title: Discovery of antifungal constituents from the Miao medicinal plant Isodon flavidus.
abstract: BACKGROUND
  Leigong Mountain is an area in the Southwest of China where there is a high incidence rate of athlete's foot, but the Miao people, a Chinese minority who reside in this mountainous area have suffered less from this disease due to their use of the herbal medicine Isodon flavidus (Hand.-Mazz.) H. Hara.
  
  
  OBJECTIVE
  The present study is to identify the active chemical constituents responsible for antifungal effects of the folk medicine plant.
  
  
  METHODS
  The natural compounds were separated from the methanol extract of the twigs and leaves of I. flavidus by phytochemical study using chromatographic methods, and their chemical structures were determined by analysis of the spectroscopic data including 1D and 2D NMR spectra. The absolute configuration of fladin A (1) was further confirmed by X-ray crystallographic analysis. The compounds were evaluated for their antifungal activity against the athlete's foot fungus Trichophyton rubrum. They were further evaluated for their antimicrobial and anti-biofilm activity against the dental pathogens Streptococcus mutans, Porphyromonas gingivalis and Candida albicans.
  
  
  RESULTS
  Phytochemical and biological studies of I. flavidus led to the discovery of two antifungal compounds, fladin A (1) and lophanic acid (2). Fladin A (1) is a novel diterpene with an unprecedented cyclic ether group formed between C-4 and C-9. Lophanic acid (2) displayed inhibition activity against the athlete's foot fungus Trichophyton rubrum with an MIC value of 7.8μg/mL, and fladin A (1) also showed inhibition activity against the fungus with a MIC value of 62.5μg/mL.
  
  
  CONCLUSIONS
  Our identification of two antifungal compounds provided strong evidence for the Miao people to use I. flavidus as a medicinal plant for treatment of athlete's foot disease. The very different chemical structures of the active compounds from those in the market presents them as potential antifungal lead compounds for follow-up study.
authors.affiliation: Guiyang College of Traditional Chinese Medicine, 50 Shidong Road, Guiyang 550002, China.
authors.forename: Ji-Xin
authors.initials: JX
authors.lastname: Li
authors.affiliation: Guiyang College of Traditional Chinese Medicine, 50 Shidong Road, Guiyang 550002, China.
authors.forename: Qi-Ji
authors.initials: QJ
authors.lastname: Li
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon Tong, Kowloon, Hong Kong, China.
authors.forename: Yi-Fu
authors.initials: YF
authors.lastname: Guan
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon Tong, Kowloon, Hong Kong, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Song
authors.affiliation: Guiyang College of Traditional Chinese Medicine, 50 Shidong Road, Guiyang 550002, China.
authors.forename: Ya-Hua
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Guiyang College of Traditional Chinese Medicine, 50 Shidong Road, Guiyang 550002, China.
authors.forename: Jing-Jie
authors.initials: JJ
authors.lastname: Zhang
authors.affiliation: Guiyang College of Traditional Chinese Medicine, 50 Shidong Road, Guiyang 550002, China.
authors.forename: Wan-Fei
authors.initials: WF
authors.lastname: Li
authors.affiliation: Guiyang College of Traditional Chinese Medicine, 50 Shidong Road, Guiyang 550002, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Du
authors.affiliation: Dows Institute for Dental Research, College of Dentistry, The University of Iowa, N413 DSB, Iowa City, IA 52242, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Dows Institute for Dental Research, College of Dentistry, The University of Iowa, N413 DSB, Iowa City, IA 52242, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Banas
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, China.
authors.forename: Xiao-Nian
authors.initials: XN
authors.lastname: Li
authors.affiliation: Guiyang College of Traditional Chinese Medicine, 50 Shidong Road, Guiyang 550002, China. Electronic address: ltpan@sina.cn.
authors.forename: Lu-Tai
authors.initials: LT
authors.lastname: Pan
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon Tong, Kowloon, Hong Kong, China. Electronic address: zhanghj@hkbu.edu.hk.
authors.forename: Hong-Jie
authors.initials: HJ
authors.lastname: Zhang
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D018360:Crystallography, X-Ray; D037602:Isodon / Q000737:chemistry*; D000432:Methanol / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D018547:Plant Stems / Q000737:chemistry; D010946:Plants, Medicinal; D066244:Proton Magnetic Resonance Spectroscopy; D012997:Solvents / Q000737:chemistry; D014008:Tinea Pedis / Q000188:drug therapy* / Q000382:microbiology; D014249:Trichophyton / Q000187:drug effects* / Q000254:growth & development
chemical_list: D000935:Antifungal Agents; D010936:Plant Extracts; D012997:Solvents; D000432:Methanol
keywords: Antifungal activity; Fladin A; Isodon flavidus; Isolation; Lophanic acid; Lophanic acid (PubChem CID: 101787485); Structure identification