Xiaolei Sun1,2, Tianshuang Xia1, Shiyao Zhang2, Jiabao Zhang1, Lingchuan Xu3, Ting Han4, Hailiang Xin5. 1. Department of Pharmacognosy, School of Pharmacy, Naval Medical University, 325 Guohe Road, Shanghai, 200433, China. 2. School of Pharmacy, Shandong University of Traditional Chinese Medicine, 4655 Daxue Road, Jinan, 250355, China. 3. School of Pharmacy, Shandong University of Traditional Chinese Medicine, 4655 Daxue Road, Jinan, 250355, China. xulingchuan518@sina.com. 4. Department of Pharmacognosy, School of Pharmacy, Naval Medical University, 325 Guohe Road, Shanghai, 200433, China. hanting@smmu.edu.cn. 5. Department of Pharmacognosy, School of Pharmacy, Naval Medical University, 325 Guohe Road, Shanghai, 200433, China. hailiangxin@163.com.
Abstract
INTRODUCTION: Osteoporosis is closely related to iron metabolism. This study aimed to investigate whether hops extract (HLE) and its active component xanthohumol (XAN) could ameliorate bone loss caused by iron overload, and explored its potential mechanism. MATERIALS AND METHODS: Iron overload mice induced by iron dextran (ID) were used in vivo, and were treated with HLE and XAN for 3 months. Bone micro-structure and bone morphology parameters were determined by Micro-CT and TRAP staining. Bone metabolism markers and oxidation indexes in serum and bone tissue were evaluated. For in vitro experiment, bone formation indexes were determined. Moreover, the expression of key proteins in protein kinase B (Akt)/glycogen synthetase kinase 3β (GSK3β)/nuclear factor E2-related (Nrf2) pathway was evaluated by Western blotting. RESULTS: HLE and XAN effectively improved the bone micro-structure of the femur in mice, altered bone metabolism biomarkers, and regulated the expression of proteins related to bone metabolism. Additionally, they significantly promoted cell proliferation, runt-related gene 2 (Runx2) expression, and increased ALP activity in ID-induced osteoblasts. Moreover, HLE and XAN markedly inhibited the increase of oxidative stress caused by iron overload in vivo and in vitro. Further studies showed that they significantly up-regulated the expression of p-Akt, p-GSK3β, nuclear-Nrf2, NAD(P)H: quinone oxidoreductase 1 (NQO1), and heme oxygenase-1 (HO-1) in ID-induced osteoblasts. CONCLUSION: These findings indicated hops and xanthohumol could ameliorate bone loss induced by iron overload via activating Akt/GSK3β/Nrf2 pathway, which brought up a novel sight for senile osteoporosis therapy.
INTRODUCTION: Osteoporosis is closely related to iron metabolism. This study aimed to investigate whether hops extract (HLE) and its active component xanthohumol (XAN) could ameliorate bone loss caused by iron overload, and explored its potential mechanism. MATERIALS AND METHODS: Iron overload mice induced by iron dextran (ID) were used in vivo, and were treated with HLE and XAN for 3 months. Bone micro-structure and bone morphology parameters were determined by Micro-CT and TRAP staining. Bone metabolism markers and oxidation indexes in serum and bone tissue were evaluated. For in vitro experiment, bone formation indexes were determined. Moreover, the expression of key proteins in protein kinase B (Akt)/glycogen synthetase kinase 3β (GSK3β)/nuclear factor E2-related (Nrf2) pathway was evaluated by Western blotting. RESULTS: HLE and XAN effectively improved the bone micro-structure of the femur in mice, altered bone metabolism biomarkers, and regulated the expression of proteins related to bone metabolism. Additionally, they significantly promoted cell proliferation, runt-related gene 2 (Runx2) expression, and increased ALP activity in ID-induced osteoblasts. Moreover, HLE and XAN markedly inhibited the increase of oxidative stress caused by iron overload in vivo and in vitro. Further studies showed that they significantly up-regulated the expression of p-Akt, p-GSK3β, nuclear-Nrf2, NAD(P)H: quinone oxidoreductase 1 (NQO1), and heme oxygenase-1 (HO-1) in ID-induced osteoblasts. CONCLUSION: These findings indicated hops and xanthohumol could ameliorate bone loss induced by iron overload via activating Akt/GSK3β/Nrf2 pathway, which brought up a novel sight for senile osteoporosis therapy.
Authors: Tommy Noh; Yankel Gabet; Jon Cogan; Yunfan Shi; Archana Tank; Tomoyo Sasaki; Braden Criswell; Alexis Dixon; Christopher Lee; Joseph Tam; Thomas Kohler; Eran Segev; Lisa Kockeritz; James Woodgett; Ralph Müller; Yang Chai; Elisheva Smith; Itai Bab; Baruch Frenkel Journal: PLoS One Date: 2009-05-04 Impact factor: 3.240