title: Cancer chemopreventive activity of compounds isolated from Waltheria indica.
abstract: BACKGROUND
  Waltheria indica L. is traditionally used in several countries against inflammatory related diseases and cancer, mainly as a decoction of the aerial parts.
  
  
  OBJECTIVE
  The transcription factor NF-κB is known to induce tumor promotion and progression and is considered a major player in inflammation-driven cancers. Therefore, inhibitors of this pathway possess cancer chemopreventive and chemotherapeutic activities. This study aimed first to confirm the use of Waltheria indica as a traditional anti-inflammatory remedy by assessing the NF-κB inhibitory activity and then to identify the major bioactive compounds. The isolated compounds were also tested for their QR inducing property, a complementary strategy in cancer chemoprevention able to target tumor initiation. Finally, the relevance of in vitro results was examined by investigating the occurrence of the active compounds in traditional preparations.
  
  
  METHODS
  Compounds were isolated from the dichloromethane extract of the aerial parts using flash chromatography and semi-preparative HPLC. NF-κB inhibitory activity of pure compounds from Waltheria indica was assessed using a luciferase reporter assay in HEK293 cells. Their QR inducing activity was also assessed in Hepa1c1c7 cells.
  
  
  RESULTS
  Twenty-nine compounds, of which 5 are new, were obtained from the dichloromethane extract and tested for their cancer chemoprevention activity. Eleven compounds inhibited NF-κB and/or induced QR in the low to mid µM range. Chrysosplenol E (20) was active in both tests. Two of the most potent NF-κB inhibitors, waltherione A (4) and waltherione C (5), as well as 20 were found in the traditional decoction, in which 4 and 5 were major compounds.
  
  
  CONCLUSIONS
  The presence of potent NF-κB inhibitors and QR inducing compounds in the decoction of the aerial parts of Waltheria indica supports its traditional use in inflammatory-related diseases and cancer chemoprevention.
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, CMU, Rue Michel-Servet 1, 1211 Geneva 4, Switzerland. Electronic address: Aymeric.Monteillier@unige.ch.
authors.forename: Aymeric
authors.initials: A
authors.lastname: Monteillier
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, CMU, Rue Michel-Servet 1, 1211 Geneva 4, Switzerland. Electronic address: Sylvian.Cretton@unige.ch.
authors.forename: Sylvian
authors.initials: S
authors.lastname: Cretton
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, CMU, Rue Michel-Servet 1, 1211 Geneva 4, Switzerland. Electronic address: Olivier.Ciclet@unige.ch.
authors.forename: Olivier
authors.initials: O
authors.lastname: Ciclet
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, CMU, Rue Michel-Servet 1, 1211 Geneva 4, Switzerland. Electronic address: Laurence.Marcourt@unige.ch.
authors.forename: Laurence
authors.initials: L
authors.lastname: Marcourt
authors.affiliation: Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G. C., Evin, Tehran, Iran. Electronic address: s_ebrahimi@sbu.ac.ir.
authors.forename: Samad Nejad
authors.initials: SN
authors.lastname: Ebrahimi
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, CMU, Rue Michel-Servet 1, 1211 Geneva 4, Switzerland. Electronic address: philippe.christen@unige.ch.
authors.forename: Philippe
authors.initials: P
authors.lastname: Christen
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, CMU, Rue Michel-Servet 1, 1211 Geneva 4, Switzerland. Electronic address: muriel.cuendet@unige.ch.
authors.forename: Muriel
authors.initials: M
authors.lastname: Cuendet
mesh_terms: D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D016588:Anticarcinogenic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004790:Enzyme Induction / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D019660:Malvaceae / Q000737:chemistry*; D008519:Medicine, Traditional / Q000379:methods; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis; D016328:NF-kappa B / Q000378:metabolism; D035261:Plant Components, Aerial; D010936:Plant Extracts / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D016588:Anticarcinogenic Agents; D016328:NF-kappa B; D010936:Plant Extracts; D016660:NAD(P)H Dehydrogenase (Quinone)
keywords: Adouetin X (PubChem CID: 5281577); Adouetin Y (PubChem CID: 5281578); Adouetin Y' (PubChem CID: 101731531); Chrysosplenol E (PubChem CID: 5315857); Inflammation; NF-κB; Oxyanin A (PubChem CID: 5281676); Quinone reductase; Traditional medicine; Vitexicarpin (PubChem CID: 5315263); Waltheria indica; Waltherione A (PubChem CID: 11474862); Waltherione C (PubChem CID: 102362412)