INTERNATIONAL JOURNAL OF AGRICULTURE & BIOLOGY ISSN Print: 1560–8530; ISSN Online: 1814–9596 20–1470/2021/25–5–1024–1034 DOI: 10.17957/IJAB/15.1760 http://www.fspublishers.org Review Article To cite this paper: Aftab A, Z Yousaf, B Shamsheer, N Riaz, M Rashid, A Younas, A Javaid (2021). Thymoquinone: biosynthesis, biological activities and therapeutic potential from natural and synthetic sources. Intl J Agric Biol 25:1024‒1034 Thymoquinone: Biosynthesis, Biological Activities and Therapeutic Potential from Natural and Synthetic Sources Arusa Aftab 1* , Zubaida Yousaf 1* , Bushra Shamsheer 1 , Nadia Riaz 1 , Madiha Rashid 1 , Afifa Younas 1 and Arshad Javaid 2 1 Department of Botany, Lahore College for Women University Lahore, Jail Road Lahore, Pakistan 2 Institute of Agricultural Sciences, University of the Punjab Lahore, Pakistan * For correspondence: mussabuswaeshal@hotmail.com; arusakashif@gmail.com Received 15 October 2020; Accepted 01 February 2021; Published 16 April 2021 Abstract Thymoquinone (TQ; 2-isopropyl-5-methyl-1,4-benzoquinone) is a secondary metabolite found in abundance in very few plant species including Nigella sativa L., Monarda fistulosa L. and Satureja montana L. It is found in crystalline triclinic form in a range of organs in these plants. TQ has been synthetically prepared from thymol (2-isopropyl-5-methylphenol); commercially it is synthesized by modification of thymol and carvacrol (5-isopropyl-2-methylphenol). TQ has substantial therapeutic potential because of its anti-cancer, hepato-protective, anti-inflammatory, antioxidant, antimicrobial and cardio-protective activities in cell culture systems and animal models. In this article, we have reviewed recent studies on the natural and synthetic sources of TQ, its biosynthetic pathway and its modes of action in human and experimental models, as well as its commercial preparation. We also compiled the medicinal effects of TQ. The biological activities of TQ support the potential of this plant secondary metabolite as a drug with a wide range of therapeutic applications. To substantiate the benefits and pharmaceutical properties of TQ, further well-designed clinical research is required. © 2021 Friends Science Publishers Keywords: Anti-cancer; Nigella sativa; Phytochemical; Phytotherapy; Thymoquinone Introduction Thymoquinone (TQ; 2-isopropyl-5-methyl-1,4-benzoquinone; Fig. 1) is the most abundant and important bioactive constituent of a number of plant species, such as Nigella sativa L. (black-caraway, black cumin, also known as nigella or kalonji). In the Middle East, many diets include plants containing TQ and are considered to be health- promoting. N. sativa (an annual herb) is cultivated around the Mediterranean, Syria, Egypt and India at larger scale for TQ extraction. The safe uses of N. sativa oil and its most important constituent TQ have been confirmed by acute and chronic toxicity studies. TQ is also a bioactive element of the volatile oil of Monarda fistulosa L. (Gali- Muhtasib et al. 2006). With the use of high-resolution X-ray powder diffraction, it was determined that TQ can be found only in a crystalline triclinic form (Pagola et al. 2004). Numerous analytical techniques, including high performance liquid chromatography (HPLC), gas chromatography (GC) and differential pulse polarography, have been used for TQ quantification in plant extracts (Michelitsch and Rittmannsberger 2003). Although TQ has poor solubility in water, an increase in the operating pressure from 100 to 120 bar at 38°C, for example, results in an increase in TQ solubility (Gurdenova and Wawrzyniak 2012). TQ is soluble in supercritical CO 2 . TQ is therapeutically important because of its anti- cancer, hepato-protective, anti-inflammatory, antioxidant, antimicrobial and cardio-protective activities in cell culture systems and animal models (Fig. 2). The understanding of these activities has been strengthened by elucidation of their molecular mechanisms (Pang et al. 2017). TQ inhibited cell proliferation and induced apoptosis in several human cancer cell lines such colon, breast, brain, pancreatic, and ovarian (Gurung et al. 2010). Several reports suggest an adjuvant role of TQ which may improve the quality of cancer patients (Woo et al. 2012). Over the last 20 years about one quarter of drugs have been directly isolated from plants, while in another quarter, natural compounds have been chemically modified (Vuorelaa et al. 2004). TQ has shown considerable anti- neoplastic activity against human cancer by specifically inhibiting the growth of tumor cells without any harmful effects on normal cells. TQ operates through diverse modes of action: cell cycle arrest, reactive oxygen species (ROS) production, anti-proliferation activity, anti-metastasis activity and apoptosis induction (Gurung et al. 2010).