User:Ahjinyoo0804/sandbox
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| Names | |
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| Preferred IUPAC name
2-Methyl-5-(propan-2-yl)cyclohexa-2,5-diene-1,4-dione | |
| Other names
Thymoquinone
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| Identifiers | |
3D model (JSmol)
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| ChEBI | |
| ChEMBL | |
| ChemSpider | |
PubChem CID
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| UNII | |
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| Properties | |
| C10H12O2 | |
| Molar mass | 164.204 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Thymoquinone is a phytochemical compound found in the plant Nigella sativa. It is also found in select cultivated Monarda fistulosa plants which can be steam distilled to produce an essential oil commonly known as black seed oil. It is mostly used for well-being due to its variety of therapeutic effects. However, its potential as treatment for different conditions including leukemia, colon cancer, breast cancer, HIV, epilepsy, hypertension, asthma, osteoporosis, and more has been a continuous interest in the pharmaceutical field.[1] Thymoquinone is also known to be less toxic than other drugs with an LD50 that ranges from 100~900mg/kg in mice depending on the method of administration.[2] Its exact mechanisms of action in different possible treatments are still being determined with a lack of prominent clinical trials.
It has been classified as a pan-assay interference compound, which binds indiscriminately to many proteins.[3] It is under preliminary research to identify its possible biological properties.[4][5][6]
Therapeutic Effects
[edit]Antioxidant, Anti-Inflammatory Activity
[edit]Thymoquinone is considered an anti-oxidant, which defends against reactive oxygen species (ROS) which are continuously produced in cells through aerobic metabolism. The presence of ROS induces oxidation of biomolecules which can be harmful to the host. Thymoquinone neutralizes the free radical-induced oxidative damage as an anti-oxidant enzyme in a variety of organs, including the liver, stomach, and kidney.[7]
Inflammation in the body is mainly mediated by cyclooxygenase and lipoxygenase, enzymes that generate prostaglandins and leukotrienes. Thymoquinone inhibits both enzymes in their pathways of arachidonic acid metabolism specifically in rats, causing anti-inflammatory effects.[8][9] Other anti-inflammatory effects of thymoquinone involves the inhibition of histamine production and release. It abolishes the effects of histamine and serotonin on the tracheal and ileum smooth muscles.[7]
Effects on the Respiratory System
[edit]Known for its effects on alleviating asthma, thymoquinone has been tested in its volatile oil form in guinea pigs and dogs. Intramuscular (i.m) or intraperitoneal (i.p) injection of thymoquinone in doses of 200μl/kg induces bronchodilation, reversing the effects of histamine-induced bronchoconstriction.[8] Thymoquinone also induces relaxation of subject's isolated trachea by inhibiting lipoxygenase products and by non-selectively blocking histamine and serotonin receptors.[7]
Anti-cancer Activity
[edit]In the presence of tumor cells, thymoquinone has shown cytotoxic effects in arresting cell cycle progression without being largely toxic to normal cells. In humans, it has induced G0/G1 arrest in HCT116 human colorectal carcinoma cells via the regulation of p53,[10] inhibited G1 to S phase progression in LNCaP prostate cancer cells,[11] and induced G2/M arrest in osteosarcoma cells with the upregulation of p21.[12]
Thymoquinone has been proven to act as an oral anti-diabetic drug by reducing blood sugar in induced diabetic rats (25mg/kg/day). Its effects are partly explained by α-glucosidase inhibition.[13] Some studies suggest thymoquinones hyperglycemic effect is due to the increase in insulin production and decrease in hepatic gluconeogenesis, reducing glucose production in diabetic animal test subjects.[14]
Continuous research is being performed to determine the exact mechanisms of action thymoquinone displays to cause these effects.
Chemical Synthesis
[edit]Thymoquinone was first extracted and isolated in 1963 by an Egyptian chemist Mostafa M. El-Dakhakhny from the plant's essential oil using silica gel column chromatography.[15] A common way to synthesize thymoquinone involves the sulfonation and oxidation of thymol and carvacrol to yield thymoquinone, thymohydroquinone, and isomers of benzoquinones. One of the first ways thymoquinone was synthesized was the addition of nitric oxide to thymol to yield nitrosothymol, following the animation to aminothymol, and the oxidation to thymoquinone.[16] Several analogs and derivatives of thymoquinone are continuously being synthesized to apply the plethora of therapeutic effects for different medical treatments.
Biosynthesis
[edit]
Thymoquinone is biosynthesized by plants through the terpene biosynthetic pathway as a secondary metabolite. It belongs to the class of monoterpenes which stem from the condensation of two isoprene units.[2] For thymoquinone, geranyl disphosphate, the precursor of the pathway, cyclizes and is converted to γ-terpinene by γ-terpinene synthase (during seed maturation).[17] Cytochrome p450 monooxygenases (P450s) then oxidizes γ-terpinene into p-cymene. Hydroxylation leads to the formation of carvacrol and further hydroxylation produces thymohydroquinone. Thymohydroquinone then undergoes oxidation to form thymoquinone.[18]
An alternative biosynthetic pathway may occur if some species of the plant accumulate thymol instead of carvacrol, where p-cymene hydroxylates to thymol. [2]
Toxicity
[edit]In moderate amounts, black seed oil (thymoquinone) usage is not harmful to humans; however, long term administration can cause liver and/or kidney toxicity due to the reduction of tissue glutathione content.[2][7] Symptoms of toxicity can include dyspnoea and peritonitis. The method of administration also affects the thymoquinone's level of toxicity- intraperitoneal injections result in more toxic effects at high dosages than oral administration due to the greater absorption into systemic circulation.[2]
History
[edit]Thymoquinone is the bioactive substance in the seeds of the Nigella sativa plant. The black-colored, funnel-shaped seeds are what's used for isolation of thymoquinone and the plant is cultivated in regions including Southern Europe, North Africa, Middle Eastern Mediterranean, and southern parts of Asia.[14]
See also
[edit]- Dithymoquinone, a dimer of thymoquinone
- 2,5-Dimethoxy-p-cymene
References
[edit]- ^ Aftab, Arusa (2021-05-01). "Thymoquinone: Biosynthesis, Biological Activities and Therapeutic Potential from Natural and Synthetic Sources". International Journal of Agriculture and Biology. 25 (05): 1024–1034. doi:10.17957/IJAB/15.1760.
- ^ a b c d e Ahmad, Anas; Mishra, Rakesh Kumar; Vyawahare, Akshay; Kumar, Ajay; Rehman, Muneeb U.; Qamar, Wajhul; Khan, Abdul Quaiyoom; Khan, Rehan (2019-12). "Thymoquinone (2-Isopropyl-5-methyl-1, 4-benzoquinone) as a chemopreventive/anticancer agent: Chemistry and biological effects". Saudi Pharmaceutical Journal. 27 (8): 1113–1126. doi:10.1016/j.jsps.2019.09.008. PMC 6921197. PMID 31885471.
{{cite journal}}: Check date values in:|date=(help)CS1 maint: PMC format (link) - ^ Baell JB (March 2016). "Feeling Nature's PAINS: Natural Products, Natural Product Drugs, and Pan Assay Interference Compounds (PAINS)". Journal of Natural Products. 79 (3): 616–28. doi:10.1021/acs.jnatprod.5b00947. PMID 26900761.
- ^ Farkhondeh T, Samarghandian S, Borji A (September 2017). "An overview on cardioprotective and anti-diabetic effects of thymoquinone". Asian Pacific Journal of Tropical Medicine. 10 (9): 849–854. doi:10.1016/j.apjtm.2017.08.020. PMID 29080612.
- ^ Leong, Xin-Fang; Choy, Ker Woon; Alias, Aspalilah (2021-12-15). "Anti-Inflammatory Effects of Thymoquinone in Atherosclerosis: A Mini Review". Frontiers in Pharmacology. 12: 758929. doi:10.3389/fphar.2021.758929. ISSN 1663-9812. PMC 8715035. PMID 34975474.
- ^ Ali, Md Yousuf; Akter, Zakia; Mei, Zhiqiang; Zheng, Meiling; Tania, Mousumi; Khan, Md Asaduzzaman (February 2021). "Thymoquinone in autoimmune diseases: Therapeutic potential and molecular mechanisms". Biomedicine & Pharmacotherapy. 134: 111157. doi:10.1016/j.biopha.2020.111157. ISSN 1950-6007. PMID 33370631. S2CID 229714190.
- ^ a b c d Darakhshan, Sara; Bidmeshki Pour, Ali; Hosseinzadeh Colagar, Abasalt; Sisakhtnezhad, Sajjad (2015-05). "Thymoquinone and its therapeutic potentials". Pharmacological Research. 95–96: 138–158. doi:10.1016/j.phrs.2015.03.011.
{{cite journal}}: Check date values in:|date=(help) - ^ a b Hussein El-Tahir, Kamal El-Din; Bakeet, Dana M. (2006-01-01). "The Black Seed Nigella sativa Linnaeus - A Mine for Multi Cures: A Plea for Urgent Clinical Evaluation of its Volatile Oil". Journal of Taibah University Medical Sciences. 1 (1, Supplement C): 1–19. doi:10.1016/S1658-3612(06)70003-8. ISSN 1658-3612.
- ^ Khan, M. Akram (1999-03). "Chemical composition and medicinal properties of Nigella sativa Linn". Inflammopharmacology. 7 (1): 15–35. doi:10.1007/s10787-999-0023-y. ISSN 0925-4692.
{{cite journal}}: Check date values in:|date=(help) - ^ Gali-Muhtasib, Hala; Diab-Assaf, Mona; Boltze, Carsten; Al-Hmaira, Josianne; Hartig, Roland; Roessner, Albert; Schneider-Stock, Regine (2004-10). "Thymoquinone extracted from black seed triggers apoptotic cell death in human colorectal cancer cells via a p53-dependent mechanism". International Journal of Oncology. 25 (4): 857–866. ISSN 1019-6439. PMID 15375533.
{{cite journal}}: Check date values in:|date=(help) - ^ Kaseb, Ahmed O.; Chinnakannu, Kannagi; Chen, Di; Sivanandam, Arun; Tejwani, Sheela; Menon, Mani; Dou, Q. Ping; Reddy, G. Prem-Veer (2007-08-15). "Androgen Receptor– and E2F-1–Targeted Thymoquinone Therapy for Hormone-Refractory Prostate Cancer". Cancer Research. 67 (16): 7782–7788. doi:10.1158/0008-5472.CAN-07-1483. ISSN 0008-5472.
- ^ Roepke, Martin; Diestel, Antje; Bajbouj, Khouloud; Walluscheck, Diana; Schonfeld, Peter; Roessner, Albert; Schneider-Stock, Regine; Gali-Muhtasib, Hala (2007-02). "Lack of p53 augments thymoquinone-induced apoptosis and caspase activation in human osteosarcoma cells". Cancer Biology & Therapy. 6 (2): 160–169. doi:10.4161/cbt.6.2.3575. ISSN 1538-4047.
{{cite journal}}: Check date values in:|date=(help) - ^ Sobhi, Widad; Boutrid, Nada; Rezgui, Abdelmalek; Rahmoune, Hakim; Benguerba, Yacine (2022-03). "Anti-hyperglycemic and hepato-protective effects of thymoquinone (Nigella sativa oil) in diabetes". Metabolism. 128: 155108. doi:10.1016/j.metabol.2021.155108.
{{cite journal}}: Check date values in:|date=(help) - ^ a b Mahomoodally, Mohamad Fawzi; Aumeeruddy, Muhammad Zakariyyah; Legoabe, Lesetja J.; Montesano, Domenico; Zengin, Gokhan (2022-10-11). "Nigella sativa L. and Its Active Compound Thymoquinone in the Clinical Management of Diabetes: A Systematic Review". International Journal of Molecular Sciences. 23 (20): 12111. doi:10.3390/ijms232012111. ISSN 1422-0067. PMC 9602931. PMID 36292966.
{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link) - ^ El–Dakhakhny, M. (1963-12). "STUDIES ON THE CHEMICAL CONSTITUTION OF EGYPTIAN NIGELLA SATIVA L. SEEDS. II 1 ) THE ESSENTIAL OIL". Planta Medica. 11 (04): 465–470. doi:10.1055/s-0028-1100266. ISSN 0032-0943.
{{cite journal}}: Check date values in:|date=(help) - ^ "THYMOQUINONE". Organic Syntheses. 6: 92. 1926. doi:10.15227/orgsyn.006.0092.
- ^ Elyasi, Rizan; Majdi, Mohammad; Krause, Sandra T.; Kücükay, Nagihan; Azizi, Abdolbaset; Degenhardt, Jörg (2022-10-01). "Identification and functional characterization of a γ-terpinene synthase in Nigella sativa L (black cumin)". Phytochemistry. 202: 113290. doi:10.1016/j.phytochem.2022.113290. ISSN 0031-9422.
- ^ Krause, Sandra T.; Liao, Pan; Crocoll, Christoph; Boachon, Benoît; Förster, Christiane; Leidecker, Franziska; Wiese, Natalie; Zhao, Dongyan; Wood, Joshua C.; Buell, C. Robin; Gershenzon, Jonathan; Dudareva, Natalia; Degenhardt, Jörg (2021-12-28). "The biosynthesis of thymol, carvacrol, and thymohydroquinone in Lamiaceae proceeds via cytochrome P450s and a short-chain dehydrogenase". Proceedings of the National Academy of Sciences. 118 (52): e2110092118. doi:10.1073/pnas.2110092118. ISSN 0027-8424. PMC 8719858. PMID 34930840.
{{cite journal}}: CS1 maint: PMC format (link)