Can You Take Black Seed Oil With Antibiotics
Introduction
COVID-nineteen Overview
The novel coronavirus that causes COVID-19 was first discovered in 2022 in Wuhan, China. Information technology has since spread globally, resulting in a worldwide pandemic. COVID-19 is an infectious disease that causes severe acute respiratory syndrome, leading to the virus causing information technology to exist formally named SARS-CoV-2. Comorbidities such as chronic diseases and acute organ injuries are strongly correlated with disease severity and mortality among COVID-xix patients,1 though the clinical features of COVID-19 are varied, ranging from asymptomatic states to acute respiratory distress syndrome (ARDS) and multiorgan dysfunction. A fever, cough, a sore pharynx, headaches, fatigue, myalgia, and breathlessness are the almost common clinical features of COVID-nineteen, however.2 By the end of the beginning week, in some patients, the illness may progress to pneumonia, respiratory failure, and death.3 This progression is more often than not associated with an extremely uncontrolled production of pro-inflammatory mediators that leads to ARDS and cytokine storm syndrome.iv Complications thus include acute lung injury, ARDS, shock, and acute kidney injury.
Several clinical trials of possible treatments for COVID-xix are underway, based on those treatments' antiviral, anti-inflammatory, immunomodulatory, antioxidant or similar activities.5,6 There are besides some previously available drugs that have been repurposed for the direction of COVID-19, such as remdesivir, hydroxychloroquine, chloroquine, umifenovir, lopinavir, oseltamivir, and favipiravir, likewise as adjunctive agents, such as zinc, vitamin D, azithromycin, ascorbic acid, nitric oxide, corticosteroids, and interleukin (IL)-vi antagonists. Growing interest is likewise developing in the use of new therapeutic methods, such as specific anti-inflammatory molecules (eg tocilizumab), anti-IL-17, and handling with mesenchymal stromal cells.vii The amplification of anti-2019nCoV-specific T lymphocytes may be some other feasible option for treatment.8 In terms of prevention, several COVID-19 vaccines are also now available.ix
Culling Therapies
Although researchers worldwide have worked exhaustively to discover a solution, every bit yet, no entirely adequate therapy for COVID-nineteen has emerged. Alternative approaches must thus be subject area to comprehensive attending, similar to the strategy used in the initial repurposing of conventional therapeutics. An case of such alternative therapy is found in the awarding of vitamin D, which has been suggested to assistance reduce the effect of the pandemic on maternal and child wellness.10 Other speculative suggestions include the thought that vitamin C could aid with COVID-19-related symptoms,xi or that honey may have a positive impact on COVID-xix recovery.12 Pharmacological intervention using natural products is considered another example of alternative medicine.13
In the by, herbal medicine has played an important function in managing communicable diseases, and a range of herbal medicinal studies on the treatment of a previous SARS coronavirus (SARS-CoV), have provided clinical evidence that herbal medicines have some advantageous furnishings with regard to the handling and prevention of epidemics, with several meaning results.14 In that location is likewise clinical evidence that the use of herbal medicines can have positive consequences in sure COVID-xix treatments.xv,16 One systematic review has shown pregnant impacts on efficacy and improvement of symptoms on combining herbal medicine with Western medicine in the treatment of COVID-xix, suggesting that herbal medicine does have a potential function to play in COVID-19 handling. Further clinical trials are, however, necessary to further ostend the efficacy, and whatsoever adverse effects, of herbal medicine as part of COVID-19 treatment.17
Several edible plants are known to act every bit natural antiviral agents, and these may have the potential to be developed into a COVID-19 nutraceutical. Such a development may offer a supplementary treatment to help people cope with this highly infectious disease and thus protect the global population confronting the current pandemic.eighteen In terms of daily diet, herbal preparations with immunomodulatory actions may offering safety therapy to prevent infection and to help comprise diseases within communities, as well as encouraging faster mail-infection healing.18
Natural Therapeutic Approaches
Some reports take emerged of the beneficial effects of certain traditional herbal medicines with regard to COVID-19. Examples include Ginseng (Panax ginseng), which has a modulatory event on human immune cells;19 ginger (Zingiber officinale), which has anti-apoptotic, anti-inflammatory, anti-tumor activities, anti-hyperglycemic, antioxidant, and analgesic properties;20 garlic (Allium sativum), which stimulates the immune organization;21 and Echinacea extract (Echinacea purpurea (L.) Moench), which has antimicrobial and antioxidant activities.22
Other herbal phyto-constituents have been reported to exist effective in reducing infectious conditions, including triterpene glycosides isolated from Heteromorpha 23 and extracts from Artemisia annua, Lycoris radiata, Pyrrosia lingua and Lindera aggregate,17,24 while natural inhibitors such as the nsP13 helicase and 3CL protease have been identified, forth with myricetin, scutellarein, and phenolic compounds from Isatis indigotica and Torreya nucifera, to exist operative against SARS-CoV enzymes.25–27 Moreover, Cinatl et al reported that glycyrrhizin elicited a significant antiviral activeness against SARS coronavirus,28 while Nigella sativa (black seed) was reported to accept potential for the direction of COVID-19 patients' symptoms.13,29–31
Nigella sativa: An Overview
Nigella sativa (Black seed), from the family Ranunculaceae, accept been found in several ancient sites, including Tutankhamun's tomb. The Persian dr. Avicenna, regarded as the begetter of early modern medicine, described the plant in his Catechism of Medicine equally offering a treatment for shortness of breath,32 which frequently accompanies pathological atmospheric condition such every bit asthma and pneumonia. Volatile oils and alkaloids are more often than not associated with biological activeness, and the volatile oils of these seeds contain nigellone, thymoquinone (TQ), thymohydroquinone, dithymoquinone, thymol, carvacrol, α and β-pinene, d-limonene, d-citronellol, p-cymene, carvacrol, t-anethole, 4-terpineol and longifolene.33,34 Nigella sativa seeds thus offer a natural product with multiple potential pharmacological activities including antidiabetic, anticancer, immunomodulatory, analgesic, antimicrobial, anti-inflammatory, bronchodilator, renal and gastro-protective, and antioxidant backdrop.35,36
Thymoquinone
Thymoquinone (2-Isopropyl-5-methylbenzo-1, four-quinone) is the chief agile ingredient of the volatile oil of black seed (Figure 1). It was first extracted by El–Dakhakhny,37 and amongst the various different active constituents reported so far, TQ remains the major bioactive principle due to its range of therapeutic benefits including antioxidant,38 anti-inflammatory,39 anti-cancer,twoscore antibacterial,41 antifungal action,42 and anticonvulsant activeness.43 Furthermore, a more specific effect of the antiviral activity of TQ and black seed stock-still oil against murine cytomegalovirus infection model has been reported.44,45 TQ may thus offer integral complementary support in conditions of uncertain core basic needs during COVID-xix treatment. However, the question of whether TQ might human activity every bit a distinct therapeutic drug for the control and/or treatment of COVID-xix still remains to exist investigated.
 | Figure 1 Chemical construction of thymoquinone. |
The Aim of the Review
This review aims to focus on the potentially benign roles of TQ against COVID-19 pathophysiology in the context of antioxidant, anti-inflammatory, immunomodulatory, epigenetic modulation, antiviral activity, docking studies on anti-COVID-19 activity, antibacterial and anticoagulant effects for the handling of COVID-xix.
Potential Benign Effects of Thymoquinone in COVID-19
N sativa, due to its wide range of bioactive components such as TQ and nigellimine, could offer a range of benefits for treating COVID-nineteen, such as blocking the introduction of the virus to pneumocytes; providing ionophores to ameliorate zinc intake, thereby improving the host immune response to SARS-CoV-2; and preventing the virus from replicating.29 TQ is the chief bioactive principle in N Sativa, and this has been found to confer a range of therapeutic advantages34 including antioxidant,38 anti-inflammatory,39,46 anticancer,40 antibacterial,41 antifungal,42 anticoagulant,47 anti-sepsis,48 and anticonvulsant activity.43 N Sativa seeds take too demonstrated immunomodulatory furnishings,49,50 while several studies suggest that N Sativa seeds take some antiviral effects.44,51,52 In improver to its immunomodulatory and antioxidant backdrop, however, North Sativa and its agile constituents have besides been noted to provide anti-ischemic furnishings in several organs, including the brain, kidney, center, liver, and intestines.53 Such evidence strongly suggests that North. sativa seeds and their active constituents may have significant therapeutic potential against COVID-19 and its complications13,54 (Figure 2).
 | Figure 2 Multitargeted protective furnishings of thymoquinone against COVID-19 pathogenesis. |
Antioxidant Effect
Reactive oxygen species (ROS) are formed during normal cellular respiration and equally a reaction to xenobiotics.55 They are highly reactive, and thus may harm and change the functions of various prison cell components, such as lipids, proteins, nucleic acids, and carbohydrates.56 Oxidative stress occurs due to imbalance between oxidants and antioxidants,57 and information technology is a crucial factor in pathogenesis of many diseases58 such as diabetes,59 inflammation,60 cardiovascular diseases,61 cancer,62 and advanced age.63 A major factor in the excessive immune response seen in some COVID-19 infections may thus be the overwhelming of the antioxidative defense mechanism and the resulting oxidative damage.55
Antioxidant backdrop require high radical-scavenging capabilities, and this is i of the essential characteristic functions of TQ. TQ works by activating the enzymes that protect cells from cellular damage caused by oxidative stress. Several studies have shown that TQ does this by increasing the expression of mRNA and stimulating various cytoprotective antioxidant enzymes, including catalases, superoxide dismutase, glutathione reductase, and glutathione-S-transferase.64–68 TQ thus offers protection against glucose or methylglyoxal induced loss of superoxide dismutase activity and fragmentation or cross-linking.69
Anti-Inflammatory Consequence
While the rapid spread of COVID-xix is concerning, the inflammatory response of the host is an important determinant of the outcome and severity of whatsoever infection.70 A cytokine storm represents cytokine overproduction, seen in the nearly severe cases of COVID-19, a process which includes T cell depletion, pulmonary disease and impairment to the lungs.71 Granulocytosis can also lead to strong superoxide explosion,72 the formation of reactive oxygen species (ROS)73 and further product of proinflammatory cytokines.74 The background of anti-inflammatory therapy complementing antiviral therapy must thus be understood in gild to manage such symptoms in COVID-19, every bit treatment should aim to command inflammation without affecting the host's ability to respond adaptively to the virus. The nuclear cistron erythroid 2 (NFE2)-related factor 2 (Nrf2) can resist oxidative stress,75 and this is e'er dysregulated in disease states, such as diabetes, liver disease, and inflammatory bowel diseases,76 likewise every bit in astringent crumbling.77 Any such conditions are thus risk factors for COVID-nineteen-induced ARDS.78
Activation of Nrf2 has also been shown to be involved in preserving lung compages in reactions to inflammatory syndrome, as well as having some therapeutic effects in various lung disorders, including respiratory infections and ARDS.79 Furthermore, Nrf2 is responsible for the transcription of certain macrophage-specific genes involved in the tissue repair that grant protection from viral infections,80 equally well as restoring redox homeostasis, which protects against oxidative stress by upregulating thioredoxin reductase, glutathione, peroxiredoxin, and NADPH.81
It has been reported that TQ decreases levels of various proinflammatory mediators, such as IL-1β, IL-half-dozen, TNFα, IFNβ, and PGE66 in rats, as well as preventing pulmonary inflammation and improving the resistance of airways to damage induced past diesel exhaust particles. TQ also decreases blood leukocyte and plasma IL-six levels.82 In a mouse model of allergic asthma, TQ reduced lung eosinophils, increased Th2 cytokines, and decreased fungus-producing goblet cells.46 TQ also inhibits inducible synthase nitric oxide (iNOS) and transforming growth factor-β1 in asthmatic murine experimental models.83–85
The experimental evidence suggests that TQ inhibits cyclooxygenase (COX) and lipoxygenase enzymes, preventing the generation of eicosanoids.86 TQ decreases the synthesis of LTs87 and inhibits prostaglandin and thromboxane synthesis by decreasing COX2 expression, accomplished by upregulating IL-1 receptor-associated kinase ane (IRAK1).88 IRAK1-mediated indicate inhibitors likewise downregulate NF-κB and activator protein ane/AP1 transcriptional activities which are required to actuate the COX-2 expression,88 and TQ further downregulates the expression of many other inflammatory cytokines and signals mediators, including interleukin IL-1, IL-vi, TNFα, and iNOS.88 These mediators can cause alveolar macrophages and neutrophils to create more damage by increasing pulmonary vascular permeability, releasing oxygen radicals and proteolytic enzymes.89 The anti-oxidant activity of TQ can likewise help in minimizing jail cell inflammation, while its ROS generation plays an important office in the synthesis of arachidonic acrid based on the activation and/or expression of the basic upstream signaling molecules poly peptide kinase B and NF-κB.90
Immunomodulatory Outcome
TQ has several major immunomodulatory effects due to the crosslink between inflammatory and immunomodulatory pathways. TQ could thus potentially suppress inflammation-induced immunosuppression based on its negative furnishings on proinflammatory eicosanoid synthesis and mediated gene expression in NF-κB.91 TQ can thus modulate many aspects of cellular and humoral immunity by inhibiting the function and expression of various inflammatory cytokines and their effector molecules.92 TQ modulates cell allowed responses, including dendritic prison cell maturity, NK-cells cytotoxicity, phagocytic involvement, chemotaxis, and the activation of T-cells. It as well tends to have a context-relating event on particular prison cell immune responses: for instance, TQ prevents the maturation of lipopolysaccharide-induced dendritic cells past blunting the expression of IL-ten, IL-12 and TNFα with enhancement of caspase iii/8 and increasing annexin 5 bounden.93 TQ also improves the survival of CD8 antigen-specific T cells and improves the sustained expression of Fifty-selectin, which may accept an important upshot on adoptive T jail cell therapy.94
Epigenetic Modulatory Effect
Diverse epigenetic pathways are involved in COVID-19 infection, and these pathways may thus be therapeutically utilized.95 Possible targets for host immune response include epigenetic enzymes.96,97 The abnormal genetic expression and protein part that narrate COVID-nineteen are acquired by genetic and epigenetic changes, and natural compounds tin can target and regulate genetic expression, directly or indirectly, based on their interference with genetic and epigenetic mechanisms.98–100 TQ is thus a promising molecule because it modulates epigenetic properties such as histone acetylation and deacetylation as well every bit Deoxyribonucleic acid methylation and demethylation.101,102 In addition, TQ plays a role in activating and deactivating noncoding RNA, acting as a potent apoptosis-induced enzyme that causes histone acetylation and deacetylation.103–105
Endogenous miRNA activity has been studied in the field of viral replication for several complex virus mechanisms.106 It has thus been shown that miR34a has an issue on the inactivation of epithelial-mesenchymal transition-transcription factors (EMT-TFs), and epithelial–mesenchymal transition is known to play a crucial office in organ fibrosis and epithelial cell malignancy.107 A promising therapeutic approach against COVID-xix thus stems from the idea of inactivating EMT-TFs using miR34a,108 as a previous written report showed that TQ may deed every bit an enhancer of miR34a activity.109 miR146a is another miR involved in the process of inflammatory cytokine inhibition, which acts via the NF-κB pathway.110 Information technology functions as a negative regulator for NF-κB, and it is a well-recognized transcript gene for the IL-6 gene.111 miR-146a-5p transcription is also regulated by NF-κB,112 and patients with COVID-nineteen take been shown to have higher levels of IL-6 and lower levels of miR-146a-5p than average, suggesting imbalances in the physiological axis of IL-6/miR-146a-5p in the pathogenesis of COVID-19 infections.113 TQ treatment, however, controls miR146a expression and can therefore reduce inflammatory reactions by interfering with NF-kB.114
Antiviral Activity
Several studies support the potential antiviral activity of TQ confronting diverse viral infections, which is mainly attributed to its multiple beneficial effects, such as antioxidant, anti-inflammatory, and immunomodulatory effects in addition to possible direct viral eradication.115,116 The antiviral effect of Nigella sativa oil, including its major active component TQ, was demonstrated in a murine cytomegalovirus (MCMV) model; this showed that Nigella sativa significantly reduced the liver and spleen viral loads, which coincided with enhanced IFN-γ production and increased CD4 (+) T cell response.44 TQ has also been shown to significantly inhibit Epstein-Barr virus (EBV) replication in EBV-infected B cells,117 while Nigella sativa has been shown to exhibit antiviral activity against the hepatitis C virus (HCV), as evidenced by reduced viral load and improved liver role in HCV patients who received Nigella sativa at 450 mg, three times a mean solar day for three successive months.51 This effect is also supported past observations of the selective inhibition of HCV virus replication by alpha-zam, a Nigella sativa seed formulation.118 Nigella sativa has also been suggested to be constructive in controlling human immunodeficiency virus (HIV) infection, with ane study reporting that treatment of HIV patients with Nigella sativa for vi months resulted in sustained sero-reversion with a significant reduction in viral load and CD4 count elevation.52
Nigella sativa extract containing TQ has also, more specifically, been reported to subtract viral replication and loads in cells infected with some coronaviruses.119 Interestingly, one in vitro report demonstrated that TQ showed meaning antiviral activity against a SARSCoV-2 strain isolated from Egyptian patients,120 possibly through blocking the entry of the virus into the cells.121 Overall, the existing studies highlight the immense potential of TQ equally an effective antiviral agent confronting COVID-19, a premise which is highly supported by the molecular docking studies examining TQ'southward effects against various virus and host cell targets, which are discussed in more detail in the post-obit section.
Molecular Docking Studies Related to Anti-COVID-19 Activeness
Molecular docking is a promising in silico method that may be used to screen diverse compounds for their antiviral potential by testing the bounden affinities of the compounds confronting different viral or host cell receptor proteins. The molecular targets of SARS-CoV-2 include various viral proteins involved in viral entry, such as fasten proteins, and replication, such as viral proteases.122 In addition, host jail cell targets, such as angiotensin-converting enzyme two (ACE2) receptor and cell surface heat shock poly peptide (HSPA5), which are involved in viral entry, may also offer potential therapeutic targets.122 Molecular docking studies take already shown that TQ could potentially inhibit COVID-xix by binding to the receptor-bounden domain on the spike poly peptide of SARS-CoV-2, which would hinder virus entry into the host prison cell.123 Additionally, it may demark to the SARS-CoV-2 envelope protein and inhibit its ion channel and pore formation activity.124 Other studies have shown that TQ might display inhibitory action against the SARS CoV2 protease, which would halt viral replication.120,125–127
TQ has as well demonstrated a good affinity confronting ACE2 receptors, which allows information technology to interfere with virus uptake into the host prison cell.121,127 Molecular dynamics simulations take shown that TQ can interfere with the attachment of SARS‐CoV‐ii to host cells by bounden to a jail cell surface, HSPA5, which is recognized by the viral spike protein and upregulated upon viral infection.128,129 These in silico studies signal a multi-targeted potential for TQ against COVID-nineteen, and thus pave the manner for further investigation of such anti-COVID-19 potential through in-vitro and in-vivo studies that may better support translation into clinical practice.
Antibacterial Activity
COVID-19 may also exist associated with serious secondary bacterial infections, such every bit bacterial pneumonia, as well as nosocomial infections resulting from the prolonged hospitalization of critically ill patients, both of which significantly increase morbidity and bloodshed in COVID-19 patients.130 Moreover, the intensive apply of antibiotics in patients suffering from COVID-xix could result in the emergence of multidrug-resistant bacteria, which could further worsen COVID-nineteen adverse outcomes.131 Interestingly, TQ exerts antibacterial activity against several Gram positive and Gram negative leaner, including Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli, which could be used to augment antibiotic effects.41,116,132 Furthermore, TQ has demonstrated pregnant antimicrobial activity against anaerobic bacteria, specifically Clostridium difficile,133 as well as clinical isolates of Mycobacterium tuberculosis,134 aslope antibacterial and resistance modifying activities with regard to methicillin-resistant Staphylococcus aureus (MRSA)135 and Listeria monocytogenes.136
Nigella sativa was also seen to be significantly effective in eradicating Helicobacter pylori in patients with non-ulcer dyspepsia.137 This suggests that TQ could play a meaning role in the prevention and management of secondary bacterial infections in COVID-19 patients in addition to its potential value for modifying bacterial resistance and potentiating antibiotic actions.
Anticoagulation Effect
Thrombotic complications take become a major problem in COVID-xix patients. Preliminary COVID-19 studies have shown that infected patients typically develop thrombocytopenia with higher D-dimer levels, while the rates of developing thrombocytopenia in patients with severe COVID-19 are fifty-fifty higher.70 Viral infections often cause systemic inflammatory responses and interfere with the balance of procoagulants and anticoagulants,138 and in severe or critically sick patients, large quantities of inflammatory mediators, hormones and immunoglobulin are released, leading to claret hypercoagulability. The level of interleukins, especially IL-6, IL-7, IL-2, granulocyte colony-=stimulating factor, monocyte chemoattractant poly peptide-1, macrophage inflammatory proteins one-alpha, and TNFα, has been similarly found to be increased in patients with COVID-nineteen.139
An earlier study plant that coagulation factors VII, VIII, 2, 5, and X were significantly increased in COVID-19 patients.140 TQ, however, interferes with blood clotting past directly decreasing gene Xa activity in the claret coagulation pathway and past downwardly-regulating TNFα, a cytokine that plays a critical part in the link betwixt inflammatory and thrombosis pathways.47
The Effect of Thymoquinone on Comorbidities
The magnitude of COVID-19 infection is increased by a variety of comorbidities. TQ may thus also be helpful in patients infected with COVID-19 where it can relieve some comorbidity.13 Serious COVID-19 complications include ARDS, pneumonia and multi-organ failure, and the risk of all of these is increased in patients with diabetes and cardiovascular diseases.141,142 N. Sativa has been shown to reduce plasma glucose levels and control haemoglobin-A1c,143 while intraperitoneal administration of TQ has been demonstrated to substantially decrease hyperglycemia in streptozotocin-induced diabetes in the rats.144 One study reported that 7% of deaths in COVID-19 patients can be ascribed to circulatory failure in myocarditis, suggesting that cardiovascular disorders play an important role in determining final adverse outcomes.145 TQ can also human action centrally as an antihypertensive agent, besides every bit having a regulatory consequence on platelet aggregation and blood clotting,146,147 and TQ protects the middle from injury induced by isoproterenol in rats.148
It is also notable that autoimmune and auto-inflammatory diseases, peculiarly in children, may impact the severity of COVID-19 infection, with overlapping symptoms leading to pediatric inflammatory multisystem syndrome (PIMS) that includes Kawasaki-similar diseases.149,150 This complex syndrome has been reported every bit "Kawa-COVID-19" considering of the clan with the symptoms of COVID-19 infection.151,152 In patients with Kawa-COVID-nineteen, C-Reactive protein (CRP), IL-half dozen, IL-eight, and TNF-α were all significantly raised,153 suggesting that Nigella sativa could play a beneficial part in controlling incidence of PIMS or Kawa-COVID-nineteen by regulating and modulating immune response and reducing the occurrence of proinflammatory cytokines IL-2, IL-4, IL-v, Two-6, IL-12, and IL-13.154
Dual Benefit of Thymoquinone as Adjunctive Therapy
TQ can exist used in combination with other therapeutic agents that may be usefully repurposed for the handling of COVID-nineteen, every bit well as alongside other supportive treatments. Given the multiple beneficial effects of TQ and its favorable safe profile,155 the offshoot use of TQ with conventional therapeutic agents would have the dual benefit of attenuating drug-induced toxicity and improving therapeutic effectiveness, which could in turn result in reducing the required effective dosage of concomitantly used drugs, thus further minimizing whatever adverse effects. The potential cardioprotective,156 neuroprotective,157 hepatoprotective,158 nephroprotective,159 and gastroprotective160 effects of TQ may thus exist employed in counteracting a range of drug-associated toxicities;161 currently, various supportive treatments such as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) render COVID-19 patients at increased risk of liver and kidney toxicity.162,163
TQ has been shown to counteract acetaminophen-induced hepatotoxicity164,165 too every bit NSAIDs-associated nephrotoxicity and gastrointestinal side effects.166 TQ can also deed synergistically with corticosteroids to protect the lungs by mitigating the inflammatory response and resulting cytokine tempest; this would allow the employ of lower steroid doses, thus reducing the gamble of potential adverse effects.167,168 TQ has further demonstrated significant protective effects confronting the renal toxicity associated with antibiotics, such as vancomycin used in COVID-xix patients with secondary bacterial respiratory infections.169 TQ could also potentially counteract the toxic effects of various repurposed drugs,170,171 such as the cardiotoxicity adventure associated with chloroquine and azithromycin161,172,173 and the potential liver and kidney toxicities associated with antivirals such as remdesivir and lopinavir.155,161,170 TQ tin also exert gastroprotective effects160 against gastric ulceration, which is associated with the IL-6 adversary, tocilizumab,174 in add-on to potentiating its anti-inflammatory effect.175
Clinical Applicability of Thymoquinone
The loftier hydrophobic and lipophilic characters of TQ lead to poor solubility, low bioavailability, and difficulty in formulation.176 The diverse pharmacokinetics of TQ have been reported in item,177–179 and TQ has poor oral bioavailability based on its depression aqueous solubility and dissolution rate.180 Moreover, TQ shows rapid polyexponential pass up following intravenous dosing,178 as well as binding with bovine serum albumin and blastoff-i acrid glycoprotein.181–183 This poor solubility and limited bioavailability are the two master problems for developing TQ for clinical use, and several chemical derivatives and novel nanoformulations accept thus been adult to improve the pharmacokinetic behaviors of TQ to increase bioavailability.184,185 TQ has, for example, been successfully encapsulated into nanolipid carriers.186–188
TQ in different dose ranges shows beneficial effects with negligible toxicity in creature models of different diseases.156–159,189–195 TQ is a well-tolerated drug in rodents, and numerous studies have been done to make up one's mind the toxicological backdrop of TQ in vitro and in vivo.196–198 Even mice treated with 0.03% TQ in their drinking water for three months showed no signs of toxicity.196 Moreover, TQ has demonstrated a high condom profile in rats based on high doses using oral and intraperitoneal administration.199,200
TQ compounds are currently used in clinical trials for the treatment of various types of cancer and other diseases.201,202 In a Stage I safety and clinical activity written report of TQ in patients with avant-garde refractory cancerous disease, TQ was well tolerated at doses ranging from 75 mg/mean solar day to 2600 mg/day, with neither toxicities nor therapeutic responses reported.203 This absence of side effects in humans is in agreement with the extremely depression toxicity of oral TQ administration in experimental animals.196
Prospects and Limitations
Despite the numerous molecular docking studies on potential anti-COVID-19 activity of TQ, experimental studies on the furnishings of TQ confronting COVID-xix and its associated complications remain limited. The multi-targeted beneficial effects of TQ and its favorable rubber profile practise, nonetheless, appear to warrant in-vivo investigations and clinical trials on its anti-COVID-nineteen potential to support the translation into clinical do to treat COVID-19 patients either alone or in combination with other potential therapies. TQ could likewise provide the additional benefits of ameliorating comorbidities and attenuating certain drug-induced adverse effects, too as improving the therapeutic effectiveness of another therapies. Novel formulations of TQ nanoparticles may, however, be required to overcome the poor bioavailability and the pharmacokinetic limitation of this compound in terms of clinical use.
Conclusion
This commodity examined the concept that certain natural compounds may target the molecular mechanisms of COVID-19, as well as potentially assisting with overcoming the diverse health complications associated with the repeated utilise or withdrawal of conventional therapeutics. TQ, the master active ingredient of Blackness seed oil, is an like shooting fish in a barrel, cost-effective natural source of anti-inflammatory, antioxidant, immune stimulant, antibacterial, anticoagulant, and antiviral properties. TQ use may thus be expected to improve COVID-nineteen comorbidities and to protect against sure antiviral drug-induced side effects and toxicities. TQ appears to be a promising therapeutic option for managing COVID-xix and its complications, and clinical trials in COVID-19 patients to examine the beneficial furnishings of TQ are thus highly recommended.
Abbreviations
ACE, angiotensin-converting enzyme; ARDS, acute respiratory distress syndrome; COVID-nineteen, coronavirus disease-2019; COX, cyclooxygenase; EBV, Epstein-Barr virus; EMT-TFs, epithelial–mesenchymal transition–transcription factors; HCV, hepatitis C virus; HIV, homo immunodeficiency virus; HSP, heat shock protein; IL, interleukin; IRAK1, interleukin-1 receptor-associated kinase one; MCMV, murine cytomegalovirus; Nrf2, the nuclear cistron erythroid two (NFE2)-related cistron 2; ROS, reactive oxygen species; SARS-CoV-2, severe acute respiratory syndrome; TQ, thymoquinone.
Disclosure
The authors report no conflicts of interest in this work.
References
1. Wang X, Fang X, Cai Z, et al. Comorbid chronic diseases and astute organ injuries are strongly correlated with illness severity and bloodshed among COVID-nineteen patients: a systemic review and meta-assay. Inquiry (Wash D C). 2020;2020:2402961. doi:10.34133/2020/2402961
ii. Wu D, Wu T, Liu Q, Yang Z. The SARS-CoV-ii outbreak: what we know. Int J Infect Dis. 2020;94:44–48. doi:10.1016/j.ijid.2020.03.004
3. Liu K, Chen Y, Lin R, Han Yard. Clinical features of COVID-19 in elderly patients: a comparison with young and center-aged patients. J Infect. 2020;80(half-dozen):e14–e18. doi:10.1016/j.jinf.2020.03.005
4. Felsenstein Southward, Herbert JA, McNamara PS, Hedrich CM. COVID-19: immunology and treatment options. Clin Immunol. 2020;215:108448. doi:x.1016/j.clim.2020.108448
5. Zhang T, He Y, Xu West, Ma A, Yang Y, Xu KF. Clinical trials for the treatment of Coronavirus affliction 2022 (COVID-xix): a rapid response to urgent need. Sci China Life Sci. 2020;63(v):774–776. doi:x.1007/s11427-020-1660-two
6. Manhas S, Anjali A, Mansoor S, et al. Covid-xix pandemic and current medical interventions. Curvation Med Res. 2020;51(6):473–481. doi:10.1016/j.arcmed.2020.05.007
7. Horie Due south, Gonzalez HE, Laffey JG, Masterson CH. Cell therapy in astute respiratory distress syndrome. J Thorac Dis. 2018;10(9):5607–5620. doi:10.21037/jtd.2018.08.28
8. Zumla A, Hui DS, Azhar EI, Memish ZA, Maeurer Thou. Reducing mortality from 2019-nCoV: host-directed therapies should exist an selection. Lancet (London, England). 2020;395(10224):e35–e36. doi:x.1016/s0140-6736(20)30305-6
9. Forni Chiliad, Mantovani A, Forni Thousand, et al. COVID-nineteen vaccines: where we stand and challenges ahead. Prison cell Death Differ. 2021;28(2):626–639. doi:10.1038/s41418-020-00720-nine
10. Ahmed N, Araf Y, Ullah M. Potential roles of vitamin D in the treatment of COVID-19 patient and improving maternal and child health during pandemic. J Adv Biotechnol Exp Ther. 2021;4:133. doi:10.5455/jabet.2021.d114
11. Farjana M, Moni A, Sohag AAM, et al. Repositioning vitamin C as a promising selection to convalesce complications associated with COVID-19. Infect Chemother. 2020;52(4):461–477. doi:10.3947/ic.2020.52.4.461
12. Hossain KS, Hossain MG, Moni A, et al. Prospects of honey in fighting against COVID-19: pharmacological insights and therapeutic promises. Heliyon. 2020;6(12):e05798. doi:ten.1016/j.heliyon.2020.e05798
13. Islam MN, Hossain KS, Sarker PP, et al. Revisiting pharmacological potentials of Nigella sativa seed: a promising option for COVID-19 prevention and cure. Phytother Res. 2021. doi:ten.1002/ptr.6895
14. Yang Y, Islam MS, Wang J, Li Y, Chen X. Traditional Chinese Medicine in the treatment of patients infected with 2019-new coronavirus (SARS-CoV-2): a review and perspective. Int J Biol Sci. 2020;16(10):1708–1717. doi:10.7150/ijbs.45538
15. Chan KW, Wong VT, Tang SCW. COVID-19: an update on the epidemiological, clinical, preventive and therapeutic evidence and guidelines of integrative Chinese-Western Medicine for the Management of 2022 Novel Coronavirus Disease. Am J Chin Med. 2020;48(iii):737–762. doi:10.1142/s0192415x20500378
16. Khanna G, Kohli SK, Kaur R, et al. Herbal immune-boosters: substantial warriors of pandemic Covid-nineteen battle. Phytomedicine. 2020:153361. doi:10.1016/j.phymed.2020.153361
17. Ang L, Song Eastward, Lee HW, Lee MS. Herbal medicine for the treatment of Coronavirus Disease 2022 (COVID-19): a Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Clin Med. 2020;9(5):1583. doi:10.3390/jcm9051583
18. Patel B, Sharma Due south, Nair N, Majeed J, Goyal RK, Dhobi G. Therapeutic opportunities of edible antiviral plants for COVID-xix. Mol Jail cell Biochem. 2021. doi:ten.1007/s11010-021-04084-7
19. Kang S, Min H. Ginseng, the 'Immunity Boost': the effects of panax ginseng on immune organisation. J Ginseng Res. 2012;36(4):354–368. doi:10.5142/jgr.2012.36.4.354
20. Shahrajabian MH, Lord's day W, Cheng Q. The power of natural Chinese medicine, ginger and ginseng root in an organic life. Heart Due east J Sci Res. 2019;27:64–71.
21. Daliri EB-Thou, Kim S-H, Park B-J, et al. Effects of different processing methods on the antioxidant and immune stimulating abilities of garlic. Food Sci Nutr. 2019;7(four):1222–1229. doi:ten.1002/fsn3.942
22. Sharifi-Rad M, Mnayer D, Morais-Braga MFB, et al. Echinacea plants equally antioxidant and antibacterial agents: from traditional medicine to biotechnological applications. Phytother Res. 2018;32(9):1653–1663. doi:10.1002/ptr.6101
23. Cheng PW, Ng LT, Chiang LC, Lin CC. Antiviral furnishings of saikosaponins on human coronavirus 229E in vitro. Clin Exp Pharmacol Physiol. 2006;33(vii):612–616. doi:10.1111/j.1440-1681.2006.04415.x
24. Li SY, Chen C, Zhang HQ, et al. Identification of natural compounds with antiviral activities against SARS-associated coronavirus. Antiviral Res. 2005;67(ane):xviii–23. doi:10.1016/j.antiviral.2005.02.007
25. Lin C-W, Tsai F-J, Tsai C-H, et al. Anti-SARS coronavirus 3C-like protease effects of Isatis indigotica root and institute-derived phenolic compounds. Antiviral Res. 2005;68(1):36–42. doi:ten.1016/j.antiviral.2005.07.002
26. Ryu YB, Jeong HJ, Kim JH, et al. Biflavonoids from Torreya nucifera displaying SARS-CoV 3CL(pro) inhibition. Bioorg Med Chem. 2010;xviii(22):7940–7947. doi:10.1016/j.bmc.2010.09.035
27. Yu MS, Lee J, Lee JM, et al. Identification of myricetin and scutellarein equally novel chemical inhibitors of the SARS coronavirus helicase, nsP13. Bioorg Med Chem Lett. 2012;22(12):4049–4054. doi:10.1016/j.bmcl.2012.04.081
28. Cinatl J, Morgenstern B, Bauer G, Chandra P, Rabenau H, Doerr HW. Glycyrrhizin, an agile component of liquorice roots, and replication of SARS-associated coronavirus. Lancet (London, England). 2003;361:2045–2046. doi:10.1016/S0140-6736(03)13615-10
29. Rahman MT. Potential benefits of combination of Nigella sativa and Zn supplements to treat COVID-xix. J Herb Med. 2020;23:100382. doi:10.1016/j.hermed.2020.100382
xxx. Maideen NMP. Prophetic medicine-Nigella Sativa (Black cumin seeds)-potential herb for COVID-19? J Pharmacopunct. 2020;23(two):62–70. doi:10.3831/kpi.2020.23.010
31. Kulyar MF-EA, Li R, Mehmood Chiliad, Waqas M, Li Chiliad, Li J. Potential influence of Nigella sativa (Black cumin) in reinforcing immune system: a hope to decelerate the COVID-19 pandemic. Phytomedicine. 2020;153277. doi:ten.1016/j.phymed.2020.153277
32. Bakhtiar Fifty, Gruner OC, Shah MH, Crook JR, Nasr SH. Avicenna. In: The Canon of Medicine (Al-Qanunfi'fifty-Tibb); 1999: Bully Books of the Islamic World, Chicago, IL : KAZI Publications 1999-2014.
33. Ghahramanloo KH, Kamalidehghan B, Akbari Javar H, Teguh Widodo R, Majidzadeh K, Noordin MI. Comparative analysis of essential oil limerick of Iranian and Indian Nigella sativa L. extracted using supercritical fluid extraction and solvent extraction. Drug Des Devel Ther. 2017;11:2221–2226. doi:10.2147/dddt.s87251
34. Haseena S, Aithal M, Das K, Saheb Due south. Phytochemical analysis of Nigella sativa and its consequence on reproductive system. J Pharm Sci Res. 2015;vii:514–517.
35. Tavakkoli A, Ahmadi A, Razavi BM, Hosseinzadeh H. Black seed (Nigella Sativa) and its constituent thymoquinone as an antitoxin or a protective amanuensis confronting natural or chemical toxicities. Iran J Pharm Res. 2017;16(Suppl):ii–23.
36. Ahmad A, Husain A, Mujeeb Thou, et al. A review on therapeutic potential of Nigella sativa: a phenomenon herb. Asian Pac J Trop Biomed. 2013;three(5):337–352. doi:10.1016/S2221-1691(xiii)60075-1
37. El–Dakhakhny Thousand. Studies on the Chemical Constitution of Egyptian Nigella Sativa L. Seeds. II1) the essential oil. Planta Med. 1963;11(04):465–470. doi:ten.1055/due south-0028-1100266
38. Hosseinzadeh H, Taiari S, Nassiri-Asl M. Event of thymoquinone, a constituent of Nigella sativa L., on ischemia–reperfusion in rat skeletal muscle. Naunyn-Schmiedeberg Arch Pharmcol. 2012;385(v):503–508. doi:10.1007/s00210-012-0726-ii
39. El Gazzar Thou, 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;vi(7):1135–1142. doi:10.1016/j.intimp.2006.02.004
40. Gali-Muhtasib H, Ocker M, Kuester D, et al. Thymoquinone reduces mouse colon tumor jail cell invasion and inhibits tumor growth in murine colon cancer models. J Prison cell Mol Med. 2008;12(1):330–342. doi:10.1111/j.1582-4934.2007.00095.x
41. Halawani E. Antibacterial activeness of thymoquinone and thymohydroquinone of Nigella sativa L. and their interaction with some antibiotics. Adv Biol Res. 2009;3:148–152.
42. Abdel Azeiz A, Darweesh M, Amin A. American science efficacy of thymoquinone against vaginal candidiasis in prednisolone-induced immunosuppressed mice. J Am Sci. 2013;9:155.
43. Hosseinzadeh H, Parvardeh S. Anticonvulsant effects of thymoquinone, the major constituent of Nigella sativa seeds, in mice. Phytomedicine. 2004;11(1):56–64. doi:10.1078/0944-7113-00376
44. Salem ML, Hossain MS. Protective result of black seed oil from Nigella sativa against murine cytomegalovirus infection. Int J Immunopharmacol. 2000;22(nine):729–740. doi:10.1016/s0192-0561(00)00036-nine
45. Mahboubi M. Natural therapeutic approach of Nigella sativa (Blackness seed) fixed oil in direction of Sinusitis. Integr Med Res. 2018;7(1):27–32. doi:10.1016/j.imr.2018.01.005
46. El Gazzar M, El Mezayen R, Nicolls MR, Marecki JC, Dreskin SC. Downregulation of leukotriene biosynthesis by thymoquinone attenuates airway inflammation in a mouse model of allergic asthma. Biochim Biophys Acta. 2006;1760(7):1088–1095. doi:10.1016/j.bbagen.2006.03.006
47. Muralidharan-Chari 5, Kim J, Abuawad A, Naeem Thou, Cui H, Mousa SA. Thymoquinone modulates claret coagulation in vitro via its effects on inflammatory and coagulation pathways. Int J Mol Sci. 2016;17(iv):474. doi:10.3390/ijms17040474
48. Alkharfy KM, Ahmad A, Jan BL, Raish 1000. Thymoquinone reduces mortality and suppresses early acute inflammatory markers of sepsis in a mouse model. Biomed Pharmacother. 2018;98:801–805. doi:ten.1016/j.biopha.2018.01.028
49. Haq A, Abdullatif M, Lobo PI, Khabar KS, Sheth KV, al-Sedairy ST. Nigella sativa: consequence on human lymphocytes and polymorphonuclear leukocyte phagocytic activeness. Immunopharmacology. 1995;xxx(2):147–155. doi:10.1016/0162-3109(95)00016-m
50. Haq A, Lobo PI, Al-Tufail M, Rama NR, Al-Sedairy ST. Immunomodulatory effect of Nigella sativa proteins fractionated by ion exchange chromatography. Int J Immunopharmacol. 1999;21(4):283–295. doi:x.1016/s0192-0561(99)00010-7
51. Barakat EM, El Wakeel LM, Hagag RS. Effects of Nigella sativa on outcome of hepatitis C in Egypt. Globe J Gastroenterol. 2013;xix(xvi):2529–2536. doi:10.3748/wjg.v19.i16.2529
52. Onifade AA, Jewell AP, Adedeji WA. Nigella sativa concoction induced sustained seroreversion in HIV patient. Afr J Tradit Complement Altern Med. 2013;ten(5):332–335.
53. Oskouei Z, Akaberi M, Hosseinzadeh H. A glance at black cumin (Nigella sativa) and its agile constituent, thymoquinone, in ischemia: a review. Iran J Basic Med Sci. 2018;21(12):1200–1209. doi:10.22038/ijbms.2018.31703.7630
54. Ahmad A, Rehman M, Ahmad P, Alkharfy Chiliad. Covid-19 and thymoquinone: connecting the dots. Phytother Res. 2020;34(11):2786–2789. doi:ten.1002/ptr.6793
55. Ray PD, Huang BW, Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Betoken. 2012;24(5):981–990. doi:10.1016/j.cellsig.2012.01.008
56. Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O. Oxidative stress and antioxidant defence. World Allergy Organ J. 2012;five(i):9–xix. doi:10.1097/WOX.0b013e3182439613
57. Betteridge DJ. What is oxidative stress? Metabolism. 2000;49(2Suppl 1):iii–viii. doi:10.1016/s0026-0495(00)80077-3
58. Hagen TM. Oxidative stress, redox imbalance, and the aging process. Antioxid Redox Bespeak. 2003;5(v):503–506. doi:10.1089/152308603770310149
59. Wright E
threescore. Di Virgilio F. New pathways for reactive oxygen species generation in inflammation and potential novel pharmacological targets. Curr Pharm Des. 2004;10(14):1647–1652. doi:10.2174/1381612043384727
61. Kattoor AJ, Pothineni NVK, Palagiri D, Mehta JL. Oxidative stress in atherosclerosis. Curr Atheroscler Rep. 2017;nineteen(eleven):42. doi:10.1007/s11883-017-0678-6
62. Waris G, Ahsan H. Reactive oxygen species: office in the development of cancer and various chronic conditions. J Carcinog. 2006;5:14. doi:10.1186/1477-3163-5-14
63. Romano Advertizing, Serviddio Thou, de Matthaeis A, Bellanti F, Vendemiale G. Oxidative stress and aging. J Nephrol. 2010;23(Suppl fifteen):S29–36.
64. Mahmoud YK, Abdelrazek HMA. Cancer: thymoquinone antioxidant/pro-oxidant event as potential anticancer remedy. Biomed Pharmacother. 2019;115:108783. doi:10.1016/j.biopha.2019.108783
65. Leisegang Grand, Almaghrawi W, Henkel R. The effect of Nigella sativa oil and metformin on male person seminal parameters and testosterone in Wistar rats exposed to an obesogenic nutrition. Biomed Pharmacother. 2021;133:111085. doi:10.1016/j.biopha.2020.111085
66. Umar S, Zargan J, Umar K, Ahmad S, Katiyar CK, Khan HA. Modulation of the oxidative stress and inflammatory cytokine response by thymoquinone in the collagen induced arthritis in Wistar rats. Chem Biol Collaborate. 2012;197(1):40–46. doi:10.1016/j.cbi.2012.03.003
67. Kassab RB, El-Hennamy RE. The role of thymoquinone every bit a potent antioxidant in ameliorating the neurotoxic result of sodium arsenate in female rat. Arab republic of egypt J Basic Appl Sci. 2017;4(3):160–167. doi:x.1016/j.ejbas.2017.07.002
68. Badary OA, Taha RA, Gamal el-Din AM, Abdel-Wahab MH. Thymoquinone is a potent superoxide anion scavenger. Drug Chem Toxicol. 2003;26(2):87–98. doi:10.1081/dct-120020404
69. Khan MA, Anwar S, Aljarbou AN, et al. Protective result of thymoquinone on glucose or methylglyoxal-induced glycation of superoxide dismutase. Int J Biol Macromol. 2014;65:16–20. doi:10.1016/j.ijbiomac.2014.01.001
70. Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of Coronavirus Affliction 2022 in China. N Engl J Med. 2020;382(18):1708–1720. doi:x.1056/NEJMoa2002032
71. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2022 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. doi:10.1016/S0140-6736(20)30183-five
72. Galani IE, Andreakos East. Neutrophils in viral infections: current concepts and caveats. J Leukoc Biol. 2015;98(4):557–564. doi:10.1189/jlb.4VMR1114-555R
73. Sies H, Jones DP. Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat Rev Mol Cell Biol. 2020;21(7):363–383. doi:10.1038/s41580-020-0230-3
74. DeDiego ML, Nieto-Torres JL, Regla-Nava JA, et al. Inhibition of NF-κB-mediated inflammation in severe acute respiratory syndrome coronavirus-infected mice increases survival. J Virol. 2014;88(2):913–924. doi:10.1128/jvi.02576-13
75. Kensler TW, Wakabayashi Due north, Biswal Southward. Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmacol Toxicol. 2007;47:89–116. doi:10.1146/annurev.pharmtox.46.120604.141046
76. Rabbani PS, Soares MA, Hameedi SG, et al. Dysregulation of Nrf2/Keap1 redox pathway in diabetes affects multipotency of stromal cells. Diabetes. 2019;68(1):141–155. doi:10.2337/db18-0232
77. Schmidlin CJ, Dodson MB, Madhavan L, Zhang DD. Redox regulation past NRF2 in aging and disease. Free Radic Biol Med. 2019;134:702–707. doi:10.1016/j.freeradbiomed.2019.01.016
78. Wu C, Chen Ten, Cai Y, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with Coronavirus Disease 2022 pneumonia in Wuhan, People's republic of china. JAMA Intern Med. 2020;180(vii):934–943. doi:10.1001/jamainternmed.2020.0994
79. Liu Q, Gao Y, Ci X. Role of Nrf2 and its activators in respiratory diseases. Oxid Med Prison cell Longev. 2019;2019:7090534. doi:10.1155/2019/7090534
80. Saddawi-Konefka R, Seelige R, Gross ET, et al. Nrf2 induces IL-17D to mediate tumor and virus surveillance. Cell Rep. 2016;16(9):2348–2358. doi:ten.1016/j.celrep.2016.07.075
81. Brüne B, Dehne N, Grossmann N, et al. Redox control of inflammation in macrophages. Antioxid Redox Betoken. 2013;19(6):595–637. doi:10.1089/ars.2012.4785
82. Nemmar A, Al-Salam S, Zia S, et al. Contrasting actions of diesel exhaust particles on the pulmonary and cardiovascular systems and the furnishings of thymoquinone. Br J Pharmacol. 2011;164(vii):1871–1882. doi:10.1111/j.1476-5381.2011.01442.x
83. Ammar El 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;xi(12):2232–2236. doi:10.1016/j.intimp.2011.10.013
84. Berger P, Girodet P-O, Manuel Tunon-de-lara J. Mast prison cell myositis: a new characteristic of allergic asthma? Allergy. 2005;lx(x):1238–1240. doi:10.1111/j.1398-9995.2005.00898.ten
85. Alkharfy K. Nitric oxide pathway as a potential therapeutic target in COVID-19. FARMACIA. 2020;68:966–969. doi:x.31925/farmacia.2020.6.ii
86. Houghton PJ, Zarka R, de Las Heras B, Hoult JR. Fixed oil of Nigella sativa and derived thymoquinone inhibit eicosanoid generation in leukocytes and membrane lipid peroxidation. Planta Med. 1995;61(one):33–36. doi:10.1055/due south-2006-957994
87. Mansour Grand, Tornhamre S. Inhibition of 5-lipoxygenase and leukotriene C4 synthase in human claret cells by thymoquinone. J Enzyme Inhib Med Chem. 2004;nineteen(5):431–436. doi:10.1080/14756360400002072
88. Hossen MJ, Yang WS, Kim D, Aravinthan A, Kim J-H, Cho JY. Thymoquinone: an IRAK1 inhibitor with in vivo and in vitro anti-inflammatory activities. Sci Rep. 2017;vii(i):42995. doi:10.1038/srep42995
89. Sharma AK, Fernandez LG, Awad AS, Kron IL, Laubach VE. Proinflammatory response of alveolar epithelial cells is enhanced by alveolar macrophage-produced TNF-blastoff during pulmonary ischemia-reperfusion injury. Am J Physiol Lung Cell Mol Physiol. 2007;293(1):L105–13. doi:10.1152/ajplung.00470.2006
xc. Korbecki J, Baranowska-Bosiacka I, Gutowska I, Chlubek D. The outcome of reactive oxygen species on the synthesis of prostanoids from arachidonic acrid. J Physiol Pharmacol. 2013;64(iv):409–421.
91. Shaterzadeh-Yazdi H, Noorbakhsh MF, Hayati F, Samarghandian S, Farkhondeh T. Immunomodulatory and anti-inflammatory effects of thymoquinone. Cardiovasc Hematol Disord Drug Targets. 2018;xviii(ane):52–60. doi:10.2174/1871529x18666180212114816
92. Majdalawieh AF, Fayyad MW. Immunomodulatory and anti-inflammatory action of Nigella sativa and thymoquinone: a comprehensive review. Int Immunopharmacol. 2015;28(1):295–304. doi:10.1016/j.intimp.2015.06.023
93. Xuan NT, Shumilina Eastward, Qadri SM, Götz F, Lang F. Effect of thymoquinone on mouse dendritic cells. Cel Physiol Biochem. 2010;25(2–3):307–314. doi:10.1159/000276563
94. Mohany M, El-Feki Thou, Refaat I, Garraud O, Badr Yard. Thymoquinone ameliorates the immunological and histological changes induced by exposure to imidacloprid insecticide. J Toxicol Sci. 2012;37(1):1–11. doi:ten.2131/jts.37.ane
95. El Baba R, Herbein One thousand. Management of epigenomic networks entailed in coronavirus infections and COVID-19. Clin Epigenetics. 2020;12(1):118. doi:10.1186/s13148-020-00912-vii
96. Chlamydas S, Papavassiliou AG. Epigenetic mechanisms regulating COVID-nineteen infection. Epigenetics. 2020;one–eight. doi:x.1080/15592294.2020.1796896
97. Chai P, Yu J, Ge S, Jia R, Fan 10. Genetic alteration, RNA expression, and Dna methylation profiling of coronavirus disease 2022 (COVID-xix) receptor ACE2 in malignancies: a pan-cancer analysis. J Hematol Oncol. 2020;xiii(1):43. doi:10.1186/s13045-020-00883-5
98. Stefanska B, Karlic H, Varga F, Fabianowska-Majewska K, Haslberger A. Epigenetic mechanisms in anti-cancer actions of bioactive food components–the implications in cancer prevention. Br J Pharmacol. 2012;167(2):279–297. doi:ten.1111/j.1476-5381.2012.02002.x
99. Patra SK, Szyf M. DNA methylation-mediated nucleosome dynamics and oncogenic Ras signaling: insights from FAS, FAS ligand and RASSF1A. FEBS J. 2008;275(21):5217–5235. doi:10.1111/j.1742-4658.2008.06658.10
100. Kar S, Parbin Southward, Deb M, et al. Epigenetic choreography of stalk cells: the Dna demethylation episode of evolution. Cell Mol Life Sci. 2014;71(6):1017–1032. doi:10.1007/s00018-013-1482-2
101. Paluszczak J, Krajka-Kuźniak V, Baer-Dubowska W. The upshot of dietary polyphenols on the epigenetic regulation of gene expression in MCF7 breast cancer cells. Toxicol Lett. 2010;192(2):119–125. doi:10.1016/j.toxlet.2009.ten.010
102. Arafa E-SA, Zhu Q, Shah ZI, et al. Thymoquinone upwardly-regulates PTEN expression and induces apoptosis in doxorubicin-resistant man breast cancer cells. Mutat Res. 2011;706(i):28–35. doi:10.1016/j.mrfmmm.2010.ten.007
103. Parbin S, Shilpi A, Kar S, et al. Insights into the molecular interactions of thymoquinone with histone deacetylase: evaluation of the therapeutic intervention potential against chest cancer. Article. Mol Biosyst. 2016;12(1):48–58. doi:10.1039/c5mb00412h
104. Lau AW, Liu P, Inuzuka H, Gao D. SIRT1 phosphorylation by AMP-activated protein kinase regulates p53 acetylation. Am J Cancer Res. 2014;four(3):245–255.
105. Nin V, Escande C, Chini CC, et al. Function of deleted in breast cancer 1 (DBC1) protein in SIRT1 deacetylase activation induced by protein kinase A and AMP-activated Protein Kinase*. J Biol Chem. 2012;287(28):23489–23501. doi:10.1074/jbc.M112.365874
106. Bruscella P, Bottini South, Baudesson C, Pawlotsky J-K, Feray C, Trabucchi M. Viruses and miRNAs: more friends than foes. Front end Microbiol. 2017;eight(824). doi:x.3389/fmicb.2017.00824
107. Sohal SS. Epithelial and endothelial cell plasticity in chronic obstructive pulmonary affliction (COPD). Respir Investig. 2017;55(two):104–113. doi:x.1016/j.resinv.2016.11.006
108. Centa A, Fonseca Equally, Ferreira S, et al. Deregulated miRNA expression is associated with endothelial dysfunction in post-mortem lung biopsies of COVID-19 patients. Am J Physiol Lung Cell Mol Physiol. 2021;320:L405–L412. doi:10.1152/ajplung.00457.2020
109. Imani S, Wei C, Cheng J, et al. MicroRNA-34a targets epithelial to mesenchymal transition-inducing transcription factors (EMT-TFs) and inhibits breast cancer cell migration and invasion. Oncotarget. 2017;8(xiii):21362–21379. doi:10.18632/oncotarget.15214
110. Feng Y, Chen L, Luo Q, Wu M, Chen Y, Shi Ten. Interest of microRNA-146a in diabetic peripheral neuropathy through the regulation of inflammation. Drug Des Devel Ther. 2018;12:171–177. doi:10.2147/DDDT.S157109
111. Su YL, Wang X, Isle of mann M, et al. Myeloid cell-targeted miR-146a mimic inhibits NF-κB-driven inflammation and leukemia progression in vivo. Blood. 2020;135(3):167–180. doi:ten.1182/blood.2019002045
112. Qiong 50, Zhen R, Linlin Z, et al. Involvement of microRNA-146a in the inflammatory response of status epilepticus rats. CNS Neurol Disorders Drug Targets. 2017;16(6):686–693. doi:10.2174/1871527316666170505123956
113. Sabbatinelli J, Giuliani A, Matacchione 1000, et al. Decreased serum levels of the inflammaging marker miR-146a are associated with clinical non-response to tocilizumab in COVID-19 patients. Mech Ageing Dev. 2021;193:111413. doi:10.1016/j.mad.2020.111413
114. Khan MA, Tania M, Fu J. Epigenetic role of thymoquinone: bear on on cellular mechanism and cancer therapeutics. Drug Discov Today. 2019;24(12):2315–2322. doi:10.1016/j.drudis.2019.09.007
115. Sommer A, Försterling H-D, Naber G. Thymoquinone: shield and sword against SARS-CoV-ii. Precis Nanomed. 2020. doi:10.33218/001c.12984
116. Forouzanfar F, Bazzaz BSF, Hosseinzadeh H. Blackness cumin (Nigella sativa) and its constituent (thymoquinone): a review on antimicrobial effects. Islamic republic of iran J Basic Med Sci. 2014;17(12):929–938.
117. Zihlif MA, Mahmoud IS, Ghanim MT, et al. Thymoquinone efficiently inhibits the survival of EBV-infected B cells and alters EBV gene expression. Integr Cancer Ther. 2013;12(three):257–263. doi:10.1177/1534735412458827
118. Oyero OG, Toyama M, Mitsuhiro N, et al. Selective inhibition of hepatitis C virus replication by alpha-zam, A Nigella sativa seed formulation. Afr J Tradit Complement Altern Med. 2016;13(6):144–148. doi:x.21010/ajtcam.v13i6.20
119. Ulasli Thou, Gurses SA, Bayraktar R, et al. The effects of Nigella sativa (Ns), Anthemis hyalina (Ah) and Citrus sinensis (Cs) extracts on the replication of coronavirus and the expression of TRP genes family. Mol Biol Rep. 2014;41(3):1703–1711. doi:ten.1007/s11033-014-3019-7
120. Seadawy MG, Gad AF, Elhoseny MF, et al. In vitro: natural compounds (Thymol, Carvacrol, Hesperidine, and Thymoquinone) against Sars-Cov2 strain isolated from Egyptian patients. bioRxiv. 2020. doi:10.1101/2020.eleven.07.367649
121. Xu H, Liu B, Xiao Z, et al. Computational and experimental studies reveal that thymoquinone blocks the entry of coronaviruses into in vitro cells. Infect Dis Ther. 2021;ten(1):483–494. doi:10.1007/s40121-021-00400-ii
122. Senger MR, Evangelista TCS, Dantas RF, et al. COVID-19: molecular targets, drug repurposing and new avenues for drug discovery. Mem Inst Oswaldo Cruz. 2020;115. doi:10.1590/0074-02760200254
123. Shaikh YI, Sameerâ shaikh ÂVS, Ahmed K, Nazeruddin GM, Pathan ÂHM. The revelation of various compounds institute in Nigella sativa L. (Black Cumin) and their possibility to inhibit COVID-19 infection based on the molecular docking and physical properties. Eng Sci. 2020;11:31–35. doi:ten.30919/es8d1127
124. Sultan Mohideen AK. Molecular docking assay of phytochemical thymoquinone as a therapeutic agent on SARS-Cov-2 envelope protein. Biointerface Res Appl Chem. 2021;11:8389–8401. doi:ten.33263/BRIAC111.83898401
125. Bouchentouf S, Noureddine M Identification of compounds from Nigella Sativa as new potential inhibitors of 2022 Novel Coronavirus (Covid-19): Molecular Docking Report; 2020.
126. Youness K, Mohammed M, Houda F. In silico investigation of the SARS CoV2 protease with thymoquinone, the Major Constituent of Nigella Sativa. Curr Drug Discov Technol. 2020;17:1–4. doi:10.2174/1570163817666200712164406
127. Sekiou O, Bouziane I, Bouslama Z, Djemel A In-silico identification of potent inhibitors of COVID-nineteen Principal Protease (Mpro) and Angiotensin Converting Enzyme 2 (ACE2) from natural products: quercetin, hispidulin, and cirsimaritin exhibited better potential inhibition than hydroxy-chloroquine against COVID-19 main protease active site and ACE2; 2020.
128. Elfiky AA. Natural products may interfere with SARS-CoV-ii attachment to the host prison cell. J Biomol Struct Dyn. 2020;one–10. doi:10.1080/07391102.2020.1761881
129. Ibrahim IM, Abdelmalek DH, Elshahat ME, Elfiky AA. COVID-nineteen spike-host cell receptor GRP78 bounden site prediction. J Infect. 2020;eighty(5):554–562. doi:10.1016/j.jinf.2020.02.026
130. Hendaus MA, Jomha FA. Covid-19 induced superimposed bacterial infection. J Biomol Struct Dyn. 2020;1–seven. doi:10.1080/07391102.2020.1772110
131. Vaillancourt Grand, Jorth P. The unrecognized threat of secondary bacterial infections with COVID-xix. mBio. 2020;eleven(4):e01806–20. doi:10.1128/mBio.01806-20
132. Chaieb G, Kouidhi B, Jrah H, Mahdouani Chiliad, Bakhrouf A. Antibacterial activeness of Thymoquinone, an active principle of Nigella sativa and its potency to preclude bacterial biofilm germination. BMC Complement Altern Med. 2011;11:29. doi:x.1186/1472-6882-11-29
133. Randhawa MA, Alenazy AK, Alrowaili MG, Basha J. An active principle of Nigella sativa L., thymoquinone, showing meaning antimicrobial activity against anaerobic bacteria. J Intercult Ethnopharmacol. 2017;vi(ane):97–101. doi:10.5455/jice.20161018021238
134. Randhawa MA. In vitro antituberculous activeness of thymoquinone, an active principle of Nigella sativa. J Ayub Med Coll Abbottabad. 2011;23(two):78–81.
135. Hariharan P, Paul-Satyaseela M, Gnanamani A. In vitro profiling of antimethicillin-resistant Staphylococcus aureus action of thymoquinone against selected type and clinical strains. Lett Appl Microbiol. 2016;62(3):283–289. doi:10.1111/lam.12544
136. Mouwakeh A, Telbisz Á, Spengler G, Mohácsi-Farkas C, Kiskó G. Antibacterial and resistance modifying activities of Nigella sativa essential oil and its active compounds confronting listeria monocytogenes. In Vivo (Brooklyn). 2018;32(4):737–743. doi:x.21873/invivo.11302
137. Salem EM, Yar T, Bamosa AO, et al. Comparative study of Nigella Sativa and triple therapy in eradication of Helicobacter Pylori in patients with not-ulcer dyspepsia. Saudi J Gastroenterol. 2010;16(three):207–214. doi:10.4103/1319-3767.65201
138. Subramaniam S, Scharrer I. Procoagulant activeness during viral infections. Front Biosci. 2018;23:1060–1081. doi:10.2741/4633
139. Aggarwal Southward, Gollapudi S, Gupta Due south. Increased TNF-alpha-induced apoptosis in lymphocytes from aged humans: changes in TNF-alpha receptor expression and activation of caspases. J Immunol. 1999;162(4):2154–2161.
140. Masi P, Hékimian Grand, Lejeune M, et al. Systemic inflammatory response syndrome is a major contributor to COVID-19-associated coagulopathy: insights from a Prospective, Single-Center Cohort Study. Circulation. 2020;142(6):611–614. doi:ten.1161/circulationaha.120.048925
141. Guo LP, Liu SX, Yang Q. Effect of thymoquinone on astute kidney injury induced by sepsis in BALB/c mice. Biomed Res Int. 2020;2020:1594726. doi:10.1155/2020/1594726
142. Gupta R, Ghosh A, Singh AK, Misra A. Clinical considerations for patients with diabetes in times of COVID-19 epidemic. Diabetes MetabSyndr. 2020;14(3):211–212. doi:x.1016/j.dsx.2020.03.002
143. Kaatabi H, Bamosa AO, Badar A, et al. Nigella sativa improves glycemic control and ameliorates oxidative stress in patients with type two diabetes mellitus: placebo controlled participant blinded clinical trial. PLoS I. 2015;10(2):e0113486. doi:10.1371/journal.pone.0113486
144. Sangi SMA, Sulaiman MI, El-Wahab MFA, Ahmedani EI, Ali SS. Antihyperglycemic event of thymoquinone and oleuropein, on streptozotocin-induced diabetes mellitus in experimental animals. Pharmacogn Magazine. 2015;eleven(Suppl 2):S251–S257. doi:10.4103/0973-1296.166017
145. Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, Cathay. Intensive Care Med. 2020;46(5):846–848. doi:10.1007/s00134-020-05991-x
146. El Tahir KEH, Ashour MMS, Al-Harbi MM. The cardiovascular deportment of the volatile oil of the black seed (Nigella sativa) in rats: elucidation of the mechanism of action. Gen Pharmacol. 1993;24(5):1123–1131. doi:10.1016/0306-3623(93)90359-half-dozen
147. Enomoto S, Asano R, Iwahori Y, et al. Hematological studies on black cumin oil from the seeds of Nigella sativa L. Biol Pharm Bull. 2001;24(3):307–310. doi:10.1248/bpb.24.307
148. Randhawa MA, Alghamdi MS, Maulik SK. The effect of thymoquinone, an active component of Nigella sativa, on isoproterenol induced myocardial injury. Pak J Pharm Sci. 2013;26(6):1215–1219.
149. Galeotti C, Bayry J. Autoimmune and inflammatory diseases post-obit COVID-19. Nat Rev Rheumatol. 2020;sixteen(8):413–414. doi:10.1038/s41584-020-0448-7
150. Verdoni Fifty, Mazza A, Gervasoni A, et al. An outbreak of severe Kawasaki-like illness at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort written report. Lancet. 2020;395(10239):1771–1778. doi:ten.1016/S0140-6736(20)31103-X
151. Pouletty Thousand, Borocco C, Ouldali N, et al. Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki affliction (Kawa-COVID-19): a multicentre cohort. Ann Rheum Dis. 2020;79(8):999–1006. doi:10.1136/annrheumdis-2020-217960
152. Toubiana J, Poirault C, Corsia A, et al. Kawasaki-similar multisystem inflammatory syndrome in children during the COVID-xix pandemic in Paris, France: prospective observational study. BMJ. 2020;369:m2094. doi:10.1136/bmj.m2094
153. Waltuch T, Gill P, Zinns LE, et al. Features of COVID-19 post-infectious cytokine release syndrome in children presenting to the emergency section. Am J Emerg Med. 2020;38(10):
154. Koshak A, Koshak E, Heinrich M. Medicinal benefits of Nigella sativa in bronchial asthma: a literature review. Saudi Pharm J. 2017;25(8):1130–1136. doi:x.1016/j.jsps.2017.07.002
155. 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
156. al-Shabanah OA, Badary OA, Nagi MN, al-Gharably NM, al-Rikabi Ac, al-Bekairi AM. Thymoquinone protects confronting doxorubicin-induced cardiotoxicity without compromising its antitumor activity. J Exp Clin Cancer Res. 1998;17(two):193–198.
157. Isaev NK, Chetverikov NS, Stelmashook EV, Genrikhs EE, Khaspekov LG, Illarioshkin SN. Thymoquinone as a potential neuroprotector in astute and chronic forms of cognitive pathology. Biochemistry (Mosc). 2020;85(ii):167–176. doi:10.1134/s0006297920020042
158. Nagi MN, Alam K, Badary OA, al-Shabanah OA, al-Sawaf HA, al-Bekairi AM. Thymoquinone protects confronting carbon tetrachloride hepatotoxicity in mice via an antioxidant machinery. Biochem Mol Biol Int. 1999;47(1):153–159. doi:10.1080/15216549900201153
159. Badary OA, Nagi MN, al-Shabanah OA, al-Sawaf HA, al-Sohaibani MO, al-Bekairi AM. Thymoquinone ameliorates the nephrotoxicity induced past cisplatin in rodents and potentiates its antitumor activity. Can J Physiol Pharmacol. 1997;75(12):1356–1361. doi:ten.1139/y97-169
160. Arslan Southward, Ethem G, Coskun O, Gürel A, Sayan H, Celik I. The protective effect of thymoquinone on ethanol-induced astute gastric damage in the rat. Nutr Res. 2005;25:673–680. doi:10.1016/j.nutres.2005.06.004
161. Alrashedi M. The protective role of thymoquinone against drugs toxicity: a review. J Pharm Res Int. 2018;1–11. doi:10.9734/JPRI/2018/44944
162. Tittarelli R, Pellegrini M, Scarpellini MG, et al. Hepatotoxicity of paracetamol and related fatalities. Eur Rev Med Pharmacol Sci. 2017;21(1 Suppl):95–101.
163. Bindu S, Mazumder Due south, Bandyopadhyay U. Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: a current perspective. BiochemPharmacol. 2020;180:114147. doi:10.1016/j.bcp.2020.114147
164. Nagi MN, Almakki HA, Sayed-Ahmed MM, Al-Bekairi AM. Thymoquinone supplementation reverses acetaminophen-induced oxidative stress, nitric oxide production and energy decline in mice liver. Nutrient Chem Toxicol. 2010;48(8–nine):2361–2365. doi:10.1016/j.fct.2010.05.072
165. Aycan IÖ, Tüfek A, Tokgöz O, et al. Thymoquinone treatment against acetaminophen-induced hepatotoxicity in rats. Int J Surg. 2014;12(three):213–218. doi:10.1016/j.ijsu.2013.12.013
166. Aycan İÖ, Elpek Ö, Akkaya B, et al. Diclofenac induced gastrointestinal and renal toxicity is alleviated past thymoquinone handling. Food Chem Toxicol. 2018;118:795–804. doi:ten.1016/j.fct.2018.06.038
167. Isik AF, Kati I, Bayram I, Ozbek H. A new amanuensis for treatment of acute respiratory distress syndrome: thymoquinone. An experimental study in a rat model. Eur J Cardiothorac Surg. 2005;28(2):301–305. doi:10.1016/j.ejcts.2005.04.012
168. Ahmad A, Alkharfy KM, Jan BL, et al. Thymoquinone handling modulates the Nrf2/HO-1 signaling pathway and abrogates the inflammatory response in an animal model of lung fibrosis. Exp Lung Res. 2020;46(iii–4):53–63. doi:ten.1080/01902148.2020.1726529
169. Basarslan F, Yilmaz Due north, Ates South, et al. Protective effects of thymoquinone on vancomycin-induced nephrotoxicity in rats. Hum Exp Toxicol. 2012;31(7):726–733. doi:x.1177/0960327111433185
170. Wong A. COVID-nineteen and toxicity from potential treatments: panacea or poison. Emerg Med Australas. 2020;32(4):697–699. doi:10.1111/1742-6723.13537
171. Cagey MA, Barbuto AF, Izadmehr Due south, Hayes BD, Burns MM. COVID-xix: therapeutics and their toxicities. J Med Toxicol. 2020;16(3):284–294. doi:ten.1007/s13181-020-00777-5
172. Ojha S, Azimullah South, Mohanraj R, et al. Thymoquinone protects against myocardial ischemic injury by mitigating oxidative stress and inflammation. Evid Based Complement Alternat Med. 2015;2015:143629. doi:10.1155/2015/143629
173. Xiao J, Ke ZP, Shi Y. The cardioprotective event of thymoquinone on ischemia-reperfusion injury in isolated rat centre via regulation of apoptosis and autophagy. J Cell Biochem. 2018;119(9):7212–7217. doi:10.1002/jcb.26878
174. Bruce-Hickman D, Sajeed SM, Pang YH, Seow CS, Chen W, Gulati Kansal M. Bowel ulceration following tocilizumab assistants in a COVID-19 patient. BMJ Open up Gastroenterol. 2020;seven(1):e000484. doi:x.1136/bmjgast-2020-000484
175. Cobourne-Duval MK, Taka E, Mendonca P, Soliman KFA. Thymoquinone increases the expression of neuroprotective proteins while decreasing the expression of pro-inflammatory cytokines and the gene expression NFκB pathway signaling targets in LPS/IFNγ -activated BV-two microglia cells. J Neuroimmunol. 2018;320:87–97. doi:x.1016/j.jneuroim.2018.04.018
176. Odeh F, Ismail SI, Abu-Dahab R, Mahmoud IS, Al Bawab A. Thymoquinone in liposomes: a study of loading efficiency and biological activeness towards breast cancer. Drug Deliv. 2012;nineteen(8):371–377. doi:10.3109/10717544.2012.727500
177. Alkharfy KM, Ahmad A, Khan RMA, Al-Asmari M. High-performance liquid chromatography of thymoquinone in rabbit plasma and its application to pharmacokinetics. J Liq Chromatogr Relat Technol. 2013;36(16):2242–2250. doi:10.1080/10826076.2012.717062
178. Alkharfy KM, Ahmad A, Khan RM, Al-Shagha WM. Pharmacokinetic plasma behaviors of intravenous and oral bioavailability of thymoquinone in a rabbit model. Eur J Drug Metab Pharmacokinet. 2015;40(3):319–323. doi:10.1007/s13318-014-0207-eight
179. Alkharfy KM, Ali FA, Alkharfy MA, et al. Effect of compromised liver function and acute kidney injury on the pharmacokinetics of thymoquinone in a rat model. Xenobiotica. 2020;50(seven):858–862. doi:10.1080/00498254.2020.1745319
180. Kalam MA, Raish Chiliad, Ahmed A, et al. Oral bioavailability enhancement and hepatoprotective effects of thymoquinone by cocky-nanoemulsifying drug delivery system. Mater Sci Eng C Mater Biol Appl. 2017;76:319–329. doi:10.1016/j.msec.2017.03.088
181. Lupidi 1000, Scire A, Camaioni E, et al. Thymoquinone, a potential therapeutic amanuensis of Nigella sativa, binds to site I of man serum albumin. Phytomedicine. 2010;17(10):714–720. doi:10.1016/j.phymed.2010.01.011
182. El-Najjar N, Ketola RA, Nissilä T, et al. Affect of protein binding on the analytical detectability and anticancer activeness of thymoquinone. J Chem Biol. 2011;4(iii):97–107. doi:10.1007/s12154-010-0052-iv
183. Lupidi Thou, Camaioni E, Khalifé H, et al. Characterization of thymoquinone binding to human α1-acid glycoprotein. J Pharm Sci. 2012;101(7):2564–2573. doi:10.1002/jps.23138
184. Wirries A, Breyer S, Quint K, Schobert R, Ocker M. Thymoquinone hydrazone derivatives crusade cell wheel arrest in p53-competent colorectal cancer cells. Exp Ther Med. 2010;1(ii):369–375. doi:10.3892/etm_00000058
185. Elmowafy M, Samy A, Raslan MA, et al. Enhancement of bioavailability and pharmacodynamic effects of thymoquinone via Nanostructured Lipid Carrier (NLC) conception. AAPS PharmSciTech. 2016;17(3):663–672. doi:ten.1208/s12249-015-0391-0
186. Ng WK, Saiful Yazan L, Yap LH, Wan NorHafiza WA, How CW, Abdullah R. Thymoquinone-loaded nanostructured lipid carrier exhibited cytotoxicity towards chest 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
187. Ong YS, Saiful Yazan L, Ng WK, et al. Acute and subacute toxicity profiles of thymoquinone-loaded nanostructured lipid carrier in BALB/c mice. Int J Nanomedicine. 2016;xi:5905–5915. doi:ten.2147/IJN.S114205
188. El-Far AH, Al Jaouni SK, Li W, Mousa SA. Protective roles of thymoquinone nanoformulations: potential nanonutraceuticals in human diseases. Nutrients. 2018;10(10):1369. doi:10.3390/nu10101369
189. Badary OA. Thymoquinone attenuates ifosfamide-induced Fanconi syndrome in rats and enhances its antitumor action in mice. J Ethnopharmacol. 1999;67(two):135–142. doi:10.1016/s0378-8741(98)00242-6
190. Badary OA, Abdel-Naim AB, Abdel-Wahab MH, Hamada FM. The influence of thymoquinone on doxorubicin-induced hyperlipidemic nephropathy in rats. Toxicology. 2000;143(3):219–226. doi:10.1016/s0300-483x(99)00179-1
191. Awad Equally, Kamel R, Sherief MA. Consequence of thymoquinone on hepatorenal dysfunction and alteration of CYP3A1 and spermidine/spermine N-ane-acetyl-transferase gene expression induced past renal ischaemia-reperfusion in rats. J Pharm Pharmacol. 2011;63(8):1037–1042. doi:10.1111/j.2042-7158.2011.01303.x
192. Bai T, Yang Y, Wu YL, et al. Thymoquinone alleviates thioacetamide-induced hepatic fibrosis and inflammation by activating LKB1-AMPK signaling pathway in mice. Int Immunopharmacol. 2014;xix(2):351–357. doi:10.1016/j.intimp.2014.02.006
193. ElKhoely A, Hafez HF, Ashmawy AM, et al. Chemopreventive and therapeutic potentials of thymoquinone in HepG2 cells: mechanistic perspectives. J Nat Med. 2015;69(3):313–323. doi:10.1007/s11418-015-0895-seven
194. Gholamnezhad Z, Havakhah Southward, Boskabady MH. Preclinical and clinical furnishings of Nigella sativa and its constituent, thymoquinone: a review. J Ethnopharmacol. 2016;190:372–386. doi:x.1016/j.jep.2016.06.061
195. Abulfadl YS, El-Maraghy NN, Ahmed AAE, Nofal South, Badary OA. Protective effects of thymoquinone on D-galactose and aluminum chloride induced neurotoxicity in rats: biochemical, histological and behavioral changes. Neurol Res. 2018;twoscore(4):324–333. doi:10.1080/01616412.2018.1441776
196. Badary OA, Al-Shabanah OA, Nagi MN, Al-Bekairi AM, Elmazar MMA. Astute and subchronic toxicity of thymoquinone in mice. Drug Dev Res. 1998;44(2‐3):56–61. doi:10.1002/(SICI)1098-2299(199806/07)44:ii/3<56::Assistance-DDR2>3.0.CO;2-ix
197. Qadri SM, Mahmud H, Föller M, Lang F. Thymoquinone-induced suicidal erythrocyte expiry. Food Chem Toxicol. 2009;47(7):1545–1549. doi:10.1016/j.fct.2009.03.037
198. Khader K, Bresgen N, Eckl PM. In vitro toxicological properties of thymoquinone. Food Chem Toxicol. 2009;47(1):129–133. doi:10.1016/j.fct.2008.10.019
199. Al-Ali A, Alkhawajah AA, Randhawa MA, Shaikh NA. Oral and intraperitoneal LD50 of thymoquinone, an active principle of Nigella sativa, in mice and rats. J Ayub Med Coll Abbottabad. 2008;20(2):25–27.
200. Abukhader MM. The consequence of road of administration in thymoquinone toxicity in male person and female rats. Indian J Pharm Sci. 2012;74(3):195–200. doi:ten.4103/0250-474x.106060
201. Tavakkoli A, Mahdian Five, Razavi BM, Hosseinzadeh H. Review on Clinical Trials of Black Seed (Nigella sativa) and its Active Constituent, Thymoquinone. J Pharmacopunct. 2017;20(iii):179–193. doi:10.3831/kpi.2017.20.021
202. Asaduzzaman Khan 1000, Tania Yard, Fu Due south, Fu J. Thymoquinone, every bit an anticancer molecule: from basic research to clinical investigation. Oncotarget. 2017;viii(31):51907–51919. doi:10.18632/oncotarget.17206
203. Alamri A, Bamosa A. Phase I Safety and Clinical Activity Report of Thymoquinone in patients with avant-garde refractory cancerous illness. Shiraz Med J. 2009;ten:107–111.
Source: https://www.dovepress.com/thymoquinone-a-promising-natural-compound-with-potential-benefits-for--peer-reviewed-fulltext-article-DDDT
0 Response to "Can You Take Black Seed Oil With Antibiotics"
Post a Comment