PMID- 31844618 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220411 IS - 2214-031X (Print) IS - 2214-0328 (Electronic) IS - 2214-031X (Linking) VI - 19 DP - 2019 Oct TI - Sargassum integerrimum inhibits oestrogen deficiency and hyperlipidaemia-induced bone loss by upregulating nuclear factor (erythroid-derived 2)-like 2 in female rats. PG - 106-117 LID - 10.1016/j.jot.2019.03.002 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: Oestrogen deficiency, high incidences of hyperlipidaemia (HLP) and accelerated bone loss frequently occur in postmenopausal women. There is an urgent need to develop functional foods or specific drugs to protect against bone loss induced by oestrogen deficiency with HLP. AIM OF THE STUDY: In this study, we investigated the potential inhibitory effects of Sargassum integerrimum (SI) on bone loss in an ovariectomized rat model with HLP. MATERIALS AND METHODS: The rats were treated for 12 weeks, and then, bone mineral density, bone biomechanical, bone microstructure, bone morphology, biomarkers of HLP oxidative stress and side effects were determined. Immunohistochemical staining and Western blot were performed to evaluate related protein expression. RESULTS: The femur bone mineral density increased (P < 0.05), and the microscopic structures (ratio of bone volume to total volume [BV/TV], connectivity density [Conn.D], trabecular number [Tb.N] and trabecular thickness [Tb.Th]) of the bone trabecula and mechanical properties (maximum and breaking load [ML and BL, respectively]) improved after SI treatment (P < 0.05). Furthermore, the levels of HLP biomarkers (total cholesterol, triglyceride and low-density lipoprotein) were significantly decreased (P < 0.05), whereas the levels of antioxidant markers (superoxide dismutase and total antioxidant capacity) were increased (P < 0.05). Similar results were obtained with immunohistochemical staining, whereas the Western blot assay showed that SI stimulated the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in bone. CONCLUSION: Our data indicate that rats exposed to SI treatment for 12 weeks did not exhibit noticeable side effects. In conclusion, SI suppressed bone loss induced by ovariectomized and the associated HLP in rats by activating Nrf2, which could be a promising treatment option for osteoporosis induced by oestrogen deficiency and HLP in postmenopausal women. TRANSLATIONAL SCOPE STATEMENT: Our study verified that SI prevented bone loss in rats with oestrogen deficiency with HLP by upregulating nuclear factor (erythroid-derived 2)-like 2. Furthermore, no side effect was observed after the long-term administration of SI. Those results suggested SI could be developed as a functional food or drug for postmenopausal osteoporosis induced by oestrogen deficiency with HLP. CI - (c) 2019 Published by Elsevier (Singapore) Pte Ltd on behalf of Chinese Speaking Orthopaedic Society. FAU - Wu, Kefeng AU - Wu K AD - Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang, Guangdong, 524023, China. FAU - Gong, Zhongqin AU - Gong Z AD - Shenzhen Ritzcon Biological Technology Co., Ltd., Shenzhen, 518000, China. FAU - Zou, Liyi AU - Zou L AD - Department of Pharmacology, Guangdong Medical University, Dongguan, 523808, Guangdong, China. FAU - Ye, Hua AU - Ye H AD - Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang, Guangdong, 524023, China. FAU - Wang, Changxiu AU - Wang C AD - School of Public Health, Guangdong Medical University, Dongguan, Guangdong, 523808, China. FAU - Liu, Yangchun AU - Liu Y AD - Jiangxi Medical College, Queen Mary College of Nanchang University, Nanchang, Jiangxi, 330000, China. FAU - Liang, Yan AU - Liang Y AD - Department of Pharmacology, Guangdong Medical University, Zhanjiang, Guangdong, 524023, China. FAU - Li, Yanping AU - Li Y AD - Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang, Guangdong, 524023, China. FAU - Ren, Jianwei AU - Ren J AD - School of Biomedical Sciences, The Chinese University of Hong Kong, New Territories, Hong Kong, China. FAU - Cui, Liao AU - Cui L AD - Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang, Guangdong, 524023, China. AD - Department of Pharmacology, Guangdong Medical University, Zhanjiang, Guangdong, 524023, China. FAU - Liu, Yi AU - Liu Y AD - Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang, Guangdong, 524023, China. LA - eng PT - Journal Article DEP - 20190327 PL - Singapore TA - J Orthop Translat JT - Journal of orthopaedic translation JID - 101625127 PMC - PMC6896726 OTO - NOTNLM OT - Bone loss OT - HLP, hyperlipidaemia OT - Hyperlipidaemia OT - Nrf2 OT - OS, oxidative stress OT - Oestrogen deficiency OT - Oxidative stress OT - SOD, superoxide dismutase OT - Sargassum integerrimum OT - TOAC, total antioxidant capacity EDAT- 2019/12/18 06:00 MHDA- 2019/12/18 06:01 PMCR- 2019/03/27 CRDT- 2019/12/18 06:00 PHST- 2018/11/27 00:00 [received] PHST- 2019/02/17 00:00 [revised] PHST- 2019/03/04 00:00 [accepted] PHST- 2019/12/18 06:00 [entrez] PHST- 2019/12/18 06:00 [pubmed] PHST- 2019/12/18 06:01 [medline] PHST- 2019/03/27 00:00 [pmc-release] AID - S2214-031X(18)30175-X [pii] AID - 10.1016/j.jot.2019.03.002 [doi] PST - epublish SO - J Orthop Translat. 2019 Mar 27;19:106-117. doi: 10.1016/j.jot.2019.03.002. eCollection 2019 Oct.