Anti-depressive activities and biotransformation of timosaponin B-III and its derivatives

Jiang, Weixin; Guo, Jing; Xue, Rui; Zhu, Kaicheng; Li, Zhixiong; Chen, Mingcang; Huang, Chenggang

doi:10.1080/14786419.2014.910663

Cited by 11 publications

(10 citation statements)

References 10 publications

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“…Figures 6A and 6B show the results of the tail suspension test (TST) and sucrose preference test (SPT) on mice before and after the 6-week CMS treatment. Two-way RM ANOVA revealed the significant effects of treatment (F (3,22) =17.08, P<0.0001) and time (F (3,66) =18.51, P<0.0001) on the results of the TST, as well as the significant effects of treatment (F (3,22) [30] , we performed the OFT. Figures 6C and 6D showed that there were no significant effects of treatment (F (3,22) =0.09703, P=0.9608) and time (F (3,66) =0.01570, P=0.9973) on total distance, as well as no significant effects of treatment (F (3,22) =0.1618, P=0.9209) and time (F (3,66) =0.2776, P=0.8414) on walking speed, suggesting that locomotor activity was virtually normal.…”

Section: +mentioning

confidence: 99%

“…Specifically, timosaponin B-II and B-III are the two main bioactive constituents that are thought to improve learning and memory. Moreover, B-III and its derivatives were reported to be important for the main antidepressive activity of timosaponin [22,23] . Although its detailed mechanism of action remains unknown, the therapeutic potential of timosaponin is obvious, and its mechanism of psychotropic action deserves further exploration.…”

Section: Introductionmentioning

confidence: 99%

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Timosaponin derivative YY-23 acts as a non-competitive NMDA receptor antagonist and exerts a rapid antidepressant-like effect in mice

Zhang

Guo

et al. 2015

Acta Pharmacol Sin

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Aim: N-methyl-D-aspartic acid (NMDA) receptor modulators have shown promising results as potential antidepressant agents, whereas timosaponins extracted from the Chinese herb Rhizoma Anemarrhenae exhibit antidepressant activities. In the present study we examined whether YY-23, a modified metabolite of timosaponin B-III, could affect NMDA receptors in rat hippocampal neurons in vitro, and evaluated its antidepressant-like effects in stressed mice. Methods: NMDA-induced currents were recorded in acutely dissociated rat hippocampal CA1 neurons using a whole-cell recording technique. C57BL/6 mice were exposed to a 6-week chronic mild stress (CMS) or a 10-d chronic social defeat stress (CSDS). The stressed mice were treated with YY-23 (20 mg·kg -1 ·d -1 ) or a positive-control drug, fluoxetine (10 mg·kg -1 ·d -1 ) for 3 weeks. Behavioral assessments were carried out every week. Results: In acutely dissociated rat hippocampal CA1 neurons, YY-23 selectively and reversibly inhibited NMDA-induced currents with an EC 50 value of 2.8 μmol/L. This inhibition of NMDA-induced currents by YY-23 was non-competitive, and had no features of voltagedependency or use-dependency. Treatment of the stressed mice with YY-23 not only reversed CMS-induced deficiency of sucrose preference and immobility time, and CSDS-induced reduction of social interaction, but also had faster onset as compared to fluoxetine. Conclusion: YY-23 is a novel non-competitive antagonist of NMDA receptors with promising rapid antidepressant-like effects in mouse models of CMS and CSDS depression.

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Section: +mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Timosaponin derivative YY-23 acts as a non-competitive NMDA receptor antagonist and exerts a rapid antidepressant-like effect in mice

Zhang

Guo

et al. 2015

Acta Pharmacol Sin

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“…(Liliaceae). Although it has been reported to exhibit antidepressive effects on behavior, including immobility time in forced swimming tests (FSTs) and tail suspension tests (TSTs), horizontal locomotion, and frequencies of rearing, grooming and defecation in an open-field test (11), the underlying mechanisms of TB-III remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Timosaponin B-III exhibits antidepressive activity in a mouse model of postpartum depression by the regulation of inflammatory cytokines, BNDF signaling and synaptic plasticity

Zhang

Wang

Xiong

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. The aim of this study was to investigate the antidepressive effects of timosaponin B-III (TB-III) and the underlying mechanism. A postpartum depression (PPD) mouse model was established by the administration of dexamethasone sodium phosphate during pregnancy. Mice with PPD were assigned to the following groups: Model, fluoxetine and high, medium and low doses of TB-III. Post-parturient mice without PPD served as a normal control group. To examine the effect of TB-III, mice were treated with TB-III, then forced swimming tests (FSTs) and tail suspension tests (TSTs) were performed to evaluate depression. Serum and hippocampal cytokines, namely tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-10, were quantified using ELISAs and protein levels of hippocampal brain-derived neurotrophic factor (BDNF), glucagon synthase kinase (GSK)-3β, glutamate receptor subunit 1 (GluR1), postsynaptic density protein 95 (PSD95) and synapsin I were quantified using western blot analysis. Compared with those in the control group, immobility time in the FST and TST, serum and hippocampal TNF-α, IL-1β and IL-6 levels and hippocampal IL-10 levels were increased significantly in the model group (P<0.01). Serum IL-10 levels and hippocampal levels of BDNF, GSK-3β, GluR1, PSD95 and synapsin I decreased significantly in the model group compared with the control group (P<0.01). Fluoxetine or TB-III (10, 20 or 40 mg/kg) treatment significantly decreased immobility times in the FST and TST (P<0.01) and significantly reversed the aforementioned alterations in cytokine and protein levels (P<0.01). Thus, TB-III exhibited a protective effect against depression in PPD and such effects may have been mediated via the regulation of inflammatory cytokines, the BNDF signaling pathway and synaptic plasticity-related proteins. IntroductionPostpartum depression (PPD) is a common mental disease (1), and an incidence of 10-15% has been indicated in the US, although this can be as high as 30% depending on the diagnostic criteria (2,3). Depression prior to pregnancy is one of the greatest risk factors for PPD (4). Psychological and physiological factors are major etiologies for PPD development (5). Psychological factors primarily include anxiety during pregnancy and personality characteristics, while physiological factors include genetic and physical factors, hormone level and the delivery process (6-8). Currently, drug therapies and psychotherapy are the two most commonly used treatments for PPD, and combined therapy is reported to be more effective than either treatment alone (9,10). However, the success rate of treatment is low and the effects are not satisfactory. Therefore, the exploration of new treatments against PPD is critical.Timosaponin B-III (TB-III) is a saponin isolated from Anemar rhenae rhizome, the dry rhizome of Anemarrhena asphodeloides Bge. (Liliaceae). Although it has been reported to exhibit antidepressive effects on behavior, including immobility time in forced swimming tests (FSTs) and tail suspension tests (TSTs)...

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“…Jiang et al. investigated the effects of timosaponin BIII in a mouse model of depression and proved a significant impact . Although there is an increasing number of studies on the pharmacological effects of Anemarrhena asphodeloides Bunge , there is still a lack of research on type 2 diabetes mellitus.…”

Section: Introductionmentioning

confidence: 99%

Lipidomics Analysis of Timosaponin BII in INS‐1 Cells Induced by Glycolipid Toxicity and Its Relationship with Inflammation

Shi

Zhu

Chen

et al. 2020

Chemistry & Biodiversity

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Anemarrhena asphodeloides BUNGE is a traditional Chinese medicine. The timosaponin BII is one of the most abundant and widely studied active ingredients in Anemarrhena asphodeloides BUNGE. Related studies have shown that timosaponin BII has potential value for development and further utilization. The protective effect of timosaponin BII on islet β cells under type 2 diabetes was investigated in the glycolipid toxic INS-1 cell model and possible biomarkers were explored by lipidomics analysis. Timosaponin BII was isolated from Anemarrhena asphodeloides BUNGE by polyamide resin and Sephadex LH-20. Then, the glycolipid toxicity INS-1 cell model was established to investigate the protective effect of timosaponin BII. The results showed that timosaponin BII could significantly influence the levels of malondialdehyde (MDA) and glutathione (GSH), thereby restoring the insulin secretion ability and cell viability of model cells. Lipidomics analysis was combined with multivariate statistical analysis for marker selection. The four most common pathological and pharmacological lipid markers were phosphatidylserine (PS), suggesting that timosaponin BII had protective effects on model cells related to the reduction oxidative stress and macrophage inflammation. RAW264.7 macrophages were stimulated by LPS to establish a model of inflammation and study the effect of timosaponin BII on the nodes of NOD-like receptor P3 (NLRP3) inflammasome pathway in the model cells. In conclusion, timosaponin BII may have the effect of protecting INS-1 pancreatic β cells through reducing IL-1β (interleukin-1β) production by inhibiting the NLRP3 inflammasome in macrophage and restoring the insulin secretion ability and cell viability by reducing oxidative stress.

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Anti-depressive activities and biotransformation of timosaponin B-III and its derivatives

Cited by 11 publications

References 10 publications

Timosaponin derivative YY-23 acts as a non-competitive NMDA receptor antagonist and exerts a rapid antidepressant-like effect in mice

Timosaponin derivative YY-23 acts as a non-competitive NMDA receptor antagonist and exerts a rapid antidepressant-like effect in mice

Timosaponin B-III exhibits antidepressive activity in a mouse model of postpartum depression by the regulation of inflammatory cytokines, BNDF signaling and synaptic plasticity

Lipidomics Analysis of Timosaponin BII in INS‐1 Cells Induced by Glycolipid Toxicity and Its Relationship with Inflammation

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