|
|
|
| Discussion of molecular mechanism and experimental verification of Radix Astragali seu Hedysari in the treatment of osteoporosis based on network pharmacology and molecular docking |
| LI Yuanmei1 GUO Shuai1 ZHANG Xinyi1 HUA Maoqi2 LIU Xifang3 |
1. The First Clinical Medical College, Shaanxi University of Chinese Medicine, Shaanxi Province, Xianyang 712046, China;
2.the Second Clinical Medical College, Henan University of Chinese Medicine, Henan Province, Zhengzhou 450053, China;
3.Neurospinal Area, Rehabilitation Hospital, Honghui Hospital Affiliated to Xi’an Jiaotong University, Shaanxi Province, Xi’an 710054, China
|
|
|
|
Abstract Objective To explore the pharmacological mechanism of Radix Astragali seu Hedysari in the treatment of osteoporosis based on network pharmacology and molecular docking, and to verify by in vitro experiment. Methods The active ingredients and drug targets of Radix Astragali seu Hedysari were obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. GeneCard, OMIM, PharmGkb, TTD, and DrugBank databases were used to screen the genes related to osteoporosis, and the intersection of targets and genes was established to construct the drug-compotion-disease-target regulatory network. Enrichment analysis of KEGG pathway was performed, and finally molecular docking and cell experiments were performed. Pre-osteoblast cell line MC3T3-E1 was selected and divided into 10, 20, 30 μmol/L groups (adding 10, 20, 30 μmol/L isorhamnosin solution), and blank group (equal volume medium). The cell proliferation of the four groups cultured for 0, 24, 48, 72 h was detected by CCK8 method. Results A total of 20 active components, 1 290 osteoporosis related genes, and 78 associated gene intersections were obtained. There were six core targets of Radix Astragali seu Hedysari against osteoporosis, and the enrichment analysis of core gene KEGG pathway showed lipid and atherosclerosis pathway, MAPK signaling pathway, etc. Molecular docking results showed that the key target of Radix Astragali seu Hedysari membranaceus had higher binding activity with active components. The main active component isorhamnetin of Radix Astragali seu Hedysari was selected for cell experiment, experiment results showed that the cell optical density values of 10, 20, and 30 μmol/L groups at 24, 48, 72 h culture were higher than those of the blank group at the same time point, the 20 and 30 μmol/L groups were higher than those of the 10 μmol/L group at the same time point, and the 30 μmol/L group was higher than those of the 20 μmol/L group at the same time point, the differences were statistically significant (P＜0.05). Conclusion The effective component of Radix Astragali seu Hedysari in the treatment of osteoporosis is isorhamnetin, Radix Astragali seu Hedysari may play a role in regulating bone metabolism and promoting osteoblast proliferation through multiple targets participating in specific signaling pathways.
|
|
|
|
|
|
[1] 彭永徳.骨质疏松症的药物治疗进展[J].中国临床保健杂志，2022，25（1）：17-21.
[2] Klop C，Welsing PMJ，Elders PJM，et al. Long-term persistence with anti-osteoporosis drugs after fracture [J]. Osteoporos Int，2015，26（6）：1831-1840.
[3] 夏维波，章振林，林华，等.原发性骨质疏松症诊疗指南（2017）[J].中国全科医学，2017，20（32）：3963-3982.
[4] 梁伟乔，钟诚，李宇明.骨质疏松症的中医病因病机认识与治疗进展[J].中国骨质疏松杂志，2020，26（1）：135-139.
[5] 邱峰，张贤，尹恒，等.老年性骨质疏松症中医证候分布规律研究[J].广州中医药大学学报，2021，38（4）：651-655.
[6] 思志强，张莹，贾英杰.中药黄芪防治骨质疏松研究进展[J].辽宁中医药大学学报，2019，21（10）：214-217.
[7] 赵进东，忻凌，余婵娟，等.中药治疗肾虚血瘀证2型糖尿病合并骨质疏松症患者用药规律研究[J].中国骨质疏松杂志，2020，26（7）：942-945，966.
[8] 乔小万，邓强，李中锋，等.基于“肾虚髓枯”理论探讨骨质疏松症的病机及中药治疗[J].中国骨质疏松杂志，2022，28（5）：760-765，780.
[9] 王庆谚.补肾益气活血方对绝经后骨质疏松症大鼠Wnt7b/β-catenin信号通路作用机制的研究[D].沈阳：辽宁中医药大学，2019.
[10] 孔令岩，柴仪，李倩，等.淫羊藿总黄酮和黄芪多糖配伍对骨质疏松大鼠的保护作用[J].中国中医骨伤科杂志，2021，29（4）：14-16，31.
[11] 李磊，刘晓勇.赤参壮骨方治疗骨质疏松症所致L3～L5段爆裂性骨折围手术期的临床疗效[J].中医研究，2022，35（3）：525-526.
[12] 黄红，林燕平，黄佳纯，等.菟丝子-黄芪治疗骨质疏松症的网络药理学机制研究[J].广州中医药大学学报，2020，37（1）：121-127.
[13] 晁杲，廖圣宝，周静，等.异鼠李素抗骨质疏松作用及机制探讨[J].中国医院药学杂志，2016，36（17）：1456-1460.
[14] 喻琴云，詹晓峰，黄彦.刺芒柄花素对去势骨质疏松大鼠P38MAPK/MMP-9信号通路的影响[J].中国临床药理学与治疗学，2017，22（12）：1371-1376.
[15] 郑红，唐薇，角建林，等.槲皮素通过促进成骨分化治疗去势骨质疏松症大鼠的分子机制[J].中药药理与临床，2017，33（5）：16-20.
[16] Zhang Z，Lin T，Meng Y，et al. FOS/GOS attenuates high-fat diet induced bone loss via reversing microbiota dysbiosis，high intestinal permeability and systemic inflammation in mice [J]. Metabolism，2021，119：154767.
[17] Shu J，Li J，Fu Y，et al. Association of ESR1 polymorphism rs2234693 and rs9340799 with postmenopausal osteoporosis in a Chinese population [J]. BMC Musculoskelet Disord，2020，21（1）：346.
[18] Zhu S，He H，Gao C，et al. Ovariectomy-induced bone loss in TNFα and IL6 gene knockout mice is regulated by different mechanisms [J]. J Mol Endocrinol，2018，60（3）：185- 198.
[19] 刘华，冯梓俊，邓玫，等.益气补肾汤治疗原发性骨质疏松症效果探讨[J].中国医药科学，2021，11（3）：90-92.
[20] 肖亚平，曾杰，焦琳娜，等.补肾中药对骨质疏松症的治疗及其信号通路调节作用的研究进展[J].中国中药杂志，2018，43（1）：21-30.
[21] 高想，鲍俊臣.补肾活血汤对骨质疏松性椎体压缩性骨折的疗效[J].中国医药科学，2022，12（24）：173-177.
[22] 陈小香，邓伟民，魏秋实，等.从GH/IGF-1轴与PI3K/Akt通路探讨老年骨质疏松症的发病机制[J].中国骨质疏松杂志，2015，21（11）：1421-1425.
[23] 高飞.AGEs通过Wnt/β-catenin通路抑制BMSCs成骨分化及PTH的干预作用[D].合肥：山西医科大学，2020.
[24] Saoji R，Das RS，Desai M，et al. Association of high-density lipoprotein, triglycerides，and homocysteine with bone mineral density in young Indian tribal women [J]. Arch Osteoporos，2018，13（1）：108.
[25] Chou CW，Chiang TI，Chang IC，et al. Expression levels of estrogen receptor α mRNA in peripheral blood cells are an independent biomarker for postmenopausal osteoporosis [J]. BBA Clin，2016，5：124-129.
[26] Rojas A，Morales M，Gonzalez I，et al. Inhibition of RAGE Axis Signaling: A Pharmacological Challenge [J]. Curr Drug Targets，2019，20（3）：340-346. |
|
|
|
