Research Progress on Chemical Constituents, Pharmacological Effects, Clinical Applications, and Adverse Reactions of Indigo Naturalis
Indigo Naturalis (Qingdai), a traditional Chinese medicine prepared from the leaves or stems of Baphicacanthus cusia, Polygonum tinctorium, or Isatis indigotica, contains both inorganic components (calcium carbonate, silicon dioxide) and organic constituents (alkaloids, organic acids, diterpenoids, triterpenoids, steroids). It exhibits antiviral, anti-inflammatory, antibacterial, antioxidant, antitumor, and immunomodulatory activities, and is clinically employed for ulcerative colitis, psoriasis, acute promyelocytic leukemia, and atopic dermatitis. However, long-term excessive consumption can induce hepatotoxicity, pulmonary arterial hypertension, acute colitis, intussusception, and renal injury. This review systematically summarizes the processing methods, chemical constituents, pharmacological effects, clinical applications, adverse reactions, and quality control of Indigo Naturalis. Current challenges include: (1) diverse plant sources and complex, experience-dependent traditional processing leading to variable quality; (2) incomplete quality standards that focus on organic components (indigo, indirubin) while neglecting the 90% inorganic fraction and trace organics; (3) unclear active constituents and mechanisms despite proven clinical efficacy; and (4) unresolved toxicity mechanisms. Quantitative data reveal indigo content ranging from 0 to 9.00% and indirubin from 0 to 0.60% by HPLC, while CaCO3 varies from 23.65% to 38.47% by ICP-OES. The review proposes future directions including digital quality characterization, novel dosage forms, and computational toxicology for precise toxicity prediction, providing a reference for in-depth research and development of Indigo Naturalis.