title: Antidepressant-like effects of the hydroalcoholic extracts of Hemerocallis citrina and its potential active components.
abstract: BACKGROUND
  Herbal therapies are potential alternatives and adjuncts for depression treatment. The present study aims to investigate the antidepressant-like effects of hydroalcoholic Hemerocallis citrina extracts and its potential neuropharmacological components.
  
  
  METHODS
  Hydroalcoholic H. citrina extracts were phytochemically analyzed. Behavioral models, including tail suspension tests and open field tests, were performed to evaluate the antidepressant-like effects of the extracts. A possible mechanism was explored by analyzing brain monoamine neurotransmitters. Toxicity and histopathological analyses were performed to determine whether or not the extracts are safe for oral administration.
  
  
  RESULTS
  The antidepressant-like effects of hydroalcoholic H. citrina extracts were mainly related to flavonoids, especially rutin and hesperidin. The extract prepared using 75% ethanol (i.e., HCE75) exhibited the highest active flavonoid content and activity. Orally administered 400 mg/kg of HCE75 significantly induced an antidepressant-like effect, whereas the combination of equivalent rutin and hesperidin dosages exhibited the same profiles. Isobologram analysis showed sub-additive antidepressant interactions between rutin and hesperidin. HCE75 (400 mg/kg, p.o.) increased the serotonin and dopamine levels in the central nervous system. Mortality and lesions were not observed upon oral administration of up to 5000 mg/kg HCE75.
  
  
  CONCLUSIONS
  The antidepressant-like effects of hydroalcoholic H. citrina extracts are mainly related to flavonoids, especially rutin and hesperidin. The serotonergic and dopaminergic systems may have major roles. The active extract is toxicologically safe for oral administration.
authors.forename: Bingjian
authors.initials: B
authors.lastname: Du
authors.forename: Xiaoshuang
authors.initials: X
authors.lastname: Tang
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.forename: Chunyue
authors.initials: C
authors.lastname: Zhang
authors.affiliation: CAU & ACC Joint-Laboratory of Space Food, College of Food Science & Nutritional Engineering, Key Laboratory of Functional Dairy Science of Beijing and Ministry of Education, Beijing Higher Institution Engineering Research Center of Animal Product, Beijing Dairy Industry Innovation Team, China Agricultural University, No,17 Qinghua East Road, Haidian, Beijing 100083, People's Republic of China. gzhao1000@163.com.
authors.forename: Guanghua
authors.initials: G
authors.lastname: Zhao
authors.forename: Fazheng
authors.initials: F
authors.lastname: Ren
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Leng
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D031421:Hemerocallis / Q000737:chemistry*; D006569:Hesperidin / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D019417:Hindlimb Suspension; D008297:Male; D008813:Mice, Inbred ICR; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D012431:Rutin / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D012701:Serotonin / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D010936:Plant Extracts; D012701:Serotonin; D012431:Rutin; D006569:Hesperidin; D004298:Dopamine