Nigella sativa L. (Black Seed): Phytochemistry, Pharmacological Insights, Clinical Evidence, and Safety Considerations

Abstract Nigella sativa L. (black seed, Kalonji ) is an ancient medicinal plant revered in Unani and other traditional systems, as well as in religious and historical texts, for managing diverse ailments affecting the digestive, respiratory, and metabolic systems. Modern pharmacological investigations have revealed its broad therapeutic potential, primarily attributed to its bioactive compound thymoquinone (TQ). This integrative critical review synthesizes the data from classical Unani texts, religious and historical references, and biomedical studies. Comprehensive searches across PubMed, Scopus, Web of Science, and Google Scholar yielded 7600 records, of which 126 met inclusion criteria in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 guidelines. The findings demonstrate that N. sativa L. possesses antimicrobial, antioxidant, anti-inflammatory, immunomodulatory, anticancer, antidiabetic, anti-obesity, gastroprotective, nephroprotective, and hepatoprotective properties. Clinical evidence supports its beneficial role in type 2 diabetes, dyslipidemia, obesity, asthma, and dermatological disorders, while preclinical studies confirm cytoprotective and organ-protective mechanisms. Toxicological assessments indicate a wide therapeutic margin and minimal adverse effects at traditional doses (1–3 g/day seeds or 5 mL/day oil). However, challenges persist regarding phytochemical variability, absence of standardized formulations, and insufficient large-scale clinical trials. Overall, N. sativa L. exemplifies a convergence of traditional wisdom and modern biomedical validation, positioning it as a promising integrative therapeutic agent.