Engineering Bacopa monnieri for improved bacoside content and its neurological evaluation

IF 3.9 3区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Applied Microbiology and Biotechnology Pub Date : 2025-04-07 DOI:10.1007/s00253-025-13453-x

Gajendra Singh Jeena, Sunil Kumar, Sachi Bharti, Neeti Singh, Ashutosh Joshi, Vaibhavi Lahane, Roshni Meghani, Akhilesh Kumar Yadav, Shubha Shukla, Vineeta Tripathi, Rakesh Kumar Shukla

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Abstract

Bacosides are triterpenoidal saponins with numerous pharmacological benefits. One of the significant drawbacks is the low availability of these bacosides. The bacoside pathway is not well elucidated, and there is no prior report of a metabolic engineering approach in this plant. In this study, we have over-expressed the active isoform of Bacopa monnieri squalene synthase (BmSQS1-OE) and silenced the B. monnieri G10H (BmG10H-1-KD), the competitive metabolic pathway, to divert the flux towards triterpene biosynthesis. Absolute quantification of bacosides in these BmSQS1(OE)-BmG10H1(KD) lines has identified improved content of bacoside A3, bacopaside II, and bacoside A. Moreover, the engineered plant extract was also found to have better efficacy on locomotor activity, neuromuscular coordination, and social interaction in a 6-hydroxydopamine (6-OHDA)-induced rat model of Parkinson’s disease (PD). Immunohistochemistry of the brain tissues indicates that an extract of enhanced bacoside contents reduces 6-OHDA-induced dopaminergic depletion, implying a potential utility in neurological disorders.

• The engineered Bacopa monnieri extract has improved amounts of various bacoside.

• The engineered Bacopa extract has shown enhanced effectiveness in a 6-hydroxydopamine (6-OHDA)-induced rat model of Parkinson’s disease (PD).

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对百草枯进行工程改造以提高百草枯苷含量及其神经学评估

马齿苋皂苷是一种三萜皂苷，具有多种药理作用。其中一个显著的缺点是这些猪粪的可用性很低。马尾草苷途径还没有很好地阐明，也没有代谢工程方法在这种植物的先前报道。在这项研究中，我们过度表达假马齿苋角鲨烯合成酶（BmSQS1-OE）的活性异构体，并沉默假马齿苋G10H （BmG10H-1-KD）这一竞争性代谢途径，将流量转向三萜生物合成。对这些BmSQS1(OE)-BmG10H1（KD）系中马齿苋皂苷的绝对定量分析发现，马齿苋皂苷A3、马齿苋皂苷II和马齿苋皂苷a的含量有所提高。此外，在6-羟多巴胺（6-OHDA）诱导的帕金森病（PD）大鼠模型中，工程植物提取物还被发现对运动活性、神经肌肉协调和社会互动有更好的作用。脑组织的免疫组织化学表明，马齿苋苷含量增加的提取物可减少6-羟多巴胺诱导的多巴胺能耗竭，这意味着它在神经系统疾病中的潜在效用。•工程假马齿苋提取物提高了各种马齿苋苷的量。•工程假马齿苋提取物在6-羟多巴胺（6-OHDA）诱导的帕金森病（PD）大鼠模型中显示出增强的有效性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Applied Microbiology and Biotechnology 工程技术-生物工程与应用微生物

CiteScore

10.00

自引率

4.00%

发文量

535

审稿时长

2 months

期刊介绍： Applied Microbiology and Biotechnology focusses on prokaryotic or eukaryotic cells, relevant enzymes and proteins; applied genetics and molecular biotechnology; genomics and proteomics; applied microbial and cell physiology; environmental biotechnology; process and products and more. The journal welcomes full-length papers and mini-reviews of new and emerging products, processes and technologies.