ABHRAKA BHASMA AND THE NEURONAL EPIGENOME: A HYPOTHETICAL FRAMEWORK LINKING NANOSTRUCTURE, MECHANOTRANSDUCTION, AND LONG-TERM POTENTIATION

Background: Abhraka Bhasma is a traditionally processed mineral preparation of Rasashastra with described Rasayana applications and associations with Majja Dhatu and cognitive functions. Contemporary physicochemical investigations have demonstrated that pharmaceutical processing can produce substantial changes in the mineral's elemental composition, crystallinity, particle characteristics, and morphology. These findings raise the possibility that the biological effects of Abhraka Bhasma may involve mechanisms beyond conventional chemical interactions. Mechanobiology provides a potential framework for investigating how the physicochemical characteristics of mineral-derived materials may interact with cellular mechanosensing, cytoskeletal signaling, nuclear regulation, and neuronal plasticity. Aim and Objectives: The aim of this review is to develop a hypothesis-driven framework linking the physicochemical characteristics of Abhraka Bhasma with mechanotransduction, epigenetic regulation, and neuronal synaptic plasticity, particularly long-term potentiation (LTP). The objectives are to review the Ayurvedic and pharmaceutical basis of Abhraka Bhasma; evaluate its contemporary physicochemical and nanoscale characteristics; examine evidence relating extracellular mechanics and mechanotransduction to neuronal function; explore the relationship between mechanical signaling, chromatin regulation, and neuronal plasticity; and identify experimentally testable pathways connecting Abhraka-derived material properties with neuronal mechanotransduction and LTP. Materials And Methods: A structured narrative literature review was conducted using databases including PubMed, Scopus, Web of Science, Google Scholar, ScienceDirect, AYUSH Research Portal, and DHARA Online, along with relevant classical Ayurvedic literature. Literature concerning Abhraka Bhasma and Rasashastra, mineral nanomaterials, mechanobiology, mechanotransduction, neuroepigenetics, mechanical memory, neuronal plasticity, and LTP was identified and critically synthesized. Evidence from these domains was integrated to develop a conceptual Abhraka–neuronal epigenome framework. No primary experimental investigation was performed. Observation And Results: The reviewed literature indicates that Abhraka Bhasma is a complex processed mineral material whose physicochemical characteristics can vary according to pharmaceutical preparation and analytical methodology. Independent evidence from mechanobiology demonstrates that extracellular mechanical conditions can influence neuronal development, synaptic organization, and network activity through mechanosensing systems involving integrin-associated structures, mechanically activated ion channels, cytoskeletal signaling, and YAP/TAZ-mediated mechanotransduction. Mechanical signaling can also influence nuclear organization, chromatin regulation, and transcriptional programs, while mechanical memory has been demonstrated predominantly in non-neuronal cellular systems. In neuronal plasticity, activity-dependent calcium signaling, gene transcription, and structural synaptic modifications contribute to persistent changes associated with LTP. Integration of these findings provides a hypothetical mechanistic framework in which the physicochemical characteristics of appropriately prepared Abhraka Bhasma could potentially interact with neuronal or glial cell–material interfaces and influence mechanotransductive and epigenetic pathways relevant to synaptic plasticity. However, direct evidence demonstrating CNS delivery, neuronal mechanotransduction, epigenetic modification, or LTP induction by Abhraka Bhasma is currently lacking. Conclusion: The available evidence supports consideration of Abhraka Bhasma as a potential subject for interdisciplinary investigation at the interface of Rasashastra, materials science, mechanobiology, and neuroepigenetics. The proposed Abhraka–neuronal epigenome framework provides a testable hypothesis rather than an established mechanism, linking mineral-derived physicochemical characteristics with possible mechanotransduction, chromatin regulation, and neuronal plasticity. Experimental studies addressing material characterization, biological availability, cell–material interactions, mechanosensitive signaling, epigenetic changes, neuronal network activity, and LTP are required to evaluate this proposed relationship.