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    6 views12 pages

    A Review of Medicinal Uses and Pharmacological Activities of Nigella Sativa

    Uploaded by

    Imtiaz Bashir

    Copyright:

    © All Rights Reserved
    Download as PDF or read online from Scribd
    Flag for inappropriate content
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    PJ BS Bosxiczs so Pakistan Journal of Biological Sciences ANSIez n Network for Scientific Information 308 Lasani Towns Sargodha Road, Faisalabad - Pakistan Pakistan Joumal of Biological Seiences ? (4): 441-451, 2004 ISSN 1028-8880 ‘© 2004 Asian Network For Slentfie Information. A Review of Medicinal Uses and Pharmacological Activities of Nigella sativa Anwwar-ul Hassan Gilani, Qaiser Jabeen and Muhammad Asad Ullah Khan Department of Biological and Biomedical Sciences, ‘The Aga Khan University Medical College, Karachi, Pakistan Abstract: Nigella sativa seeds (Kalonji) have been widely wed in traditional medicine ax diuotie, untitypertensive liver tone, digestive, antidiarheal, appetite stimulant, emmenagogue, analgesic, anthelmintic, snkibueterial and useful in skin disorders. Consequently, Kalen has been extensively stualied fer its biological activities and has been shown to be antciabetie, anticanocr andl immunomodulator, analgesic, antimicrobial, antiinflammatory, spasmolytic, bronchodilator, hepatoprotective, antihypertensive, renal protective and antioxidant properties. Key words: Nigella sativa, Thymoqui INTRODUCTION ‘The seed of Nigella sativa plant have been used 10 promote health and fight disease for centuries especially mn the Middle East and Southeast Asia. In South Asia, it is called Kalomi its Arabic name is Habat-ul-Saua and its ‘English name is Black cumin". The plant is widely grown in different parts of the world and is an anmial bert cultivated in India and Pakistan, As an oriental spice, [Nigella sativa has long heen wsed as a natural medicine for the treatment of many acute as well as chronic ‘conditions. This plant has been a great focus of research for centuries and has several taditional uses and ‘consequently tas been extensively studied for ts ‘chemnial constituents and biological activities. ‘Traditional uses: Nigella soriva is widely used natural remedy and the seeds are extensively used as spice, ‘arminative, condiment and aromatic. Traditionally, they hhave been used as diuretic, diaphortio, stomachie, liver tonie and digestive. AS a confection with ‘other ingredients, they are used in diarhea, indigestion, dyspepsia and sour belching; they also remove foul breath and watering ftom the mouth, The seeds of Nigella sativa are given with butter-milk to ewe obstinate hiccups ‘and are also useful in loss of appetite, vomiting, dropsy land puerperal diseases. They are used as emmenagoate land galactagogue and as abertiacient in large doses. In different combinations, the sds of Nigella sativa have been used in obesity and dyspnoea. They have antibilious property and are administered internally’ in intermittent fevers! The herb has been regards as a ‘valuable remedy in hepatic and digestive disorders as well yeomie, Anti ive, Antioxidant ‘as stimulant in a variety of conditions ascribed to “cold Iumours” Constant inhalation of fried seeds relieves cold ‘and catarh, They have also been used in. chronic ‘headache and migraine". The decootion ofthe seeds with some sweet oil forms a usefl application in skin diseases ‘They have been wef in mercury poisoning, seres and leprosy, Brayed in water, its application removes, swellings fom hands and feet Nigella sativa is also used cextemally in leucoderma, alopecin, eczema, freckles and pimples". The sceds of N- sativa have also been used as anthelmintic and antibacterial” Phytochemistry: In view ofits wide range of medicinal uses, the plant has under gone extensive phytochemical studies and a variety of compounds isolated. The seeds ‘of Nigella sativa contain a yellowish volatile oil (@.S- 1.6%), a. fixed oil G5.6-41 67), proteins (22.7%), aminoacids; eg albumin, globulin, lysine, leucine, isoleucine, valine", glycine, alanine, pherylalanine, arginine, asparagine, cystine, glutamic acid, aspartic acid. isoleucine, proline, serine, threonine, tryptophan and tyrosine", reducing sugars, mucilage, alkaloid, organic acids, tains, resins, toxic glucoside, metarbin, biter principles, glyeosidal saponins, melanthin resembling holleborin, melanthigenin, as, moisture and arabic acid ‘The seeds have also been found to contain fats, erode fiker, minerals eg. Fe,Na, Cu Zn, P, Cand vitamins like ‘ascorbic acc thiamine, niacin, pyridoxine and folic acid, thus ako possessing mititional value” Nigella sativa seed yield esters of fatty acids: eg palmitic aid, oleic acid, linoleic acid und dehydrosteaie. acid, higher terpenoids, aliphatic aleohols and q-Brunsaturated hydroxy fetones, Free sterols, steryl esters, steryl (Corresponding Author: De. Amwar-ul Hassan Gilani, Prolessor of Pharmacology, Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, Karachi-74800, Pakistan Phone: 0 4930051 ext 4571, Fax: (+92) 21-498 4294, 493 2085, Ema ana gileni@aku eda Pak J. Biol Soi, 7 (4): 41-451, 2004 lucorides and acylated ster ghavosides were isolated from the seed oil" A novel alkaloid nigellcine, an isoquinoline alkaloid, nigellimine and an indazole alkaloid, nigelldine, were aso isolated from the seeds of Nigella sativa". The seeds also contain ligase, phytosterols ‘and sitoster!”. ‘The active constituents of the seeds include the volatile ol consisting of carvone, an unsaturated ketone, terpene or d-limonene also called eavens, e-pinene and ‘p-cymene! The erstalline active principle, nigllone, is the only constiment of the earbony! fraction of the oil Pharmacologically active constituents of volatile oil are iymoquinone, dthymoquinone, thymobydroquinone and thymol Water stress influences the yield and ‘composition of essential oil The content of tymoquinone was highest (57.78%) when water was withheld for 12 days: In a recent study, Nigella sativa seed oil was ‘extracted with (wo different solvents; nllexane atl a ‘mistue of Chlorofon/Methanol, the later was foun ‘contain higher amcunts of total lipids. Majer faty acids ‘were linoleic acid, palmitic acid, cee acid and stearic acid and major phospholipids as phosphatidyleboline, phosphatidylethanolamine, phosphatcylserine and phosphatidylinositol. _ Phosphtidylglycerol, lysophosphatidylethanolamine and Iysophosphatidylcholine were isolated in smaller vanities! Pharmacological activities: The popularity of the plant ‘was highly enhanced by the ideological belief in the herb as a eure for multiple diseases. In fact, this plant has ‘occupied special place for its wide range of medicinal ‘value in the Islamic civilizations. Due tothe sayings of the Holy prophet, Mohammed (peace be upon him) thatthe plant is full of medicinal value", it gained immense popularity. Consequently, Kalonji has been extensively shudied particularly in the Islami world, which justifies its broad traditional therapeutic value, ‘Hypoglyeemie effects: In view ofthe folklorie we of plant ‘mite extracts for treatment of diabetes in the Middle Enst, ALAwadi and Gumoa studied a plant mitre (Nigella sativa, Mymth, Gum olybenum and Gum ‘asafoetida) for its blood glucose lowering effet in rats ‘and found it effective: Father studies on the plant mitre ‘containing. sativa, revealed that the blood glucose lowering effect was due to the inhibition of hepatic ‘luconeogenssis and the plant extract mixture may prove te bea useful therapeutic agent inthe treatment of nox insulin dependent diabetes mellite!”, An aqueous decoction of a plant mixture containing Nigella sativa ‘was found to lower the blood glucese level signifcanlly aa after oral administration!" ‘The intraperitoneal ‘administration of volatile oil of N. sativa seeds prostuced «8 significant hypoglycemic effect in normal and alloxan- induced diabetic rabbits! The hypoglycemic effect of N. sativa in combination with other herbs has alko been demonstrated ina study on alloxan-induced diabetic rats. In a more recent study, the seed extract when fziven orally decreased the elevated glucose levels in allexan-induced diabetic rabbits ater 2 months of ‘weatment! Another study was designed to investigate the possible insulinotropic properties of Nigella sativa oil in Sueplozotocin plus Nicotinamide-induced diabetes ‘mellitus inhamsters, Afer four weeks of treatment with N- sativa oil, significant deerease in blood glucose level together with sigaificant increase in serum albumin level, ‘were observed. The results showed that the hypoglycemic effect of Nigella sativa oil was, atleast partly, because of a stimulatory effeet on beta cell fnction with consequent increase in serum insulin level, ‘and possess insulinotropic properties in type IL like model {In another study. the kypoglyoemie effect of Nigella sativa was supposed to be mediated by extrapancreatic actions rather than by stimulated insulin release”, The clfect of seed oil on blood glucose concentrations was stuied in Sirepiozotovin-insiuced diabetic ats, The effect ‘of seed oil and other constituents sue as nigellone and Uymogquinone were shudied on insulin secretions of isolated rat pancreatic islets in the presence of 3, $6 or TILL mM ghicose, Oil significantly lowered the blood glucose concentrations in diabetic rts after 2, 4 and 6 ‘weeks, which was, however, not pacalleled by a stimulation of insulin release in the presence of oil, nigellone or thymoyinone; thus indicating the ‘extrapanereatic actions to be responsible for hypoglycemic effects of Nigella sativa oi. ‘A recent clinical study on human volunteers showed Ubu 1 g of N. sativa seeds twice daily caused a decrease in blood glucose level alter 2 weeks of oral treatment™. Effects on immune system and cancer: Nigella saiva seeds and its oil have been traditionally wed as a tonie to ‘remote health and prevent diseases. They were reported Aoexhibitimmunopotentiating™, immunomodulating and interferon like activities. The ethanolic extract was found ‘toinhibit cancer eels and endethelial cells progression sn The protective effect of Nigella grains a8 ‘nutraceuticals wns studied on the oxidative stress and ‘carcinogenesis induced by methylntrosourea in Sprague Dawley rats and it was found to produce about 80% Pak J. Biol Soi, 7 (4): 41-451, 2004 protection against methylnitrosoures-induced oxidative sites inflammatory response and carcinagenesi#! ‘The alecholic extract also showed the cytotoxic ‘activity and was found to cure oral eancers™. In a study, ‘crude gum, a fixed oil and two purified components of Nigella seed, thymoquinone and dithymoquinone were assayed insvivo for their cytotoxicity for several parental ‘aoa mull rug resistant hurnan tumor celles. Although fas much as 1% wit of the gum or oil was devoid of ceylotenicity. both tiymoguinone and dilhymoguinone ‘were found to be eytotoxie for several types of aman tumor cells". The proteins of Nigella sativa fractionated by ion-exchange chromatography were also found to ‘possess immunomodulatory effect. The effect of these proteins on the production of cytokines was further evaluated by using specific. enzyme-linked immunoserbant assay (ELISA). The results, however, showed that the fractionated Nigella sativa was less effective when compared with whole Nigella proteins”! ‘Topical application of the seed extract inhibited skin ‘areinogenesis in mice and intaperitncal administration (100 mg Ke body weight) delayed the onset of papilloma formatice”! The active principle of Nigella sativa seeds ‘containing certain fatty acids was stadied for anti-tumor faclvities against Eluich ascites carcinoma, Dalton’s Iymphoma ascites and Sareoma-I80 cells in viro and in vivo. The active principle showed complete inhibition in in vivo and 5(P6 eytotoncity in in vitro stain”. In mice bearing Ehrlich ascites carcinoma xenograft, thymoquinone (from volatile cil) significantly enhaneed the antitumor effect of ifosfamide (enslogue of ‘eyclophosphamide). There was also less weight less and lower mortality rate compared to ifosfamide single therapy, this thymoguinone was found to improve the therapeutic efficacy of ifosfamide by both decreasing ifesfamide-inveed nephrotexicty and improving its anti- tumor activity, In another study, thymoquinone inhibited the benzopyrene-induced —forestomacl, ‘carcinogenesis in mice, The possible modes of action were discussed to be through its antioxidant and anti- inflammatory activities coupled with enhancement of detexification process” Thymoquinene-indused —_eytotasicity was investigated in a study using canine osteosarcoma, its ‘isplatin-resstant variant. homan breast adenocarcincna, ‘uman ovarian adenocarcinoma and Macin-Darby eanine MDCK) call lines. Thymoquinone-inuved cytotoxicity ‘was determined using @ proliferation assay (MTT assay) and speptosis assays. Effects on tho cell eyele were determined using flow eytometry and thymaguinone was found to produce cell eyele ares 483 In another study, the aqueous and aleoholie extracts ‘of Nigella sativa alone or in combination with H,0, as an ‘oxidative stressor, were found tobe effective in-vitro in inactivating MCF-7 breast cancer cells” ‘The fresh aqueous extract augmented Natural Killer Cells (62.3%6) in developing eytotoxiity against YAC in vitro, Fresh aqueous extracts appeared to be more potent than old dried extracts or ethanolic extracts. Aqueous extract of Nigella sativa seeds was also found to significamly augment the splenic natural killer cells in generating estotonieity in mice against YAC tumor tangen™ Ta study using murine Cytomegalovinws as a model, intraperitoneal administration of oil _ substantially ‘decreased the viral load in liver and spleen. There was an increase in interferon-y, macrophages and CD4+T cells ‘and deerease in both namber and fanetion of NK cells. On day 10, the viru titer was undetectable in the spleen and liver of infected mice, while positive in controls" A fraction ofthe ethanolic extract of Nigella sativa seed was studied in mice against intraperitoncally implanted murine P388 leukemia and subcutaneously implanted Lewis lung carcinoma cell. The life span of treated mice ineeased by 133% as compared to dimethy1 sulphoxide-treated control mice. a- Hederin, a triterpene saponin isolated from this faction produced significant tumor inhibition rates; while, the underlying mechanisins) ‘of antitumor activity of @-Hederin remained 10 be established"! In areeent study, the stimulating effet of «-hederin ‘onthe release of nitic oxide and upregulation of inducible nitie oxide synthase gene expression in mouse macrophages were examined, Thus showing a mechanism responsible for its biological effects inching. its ‘antitumor activities ‘nether study, the anfi-tumor effect of ‘thymoguinone was investigated both insane invitro in male Swiss albino rats on fibrosarcoma indwed by 20+ ‘methylcholanthyene and it was found to inkibit wumor incidence and tumor burden significantly, The possible ‘modes of action were discussed as is antioxidant activity ‘and interference with DNA synthesis coupled with ‘enhancement of detoxification processes. In Effects on the nervous nervous system: Nigella saiva seeds revealed promising narcotic analgesic activity ‘mediated possibly through opioid receptors". The cil from the seeds exhibited CNS depressant and potent ‘analgesic effect. Tt was also found to potentiate pentoharbitone-indueed sloping time! ‘Aqnoon extract in mice revealed an analgesic effet, which peaked after 2 hours and sustained for 41. The Pak J. Biol Soi, 7 (4): 41-451, 2004 ‘oral administration of il dose- dependently suppressed dose-dependently the nociceptive response in the hot- plat test, tal-pinch test, acetic acid-induced writhing test and in the early phase of formalin test. Systemic administration of the main constituent of N. sativa seeds, thymoquinote, attenuated the nociceptive response in both eatly and late phases of formalin test ‘Results from wing diferent opioid receptor antagonists suggested that both the seed oil and thymoguinone produced antinociceptive effects through activation of ssuptaspinal and x- opioid receptor subtypes Jn another investigation, the nqueous and methanolic ‘extracts of Nigella sativa seeds produced an alteraion in the general behaviour pattems, significant reduction of spontansous motility, reduction in normal body temperature and significant analgesic action against hot plate and pressure tests, suggesting the CNS depressant totic!" Tin a more rooent study, thymoquinone was found to inhibit the oxidative stress leading to improvement in, animals having Experimental Allegic Encephalomyeltis, an autoimmune demyelinating disease of the central nervous system. Thus, suggesting the role of ‘hymoquinone in the treatment of Multiple Sclerosis Effects against microbials: The plant extact ancl its ‘constituents have been extersively studied for its their ‘antimicrobial effect against a wide range of bacterial, fungal and parasitic organisms, The methanolic extract of 1X sativa aceds was foun to exhibit anteplague action by potently inhibiting Streptococcts mutans, tus also preventing deta cares™: Alcoholic extract of the seeds showed antibacterial activity against Micrococcus pyogenes var. aureus!" Tt was also found to. possess ‘antibacterial activity. against Shigella dysenteriae, 5. sonnet, S. boyd, Vibrio. cholerae and. Escherichia ‘colt The ether extracts showed im vitro antimicrcbial activity against Gram-positive bacteria, eg Staphylococcus aureus, Oram-negative bacteria, eg Pseudomonas aeruginosa and Escherichia colt" In anole study itwas found to exhibit antibacterial activity especially against Bacillus pumilus, B. subiilis, Sirepococeus mutans, Staphylococcus tutea, Staph ‘aureus and Pseudomonas aeruginasal ‘The essential ol from the seeds of sativa in pure state and at various dilutions was screened in vitro against some mierobes and helminths and it was foun 0 ‘exhibit promising activity agninat Shigella flesner# "It ‘also showed anthelmintic activity against hook werms ‘and nodular worms The ethanolic extract was found to ‘easess anticestodal effect in children) The essential oil showed in vitro anifingal activity against Aspergillus 444 species and Curvularia lunata* as well es against pathogenic yeast Candida albicans. Tn our seoent study, we found tit the aqueots extract of the seeds possess potent in-vivo antifungal activity’ against (Candidiasis in mice”, ‘The protective effect of Nr sativa seed extract and its ‘main constituent, thymoquinone, was studied on mouse cells infected with schistosomiasis, Bone marrow cells and spleen cells were wed in vivo and i vitro respectively 10 ‘evaluate the protective effects of these compounds ‘against chromosomal aberrations induced as a result of| schistevonniasis!™, Effets against inflammation: Tracitonaly the fied cil ‘expressed from seeds of Nigella sativa is of great use in skin eruptions, paralysis, hemiplegia, back pain, ‘theumatism and related inflammatory diseases on external ‘application, The erude fined oil of Nigella sativa and Uymoguinone bolt have been foun! to inhibit the ‘icosanoid generation and membrane lipid perexidation, through the inhibition of eyclooxygense. and lipexyenase patviays of arachidonate metabolism, ts responsible forthe ani-inflammatory activity" ‘The aqueous extract was investigated for ant inflammatory, analgesie and antipyretic activities in animal ‘models. The antiinflammatory effect was demonstrated by its inhibitery effect on carrageenan induced-paw ‘edema! and analgesic effect by significant increase in ‘hotplate reaction time in mioe. However, it showed no

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