Rasashastra, an integral part of Ayurvedic therapeutics, deals with the preparation and application of metallomineral formulations for medicinal purposes. This distinct branch of Ayurveda encompasses mineral drugs, metal drugs, and animal products, along with their varieties, characteristics, processing techniques, therapeutic uses, and associated adverse effects. It can be defined as a science concerned with the study of mineral and metallic substances, dominated by knowledge about mercury, with regard to their therapeutic utility, including the processing of these substances to prepare a drug, which can be equated with “Iatrochemistry” in today’s scientific parlance.1 Although the origins of Rasashastra can be found in ancient Indian scriptures, its development as a therapeutic system began in the eighth century AD with an abundant description of metals and minerals, along with their processing techniques and therapeutic uses, in ancient classics of Charaka and Sushruta Samhita.2 The classical scriptures of Ayurveda define the calcined, nontoxic, organometallic, irreversible complexes, or compound forms of metals and minerals, generated under regulated heat as Bhasma, and the process of preparing such compound forms is termed as Marana.3 The process of Marana involves purification and incineration of metals and minerals through a variety of techniques and transforms them into a form that is biocompatible, bioassimilable, and absorbable, and appropriate for the human body, along with enhanced stability, functionality, absorption, assimilation, bioavailability, targeted ingredient delivery, and effectiveness.3 The classics of Ayurveda advocate various standards to assess the end points of incineration and conversion of metal/minerals to a Bhasma state, which includes physical characteristics such as Varna (~color), Nishchandratvam (~lusterless), Varitara (~light and fine), Ketakirajah (~particle size like pollen grains of Pandanus odorifer Forssk. Kuntze flower), and chemical characterization such as Apunarbhava (~should not revert to original state) and Niruttha (~ inability to regain metallic form). All these attributes form the cornerstone for the quality control and safety assessment of Bhasma.4 These classical quality parameters for Bhasma indeed serve as early empirical standards to evaluate safety (absence of free metal), fineness (microparticulate nature), and bioassimilation (easy absorption without toxicity). More over, the contemporary studies using X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM), and Fourier Transform Infrared (FTIR) spectroscopy confirm that these classical preparations align with nano-/micro-crystalline structures (<100 nanometer particles, often agglomerated), altered oxidation states (e.g., copper oxides in Tamra bhasma ~calcined copper), and enhanced surface properties (smoothness and luminescence) through processing, thereby improving bioavailability and pharmacotherapeutics.5–8 Similarly, many such analytical techniques have been providing deeper insights into the physicochemical nature of Bhasmas. Various preclinical and clinical studies exploring immunomodulatory, antioxidant, and organ-protective effects are gradually building a scientific evidence base for these organometallic preparations. A large number of scientific studies have been conducted, providing the pharmacological and clinical evidence on the efficacy of metals and minerals in humans. Abhraka bhasma (~calcined mica), for instance, has been shown in studies to exhibit dose-dependent cytotoxicity, apoptosis, immunomodulatory action, and suppression of teratoma formation in several cell lines. In addition, in vivo research has demonstrated improved Deoxyribonucleic Acid (DNA) repair capability, decreased genotoxicity, chemopreventive responses, immune-stimulatory effects, and control of oxidative stress.9 The immunomodulatory effects of Rajata bhasma (~calcined silver) have been demonstrated through its ability to increase immune cell activity, regulate inflammatory cytokines, and display antioxidant qualities. The outcomes are consistent with its traditional application in boosting immunity and vigor.10 METALLODRUGS: CONTEMPORARY PERSPECTIVE The shift from traditional metallomineral medicine to contemporary metallodrugs has emerged as an important turning point in the field of pharmacology. In recent decades, “Metallodrugs,” the metal-containing therapeutic compounds, have become popular, especially in the field of oncology. The advent of cisplatin, a platinum-based chemotherapy drug, causing cancer cells to undergo apoptosis, emphasizes the potential of metals as potent therapeutic agents.11 In the field of biomedicine, metal-based therapeutics and imaging agents are widely employed for the diagnosis and treatment of various disorders, including cancer. Due to their promised cytotoxic and possible anticancer effects, various metal complexes, including ions such as Copper (Cu), Gold (Au), and Zinc (Zn) chelating agents, have drawn a lot of attention as anticancer agents and have been thoroughly studied.12 Previous studies have demonstrated that various nanoparticles, such as Au, Zinc Oxide (ZnO), Cu, and Copper Oxide (CuO) nanoparticles, have wider therapeutic applications including antibacterial, antifungal, antiviral, anticancer, antiangiogenic, and anti-inflammatory roles and these have been utilized as alternatives to conventional antibiotics to combat bacterial resistance through their targeting action on several biomolecules, which hinders the emergence of resistant strains.13 Metal-based drugs are classified according to their mechanisms of action, such as covalent binders (Platinum drugs form DNA adducts; Gold agents auranofin target thiols in enzymes like thioredoxin reductase), carriers (e.g., Carbon Monoxide CO-releasing molecules), enzyme mimics (e.g., Iron Fe and Zn), and photoactivatable compounds (e.g., Ruthenium Ru polypyridyls), reflecting their diverse roles in therapy and imaging.14 Various metal complexes such as Platinum (Pt), Ruthenium (Ru), Au, Cu, and Fe are described as promising anticancer agents, and their various roles – including DNA binding and damage, protein and enzyme inhibition, reactive oxygen species production, and their mechanisms of action are well documented in studies. Furthermore, developments of metal complex-based therapeutic agents in combination with various therapies such as gene therapy, immunotherapy, hyperthermia, and photodynamic therapy have also been demonstrated.15 Metallodrugs are challenging to design and develop. The development of metallodrugs confronts many obstacles despite their potential for therapeutic use, such as off-target toxicity, acquired resistance, low aqueous stability, insufficient mechanistic understanding, and synthesis-related environmental effects. However, by using a combination of metallodrug and nanotechnological techniques, such as encasing metal-based medications in various nanostructured materials, these issues can be resolved. For instance, it would be very interesting to combine anticancer metallodrugs with liposomes, lipid nanocapsules, human proteins, ceramic materials, carbon nanotubes, and metal or metal oxide nanoparticles.16 Metallodrugs have emerged as a hot topic in medical research for the advancement of contemporary medicine. Because of the unique properties of inorganic drugs, future research must continue to focus on finding a balance between therapeutic effects and toxicity, developing suitable drug formulations, and establishing suitable standards for stability, composition, and quality control of these compounds. The organometallic drugs in Ayurveda represent a sophisticated pharmacotherapeutic tradition with deep historical roots and significant future potential. When approached with scientific rigor, ethical responsibility, and fidelity to classical principles, these formulations can contribute meaningfully to integrative health care. Their journey from ancient alchemical practices to modern evidence-based medicine exemplifies the dynamic and evolving nature of Ayurveda as an eternal science. From this issue onwards, we are pleased to introduce a new section titled “Visionary Ayush Architects”, dedicated to honoring the luminaries who have shaped the foundations and evolution of Ayush. This initiative seeks to disseminate their legacy, contributions, and enduring impact to a wider audience. Acknowledging them would ensure that their knowledge and inspiration continues to guide present and future generations, while fostering a deeper appreciation of their role in advancing Ayush and preserving its eternal wisdom. In the current issue, we are paying tribute to three distinguished stalwarts of Ayurveda — Kabiraj Laxman Mishra, Vaidyaratnam P. Sankunni Varier, and Vaidyaratna Captain Dr. G. Srinivasa Murthy — whose exemplary contributions have significantly enriched the science and tradition of Ayurveda.
PK Prajapati (Thu,) studied this question.