title: Analgesic and anti-inflammatory activity and pharmacokinetics of alkaloids from seeds of Strychnos nux-vomica after transdermal administration: effect of changes in alkaloid composition.
abstract: BACKGROUND
  Strychnos nux-vomica L. (Loganiaceae) is grown extensively in southern Asian countries. The dried seed of this plant, nux vomica, has been clinically used in Chinese folk medicine for improving blood circulation, relieving rheumatic pain, reducing swelling and treating cancer.
  
  
  OBJECTIVE
  This study was carried out to investigate the effect of removing most strychnine from the total alkaloid fraction (TAF) extracted from nux vomica on analgesic and anti-inflammatory activity and pharmacokinetics after transdermal administration.
  
  
  METHODS
  Most strychnine was removed from TAF and the resulted modified total alkaloid fraction (MTAF) was obtained. The contents of strychnine and brucine in TAF and MTAF were determined. Then the analgesic and anti-inflammatory activity of TAF, MTAF, brucine and strychnine dissolved in hydrogel was compared after transdermal administration. Furthermore, in vitro and in vivo transdermal absorption profiles of brucine after administration of TAF, MTAF and brucine dissolved in hydrogel were also compared.
  
  
  RESULTS
  In contrast to TAF, most strychnine was removed from MTAF and the ratio of brucine to strychnine was adjusted from 1:1.8 to 2.7:1. MTAF showed significant analgesic activity in all the chemical-, thermal- and physical- induced nociception models, which indicated the presence of both centrally and peripherally mediated activities. MTAF also showed significant anti-inflammatory activity against xylene-induced ear edema. But TAF and strychnine demonstrated little activity in all those pharmacological tests. Brucine showed to be effective in acetic acid-induced writhing and xylene-induced ear edema test. Brucine in MTAF was absorbed more completely than it alone at the same dosage of brucine after transdermal administration.
  
  
  CONCLUSIONS
  The results from the present study appeared to support the viewpoint that most strychnine should be removed from TAF to improve analgesic and anti-inflammatory activity. The relatively higher pharmacological activity of MTAF compared to brucine alone is partly due to the enhanced transdermal absorption of brucine.
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Xuan
authors.initials: X
authors.lastname: Wang
authors.forename: Yan-Ge
authors.initials: YG
authors.lastname: Qu
authors.forename: Zhi-Peng
authors.initials: ZP
authors.lastname: Chen
authors.forename: Hao
authors.initials: H
authors.lastname: Cai
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.forename: Fei
authors.initials: F
authors.lastname: Xu
authors.forename: Tu-Lin
authors.initials: TL
authors.lastname: Lu
authors.forename: Bao-Chang
authors.initials: BC
authors.lastname: Cai
mesh_terms: D019342:Acetic Acid; D000279:Administration, Cutaneous; D000470:Alkaloids / Q000097:blood / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000700:Analgesics / Q000097:blood / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000097:blood / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D006358:Hot Temperature; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D008517:Phytotherapy; D010936:Plant Extracts / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D012639:Seeds / Q000737:chemistry; D012869:Skin Absorption; D031461:Strychnos nux-vomica / Q000737:chemistry; D014992:Xylenes
chemical_list: D000470:Alkaloids; D000700:Analgesics; D000893:Anti-Inflammatory Agents; D010936:Plant Extracts; D014992:Xylenes; D019342:Acetic Acid