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A REVIEW ON ANTIVIRAL EFFECTS OF NIGELLA SATIVA L.

2552

 

Shamim Molla1, Md. Abul Kalam Azad1, Md Ali Azam Al Hasib1, M. Monayem Hossain1, Md.

Sohel Ahammed1, Shohel Rana1, Muhammad Torequl Islam1*

1Department of Pharmacy, Life Science Faculty, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalgang-8100, Bangladesh

dmt.islam@bsmrstu.edu.bd.

 

Abstract

Nigella​​ sativa​​ seeds​​ have​​ wide therapeutic​​ effects​​ and have​​ been reported to​​ have​​ significant​​ effects against​​ many ailments such as skin diseases,​​ jaundice, gastrointestinal problems, anorexia, conjunctivitis, dyspepsia, rheumatism, diabetes, hypertension,​​ intrinsic​​ hemorrhage, paralysis, amenorrhea, anorexia, asthma, cough, bronchitis, headache, fever,​​ influenza and​​ eczema.​​ Thymoquinone​​ (TQ) is​​ one​​ of the​​ most active constituent and has different beneficial properties.​​ Focus​​ on antimicrobial​​ effects, different​​ extracts​​ of​​ N.​​ sativa​​ as​​ well as​​ TQ, have a​​ broad antimicrobial spectrum,​​ including Gram-negative, Gram-positive bacteria,​​ viruses, parasites, schist soma​​ and​​ fungi.​​ The​​ effectiveness​​ of​​ N.​​ sativa​​ seeds​​ and​​ TQ​​ is​​ variable​​ and​​ depends​​ on​​ species​​ of target​​ microorganisms.​​ The present review paper tries to describe some​​ antiviral​​ activities​​ of​​ N.​​ sativa.​​ Such​​ as​​ murine​​ cytomegalo​​ virus​​ infection, avian​​ influenza​​ (H9N2), Chistosoma​​ Mansoni​​ Infection,​​ PPR​​ virus,​​ Broad bean​​ mosaic​​ virus,​​ HIV​​ virus, Hepatitis​​ C Virus,​​ Zucchini Yellow​​ Mosaic Virus,​​ and​​ Papaya​​ Ring​​ Spot Virus.

Keywords:​​ Nigella sativa; antiviral effects; HIV; thymoquinone

 

Introduction

Nigella​​ sativa, a dicotyledon​​ of the Ranunculaceae family,​​ has​​ been​​ employed​​ for​​ thousands​​ of​​ years​​ as a spice and food preservative,​​ as​​ well​​ as a protective and​​ curative​​ remedy​​ for​​ numerous​​ disorders,​​ and​​ is​​ known to have​​ many​​ medicinal​​ properties​​ in traditional​​ medicine​​ (Chopra​​ et​​ al.,​​ 1956,​​ Nadkarni​​ et al., 1976).​​ It is​​ the black seed referred to by​​ the prophet​​ Mohammed​​ (PBUH)​​ as having healing powers.​​ Black​​ seed​​ is​​ also​​ identified​​ as​​ the​​ curative black​​ cumin​​ in​​ the​​ Holy Bible,​​ and is​​ described as the​​ Melanthion​​ of Hippocrates and Discroides and as the Gith​​ of Pliny​​ (Attar-ur-Rahman​​ et​​ al.,1985).

Most of studies on biological effect of​​ N. sativa​​ have dealt with its crude extracts in different solvents, however, some studies used its active principles. Haq et al. (1999) fractionated whole​​ N. sativa​​ seeds using SDS-PAGE, which showed a number of protein bands ranging from 94 to 10 kDa molecular mass. Quinones thymoquinone and dithymoquinone are also important constituents of​​ N. sativa​​ (Daba et al.,1998; Nagi et al.,1999).

N.​​ sativa​​ has​​ been​​ reported to​​ have​​ various biological activities​​ (Islam​​ et al.,​​ 2019).​​ It​​ exhibited antioxidant​​ properties by suppressing chemiluminescence​​ (Daba​​ et​​ al., 1998; Nagi​​ et​​ al.,1999). Black seed preparations have also demonstrated significant​​ in vivo​​ antineoplastic activity​​ against​​ Erlich​​ ascites​​ carcinoma​​ (Worthen​​ et al.,1998),​​ and​​ in​​ vitro​​ against​​ murine​​ Dalton's​​ ascites lymphoma​​ and​​ sarcoma,​​ and​​ human​​ pancreatic​​ ade- nocarcinoma,​​ uterine sarcoma and leukemic cell lines​​ (Salomi​​ et​​ al.,​​ 1991).​​ The​​ active​​ components​​ of black seed also showed antihel-minthic​​ effects against nematodes, cestodes, tapeworms and​​ earthworms​​ (Agarwal​​ et al.,1979; Akhtar​​ et al., 1991).​​ Extracts​​ of​​ N.​​ sativa​​ also showed antimicrobial activity​​ against​​ Escherichia coli, Bacillus​​ subtitles,​​ Streptococcus faecalis,​​ Staphylococcus aureus, Pseudomonas aeruginosa​​ and the pathogenic yeast​​ Candida albicans​​ (Saxena​​ et al.,1986; Hanafy​​ et al.,1991). Black seed has also been​​ evaluated in clinical and​​ animal studies for its choleretic and cytotoxic action​​ (Mahfouz​​ et​​ al.,​​ 1962;​​ Tennekoon​​ et​​ al.,​​ 1991). In this review, we have sketched a current scnario on the anti-viral effects of​​ N. sativa​​ and its derived compounds on the basis of database information.

Methods

An​​ up to date​​ (May​​ 2019) search​​ was​​ made in the following databases: PubMed,​​ Science direct and google​​ scholar​​ with the​​ key​​ word​​ Nigella sativa’ and/or​​ ‘Virus​​ and​​ Anti-virus​​ effect’.

Findings

N. sativa​​ against murine cytomegalovirus infection

N.​​ sativa​​ oil​​ was found to act​​ against​​ murine cytomegalovirus​​ (Messerle​​ et​​ al.,​​ 1992;​​ Reynolds​​ et​​ al., 1993;​​ Smith​​ et al., 1994).​​ In another study,​​ N.​​ sativa​​ oil​​ was also found to​​ act against cytomegalovirus,​​ where​​ an​​ increase​​ in​​ macrophage​​ number​​ and​​ function,​​ and​​ interferon​​ gamma​​ (IFN-γ) production​​ was also​​ reported (Salem​​ et​​ al.,​​ 2000).

 

N. sativa​​ against avian influenza (H9N2)

Avian influenza​​ virus​​ (AIV) subtype H9N2​​ is becoming a serious threat to poultry birds. H9N2​​ AIV is an​​ emerging respiratory​​ problem, isolated from​​ different​​ birds​​ from​​ a​​ number​​ of​​ countries​​ and has been reported to have zoonotic potential​​ (Swayne,​​ 2012;​​ Ahad​​ et al.,​​ 2013; Umar​​ et al.,​​ 2016a,b).​​ Currently,​​ the​​ feed​​ industry​​ is​​ focusing​​ on​​ various substitutes for antimicrobial​​ drugs​​ (Al-​​ Mufarrej,​​ 2014).​​ Antimicrobial​​ agents​​ of​​ plant​​ origin, such​​ as​​ essential​​ oils, plant​​ extracts, and complete plant substances are considered​​ as alternatives to the​​ traditional​​ antimicrobial​​ feed​​ additives.​​ N.​​ sativa​​ oil​​ is​​ one​​ of​​ such​​ alternatives​​ that​​ could​​ be​​ used​​ as feed​​ additives​​ in​​ order​​ to​​ reduce​​ the​​ pathogen​​ load in poultry.​​ Thymoquinone​​ (TQ) has been found​​ as the​​ main bioactive​​ constituent​​ of​​ the​​ volatile​​ oil​​ of​​ N.​​ sativa​​ seeds.​​ In a study,​​ N.​​ sativa​​ was found to​​ exert an anti-influenza​​ virus activity​​ (Umar​​ et al.,​​ 2016).

 

N. sativa​​ against PPR virus

Peste​​ des​​ petits​​ ruminants​​ (PPR),​​ is​​ an​​ acute,​​ highly contagious and​​ economically important transboundary​​ viral disease​​ of sheep and goats associated​​ with high​​ morbidity and​​ mortality​​ (Balamurugan​​ et​​ al.,​​ 2014).​​ It​​ is​​ caused​​ by​​ PPR​​ virus, a​​ morbillivirus​​ of the Paramyxoviridae family. Disease​​ severity​​ depends​​ on​​ species​​ infected,​​ breed​​ or​​ virus​​ strain​​ (Wernike​​ et​​ al.,​​ 2014).​​ As​​ PPR​​ is​​ a​​ viral​​ disease,​​ there​​ exists​​ no​​ particular​​ treatment​​ for​​ the disease and post-exposure therapeutic approaches for​​ infection​​ are not described​​ much​​ in the literature​​ (Balamurugan​​ et​​ al.,​​ 2014).​​ Numerous​​ studies​​ report the​​ use​​ of​​ N.​​ sativa​​ as​​ liver tonics,​​ anti-diarrheal, analgesics, and anti-bacterial. Extensive studies​​ on the herb have​​ explored a​​ wide spectrum​​ of its pharmacological actions,​​ including​​ immunomodulatory, antimicrobial​​ and​​ antiinflammatory, properties,​​ etc. Because​​ of its​​ miraculous power​​ of healing,​​ N.​​ sativa​​ has got the place​​ among​​ the​​ top​​ ranked​​ evidence​​ based​​ herbal​​ medicines​​ (Ahmad​​ et​​ al.,​​ 2013). Current story describes the immunomodulatory and therapeutic​​ effect​​ of this herb against​​ the PPR​​ virus​​ in​​ experimentally infected​​ goats.​​ N.​​ sativa​​ prevented the​​ occurrence​​ of clinical signs and significant decrease in clinical signs, gross and histopathological​​ abnormalities.

 

N. sativa​​ against broad bean mosaic virus

Broad bean​​ (Vicia faba​​ L.) is​​ one​​ of the​​ major legumes​​ crops.​​ Broad​​ bean​​ mottle​​ disease​​ is​​ one​​ of the​​ world's​​ main​​ virus diseases in broad bean producing areas. Broad bean​​ mottle​​ virus​​ (BBMV) has spread​​ worldwide​​ wherever broad bean plants are grown. Broad bean​​ mottle​​ virus​​ (BBMV)​​ was classified​​ as a​​ member​​ of the bromovirus​​ group​​ (Hashim and El-Kiey, 1962; El-Alfy​​ et al., 1975).​​ N.​​ sativa​​ is also found to act against​​ MCMV​​ (Nafez​​ et al.,​​ 2009; Mehdi​​ et​​ al.,​​ 2010).

 

N. sativa​​ against human immunodificency virus (HIV)

Since 1980s​​ when​​ the human immunodeficiency​​ virus​​ (HIV)​​ was isolated from patients​​ with​​ opportunistic infections​​ and​​ Kaposi sarcoma, there aremillions​​ of people living​​ with this​​ dreadful​​ virus​​ (Barre-Sinoussi​​ et​​ al,​​ 1983;​​ Gallo​​ et​​ al,​​ 1983;​​ UNAIDS,​​ 2010).​​ It​​ was​​ estimated​​ that​​ no​​ infectious​​ organism has​​ claimed​​ more​​ lives​​ in​​ history​​ than​​ HIV​​ (UNAIDS,​​ 2010). Although​​ the prevalence​​ of HIV​​ infection​​ is reducing​​ globally,​​ many​​ factors​​ had​​ been​​ associated​​ with this gain.​​ The​​ advent​​ of highly active antiretroviral therapy​​ (HAART) and​​ vigorous campaign​​ on sexual behavior considerably have reduced​​ the​​ loss​​ of​​ lives​​ to​​ HIV​​ infection.​​ However,​​ HIV​​ infection​​ is​​ still​​ believed​​ to​​ be​​ incurable​​ and​​ can​​ only be​​ managed​​ with​​ HAART.​​ N.​​ sativa​​ was found to act against HIV​​ in a number​​ of reports​​ (Onifade​​ 2011,2012,2013).

 

N. sativa​​ against hepatities C virus

Acute hepatitis C​​ virus​​ (HCV) infection​​ is rarely​​ associated​​ with​​ life-threatening​​ disease,​​ with​​ 1545%​​ of infected persons recovering​​ within 6​​ months​​ without any treatment​​ (WHO,​​ 2015). However,​​ chronic infection develops in the remaining​​ 55-85%​​ out​​ of​​ which​​ 15-30%​​ eventually progress to liver​​ cirrhosis after​​ many​​ years​​ of persistent​​ virus carriage.​​ Persistent​​ HCV​​ infection​​ has​​ been​​ a​​ major risk factor for hepatocellular carcinoma​​ (HCC) development​​ (about​​ 2-6%​​ per​​ year)​​ in​​ patients​​ with cirrhosis,​​ mainly through indirect pathways,​​ which include chronic inflammation, cell death, cell proliferation,​​ and induction​​ of​​ free radicals​​ (Sangiovanni​​ et al.,​​ 2004;​​ Farinati​​ et al.,​​ 2007).​​ Treatment​​ of hepatitis C for​​ virus​​ eradication and non-progression​​ to​​ decompensated​​ liver​​ diseases​​ is achievable and highly recommended for all​​ with chronic infection.​​ The​​ recovery rate however​​ is determined​​ by the strain​​ of the infecting​​ virus, the type​​ of treatment and its​​ early institution​​ (WHO,​​ 2015). An​​ earlier treatment for hepatitis C​​ which combined interferon​​ and​​ ribavirin​​ effectively resolved​​ the​​ infection​​ leading​​ to​​ a​​ cure​​ in​​ 50%​​ of​​ the treated individuals; though​​ frequently associated​​ with​​ life​​ threatening​​ adverse​​ reactions​​ (WHO,​​ 2015).​​ N.​​ sativa​​ was found to act against​​ HCV​​ (Olufunmilayo​​ et​​ al.,​​ 2016).

 

N. sativa​​ against Zucchini yellow mosaic virus​​ Watermelon (Citrullus lanatus​​ L.;​​ family​​ Cucurbitaceae) crop is infected by a dozen of viruses of which Zucchini yellow mosaic virus (ZYMV) that belongs to the genus Potyvirus (family: Potyviridae), is regarded as one of the most destructive viruses. Watermelon infected plants exhibit symptoms that vary from mild to server mosaic, mottling and bubbling followed by leaf deformation and blister (Lisa et al.,1984). ZYMV has a positive single- stranded RNA and flexuous filamentous particles. The antiviral activity of the products including plant extracts, and synthetic chemicals is connected to their components which may act directly by interaction with virus particles in the early stage of infection​​ and​​ block​​ the​​ liberation​​ of​​ its​​ nucleic​​ acid​​ that could finally lead to stopping the​​ virus​​ multiplication​​ (Abdel-Shafi​​ et al.,​​ 2013). Nigella decoction​​ was​​ found​​ to​​ act​​ against​​ ZYMV​​ (Essam​​ et al.,​​ 2017).

 

N. sativa​​ against Newcastle disease virus

Newcastle​​ disease​​ virus​​ (NDV) has different strains​​ viz, lentogenic less​​ virulent,​​ velogenic and intermediate​​ virulent​​ mesogenic.​​ The disease has high​​ morbidity​​ and​​ mortality​​ with​​ marked​​ decrease in​​ eggs​​ production​​ in​​ laying​​ birds​​ (Alexander,​​ 2000).​​ N.​​ sativa​​ is​​ also​​ found​​ to​​ act​​ against​​ NDV​​ (Al-Garib​​ et​​ al.,​​ 2003).​​ The​​ velogenic​​ NDV​​ strains​​ kill​​ the​​ embryo​​ within​​ 48​​ hours,​​ while​​ lentogenic​​ take​​ 5​​ to​​ 7​​ days​​ to affect the​​ embryos​​ (Lam​​ et al., 1995).​​ The active component is​​ crystalline nigellone and thymoquinone that has potent anti-bacterial, anti- inflammatory immune stimulator,​​ anti-parasitic,​​ anti- histamine and anti-hypertensive​​ are the​​ main​​ effects​​ of these seeds​​ (Sultan​​ et al.,​​ 2009; Umar​​ et al.,​​ 2017).​​ The​​ antiviral​​ drug​​ Ribavirin​​ is​​ well​​ known​​ for the treatment​​ of different diseases like hepatitis. But​​ high​​ dosage​​ produced​​ different​​ types​​ of​​ organ toxicity​​ and​​ was also​​ one the causes​​ of death. Ethanolic​​ extract​​ of the​​ N.​​ sativa​​ is​​ markedly​​ effective​​ against NDV​​ in​​ term​​ of​​ decreased​​ viral​​ load and​​ mortality​​ in​​ embryonated​​ chicken​​ eggs​​ (Khan​​ et al.,​​ 2017). In summary,​​ N. sativa​​ and its derived compounds have been seen to act against a number of human, animals, birds and plant pathogenic viruses.​​ N. sativa​​ may be one of the best sources of anti-viral drugs.

 

Conflict of Interest:​​ None declared

 

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