title: Characterisation of polyphenolic compounds in Clerodendrum petasites S. Moore and their potential for topical delivery through the skin.
abstract: BACKGROUND
  Clerodendrum petasites S. Moore (CP) has been widely prescribed in Thailand and neighbouring countries for both oral and topical administration to treat asthma, fever, cough, vomiting and skin diseases, for at least 30 years. However, the nature of the active species remains poorly characterized and there have been no clinical trials concerning the topical delivery of this medicine. The study aims to characterise polyphenolic compounds in the plant, to predict the feasibility of their topical absorption and to test their ability to penetrate the skin.
  
  
  METHODS
  Identification and quantification of flavonoids and phenolic acid derivatives in an ethanolic extract of the aerial parts of the plant were carried out using high performance liquid chromatography (HPLC) with photodiode array (PDA) and mass spectrometry (MS) detection. Ambiguous isomeric compounds were distinguished by nuclear magnetic resonance (NMR) spectroscopy. The feasibility of the compounds׳ topical permeability was evaluated by predicting their maximum fluxes from their physicochemical properties. The skin penetration of compounds in the plant extract was measured in vitro over 24h.
  
  
  RESULTS
  Vanillic acid, verbascoside, 4-coumaric acid, ferulic acid, nepetin, luteolin, apigenin, naringenin, hispidulin, hesperetin and chrysin, were identified in CP. All compounds except apigenin and hispidulin are reported in this species for the first time. Hispidulin is the predominant compound (1.2% w/w in a dried ethanolic extract) followed by nepetin, verbascoside, vanillic acid, and apigenin. Across mammalian skin, hispidulin was percutaneously absorbed within 3h and vanillic acid and nepetin permeated the skin after 6h. These experimental observations were consistent with the predicted maximum fluxes of these compounds calculated from their physicochemical properties.
  
  
  CONCLUSIONS
  Many of the phenolic compounds reported in this study are well-known to possess antimicrobial, anti-inflammatory and anti-oxidant activities. The skin permeation studies reported here support traditional topical uses of the plant in skin treatments and are useful for further topical formulation optimisation.
authors.affiliation: Department of Pharmacy & Pharmacology, University of Bath, Bath, BA2 7AY, England, UK; Center of Applied Thai Traditional Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok 10700, Thailand. Electronic address: premrutai@gmail.com.
authors.forename: Premrutai
authors.initials: P
authors.lastname: Thitilertdecha
authors.affiliation: Department of Pharmacy & Pharmacology, University of Bath, Bath, BA2 7AY, England, UK.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Guy
authors.affiliation: Department of Pharmacy & Pharmacology, University of Bath, Bath, BA2 7AY, England, UK.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rowan
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D032409:Clerodendrum / Q000737:chemistry*; D020834:Ethnopharmacology; D066298:In Vitro Techniques; D057230:Limit of Detection; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D035261:Plant Components, Aerial / Q000737:chemistry*; D059808:Polyphenols / Q000008:administration & dosage / Q000302:isolation & purification / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D034421:Sus scrofa
chemical_list: D059808:Polyphenols
keywords: Clerodendrum petasites; HPLC–MS; Hispidulin (PubChem CID: 5281628); Nepetin (PubChem CID: 5317284); Phenolic compounds; Thai traditional medicine; Topical delivery; Vanillic acid (PubChem CID: 8468); Verbascoside (PubChem CID: 5281800)