Thymoquinone (2-isopropyl-5-methyl-1,4-benzoquinone, or TQ) is derived from the seeds of the black cumin plant Nigella sativa. It has been reported to have a number of beneficial properties including anti-oxidative, anti-inflammatory and anti-tumorigenic activities and, like many other natural products, derivatives and analogues of thymoquinone are being synthesised in an effort to increase its therapeutic potential.
Normal cellular metabolism gives rise to reactive oxygen species such as hydrogen peroxide (H2O2) and super oxide anion radicals (O2 -), however these products must be carefully regulated since they are highly reactive and can be toxic. An imbalance between the generation of reactive oxygen species and their subsequent detoxification is known as oxidative stress, and this is implicated in a number of disease states including Alzheimer’s disease, Parkinson’s disease and arthritis. Amyloid-β is a peptide which is deposited extracellularly and accumulates as plaques in the brains of individuals with Alzheimer’s disease, where it leads to depolarisation of mitochondrial membranes and the generation of reactive oxygen species. In a recent study, Alhebshi et al treated rat brain neurons with amyloid-β peptide and demonstrated that thymoquinone inhibited aggregation of the protein in vitro, attenuating amyloid-β-induced neurotoxicity and improving cell viability, thereby suggesting a promising role for the compound in the treatment of dementia (1).
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Aggregation: Thymoquinone (IL17 Inhibitor)
Asthma is a chronic disorder of the airway, in which various inflammatory cells generate a greater quantity of reactive oxygen species than cells from healthy individuals. These reactive oxygen species stimulate histamine release from mast cells, leading to wheezing, coughing and shortness of breath. Keyhanmanesh et al sensitised guinea pigs to ovalbumin, and then provided them with drinking water alone, or drinking water containing thymoquinone, whilst exposing them to an aerosol containing ovalbumin. They examined lung pathology by immunohistochemistry and also evaluated levels of the inflammatory mediator IL-4 in the blood, and found that thymoquinone significantly improved the pathological changes to the lung and was associated with decreased IL-4 levels in comparison to the control group (2).
Li et al showed thymoquinone to inhibit proliferation of multiple myeloma cells through suppression of the STAT3 pathway. They treated two human multiple myeloma cell lines with thymoquinone in a dose-dependent manner, then analysed the effects of the compound on cellular proliferation and induction of apoptosis, whilst simultaneously evaluating STAT3 phosphorylation levels. They demonstrated that thymoquinone treatment had no effect on the expression levels of STAT3, but inhibited STAT3 phosphorylation and the expression of several STAT3-regulated gene products. Additionally, thymoquinone inhibited proliferation and induced apoptosis (3). Constitutive activation of the STAT3 pathway has been reported in a number of human cancers and STAT3 is a viable therapeutic target (4).
Thymoquinone is a promising compound for the treatment of a variety of disorders, and has therapeutic potential as an anti-oxidative, anti-inflammatory and anti-cancer agent.
Written by Emma Easthope
