ABSTRACT
AIM To explore analgesic mechanism of Yaobitong Capsules (Notoginseng Radix et Rhizoma,Chuanxiong Rhizoma,Corydalis Rhizoma,etc.) on lumbar intervertebral discs.METHODS An array of data mining,molecular docking and network analysis were employed to investigate the active compounds and key target protein.RESULTS Among the forty-six active hits identified by virtual screening,most compounds displayed good oral bioavailability and might confer an optimal CNS exposure.And eleven molecules (coptisine,diligustilide,corypalmine,chuanxiongterpene,etc.) were further confirmed to alleviate lumbar intervertebral discs through their targeting at nineteen proteins (such as p38,CGRP,MMPs,TNFα) to inhibit the inflammatory response and the infiltration of microvasculature,to reduce the nociceptors sensitivity,and to modulate the balance of Collagen and proteoglycans in catabolic and anabolic responses.CONCLUSION Yaobitong Capsules' clear molecular working mechanism and the key active compounds are revealed by this network-assisted investigation highlight the subsequent experiments on targets and active compounds.
ABSTRACT
The molecular vibration-activity relationship in the receptor-ligand interaction of adenosine receptors was investigated by structure similarity, molecular vibration, and hierarchical clustering in a dataset of 46 ligands of adenosine receptors. The resulting dendrogram was compared with those of another kind of fingerprint or descriptor. The dendrogram result produced by corralled intensity of molecular vibrational frequency outperformed four other analyses in the current study of adenosine receptor agonism and antagonism. The tree that was produced by clustering analysis of molecular vibration patterns showed its potential for the functional classification of adenosine receptor ligands.