Engineering Bacopa monnieri for improved bacoside content and its neurological evaluation.

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. KEY POINTS: • 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).