**Background:** Scopoletin (6-methoxy-7-hydroxycoumarin) is a phenolic coumarin found in numerous medicinal and edible plants, including *Morinda citrifolia*, *Artemisia annua*, and *Lycium barbarum*. It has attracted attention due to its diverse pharmacological properties, such as antimicrobial, anticancer, anti-inflammatory, antioxidant, antidiabetic, hepatoprotective, and neuroprotective activities. However, its clinical application is limited by poor water solubility and low oral bioavailability. This review comprehensively summarizes the pharmacology, pharmacokinetics, and toxicity of scopoletin based on recent literature.
**Methods:** The authors conducted a narrative review of published studies on scopoletin, collating data from multiple databases. The review covers in vitro and in vivo experimental trials, pharmacokinetic studies in rats, dogs, and rabbits, and toxicity assessments in cell lines and animal models. No systematic search strategy or meta-analysis was performed; the paper is a descriptive summary of existing evidence.
**Key Results:**
- **Pharmacology:** Scopoletin exhibits antifungal activity against *Candida glabrata* (MIC 67.22 μg/mL) and *Candida tropicalis* (MIC 119 μg/mL), and antibacterial effects against *Staphylococcus aureus* and *Mycobacterium tuberculosis* (MIC 50 μg/mL). It shows anticancer effects by inducing apoptosis and cell cycle arrest in various cancer cell lines (e.g., IC50 7.5–25 μM in cervical cancer cells, 157 ± 25 μg/mL in PC3 cells). Anti-inflammatory activity is mediated through inhibition of NF-κB and MAPK pathways, reducing TNF-α, IL-6, and COX-2 expression. In liver disease models, scopoletin (0.01–0.05% in diet) reduces lipid accumulation and inflammation in alcoholic and non-alcoholic fatty liver disease. Antidiabetic effects include inhibition of α-glucosidase (IC50 2.93 ± 0.06 μM for AGE formation) and improvement of insulin sensitivity via PI3K/Akt and AMPK pathways. Neuroprotective effects involve inhibition of acetylcholinesterase (IC50 168.6 μM) and monoamine oxidase (IC50 19.4 μg/mL), and reduction of Aβ aggregation and oxidative stress.
- **Pharmacokinetics:** After oral administration in rats, scopoletin is rapidly absorbed (Tmax ~10 min) but has low oral bioavailability (5.59%–6.62% at doses of 5–20 mg/kg). It undergoes extensive metabolism, with less than 15% excreted unchanged in urine and less than 1% in bile. In dogs, bioavailability ranged from 5.69% to 7.08% at oral doses of 10–50 mg/kg. The compound is widely distributed in tissues, particularly heart, liver, and kidneys.
- **Toxicity:** Acute toxicity tests in rats showed no mortality or abnormal behavior at doses up to 2000 mg/kg (p.o.), indicating an LD50 > 2000 mg/kg. In vitro cytotoxicity assays demonstrated that scopoletin is non-toxic to most normal cell lines (e.g., HCvEpC IC50 90 μM, RAW 264.7 cells viable up to 50 μg/mL), while selectively inhibiting cancer cells. No long-term toxicity studies in animals were reported.
**Clinical Implications:** Scopoletin has potential as a therapeutic agent for cancer, liver disease, diabetes, neurodegenerative disorders (Alzheimer's, Parkinson's, Huntington's), and mental health conditions (anxiety, depression, schizophrenia). Its low toxicity profile supports further development, but poor oral bioavailability (≈6%) is a major limitation. Strategies to improve bioavailability, such as nanoparticle encapsulation (e.g., Soluplus-based micelles increased bioavailability by 438%) or chemical derivatization (e.g., 2-fluorobenzylpyridinium derivative with IC50 0.215 μM), are promising. The compound is also present in many edible plants, suggesting potential as a functional food ingredient. However, human studies are lacking, and further research is needed to elucidate molecular mechanisms, verify long-term safety, and optimize delivery systems.