299
Views
5
CrossRef citations to date
0
Altmetric
Review

Therapeutic Potential of Thymoquinone and Its Nanoformulations in Pulmonary Injury: A Comprehensive Review

, , , ORCID Icon, ORCID Icon, ORCID Icon, , ORCID Icon, ORCID Icon, & ORCID Icon show all
Pages 5117-5131 | Published online: 27 Jul 2021

References

  • Tong L, Bi J, Zhu X, et al. Keratinocyte growth factor-2 is protective in lipopolysaccharide-induced acute lung injury in rats. Respir Physiol Neurobiol. 2014;201:7–14. doi:10.1016/j.resp.2014.06.011
  • Xiao M, Zhu T, Zhang W, et al. Emodin ameliorates LPS-induced acute lung injury, involving the inactivation of NF-κB in mice. Int J Mol Sci. 2014;15:19355–19368. doi:10.3390/ijms151119355
  • Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med. 2000;342:1334–1349. doi:10.1056/NEJM200005043421806
  • Hutson PA, Church MK, Clay TP, Miller P, Holgate ST. Early and late-phase bronchoconstriction after allergen challenge of nonanesthetized guinea pigs. Am Rev Respir Dis. 1988;137:548–557. doi:10.1164/ajrccm/137.3.548
  • Savov JD, Brass DM, Berman KG, McElvania E, Schwartz DA. Fibrinolysis in LPS-induced chronic airway disease. Am J Physiol Lung Cell Mol Physiol. 2003;285:L940–L948. doi:10.1152/ajplung.00102.2003
  • Hele D. First siena international conference on animal models of chronic obstructive pulmonary disease; 2001 Sept-30–Oct 2; Certosa di Pontignano, University of Siena, Italy. Respir Res. 2001;3:12. doi:10.1186/rr161
  • Kobayashi T. Exposure to diesel exhaust aggravates nasal allergic reaction in guinea pigs. Am J Respir Crit Care Med. 2000;162:352–356. doi:10.1164/ajrccm.162.2.9809035
  • Coker RK, Laurent GJ, Shahzeidi S, et al. Transforming growth factors-beta 1,-beta 2, and-beta 3 stimulate fibroblast procollagen production in vitro but are differentially expressed during bleomycin-induced lung fibrosis. Am J Pathol. 1997;150:981.
  • Onclinx C, De Maertelaer V, Gustin P, Gevenois PA. Elastase-induced pulmonary emphysema in rats: comparison of computed density and microscopic morphometry. Radiology. 2006;241:763–770. doi:10.1148/radiol.2413051456
  • Gordon T, Balmes J, Fine J, Sheppard D. Airway oedema and obstruction in guinea pigs exposed to inhaled endotoxin. Br J Ind Med. 1991;48:629–635. doi:10.1136/oem.48.9.629
  • Ulich TR, Yi ES, Yin S, Smith C, Remick D. Intratracheal administration of endotoxin and cytokines: VII. The soluble interleukin-1 receptor and the soluble tumor necrosis factor receptor II (p80) inhibit acute inflammation. Clin Immunol Immunopathol. 1994;72:137–140. doi:10.1006/clin.1994.1117
  • Abd El-Hack ME, Alagawany M, Farag MR, Tiwari R, Karthik K, Dhama K. Nutritional, healthical and therapeutic efficacy of black cumin (Nigella sativa) in animals, poultry and humans. Int J Pharmacol. 2016;12:232–248. doi:10.3923/ijp.2016.232.248
  • Abd El-Hakim YM, Al-Sagheer AA, Khafaga AF, Batiha GE, Arif M, Abd El-Hack ME. Nigella sativa supplementation in ruminant diets: production, health, and environmental perspectives. In: Fawzy Ramadan M editor. Black Cumin (Nigella sativa) Seeds: Chemistry, Technology, Functionality, and Applications. Food Bioactive Ingredients. Springer; 2021:245–264. doi:10.1007/978-3-030-48798-0_17.
  • Gado AR, Ellakany HF, Elbestawy AR, et al. Herbal medicine additives as powerful agents to control and prevent avian influenza virus in poultry–a review. Ann Anim Sci. 2019;19:905–935. doi:10.2478/aoas-2019-0043
  • El-Far AH, Korshom MA, Mandour AA, El-Bessoumy AA, El-Sayed YS. Hepatoprotective efficacy of Nigella sativa seeds dietary supplementation against lead acetate-induced oxidative damage in rabbit–purification and characterization of glutathione peroxidase. Biomed Pharmacother. 2017;89:711–718. doi:10.1016/j.biopha.2017.02.044
  • Mahapatro A, Singh DK. Biodegradable nanoparticles are excellent vehicle for site directed in vivo delivery of drugs and vaccines. J Nanobiotechnol. 2011;9:55. doi:10.1186/1477-3155-9-55
  • van Rijt SH, Bein T, Meiners S. Medical nanoparticles for next generation drug delivery to the lungs. Eur Respir Soc. 2014;44:765–774. doi:10.1183/09031936.00212813
  • Babu A, Templeton AK, Munshi A, Ramesh R. Nanoparticle-based drug delivery for therapy of lung cancer: progress and challenges. J Nanomater. 2013;2013:863951. doi:10.1155/2013/863951
  • Lee W-H, Loo C-Y, Traini D, Young PM. Inhalation of nanoparticle-based drug for lung cancer treatment: advantages and challenges. Asian J Pharm Sci. 2015;10:481–489. doi:10.1016/j.ajps.2015.08.009
  • Malcolmson R, Embleton JK. Dry powder formulations for pulmonary delivery. Pharmaceut Sci Tech Today. 1998;1:394–398. doi:10.1016/S1461-5347(98)00099-6
  • Grenha A, Seijo B, Remunán-López C. Microencapsulated chitosan nanoparticles for lung protein delivery. Eur J Pharm Sci. 2005;25:427–437. doi:10.1016/j.ejps.2005.04.009
  • Kolhar P, Anselmo AC, Gupta V, et al. Using shape effects to target antibody-coated nanoparticles to lung and brain endothelium. Proc Natl Acad Sci USA. 2013;110:10753–10758. doi:10.1073/pnas.1308345110
  • Liu J, Gong T, Fu H, et al. Solid lipid nanoparticles for pulmonary delivery of insulin. Int J Pharm. 2008;356:333–344. doi:10.1016/j.ijpharm.2008.01.008
  • Zhang Q, Shen Z, Nagai T. Prolonged hypoglycemic effect of insulin-loaded polybutylcyanoacrylate nanoparticles after pulmonary administration to normal rats. Int J Pharm. 2001;218:75–80. doi:10.1016/s0378-5173(01)00614-7
  • Al-Qadi S, Grenha A, Carrión-Recio D, Seijo B, Remuñán-López C. Microencapsulated chitosan nanoparticles for pulmonary protein delivery: in vivo evaluation of insulin-loaded formulations. J Control Release. 2012;157:383–390. doi:10.1016/j.jconrel.2011.08.008
  • Saghir SA, Al-Gabri NA, Khafaga AF, et al. Thymoquinone-PLGA-PVA nanoparticles ameliorate bleomycin-induced pulmonary fibrosis in rats via regulation of inflammatory cytokines and iNOS signaling. Animals. 2019;9:951. doi:10.3390/ani9110951
  • Caroff M, Karibian D. Structure of bacterial lipopolysaccharides. Carbohydr Res. 2003;338:2431–2447. doi:10.1016/j.carres.2003.07.010
  • Beutler B, Rietschel ET. Innate immune sensing and its roots: the story of endotoxin. Nat Rev Immunol. 2003;3:169–176. doi:10.1038/nri1004
  • Raetz CR, Whitfield C. Lipopolysaccharide endotoxins. Annu Rev Biochem. 2002;71:635–700. doi:10.1146/annurev.biochem.71.110601.135414
  • Asti C, Ruggieri V, Porzio S, Chiusaroli R, Melillo G, Caselli G. Lipopolysaccharide-induced lung injury in mice. I. concomitant evaluation of inflammatory cells and haemorrhagic lung damage. Pulm Pharmacol Ther. 2000;13:61–69. doi:10.1006/pupt.2000.0231
  • Armstrong L, Medford AR, Uppington KM, et al. Expression of functional toll-like receptor-2 and-4 on alveolar epithelial cells. Am J Respir Cell Mol Biol. 2004;31:241–245. doi:10.1165/rcmb.2004-0078OC
  • McGettrick AF, O’Neill LA. Regulators of TLR4 signaling by endotoxins. Subcell Biochem. 2010;53:153–171. doi:10.1007/978-90-481-9078-2_7
  • Dinarello CA. Proinflammatory cytokines. Chest. 2000;118:503–508. doi:10.1378/chest.118.2.503
  • Hirohashi N, Morrison DC. Low-dose lipopolysaccharide (LPS) pretreatment of mouse macrophages modulates LPS-dependent interleukin-6 production in vitro. Infect Immun. 1996;64:1011–1015. doi:10.1128/iai.64.3.1011-1015.1996
  • Parratt JR. Nitric oxide in sepsis and endotoxaemia. J Antimicrob Chemother. 1998;41:31–39. doi:10.1093/jac/41.suppl_1.31
  • Hendrickson CM, Matthay MA. Viral pathogens and acute lung injury: investigations inspired by the SARS epidemic and the 2009 H1N1 influenza pandemic. Semin Respir Crit Care Med. 2013;34:475–486. doi:10.1055/s-0033-1351122
  • Hui DS, Azhar EI, Madani TA, et al. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health—The latest 2019 novel coronavirus outbreak in Wuhan, China. Int J Infect Dis. 2020;91:264–266. doi:10.1016/j.ijid.2020.01.009
  • Li X, Ma X. Acute respiratory failure in COVID-19: is it “typical” ARDS? Crit Care. 2020;24:198. doi:10.1186/s13054-020-02911-9
  • Cai A, McClafferty B, Benson J, et al. COVID-19: catastrophic cause of acute lung injury. South Dakota Med. 2020;73:252–260.
  • Shapiro SD. The macrophage in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999;160:S29–S32. doi:10.1164/ajrccm.160.supplement_1.9
  • Chakraborty A, Royce SG. Use of biologics in the treatment of asthma, COPD, ACOS, and idiopathic pulmonary fibrosis. In: Dua K, Hansbro PM, Wadhwa R, Haghi M, Pont LG, Williams KA, editors. Targeting Chronic Inflammatory Lung Diseases Using Advanced Drug Delivery Systems. Academic Press; 2020:97–115.
  • Vernooy JHJ, Dentener MA, van Suylen RJ, Buurman WA, Wouters EFM. Long-term intratracheal lipopolysaccharide exposure in mice results in chronic lung inflammation and persistent pathology. Am J Respir Cell Mol Biol. 2002;26:152–159. doi:10.1165/ajrcmb.26.1.4652
  • George CL, Jin H, Wohlford-Lenane CL, et al. Endotoxin responsiveness and subchronic grain dust-induced airway disease. Am J Physiol Lung Cell Mol Physiol. 2001;280:L203–L13. doi:10.1152/ajplung.2001.280.2.L203
  • Kaneko Y, Takashima K, Suzuki N, Yamana K. Effects of theophylline on chronic inflammatory lung injury induced by LPS exposure in guinea pigs. Allergol Int. 2007;56:445–456. doi:10.2332/allergolint.O-07-490
  • Stolk J, Rudolphus A, Davies P, et al. Induction of emphysema and bronchial mucus cell hyperplasia by intratracheal instillation of lipopolysaccharide in the hamster. J Pathol. 1992;167:349–356. doi:10.1002/path.1711670314
  • Vogelzang PF, van der Gulden JW, Folgering H, et al. Endotoxin exposure as a major determinant of lung function decline in pig farmers. Am J Respir Crit Care Med. 1998;157:15–18. doi:10.1164/ajrccm.157.1.9703087
  • Khedoe PPSJ, Wong MC, Wagenaar GTM, et al. The effect of PPE-induced emphysema and chronic LPS-induced pulmonary inflammation on therosclerosis development in APOE*3-LEIDEN mice. PLoS One. 2013;8:e80196–e. doi:10.1371/journal.pone.0080196
  • Taborsky J, Kunt M, Kloucek P, Lachman J, Zeleny V, Kokoska L. Identification of potential sources of thymoquinone and related compounds in Asteraceae, Cupressaceae, Lamiaceae, and Ranunculaceae families. Cent Eur J Chem. 2012;10:1899–1906. doi:10.2478/s11532-012-0114-2
  • Havlik J, Kokoska L, Vasickova S, Valterova I. Chemical composition of essential oil from the seeds of Nigella arvensis L. and assessment of its actimicrobial activity. Flavour Fragr J. 2006;21:713–717. doi:10.1002/ffj.1713
  • Goyal SN, Prajapati CP, Gore PR, et al. Therapeutic potential and pharmaceutical development of thymoquinone: a multitargeted molecule of natural origin. Front Pharmacol. 2017;8:656. doi:10.3389/fphar.2017.00656
  • Younus H. Molecular and Therapeutic Actions of Thymoquinone: Actions of Thymoquinone. 1st ed. Singapore: Springer; 2018.
  • Nemmar A, Al-Salam S, Zia S, et al. Contrasting actions of diesel exhaust particles on the pulmonary and cardiovascular systems and the effects of thymoquinone. Br J Pharmacol. 2011;164:1871–1882. doi:10.1111/j.1476-5381.2011.01442.x
  • Al-Gabri N, Ali A-M, Al-Attar E-S, Hamed M. Pathological study on the role of thymoquinone in experimentally induced acute lung injury in rats. Zagazig Vet J. 2017;45:228–237. doi:10.21608/ZVJZ.2017.7948
  • Al-Gabri NA, Qaid MM, El-shaer NH, Ali MH, Abudabos AM. Thymoquinone ameliorates pulmonary vascular damage induced by Escherichia coli–derived lipopolysaccharide via cytokine downregulation in rats. Environ Sci Pollut Res Int. 2019;26:18465–18469. doi:10.1007/s11356-019-05229-4
  • Pourgholamhossein F, Sharififar F, Rasooli R, et al. Thymoquinone effectively alleviates lung fibrosis induced by paraquat herbicide through down-regulation of pro-fibrotic genes and inhibition of oxidative stress. Environ Toxicol Pharmacol. 2016;45:340–355. doi:10.1016/j.etap.2016.06.019
  • Barnawi J, Tran HB, Roscioli E, et al. Pro-phagocytic effects of thymoquinone on cigarette smoke-exposed macrophages occur by modulation of the sphingosine-1-phosphate signalling system. COPD. 2016;13:653–661. doi:10.3109/15412555.2016.1153614
  • Keyhanmanesh R, Boskabady MH, Khamneh S, Doostar Y. Effect of thymoquinone on the lung pathology and cytokine levels of ovalbumin-sensitized guinea pigs. Pharmacol Rep. 2010;62:910–916. doi:10.1016/s1734-1140(10)70351-0
  • Suddek GM, Ashry NA, Gameil NM. Thymoquinone attenuates cyclophosphamide-induced pulmonary injury in rats. Inflammopharmacology. 2013;21:427–435. doi:10.1007/s10787-012-0160-6
  • El Gazzar M, El Mezayen R, Marecki JC, Nicolls MR, Canastar A, Dreskin SC. Anti-inflammatory effect of thymoquinone in a mouse model of allergic lung inflammation. Int Immunopharmacol. 2006;6:1135–1142. doi:10.1016/j.intimp.2006.02.004
  • Ali MY, Akter Z, Mei Z, Zheng M, Tania M, Khan MA. Thymoquinone in autoimmune diseases: therapeutic potential and molecular mechanisms. Biomed Pharmacother. 2021;134:111157. doi:10.1016/j.biopha.2020.111157
  • El Gazzar MA, El Mezayen R, Nicolls MR, Dreskin SC. Thymoquinone attenuates proinflammatory responses in lipopolysaccharide-activated mast cells by modulating NF-kappaB nuclear transactivation. Biochim Biophys Acta. 2007;1770:556–564. doi:10.1016/j.bbagen.2007.01.002
  • Ng WK, Saiful Yazan L, Yap LH, Wan Nor Hafiza WA, How CW, Abdullah R. Thymoquinone-loaded nanostructured lipid carrier exhibited cytotoxicity towards breast cancer cell lines (MDA-MB-231 and MCF-7) and cervical cancer cell lines (HeLa and SiHa). Biomed Res Int. 2015;2015:263131. doi:10.1155/2015/263131
  • Cingi C, Eskiizmir G, Burukoğlu D, Erdoğmuş N, Ural A, Ünlü H. The histopathological effect of thymoquinone on experimentally induced rhinosinusitis in rats. Am J Rhinol Allergy. 2011;25:e268–e272. doi:10.2500/ajra.2011.25.3703
  • Kanter M. Effects of Nigella sativa seed extract on ameliorating lung tissue damage in rats after experimental pulmonary aspirations. Acta Histochem. 2009;111:393–403. doi:10.1016/j.acthis.2008.10.008
  • Erdurmus M, Yagci R, Yilmaz B, et al. Inhibitory effects of topical thymoquinone on corneal neovascularization. Cornea. 2007;26:715–719. doi:10.1097/ICO.0b013e31804f5a45
  • Sezen ŞC, Kucuk A, Özer A, et al. Assessment of the effects of levosimendan and thymoquinone on lung injury after myocardial ischemia reperfusion in rats. Drug Des Devel Ther. 2018;12:1347–1352. doi:10.2147/DDDT.S160092
  • Basavaraj S, Betageri GV. Can formulation and drug delivery reduce attrition during drug discovery and development—review of feasibility, benefits and challenges. Acta Pharmaceutica Sinica B. 2014;4:3–17. doi:10.1016/j.apsb.2013.12.003
  • Pillai K, Akhter J, Morris DL. Super aqueous solubility of albendazole in β-cyclodextrin for parenteral application in cancer therapy. J Cancer. 2017;8:913–923. doi:10.7150/jca.17301
  • Kazan A, Yesil‐Celiktas O, Zhang YS. Fabrication of thymoquinone‐loaded albumin nanoparticles by microfluidic particle synthesis and their effect on planarian regeneration. Macromol Biosci. 2019;19:1900182–1900187. doi:10.1002/mabi.201900182
  • Gavhane YN, Yadav AV. Loss of orally administered drugs in GI tract. Saudi Pharm J. 2012;20:331–344. doi:10.1016/j.jsps.2012.03.005
  • AbuKhader MM, Khan SA. Thymoquinone and nanoparticles: a promising approach for the clinical trials. J Bionanosci. 2017;11:258–265. doi:10.1166/jbns.2017.1447
  • Ulfa SM, Sholikhah S, Utomo EP, editors. Synthesis of thymoquinone derivatives and its activity analysis: in-silico approach. Proceedings of the International Conference on Chemistry, Chemical Process and Engineering (IC3PE); Yogyakarta, Indonesia; AIP Publishing LLC; 2017. doi:10.1063/1.4978175.
  • Seigneuric R, Markey L, Nuyten DSA, et al. From nanotechnology to nanomedicine: applications to cancer research. Curr Mol Med. 2010;10:640–652. doi:10.2174/156652410792630634
  • Ventola CL. The nanomedicine revolution: part 1: emerging concepts. P T. 2012;37:512–525.
  • Badary OA, Hamza MS, Tikamdas R. Thymoquinone: a promising natural compound with potential benefits for COVID-19 prevention and cure. Drug Des Devel Ther. 2021;15:1819–1833. doi:10.2147/DDDT.S308863
  • Rathore C, Rathbone MJ, Chellappan DK, et al. Nanocarriers: more than tour de force for thymoquinone. Expert Opin Drug Deliv. 2020;17:479–494. doi:10.1080/17425247.2020.1730808
  • Feinberg AP, Ohlsson R, Henikoff S. The epigenetic progenitor origin of human cancer. Nat Rev Genet. 2006;7:21–33. doi:10.1038/nrg1748
  • Colnaghi R, Carpenter G, Volker M, O’Driscoll M. The consequences of structural genomic alterations in humans: genomic disorders, genomic instability and cancer. Semin Cell Dev Biol. 2011;22:875–885. doi:10.1016/j.semcdb.2011.07.010
  • Irigaray P, Newby JA, Clapp R, et al. Lifestyle-related factors and environmental agents causing cancer: an overview. Biomed Pharmacother. 2007;61:640–658. doi:10.1016/j.biopha.2007.10.006
  • Ding L, Getz G, Wheeler D, et al. Somatic mutations affect key pathways in lung adenocarcinoma. Nature. 2008;455:1069–1075. doi:10.1038/nature07423
  • Hainaut P, Hernandez T, Robinson A, et al. IARC Database of p53 gene mutations in human tumors and cell lines: updated compilation, revised formats and new visualisation tools. Nucleic Acids Res. 1998;26:205–213. doi:10.1093/nar/26.1.205
  • Gali-Muhtasib H, Diab-Assaf M, Boltze C, et al. Thymoquinone extracted from black seed triggers apoptotic cell death in human colorectal cancer cells via a p53-dependent mechanism. Int J Oncol. 2004;25:857–866. doi:10.3892/ijo.25.4.857
  • El-Mahdy MA, Zhu Q, Wang QE, Wani G, Wani AA. Thymoquinone induces apoptosis through activation of caspase-8 and mitochondrial events in p53-null myeloblastic leukemia HL-60 cells. Int J Cancer. 2005;117:409–417. doi:10.1002/ijc.21205
  • Fahmy UA, Ahmed OA, El- Moselhy MA, Asfour HZ, Alhakamy NA. Thymoquinone loaded zein nanoparticles improves the cytotoxicity against breast cancer cells. Int J Pharmacol. 2020;16:554–561. doi:10.3923/ijp.2020.554.561
  • Ganea GM, Fakayode SO, Losso JN, van Nostrum CF, Sabliov CM, Warner IM. Delivery of phytochemical thymoquinone using molecular micelle modified poly (D, L lactide-co-glycolide) (PLGA) nanoparticles. Nanotechnology. 2010;21:285104. doi:10.1088/0957-4484/21/28/285104
  • Odeh F, Ismail SI, Abu-Dahab R, Mahmoud IS, Al Bawab A. Thymoquinone in liposomes: a study of loading efficiency and biological activity towards breast cancer. Drug Deliv. 2012;19:371–377. doi:10.3109/10717544.2012.727500
  • Abu-Dahab R, Odeh F, Ismail SI, Azzam H, Al Bawab A. Preparation, characterization and antiproliferative activity of thymoquinone-beta-cyclodextrin self-assembling nanoparticles. Pharmazie. 2013;68:939–944. doi:10.1691/ph.2013.3033
  • Soni P, Kaur J, Tikoo K. Dual drug-loaded paclitaxel–thymoquinone nanoparticles for effective breast cancer therapy. J Nanopart Res. 2015;17:18. doi:10.1007/s11051-014-2821-4
  • Dehghani H, Hashemi M, Entezari M, Mohsenifar A. The comparison of anticancer activity of thymoquinone and nanothymoquinone on human breast adenocarcinoma. Iran J Pharm Res. 2015;14:539–546. doi:10.1007/s11051-014-2821-4
  • Bhattacharya S, Ahir M, Patra P, et al. PEGylated-thymoquinone-nanoparticle mediated retardation of breast cancer cell migration by deregulation of cytoskeletal actin polymerization through miR-34a. Biomaterials. 2015;51:91–107. doi:10.1016/j.biomaterials.2015.01.007
  • Ahmad R, Kaus NHM, Hamid S. Synthesis and characterization of PLGA-PEG thymoquinone nanoparticles and its cytotoxicity effects in tamoxifen-resistant breast cancer cells. In: Pham PV editor. Cancer Biology and Advances in Treatment. Springer; 2018:65–82. doi:10.1007/5584_2018_302.
  • Rajput S, Puvvada N, Kumar BNP, et al. Overcoming akt induced therapeutic resistance in breast cancer through siRNA and thymoquinone encapsulated multilamellar gold niosomes. Mol Pharm. 2015;12:4214–4225. doi:10.1021/acs.molpharmaceut.5b00692
  • El-Ashmawy NE, Khedr EG, Ebeid EZM, Salem ML, Zidan AA, Mosalam EM. Enhanced anticancer effect and reduced toxicity of doxorubicin in combination with thymoquinone released from poly- N -acetyl glucosamine nanomatrix in mice bearing solid Ehrlish carcinoma. Eur J Pharm Sci. 2017;109:525–532. doi:10.1016/j.ejps.2017.09.012
  • Ong YS, Saiful Yazan L, Ng WK, et al. Thymoquinone loaded in nanostructured lipid carrier showed enhanced anticancer activity in 4T1 tumor-bearing mice. Nanomedicine. 2018;13:1567–1582. doi:10.2217/nnm-2017-0322
  • Anderson B, Ho J, Brackett J, Finkelstein D, Laffel L. Parental involvement in diabetes management tasks: relationships to blood glucose monitoring adherence and metabolic control in young adolescents with insulin-dependent diabetes mellitus. J Pediatr. 1997;130:257–265. doi:10.1016/s0022-3476(97)70352-4
  • Kumar A, Ilavarasan R, Jayachandran T, et al. Anti-diabetic activity of Syzygium cumini and its isolated compound against streptozotocin-induced diabetic rats. J Med Plants Res. 2008;2:246–249. doi:10.5897/JMPR.9000093
  • Gothai S, Ganesan P, Park SY, Fakurazi S, Choi DK, Arulselvan P. Natural phyto-bioactive compounds for the treatment of type 2 diabetes: inflammation as a target. Nutrients. 2016;8:461. doi:10.3390/nu8080461
  • Rani R, Dahiya S, Dhingra D, Dilbaghi N, Kim KH, Kumar S. Improvement of antihyperglycemic activity of nano-thymoquinone in rat model of type-2 diabetes. Chem Biol Interact. 2018;295:119–132. doi:10.1016/j.cbi.2018.02.006
  • Lebda MA, El-Far AH, Noreldin AE, Elewa YHA, Al Jaouni SK, Mousa SA. Protective effects of miswak (Salvadora persica) against experimentally induced gastric ulcers in rats. Oxid Med Cell Longev. 2018;2018:6703296. doi:10.1155/2018/6703296
  • Abdelwahab SI, Sheikh BY, Taha MM, et al. Thymoquinone-loaded nanostructured lipid carriers: preparation, gastroprotection, in vitro toxicity, and pharmacokinetic properties after extravascular administration. Int J Nanomedicine. 2013;8:2163–2172. doi:10.2147/IJN.S44108
  • Fahmy UA, Alaofi AL, Awan ZA, Alqarni HM, Alhakamy NA. Optimization of thymoquinone-loaded coconut oil nanostructured lipid carriers for the management of ethanol-induced ulcer. AAPS PharmSciTech. 2020;21:137. doi:10.1208/s12249-020-01693-1
  • Piñeiro-Carrero VM, Piñeiro EO. Liver. Pediatrics. 2004;113:1097–1106.
  • Singh A, Ahmad I, Akhter S, et al. Nanocarrier based formulation of thymoquinone improves oral delivery: stability assessment, in vitro and in vivo studies. Colloids Surf B Biointerfaces. 2013;102:822–832. doi:10.1016/j.colsurfb.2012.08.038
  • Elmowafy M, Samy A, Raslan MA, et al. Enhancement of bioavailability and pharmacodynamic effects of thymoquinone via nanostructured lipid carrier (NLC) formulation. AAPS PharmSciTech. 2016;17:663–672. doi:10.1208/s12249-015-0391-0
  • Kalam MA, Raish M, Ahmed A, et al. Oral bioavailability enhancement and hepatoprotective effects of thymoquinone by self-nanoemulsifying drug delivery system. Mater Sci Eng C Mater Biol Appl. 2017;76:319–329. doi:10.1016/j.msec.2017.03.088
  • Mohd Sairazi NS, Sirajudeen KNS. Natural products and their bioactive compounds: neuroprotective potentials against neurodegenerative diseases. Evid Based Complement Alternat Med. 2020;2020:6565396. doi:10.1155/2020/6565396
  • Alam S, Khan ZI, Mustafa G, et al. Development and evaluation of thymoquinone-encapsulated chitosan nanoparticles for nose-to-brain targeting: a pharmacoscintigraphic study. Int J Nanomed. 2012;7:5705–5718. doi:10.2147/IJN.S35329
  • Xiao XY, Zhu YX, Bu JY, Li GW, Zhou JH, Zhou SP. Evaluation of neuroprotective effect of thymoquinone nanoformulation in the rodent cerebral ischemia-reperfusion model. Biomed Res Int. 2016;2016:2571060. doi:10.1155/2016/2571060
  • Huang L, Hu J, Huang S, et al. Nanomaterial applications for neurological diseases and central nervous system injury. Prog Neurobiol. 2017;157:29–48. doi:10.1016/j.pneurobio.2017.07.003
  • Ahmad N, Ahmad R, Alam MA, Samim M, Iqbal Z, Ahmad FJ. Quantification and evaluation of thymoquinone loaded mucoadhesive nanoemulsion for treatment of cerebral ischemia. Int J Biol Macromol. 2016;88:320–332. doi:10.1016/j.ijbiomac.2016.03.019
  • Ismail N, Ismail M, Azmi NH, et al. Thymoquinone-rich fraction nanoemulsion (TQRFNE) decreases Aβ40 and Aβ42 levels by modulating APP processing, up-regulating IDE and LRP1, and down-regulating BACE1 and RAGE in response to high fat/cholesterol diet-induced rats. Biomed Pharmacother. 2017;95:780–788. doi:10.1016/j.biopha.2017.08.074
  • Bauer P, Laccone F, Rolfs A, et al. Trinucleotide repeat expansion in SCA17/TBP in white patients with Huntington’s disease-like phenotype. J Med Genet. 2004;41:230–232. doi:10.1136/jmg.2003.015602
  • Ramachandran S, Thangarajan S. A novel therapeutic application of solid lipid nanoparticles encapsulated thymoquinone (TQ-SLNs) on 3-nitroproponic acid induced Huntington’s disease-like symptoms in wistar rats. Chem Biol Interact. 2016;256:25–36. doi:10.1016/j.cbi.2016.05.020
  • Ramachandran S, Thangarajan S. Thymoquinone loaded solid lipid nanoparticles counteracts 3-Nitropropionic acid induced motor impairments and neuroinflammation in rat model of Huntington’s disease. Metab Brain Dis. 2018;33:1459–1470. doi:10.1007/s11011-018-0252-0
  • Kulyar MF, Li R, Mehmood K, Waqas M, Li K, Li J. Potential influence of Nagella sativa (Black cumin) in reinforcing immune system: a hope to decelerate the COVID-19 pandemic. Phytomedicine. 2021;85:153277. doi:10.1016/j.phymed.2020.153277
  • Chakraborty A, Boer JC, Selomulya C, Plebanski M, Royce SG. Insights into endotoxin-mediated lung inflammation and future treatment strategies. Expert Rev Respir Med. 2018;12:941–955. doi:10.1080/17476348.2018.1523009
  • Chakraborty A, Royce SG, Selomulya C, Plebanski M. A novel approach for non-invasive lung imaging and targeting lung immune cells. Int J Mol Sci. 2020;21:1613. doi:10.3390/ijms21051613
  • Ammar E-SM, Gameil NM, Shawky NM, Nader MA. Comparative evaluation of anti-inflammatory properties of thymoquinone and curcumin using an asthmatic murine model. Int Immunopharmacol. 2011;11:2232–2236. doi:10.1016/j.intimp.2011.10.013
  • Paul S, Chakrabarty S, Ghosh S, et al. Targeting cellular microtubule by phytochemical apocynin exhibits autophagy-mediated apoptosis to inhibit lung carcinoma progression and tumorigenesis. Phytomedicine. 2020;67:153152. doi:10.1016/j.phymed.2019.153152
  • Chakraborty A, Royce SG, Plebanski M, Selomulya C. Glycine microparticles loaded with functionalized nanoparticles for pulmonary delivery. Int J Pharm. 2019;570:118654. doi:10.1016/j.ijpharm.2019.118654
  • Darakhshan S, Bidmeshki Pour A, Hosseinzadeh Colagar A, Sisakhtnezhad S. Thymoquinone and its therapeutic potentials. Pharmacol Res. 2015;95–96:138–158. doi:10.1016/j.phrs.2015.03.011
  • Shaterzadeh-Yazdi H, Noorbakhsh M-F, Hayati F, Samarghandian S, Farkhondeh T. Immunomodulatory and anti-inflammatory effects of thymoquinone. Cardiovasc Hematol Disord Drug Targets. 2018;18:52–60. doi:10.2174/1871529X18666180212114816
  • Nihei T, Suzuki H, Aoki A, et al. Development of a novel nanoparticle formulation of thymoquinone with a cold wet-milling system and its pharmacokinetic analysis. Int J Pharmaceut. 2016;511:455–461. doi:10.1016/j.ijpharm.2016.07.038
  • Shaarani S, Hamid S, Mohd kaus N. The Influence of pluronic F68 and F127 nanocarrier on physicochemical properties, in vitro release, and antiproliferative activity of thymoquinone drug. Pharmacognosy Res. 2017;9:12–20. doi:10.4103/0974-8490.199774
  • Khattabi AM, Talib WH, Alqdeimat DA. The effect of polymer length on the in vitro characteristics of a drug loaded and targeted silica nanoparticles. Saudi Pharmaceut J. 2018;26:1022–1026. doi:10.1016/j.jsps.2018.05.010