BRITISH JOURNAL OF PHARMACOLOGY
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2022
·Vol. 179
·期 16
·4078-4091
·
IF 9.473
Hailou Zhang,Yan Sun,Suk-yu Yau,Yanmeng Zhou,Xinxin Song,Han-Ting Zhang,Boran Zhu,Haoxin Wu,Gang Chen
Background and Purpose Current mainstream antidepressants have limited efficacy with a delayed onset of action. Yueju, a herbal medicine, has a rapid antidepressant action. Identification of the active ingredients in Yueju and the mechanism/s involved was carried out. Experimental Approach Key molecule/s and compounds involved in this antidepressant action was identified by transcriptomic and HPLC analysis, respectively. Antidepressant effects were evaluated using various behavioural experiments. The signalling involved was assessed using site-directed pharmacological intervention or optogenetic manipulation. Key Results Transcriptomic analysis showed that Yueju up-regulated pituitary adenylate cyclase activating polypeptide (PACAP) expression in the hippocampus. Two iridoids, geniposide and shanzhiside methyl ester, were identified and quantified from Yueju. Only co-treatment with both, at an equivalent concentrations found in Yueju, increased PACAP expression and elicited a rapid antidepressant action, which were blocked by intra-dentate gyrus infusion of a PACAP antagonist or optogenetic inactivation of PACAP expressing neurons. Geniposide and shanzhiside methyl ester co-treatment rapidly inhibited CaMKII phosphorylation and enhanced mTOR/4EBP1/P70S6k/BDNF ignalling, while intra-dentate gyrus infusions of a CaMKII activator blunted the rapid antidepressant action and BDNF expression up-regulation induced by the co-treatment. A single co-treatment of them rapidly improved depression-like behaviours and up-regulated hippocampal PACAP signalling in the repeated corticosterone-induced depression model, further confirming the involvement of PACAP. Conclusion and Implications Geniposide and shanzhiside methyl ester co-treatment had a synergistic rapid onset antidepressant action by triggering hippocampal PACAP activity and associated CaMKII–BDNF signalling. This mechanism could be targeted for development of fast onset antidepressants. Graphical
研究领域:
药理学
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神经科学
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中药
✓ 已验证
DOI
PubMed
高影响因子
Food Frontiers
·
2025
·
IF 6.9
Shu-zhen Ran,Rui Peng,Qin-wan Guo,Li-juan Ma,Jian-bo Wan,Jun-qing Huang,Zi-ying Wang,Gang Chen
Panax notoginseng Leaf (PNL), an edible-medicinal botanical resource, shows potential as functional ingredients for alleviating depression, owing to their unique saponin composition. This study investigates the regulatory effects of PNL-derived saponins on pituitary adenylate cyclase-activating polypeptide (PACAP) and their related antidepressant mechanisms. Our findings demonstrate that PNL supplementation significantly alleviates depressive-like behaviors. Mechanistically, PNL upregulates PACAP expression in the hippocampus and activates the downstream CREB and mTOR signaling pathways, leading to increased expression of synaptic plasticity markers, including BDNF and PSD95, while concurrently inhibiting microglial activation and the production of pro-inflammatory cytokines. Among the major saponins in PNL, ginsenosides Rb3 and Rc were found to synergistically enhance PACAP expression in the cultured PC12 cells. These results underscore the potential of PNL for novel functional food ingredients, highlighting the antidepressant synergism of its naturally occurring ginsenosides (Rb3/Rc), and provide a natural antidepressant strategy.
研究领域:
药理学
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神经科学
·
植物学
·
生物化学
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精神病学
✓ 已验证
产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF MEDICAL RESEARCH
·
2023
·Vol. 28
·期 1
·1-9
·
IF 4.2
Yan Xiang,Zhang Yayue,Lang Haiyan,Huang Ziming,Chen Xinyi,He Hao,Zhao Qian,Wang Jun
RationaleImmune thrombocytopenia (ITP) is thought to be a result of immune dysfunction, which is treated by glucocorticoids such as prednisone. Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) have immunomodulatory properties, but their role in intestinal immune control is unclear. The major goal of this study was to look at the effects of prednisone on platelet, VIP, and PACAP levels in ITP mice, as well as the regulatory system that controls intestinal immunity.Methods Eighteen BALB/c mice were randomly divided into three groups: blank control group, model control group, and prednisone group, with six mice in each group. The ITP animal model control group and the prednisone group were injected with anti-platelet serum (APS) to replicate the ITP animal model. The prednisone group began prednisone intervention on the 8th day. Platelet count was dynamically measured before APS injection, on the 4th day of injection, on the 1st day of administration, on the 4th day of administration, and at the end of the experiment. After the experiment, the expression of p53 protein in mouse mesenteric lymph node lymphocytes was detected by immunohistochemistry. The changes in lymphocyte apoptosis rate in mouse mesenteric lymph nodes were detected by in situ terminal transferase labeling (TUNEL). The contents of VIP and PACAP in the mouse brain, colon, and serum were detected by enzyme-linked immunosorbent assay (ELISA). The contents of IFN-γ, IL-4, IL-10, IL-17A in the mouse spleen were detected by ELISA.Results ①Changes of peripheral platelet count: there was no significant difference in platelet count among the three groups before modeling; on the 4th day, the platelet count decreased in the model control group and prednisone group; on the 8th day, the number of platelets in model control group and prednisone group was at the lowest level; on the 12th day, the platelet count in prednisone group recovered significantly; on the 15th day, the platelet count in prednisone group continued to rise. ②Changes of VIP, PACAP: compared with the blank control group, VIP and PACAP in the model control group decreased significantly in the brain, colon, and serum. Compared with the model control group, the levels of VIP and PACAP in the brain, colon, and serum in the prednisone group were increased except for serum PACAP. ③Changes of mesenteric lymphocytes: the expression of p53 protein in the mesenteric lymph nodes of model control group mice was significantly higher than that of blank control group mice. After prednisone intervention, the expression of p53 protein decreased significantly.④Changes of cytokines in spleen: compared with blank control group, IFN- γ, IL-17A increased and IL-4 and IL-10 decreased in model control group. After prednisone intervention, IFN- γ, IL-17A was down-regulated and IL-4 and IL-10 were upregulated.Conclusion sPrednisone-upregulated VIP and PACAP levels decreased P53 protein expression and apoptosis rate in mesenteric lymph node lymphocytes and affected cytokine expression in ITP model mice. Therefore, we speculate that the regulation of intestinal immune function may be a potential mechanism of prednisone in treating ITP.
研究领域:
免疫学
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药理学
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血液学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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