Timosaponin AIII(Timosaponin AIII) - 药物靶点：Integrin_在研适应症：肿瘤_专利_临床

概要

基本信息

药物类型

小分子化药

别名

TAIII

靶点

Integrin

作用机制

整合素家族拮抗剂

治疗领域

肿瘤

在研适应症

肿瘤

非在研适应症-

原研机构

Oita University

在研机构

Oita University

非在研机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

关联

100 项与 Timosaponin AIII 相关的临床结果

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100 项与 Timosaponin AIII 相关的转化医学

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100 项与 Timosaponin AIII 相关的专利（医药）

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3

项与 Timosaponin AIII 相关的文献（医药）

2025-01-01·Journal of Advanced Research

Elucidation of the biosynthetic pathways of timosaponins reveals the antifungal mechanisms in Anemarrhena asphodeloides

Article

作者: Shi, Ningwei ; Liu, Chenxu ; Duan, Lixin ; Zhu, Min ; Liu, Zhongqiu ; Ji, Aijia ; Chen, Yidu ; Yang, Tingxing ; Wang, Lijun ; Li, Yu ; Huang, Ruoshi ; Ji, Zhongju ; Yi, Runxiang ; Fan, Baolian ; Yang, Lu ; Liang, Jincai

INTRODUCTION:

Timosaponins, as steroidal saponins, are the primary active constituents and quality biomarkers in Anemarrhena asphodeloides Bunge. Despite their significance, the biosynthetic pathways of timosaponins have not been thoroughly investigated.

OBJECTIVES:

This study aims to delineate the biosynthetic pathway of timosaponins in A. asphodeloides, elucidate the catalytic mechanisms of the key cycloartenol synthase (CAS), and investigate the antifungal properties of timosaponins.

METHODS:

Genes were cloned from A. asphodeloides and heterologous expressed in yeast, tobacco or bacillus coli. Site-directed mutagenesis and molecular docking were used to elucidate the catalytic mechanism of CAS. Antifungal assays were conducted to evaluate the antifungal activities of timosaponins.

RESULTS:

In this study, we elucidated the biochemical functions of seven genes involved in timosaponins biosynthesis in A. asphodeloides. Among three candidate OSC genes, AaOSCR12 was identified as the gene encoding cycloartenol synthase, which is responsible for the skeleton cyclization in timosaponin biosynthesis. Six residues (257H, 369N, 448T, 507V, 558P, 616Y) were identified as the critical catalytic active sites of CAS (AaOSCR12). Sterol methyltransferase (AaSMT1) and sterol side-chain reductase (AaSSR2) were found to be the subsequent enzymes and the branching points leading to phytosterol and cholesterol biosynthesis, respectively. Two oxide reductase genes, AaCYP90B27 and AaCYP90B2, were responsible for post-modification of cholesterol, serving as a precursor of timosaponins. A key 26-O-β-glucosidase (AaF26G1) was identified as facilitating the conversion of furostanol-type timosaponins into spirostanol-type timosaponins. Antifungal assays revealed that spirostanol-type timosaponin AⅢ exhibits superior antifungal activity compared to furostanol-type timosaponin BⅡ, potentially linked to plant defense mechanisms involving AaF26G1.

CONCLUSION:

This study utilized a multi-chassis cross-identification strategy, revealing key enzymes in the timosaponin biosynthetic pathway and offering novel insights into plant defense mechanisms against microbial pathogens.

IMMUNOLOGICAL INVESTIGATIONS

Timosaponin A-III Alleviates Asthma-Induced Airway Inflammation, Th17 Cell Differentiation, and STAT3/RORγt Pathway

Article

作者: Zhao, Ruiqi ; Yuan, Jiabo ; Wang, Lijie ; Li, Zhuying ; Wang, Congyao

INTRODUCTION:

T helper 17 (Th17) cells have a significant effect in the pathogenesis of asthma, and signal transducer and activator of transcription 3 (STAT3) pathway activation is critical for Th17 cell differentiation. Timosaponin A-III (TA3) was reported to inhibit the STAT3 pathway. Here, we investigated whether TA3 improved asthma by inhibiting the STAT3 pathway.

METHODS:

Ovalbumin (OVA)-induced asthma murine models were developed, and TA3 (10 or 20 mg/kg) was gavage daily during OVA challenge. Murine naïve CD4⁺T cells were triggered for Th17 differentiation, and TA3 (5 or 10 μM) was used to treat cells during induction of Th17 differentiation.

RESULTS:

In vivo experiments showed that TA3 decreased airway inflammation, goblet cell and smooth muscle hyperplasia, α-smooth muscle actin and collagen deposition, Th17 differentiation, and STAT3/RORγt signaling activation in mice exposed to OVA. The inhibitory effect of TA3 on STAT3/RORγt signaling activation was also observed in in vitro experiments. Compared to positive control static (a specific inhibitor of STAT3), TA3 had a similar effect on Th17 differentiation.

DISCUSSION:

These findings indicate that TA3 may ameliorate Th17 cell differentiation by suppressing STAT3/RORγt signaling. Our data provide evidence of the potential benefits of TA3 for the treatment of asthma.

CLINICAL RHEUMATOLOGY

Fecal metabolomic analysis of the role of gut microbiota and short-chain fatty acids in the therapeutic mechanism of Timosaponin AIII in Sjögren’s syndrome

Article

作者: Li, Kesong ; Jiang, Quan ; Pang, Fengtao ; Tang, Xiaopo

Abstract:

Introduction/objectives:

Sjogren’s syndrome (SS) is a chronic inflammatory and difficult-to-treat autoimmune disease. Timosaponin AIII (TAIII), a plant-derived steroidal saponin, effectively inhibits cell proliferation, induces apoptosis, and exhibits anti-inflammatory properties. This study explored the mechanisms of action of TAIII in SS treatment by studying gut microbiota and short-chain fatty acids (SCFAs) using fecal metabolomics.

Methods:

The model group used non-obese diabetic (NOD) mice. The treatment group was classified into TAIII and hydroxychloroquine groups. The gut microbiota, SCFAs, and metabolites were analyzed using 16S rRNA sequencing, gas chromatography–mass spectrometry analysis, and liquid chromatography–mass spectrometry, respectively.

Results:

TAIII effectively alleviated dry mouth in NOD mice, slowed the progression of salivary gland tissue injury, reduced inflammatory factor expression, and increased the levels of aquaporins 1 and 5. TAIII regulated SCFA content and tryptophan metabolism by altering the abundance of the Rikenellaceae_RC9_gut_group, thereby reducing the inflammatory response. TAIII can improve imbalances in the gut microbiota and the metabolic levels of related SCFAs and tryptophan, thereby reducing the level of inflammation.

Conclusion:

The significant differences observed in the abundance of the Rikenellaceae_RC9_gut_group between the treatment and control groups indicated the potential relationship between bacteria and metabolites in SS. Key Points• The safe and effective treatment of SS with traditional Chinese medicine• Multi-means study on intestinal flora, short-chain fatty acids, and metabonomics

100 项与 Timosaponin AIII 相关的药物交易

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