title: Ophiocordyceps formosana improves hyperglycemia and depression-like behavior in an STZ-induced diabetic mouse model.
abstract: BACKGROUND
  A newly defined Cordyceps species, Ophiocordyceps formosana (O. formosana) has been implicated in multitudinous bioactivities, including lowering glucose and cholesterol levels and modulating the immune system. However, few literatures demonstrate sufficient evidence to support these proposed functions. Although the use of Cordyceps spp. has been previously addressed to improve insulin insensitivity and improve the detrimental symptoms of depression; its mechanistic nature remains unsettled. Herein, we reveal the effects of O. formosana in ameliorating hyperglycemia accompanied with depression.
  
  
  METHODS
  Diabetes was induced in mice by employing streptozotocin(STZ), a chemical that is toxic to insulin-producing β cells of the pancreas. These streptozotocin (STZ)-induced diabetic mice showed combined symptoms of hyperglycemia and depressive behaviors. Twenty-four STZ-induced mice were randomly divided into 3 groups subjected to oral gavage with 100 μL solution of either PBS or 25 mg/mL Ophiocordyceps formosana extract (OFE) or 2 mg/mL rosiglitazone (Rosi, positive control group). Treatments were administered once per day for 28 days. An additional 6 mice without STZ induction were treated with PBS to serve as the control group. Insulin sensitivity was measured by a glucose tolerance test and levels of adiponectin in plasma and adipose tissue were also quantified. Behavioral tests were conducted and levels of monoamines in various brain regions relating to depression were evaluated.
  
  
  RESULTS
  HPLC analysis uncovered three major constituents, adenosine, D-mannitol and cordycepin, within O. formosana similar to other prestigious medicinal Cordyceps spp.. STZ-induced diabetic mice demonstrated decreased body weight and subcutaneous adipose tissue, while these symptoms were recovered in mice receiving OFE treatment. Moreover, the OFE group displayed improved insulin sensitivity and elevated adiponectin within the plasma and adipose tissue. The anti-depressive effect of OFE was observed in various depression-related behavior tests. Concurrently, neurotransmitters, like 5-HT and dopamine in the frontal cortex, striatum and hippocampus were found to be up-regulated in OFE-treated mice.
  
  
  CONCLUSIONS
  Our findings illustrated, for the first time, the medicinal merits of O. formosana on Type I diabetes and hyperglycemia-induced depression. OFE were found to promote the expression of adiponectin, which is an adipokine involved in insulin sensitivity and hold anti-depressive effects. In addition, OFE administration also displayed altered levels of neurotransmitters in certain brain regions that may have contributed to its anti-depressive effect. Collectively, this current study provided insights to the potential therapeutic effects of O. formosana extracts in regards to hyperglycemia and its depressive complications.
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, Taipei, 10617, Taiwan.
authors.forename: Chao-Wei
authors.initials: CW
authors.lastname: Huang
authors.affiliation: Mucho Biotechnology Inc., Taipei, 10684, Taiwan.
authors.forename: Tzu-Wen
authors.initials: TW
authors.lastname: Hong
authors.affiliation: Department of Plant Pathology and Microbiology, National Taiwan University, Taipei, 10617, Taiwan.
authors.forename: Ying-Jing
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: Department of Plant Pathology and Microbiology, National Taiwan University, Taipei, 10617, Taiwan.
authors.forename: Ko-Chien
authors.initials: KC
authors.lastname: Chen
authors.affiliation: Department of Psychology, National Taiwan University, Taipei, 10617, Taiwan.
authors.forename: Ju-Chun
authors.initials: JC
authors.lastname: Pei
authors.affiliation: Department of Athletics, National Taiwan University, Taipei, 10617, Taiwan.
authors.forename: Tai-Yuan
authors.initials: TY
authors.lastname: Chuang
authors.affiliation: Department of Psychology, National Taiwan University, Taipei, 10617, Taiwan.
authors.forename: Wen-Sung
authors.initials: WS
authors.lastname: Lai
authors.affiliation: Mucho Biotechnology Inc., Taipei, 10684, Taiwan.
authors.forename: Sheng-Hong
authors.initials: SH
authors.lastname: Tsai
authors.affiliation: Mucho Biotechnology Inc., Taipei, 10684, Taiwan.
authors.forename: Richard
authors.initials: R
authors.lastname: Chu
authors.affiliation: Institute of Food Science and Technology, National Taiwan University, Taipei, 10617, Taiwan.
authors.forename: Wei-Cheng
authors.initials: WC
authors.lastname: Chen
authors.affiliation: Institute of Food Science and Technology, National Taiwan University, Taipei, 10617, Taiwan.
authors.forename: Lee-Yan
authors.initials: LY
authors.lastname: Sheen
authors.affiliation: Graduate School of Comprehensive Human Sciences, University of Tsukuba 1-1-1, Tennodai, Tsukuba, 305-8575, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, Taipei, 10617, Taiwan. sding@ntu.edu.tw.|Institute of Biotechnology, National Taiwan University, Taipei, 10617, Taiwan. sding@ntu.edu.tw.
authors.forename: Shih-Torng
authors.initials: ST
authors.lastname: Ding
authors.affiliation: Department of Plant Pathology and Microbiology, National Taiwan University, Taipei, 10617, Taiwan. shentl@ntu.edu.tw.|Institute of Biotechnology, National Taiwan University, Taipei, 10617, Taiwan. shentl@ntu.edu.tw.
authors.forename: Tang-Long
authors.identifier: http://orcid.org/0000-0001-6264-3608
authors.initials: TL
authors.lastname: Shen
mesh_terms: D052242:Adiponectin; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001688:Biological Products / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D003863:Depression / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental; D006943:Hyperglycemia / Q000097:blood*; D006999:Hypocreales / Q000737:chemistry*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013311:Streptozocin
chemical_list: D052242:Adiponectin; D001688:Biological Products; D001786:Blood Glucose; D013311:Streptozocin
keywords: Depression; Insulin insensitivity; Ophiocordyceps formosana