, W.; Wang, B.; Wu, Y.; Shou, D. Timosaponin AIII attenuates inflammatory injury in AGEs-induced osteoblast and alloxan-induced diabetic osteoporosis zebrafish by modulating the RAGE/MAPK signaling pathways. Phytomedicine, 2020, 75, 153247.
[http://dx.doi.org/10.1016/j.phymed.2020.153247] [PMID: 32502823]
[21]
Wang, N.; Xu, P.; Yao, W.; Zhang, J.; Liu, S.; Wang, Y.; Zhang, Y. Structural elucidation and anti-diabetic osteoporotic activity of an arabinogalactan from Phellodendron chinense Schneid. Carbohydr. Polym., 2021, 271, 118438.
[http://dx.doi.org/10.1016/j.carbpol.2021.118438] [PMID: 34364577]
[22]
Wang, J.; Jiang, J.; Xie, Y.; Wei, X.; Li, J.; Duan, J.; Xiong, X. Population pharmacokinetics of naringin in total flavonoids of Drynaria fortunei (Kunze) J. Sm. in Chinese women with primary osteoporosis. Chin. J. Integr. Med., 2012, 18(12), 925-933.
[http://dx.doi.org/10.1007/s11655-012-1296-0] [PMID: 23239001]
[23]
Song, S.; Zhai, Y.; Li, C.; Yu, Q.; Lu, Y.; Zhang, Y.; Hua, W.; Wang, Z.; Shang, P. Effects of total flavonoids from Drynariae rhizoma prevent bone loss in vivo and in vitro. Bone Rep., 2016, 5, 262-273.
[http://dx.doi.org/10.1016/j.bonr.2016.09.001] [PMID: 28580395]
[24]
Guha, I.; Klintström, B.; Klintström, E.; Zhang, X.; Smedby, Ö.; Moreno, R.; Saha, P.K. A comparative study of trabecular bone micro-structural measurements using different CT modalities. Phys. Med. Biol., 2020, 65(23), 235029-235029.
[http://dx.doi.org/10.1088/1361-6560/abc367] [PMID: 33086213]
[25]
Burghardt, A.J.; Kazakia, G.J.; Sode, M.; de Papp, A.E.; Link, T.M.; Majumdar, S. A longitudinal HR-pQCT study of alendronate treatment in postmenopausal women with low bone density: Relations among density, cortical and trabecular microarchitecture, biomechanics, and bone turnover. J. Bone Miner. Res., 2010, 25(12), 2558-2571.
[http://dx.doi.org/10.1002/jbmr.157] [PMID: 20564242]
[26]
Hu, L. The effect of alfacalcidol combined with zoledronic acid on bone mineral density, OPG, and BMP-2 in patients with osteoporosis. Zhongguo Guzhi Shusong Zazhi, 2019, 25(1), 93-96.
[http://dx.doi.org/10.3969/j.issn.1006-7108.2019.01.017]
[27]
Chaikuad, A.; Alfano, I.; Kerr, G.; Sanvitale, C.E.; Boergermann, J.H.; Triffitt, J.T.; von Delft, F.; Knapp, S.; Knaus, P.; Bullock, A.N. Structure of the bone morphogenetic protein receptor ALK2 and implications for fibrodysplasia ossificans progressiva. J. Biol. Chem., 2012, 287(44), 36990-36998.
[http://dx.doi.org/10.1074/jbc.M112.365932] [PMID: 22977237]

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