Total flavonoids of <em>Rhizoma Drynariae</em> combined with calcium attenuate osteoporosis by reducing reactive oxygen species generation

Mu,Panyun; Hu,Yimei; Ma,Xu; Shi,Jingru; Zhong,Zhendong; Huang,Lingyuan

doi:10.3892/etm.2021.10050

Total flavonoids of Rhizoma Drynariae combined with calcium attenuate osteoporosis by reducing reactive oxygen species generation

Authors:
- Panyun Mu
- Yimei Hu
- Xu Ma
- Jingru Shi
- Zhendong Zhong
- Lingyuan Huang
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Affiliations: Department of Orthopedics, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610075, P.R. China, Laboratory Animal Research Institute of Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China, Chengdu Lilai Biotechnology Co., Ltd., Chengdu, Sichuan 610041, P.R. China
Published online on: April 14, 2021 https://doi.org/10.3892/etm.2021.10050
Article Number: 618
Copyright: © Mu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

In the present study, the effects of total flavonoids of Rhizoma Drynariae (TFRD) and calcium carbonate (CaCO₃) on osteoporosis (OP) were assessed in a rat model of OP. For this purpose, 36 Sprague‑Dawley rats, aged 3 months, were randomly divided into a group undergoing sham surgery (sham‑operated group), model group (OP group), CaCO₃ group (OP + CaCO₃ group), TFRD group (OP + TFRD group), TFRD combined with CaCO₃ group (OP + TFRD + CaCO₃ group) and TFRD and CaCO₃ combined with N‑acetyl cysteine group (OP + TFRD + CaCO₃ + NAC group). The rat model of OP was established by bilateral ovariectomy. The changes in bone mineral density (BMD), bone volume parameters and bone histopathology in the rats from each group were observed. The levels of serum reactive oxygen species, superoxide dismutase (SOD), malondialdehyde, glutathione peroxidase (GSH‑Px), interleukin (IL)‑6, IL‑1β, TNF‑α, and the levels of bone tissue runt‑related transcription factor 2 (RUNX2), osteoprotegerin (OPG), osteocalcin (BGP), PI3K, p‑PI3K, AKT, p‑AKT, mammalian target of rapamycin (mTOR) and p‑mTOR were measured in the rats of each group. The induction of OP was associated with a marked decrease in BMD, bone mineral content, bone volume fraction and trabecular thickness, and decreased serum levels of SOD and GSH‑Px. Moreover, the expressions of RUNX2, OPG, BGP were downregulated and an upregulation of p‑PI3K, p‑AKT and p‑mTOR were observed in osteoporotic rats. However, treatment with TFRD and CaCO₃ restored all the aforementioned parameters to almost normal values. Furthermore, the findings on histopathological evaluation were consistent with the biochemical observations. Taken together, the findings of the present study demonstrated that TFRD and CaCO₃ significantly increased the antioxidant capacity in rats with OP, increased BMD and reduced bone mineral loss, and may be useful for the prevention and treatment of OP.

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1	Raisz LG: Pathogenesis of osteoporosis: Concepts, conflicts, and prospects. J Clin Invest. 115:3318–3325. 2005.PubMed/NCBI View Article : Google Scholar
2	Cano A, Chedraui P, Goulis DG, Lopes P, Mishra G, Mueck A, Senturk LM, Simoncini T, Stevenson JC, Stute P, et al: Calcium in the prevention of postmenopausal osteoporosis: EMAS clinical guide. Maturitas. 107:7–12. 2018.PubMed/NCBI View Article : Google Scholar
3	Bonaccorsi G, Piva I, Greco P and Cervellati C: Oxidative stress as a possible pathogenic cofactor of post-menopausal osteoporosis: Existing evidence in support of the axis oestrogen deficiency-redox imbalance-bone loss. Indian J Med Res. 147:341–351. 2018.PubMed/NCBI View Article : Google Scholar
4	Zeng Q, Li N, Wang Q, Feng J, Sun D, Zhang Q, Huang J, Wen Q, Hu R, Wang L, et al: The Prevalence of Osteoporosis in China, a Nationwide, Multicenter DXA Survey. J Bone Miner Res. 34:1789–1797. 2019.PubMed/NCBI View Article : Google Scholar
5	Omsland TK and Magnus JH: Forecasting the burden of future postmenopausal hip fractures. Osteoporos Int. 25:2493–2496. 2014.PubMed/NCBI View Article : Google Scholar
6	Manolagas SC: From estrogen-centric to aging and oxidative stress: A revised perspective of the pathogenesis of osteoporosis. Endocr Rev. 31:266–300. 2010.PubMed/NCBI View Article : Google Scholar
7	Wang J, Wang G, Gong L, Sun G, Shi B, Bao H and Duan Y: Isopsoralen regulates PPAR γ/WNT to inhibit oxidative stress in osteoporosis. Mol Med Rep. 17:1125–1131. 2018.PubMed/NCBI View Article : Google Scholar
8	An J, Yang H, Zhang Q, Liu C, Zhao J, Zhang L and Chen B: Natural products for treatment of osteoporosis: The effects and mechanisms on promoting osteoblast-mediated bone formation. Life Sci. 147:46–58. 2016.PubMed/NCBI View Article : Google Scholar
9	Shieh P, Jan CR and Liang WZ: The protective effects of the antioxidant N-acetylcysteine (NAC) against oxidative stress-associated apoptosis evoked by the organophosphorus insecticide malathion in normal human astrocytes. Toxicology. 417:1–14. 2019.PubMed/NCBI View Article : Google Scholar
10	Chen L, Wang G, Wang Q, Liu Q, Sun Q and Chen L: N-acetylcysteine prevents orchiectomy-induced osteoporosis by inhibiting oxidative stress and osteocyte senescence. Am J Transl Res. 11:4337–4347. 2019.PubMed/NCBI
11	Raffaele M, Barbagallo I, Licari M, Carota G, Sferrazzo G, Spampinato M, Sorrenti V and Vanella L: N-Acetylcysteine (NAC) ameliorates lipid-related metabolic dysfunction in bone marrow stromal cells-derived adipocytes. Evid Based Complement Alternat Med. 2018(5310961)2018.PubMed/NCBI View Article : Google Scholar
12	Matera MG, Calzetta L and Cazzola M: Oxidation pathway and exacerbations in COPD: The role of NAC. Expert Rev Respir Med. 10:89–97. 2016.PubMed/NCBI View Article : Google Scholar
13	Dludla PV, Dias SC, Obonye N, Johnson R, Louw J and Nkambule BB: A Systematic Review on the Protective Effect of N-Acetyl Cysteine Against Diabetes-Associated Cardiovascular Complications. American journal of cardiovascular drugs: drugs, devices, and other interventions. 18:283–298. 2018.PubMed/NCBI View Article : Google Scholar
14	Yamada M, Tsukimura N, Ikeda T, Sugita Y, Att W, Kojima N, Kubo K, Ueno T, Sakurai K and Ogawa T: N-acetyl cysteine as an osteogenesis-enhancing molecule for bone regeneration. Biomaterials. 34:6147–6156. 2013.PubMed/NCBI View Article : Google Scholar
15	Sheweita SA and Khoshhal KI: Calcium metabolism and oxidative stress in bone fractures: Role of antioxidants. Curr Drug Metab. 8:519–525. 2007.PubMed/NCBI View Article : Google Scholar
16	Zhou RP, Lin SJ, Wan WB, Zuo HL, Yao FF, Ruan HB, Xu J, Song W, Zhou YC, Wen SY, et al: Chlorogenic Acid Prevents Osteoporosis by Shp2/PI3K/Akt Pathway in Ovariectomized Rats. PLoS One. 11(e0166751)2016.PubMed/NCBI View Article : Google Scholar
17	Xi JC, Zang HY, Guo LX, Xue HB, Liu XD, Bai YB and Ma YZ: The PI3K/AKT cell signaling pathway is involved in regulation of osteoporosis. J Recept Signal Transduct Res. 35:640–645. 2015.PubMed/NCBI View Article : Google Scholar
18	Yuan FL, Xu RS, Jiang DL, He XL, Su Q, Jin C and Li X: Leonurine hydrochloride inhibits osteoclastogenesis and prevents osteoporosis associated with estrogen deficiency by inhibiting the NF-κB and PI3K/Akt signaling pathways. Bone. 75:128–137. 2015.PubMed/NCBI View Article : Google Scholar
19	Wang H, Zhao W, Tian QJ, Xin L, Cui M and Li YK: Effect of lncRNA AK023948 on rats with postmenopausal osteoporosis via PI3K/AKT signaling pathway. Eur Rev Med Pharmacol Sci. 24:2181–2188. 2020.PubMed/NCBI View Article : Google Scholar
20	Song S, Gao Z, Lei X, Niu Y, Zhang Y, Li C, Lu Y, Wang Z and Shang P: Total flavonoids of Drynariae Rhizoma prevent bone loss induced by Hindlimb unloading in rats. Molecules. 22(22)2017.PubMed/NCBI View Article : Google Scholar
21	Fang J, Yang L, Shen JZ, et al: Effects of total flavonoids of Rhizoma Drynariae on glutamate signal Glu, mGluR5 and EAAT1 in bone of ovariectomized rats. Chin J Biochem Drugs. 34:10–12,16. 2014.
22	Zhu F, Liu Z and Ren Y: Mechanism of melatonin combined with calcium carbonate on improving osteoporosis in aged rats. Exp Ther Med. 16:192–196. 2018.PubMed/NCBI View Article : Google Scholar
23	Ensrud KE and Crandall CJ: Osteoporosis. Ann Intern Med. 167:ITC17–ITC32. 2017.PubMed/NCBI View Article : Google Scholar
24	Bidwell JP, Alvarez MB, Hood M Jr and Childress P: Functional impairment of bone formation in the pathogenesis of osteoporosis: The bone marrow regenerative competence. Curr Osteoporos Rep. 11:117–125. 2013.PubMed/NCBI View Article : Google Scholar
25	Weaver CM, Alexander DD, Boushey CJ, Dawson-Hughes B, Lappe JM, LeBoff MS, Liu S, Looker AC, Wallace TC and Wang DD: Calcium plus vitamin D supplementation and risk of fractures: an updated meta-analysis from the National Osteoporosis Foundation. Osteoporos Int. 27:367–376. 2016.PubMed/NCBI View Article : Google Scholar
26	Shuid AN, Mohamad S, Mohamed N, Fadzilah FM, Mokhtar SA, Abdullah S, Othman F, Suhaimi F, Muhammad N and Soelaiman IN: Effects of calcium supplements on fracture healing in a rat osteoporotic model. Orthop Res. 28:1651–1656. 2010.PubMed/NCBI View Article : Google Scholar
27	Paschalis EP, Gamsjaeger S, Hassler N, Fahrleitner-Pammer A, Dobnig H, Stepan JJ, Pavo I, Eriksen EF and Klaushofer K: Vitamin D and calcium supplementation for three years in postmenopausal osteoporosis significantly alters bone mineral and organic matrix quality. Bone. 95:41–46. 2017.PubMed/NCBI View Article : Google Scholar
28	Zhang F, Xie J, Wang G, Zhang G and Yang H: Anti-osteoporosis activity of Sanguinarine in preosteoblast MC3T3-E1 cells and an ovariectomized rat model. J Cell Physiol. 233:4626–4633. 2018.PubMed/NCBI View Article : Google Scholar
29	Cervellati C, Bonaccorsi G, Cremonini E, Bergamini CM, Patella A, Castaldini C, Ferrazzini S, Capatti A, Picarelli V, Pansini FS, et al: Bone mass density selectively correlates with serum markers of oxidative damage in post-menopausal women. Clin Chem Lab Med. 51:333–338. 2013.PubMed/NCBI View Article : Google Scholar
30	Cervellati C and Bergamini CM: Oxidative damage and the pathogenesis of menopause related disturbances and diseases. Clin Chem Lab Med. 54:739–753. 2016.PubMed/NCBI View Article : Google Scholar
31	Wu X, Li J, Zhang H, Wang H, Yin G and Miao D: Pyrroloquinoline quinone prevents testosterone deficiency-induced osteoporosis by stimulating osteoblastic bone formation and inhibiting osteoclastic bone resorption. Am J Transl Res. 9:1230–1242. 2017.PubMed/NCBI
32	Orchard T, Yildiz V, Steck SE, Hébert JR, Ma Y, Cauley JA, Li W, Mossavar-Rahmani Y, Johnson KC, Sattari M, et al: Dietary inflammatory index, bone mineral density, and risk of fracture in postmenopausal women: Results from the Women's Health Initiative. J Bone Miner Res. 32:1136–1146. 2017.PubMed/NCBI View Article : Google Scholar
33	Chen B and Li HZ: Association of IL-6 174G/C (rs1800795) and 572C/G (rs1800796) polymorphisms with risk of osteoporosis: A meta-analysis. BMC Musculoskelet Disord. 21(330)2020.PubMed/NCBI View Article : Google Scholar
34	Al-Daghri NM, Aziz I, Yakout S, Aljohani NJ, Al-Saleh Y, Amer OE, Sheshah E, Younis GZ and Al-Badr FBM: Inflammation as a contributing factor among postmenopausal Saudi women with osteoporosis. Medicine (Baltimore). 96(e5780)2017.PubMed/NCBI View Article : Google Scholar
35	Wang Q, Li Y and Zhang Y, Ma L, Lin L, Meng J, Jiang L, Wang L, Zhou P and Zhang Y: lncRNA MEG3 inhibited osteogenic differentiation of bone marrow mesenchymal stem cells from postmenopausal osteoporosis by targeting miR-133a-3p. Biomed Pharmacother. 89:1178–1186. 2017.PubMed/NCBI View Article : Google Scholar
36	Zhu W, He X, Hua Y, Li Q, Wang J and Gan X: The E3 ubiquitin ligase WWP2 facilitates RUNX2 protein transactivation in a mono-ubiquitination manner during osteogenic differentiation. J Biol Chem. 292:11178–11188. 2017.PubMed/NCBI View Article : Google Scholar
37	Zhu XB, Lin WJ, Lv C, Wang L, Huang ZX, Yang SW and Chen X: MicroRNA-539 promotes osteoblast proliferation and differentiation and osteoclast apoptosis through the AXNA-dependent Wnt signaling pathway in osteoporotic rats. J Cell Biochem. 119:8346–8358. 2018.PubMed/NCBI View Article : Google Scholar
38	Dufresne SS, Dumont NA, Bouchard P, Lavergne É, Penninger JM and Frenette J: Osteoprotegerin protects against muscular dystrophy. Am J Pathol. 185:920–926. 2015.PubMed/NCBI View Article : Google Scholar
39	Wolski H, Drews K, Bogacz A, Kamiński A, Barlik M, Bartkowiak-Wieczorek J, Klejewski A, Ożarowski M, Majchrzycki M and Seremak-Mrozikiewicz A: The RANKL/RANK/OPG signal trail: Significance of genetic polymorphisms in the etiology of postmenopausal osteoporosis. Ginekol Pol. 87:347–352. 2016.PubMed/NCBI View Article : Google Scholar
40	Mukherjee A and Rotwein P: Selective signaling by Akt1 controls osteoblast differentiation and osteoblast-mediated osteoclast development. Mol Cell Biol. 32:490–500. 2012.PubMed/NCBI View Article : Google Scholar
41	Ouyang N, Zhang P, Fu R, Shen G, Jiang L and Fang B: Mechanical strain promotes osteogenic differentiation of bone mesenchymal stem cells from ovariectomized rats via the phosphoinositide 3 kinase/Akt signaling pathway. Mol Med Rep. 17:1855–1862. 2018.PubMed/NCBI View Article : Google Scholar
42	Kita K, Kimura T, Nakamura N, Yoshikawa H and Nakano T: PI3K/Akt signaling as a key regulatory pathway for chondrocyte terminal differentiation. Genes to cells: Devoted to molecular & cellular mechanisms. 13:839–850. 2008.PubMed/NCBI View Article : Google Scholar
43	Li M, Luo R, Yang W, Zhou Z and Li C: miR-363-3p is activated by MYB and regulates osteoporosis pathogenesis via PTEN/PI3K/AKT signaling pathway. In Vitro Cell Dev Biol Anim. 55:376–386. 2019.PubMed/NCBI View Article : Google Scholar
44	Zhang Y, Cao X, Li P, Fan Y, Zhang L, Li W and Liu Y: PSMC6 promotes osteoblast apoptosis through inhibiting PI3K/AKT signaling pathway activation in ovariectomy-induced osteoporosis mouse model. J Cell Physiol. 235:5511–5524. 2020.PubMed/NCBI View Article : Google Scholar