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[1]李律宇,羅淼,李寧,等.基于網(wǎng)絡(luò)藥理學(xué)方法、分子對(duì)接技術(shù)及動(dòng)物實(shí)驗(yàn)探討參威骨痹湯治療骨質(zhì)疏松癥的作用機(jī)制[J].中醫(yī)正骨,2024,36(05):1-12,44.
　LI Lyuyu,LUO Miao,LI Ning,et al.Analysis of mechanism of Shenwei Gubi Tang(參威骨痹湯)against osteoporosis based on the network pharmacology approach,molecular docking techniques and animal experimentation[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2024,36(05):1-12,44.
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基于網(wǎng)絡(luò)藥理學(xué)方法、分子對(duì)接技術(shù)及動(dòng)物實(shí)驗(yàn)探討參威骨痹湯治療骨質(zhì)疏松癥的作用機(jī)制()
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《中醫(yī)正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第36卷
期數(shù):
2024年05期
頁(yè)碼:
1-12,44
欄目:
基礎(chǔ)研究
出版日期:
2024-05-20

文章信息/Info

Title:
Analysis of mechanism of Shenwei Gubi Tang(參威骨痹湯)against osteoporosis based on the network pharmacology approach,molecular docking techniques and animal experimentation
作者:
李律宇1; 羅淼2; 李寧3; 李德光1; 廖江龍1; 鄧力1; 劉敏2; 王曉穎1; 冮順奎1
1.昆明市中醫(yī)醫(yī)院,云南 昆明 650500; 2.云南中醫(yī)藥大學(xué)第三附屬醫(yī)院,云南 昆明 650500; 3.云南中醫(yī)藥大學(xué)第一臨床醫(yī)學(xué)院,云南 昆明 650500
Author(s):
LI Lyuyu1; LUO Miao2;  LI Ning3; LI Deguang1; LIAO Jianglong1; DENG Li1; LIU Min2; WANG Xiaoying1;  GANG Shunkui1
1.Kunming Municipal Hospital of Traditional Chinese Medicine,Kunming 650500,Yunnan,China 2.The Third Affiliated Hospital of Yunnan University of Chinese Medicine,Kunming 650500,Yunnan,China 3.The First Clinical Medical College of Yunnan University of Chinese Medicine,Kunming 650500,Yunnan,China
關(guān)鍵詞:
骨質(zhì)疏松;  參威骨痹湯;  網(wǎng)絡(luò)藥理學(xué);  分子對(duì)接模擬;  動(dòng)物實(shí)驗(yàn)
Keywords:
osteoporosis;  Shenwei Gubi Tang;  network pharmacology;  molecular docking simulation;  animal experimentation
摘要:
目的:探討參威骨痹湯治療骨質(zhì)疏松癥(osteoporosis,OP)的作用機(jī)制。方法:①網(wǎng)絡(luò)藥理學(xué)研究。采用超高效液相色譜-質(zhì)譜法鑒定參威骨痹湯中的化合物,采用網(wǎng)絡(luò)藥理學(xué)方法初步篩選參威骨痹湯治療OP的關(guān)鍵活性成分和靶點(diǎn)。②分子對(duì)接驗(yàn)證。采用分子對(duì)接技術(shù)驗(yàn)證網(wǎng)絡(luò)藥理學(xué)研究確定的參威骨痹湯治療OP的關(guān)鍵活性成分與靶點(diǎn)的結(jié)合效果,從中篩選結(jié)合效果最好的組合。③動(dòng)物實(shí)驗(yàn)驗(yàn)證。將60只雌性C57BL/6JNifdc小鼠隨機(jī)等分為5組,模型組和參威骨痹湯低、中、高劑量組小鼠通過(guò)雙側(cè)卵巢切除手術(shù)進(jìn)行OP造模,假手術(shù)組小鼠僅切取卵巢周?chē)润w積的脂肪組織。參威骨痹湯低、中、高劑量組小鼠分別按照14.95 g·kg-1·d-1、29.9 g·kg-1·d-1、59.8 g·kg-1·d-1以參威骨痹湯藥液灌胃,假手術(shù)組和模型組小鼠以等體積生理鹽水灌胃。藥物干預(yù)8周后,取股骨進(jìn)行Micro-CT檢查和組織病理學(xué)觀察(HE染色和抗酒石酸酸性磷酸酶染色),采用實(shí)時(shí)定量PCR技術(shù)測(cè)定脛骨組織中根據(jù)網(wǎng)絡(luò)藥理學(xué)和分子對(duì)接技術(shù)確定的關(guān)鍵靶點(diǎn)基因的mRNA表達(dá)水平。結(jié)果:①網(wǎng)絡(luò)藥理學(xué)研究結(jié)果。網(wǎng)絡(luò)藥理學(xué)研究結(jié)果顯示,SRC、促分裂原活化的蛋白激酶3(mitogen-activated protein kinase 3,MAPK3)、MAPK1、磷脂酰肌醇3-激酶調(diào)節(jié)亞基1(phosphatidylinositol-3-kinase regulatory subunit 1,PI3KR1)、信號(hào)轉(zhuǎn)導(dǎo)及轉(zhuǎn)錄活化因子3為參威骨痹湯治療OP的關(guān)鍵靶點(diǎn),五味子丙素、10-姜酚、對(duì)羥基苯甲酸丁酯、倍半萜內(nèi)酯和香豆雌酚為參威骨痹湯治療OP的關(guān)鍵活性成分。②分子對(duì)接驗(yàn)證結(jié)果。分子對(duì)接結(jié)果顯示,參威骨痹湯治療OP關(guān)鍵活性成分與關(guān)鍵靶點(diǎn)的結(jié)合能均小于-5 kJ·mol-1,表明結(jié)合效果良好,其中靶點(diǎn)SRC、MAPK3、PI3KR1與活性成分五味子丙素、10-姜酚、對(duì)羥基苯甲酸丁酯的結(jié)合效果更好。③動(dòng)物實(shí)驗(yàn)驗(yàn)證結(jié)果。Micro-CT檢查及組織病理學(xué)觀察結(jié)果顯示,參威骨痹湯能改善OP模型小鼠的骨質(zhì)疏松程度,其中中劑量參威骨痹湯效果更好。實(shí)時(shí)定量PCR測(cè)定結(jié)果顯示,參威骨痹湯中劑量組脛骨組織中SRC mRNA和MAPK3 mRNA表達(dá)水平低于模型組,PI3KR1 mRNA表達(dá)水平與模型組比較差異無(wú)統(tǒng)計(jì)學(xué)意義。結(jié)論:參威骨痹湯治療OP的機(jī)制可能是通過(guò)五味子丙素、10-姜酚、對(duì)羥基苯甲酸丁酯等成分調(diào)控SRC、PI3KR1、MAPK3的表達(dá)來(lái)調(diào)節(jié)骨代謝。
Abstract:
Objective:To explore the mechanism of Shenwei Gubi Tang(參威骨痹湯,SWGBT)against osteoporosis(OP).Methods:①Network pharmacology research.The ingredients in SWGBT were identified by using ultra-high performance liquid chromatography-quadrupole-orbitrap mass spectrometry(UHPLC-QE-MS),and the key active ingredients and action targets of SWGBT against OP were preliminarily screened using the network pharmacology approach.②Validation by molecular docking.The binding effects between the key active ingredients and the targets of SWGBT against OP determined by network pharmacology were validated by molecular docking techniques,and the combination with the best binding effect was screened.③Verification by animal experimentation.Sixty female C57BL/6JNifdc mice were selected and randomized into model group,low-dose SWGBT(L-SWGBT)group,medium-dose SWGBT(M-SWGBT)group,high-dose SWGBT(H-SWGBT)group and sham-operated group.The mice in model group,L-SWGBT group,M-SWGBT group and H-SWGBT group were subjected to bilateral ovariectomy for inducing OP; while the ones in sham-operated group were merely removed an equal volume of peri-ovarian adipose tissues.After successful modeling,the mice in L-SWGBT group,M-SWGBT group and H-SWGBT group were intervened by intragastric administration with 14.95,29.9,59.8 g/(kg·d)SWGBT,respectively; while the ones in sham-operated group and model group with the same dose of normal saline.After 8-week drug intervention,the rats were sacrificed and their femurs were harvested for Micro-CT examination and observation on histopathological changes through HE staining and tartrate-resistant acid phosphatase(TRAP)staining.Furthermore,the mRNA expression levels of key target genes(determined by network pharmacology approach and molecular docking techniques)in tibia tissues were detected by using real-time quantitative PCR(RT-qPCR).Results:①The results of network pharmacology research showed that SRC,mitogen-activated protein kinase 3(MAPK3),MAPK1,phosphatidylinositol-3-kinase regulatory subunit 1(PI3KR1),and signal transducer and activator of transcription 3(STAT3)were the key targets of SWGBT against OP,and the schisandrin C,10-gingerol,butyl p-hydroxybenzoate,sesquiterpene lactone,and coumestrol were the key active ingredients of SWGBT against OP.②The results of molecular docking showed that the key active ingredients of SWGBT against OP had good binding ability to the key targets with the binding energy less than -5.0 kJ/mol,and the targets including SRC,MAPK3,and PI3KR1 exhibited better binding effects with the active ingredients including schisandrin C,10-gingerol,and butyl p-hydroxybenzoate.③The results of Micro-CT examination and histopathological observation showed that the SWGBT could improve the degree of OP in OP model mice,with the medium-dose SWGBT displaying better effects.The results of RT-qPCR showed that the mRNA levels of SRC and MAPK3 were lowly expressed in the tibia tissues of OP model mice in M-SWGBT group compared to model group,while,the mRNA expression level of PI3KR1 was not significantly different from that of model group.Conclusion:The SWGBT may regulate bone metabolism for treatment of OP through adjusting the expression of SRC,PI3KR1 and MAPK3 via the ingredients such as schisandrin C,10-gingerol and butyl p-hydroxybenzoate.

參考文獻(xiàn)/References:

[1] NOH J Y,YANG Y,JUNG H.Molecular mechanisms and emerging therapeutics for osteoporosis[J].Int J Mol Sci,2020,21(20):7623.
[2] NGUYEN D T,HO-LE T P,PHAM L,et al.BONEcheck:a digital tool for personalized bone health assessment[J].Osteoporos Sarcopenia,2023,9(3):79-87.
[3] 中華醫(yī)學(xué)會(huì)骨質(zhì)疏松和骨礦鹽疾病分會(huì).中國(guó)骨質(zhì)疏松癥流行病學(xué)調(diào)查及“健康骨骼”專(zhuān)項(xiàng)行動(dòng)結(jié)果發(fā)布[J].中華骨質(zhì)疏松和骨礦鹽疾病雜志,2019,12(4):317-318.
[4] 李律宇,楊春艷,侯敏,等.參威骨痹湯治療肝腎虧虛、寒濕痹阻型骨關(guān)節(jié)炎103例臨床觀察[J].云南中醫(yī)學(xué)院學(xué)報(bào),2015,38(4):67-69.
[5] KIM Y,BRODT M D,TANG S Y,et al.MicroCT for scanning and analysis of mouse bones[J].Methods Mol Biol,2021,2230:169-198.
[6] 彭廣,葛殊瑋,王凡,等.孫達(dá)武教授治療老年性骨質(zhì)疏松癥臨證經(jīng)驗(yàn)[J].光明中醫(yī),2024,39(2):251-254.
[7] 郭超,張興彩,王衛(wèi)國(guó),等.基于網(wǎng)絡(luò)藥理學(xué)探討“山藥-杜仲”藥對(duì)治療骨質(zhì)疏松癥的作用機(jī)制[J].西部中醫(yī)藥,2024,37(2):48-53.
[8] 王柳蘊(yùn),李蕓佳,胡熠婷,等.基于臟腑理論探討骨質(zhì)疏松癥的治療[J].光明中醫(yī),2023,38(17):3479-3482.
[9] 張希,東方梓涵,李江,等.小紅參免疫作用及質(zhì)量標(biāo)志物預(yù)測(cè)分析[J].亞太傳統(tǒng)醫(yī)藥,2022,18(7):193-197.
[10] 張光云,童英,楊麗萍,等.小紅參臨床應(yīng)用與藥理學(xué)研究概況[J].中國(guó)民族民間醫(yī)藥,2020,29(12):51-54.
[11] 李慧,包永睿,王帥,等.中藥茜草抗氧化、抗炎、抗腫瘤不同藥用部位精準(zhǔn)研究[J].世界科學(xué)技術(shù)-中醫(yī)藥現(xiàn)代化,2019,21(3):401-407.
[12] 趙繼榮,楊文通,陳文,等.威靈仙有效化學(xué)成分及鎮(zhèn)痛機(jī)制研究進(jìn)展[J].中華中醫(yī)藥學(xué)刊,2022,40(9):9-12.
[13] 郎小琴,高越,周葉,等.牛膝多糖對(duì)老年骨質(zhì)疏松大鼠模型骨代謝及生物力學(xué)特征的影響[J].中華全科醫(yī)學(xué),2019,17(4):547-550.
[14] 王艷,周廣舉,嚴(yán)宗遜,等.川牛膝在去卵巢大鼠體內(nèi)的骨保護(hù)作用[J].中國(guó)骨質(zhì)疏松雜志,2015,21(8):918-921.
[15] 董佳梓,鞠大宏,賈朝娟,等.桑寄生、枸杞子、桑椹對(duì)去卵巢大鼠骨質(zhì)疏松癥的治療作用及其機(jī)理探討[J].中國(guó)中醫(yī)基礎(chǔ)醫(yī)學(xué)雜志,2010,16(6):483-486.
[16] 熊偉,趙亮.鹽炙杜仲對(duì)維甲酸誘導(dǎo)骨質(zhì)疏松大鼠生化指標(biāo)及骨密度的影響[J].時(shí)珍國(guó)醫(yī)國(guó)藥,2020,31(8):1866-1867.
[17] 曹劉丹,胡晨,顧瓊,等.獨(dú)活化學(xué)成分及抗骨質(zhì)疏松活性評(píng)價(jià)[J].時(shí)珍國(guó)醫(yī)國(guó)藥,2022,33(12):2918-2923.
[18] LI Y,ZHANG J,ZHANG L,et al.Systems pharmacology to decipher the combinational anti-migraine effects of Tianshu formula[J].J Ethnopharmacol,2015,174:45-56.
[19] 馬艷春,吳文軒,胡建輝,等.當(dāng)歸的化學(xué)成分及藥理作用研究進(jìn)展[J].中醫(yī)藥學(xué)報(bào),2022,50(1):111-114.
[20] THOMAS S M,BRUGGE J S.Cellular functions regulated by Src family kinases[J].Annu Rev Cell Dev Biol,1997,13:513-609.
[21] BOYCE B F,YONEDA T,LOWE C,et al.Requirement of pp60c-src expression for osteoclasts to form ruffled borders and resorb bone in mice[J].J Clin Invest,1992,90(4):1622-1627.
[22] ZHENG L Z,WANG X L,CAO H J,et al.Src siRNA prevents corticosteroid-associated osteoporosis in a rabbit model[J].Bone,2016,83:190-196.
[23] SALVADORI L,BELLADONNA M L,CASTIGLIONI B,et al.Kymasin up natural product inhibits osteoclastogenesis and improves osteoblast activity by modulating Src and p38 MAPK[J].Nutrients,2022,14(15):3503.
[24] MARZIA M,SIMS N A,VOIT S,et al.Decreased c-Src expression enhances osteoblast differentiation and bone formation[J].J Cell Biol,2000,151(2):311-320.
[25] TANIGUCHI C M,EMANUELLI B,KAHN C R.Critical nodes in signalling pathways:insights into insulin action[J].Nat Rev Mol Cell Biol,2006,7(2):85-96.
[26] MI B,XIONG Y,CHEN L,et al.CircRNA AFF4 promotes osteoblast cells proliferation and inhibits apoptosis via the Mir-7223-5p/PIK3R1 axis[J].Aging(Albany NY),2019,11(24):11988-12001.
[27] CUI J,LI X,WANG S,et al.Triptolide prevents bone loss via suppressing osteoclastogenesis through inhibiting PI3K-AKT-NFATc1 pathway[J].J Cell Mol Med,2020,24(11):6149-6161.
[28] HAN J,LI L,ZHANG C,et al.Eucommia,cuscuta,and dryna-ria extracts ameliorate glucocorticoid-induced osteoporosis by inhibiting osteoclastogenesis through PI3K/Akt pathway[J].Front Pharmacol,2021,12:772944.
[29] LI M,YANG N,HAO L,et al.Melatonin inhibits the ferroptosis pathway in rat bone marrow mesenchymal stem cells by activating the PI3K/AKT/mTOR signaling axis to attenuate steroid-induced osteoporosis[J].Oxid Med Cell Longev,2022:8223737.
[30] ZHANG Y T,HU C,ZHANG S X,et al.Euphoesulatin a prevents osteoclast differentiation and bone loss via inhibiting RANKL-induced ROS production and NF-κB and MAPK signal pathways[J].Bioorg Chem,2022,119:105511.
[31] XU M,SONG D,XIE X,et al.CGK733 alleviates ovariectomy-induced bone loss through blocking RANKL-mediated Ca2+ oscillations and NF-κB/MAPK signaling pathways[J].iScience,2023,26(10):107760.
[32] XIAO L,ZHONG M,HUANG Y,et al.Puerarin alleviates osteoporosis in the ovariectomy-induced mice by suppressing osteoclastogenesis via inhibition of TRAF6/ROS-dependent MAPK/NF-κB signaling pathways[J].Aging(Albany NY),2020,12(21):21706-21729.
[33] LI X,JIANG J,YANG Z,et al.Galangin suppresses RANKL-induced osteoclastogenesis via inhibiting MAPK and NF-κB signalling pathways[J].J Cell Mol Med,2021,25(11):4988-5000.
[34] HOU G Q,GUO C,SONG G H,et al.Lipopolysaccharide(LPS)promotes osteoclast differentiation and activation by enhancing the MAPK pathway and COX-2 expression in RAW264.7 cells[J].Int J Mol Med,2013,32(2):503-510.
[35] ZHANG J,ZHENG X,ZHAO F,et al.UHMWPE wear particles and dendritic cells promote osteoclastogenesis of RAW264.7 cells through RANK-activated NF-κB/MAPK/AKT pathways[J].Int J Clin Exp Pathol,2017,10(9):9400-9408.
[36] ROSKOSKI R Jr.ERK1/2 MAP kinases:structure,function,and regulation[J].Pharmacol Res,2012,66(2):105-143.
[37] KYRIAKIS J M,AVRUCH J.Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation[J].Physiol Rev,2001,81(2):807-869.
[38] HU X H,YANG X Y,LIAN J,et al.Moringa oleifera leaf attenuate osteoporosis in ovariectomized rats by modulating gut microbiota composition and MAPK signaling pathway[J].Biomed Pharmacother,2023,161:114434.

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[1]李林軍.應(yīng)用膨脹式椎弓根螺釘內(nèi)固定治療合并骨質(zhì)疏松的 胸腰椎退行性疾病[J].中醫(yī)正骨,2015,27(08):49.
[2]韓艷,溫利平,劉娜,等.補(bǔ)腎活血方對(duì)去卵巢大鼠骨代謝及骨密度的影響[J].中醫(yī)正骨,2015,27(12):7.
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　Huang Jianhua*,Huang Jianwu,Li Huihui,et al.Effect of JIAWEI ZUOGUI pill on bone mineral density in postmenopausal osteoporosis patients with deficiency of liver and kidney[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2013,25(05):19.
[7]項(xiàng)旻,楊虹,林愛(ài)菊,等.絕經(jīng)后2型糖尿病患者骨質(zhì)疏松與血微量元素的關(guān)系研究[J].中醫(yī)正骨,2013,25(12):20.
　Xiang Min*,Yang Hong,Lin Aiju,et al.Clinical study on the relationship between osteoporosis and serum trace elements levels in postmenopausal women with type 2 diabetes[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2013,25(05):20.
[8]史曉林,李春雯,張志強(qiáng).弱陽(yáng)離子磁珠分離技術(shù)和基質(zhì)輔助激光解吸電離飛行時(shí)間質(zhì)譜技術(shù)在原發(fā)性Ⅰ型骨質(zhì)疏松癥血清標(biāo)志蛋白篩選中的應(yīng)用[J].中醫(yī)正骨,2014,26(03):5.
　Shi Xiaolin*,Li Chunwen,Zhang Zhiqiang..Application of magnetic beads based weak cation exchange separation technology and matrix-assisted laser desorption-ionization time of flight mass spectrometry technology in screening serum protein markers of primary type-Ⅰ osteoporosis[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2014,26(05):5.
[9]李明,徐明雄,馮左基,等.自擬壯骨方治療絕經(jīng)后骨質(zhì)疏松癥的療效及作用機(jī)制研究[J].中醫(yī)正骨,2014,26(09):21.
　Li Ming*,Xu Mingxiong,Feng Zuoji,et al.Study on the curative effect and mechanism of action of self-made ZHUANGGU decoction in treatment of postmenopausal osteoporosis[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2014,26(05):21.
[10]陳俊杰,李晴晴,夏瑢.脂代謝及血清內(nèi)脂素水平與絕經(jīng)后骨質(zhì)疏松癥的 相關(guān)性研究[J].中醫(yī)正骨,2012,24(04):16.
　CHEN Jun-jie*,LI Qing-qing,XIA Rong.*.Study on the correlations between the levels of lipid metabolism and serum visfatin and postmenopausal osteoporosis[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2012,24(05):16.

備注/Memo

備注/Memo:
基金項(xiàng)目:云南省科學(xué)技術(shù)廳-中醫(yī)聯(lián)合專(zhuān)項(xiàng)面上項(xiàng)目(202101AG070053,202301AZ070001-091)
通訊作者:冮順奎 E-mail:[email protected]
更新日期/Last Update: 1900-01-01