Abstract

General Background: Antibiotic resistance has emerged as a major global health crisis in recent decades, driven by the rise of multi-drug resistant pathogens. Specific Background: As conventional antibiotics become less effective, there is growing interest in exploring natural sources, such as medicinal plants, for novel antimicrobial agents. Knowledge Gap: Despite the traditional use of Nigella sativa in various cultures, the precise mechanisms underlying its antimicrobial properties remain inadequately understood. Aims: This mini-review aims to highlight the potential of Nigella sativa seeds and oil as promising antimicrobial agents, focusing on their bioactive compounds and therapeutic applications. Results: Findings indicate that the therapeutic potential of N. sativa is largely attributed to thymoquinone and other key constituents, including linoleic acid, nigellone, nigilline, melanthin, and trans-anethole, which exhibit diverse pharmacological activities such as antimicrobial, anti-inflammatory, antioxidant, and gastroprotective effects. Novelty: This review underscores the relevance of N. sativa as a safe, natural alternative in antimicrobial therapy, rooted in traditional medicine yet supported by emerging scientific evidence. Implications: Future research should focus on elucidating the molecular mechanisms of N. sativa’s bioactivity and isolating specific active compounds to facilitate drug development against resistant pathogens.

Highlights:

1. Rising antibiotic resistance demands alternative antimicrobial sources.
2. Nigella sativa shows therapeutic potential via thymoquinone and key compounds.
3. Supports future drug development from natural, plant-based bioactive agents.

Keywords: Nigella sativa; Black seed ; Antibacterial; Antibiotics resistance

Introduction

Surely, antibiotics, the marvelous drugs of the 20th century, have successively miniature the human mortality and morbidity during their golden period (from 1940s to 1980s) [1]. However, pathogens have gradually developed resistance to these antibiotics. Recently, the antibiotics resistance has become a serious global health interest, with a huge economic burden on the community by increasing the cost of the treatment and raises the rates of hospitalization, particularly in the developing countries which already suffers from economic crises, poor sanitation and misuse of antibiotic drugs [2]. So far, it turns out that the development of new antibiotics, which are costly and time-consuming process, has become useless, as pathogens rabidly develop resistance to these new antibiotics. This has led to an increasing interest in searching for effective alternatives for the current antibiotics with different mode of action on microbes. Hence, medicinal plants appeared to be the best alternative source for new antimicrobial drugs [3]. Since the dawn of man’s evolution, plants have been used as traditional folk medicine for curing various diseases ailments [4].Traditionally, medicinal plants have been used in the formulation of herbal drugs due to their relative safety as compared to allopathic medicines [5]. In literature, numerous studies reported that some plant’s photochemical compounds have potent antimicrobial activity, such as Phenolics, flavonoids, alkaloids, terpenoids, saponins, tannins, anthraquinones, among others; which may kill the bacteria or fungal cells by inhibiting the growth, affect on cellular membrane permeability, interference with some metabolic processes and modulating the signal transduction or gene expression [6].The Medical plants have been a major source of therapeutic agent since ancient times to cure human disease. The World Health Organization (WHO) estimated that up to 80% of people still rely on herbal remedies for their health care [7]. Accordingly, with the urgent need for new antimicrobial drugs, the efforts toward innovate new antibiotics must behaves different approaches and get benefit from the hidden treasures of medicinal plants. This mini-review highlights the significance of this Nigella sativa plant product as an alternative and promising source for new antimicrobial drugs.

The Nigella sativa, is an annual flowering plant, which is a member of the Ranunculaceae family [8], can be found all over the world but grows mainly in Eastern Europe, Middle East, and Western Asia [9], It’s native to Turkey, Pakistan and Iran It is a small shrub with tapering green leaves and rosaceous white and purplish flowers. Its fruit contains tiny dark black in color seeds [10]. The plant produces small black seeds that are flat, trigonous, and angular in appearance, about 2 to 3.5 mm in length, and 1 to 2 mm in width [11]. In addition, these dark gray- or black-colored seeds are similar in appearance to sesame seeds [12] and are thought to be the most impressive part of the plant in terms of their valuable health impacts [13].

Nigella Sativa seeds, a medicinal herb frequently known as black seed and its oil has been used for their medicinal, aromatic or flavoring properties since ancient times in different civilizations [14]. In the worship of Islam, the Nigella Sativa seeds has been given a great importance because of its number of usage. Depend on the religion it is one of the greatest healing plants. The Islamic prophet Muhammad once stated that the black seed can heal every disease except death [15]. The seeds, which have two kinds of oil, fixed and essentials [16], also contain other things such as proteins, alkaloids, and saponins [17]. Much of the biological activity of the seeds has been shown due to the presence of thymoquinone [18] , which is the major component of the essential oil but also present in the fixed oil. They have a very low degree of toxicity [19]. Many studies such as Ali and Blunden (2003) has shown that taking either the seed extract or its oil will not induce significant toxicity or adverse effects on liver or kidney functions [20].Therefore, this study proves that N. sativa seed or oil are safe to be used with no significant toxicological or adverse effect [21]. Many studies were interested in this scope such as the seeds of the N. sativa locally known as “Kalonji” which has been used in traditional [22] and alternative medicine for the treatment of a variety of diseases, for example, diarrhea and asthma [23]. Also, many ancient cultures especially in Asia such as Arabian and African countries used black seed oil in various allergies treatment [24]. Avicenna, most famous for his volumes called [The Canon of Medicine], refers to Nigella as the seed that stimulates the body's energy and helps recovery from fatigue and dispiritedness Of all the plant organs it is only the seeds which attracted most of the researchers [25].

Figure 1.

Result and Discussion

Properties and Composition of Nigella sativa seeds

Nigella sativa seeds are black externally and white internally, small, dicotyledonous, angular, trigonus and regulose-tubercular, having typical dimensions of 2–3.5 mm by 1–2 mm. The microscopic analysis of seed powder reveals the presence of brown-black parenchymatous cells and oil globules [26]. .Interestingly, these tiny seeds are rich in bioactive and chemical compounds. In general, it contains about 32-40% fixed oils, 0.4-0.45% volatile oil 8-9 types of essential amino acids beside some vitamins, and carbohydrates [27]. In addition, some interesting derivatives of alkaloids, steroids, saponins, terpenes, monoterpenes and phenolic compounds were isolated from the black seed [28]. Among these pure compounds of pharmacological benefits isolated from the black seed are nigellicine, nigellicimine, nigellicimine N-oxide, carvone, thymoquinone, thymol and many more [29]. Many of the pharmacological activities mentioned above have been attributed to quinone constituents in the seed [30]. The wealth, complex, and diverse chemical compounds involved in the seeds of Nigella sativa may provide exceptional opportunity for development and innovation of new health promoting medication including antimicrobial drugs.

Active material is that extracted by ethyl alcohol and cold water for

the black seeds (Nigella sativa) contain flavonids, alkaloids, thymoquinone and tannins [31], While hot water and ethanol extracts of Nigella sativa contain alkaloids, saponins, flavonoids, tannins, glycosides, terpins and steroids , these composition showed in table [32].

The essential oil isolated from N. sativa has functional importance owing

to its rich profile of volatiles, which include thymoquinone, thymol, dithymoquinone, α-Pinene, β-Pinene, p-Cymene and thymohydroquinone [33]. p-Cymene and thymoquinone have been demonstrated to be the principal bioactive ingredients among all the components isolated from black cumin seed essential oil [34] , this composition are showing in Figure(2) and table (2).

Thymoquinone especially Nigellon is the carbonyl polymer of thymoquinone and has a medicinal property that includes antimicrobial, antitumor, antiviral, anti-inflammatory, reduction blood sugar, muscle relaxation and anti oxidation [35].

Figure 2.Chemical structures of the selected bioactive compounds found in N. sativa seed and seed essential oil.

Uses of seeds and oil of N. sativa

-Traditional medicinal uses

In different folk medicine systems, a range of medicinal benefits have been ascribed to N. sativa’s seeds and oil. Especially, Muslims give great importance to the plant and recognize it as one of the greatest healing medicaments owing [36]. Black seeds are used as a carminative, aromatic, stimulant, diuretic, anthelmintic, galactagogue and diaphoretic, they are used as a condiment in curries. A tincture prepared from the seeds is useful in indigestion, loss of appetite, diarrhea, dropsy, amenorrhea, dysmenorrhea and in the treatment of worms and skin eruptions. Externally the oil is used as an antiseptic, to arrest vomiting, seeds are roasted and given internally [37].

-Therapeutic Uses

Nigella sativa seeds have been frequently used in folk medicine for treatment of various diseases [38]. Several scientific studies have been conducted by the researchers to evaluate the biological and pharmaceutical effects of seed and seed oil of N. sativa, Such pharmaceutical and therapeutic properties can be attributed to the presence of different bioactive constituents, especially the main bioactive compound, thymoquinone [39].

Nigella sativa seeds and oil an Antibacterial Effect

Due to growing microbial resistance against synthetic antibiotics; there is need to explore new plant bioactives or plant extracts as natural and safer alternative antimicrobial agents to treat microbial infections. Numerous studies indicated that seeds of Nigella sativa and oil were tested and examined for effectiveness against several bacterial isolates, with distilled water as control. A clear zone of inhibition of growth was observed in the case of Staphylococcus aureus, the development of which is owing to the two important bioactive ingredients of N. sativa—thymoquinone and melanin [40].

In another study indicated that Oils extracted from N. sativa showed significant antibacterial effect against multidrug-resistant Staphylococcus aureus isolated from wounded diabetic and burn patients from Southeast Nigeria [41]. Oil of Nigella sativa revealed effective antibacterial activity against considerable number of methicillin resistant and coagulase negative Staphylococcus aureus, safety of that oil was examined, and there was no cytotoxic influence on the proliferation of gingival fibroblasts [42]. Another study showed that the black seed oil was recommended to be used as an antimicrobial agent in food production to prevent spoilage. Based on the results that showed that this oil at 2.0% concentration was able to inhibit the growth of twenty-four pathogenic, spoilage and lactic acid bacteria [43].

Ethanol and n-hexane extracts of the black seeds recorded remarkable

dose dependent antibacterial effects against different gram-positive and

gram-negative strains, namely Bacillus cereus, Bacillus subtilis, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumonia and Salmonella typhmurium. However, no antibacterial activity detected against Pseudomonas aeruginosa and Enterobacter aerogens [44]. Methanol and water extract of the black seed reported remarkable antibacterial efficacy towards for many types of bacteria such as Streptococcus pyogene, Pseudomonas aeruginosa, Klebsiella pneumonia, and Proteus vulgaris, the greater antibacterial effect was against the gram-positive bacteria [45].

An active principle isolated from seeds of Nigella sativa called thymoquinone showed a broad spectrum of activity against different gram-positive and gram negative bacteria, standard isolates namely Bacillus cereus, Listeria monocytogene, Enterococcus faecalis, Micrococcus luteus NCIMB 8166, Staphylococcus aureus ATCC 25923, Staphylococcus epidermidis CIP 106510, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 35218 Salmonella enteric, serovar typhmurium ATCC 14028, Vibrio lginolyticus ATCC 33787 and Vibrio paraheamolyticus ATCC 17802, thymoquinone was able to prevent bacterial biofilm formation [46]. The antibacterial activity of the black seed was also evaluated in-vivo, a groups of male mice were infected with Staphylococcus aureus and Escherichia coli, and subjected to varied doses of methanol, chloroform and essential oil of the black seed. All extracts and oil revealed significant dose dependent antibacterial effects compared with the positive control group which administered gentamicin [28]. Another study showed that saponin compounds Isolate from N. sativa (seeds) showed significant inhibiting effect on the growth of some bacteria, which include: Staphylococcus aureus, Bacillus subtilis, Salmonella typhi, Klebsiella pneumoniae, Proteus vulgaris and Pseudomonas aeruginosa [47].

Many experiment was conducted to test in vitro the effect of active materials that extracted by cold water and Ethyl Alcohol for the black seeds N. sativa on inhibition growth of Escherichia coli, S. aureus, Pseudomonas aeruginosa, Enterobacter, Proteus, Klebsiella for its clinical importance due to the cause of numerous disease. The experiment proved the extracts of Nigella sativa; contain Flavonids, alkaloids, thymoquinone and tannins, showed effective inhibition growth of these microorganisms and the highest inhibition effect was against the growth of Enterobacter[31].

Thymoquinone and thymohydroquinone compounds that’s extract from N. sativa seeds have antibacterial activity and their activity could be potentiated by antibiotics especially in case of S. aureus[48].

Conclusion

Index indicates that N. sativa seeds and oil have a potential medicinal value and are relatively safe to clean out. In Future research should focus on the mechanisms by which N. sativa seeds medically effected and understand its mechanism of bioactivity and diagnostic the active components that have medicinal effectiveness.

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