啤酒花活性成分黄腐酚治疗骨质疏松症的机制研究进展

doi:10.20047/j.issn1673-7210.2022.29.07

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摘要黄腐酚（XN）是啤酒花中特有的一种黄酮类化合物，可促进成骨细胞（OB）分化和抑制破骨细胞（OC）分化，调节骨代谢。本文通过检索近10年CNKI、维普、万方、pubmed等数据库相关文献，就XN参与OB和OC分化及相关信号通路的文献进行分析，结果表明XN可上调Runx2的表达，促进OB的增殖分化。并可下调PPARγ的表达，抑制脂肪细胞的分化，从而调节成骨与成脂分化平衡。同时，XN亦可通过上调Nrf2的表达促进体内抗氧化物的产生，从而减少氧化应激对OB的损害。另外，XN可抑制NF-κB、Ca2+/NFATc1、MAPK等通路，抑制OC的分化成熟。通过综述进一步明确了XN调节骨代谢的作用机制，为开发防治骨质疏松症的药物提供新的靶点。

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	赵怡凡1 刘天鹏1 赵少川1 芮琛1 杨锋2

关键词 ：黄腐酚, 骨质疏松症, 成骨细胞, 破骨细胞, 机制

Abstract：Xanthohumol (XN) is a special flavonoid in hops, which can promote osteoblast differentiation and inhibit osteocbast (OB) differentiation, and regulate osteoclast (OC) metabolism. In this paper, literatures related to the involvement of xanthohumol in OB and OC differentiation and related signal pathways were analyzed by searching CNKI, VIP, Wanfang, PubMed and other databases in the last 10 years. The results showed that XN could up-regulate the expression of Runx2 and promote the proliferation and differentiation of OB. In addition, the expression of PPARγ was down-regulated, and the differentiation of adipocytes was inhibited, thus regulating the balance of osteogenic and adipogenic differentiation. Meanwhile, XN can also promote the production of antioxidants in vivo by up-regulating Nrf2 expression, thus reducing the damage of oxidative stress to OB. In addition, XN inhibited NF-κB, Ca2+/NFATc1, MAPK and other pathways, and inhibited OC differentiation and maturation. This review further clarified the mechanism of XN regulating bone metabolism, and provided a new target for the development of drugs for the prevention and treatment of osteoporosis.

Key words： Xanthohumol Osteoporosis Osteoblast Osteoclast Mechanism

基金资助:国家自然科学基金资助项目（81973889）；
陕西高校青年创新团队（陕教〔2019〕90号）；
陕西省中医药管理局中医药传承创新暨“秦药”开发重点科学研究项目（2021-01-22-009）。

通讯作者: 杨锋（1977.2-），男，博士，主任医师；研究方向：骨与关节退行性病变。

引用本文:

赵怡凡1 刘天鹏1 赵少川1 芮琛1 杨锋2. 啤酒花活性成分黄腐酚治疗骨质疏松症的机制研究进展[J]. 中国医药导报, 2022, 19(29): 34-37,45.
ZHAO Yifan1 LIU Tianpeng1 ZHAO Shaochuan1 RUI Chen1 YANG Feng2. Research progress on the mechanism of xanthohumol, the active ingredient of hops, in the treatment of osteoporosis. 中国医药导报, 2022, 19(29): 34-37,45.

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[1] 徐俪筝，陈鸣声，司磊.骨质疏松症卫生经济学评价研究的现状、挑战及建议[J].中华内分泌代谢杂志，2021，
[2] 王文汇.抗骨质疏松药物的作用及进展[J].中国医刊，2021，56（11）：1189-1192.
[3] 林灿彬.不同类型双膦酸盐药物治疗骨质疏松的临床疗效[J].临床合理用药杂志，2021，14（32）：109-111.
[4] 袁春燕，任慕兰.绝经后骨质疏松的性激素治疗[J].实用妇产科杂志，2020，36（7）：494-497.
[5] 屈杭帅，郑敬民.植物黄酮抗骨质疏松作用的研究进展[J].中国骨质疏松杂志，2021，27（10）：1529-1533.
[6] 刘晓燕，夏天爽，董志敏，等.啤酒花抗骨质疏松的应用及展望[J].药学实践杂志，2020，38（6）：492-495.
[7] Aggarwal D，Upadhyay SK，Singh R，et al. Recent patents on therapeutic activities of xanthohumol：a prenylated chalconoid from hops （Humulus lupulus L.） [J]. Pharm Pat Anal，2021，10（1）：37-49.
[8] Okamoto K，Nakashima T，Shinohara M，et al. Osteoimmunology：The Conceptual Framework Unifying the Immune and Skeletal Systems [J]. Physiol Rev，2017，97（4）：1295-1349.
[9] Muruganandan S，Ionescu AM，Sinal CJ. At the Crossroads of the Adipocyte and Osteoclast Differentiation Programs：Future Therapeutic Perspectives [J]. Int J Mol Sci，2020， 21（7）：2277.
[10] Zhang Y，Bobe G，Miranda CL，et al. Tetrahydroxanthohumol，a xanthohumol derivative，attenuates high-fat diet-induced hepatic steatosis by antagonizing PPARγ [J]. Elife，2021，10：e66398.
[11] Fang Y，Chu L，Li L，et al. Tetramethylpyrazine Protects Bone Marrow-Derived Mesenchymal Stem Cells against Hydrogen Peroxide-Induced Apoptosis through PI3K/Akt and ERK1/2 Pathways [J]. Biol Pharm Bull，2017，40（12）：2146-2152.
[12] 孙晓蕾.啤酒花及黄腐酚改善铁超载致学习记忆损伤及骨丢失作用研究[D].济南：山东中医药大学，2021.
[13] Komori T. Runx2，an inducer of osteoblast and chondrocyte differentiation [J]. Histochem Cell Biol，2018，149（4）：313-323.
[14] Wei J，Shimazu J，Makinistoglu MP，et al. Glucose Uptake and Runx2 Synergize to Orchestrate Osteoblast Differentiation and Bone Formation [J]. Cell，2015，161（7）：576-1591.
[15] Schiltz C，Prouillet C，Marty C，et al. Bone loss induced by Runx2 over-expression in mice is blunted by osteoblastic over-expression of TIMP-1 [J]. J Cell Physiol，2010，222（1）：219-229.
[16] Jeong HM，Han EH，Jin YH，et al. Xanthohumol from the hop plant stimulates osteoblast differentiation by RUNX2 activation [J]. Biochem Biophys Res Commun，2011，409（1）：82-89.
[17] 夏天爽，丁卢颖，张嘉宝，等.啤酒花及其活性成分黄腐酚抗糖皮质激素性骨质疏松的作用研究[J].药学实践杂志，2021，39（3）：221-225.
[18] Li J，Li Y，Wang Y，et al. Preventive effects of siRNA targeting PPARγ gene on steroid-induced osteonecrosis in rabbits [J]. Connect Tissue Res，2014，55（5/6）：322-330.
[19] Imai T，Takakuwa R，Marchand S，et al. Peroxisome proliferator-activated receptor gamma is required in mature white and brown adipocytes for their survival in the mouse [J]. Proc Natl Acad Sci U S A，2004，101（13）：4543-4547.
[20] Kiyofuji A，Yui K，Takahashi K，et al. Effects of xanthohumol-rich hop extract on the differentiation of preadipocytes [J]. J Oleo Sci，2014，63（6）：593-597.
[21] Yang JY，Della-Fera MA，Rayalam S，et al. Effect of xanthohumol and isoxanthohumol on 3T3-L1 cell apoptosis and adipogenesis [J]. Apoptosis，2007，12（11）：1953-1963.
[22] Zhang Q，Cheng X，Zhang H，et al. Dissecting molecular mechanisms underlying H2O2-induced apoptosis of mouse bone marrow mesenchymal stem cell：role of Mst1 inhibition [J]. Stem Cell Res Ther，2020，11（1）：526.
[23] Park C，Lee H，Han MH，et al. Cytoprotective effects of fermented oyster extracts against oxidative stress-induced DNA damage and apoptosis through activation of the Nrf2/HO-1 signaling pathway in MC3T3-E1 osteoblasts [J]. Excli J，2020，19：1102-1119.
[24] Suh KS，Chon S，Choi EM. Cytoprotective effects of xanthohumol against methylglyoxal-induced cytotoxicity in MC3T3-E1 osteoblastic cells [J]. J Appl Toxicol，2018， 38（2）：180-192.
[25] Kang JY，Kang N，Yang YM，et al. The Role of Ca2+-NFATc1 Signaling and Its Modulation on Osteoclastogenesis [J]. Int J Mol Sci，2020，21（10）：3646.
[26] Yuan FL，Xu RS，Jiang DL，et al. Leonurine hydrochloride inhibits osteoclastogenesis and prevents osteoporosis associated with estrogen deficiency by inhibiting the NF-κB and PI3K/Akt signaling pathways [J]. Bone，2015， 75：128-137.
[27] Li J，Zeng L，Xie J，et al. Inhibition of Osteoclastogenesis and Bone Resorption in vitro and in vivo by a prenyl-flavonoid xanthohumol from hops [J]. Sci Rep，2015，5：17605.
[28] 谢娟.中草药单体黄腐酚抑制破骨细胞分化及其功能的机制研究[D].长沙：湖南师范大学，2012.
[29] Park JH，Lee NK，Lee SY. Current Understanding of RANK Signaling in Osteoclast Differentiation and Maturation [J]. Mol Cells，2017，40（10）：706-713.
[30] Suh KS，Rhee SY，Kim YS，et al. Xanthohumol modulates the expression of osteoclast-specific genes during osteoclastogenesis in RAW264.7 cells [J]. Food Chem Toxicol，2013，62：99-106.
[31] Zou B，Zheng J，Deng W，et al. Kirenol inhibits RANKL-induced osteoclastogenesis and prevents ovariectomized-induced osteoporosis via suppressing the Ca2+-NFATc1 and Cav-1 signaling pathways [J]. Phytomedicine，2021， 80：153377.
[32] Liu W，Xie G，Yuan G，et al. 6’-O-Galloylpaeoniflorin Attenuates Osteoclasto-genesis and Relieves Ovariectomy-Induced Osteoporosis by Inhibiting Reactive Oxygen Species and MAPKs/c-Fos/NFATc1 Signaling Pathway [J]. Front Pharmacol，2021，12：641277.
[33] He Y，Staser K，Rhodes SD，et al. Erk1 positively regulates osteoclast differentiation and bone resorptive activity [J]. PLoS One，2011，6（9）：e24780.