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Home , Nigella, Nigella sativa, Sativum

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Letter to Editor SOJ Pharmacy & Pharmaceutical Sciences Open Access A , Sativa Can Be Effective on Novel Coronavirus (Sars-Cov-2) and Pulmonary Diseases (Hypothesis) This paper has been proposed as a result of the common thinking and work of the COVID19/STORM team Farmanli Orkhan*1, Bastug Samet2, Donmez Omer Faruk3, Gokdemir Cihan4, Uckun Ilknur5, Pamuk Ibrahim6, Jafarov Alemdar7 1Department of Pathology, Marmara University School of Medicine 2Faculty of Pharmacy, Istanbul University 3Faculty of Medicine, Istanbul Medeniyet University 4Faculty of Medicine, Marmara University 5Faculty of Medicine, Kırıkkale University 6Department of Eye diseases, Istanbul Education and Research Hospital 7Department of Hematology, Azerbaijan Medical University

Received: 15 April 2020; Accepted: 20 April 2020; Published: 27 April 2020

*Corresponding author: Dr.Orkhan Farmanli, Department of Pathology, Marmara University School of Medicine, Turkey, Email: dr.orkhanfarmanli4652@ gmail.com

of pneumonia with an unknown etiology in Wuhan, China [2]. Abstract The pathogen, novel coronavirus SARS-CoV-2 was detected by In late December 2019, a group of patients applied to hospitals local hospitals using a monitoring mechanism for “pneumonia with a diagnosis of pneumonia with an unknown etiology in Wuhan, of unknown etiology”, which was established to identify new China. The pathogen, novel coronavirus SARS-CoV-2 was detected pathogens in a timely manner after the 2003 SARS outbreak. On by local hospitals using a monitoring mechanism for “pneumonia of unknown etiology”, which was established to identify new pathogens January 30, 2020, the World Health Organization (WHO) declared in a timely manner after the 2003 SARS outbreak. is COVID-19 as a “public health emergency of international concern” an annual . Nigella sativa has been considered for treatment of [3]. various diseases and is one of the most widely investigated . In this review, we will especially focus on the antibacterial, antiviral Nigella sativa is an annual herb. Nigella sativa has been effects of Nigella sativa. Most importantly, we aimed to review considered for treatment of various diseases and is one the whether it is effective against the current SARS-CoV-2 (COVID19), and most widely investigated herbs. This is known by different against bacterial and viral superinfection accompanying this virus, names, for example black (English), black and whether it can be effective in the treatment of SARS-CoV-2 related (USA), and corekotu (Turkish) [4]. lung diseases. Many active compounds of black seeds have been isolated, Keywords: Nigella sativa; SARS-Cov-2; COVID19; antiviral; antibacterial; pulmonary diseases; hypothesis Introduction andidentified essential and oil reported [5]. so far. The ingredients of Nigella sativa (black cumin) includes: proteins, , fixed oil, saponin Coronavirus (COVs) is a large single strand RNA virus family. Some of these mixed oils contain unsaturated fatty acids Novel coronaviruses appear regularly, especially due to the which includes: arachidonic, linoleic, linolenic, eicosadienoic, high prevalence and wide distribution of coronaviruses, large palmitic, oleic, stearic acid and more [5, 6]. genetic diversity and frequent recombination of their genomes Nigella sativa contains essential oils such as thymoquinone [1]. Among the previous outbreaks of coronaviruses include (TQ), thymohydroquinone (THQ), nigellone, dithymoquinone, severe Acute Respiratory Syndrome (SARS) -CoV and Middle and more. Quinine, where East Respiratory Syndrome (MERS) -CoV, previously described as factors with a major public health threat. In late December TQ is mostly abundant, is responsible for most of the 2019, a group of patients applied to hospitals with a diagnosis pharmacological effects. Moreover, Nigella sativa seeds also have different vitamins and minerals such as Fe, Ca, K, Zn, P, Cu [5]. Symbiosis Group *Corresponding author email: [email protected] Copyright: A Traditional Medicine, Nigella Sativa Can Be Effective on Novel © 2020 Orkhan Farmanli. Coronavirus (Sars-Cov-2) and Pulmonary Diseases (Hypothesis)

many studies prove that Nigella sativa has very strong and useful effect as an antibacterial agent.

Antiviral Activity of Nigella Sativa We searched Nigella sativa for its antiviral activity and found 19 articles in PubMed. We have examined all of these publications and presented their results under this title. In a study that belongs to Oyero et al. Alpha-Zam(a Nigella sativa formulation) selectively inhibited HCV replication [12].This study leads us to consider Nigella sativa as a new antiviral agent against HCV infection. Furthermore, in another study belongs to Barakat et al. after 3 months of Nigella sativa treatment decreased viral load of HCV[13]. In one study belongs to Zaher et al. showed Nigella sativa’s antiviral activity against isolated Infectious Laryngotracheitis Virus [14]. Another Extensive studies were done to identify the biological study belongs to Umar et al. in infected with H9N2 turkeys, Nigella activities and therapeutic potential of the Nigella sativa. As a sativa’s immune-stimulant and immunomodulator activities decreased result of the studies carried out so far, nigella sativa has been pathogenicity of H9N2 and inhibited viral replication [15]. reported as having the following therapeutic effects; antioxidant, When we searched for the effect of Nigella sativa on HIV in PubMed, gastroprotective, anti-ulcer, antiasthmatic, anti-cancer, anti- we found 7 publications. We have examined all of these publications and presented some of their results under this title. In a study that belongs hepatoprotective effect, antibacterial activity, antiviral activity to Mandana Behbahani, honey obtained from Petro selinum , andinflammatory, more [4]. immunomodulatory and anti-tumor properties, In this review, we will especially focus on the antibacterial, Nigella sativa, Citrus sinensis, Zataria multiflora, Citrus aurantium and antiviral effects of Nigella sativa. Most importantly, we aimed Onifade et al. established that Nigella Sativa reduced the viral load in Zizyphus mauritiana have a strong anti-HIV1 activity [16]. to review whether it is effective against the current SARS- 6 months in a study on an HIV positive patient [17]. Gurmu et al. have CoV-2 (COVID19) and against bacterial, viral superinfection interviewed 300 patients used Nigella sativa and similar traditional accompanying to this virus, and whether it can be effective in the medicine methods. As a result, they suggested that Nigella sativa can treatment of SARS-CoV-2 related lung diseases. be used additionally in HIV / AIDS patients [18]. In another study by Onifade et al. A 27-year-old HIV-positive woman is diagnosed in the Antibacterial Activity of Nigella Sativa antenatal period. This patient received Nigella sativa treatment instead of antiretroviral treatment. In repeated serology tests, the patient’s HIV Nigella sativa has very well-known antibacterial effect which is test results were negative[19]. shown in many in vitro and in vivo studies [6]. Hanafy et al. showed that dietyl ether extracted Nigella sativa is very effective against Gram The Effect 0f Nigella Sativa 0n Pulmonary positive and negative microorganisms. Also, the same study showed Disorders that Nigella sativa extracts are very useful as treatment of Staphylococcal infections in mice[7]. In another study, Hannan et al. used ethanolic In Vitro and in Vivo Effects of Thymoquinone on extracts of Nigella sativa against Methicillin resistant Staphylacoccus Pulmonary Disorders in Different Experimental aureus (MRSA) and study results showed that all tested strains of Studies MRSA were sensitive to extract and the extract had an MIC range of Pulmonary diseases such as Chronic Obstructive Pulmonary 0.2-0.5 mg/ml [8]. Hasan et al. designed a study that compares the effectiveness of aqueous extract and methanol extract of Nigella sativa. as causes of morbidity and death all over the world and could Although aqueous extract of Nigella sativa is less effective compared to Disease (COPD), asthma, lung fibrosis and lung cancer are known the methanol extract, aqueous extract of Nigella sativa at 100 mg/ml is showed that Thymoquinone(TQ) which is the major component effective against Pseudomonas aeruginosa in disc effusion method [9]. occur following abnormal inflammatory process. It has been Hosseinzadeh et al. showed that the methanol and chloroform extracts of Nigella sativa seed total extract as well as the essential oil oxidantof the volatile and anti- oil of apoptoticNigella sativa activities (54%) in has various beneficial experimental protective caused a dose dependent antibacterial activity on Gram-positive and studieseffects against [20]. Ahmet various Feridun diseases Isik through et al, anti-inflammatory,designed one of these anti- Gram-negative organisms in vivo study [10]. According to Eida et al., studies and revealed that thymoquinone improved oxygenation a research designed to evaluate the therapeutic effect of the aqueous while both thymoquinone and steroids protect lung tissue extract of Nigella sativa (NS) at different doses on B. hominis in vitro from Acute Lung Injury (ALI) and Acute Respiratory Distress and in vivo in comparison to MTZ as a control drug and results of both Syndrome (ARDS) histopathologically[21]. Mohamed El Gazzar in vivo and in vitro studies reveal potent lethal effect on B. Hominis without any cytopathic effects in infected mice [11]. These and other et al showed that TQ attenuates allergic airway inflammation by inhibiting Th2 cytokines and eosinophil infiltration into the

Citation: Farmanli Orkhan, Bastug Samet, Donmez Omer Faruk, Gokdemir Cihan et al, (2020) A Traditional Medicine, Nigella Page 2 of 5 Sativa Can Be Effective on Novel Coronavirus (Sars-Cov-2) and Pulmonary Diseases (Hypothesis). SOJ Pharm Sci 7(1):1-5. DOI: 10.15226/2374-6866/7/1/001100 Copyright: A Traditional Medicine, Nigella Sativa Can Be Effective on Novel © 2020 Orkhan Farmanli. Coronavirus (Sars-Cov-2) and Pulmonary Diseases (Hypothesis)

Nigella Sativa L. Dosage and Part Used during the allergic response in the lung in his in vivo experimental model[22].airways; thus In demonstratinganother in vivo its experiment, potential anti-inflammatory completed on guinea role During PubMed searchwe made, we found that Nigella sativa was pigs showed that thymoquinone has a preventive effect on model used in different ways. In particular, different doses and usage patterns of asthma, according to Keyhanmanesh et al [23]. Ulasli et al have been reported according to the disease [27]. Although its use in studied an in vitro experimental model of lung cancer cells and the form of oil obtained from seeds is common it has also been shown revealed the molecular basis and utility of the anti-tumor activity to be used as an extract in some studies [25, 27-29, 30,31]. For its use of TQ [24]. These and other many studies suggest that TQ has as medicinal tea, a teaspoon of crushed seeds is added to a glass of boiling water and can be taken twice a day as a tonic [32]. In addition, its likely favorable effects in other pulmonary diseases such as intravenous, intramuscular, intraperitoneal use have been reported in pneumonia.very beneficial In thiseffect way, on furthervarious inpulmonary vivo and indisorders vitro experiments and show animals in some studies [28,31]. Especially in the literature on antiviral are needed to see TQ’s likely effects and for its clinical usage. uses, 10 ml of oral intake has been reported 3 times a day [27]. Nigella sativa has also been reported to have a hypotensive effect in studies [28]. Therefore, we recommend that hypotensive patients to be under The Use of Nigella Sativa on Coronavirus doctor’s control. It has been reported to be safe for use in pregnant As explained in the previous sections, which has been demonstrated women [33]. As a result of the compilation we have made regarding the by its antibacterial and antiviral effects, many researches and way of use, we anticipate that Nigella sativa can be used in the form of experimental models, there are only two studies in the literature on the 10 ml 3 times a day in the treatment and especially in the prevention of effect of Nigella sativa on Coronavirus. One of these studies was done SARS-CoV-2 (COVID19). Although it can be used differently, oral use can by Mustafa Ulasli et al. , published in 2014. In the study; Nigella sativa, be envisaged especially for its preventive effect, but it requires further Anthemis hyalina, Citrus sinensis plant extracts were used and their clinical studies that the use of im and / or iv may be more effective effect on Coronavirus and TRP gene family was examined. After the during pulmonary disease due to SARS-CoV-2 (COVID19). treatment with the extract, IL 8 levels and extracellular release of the As a result, when we examine the article titled “A rapid advice virus in CoV infected cells were examined. As a result of the study, no guideline for the diagnosis and treatment of 2019 novel coronavirus virus was detected in the cells receiving Anthemis hyalina extract. After (2019-nCoV) infected pneumonia (standard version)” published by treatment with Nigella sativa extract, it was found that there was a great Jin et al., [34]we see that traditional treatment methods have a very decrease in the number of viruses, but there were no changes in the important role in the treatment and especially in the prevention of the cells treated with Citrus sinensis extract[25]. Another study was done disease. Interestingly, when we search for articles, we also encountered by Christie Chen et al., published in 2014. Chen et al. investigated the studies that some traditional medicines are effective on coronavirus. effect of Rhodiola rosea (goldenroot), Nigella sativa (black cumin) and We summarized the traditional medicine used in these studies and the Sambucus nigra (common elderberry) extracts on avian IBV (Infectious results of which type of coronavirus was studied in Table 1. As a result Bronchitis Virus) replication. Unlike Nigella sativa and Rhodiola, they of the literature review, in studies related to Nigella sativa, we found that have found that Rosea sambucus nigra inhibited early viral replication there are positive results regarding the use of this traditional medicine [26]. Although Nigella sativa has two different effects in these two in antibacterial, anti-viral, pulmonary diseases.Further laboratory and studies, we suggest that further studies should be established to make clinical studies are required to prove the effect of Nigella sativa on SARS- sure that this estimation can be effective against SARS-CoV-2 , which is CoV-2 (COVID19). molecularly similar to SARS-CoV

Traditional Medicine Agent Affected Coronavirus Type References Jing-Ru Wenga et al., Antiviral activity of Sambucus Formosana Nakai ethanol extract and related Sambucus Formosana Nakai, also known by Sambucus Human coronavirus NL63 (HCoV- phenolic acid constituents against human chinensis NL63) coronavirus NL63, Virus Research, Volume 273, November 2019, 197767 Zhenwei Wang et al., Clinical characteristics and therapeutic procedure for four cases with 2019 Shufeng Jiedu (SFJDC, a traditional Chinese 2019-nCoV novel coronavirus pneumonia receiving combined medicine) Chinese and Western medicine treatment, BioScience Trends. 2020; 14(1):64-68 Yu-Chi Tsai et al., Antiviral Action of Tryptanthrin Human coronavirus NL63 (HCoV- Isolated from Strobilanthes cusia against Strobilanthes cusia NL63) Human Coronavirus NL63, Biomolecules 2020, 10, 366

Citation: Farmanli Orkhan, Bastug Samet, Donmez Omer Faruk, Gokdemir Cihan et al, (2020) A Traditional Medicine, Nigella Page 3 of 5 Sativa Can Be Effective on Novel Coronavirus (Sars-Cov-2) and Pulmonary Diseases (Hypothesis). SOJ Pharm Sci 7(1):1-5. DOI: 10.15226/2374-6866/7/1/001100 Copyright: A Traditional Medicine, Nigella Sativa Can Be Effective on Novel © 2020 Orkhan Farmanli. Coronavirus (Sars-Cov-2) and Pulmonary Diseases (Hypothesis)

Shuanghuanglian oral liquid (SHL), a Chinese Li Ni et al., Combination of western medicine and traditional patent medicine containing extracts of three SARS-CoV2 Chinese traditional patent medicine in treating a Chinese herbs, namely, honeysuckle, forsythia, and family case of COVID-19 in Wuhan, Front. Med. Scutellaria baicalensis Li Runfeng et al., Lianhuaqingwen exerts anti-

Lianhuaqingwen SARS-CoV2 coronavirus (SARS-CoV-2), Pharmacological viral and anti-inflammatory activity against novel Research (2020) In vitro inhibition of coronavirus replications by the traditionally used medicinal herbal extracts, Cimcifuga racemose, Melia azedarach, Coptis chinensis, SARS CoV Cimicifuga rhizoma, Meliae cortex, Coptidis Phellodendron amurense, Sophora subprostrata rhizoma, and Phellodendron cortex. Journal of Clinical Virology 41 (2008) 122-128 Morus alba+ Chrysanthemum vulgare+ Prunus armeniaca+ Forsythia koreana+ piperita Immunomodulatory activities of the herbal formula Kwan Du Bu Fei Dang in healthy subjects: SARS-CoV Phragmites communis+ Scutellaria pekinensis+ a randomised, double-blind, placebo-controlled X+ Platycodon grandiflorum+ Glycyrrhiza glabra+ Isatisindigotica+ Astragalus membranaceus+ study. Hong Kong Med J 2011;17(Suppl 2):S41-3 Saposhnikovia divaricata Immunomodulatory activities of the herbal formula Kwan Du Bu Fei Dang in healthy subjects: (HC), Ganoderma lucidum SARS-CoV a randomised, double-blind, placebo-controlled study. Hong Kong Med J 2011;17(Suppl 2):S41-3

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Citation: Farmanli Orkhan, Bastug Samet, Donmez Omer Faruk, Gokdemir Cihan et al, (2020) A Traditional Medicine, Nigella Page 4 of 5 Sativa Can Be Effective on Novel Coronavirus (Sars-Cov-2) and Pulmonary Diseases (Hypothesis). SOJ Pharm Sci 7(1):1-5. DOI: 10.15226/2374-6866/7/1/001100 Copyright: A Traditional Medicine, Nigella Sativa Can Be Effective on Novel © 2020 Orkhan Farmanli. Coronavirus (Sars-Cov-2) and Pulmonary Diseases (Hypothesis)

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Citation: Farmanli Orkhan, Bastug Samet, Donmez Omer Faruk, Gokdemir Cihan et al, (2020) A Traditional Medicine, Nigella Page 5 of 5 Sativa Can Be Effective on Novel Coronavirus (Sars-Cov-2) and Pulmonary Diseases (Hypothesis). SOJ Pharm Sci 7(1):1-5. DOI: 10.15226/2374-6866/7/1/001100