Thymoquinone is an orally active natural product isolated from Nigella glandulifera. Thymoquinone downregulates the VEGFR2-PI3K-Akt pathway, inhibits the expression of NF-κB and MMP-9, downregulates TWIST1 expression, and activates the Nrf2 pathway to exert various biological activities. Thymoquinone can be used in research related to Alzheimer's disease, cancer, cardiovascular diseases, infectious diseases, and inflammation[1-4].
In vitro, Thymoquinone (25–100μM) was used to treat the human breast cancer cell line MCF-7 for 12–72 hours. Thymoquinone significantly inhibited cell proliferation, induced apoptosis, and caused S-phase and G2-phase cell cycle arrest[5]. Thymoquinone (20μM) was used to treat the colorectal cancer cell lines RKO and SW1116 for 24 hours. In RKO cells, Thymoquinone significantly induced DNA fragmentation, caspase activation, and upregulation of pro-apoptotic genes. In SW1116 cells, Thymoquinone significantly inhibited caspase activity and induced caspase-independent necrotic cell death[6].
In vivo, Thymoquinone (100mg/kg/day) was administered by gavage to LDL-R-/- mice for 8 weeks. Thymoquinone significantly alleviated hyperlipidemia-induced liver injury[7]. Thymoquinone (20mg/kg and 40mg/kg; three times per week) was administered via intraperitoneal injection to C57BL/6J mice for one month. Thymoquinone (40mg/kg) significantly improved age-related hearing loss[8].
References:
[1] Zeinvand-Lorestani H, Nili-Ahmadabadi A, Balak F, et al. Protective role of thymoquinone against paraquat-induced hepatotoxicity in mice. Pestic Biochem Physiol. 2018 Jun;148:16-21.
[2] Nagi MN, Mansour MA. Protective effect of thymoquinone against doxorubicin-induced cardiotoxicity in rats: a possible mechanism of protection. Pharmacol Res. 2000 Mar;41(3):283-9.
[3] Elibol B, Beker M, Terzioglu-Usak S, et al. Thymoquinone administration ameliorates Alzheimer's disease-like phenotype by promoting cell survival in the hippocampus of amyloid beta1-42 infused rat model. Phytomedicine. 2020 Dec;79:153324.
[4] Su X, Ren Y, Yu N, et al. Thymoquinone inhibits inflammation, neoangiogenesis and vascular remodeling in asthma mice. Int Immunopharmacol. 2016 Sep;38:70-80.
[5] Motaghed M, Al-Hassan FM, Hamid SS. Cellular responses with thymoquinone treatment in human breast cancer cell line MCF-7. Pharmacognosy Res. 2013 Jul;5(3):200-6.
[6] Kurowska N, Książek M, Borkowska P, et al. Cell Line-Dependent Cell Death Pathways Induced by Thymoquinone in Colorectal Cancer Cells. Molecules. 2026 Feb 2;31(3):512.
[7] Wang F, Yao W, Yu D, et al. Protective role of thymoquinone in hyperlipidemia-induced liver injury in LDL-R-/-mice. BMC Gastroenterol. 2023 Aug 11;23(1):276.
[8] Salam SA, Mostafa F, Alnamshan MM, et al. Thymoquinone ameliorates age-related hearing loss in C57BL/6J mice by modulating Sirt1 activity and Bak1 expression. Biomed Pharmacother. 2021 Nov;143:112149.