Prediction and verification of biological basis and mechanism for traditional Chinese drugs of reinforcing kidney for supplementing essence in treating diseases related to deficiency of kidney essence
10.16438/j.0513-4870.2019-0637
- VernacularTitle:补肾益精中药治疗肾精亏虚证相关疾病的生物学物质基础及作用机制的预测与验证
- Author:
Chao WU
1
;
Jia-hui WEI
1
;
Han CHEN
1
;
Tao-ren RUAN
1
;
Zhuo-heng LI
1
;
Ji-fen ZHANG
1
;
Xiao-yu XU
1
Author Information
1. Chongqing Key Laboratory of New Drug Screening from Traditional Chinese Medicine, Pharmacology of Chinese Materia Medica - the Key Discipline Constructed by the State Administration of Traditional Chinese Medicine, College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing 400715, China
- Publication Type:Research Article
- Keywords:
eficiency of kidney essence;
network pharmacology;
traditional Chinese drugs of reinforcing kidney for supplementing essence;
italic>Rehmanniae radix praeparata;
erythropoietin
- From:
Acta Pharmaceutica Sinica
2020;55(3):463-472
- CountryChina
- Language:Chinese
-
Abstract:
"Kidney essence" is a profound concept in the theory of traditional Chinese medicine. But its biological basis is unknown until now, resulting in the therapeutic effects of traditional Chinese drugs on reinforcing kidney for supplementing essence hard to be evaluated. This study aimed, to explore the potential biological basis and mechanism of traditional Chinese drugs of reinforcing kidney for supplementing essence on diseases related to deficiency of kidney essence through network pharmacology analysis on the intersection of targets of drugs and diseases. The targets for ingredients in Rehmanniae radix praeparata (RRP), Polygoni multiflori radix praeparata (PMRP) and Polygonati rhizome (PR) were gathered from TCMSP and TCMID database. Osteoporosis, Alzheimer's disease, anemia, infertility and oligospermia targets were collected from OMIM and DisGeNET database. Drug-compound-target-disease (DCTD) network was established with Cytoscape 3.6.1 software, then Clue GO and DAVID database was used to acquire the annotation about GO terms and signaling pathways. Natural aging mice, an acknowledged syndrome model of deficiency of kidney essence, and RRP were used to verify the predictive targets by Western blot analysis. All animal experiments were conducted in accordance with the international guidelines and regulations for the care and use of animals. DCTD network showed that the intersection of drugs and diseases included 175 common targets. After topology analysis, 71 key were screened out targets which were associated with GO annotation exhibited that biological processes (including transcription regulation, RNA metabolism regulation, and DNA-dependent transcription regulation), cell composition (including nuclear lumen, organelle lumen, and membrane closure lumen), molecular function (including transcription regulation, transcription factor activity, and enzyme binding), and signaling pathway (including peroxisome proliferator-activated receptor alpha (PPARα), mitogen-activated protein kinase (MAPK), hypoxia-inducible factor 1 (HIF-1), erythropoietin (EPO) and other signaling pathways. In natural aging mice, the expressions of HIF-1α, growth factor receptor-bound protein 2 (GRB2), MAPK3, signal transducer and activator of transcription 5A (STAT5A), transcription factor AP-1 (JUN) and proto-oncogene c-Fos (FOS) in EPO pathway were significantly decreased. RRP significantly reversed the decrease of the above targets. Above all, these results indicated that the therapeutic effects of traditional Chinese drugs of reinforcing kidney for supplementing essence on deficiency of kidney essence may be related to the regulation of nuclear transcriptional activity and EPO signaling pathway.
