Two standardized fractions of Gardenia jasminoides Ellis with rapid antidepressant effects are differentially associated with BDNF up-regulation in the hippocampus.
BACKGROUND
Gardenia jasminoides Ellis (GJ) is one of the five constituents of Yueju pill, a Traditional Chinese Medicine for treatment of syndromes associated with mood disorders. Recently, preclinical and clinical studies suggest that Yueju pill confers rapid antidepressant effects. GJ is identified as the constituent primary for Yueju pill's rapid antidepressant effects. GJ's antidepressant action is temporally associated with up-regulated expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. The present study aimed to identify chemical fractions responsible for the rapid antidepressant efficacy of GJ and its association with BDNF signaling.


METHODS
Four fractions of GJ were extracted using standardized procedure. The four fractions were screened for rapid antidepressant potential, using the behavioral paradigm of forced swimming test (FST) and tail suspension test (TST) assessed at 24h post a single administration. A single dose of the putatively effective fractions was further tested in mice exposed to chronic mild stress (CMS), followed with a comprehensive behavioral testing including TST, FST, sucrose preference test (SPT), and novelty suppressed-feeding (NSF). To test the association of BDNF signaling with rapid antidepressant effects of effective factions, the expressions of BDNF and its receptor tropomyosin receptor kinase B (TrkB) in the hippocampus were assessed at different times post a single administration of effective fractions.


RESULTS
Both petroleum ether (GJ-PE) and n-butyl alcohol fraction (GJ-BO) fractions of GJ displayed rapid antidepressant potential in the FST. In the TST, the antidepressant effects of GJ-PE lasted for a longer time than GJ-BO. Acute administration of either GJ-PE or GJ-BO significantly reversed the behavioral deficits in the tests of TST, FST, SPT and NSF in chronically stressed mice, confirming both fractions conferred rapid antidepressant efficacy. Interestingly, GJ-PE, but not GJ-BO, increased the expression of BDNF and TrkB in the hippocampus post a single administration.


CONCLUSIONS
Two standardized fractions GJ-PE and GJ-BO exhibited comparable rapid antidepressant-like effects on the CMS mice. However, only the effects of GJ-PE was associated with BDNF signaling.
Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China; Key Laboratory of Integrative Biomedicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Li
L
Ren
Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China; Key Laboratory of Integrative Biomedicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Weiwei
W
Tao
Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China; Key Laboratory of Integrative Biomedicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Hailou
H
Zhang
Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China; Key Laboratory of Integrative Biomedicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Wenda
W
Xue
Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China; Key Laboratory of Integrative Biomedicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Juanjuan
J
Tang
Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China; Key Laboratory of Integrative Biomedicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Ruyan
R
Wu
Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China; Key Laboratory of Integrative Biomedicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Baomei
B
Xia
Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China; Key Laboratory of Integrative Biomedicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Haoxing
H
Wu
Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China; Key Laboratory of Integrative Biomedicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: chengang@njutcm.edu.cn.
Gang
G
Chen
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D032062:Gardenia; D019417:Hindlimb Suspension; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D020813:Receptor, trkB / Q000378:metabolism; D013315:Stress, Psychological / Q000188:drug therapy* / Q000378:metabolism; D013550:Swimming; D015854:Up-Regulation / Q000187:drug effects
D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D010936:Plant Extracts; D020813:Receptor, trkB
BDNF; Chemical fractions; Chronic stress; Gardenia Jasminoides Ellis; Geniposide (Pubchem CID: 107848); Gerdenoside (Pubchem CID: 442423); Rapid antidepressant; TrkB; crocetin (Pubchem CID: 5281232); crocin-1(Pubchem CID: 5281233); crocin-2 (Pubchem CID: 91746171); genipin (Pubchem CID:442424); geniposidic acid (Pubchem CID: 443354)