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Rapid Antidepressant Activity of Ethanol Extract of Gardenia jasminoides Ellis Is Associated with Upregulation of BDNF Expression in the Hippocampus.

ABSTRACT: Ethanol extract of Yueju pill, a Traditional Chinese Medicine herbal formula widely used to treat mood disorders, demonstrates rapid antidepressant effects similar to ketamine, likely via instant enhancement of brain-derived neurotrophic factor (BDNF) expression in the hippocampus. Here we investigated ethanol extracts of the constituent herbs of Yueju responsible for rapid antidepressant effects. Screening with tail suspension test in Kunming mice at 24 hours after a single administration of five individual constituent herbs of Yueju, we found that only Gardenia jasminoides Ellis (GJ) showed a significant effect. The antidepressant response started at 2 hours after GJ administration. Similar to Yueju and ketamine, a single administration of GJ significantly reduced the number of escape failures in the learned helplessness test. Furthermore, GJ decreased latency of food consumption in the novelty suppressed-feeding test. Additionally, starting from 2 hours and continuing for over 20 hours after GJ administration, BDNF expression in the hippocampus was upregulated, temporally linked with the antidepressant response. These findings suggest that GJ has rapid antidepressant effects, which are associated with the elevated expression of BDNF in the hippocampus. In Yueju formula, Yue represents GJ, as thus our study demonstrates the primary role of GJ in rapid antidepressant efficacy of Yueju.

SUBMITTER: Zhang H

PROVIDER: S-EPMC4387974 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Rapid Antidepressant Activity of Ethanol Extract of Gardenia jasminoides Ellis Is Associated with Upregulation of BDNF Expression in the Hippocampus.

Zhang Hailou H Xue Wenda W Wu Runjie R Gong Tong T Tao Weiwei W Zhou Xin X Jiang Jingjing J Zhang Ying Y Zhang Nan N Cui Yi Y Chen Chang C Chen Gang G

Evidence-based complementary and alternative medicine : eCAM 20150324

Ethanol extract of Yueju pill, a Traditional Chinese Medicine herbal formula widely used to treat mood disorders, demonstrates rapid antidepressant effects similar to ketamine, likely via instant enhancement of brain-derived neurotrophic factor (BDNF) expression in the hippocampus. Here we investigated ethanol extracts of the constituent herbs of Yueju responsible for rapid antidepressant effects. Screening with tail suspension test in Kunming mice at 24 hours after a single administration of fi ...[more]

PMID: 25878718

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Project description:BACKGROUND: The petal senescence of ethylene insensitive species has not been investigated thoroughly while little is known about the temporal and tissue specific expression patterns of transcription factors (TFs) in this developmental process. Even less is known on flower senescence of the ornamental pot plant Gardenia jasminoides, a non climacteric flower with significant commercial value. RESULTS: We initiated a de novo transcriptome study to investigate the petal senescence in four developmental stages of cut gardenia flowers considering that the visible symptoms of senescence appear within 4 days of flower opening. De novo assembly of transcriptome sequencing resulted in 102,263 contigs with mean length of 360 nucleotides that generated 57,503 unigenes. These were further clustered into 20,970 clusters and 36,533 singletons. The comparison of the consecutive developmental stages resulted in 180 common, differentially expressed unigenes. A large number of Simple Sequence Repeats were also identified comprising a large number of dinucleotides and trinucleotides. The prevailing families of differentially expressed TFs comprise the AP2/EREBP, WRKY and the bHLH. There are 81 differentially expressed TFs when the symptoms of flower senescence become visible with the most prevailing being the WRKY family with 19 unigenes. No other WRKY TFs had been identified up to now in petal senescence of ethylene insensitive species. A large number of differentially expressed genes were identified at the initiation of visible symptoms of senescence compared to the open flower stage indicating a significant shift in the expression profiles which might be coordinated by up-regulated and/or down-regulated TFs. The expression of 16 genes that belong to the TF families of WRKY, bHLH and the ethylene sensing pathway was validated using qRT--PCR. CONCLUSION: This de novo transcriptome analysis resulted in the identification of TFs with specific temporal expression patterns such as two WRKYs and one bHLH, which might play the role of senescence progression regulators. Further research is required to investigate their role in gardenia flowers in order to develop tools to delay petal senescence.

Project description:Estrogen-stimulating principles have been demonstrated to relieve postmenopausal syndrome effectively. Gardenia jasminoides Ellis (GJE) is an herbal medicine possessing multiple pharmacological effects on human health with low toxicity. However, the therapeutic effects of GJE on the management of postmenopausal syndrome and its mechanism of action have not been fully elucidated. In this study, network pharmacology-based approaches were employed to examine steroidogenesis under the influence of GJE. In addition, the possibility of toxicity of GJE was ruled out and four probable active compounds were predicted. In parallel, a chromatographic fraction of GJE with estrogen-stimulating effect was identified and nine major compounds were isolated from this active fraction. Among the nine compounds, four of them were identified by network pharmacology, validating the use of network pharmacology to predict active compounds. Then the phenotypic approaches were utilized to verify that rutin, chlorogenic acid (CGA) and geniposidic acid (GA) exerted an estrogen-stimulating effect on ovarian granulosa cells. Furthermore, the results of target-based approaches indicated that rutin, CGA, and GA could up-regulate the FSHR-aromatase pathway in ovarian granulosa cells. The stimulation of estrogen production by rat ovarian granulosa cells under the influence of the three compounds underwent a decline when the follicle-stimulating hormone receptor (FSHR) was blocked by antibodies against the receptor, indicating the involvement of FSHR in the estradiol-stimulating activity of the three compounds. The effects of the three compounds on estrogen biosynthesis- related gene expression level were further confirmed by Western blot assay. Importantly, the MTT results showed that exposure of breast cancer cells to the three compounds resulted in reduction of cell viability, demonstrating the cytotoxicity of the three compounds. Collectively, rutin, chlorogenic acid and geniposidic acid may contribute to the therapeutic potential of GJE for the treatment of postmenopausal syndrome.

Project description:BackgroundAcetaminophen (APAP)-induced hepatotoxicity is a potentially life-threatening condition. Gardenia jasminoides fruit extract (GJE), which contains geniposide (Gen) as its major active constituent, possesses anti-inflammatory and antioxidant properties and may help address the underlying pathogenesis of APAP-induced hepatotoxicity. This study aimed to evaluate the effects of GJE in a mouse model of APAP-induced hepatotoxicity.MethodsTwenty-four male ICR mice were divided into 4 groups (n = 6/group): [1] Control group, mice were given distilled water; [2] APAP group, mice received a single dose of 600 mg/kg APAP; [3] APAP + low-dose GJE group, mice received APAP followed 30 min later by 2 doses of low-dose GJE (0.44 g/kg/dose, containing Gen 100 mg/kg/dose) 8 h apart; [4] APAP + high-dose GJE group, mice received APAP followed by 2 doses of high-dose GJE (0.88 g/kg/dose, containing Gen 200 mg/kg/dose). All mice were euthanized 24 h after APAP administration. Liver tissue was used for histological examination and to measure glutathione (GSH) and malondialdehyde (MDA) levels. Serum was used to determine levels of ALT and inflammatory cytokines (tumor necrosis factor- α (TNF-α) and interleukin-6 (IL-6)).ResultsLiver histopathology showed moderate to severe hepatic necroinflammation in the APAP group, whereas only mild necroinflammation was observed in both treatment groups. Serum ALT levels were significantly elevated in the APAP group compared to the control group but were significantly reduced after low- and high-dose GJE treatment. Serum TNF- α levels were significantly higher in the APAP group than in the control group and were significantly lower after high-dose GJE treatment (135.5 ± 477.2 vs. 35.5 ± 25.8 vs. 74.7 ± 47.2 vs. 41.4 ± 50.8 pg/mL, respectively). Serum IL-6 followed a similar pattern. Hepatic GSH levels were significantly lower in the APAP group compared to the control group but significantly increased after both low- and high-dose GJE treatment (19.9 ± 4.5 vs. 81.5 ± 12.4 vs. 71.4 ± 7.8 vs. 82.6 ± 6.6 nmol/mg protein, respectively). Conversely, hepatic MDA levels were significantly elevated in the APAP group compared with the control group but significantly decreased after high-dose GJE treatment (108.6 ± 201.5 vs. 40.5 ± 18.0 vs. 40.5 ± 16.8 nmol/mg protein, respectively).ConclusionsTreatment with G. jasminoides fruit extract can alleviate APAP-induced hepatotoxicity, likely through its anti-inflammatory and antioxidant properties.

Project description:Gardenia jasminoides Ellis is abundant in crocin and has a longstanding historical usage both as a dietary and natural ethnic medicine. Enhanced studies have increasingly revealed the intricate interplay between glycolipid metabolism and gut microbiota, wherein their imbalance is regarded as a pivotal indicator of metabolic disorders. Currently, the precise molecular mechanism of the crude extract of crocin from Gardenia jasminoides Ellis (GC) targeting gut microbiota to regulate glycolipid metabolism disorder is still unclear. Firstly, we explored the effect of GC on digestive enzymes (α-amylase and α-glucosidase) in vitro. Secondly, we investigated the effect of GC on the physical and chemical parameters of high-fat diet (HFD) rats, such as body weight change, fasting blood glucose and lipid levels, and liver oxidative stress and injury. Then, 16S rDNA sequencing was used to analyze the effects of GC on the composition and structure of gut microbiota. Finally, the impact of GC on the TLR4/Myd88/NF-κB signaling pathway in the intestine was assessed by Western Blotting. In the present study, GC was found to exhibit a hypoglycemic effect in vitro, by inhibition of digestive enzymes. In animal experiments, we observed that GC significantly reduced fasting blood glucose, TC, and TG levels while increasing HDL-C levels. Additionally, GC demonstrated hepatoprotective properties by enhancing liver antioxidative capacity through the upregulation of SOD, CAT, and GSH-Px, while reducing ROS. 16S rDNA sequencing results showed that GC had a significant effect on the gut microbiota of HFD rats, mainly by reducing the ratio of Firmicutes/Bateroidota, and significantly affected the genera related to glycolipid metabolism, such as Akkermansia, Ligilactobacillus, Lactobacillus, Bacteroides, Prevotellaceae, etc. The Western Blotting results demonstrated that GC effectively downregulated the protein expressions of TLR4, Myd88, and NF-κB in the intestine of HFD rats, indicating that GC could target the TLR4/Myd88/NF-κB pathway to interfere with glycolipid metabolism disorder. Correlation analysis revealed that GC could target the Akkermansia-TLR4/Myd88/NF-κB pathway axis which attenuates glycolipid metabolism disorder. Therefore, this study establishes the foundation for GC as a novel therapeutic agent for glycolipid metabolism disorder chemoprevention, and it introduces a novel methodology for harnessing the potential of natural botanical extracts in the prevention and treatment of metabolic syndrome.

Dataset Information

Rapid Antidepressant Activity of Ethanol Extract of Gardenia jasminoides Ellis Is Associated with Upregulation of BDNF Expression in the Hippocampus.

Publications

Rapid Antidepressant Activity of Ethanol Extract of Gardenia jasminoides Ellis Is Associated with Upregulation of BDNF Expression in the Hippocampus.

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