Presented By Name: Mohammad Akram RandhawaCountry: KSA

3rd International Conference and Exhibition on Traditional & Alternative Medicine

August 03-05, 2015 Birmingham, UK

In Association with

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A review of the dermatological effects and applications of Nigella sativa (Black seed)

Department of PharmacologyCollege of Medicine, Northern Border University

Arar, Saudi Arabia

الرحيم الرحمن الله بسم

Prof. Mohammad Akram Randhawa

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Introduction• Nigella sativa (N. sativa)

belongs to the family of Ranunculaceae

• A small shrub, commonly grows in Eastern Europe, Middle East & Western Asia.

• Its tiny seeds are known as “Habba Al-Sauda” in Arabic and “Black Seed” in English.

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Introduction (Cont.)• Its seed & oil were

frequently used in ancient remedies (Unani, Ayurveda, Chinese and Arabic).

• Many uses of N. sativa seed are mentioned by Ibne-Sina (980-1037) in his famous book Al-Qanoon fi el-Tib.

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Introduction (Cont.)Active components isolated from seeds of N. sativa include: Thymoquinone, thymohydroquinone, dithymoquinone, thymol, carvacrol, nigellimine-N-oxide, nigellicine, nigellidine and alpha-hederin.

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Introduction (Cont.)• N. sativa seed & its ingredients possess many

pharmacological effects: • Immune stimulation, anti-inflammatory,

antioxidant, hypoglycemic, antihypertensive, antiasthmatic, antibacterial, antifungal, antiviral, antiparasitic, and anticancer effects.

• Reviewed by Randhawa & Alghamdi (2002), Ali & Blunden (2003), Padhye et al (2008).

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Introduction (Cont.)• This presentation is aimed to review the

dermatological effects and applications of N. sativa reported in the literature.

• Relevant studies have been categorized as: o Antibacterial, antifungal, antiviral,

antiparasitic. o Effect on wound healing, psoriasis, acne

vulgaris, vitiligo and skin cancer.o Percutaneous absorption, cosmetic

applications and cutaneous side effects.

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Antibacterial • Topozada et al (1965), were first to report anti-

bacterial effect of phenolic fraction of N. sativa oil.• El-Fatatry (1975) isolated thymohydroquinone from

N. sativa & showed its activity against gram(+) microorganisms, including Staph aureus.

• Later, ether extract of N. sativa was reported to possess inhibitory effect on both gram (+) (Staph aureus) and gram (-) bacteria (Pseudomonas aerogenosa and E. coli)

• (Hanafi & Hatem, 1991) .

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Antibacterial (Cont.)• Ether extract of N. sativa also showed synergistic

or additive effect with:• Streptomycin, gentamycin, spectinomycin,

erythromycin, tobramycin, doxycycline, chloramphenicol, nalidixic acid, ampicillin, lincomycin and co-trimoxazole

• (Hanafi & Hatem, 1991) .• N. sativa extracts also demonstrated promising

results against multi-drug-resistant Staph aureus and Pseud aeruginosa.

• (Morsi, 2000;; Salman et al, 2005).

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Antibacterial (Cont.)• Staphylococci usually

cause pustular skin lesions.

• Pustular skin infections in neonates were treated with N. sativa extract as good as topical mupirocin (Rafati et al, 2014).

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Antifungal• Hanafi & Hatem (1991) were first to

demonstrate inhibitory effect of ether extract of N. sativa against Candida albicans.

• Later, ether extract of N. sativa was reported to inhibit growth of Candida albican yeasts in experimental animal infections (Khan et al, 2003).

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Antifungal (Cont.)• Thymoquinone, a component of N. sativa,

inhibited opportunistic fungi:• Aspergillus niger, Fusarium solani,

Scopulariopsis brevicaulis• Comparable to amphotericin-B • (Randhawa et al, 2005; Aljabre, 2005;

Alqorashi et al, 2007).

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Antifungal (Cont.)Dermatophytes cause skin lesions, commonly called as ‘Tinea’ on different parts of the body.

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Antifungal (Cont.)• Ether extract of N. sativa inhibited

dermatophytes isolated from sheep skin infection (Kader et al, 1995).

• Aljabre et al (2005) reported moderate effect of thymoquinone against clinical isolates of three main groups of dermatophytes: Trichophyton, Epidermophyton & Microsporum.

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Antifungal (Cont.)• Taha et al (2010) found antifungal effect of

thymoquinone, thymohydroquinone & thymol against clinical isolates of molds, yeasts and dermatophytes.

• Recently, N. sativa extract has been shown to inhibit the growth of Madurella mycetomatis, an important causative fungus of mycetoma (Elfadil et al, 2015).

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Antiviral• N. sativa oil given intraperitoneally for 10 days

to mice infected with murine cytomegalovirus, eradicated the virus from liver and spleen.This action was possibly related to increase in M-phi & CD4 +ve T cells and INF-gamma (Salem & Hossain, 2000).

• N. sativa extract was also shown to possess protease inhibitory effect on human immune deficiency virus (Ma C, 1994).

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Antiparasitic• In experimentally infected Schistosoma mansoni

mice, the antischistosomal activity of N. sativa oil was found to be comparable to prazequantel.

• When given in combination with prazequantel there was potenciation of its effect (Mahmoud et al, 2002).

• Moreover, N. sativa seed showed biocidal activity against miracidia, cercariae and adult worms of Schistosoma mansoni, as well as an inhibitory effect on egg-laying of adult female worms

• (Mohamed et al, 2005).

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Antiparasitic (Cont.)• Ointment from alcoholic

extract of N. sativa seeds, applied daily for 15 weeks, significantly reduced lesion size and inflammation of cutaneous leishmaniasis produced experimentally in mice

• (Bafghi et al, 2011).

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Wound healing• N. sativa seed and its oil were found to

promote wound healing in farm animals (Ahmed et al, 1995).

• Recently, using human gingival fibroblast as a monolayer, aqueous extract of N. sativa was shown to exhibit free radical scavenging activity and induced gingival fibroblast proliferation

• Associated with accelerated wound closure activity despite its non-significant effect on collagen synthesis (Ab Rahman et al, 2014).

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Psoriasis• Antipsoriatic activity of

ethanolic extract of N. sativa seed was evaluated:

o In vivo by using mouse tail model for psoriasis

o In vitro by SRB Assay (Sulphorhodamine-B Assay), employing HaCaT human keratinocyte cell lines.

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Psoriasis (Cont.)• In mouse tail model, epidermal differentiation

produced by the extract, positive control (tazarotene) and negative control was 71.36 ± 2.64%, 90.03 ± 2.00%n and 17.30 ± 4.09%, respectively.

• In keratinocyte cell lines, IC50 values for antiproliferant activity of the extract and positive control (asiaticoside) were 239 μg/ml and 20.13, respectively (Dwarampudi et al, 2012).

Acne vulgaris• In a clinical study, N. sativa

oil lotion 10% significantly reduced mean lesion count of papules and pustules after 2 months of therapy (Abdul-Ameer & Al-Harchan, 2010).

• Results were attributed to antimicrobial, anti-inflammatory and immunomodulatory effects of N. sativa.

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Vitiligo• Lyophilized seed extract of N.

sativa and thymoquinone, showed significant darkening of isolated melanophores of wall lizard skin .

• Pigment cells responded by dispersion of melanin,

• which was antagonized by anticholinergic drugs, atropine and hyoscine,

• and potentiated by an anticholinestrase agent, neostigmine

• (Ali & Meitei, 2011).

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Vitiligo (Cont.)• In a randomized clinical study, N. sativa oil

applied to vitiligo lesions twice daily for six months, significantly decreased vitiligo area scoring index (Ghorbanibirganet al, 2014).

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Hypersensitivity reactions• N. sativa extract ,

thymoquinone and nigellone) were shown to counter the manifestations of allergic reactions

• and inhibit histamine release from mast cells

• (Chakravorty, 1993).

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Hypersensitivity reactions (Cont.)• In a clinical study, Nigella, Betamethasone

and Eucerin ointments were applied topically twice daily for 4 weeks in new cases of hand eczema.

• Nigella and Betamethasone showed rapid improvement in hand eczema and quality of life, as compared to Eucerin (Yousefi , 2013).

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Skin cancer• (El-Kadi & Kandil, 1986) were first to suggest

anticancer activity of N. sativa when they found enhancement of natural killer (NK) cell activity in advanced cancer patients receiving N. sativa seed.

• Regarding skin, Solami et al (1991) reported that topical application of N. sativa and Crocus sativus extracts delayed onset and reduced number of papillomas induced in mice by dimethylbenz [a] anthracene (DMBA) / croton oil.

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• Thymoquinone was also shown to possess antitumor activity in tumor cell lines:

o Mouse keratinocytes, papilloma (SP-1) and spindle-17 carcinoma cells (Gali-Muhtasib et al, 2004).

o Squamous cell carcinoma (SCC VII) and fibrosarcoma (FsaR) (Ivankovic et al, 2006).

Skin cancer (Cont.)

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Skin cancer (Cont.)• Thymoquinone and diosgenin, the active

ingredients obtained from N. sativa and fenugreek (Trigonella foenumgraecum), respectively, showed potent bioactivity against squamous cell carcinoma in vitro.

• Thymoquinone and diosgenin, reduced tumor volume & mass & increased apoptosis in a mouse xeno-graft model, in vivo

• (Das et al, 2012).

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Skin cancer (Cont.)• Thymoquinone inhibited migration and

metastasis of mouse melanoma cells, when studied by:

• In vitro cell migration assay• In vivo mouse melanoma model• Ahmad et al (2013)

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Percutaneous absorption• N. sativa oil was shown to increase absorption

of model lipophilic drug (carvedilol), using excised rat abdominal skin.

• Increased permeability of carvedilol was possibly due to higher content of linoleic acid and other unsaturated fatty acids in N. sativa oil (Amin et al, 2008 and 2010).

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Cosmetic application• Emulsions with N. sativa seedcakes was

shown to reduce skin irritation and improve skin hydration as compared to placebo.

• Authors suggested the potential use of seedcakes in anti-aging, moisturizing, mitigating, and protective cosmetics due to their antioxidant and anti-inflammatory activities (Ratz-Łyko et al, 2015).

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Cutaneous side effects• Contact dermatitis developed after the

application of ointment made from the N. sativa seed oil (Zedlitz et al, 2002).

• Bullous drug eruption with sub-epidermal detachment and necrosis of the epidermal surface was reported in a 53 year old woman after two weeks of applying N. sativa oil to her skin (Gelot, et al 2012)

• These reactions could be due to impurities in commercial black seed oil.

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Conclusions• Research articles on N. sativa seed and

its ingredients strongly indicate to their pharmacological potential on skin for:

Microbial & parasitic infections, psoriasis, acni, vitiligo, hypersensitivity reactions & squamous cell carcinoma

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Conclusions (Cont.)• There is possibility for the development

of new drugs for topical therapies from N, sativa seed, its oil and active components.

• Laboratory and clinical studies are needed to evaluate the efficacy of such preparations.

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Thanks a lot

Traditional Medicine-2016Website: http://traditionalmedicine.conferenceseries.com/

Meet the eminent gathering once again at

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October 03-05, 2016