title: Antagonism of Cortex Periplocae extract-induced catecholamines secretion by Panax notoginseng saponins in cultured bovine adrenal medullary cells by drug combinations.
abstract: BACKGROUND
  Traditional Chinese Medicine (TCM) operates on the general principle that compatible components of different herbal decoction may work together to synergistically enhance therapeutic efficacy or reduce adverse effects. Cortex Periplocae is an herb that has been used in TCM clinics for a long time in the treatment of chronic heart failure. However, recently, the use of this herb has been restricted because of widespread abuse and misapplications. Radix Notoginseng is another herb that is used in TCM because of its protective role on cardiomyocytes. From our previous studies on these two herbs in a mouse model, we observed an increased LD50 after oral administration of Cortex Periplocae extract (CPE) and Panax notoginseng saponins (PNS) in a ratio of 1:1 compared with Cortex Periplocae extract used alone.
  
  
  OBJECTIVE
  This study aimed to investigate whether there are mutual synergistic effects of the two herbal extracts, CPE and PNS, on catecholamines (CAs) secretion, and their possible underlying mechanism(s) for such effects.
  
  
  METHODS
  CPE and PNS were quantified by the LC-MS/MS method. HPLC-ECD was used to determine the CAs secreted into the medium by bovine adrenal medulla cells (BAMCs) and calcium influx was measured using a Calcium 4 reagent kit.
  
  
  RESULTS
  We found that the stimulatory effect of CPE on CAs secretion was inhibited when used together with PNS. For a better clarification of the different constituents of the extracts, a quantitative analysis was carried out. Periplocin was found to be the main active component of CPE valued as 0.99% and saponins were the principal constituents of PNS. These results also showed that CPE increased the secretion of CAs in a dose-dependent manner while the actions of PNS were seen to be inhibitory. Periplocin monomer of CPE could be implicated for the actions of CPE since it plays the role of increasing the ACh-induced CAs secretion in a calcium-dependent manner. We therefore conclude that; CPE and PNS exert antagonistic effects in regulating the concentration of intracellular calcium.
  
  
  CONCLUSIONS
  PNS inhibits CPE-induced CAs secretion by suppressing calcium influx in bovine adrenal medulla cells while periplocin, one of the main components of CPE has the same secretagogue effect as CPE.
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Guo
authors.forename: Haoping
authors.initials: H
authors.lastname: Mao
authors.forename: Guixiang
authors.initials: G
authors.lastname: Pan
authors.forename: Han
authors.initials: H
authors.lastname: Zhang
authors.forename: Ganwei
authors.initials: G
authors.lastname: Fan
authors.forename: Weiwei
authors.initials: W
authors.lastname: Li
authors.forename: Kun
authors.initials: K
authors.lastname: Zhou
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yanagihara
authors.forename: Xiumei
authors.initials: X
authors.lastname: Gao
mesh_terms: D000313:Adrenal Medulla / Q000166:cytology; D000818:Animals; D002395:Catecholamines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D004347:Drug Interactions; D053723:Panax notoginseng; D031109:Periploca; D024301:Plant Bark; D010936:Plant Extracts / Q000008:administration & dosage*; D018517:Plant Roots; D012503:Saponins / Q000008:administration & dosage*
chemical_list: D002395:Catecholamines; D010936:Plant Extracts; D012503:Saponins