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OBJECTIVE@#To study the antidepressant-like effect and action mechanism of geniposide and eleutheroside B combination treatment on the lipopolysaccharide (LPS)-induced depression mice model.@*METHODS@#Depression mice model was established by lipopolysaccharide (LPS) injection. Totally 48 mice were randomly divided into 6 groups (8 rats per group) according to a random number table, including normal, model, fluoxetine (20 mg/kg), geniposide (100 mg/kg) + eleutheroside B (100 mg/kg), geniposide + eleutheroside B + WAY 100635 (0.03 mg/kg), geniposide + eleutheroside B+ N-methyl-D-aspartic acid receptor (NMDA, 75 mg/kg) groups, respectively. After continuous administration for 10 days, autonomic activity tests after 30 min of administration were performed on the 10th day. On the 11th day, except for the normal group, the mice in the other groups were intraperitoneally injected with LPS (1 mg/kg), and the behavioral tests were performed 4 h later. Enzyme linked immunosorbent assay was used to detect tumor necrosis factor alpha (TNF- α) and interleukin-1 β (IL-1 β) levels in mice serum. The mRNA expression of indoleamine 2,3-dioxygenase (IDO) and nuclear transcription factor (NF- κB) were detected by real-time quantitative polymerase chain reaction. Western-blot analysis was used to detect IDO and NF- κB protein expressions in hippocampus tissue.@*RESULTS@#Compared with the normal group, a single administration of LPS increased the immobility time in the forced swimming test (FST) and tail suspension test (TST, P<0.01), without affecting autonomous activity. Compared with the model group, fluoxetine and geniposide + eleutheroside B administration significantly improved the immobility time of depressed mice in the FST and TST, decreased serum IL-1 β content, inhibited the expression levels of NF- κ B gene and protein in hippocampus tissues (P<0.05 or P<0.01). Compared with the model group, geniposide + eleutheroside B treatment significantly reduced serum TNF-α content and inhibited IDO mRNA and protein expressions in hippocampus (P<0.05 or P<0.01). In addition, NMDA partly prevented the inhibition of IDO mRNA expression by geniposide + eleutheroside B; NMDA and WAY-100635 also partly prevented the reduction of IL-1 ß content induced by geniposide + eleutheroside B treatment (P<0.05 or P<0.01).@*CONCLUSIONS@#The combination of geniposide and eleutheroside B showed a certain antidepression-like effect. Its main mechanism of action may be contributed to inhibiting the activation of NF- κB, decreasing the proinflammatory cytokines such as TNF-α, IL-1 β, and inhibiting in the neuroinflammatory reaction. Additionally, it also affects tryptophan metabolism, reduces the expression of a key enzyme of tryptophan metabolism, IDO. And this antidepressant-like effect may be mediated by 5-hydroxytryptamine and glutamate systems.
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[ ABSTRACT] AIM:To explore the effects and mechanism of eleutheroside ( ETS) B or E on the proliferation of HBZY-1 cells treated with high glucose.METHODS:The HBZY-1 cells were cultured under high glucose condition.The 4th generation of HBZY-1 cells was used for determining the optimal cell density, which was consistent with the growth reg-ulation curve of the cells.The cells were divided into 6 groups:low glucose ( LG) group, high glucose ( HG) group, high glucose plus ETS-B/E ( low dose, medium dose and high dose) groups, and high glucose plus losartan ( LTG) group.Af-ter all cells were treated with the corresponding drugs at 24 h, 48 h and 72 h, the inhibitory rate of the proliferation was measured, and the expression of TGF-β1 and PPARγwas detected by immunocytochemistry and Western blotting.RE-SULTS:The best cell density was 2 000 cells/well, which was complied with the basic rules of the cell growth, and high glucose significantly promoted the HBZY-1 cell proliferation.At each time point, the inhibitory effects of ETS-B/E were significantly different between HG group and LTG group on the proliferation of the HBZY-1 cells ( P<0.05) .The expres-sion of TGF-β1 was significantly inhibited, and the expression of PPARγwas significantly promoted by ETS-B/E ( P<0.05).ETS-E showed stronger effect than ETS-B (P<0.05) in a concentration-and time-dependent manner.CONCLU-SION:ETS-B/E significantly inhibits the proliferation of HBZY-1 cells under high glucose condition by decreasing TGF-β1 expression and promoting PPARγexpression.
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AIM:To observe the absorption characteristics,absorption sites,and mechanism of eleutheroside B from Radix acathopanacis senticosi in various intestinal segments in rat and provide theoretical evidences for designing its preparation. METHODS: In situ perfusion method in rats.The absorption characteristics and absorption sites of eleutheroside B in intestine were applied. RESULTS: Absorbed dose and intestinal surface permeation rate of various intestinal segments decreased in turns in duodenum,jejunum,ileum,and colon;The concentration of eleutheroside B degraded through intestinal enzyme declined in turns in same manner. CONCLUSION: The poor bioavailability of eleutheroside B is not only due to absorption but also due to enzymolysis.