Black seed

Black seed/Drug Interactions:

  • AnalgesicsAnalgesics: Based on animal study, polyphenols from Nigella sativa seeds decreased abdominal writhing and suppressed the nociceptive response (90). In animal study, aqueous and methanol extracts of defatted Nigella sativa seeds demonstrated analgesic activity, potentially by depressing the central nervous system (92). The analgesic and anti-inflammatory effects of an aqueous extract of Nigella sativa, Nigella sativa oil (166), and the constituent thymoquinone (166) have also been shown in other animal study (53).
  • AnthelminticsAnthelmintics: Nigella sativa extract or oil was shown to have antischistosomiasis effects (Schistosoma mansoni) in animal study and in vitro (167; 168; 169; 170), and antiparasitic effects against Aspiculuris tetraptera and Hymenolepis nana (171), Trichinella spiralis (172), fascioliasis (173), and others (unspecified) (174) in animal study.
  • Antianxiety agentsAntianxiety agents: Based on animal study, extracts of seeds of Nigella sativa had anxiolytic effects (27). Levels of 5-hydroxytryptamine (5-HT) and tryptophan were increased, and levels of brain 5-HIAA decreased significantly. In mice, anxiolytic activity of various constituents was shown when injected intraperitoneally (thymoquinone, a-pinene, p-cymene) (175).
  • Antiarthritic agentsAntiarthritic agents: Based on animal study, thymoquinone had antiarthritic effects; serum nitric oxide, urea, and creatine levels were reduced (28).
  • Antiasthma drugsAntiasthma drugs: Based on animal study, thymoquinone induced the relaxation of precontracted tracheal preparation (176). Improved pulmonary function tests and asthma symptoms have also been shown in clinical trials investigating the effect of an aqueous extract of Nigella sativa (3; 4).
  • AntibioticsAntibiotics: Several Nigella sativa extracts, as well as constituents such as thymoquinone, have been shown to exert antibacterial effects in animal study and in vitro (177; 178; 82; 12; 179; 10; 61; 174; 19; 180; 20; 102), against both Gram-negative bacterial isolates (178) and Gram-positive isolates (82; 16).
  • AnticholinergicsAnticholinergics: Based on animal study, atropine, mepyramine, and cyproheptadine had antagonistic effects against the volatile oil of black seed on the respiratory and cardiovascular systems (181; 113).
  • AnticoagulantsAnticoagulants: Based on in vitro study, the oil of Nigella sativa seed increased tissue-type plasminogen activator (t-PA) and t-PA antigen (182). Based on in vitro study, an extract of Nigella sativa seed oil inhibited platelet aggregation and blood coagulation (11). In male albino rats, Nigella sativa induced hyperfibrinogenemia, transient prothrombin time prolongation, thrombin time reduction, transient activated partial thromboplastin time (APTT) reduction, and an increase in the albumin level and ALT activity (183).
  • Anticonvulsant agentsAnticonvulsant agents: Based on clinical study, Nigella sativa seed had anticonvulsant effects in children already using antiepileptic agents (131). In animal study, thymoquinone reduced adverse effects associated with sodium valproate (175).
  • Antidiabetic agentsAntidiabetic agents: Improved glucose tolerance and reduced blood glucose has been shown in animal diabetic models (115; 48; 116; 117; 118; 119; 120; 121; 122; 123) and human study (124). Other improvements in diabetic animal models include increased serum insulin if lowered (48; 119; 122; 184), reduced serum insulin (117), and reduced glycated hemoglobin (123).
  • AntifungalsAntifungals: Based on in vitro study, Nigella sativa seed extract and oil had antifungal effects against Candida albicans and Trichophyton and Aspergillus species (12; 13; 14; 15; 16; 17; 18; 19; 20). In animal study, treatment with Nigella sativa oils reduced aflatoxicosis (185) and candidiasis (186).
  • AntihistaminesAntihistamines: Based on clinical trial, black seed oil reduced allergy severity (5; 187).
  • AntihypertensivesAntihypertensives: Based on animal study, Nigella sativa seed extract had hypotensive effects (50) as did the volatile oil of the seed (113). Based on randomized controlled trial, boiled extract of Nigella sativa reduced systolic blood pressure in otherwise healthy, mildly hypertensive patients (114).
  • Antilipemic agentsAntilipemic agents: Based on human study, black seed oil was shown to modulate lipid levels (5; 124). Based on animal study, Nigella sativa or thymoquinone has been shown to protect against induced increases in, or to reduce, triglyceride and cholesterol levels (66; 125; 126; 127; 74; 128; 129), to increase or decrease levels of HDL cholesterol (125; 126; 127; 128; 129) and to reduce fatty streaks, total cholesterol, and LDL cholesterol (130).
  • Antineoplastic agentsAntineoplastic agents: Based on laboratory studies, various constituents of Nigella sativa, such as thymoquinone (8; 39; 46) and alpha-hederin (79) induced cytotoxic and apoptotic or necrotic effects. Based on animal study, thymoquinone potentiated the antineoplastic effects of gemcitabine and oxaliplatin (188). Nigella sativa seeds in combination with Hemidesmus indicus root and Smilax glabra rhizome, or low concentrations of Nigella sativa extract (78; 189; 67), also induced similar effects.
  • Antiobesity agentsAntiobesity agents: Based on animal study, an herbal mixture containing black seed improved obesity and associated metabolic problems (104).
  • AntiprotozoalsAntiprotozoals: Nigella sativa seeds have been shown to exert anticestodal effects in humans (93) and animals. Based on in vitro study, an aqueous extract of Nigella sativa had antiprotozoal effects against the intestinal parasite Blastocystis hominis (190).
  • AntipyreticsAntipyretics: Based on animal study, the aqueous extract of Nigella sativa had antipyretic effects (53).
  • Antiretroviral agentsAntiretroviral agents: Based on animal study, black seed oil and thymoquinone reduced highly active antiretroviral therapy (HAART)-induced hyperinsulinemia (64) and suppressed production of reactive oxygen species (65).
  • Antiulcer agentsAntiulcer agents: Based on in vitro study, extracts of seeds of Nigella sativa had antibacterial effects against Helicobacter pylori (102).
  • AntiviralsAntivirals: Based on animal study, black seed oil had antiviral effects against murine cytomegalovirus (MCMV) (26). This effect coincided with an increase in serum level of interferon-gamma.
  • Brucellosis vaccineBrucellosis vaccine: Based on animal study, the ethanolic extract of the seeds of Nigella sativa and the volatile oil and polysaccharides extracted from the seeds had adjuvant effects with the brucellosis vaccine (191).
  • Cardiovascular agentsCardiovascular agents: In animal study, Nigella sativa reduced fatty streaks (130).
  • CisplatinCisplatin: Based on animal study, an extract of Nigella sativa protected against cisplatin-induced falls in hemoglobin levels and leukocyte counts (192), and thymoquinone, fixed oil, and ethanolic extract of black seed protected against cisplatin-induced nephrotoxicity (193; 73). Both showed significant protection.
  • CNS depressantsCNS depressants: Based on animal study, aqueous and methanol extracts of defatted Nigella sativa seeds had CNS depressant effects (92).
  • Cyclosporine ACyclosporine A: In animal study, thymoquinone protected against cyclosporine A-induced cardiotoxicity and oxidative stress (194; 40). Based on animal study, Nigella sativa had renoprotective effects against cyclosporine nephrotoxicity (195).
  • Cytochrome P450-metabolized agentsCytochrome P450-metabolized agents: Based on animal study, black seed oil alleviated depression of cytochrome P450 associated with carbon tetrachloride (196).
  • DiureticsDiuretics: Based on animal study, Nigella sativa seed extract increased diuresis and urinary excretion of Cl, Na, K, and urea (50).
  • DoxorubicinDoxorubicin: In animal study, thymoquinone protected against doxorubicin-induced cardiotoxicity (197; 198). Based on animal study, Nigella sativa had renoprotective effects against doxorubicin-induced hyperlipidemic nephropathy (74).
  • Fertility agentsFertility agents: Based on animal study, a hexane extract from black seed has been shown to inhibit conception (159).
  • Gastrointestinal agents, miscellaneousGastrointestinal agents, miscellaneous: Thymoquinone, a constituent of Nigella sativa, has been shown to protect against alcohol-induced gastric ulcers, perhaps due to its free-radical-scavenging activity (57; 199). Based on animal study, Nigella sativa oil protected against ethanol induced ulcer; mucin content and glutathione level were increased, and mucosal histamine was decreased (200; 199). Based on animal study, Nigella sativa protected against stress induced gastritis (201). In animal study, other gastroprotective effects included protective effects of thymoquinone against experimental colitis in rats, potentially due to its antioxidant effects (202); gastroprotective effects of an aqueous suspension of Nigella sativa on necrotizing agents-induced gastric ulcer (203); and gastroprotective activity of Nigella sativa oil and thymoquinone against gastric mucosal injury induced by ischemia/reperfusion (103).
  • GentamicinGentamicin: Based on animal study, Nigella sativa had renoprotective effects against gentamicin-induced nephrotoxicity (204; 205).
  • Hepatotoxic agentsHepatotoxic agents: Based on animal study, Nigella sativa and thymoquinone had hepatoprotective effects against bile duct ligation induced-liver injury (62), ischemia reperfusion (206), heavy metals (207), carbon tetrachloride (208; 209; 210; 211; 212; 213; 214; 215), Schistosomiasis mansoni (170), D-galactosamine (125), high cholesterol (216), sodium valproate (175), and diabetes-induced injury (121).
  • Hormonal agentsHormonal agents: Based on in vitro study, the combination of thymoquinone and hormones, such as testosterone, estrogen, and parathyroid hormones, inhibited the growth of LNCaP (prostate cancer) cells (217). In animal study, Nigella sativa increased the area of insulin immunoreactive beta-cells in diabetic rats over parathyroid hormone alone (218). A similar additive effect was seen for bone histomorphometry and mechanical strength (88).
  • IbuprofenIbuprofen: Based on in vitro study, thymoquinone had displacement effects against ibuprofen (219).
  • IfosfamideIfosfamide: Based on animal study, Nigella sativa had renoprotective effects against ifosfamide-induced nephrotoxicity (220).
  • ImmunosuppressantsImmunosuppressants: Based on animal study, treatment with Nigella sativa oil increased the phagocytic activity and phagocytic index of peritoneal macrophages and lymphocyte count in peripheral blood in diabetic hamsters (118). Nigella sativa also reversed the immunosuppression induced by lead and calcium in animal study (221). Based on laboratory study, a melanin extract from Nigella sativa L. may induce the expression of three cytokines (TNF-alpha, IL-6, and VEGF) that enhance immunogenicity and promote tumor regression (68). Black seed has also been shown to modulate the immune system by altering levels of inflammatory mediators (6). In an animal allergic asthma model, Nigella sativa oil reduced peripheral blood eosinophil count, IgG1 and IgG2a levels, cytokine profiles, and inflammatory cells in lung tissue (222). Based on animal study, the volatile oil of Nigella sativa seeds (NSVO) may act as a potential immunosuppressive agent (67).
  • Leukotriene receptor antagonistsLeukotriene receptor antagonists: Based on laboratory study, thymoquinone, a major constituent of black seed, potently inhibited the formation of leukotrienes in human blood cells (223).
  • LevodopaLevodopa: Based on in vitro study in SH-SY5Y human neuroblastoma cells, thymoquinone protected against levodopa toxicity (95).
  • Neurologic agentsNeurologic agents: Based on animal study, thymoquinone offered protection and cure against chronic relapsing experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis (83). In animal study, Nigella sativa and thymoquinone were neuroprotective following chronic toluene blue exposure (224; 225). Neuroprotective effects of Nigella sativa and thymoquinone were also shown in an experimental spinal cord injury model (101), a forebrain ischemia model (42), and an experimental allergic encephalomyelitis model (84).
  • NicotinamideNicotinamide: Based on animal study, black seed oil had hypoglycemic effects in diabetes mellitus induced by streptozotocin plus nicotinamide (226).
  • Nonsteroidal anti-inflammatory agents (NSAIDs), COX 2 inhibitorsNonsteroidal anti-inflammatory agents (NSAIDs), COX 2 inhibitors: Anti-inflammatory effects of thymoquinone have been shown in animal models, such as an allergic asthma model (reduced levels of leukotriene (LTB)4 and LTC4, and a decrease in Th2 cytokines and bronchoalveolar lavage fluid and lung tissue eosinophilia) (227; 228) a rheumatoid arthritis model (229), and others (53; 22). Black seed oil and its constituents, such as thymoquinone, decreased production of 5-lipoxygenase products, as shown in vitro (230; 231), and has decreased cytokine production (IL-5 and IL-13 but not IL-10) (232). Based on laboratory study, thymoquinone, a major constituent of black seed, potently inhibited the formation of leukotrienes in human blood cells (223). Based on laboratory study, thymoquinone (TQ), in addition to other major constituents (dithymoquinone, thymohydroquinone, and thymol), may inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) activity (233).
  • OxytetracyclineOxytetracycline: Based on animal study, black seed had immunoprotective effects in oxytetracycline-treated pigeons (234).
  • OxytocicsOxytocics: Based on animal study, black seed has been shown to decrease or inhibit uterine contractions (132).
  • PentylenetetrazolPentylenetetrazol: Based on animal study, black seed oil reduced seizures associated with pentylenetetrazol (235).
  • Permeation enhancersPermeation enhancers: Based on in vitro study, black seed oil acted as a drug permeation enhancer across isolated rat skin (236).
  • Radioprotective drugsRadioprotective drugs: Based on animal study, Nigella sativa oil had radioprotective effects against hemopoietic damage and immunosuppression (96). Hemolysin antibody titers, delayed-type hypersensitivity reaction, leukopenia, and decreased plasma total protein and globulin concentrations and lymphoid follicles of spleen and thymus gland were normalized. In rats, Nigella sativa reduced irradiation-induced oxidative stress markers and increased antioxidant enzymes (237).
  • Renally eliminated agentsRenally eliminated agents: Based on animal study, Nigella sativa had renoprotective effects against ischemia-reperfusion injury of kidneys (71; 72), gentamicin-induced nephrotoxicity (204; 205), doxorubicin-induced hyperlipidemic nephropathy (74), ifosfamide-induced nephrotoxicity (220), cisplatin-induced nephrotoxicity (238; 193), heavy metals (207; 239), and cyclosporine nephrotoxicity (195). Serum urea and creatinine levels were reduced, as were the tubular necrosis score (71); oxidative stress (204; 195; 205); suppressed doxorubicin-induced proteinuria, albuminuria, and urinary excretion of N-acetyl-beta-D-glucosaminidase (74); and renal microsomal lipid peroxidation, gamma-glutamyl transpeptidase, xanthine oxidase, recovery of renal glutathione content and antioxidant enzymes, and reversal in the enhancement of blood urea nitrogen, serum creatinine, renal ornithine decarboxylase activity, and DNA synthesis (240).
  • ReserpineReserpine: Based on animal study, reserpine had antagonistic effects against the volatile oil of black seed on the respiratory and cardiovascular systems (181; 113).
  • Respiratory agentsRespiratory agents: In human study, extract of Nigella sativa had antiasthmatic or respiratory effects (4; 2; 3). Based on animal study, thymoquinone decreased tracheal responsiveness and improved white blood cell counts in lung lavage of sensitized guinea pigs (241). Following pulmonary aspiration, oral Nigella sativa volatile oil reduced inflammatory pulmonary responses, such as peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar edema, alveolar exudate, alveolar macrophages, interstitial fibrosis, and granuloma and necrosis formation (242). There was also a reduction in the activity of inducible nitric oxide synthase and a rise in surfactant protein D in lung tissue. In guinea pigs, the oil had tracheal relaxant effects (243). Extracts of Nigella sativa have been shown to have tracheal relaxant effects in other animal models (244).
  • RotenoneRotenone: Based on in vitro study, thymoquinone had neuroprotective effects against rotenone toxicities (245).
  • Smooth muscle relaxantsSmooth muscle relaxants: In isolated rat epididymal vas deferens, thymoquinone had smooth muscle relaxant effects, perhaps by interfering with calcium (246). In guinea pigs, the oil had tracheal relaxant effects (243). Extracts of Nigella sativa have been shown to have tracheal relaxant effects in other animal models (244). Pretreatment with thymoquinone resulted in reduced contraction of isolated rat pulmonary arterial rings (247). Nigellone decreased tracheal contraction in animal study (248).
  • WarfarinWarfarin: Based on in vitro study, thymoquinone has displacement effects against warfarin (219).

    • Black seed/Herb/Supplement Interactions:

  • AnalgesicsAnalgesics: Based on animal study, polyphenols from Nigella sativa seeds decreased abdominal writhing in the acetic acid-induced writhing test when given orally, suppressed the nociceptive response in the early and late phases of the formalin test when given orally and intraperitoneally, and reduced carrageenan-induced paw edema when given intraperitoneally (90). Also, aqueous and methanol extracts of defatted Nigella sativa seeds had analgesic activity, potentially by depressing the central nervous system (92). Analgesic and anti-inflammatory effects of an aqueous extract of Nigella sativa, Nigella sativa oil (166), and the constituent thymoquinone (166) have also been shown in other animal studies (53).
  • Antiarthritic herbs and supplementsAntiarthritic herbs and supplements: Based on animal study, thymoquinone had antiarthritic effects; serum nitric oxide, urea, and creatine levels were reduced (28).
  • Antiasthma herbs and supplementsAntiasthma herbs and supplements: Based on animal study, thymoquinone induced the relaxation of precontracted tracheal preparation (176). Improved pulmonary function tests and asthma symptoms have also been shown in human clinical trials investigating the effect of an aqueous extract of Nigella sativa (3; 4).
  • AntibacterialsAntibacterials: Several Nigella sativa extracts, as well as constituents such as thymoquinone, have exerted antibacterial effects in animal study and in vitro (177; 178; 82; 12; 179; 10; 61; 174; 19; 180; 20; 102), against both Gram-negative bacterial isolates (178) and Gram-positive isolates (82; 16).
  • Anticholinergic herbsAnticholinergic herbs: Based on animal study, atropine, mepyramine, and cyproheptadine had antagonistic effects against the volatile oil of black seed on the respiratory and cardiovascular systems (181; 113).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: Based on in vitro study, the oil of Nigella sativa seed increased tissue-type plasminogen activator (t-PA) and t-PA antigen (182). Based on in vitro study, an extract of Nigella sativa seed oil inhibited platelet aggregation and blood coagulation (11). In male albino rats, Nigella sativa induced hyperfibrinogenemia, transient prothrombin time prolongation, thrombin time reduction, transient activated partial thromboplastin time (APTT) reduction, and an increase in the albumin level and ALT activity (183).
  • AnticonvulsantsAnticonvulsants: Based on clinical study, Nigella sativa seed had anticonvulsant effects in children already using antiepileptic agents (131). In animal study, thymoquinone reduced adverse effects associated with sodium valproate (175). Nigella sativa may demonstrate interactions with herbs and supplements with similar effects.
  • AntifungalsAntifungals: Based on in vitro study, Nigella sativa seed extract and oil had antifungal effects against Candida albicans and Trichophyton and Aspergillus species (12; 13; 14; 15; 16; 17; 18; 19; 20). In animal study, treatment with Nigella sativa oils reduced aflatoxicosis (185) and candidiasis (186).
  • AntihistaminesAntihistamines: Based on clinical trial, black seed oil reduced allergy severity (5; 187).
  • Anti-inflammatory herbsAnti-inflammatory herbs: Anti-inflammatory effects of thymoquinone have been shown in animal models (227; 228), rheumatoid arthritis models (229), and others (53; 22). Black seed oil and its constituents, such as thymoquinone, decreased production of 5-lipoxygenase products, as shown in vitro (230; 231), and has decreased cytokine production (IL-5 and IL-13 but not IL-10) (232). Based on laboratory study, thymoquinone, a major constituent of black seed, potently inhibited the formation of leukotrienes in human blood cells (223). Based on laboratory study, thymoquinone (TQ), in addition to other major constituents (dithymoquinone, thymohydroquinone, and thymol), may inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) activity (233).
  • AntilipemicsAntilipemics: Based on human study, black seed oil was shown to modulate lipid levels (5; 124). Based on animal study Nigella sativa or thymoquinone has been shown to protect against induced increases in, or to reduce, triglyceride and cholesterol levels (66; 125; 126; 127; 74; 128; 129) and to increase or decrease levels of HDL cholesterol (125; 126; 127; 128; 129), and to reduce fatty streaks, total cholesterol, and LDL cholesterol (130).
  • AntineoplasticsAntineoplastics: Based on laboratory study, various constituents of Nigella sativa, such as thymoquinone (8; 39; 46) and alpha-hederin (79) have demonstrated cytotoxic and apoptotic or necrotic effects . Nigella sativa seeds in combination with Hemidesmus indicus root and Smilax glabra rhizome, or low concentrations of Nigella sativa extract (78; 189; 67), have also demonstrated similar effects.
  • Antiobesity herbs and supplementsAntiobesity herbs and supplements: Based on animal study, an herbal mixture containing black seed improved obesity and associated metabolic problems (104). Based on animal study, an herbal mixture (consisting of T. chebula, senae, rhubarb, aniseed, fennel, licorice, and black seed) improved obesity and associated metabolic problems (104). The effects of black seed monotherapy, however, are unclear.
  • AntioxidantsAntioxidants: Thymoquinone, a constituent of Nigella sativa, has been shown to protect against alcohol-induced gastric ulcers, perhaps due to its free-radical-scavenging activity (57). Incubation of erythrocytes with Nigella sativa has been shown to protect the cells against oxidative damage (23). Based on animal and in vitro study, Nigella sativa, thymoquinone, and other constituents had antioxidant effects (249; 250; 251; 84; 252; 253; 121; 170; 254; 216; 40; 255; 86; 256; 257; 258; 259; 260; 261; 262; 215; 199; 103; 75; 240; 263). Examples included reduced formation of hydroxyl radical and upregulation of the superoxide dismutase 1 (SOD1), catalase, and glutathione peroxidase 2 (GPX) enzymes (250; 101); decreased lipid peroxidation (264; 87; 25); regulated nitric oxide levels (84); free radical scavenging (256); iron chelation (25); and decreased malondialdehyde levels (251; 265; 101).
  • AntiparasiticsAntiparasitics: Nigella sativa seeds have been shown to exert anticestodal effects in humans (93) and animals. Based on in vitro study, aqueous extract of Nigella sativa had antiprotozoal effects against the intestinal parasite Blastocystis hominis (190). Nigella sativa extract or oil was shown to have antischistosomiasis effects (Schistosoma mansoni) in animal study and in vitro (167; 168; 169; 170) and antiparasitic effects against Aspiculuris tetraptera and Hymenolepis nana (171), Trichinella spiralis (172), fascioliasis (173), and unspecified others (174) in animal study.
  • AntipyreticsAntipyretics: Based on animal study, the aqueous extract of Nigella sativa had antipyretic effects (53).
  • Antiulcer herbs and supplementsAntiulcer herbs and supplements: Based on in vitro study, extracts of seeds of Nigella sativa had antibacterial effects against Helicobacter pylori (102).
  • AntiviralsAntivirals: Based on animal study, black seed oil had antiviral effects against murine cytomegalovirus (MCMV) (26). This effect coincided with an increase in serum level of interferon-gamma.
  • AnxiolyticsAnxiolytics: Based on animal study, extracts of seeds of Nigella sativa had anxiolytic effects (27). Levels of 5-hydroxytryptamine (5-HT) and tryptophan were increased, and levels of brain 5-HIAA decreased significantly. In mice, anxiolytic activity of various constituents was shown when injected intraperitoneally (thymoquinone, a-pinene, p-cymene) (175).
  • Cardiovascular herbs and supplementsCardiovascular herbs and supplements: In animal study, Nigella sativa reduced fatty streaks (130).
  • Cytochrome P450-metabolized herbs and supplementsCytochrome P450-metabolized herbs and supplements: Based on animal study, black seed oil alleviated depression of cytochrome P450 associated with carbon tetrachloride (196).
  • DiureticsDiuretics: Based on animal study, Nigella sativa seed extract increased diuresis and urinary excretion of Cl, Na, K, and urea (50).
  • Fertility agentsFertility agents: Based on animal study, a hexane extract from black seed has been shown to inhibit conception (159).
  • GalactagoguesGalactagogues: The galactogogue action of Nigella sativa have been discussed (55). Further details are lacking at this time.
  • Gastrointestinal herbs and supplementsGastrointestinal herbs and supplements: Thymoquinone, a constituent of Nigella sativa, has been shown to protect against alcohol-induced gastric ulcers, perhaps due to its free-radical-scavenging activity (57; 199). Based on animal study, Nigella sativa oil protected against ethanol induced ulcer, mucin content and glutathione level were increased, and mucosal histamine was decreased (200; 199). Based on animal study, Nigella sativa protected against stress-induced gastritis (201). In animal study, other gastroprotective effects include protective effects of thymoquinone against experimental colitis in rats, potentially due to its antioxidant effects (202); gastroprotective effects of an aqueous suspension of Nigella sativa on necrotizing agents-induced gastric ulcer (203); and gastroprotective activity of Nigella sativa oil and thymoquinone against gastric mucosal injury induced by ischemia/reperfusion (103).
  • Hemidesmus indicusHemidesmus indicus: Based on animal study, the combination of Nigella sativa, Hemidesmus indicus, and Smilax glabra offered protection against hepatocarcinogenesis (266).
  • Hepatotoxic herbs and supplementsHepatotoxic herbs and supplements: Based on animal study, Nigella sativa and thymoquinone had hepatoprotective effects against bile duct ligation induced-liver injury (62), ischemia reperfusion (206), heavy metals (207), carbon tetrachloride (208; 209; 210; 211; 212; 213; 214; 215), Schistosomiasis mansoni (170), D-galactosamine (125), high cholesterol (216), sodium valproate (175), and diabetes-induced injury (121). Nigella sativa may demonstrate interactions with herbs and supplements with similar effects.
  • Hormonal herbs and supplementsHormonal herbs and supplements: Based on in vitro study, the combination of thymoquinone and hormones, such as testosterone, estrogen, and parathyroid hormones inhibited the growth of LNCap (prostate cancer) cells (217). Nigella sativa may demonstrate interactions with herbs and supplements with similar effects. In animal study, Nigella sativa increased the area of insulin immunoreactive beta-cells in diabetic rats over parathyroid hormone alone (218). A similar additive effect was seen for bone histomorphometry and mechanical strength (88).
  • HypoglycemicsHypoglycemics: Improved glucose tolerance and reduced blood glucose have been shown in animal diabetic models (115; 48; 116; 117; 118; 119; 120; 121; 122; 123) and human study (124). Other improvements in diabetic animal models included increased serum insulin if lowered (48; 119; 122; 184), reduced serum insulin (117), and reduced glycated hemoglobin (123).
  • HypotensivesHypotensives: Based on animal study, Nigella sativa seed extract had hypotensive effects (50) as did the volatile oil of the seed (113). Based on a randomized controlled trial, boiled extract of Nigella sativa reduced systolic blood pressure in otherwise healthy, mildly hypertensive patients (114).
  • ImmunostimulantsImmunostimulants: Based on animal study, treatment with Nigella sativa oil increased the phagocytic activity and phagocytic index of peritoneal macrophages and lymphocyte count in peripheral blood in diabetic hamsters (118). Nigella sativa also reversed the immunosuppression induced by lead and calcium in animal study (221). Based on laboratory study, a melanin extract from Nigella sativa may induce the expression of three cytokines (TNF-alpha, IL-6, and VEGF), which enhance immunogenicity and promote tumor regression (68). Black seed has been shown to modulate the immune system by altering levels of inflammatory mediators (6).
  • ImmunosuppressantsImmunosuppressants: In an animal allergic asthma model, Nigella sativa oil reduced peripheral blood eosinophil count, IgG1 and IgG2a levels, cytokine profiles, and inflammatory cells in lung tissue (222). Based on animal study, the volatile oil of Nigella sativa seeds (NSVO) may act as a potential immunosuppressive agent (67).
  • IronIron: Based on animal study, consumption of black seeds increases iron status (267).
  • LycopeneLycopene: Based on in vitro study, a combination of selenomethione, lycopene, and thymoquinone had antiproliferative effects in cancer cells (268).
  • Neurologic herbs and supplementsNeurologic herbs and supplements: Based on animal study, thymoquinone offered protection and cure against chronic relapsing experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis (83). In animal study, Nigella sativa and thymoquinone were neuroprotective following chronic toluene blue exposure (224; 225). Neuroprotective effects of Nigella sativa and thymoquinone were also shown in an experimental spinal cord injury model (101), a forebrain ischemia model (42), and an experimental allergic encephalomyelitis model (84). Based on animal study, aqueous and methanol extracts of defatted Nigella sativa seeds had CNS depressant effects (92).
  • NicotinamideNicotinamide: Based on animal study, black seed oil had hypoglycemic effects in streptozotocin plus nicotinamide-induced diabetes mellitus (226).
  • Permeation enhancersPermeation enhancers: Based on in vitro study, black seed oil acted as a drug permeation enhancer across isolated rat skin (236).
  • Phyllanthus niruriPhyllanthus niruri: Based on human study a combination of Nigella sativa and Phyllanthus niruri extract resulted in a requirement of less analgesics and a reduction in sore throat in patients with acute tonsillopharyngitis (269).
  • Radioprotective agentsRadioprotective agents: Based on animal study, Nigella sativa oil had radioprotective effects against hemopoietic damage and immunosuppression (96). Hemolysin antibody titers, delayed-type hypersensitivity reaction, leukopenia, and decreased plasma total protein and globulin concentrations and lymphoid follicles of spleen and thymus gland were normalized. In rats, Nigella sativa reduced irradiation-induced oxidative stress markers and increased antioxidant enzymes (237).
  • Renally eliminated herbs and supplementsRenally eliminated herbs and supplements: Based on animal study, Nigella sativa had renoprotective effects (71; 72; 204; 205; 74; 220; 238; 193; 207; 239; 195). Serum urea and creatinine levels were reduced as was the tubular necrosis score (71) and oxidative stress (204; 195; 205).
  • Respiratory agentsRespiratory agents: In human study, extract of Nigella sativa had antiasthmatic or respiratory effects (4; 2; 3). Based on animal study, thymoquinone decreased tracheal responsiveness and improved white blood cell counts in lung lavage of sensitized guinea pigs (241). Following pulmonary aspiration, oral Nigella sativa volatile oil reduced inflammatory pulmonary responses, such as peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar edema, alveolar exudate, alveolar macrophages, interstitial fibrosis, and granuloma and necrosis formation (242). There was also a reduction in the activity of inducible nitric oxide synthase and a rise in surfactant protein D in lung tissue. In guinea pigs, the oil had tracheal relaxant effects (243). Extracts of Nigella sativa have been shown to have tracheal relaxant effects in other animal models (244).
  • SeleniumSelenium: Based on in vitro study, a combination of selenium and thymoquinone had antiproliferative effects in cancer cells (270; 268).
  • Smilax glabraSmilax glabra: Based on animal study, the combination of Nigella sativa, Hemidesmus indicus, and Smilax glabra offered protection against hepatocarcinogenesis (266).
  • Smooth muscle relaxantsSmooth muscle relaxants: In isolated rat epididymal vas deferens, thymoquinone had smooth muscle relaxant effects, perhaps by interfering with calcium (246). In guinea pigs, the oil had tracheal relaxant effects (243). Extracts of Nigella sativa have been shown to have tracheal relaxant effects in other animal models (244). Pretreatment with thymoquinone resulted in reduced contraction of isolated rat pulmonary arterial rings (247). Nigellone decreased tracheal contraction in animal study (248).
  • Uterine stimulantsUterine stimulants: Based on animal study, black seed has been shown to decrease or inhibit uterine contractions (132).

    • Black seed/Food Interactions:

  • Broad beanBroad bean: Supplementing broad bean (Vicia faba) or corn (Zea mays) meal protein with Nigella sativa cake protein increased the growth rate of rats, as well as serum protein and lipids (271).
  • CornCorn: Supplementing broad bean (Vicia faba) or corn (Zea mays) meal protein with Nigella sativa cake protein increased the growth rate of rats, as well as serum protein and lipids (271).
  • EggsEggs: Black cumin supplementation into the diet of the laying hen increased egg weight and decreased egg cholesterol (272).
  • HoneyHoney: Based on animal study, thymoquinone induced the relaxation of precontracted tracheal preparation; this was likely mediated by inhibition of lipoxygenase products of arachidonic acid metabolism or by nonselective blocking of the histamine and serotonin (176). The authors suggested that this supports the traditional use of black seeds in combination with honey to treat bronchial asthma. Also, in animal study the combination of honey and Nigella sativa increased protection against oxidative stress and carcinogenesis over Nigella sativa alone (262).
  • Iron-containing foodsIron-containing foods: Based on animal study, consumption of black seeds increased iron status (267).

    • Black seed/Lab Interactions:

  • Blood coagulationBlood coagulation: Based on in vitro study, an extract of Nigella sativa seed oil inhibited platelet aggregation and blood coagulation (11). In male albino rats, Nigella sativa induced hyperfibrinogenemia, transient prothrombin time prolongation, thrombin time reduction, and transient activated partial thromboplastin time (APTT) reduction (183).
  • Blood glucoseBlood glucose: Based on human study (124) and animal diabetic models, improved glucose tolerance and reduced blood glucose have been shown in animal diabetic models (115; 48; 116; 117; 118; 119; 120; 121; 122; 123; 142). Crushed seeds and oil lowered blood glucose in human study (273).
  • Blood pressureBlood pressure: Based on animal study, Nigella sativa seed extract had hypotensive effects (50), as did the volatile oil of the seed (113).
  • Blood urea nitrogenBlood urea nitrogen: Based on animal study, Nigella sativa reduced blood urea nitrogen (240).
  • CatecholaminesCatecholamines: Both Nigella sativa oil and thymoquinone improved norepinephrine, dopamine, and serotonin status in a diabetic animal model (251).
  • Cell countsCell counts: Based on human study, crushed seeds increased white blood cell counts (273). Based on animal study, the volatile oil of Nigella sativa seeds (NSVO) has been shown to induce immunomodulating effects (67). In an animal allergic asthma model, Nigella sativa oil reduced peripheral blood eosinophil count and inflammatory cells in lung tissue (222). Based on animal study, Nigella sativa injection decreased the reduced red blood cell count, white blood cell count, packed cell volume, and hemoglobin levels (274). Decreased leukocytes and platelets (142) and increased hematocrit (142) were shown in other animal studies.
  • CytokinesCytokines: Melanin, a constituent of Nigella sativa seed, has been shown to induce interleukin-8 (IL-8) (68), tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), and vascular endothelial growth factor (VEGF) (68) production. In an animal allergic asthma model, Nigella sativa oil reduced cytokine profiles (222).
  • Glycated hemoglobinGlycated hemoglobin: Based on animal study, thymoquinone or Nigella sativa reduced levels of glycated hemoglobin (275; 123).
  • Heart rateHeart rate: In isolated guinea pig hearts, Nigella sativa extract inhibited heart rate and contractability (58; 162).
  • Hormone levelsHormone levels: Based on in vitro study, the combination of thymoquinone and hormones, such as testosterone, estrogen, and parathyroid hormones, inhibited the growth of LNCap (prostate cancer) cells (217). In animal study, Nigella sativa increased the area of insulin immunoreactive beta-cells in diabetic rats over parathyroid hormone alone (218). A similar additive effect was seen for bone histomorphometry and mechanical strength (88).
  • ImmunoglobulinImmunoglobulin: In an animal allergic asthma model, Nigella sativa oil reduced IgG1 and IgG2a levels (222).
  • InsulinInsulin: Based on an animal diabetic model, Nigella sativa volatile oil increased the intensity of staining for insulin and preserved beta-cell numbers (276). In a similar model, thymoquinone improved levels of insulin (275). Other improvements in diabetic animal models include increased serum insulin if lowered (48; 119; 122; 184) and reduced serum insulin (117).
  • IronIron: Based on animal study, consumption of black seed increased iron status (267). Based on animal study, Nigella sativa fixed oil increased hemoglobin levels (145; 142) as did the crushed seed and oil in human study (273). In N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-injected rabbits, serum levels of iron of Nigella sativa treated animals was 276.3?10.71ng/dL (277).
  • Lipid panelLipid panel: Based on human study, black seed oil was shown to modulate lipid levels (5; 124). Based on animal study Nigella sativa or thymoquinone has been shown to protect against induced increases in or to reduce triglyceride and cholesterol levels (66; 125; 126; 127; 74; 128; 129; 142; 278); to increase or decrease levels of HDL cholesterol (125; 126; 127; 128; 129; 278); and to reduce fatty streaks, total cholesterol, and LDL cholesterol (130).
  • Liver enzymes: Liver enzymes: Based on animal study, Nigella sativa reduced liver enzymes (aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels) (206; 209; 211; 170), and IL-10 was increased (196). Based on animal study, Nigella sativa reduced gamma-glutamyl transpeptidase (GGT) (240). No changes in liver enzymes were found in some studies (145). In rats, an aqueous extract of Nigella sativa seeds resulted in increased serum gamma-glutamyltransferase (149), and in human study, the oil increased ALT, AST, GGT, and ALP, and the crushed seed increased GGT and ALP (273).
  • MineralsMinerals: Based on animal study, Nigella sativa seed extract increased diuresis and urinary excretion of Cl, Na, and K (50). Based on animal study, Nigella sativa injection decreased elevated serum K and Ca levels (274).
  • ProlactinProlactin: Based on human study, crushed seeds and oil reduced prolactin levels (273).
  • Prostate-specific antigenProstate-specific antigen: Based on in vitro study, thymoquinone decreased prostate-specific antigen levels (279).
  • Serum creatinineSerum creatinine: Based on animal study, Nigella sativa reduced levels of serum creatinine (71; 240; 28), but based on human study, serum creatinine was increased (280).
  • Serum ureaSerum urea: Based on animal study, Nigella sativa reduced levels of serum urea (71; 28).
  • Tissue-type plasminogen activatorTissue-type plasminogen activator: Based on in vitro study, the oil of Nigella sativa seed increased tissue-type plasminogen activator (t-PA) and t-PA antigen (182).
  • Trace elementsTrace elements: In N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-injected rabbits, serum levels of zinc, copper, and iron of Nigella sativa-treated animals were 155.3 ? 25.8, 234.8 ? 31.9, and 276.3 ? 10.71ng/dL, respectively (277).
  • Tubular necrosis scoreTubular necrosis score: Based on animal study, Nigella sativa reduced the tubular necrosis score (71).
  • Urinary N-acetyl-beta-D-glucosaminidaseUrinary N-acetyl-beta-D-glucosaminidase: Based on animal study, Nigella sativa suppressed doxorubicin-induced urinary excretion of N-acetyl-beta-D-glucosaminidase (74).
  • Urinary proteinUrinary protein: Based on animal study, Nigella sativa suppressed doxorubicin-induced proteinuria and albuminuria (74).
  • Xanthine oxidaseXanthine oxidase: Based on animal study, Nigella sativa reduced xanthine oxidase (240).