title: Sulfur fumigation reducing systemic exposure of ginsenosides and weakening immunomodulatory activity of ginseng.
abstract: BACKGROUND
  Ginseng (Ginseng Radix et Rhizoma) is used worldwide for its miracle tonic effects, especially for its immunomodulatory activities. Sulfur fumigation, a fast and convenient method to prevent pesticidal and bacterial contamination in the food industry, has been recently employed during post-harvest processing of ginseng. Our previous studies demonstrated that sulfur fumigation significantly altered the chemical profile of the bioactive ingredients in ginseng. However, the effects of sulfur fumigation on the pharmacokinetics and bioactivities of ginseng remain unknown.
  
  
  OBJECTIVE
  To examine the effects of sulfur fumigation on the pharmacokinetics and immunomodulatory activities of ginseng.
  
  
  METHODS
  For pharmacokinetic studies, male Sprague-Dawley rats exposed to single/multiple dosages of non-fumigated ginseng (NFG) and sulfur fumigated ginseng (SFG) were investigated using HPLC-MS/MS analysis. For bioactivity studies, male ICR mice were used to compare the immunomodulatory effects of NFG or SFG under both normal and cyclophosphamide (CY)-induced immunocompromised conditions using white blood cell counts, serum cytokine levels, and spleen and thymus weight indices.
  
  
  RESULTS
  Sulfur fumigation significantly reduced the contents of the bioactive ginsenosides in ginseng, which resulted in drastically low systemic exposure of ginsenosides in SFG-treatment group compared to NFG-treatment group. This observation was consistent with the bioactivities obtained in NFG- and SFG-treatment groups. The bioactivity studies also demonstrated the immunomodulatory effects of NFG but not SFG in the CY-induced immunosuppressed mice.
  
  
  CONCLUSIONS
  Sulfur fumigation significantly reduced contents of bioactive ginsenosides in ginseng, leading to dramatic decrease in the systemic exposure of these ginsenosides in the body and detrimental reduction of immunomodulatory effects of ginseng. Our results provided scientific evidences and laid a solid foundation for the needs of thorough evaluation of the significant impact of sulfur fumigation on ginseng and other medicinal herbs.
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR; Joint Research Laboratory of Promoting Globalization of Traditional Chinese Medicines between The Chinese University of Hong Kong and Shanghai Institute of Materia Medica, Chinese Academy of Sciences, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Ma
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR; Joint Research Laboratory of Promoting Globalization of Traditional Chinese Medicines between The Chinese University of Hong Kong and Shanghai Institute of Materia Medica, Chinese Academy of Sciences, PR China.
authors.forename: Winnie Lai Ting
authors.initials: WL
authors.lastname: Kan
authors.affiliation: Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, PR China; Department of Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine and Jiangsu Branch of China Academy of Chinese Medical Sciences, Nanjing, Jiangsu, PR China.
authors.forename: He
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, PR China; Department of Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine and Jiangsu Branch of China Academy of Chinese Medical Sciences, Nanjing, Jiangsu, PR China. Electronic address: songlinli64@126.com.
authors.forename: Song-Lin
authors.initials: SL
authors.lastname: Li
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR; Joint Research Laboratory of Promoting Globalization of Traditional Chinese Medicines between The Chinese University of Hong Kong and Shanghai Institute of Materia Medica, Chinese Academy of Sciences, PR China. Electronic address: linge@cuhk.edu.hk.
authors.forename: Ge
authors.initials: G
authors.lastname: Lin
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003520:Cyclophosphamide / Q000494:pharmacology; D005651:Fumigation; D036145:Ginsenosides / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000494:pharmacology*; D007107:Immune System / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016867:Immunocompromised Host; D007155:Immunologic Factors / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007376:Interleukin-2 / Q000097:blood; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D008813:Mice, Inbred ICR; D005894:Panax / Q000737:chemistry*; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000494:pharmacology*; D010946:Plants, Medicinal; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D013455:Sulfur / Q000737:chemistry*; D053719:Tandem Mass Spectrometry; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology
chemical_list: D036145:Ginsenosides; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D010936:Plant Extracts; D013455:Sulfur; D003520:Cyclophosphamide
keywords: Ginseng; Immunomodulation; Pharmacodynamics; Pharmacokinetics; Quality control; Sulfur fumigation