[Translation] Evaluation of the safety, tolerability and pharmacokinetics of Anemarrhena saponin BⅡ capsules after a single dose in healthy subjects: a single-center, double-blind, randomized, placebo-controlled, single-dose escalation phase I clinical study

主要目的：评估知母皂苷BII胶囊在健康受试者中单次递增给药的安全性和耐受性。次要目的：评估知母皂苷BII胶囊在健康受试者中单次递增给药后的药代动力学特征。探索性目的：初步的物料平衡研究。

[Translation]

Primary objective: To evaluate the safety and tolerability of single ascending doses of Anemarrhena Saponin BII Capsules in healthy subjects. Secondary objective: To evaluate the pharmacokinetic characteristics of Anemarrhena Saponin BII Capsules in healthy subjects after single ascending doses. Exploratory objective: Preliminary material balance study.

Start Date29 May 2021

Sponsor / Collaborator

Academy of Military Medical Sciences

[+1]

100 Clinical Results associated with Timosaponin BII

100 Translational Medicine associated with Timosaponin BII

100 Patents (Medical) associated with Timosaponin BII

159

Literatures (Medical) associated with Timosaponin BII

25 Oct 2024·Sheng li xue bao : [Acta physiologica Sinica]

A novel positive modulator of GABA_A receptor exhibiting antidepressive properties.

Article

Author: Li, Tian-Yu ; Wang, Yang ; Zheng, Yin-Li ; Shen, Fu-Yi ; Li, Yang ; Guo, Fei ; Wang, Xian ; Pan, Jing-Pei ; Du, Wei-Jia ; Liu, Zhi-Qiang

γ-Aminobutyric acid (GABA) neurotransmission alterations have been implicated to play a role in depression pathogenesis. While GABA_A receptor positive allosteric modulators are emerging as promising in clinical practice, their precise antidepressant mechanism remains to be further elucidated. The aim of the present study was to investigate the effects of LY-02, a novel compound derived from the metabolite of timosaponin, on depression in animals and its mechanism. The results of behavioral tests showed that LY-02 exhibited better antidepressant effects in both male C57BL/6 mice and Sprague Dawley (SD) rats. The results of cellular voltage clamp experiments showed that LY-02 enhanced GABA-mediated currents in HEK293T cells expressing recombinant α6β3δ subunit-containing GABA_A receptors. Electrophysiological recording from brain slices showed that LY-02 decreased the amplitude of spontaneous inhibitory postsynaptic current (sIPSC) and increased action potentials of pyramidal neurons in the medial prefrontal cortex (mPFC) of C57BL/6 mice. Western blot results showed that LY-02 dose-dependently up-regulated the protein expression levels of brain-derived neurotrophic factor (BDNF), tropomyosin related kinase B (TrkB) and postsynaptic density protein 95 (PSD-95) in mPFC of mice. The above results suggest that LY-02, as a positive modulator of GABA_A receptors, reduces inhibitory neurotransmission in pyramidal neurons. It further activates the BDNF/TrkB signaling pathway, thus exerting antidepressant effects. It suggests that LY-02 is a potential novel therapeutic agent for depression treatment.

11 Oct 2024·Biological and Pharmaceutical Bulletin

Timosaponin AIII Disrupts Cell–Extracellular Matrix Interactions through the Inhibition of Endocytic Pathways

Article

Author: Terabayashi, Takeshi ; Ishizaki, Toshimasa ; Hanada, Katsuhiro ; Akamine, Takahiro ; Takezaki, Daisuke ; Katoh, Akira ; Matsuoka, Shigeru ; Sasaki, Takako

Timosaponin AIII (TAIII), a steroidal saponin isolated from the root of Anemarrhena asphodeloides Bunge, exhibits various pharmacological activities, including anti-cancer properties. TAIII inhibits the migration and invasion of various cancer cell types. However, the mechanism underlying how TAIII regulates the motility of cancer cells remains incompletely understood. In this study, we demonstrate that TAIII disrupted cell-extracellular matrix (ECM) interactions by inhibiting internalization of cell surface proteins, such as integrins. We found that TAIII inhibited cell adhesion on various ECMs. Structure-activity relationship analysis demonstrated that TAIII exhibited unique activity among the saponins from Anemarrhena asphodeloides Bunge and that the number and position of saccharide moieties were important for TAIII to exert its activity. Time lapse imaging revealed that TAIII also suppressed cell spreading on the ECM, membrane ruffling, and lamellipodia formation. Furthermore, we examined integrin β1 behaviors in response to TAIII treatment and found that TAIII blocked its internalization. These findings contribute to delineating the potential molecular mechanisms by which TAIII exerts anti-metastatic activity.

01 Oct 2024·Biochemical Pharmacology

Anti-tumor effect and mechanisms of Timosaponin AIII across diverse cancer progression

Review

Author: Zhou, Haixia ; Zhou, Xiaofeng ; Tu, Hanyun ; Luo, Zepeng ; Yan, Yu ; Qi, Qi ; Luo, Zhongping

Timosaponin AIII (TAIII), a steroidal saponin derived from Anemarrhena asphodeloides Bunge, has gained attention for its versatile therapeutic properties. While well-established for its anti-inflammatory, antidepressant, and anticoagulant properties, emerging research highlights its potent anti-tumor capabilities. This review synthesizes recent findings on the intricate mechanisms and diverse functions of TAIII in cancer therapy, elucidating its impact on various tumor cells, encompassing the effects of TAIII on critical aspects of cancer progression, including metastasis, apoptosis, and autophagy. Additionally, the shared features of TAIII-induced anti-tumor activities, the factors contributing to the multifaceted anti-cancer activities of TAIII, and an exploration of the advantages and disadvantages associated with the regulation of multiple anti-tumor pathways by TAIII are discussed. Furthermore, the detailed regulation of signaling pathways is delineated and tailored to specific cancer types, providing a comprehensive overview of the potential development of TAIII as a promising anti-tumor agent.

100 Deals associated with Timosaponin BII

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Indication	Highest Phase	Country/Location	Organization	Date
Dementia, Vascular	Phase 1	CN	Beijing Wellso Pharmaceutical Co., Ltd.	29 May 2021
Dementia, Vascular	Phase 1	CN	Academy of Military Medical Sciences	29 May 2021

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