Thymoquinone

Thymoquinone is the principal constituent of black seed oil at 27 to 55 percent. As a reactive quinone, it is readily attacked by nucleophiles such as amines and thiols. It is a potent skin sensitizer and reproductive toxicant.

Skin. Thymoquinone 1 percent in alcohol was used as a reference irritant in patch testing on 600 eczema sufferers and 33 healthy controls. Positive local erythema occurred in 53 to 63 percent across all three groups. The compound is a significant contact sensitizer.

Oral. Acute oral LD50 in rats was 794 mg/kg and in mice 871 mg/kg. Intraperitoneal LD50 in rats was 57.5 mg/kg and in mice 90 to 105 mg/kg. Parenteral routes are much more toxic than oral.

Subchronic. Mice given thymoquinone in drinking water at 0.01, 0.02 and 0.03 percent, equivalent to 30 to 90 mg/kg/day for 90 days, showed no toxicity. Intraperitoneal injection of 8 mg/kg/day in rats caused death in most animals within a week with severe peritonitis.

Reproductive. A single intraperitoneal dose of 15, 35 or 50 mg/kg in pregnant rats on gestational day 11 or 14 caused dose-dependent fetal resorption and maternal toxicity at the two higher doses. The NOAEL was 15 mg/kg. At 50 mg/kg on day 11, 100 percent of implants were resorbed.

Cardiovascular. Thymoquinone potently inhibits VEGF-induced angiogenesis in vitro and inhibits tumor vascularization in mouse prostate cancer.

Kidney. Protects rat kidney from ifosfamide and cisplatin damage at low doses.

Mutagenicity. Antimutagenic activity in mouse cells infected with schistosomiasis. In rat hepatocytes, concentrations above 1.25 mM caused increased chromosome aberrations.

Cancer. Shows broad anticancer activity in vitro and in vivo, inducing apoptosis in many cancer cell lines while sparing normal cells.

Thymoquinone is the central compound behind the broad pharmacological research on nigella oil, from anti-inflammatory to anticancer activity. However, its high reactivity and significant reproductive toxicity demand particular caution for pregnancy and topical products.

Intraperitoneal and oral routes show a large toxicity gap. Oral dosing is typically 10 to 15 times less toxic.