title: Analysis of molecular networks and targets mining of Chinese herbal medicines on anti-aging.
abstract: BACKGROUND
  Many kidney-tonifying Chinese herbal medicines exert effects on anti-aging by comprehensive interactions of multiple targets. However, the interactions of multi-targets targeted by effective ingredients of kidney-tonifying Chinese herbal medicines are unknown. In this study, to explore the systems pharmacology mechanisms of kidney-tonifying Chinese medicines on anti-aging, we establish the molecular networks with the interactions of multi-targets, analyze bio-functions and pathways with IPA, and calculated the mutual interaction pairs of targets (target pairs) with data mining, respectively.
  
  
  METHODS
  Kidney-tonifying Chinese medicines with anti-aging effects were screened from the Chinese Pharmacopoeia and the literatures. Target proteins of these herbal medicines were obtained from bioinformatics databases. Comparisons of molecular networks, bio-functions and pathways given by Ingenuity Pathway Analysis system showed the similarities and the differences between kidney Yin-tonifying herbal medicines and kidney Yang-tonifying herbal medicines. Target pairs with high correlation related to anti-aging were also discovered by data mining algorithm. And regulatory networks of targets were built based on the target pairs.
  
  
  RESULTS
  Twenty-eight kidney-tonifying herbal medicines with anti-aging effects and 717 related target proteins were collected. The main bio-functions that all targets enriched in were "Cell Death and Survival", "Free Radical Scavenging" and "Cellular Movement", etc. The results of comparison analysis showed that kidney Yin-tonifying herbal medicines focused more on "Cancer related signaling", "Apoptosis related signaling" and "Cardiovascular related signaling". And kidney Yang-tonifying herbal medicines focused more on "Cellular stress and injury related signaling" and "Cellular growth, proliferation and development related signaling". Moreover, the results of regulatory network showed that the anti-aging related target pairs with high correlated degrees of Kidney Yin-tonifying herbal medicines included TNF-PTGS2, TNF-CASP3, PTGS2-CASP3, CASP3-NOS2 and TNF-NOS2, and that of kidney Yang-tonifying herbal medicines included REAL-TNF, REAL-NFKBIA, REAL-JUN, PTGS2-SOD1 and TNF-IL6.
  
  
  CONCLUSIONS
  In this study, we achieved some important targets, target pairs and regulatory networks with bioinformatics and data mining, to discuss the systems pharmacology mechanisms of kidney-tonifying herbal medicines acting on anti-aging. Mutual target pairs related to anti-aging found in this study included TNF-PTGS2, TNF-CASP3, PTGS2-CASP3, CASP3-NOS2, TNF-NOS2, REAL-TNF, REAL-NFKBIA, REAL-JUN, PTGS2-SOD1 and TNF-IL6. Target pairs and regulatory networks of targets could reflect more potential interactions between targets and comprehensive effects on anti-aging. Compared with the existing researches, it was found that the kidney-tonifying herbal medicines may exert anti-aging effects in multiple pathways in this study.
authors.affiliation: Guangzhou University of Chinese Medicine, Airport Road NO.12, Guangzhou, People's Republic of China. jiangqiyu@gzucm.edu.cn.
authors.forename: Qi-Yu
authors.initials: QY
authors.lastname: Jiang
authors.affiliation: Guangzhou University of Chinese Medicine, Airport Road NO.12, Guangzhou, People's Republic of China.
authors.forename: Mei-Si
authors.initials: MS
authors.lastname: Zheng
authors.affiliation: Guangzhou University of Chinese Medicine, Airport Road NO.12, Guangzhou, People's Republic of China.
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Yang
authors.affiliation: Guangzhou University of Chinese Medicine, Airport Road NO.12, Guangzhou, People's Republic of China. sunxiaosheng@gzucm.edu.cn.
authors.forename: Xiao-Sheng
authors.initials: XS
authors.lastname: Sun
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000235:genetics; D019295:Computational Biology; D057225:Data Mining; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects*; D006801:Humans; D010946:Plants, Medicinal / Q000737:chemistry; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004365:Drugs, Chinese Herbal; D011506:Proteins
keywords: Anti-aging; Bioinformatics; Data mining; Kidney-tonifying; Molecular Network