Pharmacology, Toxicology, and Rational Application of Cinnabar, Realgar, and Their Formulations

Abstract

Ethnopharmacological Relevance. Mineral medicines are widely used traditional Chinese medicines with curative effects. These medicines are used for many refractory diseases. Aim of the Review. In this review, cinnabar (HgS) and realgar (As₂S₂) serve as examples of mineral medicines, and their pharmacology, therapeutic toxicity, use in traditional medicine mixtures, and research perspectives are discussed. Materials and Methods. A search was performed for the literature on cinnabar and realgar in PubMed, the Chinese Pharmacopeia, Google, and other sources. The search included studies using single herbs, traditional formulations, or novel dosage forms. Results. Cinnabar and cinnabar formulas exhibit good efficacy for sedation, sleep improvement, anxiety alleviation, and brain protection. However, previous studies on neurotransmitters have reached different conclusions, and detailed pharmacological mechanisms are lacking. Realgar and its formulas exert promising antitumor activity through regulation of cell cycle arrest, intrinsic and extrinsic apoptosis, induction of differentiation, autophagy, metabolic reprogramming, matrix metalloproteinase-9 (MMP-9) signaling, and reactive oxygen species (ROS) generation. In addition, realgar can be used to treat a variety of refractory diseases by regulating immunity and exerting antibacterial, antiviral, and other effects. However, the existing pharmacological research on the use of realgar for epidemic prevention is insufficient, and animal experiments and research at the cellular level are lacking. Inappropriate applications of cinnabar and realgar can cause toxicity, including neurotoxicity, liver toxicity, kidney toxicity, and genotoxicity. The toxicological mechanism is complex, and molecular-level research is limited. For clinical applications, theory and clinical experience must be combined to guide scientific and rational drug use and to achieve reduced toxicity and increased efficacy through the use of modern preparation methods or combined drugs. Notably, when cinnabar and realgar are used to treat targeted diseases, these agents have a bidirectional effect of “treatment” and “toxicity” on the central nervous system in pathological and normal states. The pharmacological and toxicological mechanisms need to be elucidated in greater detail in the future. Overall, systematic research is needed to provide a basis for better promotion of the rational use of cinnabar and realgar in the clinic. Conclusion. Mineral medicines are multicomponent, multiactivity, and multitargeted substances. The pharmacology and mechanisms of the toxicity and action of realgar and cinnabar are extremely complex. A number of Chinese medicinal preparations of realgar and cinnabar have demonstrated unique efficacy in the treatment of refractory diseases.