title: The Osmanthus fragrans flower phenylethanoid glycoside-rich extract: Acute and subchronic toxicity studies.
abstract: BACKGROUND
  Osmanthus fragrans var. thunbergii (O. fragrans) flower has been consumed as folk medicine for thousands of years. O. fragrans flower extract is a well-characterized phenylethanoid glycoside-rich extract, which has been used as a natural anti-oxidant. The aim of this study was to evaluate the safety of O. fragrans flower phenylethanoid glycoside-rich extract (OFFE).
  
  
  METHODS
  The OFFE was extracted by 80% (v/v) aqueous ethanol with 0.01% sodium isoascorbate (w/v) from the O. fragrans flower and purified on HPD300 resins. The total phenylethanoid glycosides content and individual phenylethanoid glycosides was determined by photocolorimetric method and reversed phase UPLC respectively. An acute oral toxicity study, reverse mutation test, bone marrow cell micronucleus test, and sperm abnormality test as well as a 90-day oral toxicity study were performed on experimental animals.
  
  
  RESULTS
  The total content of phenylethanoid glycosides in OFFE was 73.4g acteoside equivalent per 100g of extract, include acteoside (52.5g per 100g of extract), salidroside (13.8g per 100g of extract), and isoacteoside (2.6g per 100g of extract) and so on. No acute lethal effect at the maximal tested OFFE dose of 10g/kg body weight (bw) in either rats or mice was observed, suggesting that OFFE can be considered nontoxic. No evidence for mutagenicity was detected in any of the three mutagenic tests. Administration at levels of 0.50, 1.00, and 2.00g/kg bw to rats for 90 days failed to induce any significant hematological, clinical, chemical, or histopathological changes. The no-observed adverse-effect-level for OFFE was >2.00g/kg bw for the study on subchronic toxicity.
  
  
  CONCLUSIONS
  The results showed that consuming OFFE has no adverse effects and poses no health risk in the acute oral toxicity study, subchronic oral toxicity study, and in the micronucleus test, which may provide supportive evidence for the safety of OFFE powder that has been used in medicine as well as in functional foods, and dietary supplements.
authors.affiliation: Zhejiang University, College of Biosystems Engineering and Food Science, Fuli Institute of Food Science, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang R&D Center for Food Technology and Equipment, Hangzhou 310058, China; Laboratory of Quality & Safety Risk Assessment for Agro-products on Storage and Preservation, Minstry of Agriculture, Hangzhou 310058, China. Electronic address: bylu@zju.edu.cn.
authors.forename: Baiyi
authors.initials: B
authors.lastname: Lu
authors.affiliation: Zhejiang University, College of Biosystems Engineering and Food Science, Fuli Institute of Food Science, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang R&D Center for Food Technology and Equipment, Hangzhou 310058, China; Laboratory of Quality & Safety Risk Assessment for Agro-products on Storage and Preservation, Minstry of Agriculture, Hangzhou 310058, China.
authors.forename: Maiquan
authors.initials: M
authors.lastname: Li
authors.affiliation: Zhejiang University, College of Biosystems Engineering and Food Science, Fuli Institute of Food Science, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang R&D Center for Food Technology and Equipment, Hangzhou 310058, China; Laboratory of Quality & Safety Risk Assessment for Agro-products on Storage and Preservation, Minstry of Agriculture, Hangzhou 310058, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Department of Applied Technology, Zhejiang Economic & Trade Polytechnic, Hangzhou 310018, China.
authors.forename: Weisu
authors.initials: W
authors.lastname: Huang
authors.affiliation: Zhejiang University, College of Biosystems Engineering and Food Science, Fuli Institute of Food Science, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang R&D Center for Food Technology and Equipment, Hangzhou 310058, China; Laboratory of Quality & Safety Risk Assessment for Agro-products on Storage and Preservation, Minstry of Agriculture, Hangzhou 310058, China.
authors.forename: Yirong
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Zhejiang University, College of Biosystems Engineering and Food Science, Fuli Institute of Food Science, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang R&D Center for Food Technology and Equipment, Hangzhou 310058, China; Laboratory of Quality & Safety Risk Assessment for Agro-products on Storage and Preservation, Minstry of Agriculture, Hangzhou 310058, China.
authors.forename: Shuqin
authors.initials: S
authors.lastname: Mao
authors.affiliation: Zhejiang University, College of Biosystems Engineering and Food Science, Fuli Institute of Food Science, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang R&D Center for Food Technology and Equipment, Hangzhou 310058, China; Laboratory of Quality & Safety Risk Assessment for Agro-products on Storage and Preservation, Minstry of Agriculture, Hangzhou 310058, China.
authors.forename: Yajing
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Zhejiang University, College of Biosystems Engineering and Food Science, Fuli Institute of Food Science, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang R&D Center for Food Technology and Equipment, Hangzhou 310058, China; Laboratory of Quality & Safety Risk Assessment for Agro-products on Storage and Preservation, Minstry of Agriculture, Hangzhou 310058, China.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Lou
mesh_terms: D000818:Animals; D005260:Female; D035264:Flowers; D006027:Glycosides / Q000032:analysis / Q000633:toxicity*; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests; D029592:Oleaceae; D010936:Plant Extracts / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013094:Spermatozoa / Q000187:drug effects; D023382:Toxicity Tests, Acute; D059550:Toxicity Tests, Subchronic
chemical_list: D006027:Glycosides; D010936:Plant Extracts
keywords: Acteoside; Acteoside (PubChem CID: 354009); Acute toxicity sudy; Caffeic acid (PubChem CID: 689043); Chlorogenic acid (PubChem CID: 1794427); Isoacteoside (PubChem CID: 6438553); Nontoxic; OFFE; Phenylethanoid glycoside; Salidroside (PubChem CID: 159278); Subchronic toxicity study