Comparative Metabolomics and Network Pharmacology Analysis Reveal Shared Neuroprotective Mechanisms of Bacopa monnieri (L.) Wettst and Centella asiatica (L.) Urb

• Published in: Molecular neurobiology 2024-12, Vol.61 (12), p.10956-10978
• Main Authors: Parate, Sakshi Sanjay, Upadhyay, Shubham Sukerndeo, S., Amrutha, Karthikkeyan, Gayathree, Pervaje, Ravishankar, Abhinand, Chandran S., Modi, Prashant Kumar, Prasad, Thottethodi Subrahmanya Keshava
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Animals; Apoptosis; Apoptosis - drug effects; Bacopa - chemistry; Bacopa monnieri; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell culture; Centella - chemistry; Centella asiatica; Kinases; MAP kinase; Mass spectrometry; Mass spectroscopy; Metabolites; Metabolome - drug effects; Metabolomics; Metabolomics - methods; Molecular Docking Simulation; Network Pharmacology; Neurobiology; Neurology; Neuroprotection; Neuroprotective Agents - pharmacology; Neurosciences; Original Article; PC12 Cells; Pharmacology; Phytochemicals; Plant Extracts - pharmacology; Proteins; Rats; Reactive Oxygen Species - metabolism; Scientific imaging; TOR protein; Triterpenes - metabolism; Triterpenes - pharmacology
• ISSN: 0893-7648; 1559-1182; 1559-1182
• DOI: 10.1007/s12035-024-04223-3

Bacopa monnieri (L.) Wettst and Centella asiatica (L.) Urb., two nootropics, are recognized in Indian Ayurvedic texts. Studies have attempted to understand their action as memory enhancers and neuroprotectants, but many molecular aspects remain unknown. We propose that Bacopa monnieri (L.) Wettst and Centella asiatica (L.) Urb. share common neuroprotective mechanisms. Mass spectrometry–based untargeted metabolomics and network pharmacology approach were used to identify potential protein targets for the metabolites from each extract. Phytochemical analyses and cell culture validation studies were also used to assess apoptosis and ROS activity using aqueous extracts prepared from both herbal powders. Further, docking studies were also performed using the LibDock protocol. Untargeted metabolomics and network pharmacology approach unveiled 2751 shared metabolites and 3439 and 2928 non-redundant metabolites from Bacopa monnieri and Centella asiatica extracts, respectively, suggesting a potential common neuroprotective mechanism among these extracts. Protein-target prediction highlighted 92.4% similarity among the proteins interacting with metabolites for these extracts. Among them, kinases mapped to MAPK, mTOR, and PI3K-AKT signaling pathways represented a predominant population. Our results highlight a significant similarity in the metabolome of Bacopa monnieri (L.) Wettst and Centella asiatica (L.) Urb., and their potential protein targets may be attributed to their common neuroprotective functions. Graphical Abstract Workflow employed for phytochemical assays, mass spectrometry-based metabolomics, protein-target identification, cell culture validations, and docking studies. Comparison of Bacopa monnieri and Centella asiatica  non-redundant metabolite identification at MS level,as well as at MS/MS level