# Nigella Plants – Traditional Uses, Bioactive Phytoconstituents, Preclinical and Clinical Studies

**Authors:** Bahare Salehi, Cristina Quispe, Muhammad Imran, Iahtisham Ul-Haq, Jelena Živković, Ibrahim M. Abu-Reidah, Surjit Sen, Yasaman Taheri, Krishnendu Acharya, Hamed Azadi, María del Mar Contreras, Antonio Segura-Carretero, Dima Mnayer, Gautam Sethi, Miquel Martorell, Ahmad Faizal Abdull Razis, Usman Sunusi, Ramla Muhammad Kamal, Hafiz Ansar Rasul Suleria, Javad Sharifi-Rad

PMC · DOI: 10.3389/fphar.2021.625386 · Frontiers in Pharmacology · 2021-04-26

## TL;DR

This review explores the traditional uses, bioactive compounds, and health benefits of Nigella plants, especially Nigella sativa, and highlights the need for more clinical research.

## Contribution

The paper provides a comprehensive review of Nigella's phytochemicals and pharmacological effects, emphasizing the need for standardized clinical trials.

## Key findings

- Nigella seeds are rich in linoleic acid and bioactive compounds like thymoquinone.
- Nigella sativa is the most studied species and shows potential as a functional food ingredient.
- More clinical trials are needed to standardize its use and understand long-term effects.

## Abstract

Nigella is a small genus of the family Ranunculaceae, which includes some popular species due to their culinary and medicinal properties, especially in Eastern Europe, Middle East, Western, and Central Asia. Therefore, this review covers the traditional uses and phytochemical composition of Nigella and, in particular, Nigella sativa. The pharmacological studies reported in vitro, in vivo, and in humans have also been reviewed. One of the main strength of the use of Nigella is that the seeds are rich in the omega-6 fatty acid linoleic acid and provide an extra-source of dietary phytochemicals, including the bioactive thymoquinone, and characteristics saponins, alkaloids, and flavonoids. Among Nigella species, N. sativa L. is the most studied plant from the genus. Due to the phytochemical composition and pharmacological properties, the seed and seed oil from this plant can be considered as good candidates to formulate functional ingredients on the basis of folklore and scientific knowledge. Nonetheless, the main limations are that more studies, especially, clinical trials are required to standardize the results, e.g. to establish active molecules, dosage, chemical profile, long-term effects and impact of cooking/incorporation into foods.

## Linked entities

- **Chemicals:** linoleic acid (PubChem CID 5280450), thymoquinone (PubChem CID 10281), saponins (PubChem CID 6540709)
- **Species:** Nigella sativa (taxon 555479), Nigella (taxon 3443)

## Full-text entities

- **Genes:** Ggt1 (gamma-glutamyltransferase 1) [NCBI Gene 116568] {aka GGLUT, Ggt, Ggtp}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, Ppargc1a (PPARG coactivator 1 alpha) [NCBI Gene 83516] {aka LRPGC1, PGC-1v, PGCvf, PGCvf-1, PGCvf1, Ppargc1}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, Afp (alpha-fetoprotein) [NCBI Gene 24177], Becn1 (beclin 1) [NCBI Gene 114558] {aka Beclin1}, Cat (catalase) [NCBI Gene 24248] {aka CS1, Cas1, Cat01, Catl, Cs-1}, AGT (angiotensinogen) [NCBI Gene 183] {aka ANHU, SERPINA8, hFLT1}, Casp3 (caspase 3) [NCBI Gene 25402] {aka CPP32-beta, Lice, Yama}, Lipe (lipase E, hormone sensitive type) [NCBI Gene 25330] {aka HSL, REH}, Ucp1 (uncoupling protein 1) [NCBI Gene 24860] {aka Ucp, Ucpa, Uncp}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, Cat (catalase) [NCBI Gene 12359] {aka 2210418N07, Cas-1, Cas1, Cs-1}, Got2 (glutamic-oxaloacetic transaminase 2) [NCBI Gene 25721] {aka ASPATA, mAAT}, PCNA (proliferating cell nuclear antigen) [NCBI Gene 5111] {aka ATLD2}, GCG (glucagon) [NCBI Gene 2641] {aka GLP-1, GLP1, GLP2, GRPP}, TPO (thyroid peroxidase) [NCBI Gene 7173] {aka MSA, TDH2A, TPX}, UCP1 (uncoupling protein 1) [NCBI Gene 7350] {aka SLC25A7, UCP}, Casp1 (caspase 1) [NCBI Gene 25166] {aka Ice, Il1bc, p45}, Egfr (epidermal growth factor receptor) [NCBI Gene 24329] {aka ERBB1, ErbB-1, Errp}, Lep (leptin) [NCBI Gene 16846] {aka ob, obese}, Mlxipl (MLX interacting protein-like) [NCBI Gene 58805] {aka ChREBP, Mlx, WS-bHLH, Wbscr14, bHLHd14}, PPARD (peroxisome proliferator activated receptor delta) [NCBI Gene 5467] {aka FAAR, NR1C2, NUC1, NUCI, NUCII, PPARB}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, PRKAA1 (protein kinase AMP-activated catalytic subunit alpha 1) [NCBI Gene 5562] {aka AMPK, AMPK alpha 1, AMPKa1}, Gsr (glutathione-disulfide reductase) [NCBI Gene 116686], Slc2a4 (solute carrier family 2 member 4) [NCBI Gene 25139] {aka Glut4}, Glb1 (galactosidase, beta 1) [NCBI Gene 316033], PTPN1 (protein tyrosine phosphatase non-receptor type 1) [NCBI Gene 5770] {aka PTP1B}, INSR (insulin receptor) [NCBI Gene 3643] {aka CD220, HHF5}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, Ache (acetylcholinesterase) [NCBI Gene 83817], p53-ps (Wistar clone pR53P1 p53 pseudogene) [NCBI Gene 301300], FOS (Fos proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 2353] {aka AP-1, C-FOS, p55}, Bcl2l1 (Bcl2-like 1) [NCBI Gene 24888] {aka Bcl-xl, Bcl2l, Bclx, bcl-X}, Slc17a5 (solute carrier family 17 (anion/sugar transporter), member 5) [NCBI Gene 235504] {aka 4631416G20Rik, 4732491M05, AST, ISSD, NSD, SD}, ADIPOQ (adiponectin, C1Q and collagen domain containing) [NCBI Gene 9370] {aka ACDC, ACRP30, ADIPQTL1, ADPN, APM-1, APM1}, Gusb (glucuronidase, beta) [NCBI Gene 24434] {aka Ac2-223, Gus-s}, IL23A (interleukin 23 subunit alpha) [NCBI Gene 51561] {aka IL-23, IL-23A, IL23P19, P19, SGRF}, Plin1 (perilipin 1) [NCBI Gene 25629] {aka PERIA, Plin}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468] {aka CIMT1, FPLD3, GLM1, NR1C3, PPARG1, PPARG2}, Mapk14 (mitogen activated protein kinase 14) [NCBI Gene 81649] {aka CRK1, CSBP, CSPB1, Csbp1, Csbp2, Exip}, Bcl2 (BCL2, apoptosis regulator) [NCBI Gene 24224] {aka Bcl-2}, CAT (catalase) [NCBI Gene 847], AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, Lep (leptin) [NCBI Gene 25608] {aka OB, obese}, Nup62 (nucleoporin 62) [NCBI Gene 18226] {aka D7Ertd649e, Nupc1, p62}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Sirt1 (sirtuin 1) [NCBI Gene 309757] {aka Sir2}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, Slc2a2 (solute carrier family 2 member 2) [NCBI Gene 25351] {aka GTT2, Glut2}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, PNLIP (pancreatic lipase) [NCBI Gene 5406] {aka PL, PNLIPD, PTL}, Hpgds (hematopoietic prostaglandin D synthase) [NCBI Gene 54486] {aka H-PGDS, Ptgds2}, Il10 (interleukin 10) [NCBI Gene 25325] {aka IL10X, If2a}, SIRT1 (sirtuin 1) [NCBI Gene 23411] {aka SIR2, SIR2L1, SIR2alpha}, HMOX1 (heme oxygenase 1) [NCBI Gene 3162] {aka HMOX1D, HO-1, HSP32, bK286B10}, Pparg (peroxisome proliferator-activated receptor gamma) [NCBI Gene 25664] {aka PPARgamma2}
- **Diseases:** infarct (MESH:D007238), insomnia (MESH:D007319), hematuria (MESH:D006417), kidney injury (MESH:D007674), ND (MESH:C537849), amnesia (MESH:D000647), cardiac complications (MESH:D006331), Psoriasis (MESH:D011565), scorpion stings (MESH:D065008), snake bites (MESH:D012909), vitiligo lesions (OMIM:606579), nasal (MESH:D009668), itching (MESH:D011537), RA (MESH:D001172), mitochondrial oxidative damage (MESH:D028361), left ventricular hypertrophy (MESH:D017379), HT (MESH:D050031), -cancer (MESH:D009369), trachoma (MESH:D014141), respiratory symptoms (MESH:D012818), allergy (MESH:D004342), Hypotensive (MESH:D007022), runny nose (MESH:D000086722), malaria (MESH:D008288), hyperglycemic (MESH:D006944), tachycardia (MESH:D013610), hyperglycemia (MESH:D006943), rhinosinusitis (MESH:D000092562), Metabolic Disorders (MESH:D008659), asthma (MESH:D001249), cognitive deficit (MESH:D003072), hepatocellular carcinoma (MESH:D006528), cardiovascular diseases (MESH:D002318), toxicity (MESH:D064420), hyper- (MESH:D007589), breast cancer (MESH:D001943), bacterial diseases (MESH:D001424), BP (MESH:D006973), sneezing attacks (MESH:D012912), Rheumatic Artritis (MESH:D012216), Reproductive System Disorders (MESH:D060737), Skin Diseases (MESH:D012871), Diabetes (MESH:D003920), weight loss (MESH:D015431), eczematous lesions (MESH:D017443), hypercholesterolemic (MESH:D006938), tinnitus (MESH:D014012), learning and memory impairments (MESH:D007859), proinflammatory cytokine (MESH:D000080424), vitiligo (MESH:D014820), breast carcinogens (MESH:D061325), Hypercholesterolemia (MESH:D006937), fatty streak (MESH:D058226), sexual tonic (MESH:D050035), myocardial infarct (MESH:D009203), rheumatoid artritis (MESH:D011695), abdominal pain (MESH:D015746), headaches (MESH:D006261), mucosal congestion (MESH:D002311), endothelial dysfunction (MESH:D014652)
- **Chemicals:** beta-elemene (MESH:C445979), T3 (MESH:D014284), ATP (MESH:D000255), n-hexane (MESH:C026385), beta-carotene (MESH:D019207), phenol (MESH:D019800), iron oxide (MESH:C000499), p-cymene (MESH:C007210), sodium chloride (MESH:D012965), H2O2 (MESH:D006861), rhamnocitrin (MESH:C541117), fat (MESH:D005223), TBARS (MESH:D017392), isoproterenol (MESH:D007545), water (MESH:D014867), aspirin (MESH:D001241), silymarin (MESH:D012838), Alkaloids (MESH:D000470), trans-Cinnamic acid (MESH:C029010), 1,2-epoxy-menth-4(8)-ene (-), pyrogallol (MESH:D011748), diethylnitrosamine (MESH:D004052), sinapic acid (MESH:C073734), steroid (MESH:D013256), cycloartenol (MESH:C100089), atorvastatine (MESH:D000069059), TG (MESH:D014280), fructose (MESH:D005632), hederin (MESH:D009828), unsaturated fatty acids (MESH:D005231), charcoal (MESH:D002606), carbohydrates (MESH:D002241), oleic acid (MESH:D019301), nitrogen (MESH:D009584), protocatechuic acid (MESH:C009091), omega-6 fatty acid (MESH:D043371), Betamethasone (MESH:D001623), kalopanaxsaponin I (MESH:C117027), nigellidine-4-O-sulfite (MESH:C531293), leucine (MESH:D007930), starch (MESH:D013213), free fatty acids (MESH:D005230), Saponins (MESH:D012503), Cu (MESH:D003300), Chlorogenic acid (MESH:D002726), hesperidin (MESH:D006569), higenamine (MESH:C012348), nigeglanine (MESH:C493028), ferulic acid (MESH:C004999), Zn (MESH:D015032), NAD+ (MESH:D009243), Quercitrin (MESH:C012526), terpene (MESH:D013729), Fe (MESH:D007501), kalopanaxsaponin A (MESH:C460644), 2,5-dihydroxybenzoic acid (MESH:C010925), beta-sitosterol (MESH:C025473), glucose (MESH:D005947), syringic acid (MESH:C001945), alpha-thujene (MESH:C000590711)
- **Species:** Garidella (genus) [taxon 555464], Nigella ciliaris (species) [taxon 555470], Amycolatopsis orientalis (species) [taxon 31958], Nigella arvensis (wild fennel, species) [taxon 342649], Homo sapiens (human, species) [taxon 9606], Nigella damascena (jack-in-the-green, species) [taxon 3444], Rattus norvegicus (brown rat, species) [taxon 10116], Nigella (genus) [taxon 3443], Garidella nigellastrum (species) [taxon 555465], Oryctolagus cuniculus (domestic rabbit, species) [taxon 9986], Nigella orientalis (species) [taxon 555476], Mus musculus (house mouse, species) [taxon 10090], Nigella oxypetala (species) [taxon 555477], Nigella segetalis (species) [taxon 555480], Nigella elata (species) [taxon 555473], Nigella glandulifera (species) [taxon 1439910], Nigella stellaris (species) [taxon 555481], Nigella sativa (black-caraway, species) [taxon 555479]
- **Cell lines:** T47D — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0553), HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027), 3T3-L1 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0123), MCF-7 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0031), SiHa — Homo sapiens (Human), Human papillomavirus-related cervical squamous cell carcinoma, Cancer cell line (CVCL_0032), HeLa — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0030), A-549 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_0023), C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU)

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC8107825/full.md

## References

227 references — full list in the complete paper: https://tomesphere.com/paper/PMC8107825/full.md

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Source: https://tomesphere.com/paper/PMC8107825