Multiomics analysis reveals early administration of the Medhya rasayana formulation of Bacopa monnieri (L.) Wettst. and Centella asiatica (L.) Urb. prevents neuroinflammation and cognitive deficits in an AβO-injected AD mouse model.

Ethnopharmacological relevance: Medhya rasayana is a classical Ayurvedic formulation comprising of neuroactive herbs such as Bacopa monnieri (L.) Wettst and Centella asiatica (L.) Urb., whose nomenclature corresponds to the latest revision in World Flora Online (accessed on July 31, 2025). It is traditionally used to enhance memory, cognition, and overall brain health, as well as to manage mental illness and neurological disorders across different age groups. However, the underlying molecular mechanism remains largely undefined.

Aim of the study: In this study, we aimed to investigate whether a rasayana preparation of B. monnieri (Bm) and C. asiatica (Ca) delays the onset or progression of Alzheimer's disease (AD) in an amyloid beta oligomer (AβO)-injected mouse model by preventing key hallmarks, including cognitive impairment and neuroinflammation.

Materials and methods: Bm and Ca rasayana formulations were orally administered to healthy 16-week-old mice for two months, followed by the induction of AD via stereotaxic injection of AβO into the hippocampus. Seven days post-AβO injection, a battery of behavioural tests were conducted to evaluate the impact of rasayanas on cognitive outcomes. Furthermore, transcriptomic (RNA-seq) and metabolomic (LC‒MS) profiling of hippocampal tissue was performed to investigate the molecular and biochemical effects of rasayana intervention.

Results: The results of the behavioral data revealed that AβO injection impaired spatial and social memory, whereas rasayana pretreatment preserved cognitive function and prevented AβO-induced deficits in the AD mouse model. Furthermore, transcriptomic analysis of the hippocampus with or without rasayana pretreatment revealed that the rasayana formulation beneficially modulated key biological processes, including the inflammatory response, cytokine and TNF regulation, positive regulation of the MAPK cascade, and antigen processing and presentation. Metabolomic analysis further revealed that rasayana pretreatment conferred neuroprotection via glutathione and pyrimidine metabolism.

Conclusion: Our findings indicate that pretreatment with Bm and Ca rasayana prevents AβO-induced neuroinflammation and cognitive deficits in an AD mouse model by suppressing proinflammatory pathways and restoring redox balance, suggesting its potential for delaying the onset of disease progression.