Engineering Bacopa monnieri for improved bacoside content and its neurological evaluation.
Gajendra Singh Jeena1, Sunil Kumar1, Sachi Bharti2,3
1Plant Biotechnology Division, Central Institute of Medicinal and Aromatic Plants, CSIR-CIMAP) PO CIMAP, Near Kukrail Picnic Spot, Lucknow, 226015, India.
Applied Microbiology and Biotechnology
|April 8, 2025
Summary
Metabolic engineering of Bacopa monnieri increased bacoside production. The enhanced extract improved motor function and reduced dopaminergic depletion in a rat model of Parkinson's disease (PD).
Area of Science:
- Plant Biotechnology
- Metabolic Engineering
- Neuropharmacology
Background:
- Bacosides, triterpenoidal saponins from Bacopa monnieri, possess significant pharmacological benefits but suffer from low availability.
- The specific metabolic pathway for bacoside biosynthesis remains poorly understood, hindering efforts to enhance production.
- Previous research has not explored metabolic engineering strategies for increasing bacoside content in Bacopa monnieri.
Purpose of the Study:
- To engineer Bacopa monnieri to enhance bacoside biosynthesis and content.
- To investigate the therapeutic potential of engineered Bacopa monnieri extract in a Parkinson's disease (PD) rat model.
Main Methods:
- Over-expression of Bacopa monnieri squalene synthase (BmSQS1-OE) to boost precursor supply.
- Silencing of B. monnieri G10H (BmG10H-1-KD) to redirect metabolic flux towards triterpene biosynthesis.
- Absolute quantification of bacosides in engineered lines and assessment of extract efficacy in a 6-hydroxydopamine (6-OHDA)-induced PD rat model.
Main Results:
- Engineered BmSQS1(OE)-BmG10H1(KD) Bacopa monnieri lines exhibited significantly improved content of bacoside A3, bacopaside II, and bacoside A.
- The engineered plant extract demonstrated enhanced efficacy in improving locomotor activity, neuromuscular coordination, and social interaction in PD rats.
- Immunohistochemistry revealed that the enhanced bacoside extract reduced 6-OHDA-induced dopaminergic depletion in rat brain tissues.
Conclusions:
- Metabolic engineering strategies, including BmSQS1 over-expression and BmG10H silencing, effectively enhance bacoside accumulation in Bacopa monnieri.
- The engineered Bacopa monnieri extract shows therapeutic potential for neurological disorders, particularly Parkinson's disease, by mitigating dopaminergic neurodegeneration.
