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Avicenna Journal of Phytomedicine logoLink to Avicenna Journal of Phytomedicine
. 2016 Jan-Feb;6(1):9–20.

Gastrointestinal effects of Nigella sativa and its main constituent, thymoquinone: a review

Farzaneh Shakeri 1, Zahra Gholamnezhad 1, Bruno Mégarbane 2, Ramin Rezaee 3, Mohammad Hosein Boskabady 1,*
PMCID: PMC4884214  PMID: 27247918

Abstract

Gastrointestinal (GI) diseases affect a large number of people all over the world. Uncontrolled acid secretion and occurrence of gastric ulcers are common disorders of GI tract which pose serious problems to human health. Many synthetic drugs have been used to treat GI disorders but a definite cure has not been discovered so far and the available medications cause several side effects.

Nigella sativa (N. sativa) (Ranunculacea) has several therapeutic effects which are attributed to its constituents like nigellicine, nigellidine, thymoquinone, dithymoquinone, thymol and carvacrol. Several beneficial pharmacological properties of this plant such as anti-oxidant, anti-bacterial, anti-histaminic, anti-hypertensive, hypoglycemic, anti-fungal, anti-inflammatory, anti-cancer and immunomodulatory effects were reported and different therapeutic properties such as reliving bronchial asthma, jaundice, hydrophobia, paralysis, conjunctivitis, piles, skin diseases, anorexia, headache, dysentery, infections, obesity, back pain, hypertension and gastrointestinal problems, have been described for the seeds of N. sativa and its oil.

The present review provides a detailed summery of scientific researches regarding gastrointestinal effect of N. sativa and its main constituent, thymoquinone.

Key Words: Nigella sativa, Gastrointestinal disease, Thymoquinone

Introduction

Gastrointestinal diseases refer to conditions involving the esophagus, stomach, small intestine, large intestine, rectum, liver, gallbladder and pancreas. Symptoms of gastrointestinal disorders include pain, heartburn, dyspepsia, abdominal distension, nausea, vomiting, bloating, constipation and diarrhea. Among these, functional and motility disorders are the most common conditions seen in clinical practice and among the general population. The prevalence of these disorders in western countries is about 10-20%. Gastrointestinal diseases are chronic conditions which need long term medication and decrease the quality of life (Drossman, 1993). Commonly used drugs have several side effects like osteoporosis, disturbance in small intestine flora, kidney stones, anemia and increased chance of occurrence of drug-induced diseases such as gastric cancer. Therefore, due to the side effects of conventional medicine, the use of natural products in the treatment of various diseases has been in the center of attention in the last few decades.

Herbal medicine has been traditionally used for the treatment of different ailments. Nigella sativa (N. sativa) is used as an important drug in the traditional medicine like Unani and Ayurveda (Goreja, 2003 ▶; Sharma et al., 2005 ▶). Almost 80% of the populations of developing countries rely mainly on herbal medicine in primary medical therapy (Mantle et al., 2000 ▶). Medicinal plants are the source of enormous drugs and many important drugs were derived directly or indirectly from plants or from molecules of plant origin.

N. sativa, commonly known as black seed or black cumin, is an annual flowering plant from the family of Ranunculaceae, which is native to southern Europe, North Africa and Southwest Asia. N. sativa seeds include oil, protein, carbohydrate, fiber, saponin, moisture and the oil extracted from N. sativa is mostly consisted of linoleic acid, oleic, dihomolinoleic acid, palmitic acid stearic acid, myristic acid, stroles and eicodadienoic acid (El-Tahir and Bakeet, 2006 ▶).

Based on the use of N. sativa in folk medicine as a natural remedy for a number of diseases, scientists have studied its effects on conditions such as asthma (Boskabady et al., 2010 ▶), hypertension (Dehkordi and Kamkhah, 2008 ▶), diabetes (Bamosa et al., 2010 ▶) and inflammation (Chehl et al., 2009 ▶). Moreover, this herb is known to have antioxidant (Burits and Bucar, 2000 ▶), analgesic and anti-pyretic (Al-Ghamdi, 2001 ▶), anti-schistosomiasis (Mohamed et al., 2005 ▶), anti-fungal (Islam et al., 1989 ▶), anti-bacterial (Morsi, 1999 ▶), anti-convulsant (Raza et al., 2008 ▶), anti-cancer (Mahmoud and Torchilin, 2013), hepatoprotective (Kanter et al., 2005a) and Neuroprotective activities (Khazdair, 2015 ▶). In addition, it showed healing potential in gastrointestinal disturbances (Al Mofleh et al., 2008 ▶).

In last three decades, numerous researches have been done to identify plant-derived natural substances and understand the mechanisms of their pharmacological actions. N. sativa extract increases the activity of antioxidant enzymes (catalase, glutathione peroxidase, and glutathione-s-transferase) and acts as a free radical scavenger. As an anti-cancer agent, its effects such as modulation of the activities of molecular targets including p53, p73, PTEN, STAT3, PPAR-g, activation of caspases, and generation of ROS have been demonstrated. It also suppresses inflammatory mediators, leukotrienes, prostaglandins, and B cell-mediated immune response while balances Th1/ Th2 responses and potentiates T cell and natural killer cell-mediated immune responses (Gholamnezhad et al., 2014 ▶), as an anti-inflammatory and immunomodulatory agent. In this regard, several studies demonstrated that N. sativa has anti-cancer, hepatoprotective, anti-bacterial, anti-schistosomiasis, anti-inflammatory and antioxidant activities in gastrointestinal system (Gholamnezhad et al., 2015 ▶).

In this review, the gastrointestinal effects of N. sativa and thymoquinone (TQ) were reviewed.

Methods

To collect the related data on gastrointestinal effects of N. sativa and its main constituent, TQ, online literature resources including Medline, Pubmed, Science Direct, Scopus, and Google Scholar websites was checked from 1989 to 2015.

Gastrointestinal effects

Anti-cancer effect

Colorectal cancers (development of cancer in the colon or rectum) start as a polyp – a growth that starts in the inner lining of the colon or rectum and progresses toward the center. The preventive effect of N. sativa oil on rat colon cancer induced by 1,2-dimethylhydrazine was investigated. The animals were divided into four groups: Group 1 served as control; Group 2 received oil at post-initiation stage; Group 3 received oil at the initiation stage and Group 4 received 0.9% saline and oil from the beginning until the end of the study. The results of this study showed that N. sativa oil significantly reduced the total number of aberrant crypt foci in the post-initiation stage (group 2) whereas it showed no significant inhibitory effect on initiation stage (group 3). The results indicated that N. sativa oil has potent preventive effect on colon carcinogenesis in the post-initiation stage (Salim and Fukushima, 2003 ▶).

The preventive effect of TQ, the main constituent of N. sativa on HCT-116 human colorectal cancer cells was evaluated. The results showed that TQ is a potent agent against colon cancer cells and triggers apoptosis via a p53-dependent mechanism (Gali-Muhtasib et al., 2004 ▶). On the other hand, another study revealed that TQ has no effect against HEp-2 cancer cells (Rooney and Ryan, 2005 ▶).

The effect of TQ on pancreatic cancer cells and mucin 4 (MUC4) expressions was evaluated. MUC4 is expressed in pancreatic cancer and it contributes to the regulation of differentiation, proliferation, metastasis, invasiveness, migration, and motility of malignant cells (Chaturvedi et al., 2007 ▶; Singh et al., 2004 ▶). The results showed that TQ has cytotoxic effects against pancreatic cancer cell line FG/COLO357 and down-regulated MUC4 expression through JNK and p38 MAPK pathways in a dose (0–100 µmol/L) and time-dependent manner (Torres et al., 2010 ▶).

Also, another study reported that pretreatment of pancreatic cancer cells with TQ (25 Mmol/L) for 48 h followed by gemcitabine or oxaliplatin, reduced growth of cancer cells (Banerjee et al., 2009 ▶).

The effect of TQ (4 mg/kg/day) on diethylnitrosamine -induced hepatic carcinogenesis in rats was also studied. Findings documented that TQ could inhibit the development of DENA-induced liver cancer via decreasing oxidative stress and preserving the activity and expression of antioxidant enzymes (Sayed-Ahmed et al., 2010 ▶).

The anti-cancer effects of N. sativa and TQ were summarized in Table 1.

Table 1.

Anti cancer effect of N. sativa and thymoquinone in GI tract

Plant preparation Experimental model Effect Reference
N. Sativa oil Colon cancer aberrant crypt foci were induced using1,2-dimethylhydrazine Reduced total number of aberrant crypt foci (Salim and Fukushima, 2003)
Thymoquinone HCT-116 human colorectal cancer cells Triggered apoptosis via a p53-dependent mechanism (Gali-Muhtasib et al., 2004)
Thymoquinone Pancreatic cancer cells Cytotoxicity of pancreatic cancer cell line FG/COLO357M
Down regulated MUC4 expression through JNK and p38 MAPK pathways		 (Torres et al., 2010)
Thymoquinone Pancreatic cancer cells Reduced growth of cancer cells (Banerjee et al., 2009)
Thymoquinone Diethylnitrosamine induced hepatic carcinogenesis Reduced oxidative stress
Preserved the activity and expression of antioxidant enzymes 		(Sayed-Ahmed et al., 2010)
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Hepatoprotective effect

The protective effect of N. sativa (0.2 mL/kg, intraperitoneal: i.p.) against hepatic ischemia/reperfusion injury was investigated in rats. Levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH), total antioxidant capacity (TAC), catalase (CAT), total oxidative status (TOS), oxidative stress index (OSI) and myeloperoxidase (MPO) were measured. The results showed that N. sativa has a potential effect against hepatic ischemia/reperfusion injury and could act as a potent antioxidant agent (Yildiz et al., 2008 ▶).

In another study, the effects of N. sativa (0.2 mL/ kg, i.p.) on cholestatic liver injury were evaluated in rats. The authors found that N. sativa has a preventing effect on cholestatic liver injury in rats. The results also suggested that the reduction of neutrophil infiltration and oxidative stress in the liver was probably responsible for this protective effect (Coban et al., 2010 ▶).

In addition, the protective effect of N. sativa seeds (5% of the diet weight) against lead acetate-induced liver toxicity was documented in male rats. N. sativa seeds caused significant elevation in AST, improved biochemical and histopathological profiles and reduced damage areas (Farrag et al., 2007 ▶).

The protective effects of N. sativa oil (0. 2 mL/kg, i.p.) and Urticadioica oil (2 mL/kg, i.p.) on carbon tetrachloride (CCl4)-induced liver toxicity were studied in rats. Findings showed that N. sativa and U. dioica reduced lipid peroxidation and liver enzymes, and enhanced antioxidant defense system activity in CCl4-treated rats (Kanter et al., 2005a ▶).

The effect of TQ (10 mg/kg, orally) on hepato-renal dysfunction, CYP3A1 and spermidine/spermine N-1-acetyl-transferase gene expression induced by renal ischaemia/reperfusion was evaluated in rats. According to this study, TQ has a protective action on renal ischaemia/reperfusion-induced damage via an antioxidant mechanism and could decrease CYP3A1 and SSAT gene expression (Awad et al., 2011 ▶).

The protective effect of TQ against tert-butyl hydroperoxide toxicity was evaluated in isolated rat hepatocytes. The results showed that pre-treatment of hepatocytes with 1 mM TQ reduced the leakage of cytosolic enzymes, ALT and AST (Daba and Abdel-Rahman, 1998 ▶).

Oral administration of a single dose (100 mg/Kg) of TQ to male Swiss albino mice resulted in a protective effect against CCl4-induced hepatotoxicity which was probably due to the antioxidant property of TQ (Nagi et al., 1999 ▶).

In another study, the protective effect of TQ (4.5, 9 and 18 mg/kg, i.p.) on Aflatoxin B1 -induced liver toxicity was evaluated in mice. Findings of this study showed that TQ significantly decreased AST, ALT, ALP and MDA levels. This protective effect may be mediated through increased resistance to oxidative stress as well as reduction in lipid peroxidation (Nili-Ahmadabadi et al., 2011 ▶).

Thymoquinone showed protective effects against lipopolysaccharide -induced endotoxemia due to its anti-inflammatory, anti-apoptotic and antioxidant activities (Helal, 2010 ▶).

TQ (10 mg/kg, oral) protective effect on sodium fluoride-induced hepatotoxicity and oxidative stress in rats was shown as it improved the antioxidant status and reduced the alterations in biochemical parameters. This protective effect was perhaps due to the ability of TQ to antagonize increased lipid peroxidation (LPO) and in turn stabilizing the integrity of the cellular membranes and decreasing the leakage of liver enzymes (Abdel-Wahab, 2013 ▶). Also, it was shown that TQ (50 mg/kg body weight) significantly inhibited tamoxifen-induced hepatic glutathione depletion and normalized the activity of SOD (Suddek, 2014 ▶).

TQ (0.5, 1 and 2mg/kg/day, oral) combated against acetaminophen-induced hepatotoxicity and decreased acetaminophen-induced hepatotoxicity in a dose-dependent manner as evidenced by reduction in serum ALT activities. Hepatoprotective effect of TQ was probably mediated by increased resistance to oxidative and nitrosative stress and improved mitochondrial energy production (Nagi et al., 2010 ▶).

In a clinical study, the effects of ethanolic extracts of N. sativa, Zingiber officinale (Z. officinale) and their mixture were evaluated in patients with hepatitis C virus (HCV) infection. Patients were divided into five groups: I) Healthy subjects, II) HCV control; III) HCV patients receiving a capsule containing 500 mg N. sativa extract twice daily; IV) HCV patients receiving a capsule containing 500 mg Z. officinale extract twice daily and V) HCV patients receiving a capsule containing 500 mg Z. officinale and 500 mg N. sativa extracts twice daily. The results showed that ethanolic extracts of N. sativa and Z. officinale had a significant effect in HCV patients as shown by a decrease in viral load and restoration of liver functions (Adel et al., 2013 ▶).

The hepatoprotective effects of N. sativa and TQ were summarized in Table 2.

Table 2.

Hepatoprotective effect of N. sativa and thymoquinone

Plant preparation Experimental model Effect Reference
N. Sativa Hepatic ischemia–reperfusion injury Reduced levels of liver enzymes
Antioxidant activity		 (Yildiz et al., 2008)
N. Sativa Cholestatic liver injury Reduced neutrophil infiltration
Reduced oxidative stress		 (Coban et al., 2010)
N. sativa seed Lead acetate induced liver toxicity Increased AST (Farrag et al., 2007)
N. sativa oil Trinitrobenzenesulphonic acid (TNBS)-induced colitis Increased CAT activity
Decreased LDH activity, TNF-α, IL-1β, IL-6		 (Emekli-Alturfan et al., 2011)
N. sativa oil Carbon tetrachloride (CCl4) induced liver toxicity Reduced lipid peroxidation and liver enzymes,
Increased antioxidant defense system activity		 (Kanter et al., 2005a)
Ethanolic extracts Hepatitis C virus (HCV) infection Decreased viral load (Adel et al., 2013)
Thymoquinone Tert-butyl hydroperoxide (TBHP) induced liver toxicity Reduced leakage of cytosolic enzymes, ALT and AST (Daba and Abdel-Rahman, 1998)
Thymoquinone Carbon tetrachloride (CCl4) induced liver toxicity Antioxidant properties (Nagi et al., 1999)
Thymoquinone Aflatoxin B1 (AFB1) induced liver toxicity Reduced AST, ALT, ALP and MDA levels (Nili-Ahmadabadi et al., 2011)
Thymoquinone Sodium fluoride-induced hepatotoxicity Antagonize the increased LPO
Reduced the leakage of liver enzymes		 (Abdel-Wahab, 2013)
Thymoquinone Tamoxifen induced liver toxicity Inhibited glutathione depletion
Normalized the activity of SOD		 (Suddek, 2014)
Thymoquinone Hepatorenal dysfunction induced by renal ischaemia-reperfusion Reduced damage via an antioxidant mechanism
Reduced of CYP3A1 and SSAT gene expression		 (Awad et al., 2011)
Thymoquinone Acetaminophen induced hepatotoxicity Reduced in ALT activity (Nagi et al., 2010)
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Anti-bacterial and anti-schistosomiasis effects

The effect of N. sativa seed (0%, 1%, 2% and 3% of diet) on performance, intestinal Escherichia coli (E. coli) colonization and jejunal morphology in laying hens was evaluated. The results showed that ileal E. coli numeration reduced with 1% N. sativa. However, the best intestinal health indices were obtained following administration of 2% N. sativa (Boka et al., 2014 ▶).

The effect of TQ (10 mg/kg, i.p.) against bacterial translocation and inflammatory responses induced by mechanical intestinal obstruction was studied in rats. The results indicated that TQ decreased inflammatory cytokines, oxidative damage, bacterial translocation and improved intestinal barrier function in rats with intestinal obstruction (Kapan et al., 2012 ▶).

In a clinical trial, the effect of N. sativa seed in comparison with a triple therapy including clarithromycin, amoxicillin, and omeprazole against Helicobacter pylori (H. pylori) was evaluated in patients with non-ulcer dyspepsia. Patients were randomly divided into four groups: I) Triple therapy; II) 1 g/day N. sativa + 40 mg omeprazole; III) 2 g/day N. sativa + 40 mg omeprazole and IV) 3 g/day N. sativa + 40 mg omeprazole for four weeks. The results indicated that 2 g/day N. sativa + 40 mg omeprazole has the best therapeutic effect on H. pylori activity (Salem et al., 2010 ▶).

The antioxidant and anti-schistosomal effects of garlic aqueous extract (125 mg kg -1, i.p.) and N. sativa oil (0.2 mg kg, i.p.) in normal mice and Schistosoma mansoni (S. mansoni)-infected mice were studied. Hematological parameters and levels of MDA, GSH, LDH, AST, and ALT were assessed in the liver. The results revealed that garlic extract and N. sativa oil reversed most of the hematological and biochemical changes and markedly improved the antioxidant capacity of treated infected mice as compared to untreated infected mice (Shenawy et al., 2008 ▶).

The effect of oral administration of N. Sativa oil (2.5 and 5 ml/kg) alone or in combination with praziquantel on liver injury induced by S. mansoni was investigated in mice. The results showed that N. Sativa oil reduced the number of S. mansoni worms in the liver and decreased the total number of ova deposited in both the liver and intestine. When N. Sativa oil was administered in combination with praziquantel, the most prominent effect was a further reduction in the dead ova number more than that induced by praziquantel alone (Mahmoud et al., 2002 ▶).

The schistosomicidal effect of N. sativa seed against S. mansoni miracidia, cercariae, and adult worms was evaluated. Findings showed that N. sativa seed had a strong biocidal effect against all stages of the parasite life and showed inhibitory effect on egg-laying in adult female worms. The results also indicated that N. sativa seed induced oxidative stress against adult worms which was determined by reduction in the activities of antioxidant enzymes (Mohamed et al., 2005 ▶).

The anti-bacterial and anti-schistosomiasis effects of N. sativa and TQ were summarized in Table 3.

Table 3.

Anti-bacterial and anti-schistosomiasis effect of N. sativa and thymoquinone in GI tract

Plant preparation Experimental model Effect Reference
N. sativa seed Intestinal escherichia coli colonization Reduced numeration of ileal E. coli (Boka et al., 2014)
N. sativa seed Schistosomamansoni infection Biocidal effect in all stages of the parasite Inhibitory effect on egg-laying of adult female worms (Mohamed et al., 2005)
N. sativa seed Patients with H. pylori Potential effect on H. pylori activity (Salem et al., 2010)
N. sativa oil Schistosomamansoni infection Reduced the number of S. mansoni worms in the liver
Reduced the total number of ova		 (Mahmoud et al., 2002)
N. sativa oil Schistosomamansoni infection Inhibited most of the hematological and biochemical changes
Improved the antioxidant capacity		 (Shenawy et al., 2008)
Thymoquinone Bacterial translocation induced by mechanical intestinal obstruction Reduced inflammatory cytokines, oxidative damage, bacterial translocation
Improved intestinal barrier function		 (Kapan et al., 2012)
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Anti-inflammatory and antioxidant effects

The effects of N. sativa oil (0.88 g/kg, orally) on gastric secretion and ethanol-induced ulcer in adult male rats were assayed. The results showed that N. sativa oil increased gastric mucin content, free acidity and glutathione level, and decreased gastric mucosal histamine content. It is concluded that N. sativa oil has a protective effect on ethanol-induced ulcer (El-Dakhakhny et al., 2000 ▶).

In another study, gastroprotective effects of N. sativa oil (2.5 and 5 ml/kg, orally) and TQ (5, 20, 50 and 100 mg/kg, orally) against gastric mucosal injury induced by ischaemia/reperfusion were evaluated in male Wistar rats. The results indicated that N. sativa oil and TQ at 5 and 20 mg/kg reduced LDH, LPO and increased GSH and SOD. It is concluded that N. sativa oil and TQ had a protective effect on gastric injury (El-Abhar et al., 2003 ▶).

The effects of N. sativa oil (10 mL/kg body weight, orally) and TQ (10 mg/kg body weight, orally) against acute alcohol-induced gastric mucosal injury were investigated in male albino rats. The findings showed that N. sativa oil caused a reduction in ulcer index and MDA level and promoted healing of gastric injury and SOD, GSH and GST levels. Likewise, TQ has a protective activity on gastric lesions but less than that of N. sativa (Kanter et al., 2005b ▶)

The gastroprotective and anti-secretory effects of N. sativa seed powder (1.0, 1.5 and 2.0 g/kg, oral), aqueous and ethanolic extracts of N. sativa seed powder (2.0 g/kg, oral), and N. sativa ethanol-ethyl acetate fraction (2.0 g/kg, oral) were investigated in indomethacin-treated rats. The results showed that N. sativa seed powder decreased indomethacin-induced gastric lesions in a dose-dependent manner. Ethanolic extract of N. sativa significantly reduced gastric secretion volume, pH, acid-output and ulcer index, whereas aqueous extract only decreased gastric acid-output (Rifat-uz-Zaman and Khan, 2004 ▶).

In another study, the protective effect of N. sativa oil (10 ml/kg body weight) against piroxicam-induced gastric mucosal injury in adult male albino rats was investigated using light and scanning electron microscope. The results showed that N .sativa oil improved the structure of the mucosa in rats that received piroxicam and increased mucus secretion (Mohammed et al., 2010 ▶).

The protective effect of N. sativa oil (10 ml/kg body weight) on stress-induced gastric ulcer in hypothyroid rats was studied. Animals were randomly divided into six groups: I) Control; II) Surgically thyroidectomized group; III) Acute cold restraint stressed group; IV) Surgically thyroidectomized and stressed group; V) N. sativa oil group and VI) Surgically thyroidectomized and stressed receiving N. sativa oil group. Findings indicated a reduction in thyroid hormone level and an increase in stress-induced gastritis which can be inhibited by N. sativa oil (Abdel Sater, 2009 ▶).

The effects of two-week administration of N. Sativa oil (0.88 mL/kg/day, orally), omeprazole (30 mg/kg body weight/day, orally) and corn oil (2 mL/kg/day, orally) on ethanol-induced gastric lesions were studied in rats. The results indicated that N. sativa oil significantly increased glutathione and antioxidant enzymes and decreased lipid peroxides and protein carbonyl content. It is concluded that co-administration of omeprazole and N. sativa oil significantly improved all of the studied parameters (El-Masry et al., 2010 ▶).

In one study, the effects of TQ (10 and 20mg/kg), omeprazole (10 and 20mg/kg) or co-administration of TQ (10mg/kg) and omeprazole (10mg/kg) on gastric mucosal ischemia/reperfusion injury induced by pyloric ligation (30 min), ischemia (30 min)/reperfusion (120 min) were investigated in rats. The results revealed that TQ had gastroprotective effects which were mediated by inhibiting proton pump, acid secretion and neutrophil infiltration, and increasing mucin secretion, and nitric oxide production (Magdy et al., 2012).

The antioxidative and anti-histaminergic effects of N. sativa (500mg/kg, oral) and TQ (10mg/kg, orally) on ethanol-induced gastric mucosal damage were investigated in rat. The results showed that N. sativa significantly decreased the number of mast cells, the area of gastric erosions, histamine levels and myeloperoxidase activity. However, TQ effect was less pronounced as compared to that of N. sativa. The results also suggested that gastroprotective effects of N. sativa could be due to its anti-peroxidative, anti-oxidant and anti-histaminergic effects (Kanter et al., 2006 ▶).

The effect of N. seed oil (2.5 ml/kg, orally) on gastric tissues in experimental colitis (trinitrobenzenesulphonic acid -induced colitis) was studied. The levels of sialic acid (SA), GSH, MDA and CAT and SOD activities in gastric tissue samples and TNF-α, IL-1β and IL-6 and LDH levels in blood samples were determined. N. sativa seed oil significantly increased gastric tissue CAT activity and decreased LDH activity and TNF-α, IL-1β, IL-6 levels. Findings of this study indicated that N. sativa seed oil has a modulatory effect on inflammatory response in colitis (Emekli-Alturfan et al., 2011 ▶).

The effect of TQ (5 and 10 mg/kg) and sulfasalazine (500 mg/kg) as an anticolitis drug on acetic acid-induced colitis (by intracolonic injection of 3% acetic acid) was investigated in rats. Findings revealed that TQ has a more pronounced protective effect on colitis as compared to sulfasalazine and this effect may be possibly mediated through its antioxidant action (Mahgoub, 2003 ▶).

The effect of TQ (100 mg/kg, orally) on chronic pancretitis induced by high fat diet and ethanol was studied in rats. Findings revealed that TQ has a protective effect on pancretitis via reducing the secretion of amylase and lipase from pancreas, inflammatory cytokine and lipid peroxidation (Suguna et al., 2013 ▶).

Various gastroprotective, anti-inflammatory and anti-oxidant effects of N. sativa and TQ were summarized in Table 4.

Table 4.

Anti-inflammatory and antioxidant effect of N. sativa and thymoquinone in GI tract

Plant preparation Experimental model Effect Reference
N. Sativa Ethanol induced gastric mucosal damage Reduced the number of MC , the area of gastric erosions, histamine levels and myeloperoxidase activity (Kanter et al., 2006)
N. sativa seed Gastric lesions induced by indomethacin Reduced the gastric lesions (Rifat-uz-Zaman and Khan, 2004)
Aqueous extract Gastric lesions induced by indomethacin Reduced gastric acid-output (Rifat-uz-Zaman and Khan, 2004)
Ethanolic extract Gastric lesions induced by indomethacin Reduced gastric secretion volume, pH, acid-output and ulcer index. (Rifat-uz-Zaman and Khan, 2004)
ethanol ethyl acetate 51 fractions Gastric lesions induced by indomethacin Potential effect on pepsin activity, ulcer index and gastric secretion (Rifat-uz-Zaman and Khan, 2004)
N. Sativa oil Gastric mucosal injury induced by ischaemia reperfusion Reduced LDH, LPX
Increased GSH, SOD		 (El-Abhar et al., 2003)
N. Sativa oil Alcohol-induced gastric mucosal injury Reduced in the ulcer index, MDA
Promoted healing of gastric injury, SOD, GSH, GST.		 (Kanter et al., 2005b)
N. Sativa oil Piroxicam induced gastric mucosal injury Improved the structure of the mucosa Increased in mucus secretion (Mohammed et al., 2010)
N. Sativa oil Stress gastriculcer in hypothyroidal rats Reduced in thyroid hormone level increased stress gastritis, and this effect can be inhibited by treatment with N. sativa oil (Abdel Sater, 2009)
N. Sativa oil Trinitrobenzene sulfonic acid (TNBS)induced experimental colitis Reduced the proinflammatory cytokines, lactate dehydrogenase, myeloperoxidase, triglyceride, cholesterol and increasd superoxide dismutase activity. (Isik et al., 2011)
N. Sativa oil Ethanol induced gastric lesions Increased glutathione and antioxidant enzymes
Reduced lipid peroxides and protein carbonyl content		 (El-Masry et al., 2010)
N. Sativa oil Ethanol induced ulcer Increased the gastric mucin, free acidity and glutathione level
Reduced the gastric mucosal histamine content		 (El-Dakhakhny et al., 2000)
Thymoquinone Acetic acid-induced colitis Antioxidant activity (Mahgoub, 2003)
Thymoquinone Gastric mucosal ischemia/reperfusion (I/R) injury Inhibited proton pump, acid secretion and neutrophil infiltration
Increased mucin secretion, and nitric oxide production		 (Magdy et al., 2012)
Thymoquinone Chronic pancretitis induced by high fat diet and ethanol Reduced the secretion of amylase and lipase from pancreas, inflammatory cytokine and lipid peroxidation (Suguna et al., 2013)
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Conclusion

N. sativa and its main constituent, TQ showed anti-cancer, hepatoprotective, anti-bacterial, anti-schistosomiasis, gastroprotective, anti-inflammatory and antioxidant effects in animal models of gastrointestinal disorders including cancers, hepatotoxicity, ischemia/reperfusion injury, cholestatic liver, non-ulcer dyspepsia, schistosomiasis infection, colitis and panceratitis. These effects supported the preventive and therapeutic effect of N. sativa and its constituents on inflammatory, oxidative and toxic injury due to various toxins, microbes and food allergens. Clinical studies also indicated preventive effect as well as relieving effect of this plant and its constituents on various gastrointestinal disorders. Therefore, N. sativa have both preventive and therapeutic effects on gastro-intestinal diseases.

However, further clinical and experimental investigations are required to reveal the exact perspective of molecular and cellular basis of the effects of N. sativa and its constituents.

References

  1. Abdel-Wahab WM. Protective effect of thymoquinone on sodium fluoride-induced hepatotoxicity and oxidative stress in rats. J Basic Appl Zool. 2013;66:263–270. [Google Scholar]
  2. Abdel Sater KA. Protective effect of Nigella sativa oil on stress gastric ulcer in hypothyroidal rats. Internet J Nutr Wellness. 2009;7:314–324. [Google Scholar]
  3. Adel A-M, Morsy BM, Mahmoud AM, Abo-Seif MA, Zanaty MI. Beneficial therapeutic effects of Nigella sativa and/or Zingiber officinale in HCV patients in Egyp. EXCLI J. 2013;12:943–955. [PMC free article] [PubMed] [Google Scholar]
  4. Al-Ghamdi M. The anti-inflammatory, analgesic and antipyretic activity of Nigella sativa. J Ethnopharmacol. 2001;76:45–48. doi: 10.1016/s0378-8741(01)00216-1. [DOI] [PubMed] [Google Scholar]
  5. Al Mofleh, Ibrahim A, Alhaider , Abdulqader A, Mossa , Jaber S, Al-Sohaibani , Mohammed O, Al-Yahya , Mohammed A, Rafatullah , Syed Shaik, Shaffi A. Gastroprotective effect of an aqueous suspension of black cumin Nigella sativa on necrotizing agents-induced gastric injury in experimental animals. Saudi J Gastroenterol. 2008;14:128–34. doi: 10.4103/1319-3767.41731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Awad AS, Kamel R, Sherief MAE. Effect of thymoquinone on hepatorenal dysfunction and alteration of CYP3A1 and spermidine/spermine N‐1‐acetyl‐transferase gene expression induced by renal ischaemia–reperfusion in rats. J Pharm Pharacol. 2011;63:1037–1042. doi: 10.1111/j.2042-7158.2011.01303.x. [DOI] [PubMed] [Google Scholar]
  7. Bamosa AO, Kaatabi H, Lebda FM, Elq A-MA, Al-Sultan A. Effect of Nigella sativa seeds on the glycemic control of patients with type 2 diabetes mellitus. Indian J Physiol Pharmacol. 2010;54:344–54. [PubMed] [Google Scholar]
  8. Banerjee S, Kaseb AO, Wang Z, Kong DM, Mussop P, Subhash S, Fazlul HM, Ramzi M. Antitumor activity of gemcitabine and oxaliplatin is augmented by thymoquinone in pancreatic cancer. Cancer Res. 2009;69:5575–5583. doi: 10.1158/0008-5472.CAN-08-4235. [DOI] [PubMed] [Google Scholar]
  9. Boka J, Mahdavi A, Samie A, Jahanian R. Effect of different levels of black cumin (Nigella sativa L) on performance, intestinal Escherichia coli colonization and jejunal morphology in laying hens. J Anim Physiol Anim Nutr. 2014;98:373–383. doi: 10.1111/jpn.12109. [DOI] [PubMed] [Google Scholar]
  10. Boskabady M, Mohsenpoor N, Takaloo L. Antiasthmatic effect of Nigella sativa in airways of asthmatic patients. Phytomedicin. 2010;17:707–713. doi: 10.1016/j.phymed.2010.01.002. [DOI] [PubMed] [Google Scholar]
  11. Burits M, Bucar F. Antioxidant activity of Nigella sativa essential oil. Phytotherapy Research. 2000:323–8. doi: 10.1002/1099-1573(200008)14:5<323::aid-ptr621>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]
  12. Chaturvedi P, Singh AP, Moniaux N, Senapati S, Chakraborty S, Meza JL, Batra SK. MUC4 mucin potentiates pancreatic tumor cell proliferation, survival, and invasive properties and interferes with its interaction to extracellular matrix proteins. Mol Cancer Res. 2007;5:309–320. doi: 10.1158/1541-7786.MCR-06-0353. [DOI] [PubMed] [Google Scholar]
  13. ChehlN , Chipitsyna G, Gong Q, Yeo CJ, Arafat HA. Anti‐inflammatory effects of the Nigella sativa seed extract, thymoquinone, in pancreatic cancer cells. HPB. 2009;11:373–381. doi: 10.1111/j.1477-2574.2009.00059.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Coban S, Yildiz F, Alpaslan Al, Behcet A, Nurten B, MuharremC The effects of Nigella sativa on bile duct ligation induced‐liver injury in rats. Cell Biochem Funct. 2010;28:83–88. doi: 10.1002/cbf.1624. [DOI] [PubMed] [Google Scholar]
  15. Daba MH, Abdel-Rahman MS. Hepatoprotective activity of thymoquinone in isolated rat hepatocytes. Toxicol Lett. 1998;95:23–29. doi: 10.1016/s0378-4274(98)00012-5. [DOI] [PubMed] [Google Scholar]
  16. Dehkordi FR, Kamkhah AF. Antihypertensiveeffect of Nigella sativa seed extract in patients with mild hypertension. Fundam Clin Pharmacol. 2008;22:447–452. doi: 10.1111/j.1472-8206.2008.00607.x. [DOI] [PubMed] [Google Scholar]
  17. El-Abhar H, Abdallah D, Saleh S. Gastroprotective activity of Nigella sativa oil and its constituent, thymoquinone, against gastric mucosal injury induced by ischaemia/reperfusion in rats. J Ethnopharmacol. 2003;84:251–258. doi: 10.1016/s0378-8741(02)00324-0. [DOI] [PubMed] [Google Scholar]
  18. El-Dakhakhny M, Barakat M, El-Halim MA, Aly S. Effects of Nigella sativa oil on gastric secretion and ethanol induced ulcer in rats. J Ethnopharmacol. 2000;72:299–304. doi: 10.1016/s0378-8741(00)00235-x. [DOI] [PubMed] [Google Scholar]
  19. El-Masry TA, Elahwel AM, Emara AM. Study on treating ethanol-induced gastric lesions with omeprazole, Nigella sativa oil, or both. Toxicol Environ Chem. 2010;92:1765–1782. [Google Scholar]
  20. El-Tahir KE-DH, Bakeet DM. The black seed Nigella sativa Linnaeus-A mine for multi cures: a plea for urgent clinical evaluation of its volatile oil. J Taibah Univ Med Sci. 2006;1:1–19. [Google Scholar]
  21. Emekli-Alturfan E, Yarat A, Tunali-Akbay T, Isik F, Yenidogan G, Sener G, Sehirli O, Pisiriciler R, Altintas A. Effect of Black Cumin (Nigella Sativa) Seed Oil on Gastric Tissue in Experimental Colitis. Adv Environ Biol. 2011;5:483–90. [Google Scholar]
  22. Farrag A, Mahdy KA, Abdel RG, Osfor MM. Protective effect of Nigella sativa seeds against lead-induced hepatorenal damage in male rats. Pak J Biol Sci. 2007;10:2809–2816. doi: 10.3923/pjbs.2007.2809.2816. [DOI] [PubMed] [Google Scholar]
  23. Gali-Muhtasib H, Diab-Assaf M, Boltze C, Al-Hmaira J, Hartig R, Roessner A, Schneider-Stock R. Thymoquinone extracted from black seed triggers apoptotic cell death in human colorectal cancer cells via a p53-dependent mechanism. Int J Oncol. 2004;25:857–866. [PubMed] [Google Scholar]
  24. Gholamnezhad Z, Boskabady MH, Hosseini M. Effect of Nigella sativa on immune response in treadmill exercised rat. BMC Complement Altern Med. 2014;14:437. doi: 10.1186/1472-6882-14-437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Gholamnezhad Z, Keyhanmanesh R, Boskabady MH. Anti-inflammatory, antioxidant, and immunomodulatory aspects of Nigella sativa for its preventive and bronchodilatory effects on obstructive respiratory diseases: A review of basic and clinical evidence. J Funct Food. 2015;17:910–27. [Google Scholar]
  26. Goreja WG. Black seed:nature's miracle remedy (papreback) New York: Karger Publishers; 2003. pp. 1–51. [Google Scholar]
  27. Helal GK. Thymoquinone supplementation ameliorates acute endotoxemia-induced liver dysfunction in rats. Pak J Pharm Sci. 2010;23:131–137. [PubMed] [Google Scholar]
  28. Isik F, Akbay TT, Yarat A, Genc Z, Pisiriciler R, Caliskan-Ak E, Cetinel S, Altıntas A, Sener G. Protective effects of black cumin (Nigella sativa) oil on TNBS-induced experimental colitis in rats. Dig Dis Sci. 2011;56:721–730. doi: 10.1007/s10620-010-1333-z. [DOI] [PubMed] [Google Scholar]
  29. Islam S, Ahsan M, Hassan CM, Malek MA. Antifungal activities of the oils of Nigella sativa seeds. Pak J Pharm Sci. 1989;2:25–28. [PubMed] [Google Scholar]
  30. Kanter M, Coskun O, Budancamanak M. Hepatoprotective effects of Nigella sativa L and Urtica dioica L on lipid peroxidation, antioxidant enzyme systems and liver enzymes in carbontetrachloride-treated rats. World J Gastroenterol. 2005a;11:6684–8. doi: 10.3748/wjg.v11.i42.6684. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Kanter M, Coskun O, Uysal H. The antioxidative and antihistaminic effect of Nigella sativa and its major constituent, thymoquinone on ethanol-induced gastric mucosal damage. Arch Toxicol. 2006;80:217–224. doi: 10.1007/s00204-005-0037-1. [DOI] [PubMed] [Google Scholar]
  32. Kanter M, Demir H, Karakaya C, Ozbek H. Gastroprotective activity of Nigella sativa L oil and its constituent, thymoquinone against acute alcohol-induced gastric mucosal injury in rats. World J Gastroenterol. 2005b;11:6662–6. doi: 10.3748/wjg.v11.i42.6662. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. KapanM , Tekin R, Onder A, Firat U, Evliyaoglu O, Taskesen F, Arikanoglu Z. Thymoquinone ameliorates bacterial translocation and inflammatory response in rats with intestinal obstruction. Int J Surg. 2012;10:484–488. doi: 10.1016/j.ijsu.2012.06.006. [DOI] [PubMed] [Google Scholar]
  34. Khazdair MR. The Protective Effects of Nigella sativa and Its Constituents on Induced Neurotoxicity. J Toxicol. 2015;2015:1–7. doi: 10.1155/2015/841823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Magdy M-A, Hanan E-A, Nabila E-M. Thymoquinone: Novel gastroprotective mechanisms. Eur J Pharmacol. 2012;697:126–131. doi: 10.1016/j.ejphar.2012.09.042. [DOI] [PubMed] [Google Scholar]
  36. Mahgoub AA. Thymoquinone protects against experimental colitis in rats. Toxicol Lett. 2003;143:133–143. doi: 10.1016/s0378-4274(03)00173-5. [DOI] [PubMed] [Google Scholar]
  37. Mahmoud M, El-Abhar H, Saleh S. The effect of Nigella sativa oil against the liver damage induced by Schistosoma mansoni infection in mice. J Ethnopharmacol. 2002;79:1–11. doi: 10.1016/s0378-8741(01)00310-5. [DOI] [PubMed] [Google Scholar]
  38. Mahmoud SS, Torchilin VP. Hormetic/cytotoxic effects of Nigella sativa seed alcoholic and aqueous extracts on MCF-7 breast cancer cells alone or in combination with doxorubicin. Cell Biochem Biophys. 2013;66:451–460. doi: 10.1007/s12013-012-9493-4. [DOI] [PubMed] [Google Scholar]
  39. Majdalawieh AF, Hmaidan R, Carr RI. Nigella sativa modulates splenocyte proliferation, Th1/Th2 cytokine profile, macrophage function and NK anti-tumor activity. J Ethnopharmacol. 2010;131:268–275. doi: 10.1016/j.jep.2010.06.030. [DOI] [PubMed] [Google Scholar]
  40. Mantle D, Pickering AT, Perry EK. Medicinal plant extracts for the treatment of dementia. CNS drugs. 2000;13:201–213. [Google Scholar]
  41. Mohamed AM, Metwally NM, Mahmoud SS. Sativa seeds against Schistosoma mansoni different stages. Mem Inst OswaldoCruz. 2005;100:205–211. doi: 10.1590/s0074-02762005000200016. [DOI] [PubMed] [Google Scholar]
  42. Mohammed SS, Naim MM, Mahmoud SH. Possible Protective Effect of Nigella Sativa Oil Against Piroxicam‐Induced Gastric Mucosal Damage in Adult Male Albino Rats (Light and Scanning Electron Microscopic Study) Egypt J Histo. 2010;33:127–139. [Google Scholar]
  43. Morsi NM. Antimicrobial effect of crude extracts of Nigella sativa on multiple antibiotics-resistant bacteria. Acta Micro biol Pol. 1999;49:63–74. [PubMed] [Google Scholar]
  44. Nagi MN, Alam K, Badary OA, Al‐Shabanah OA, Al‐Sawaf HA, Al‐Bekairi AM. Thymoquinone protects against carbon tetrachloride hetatotoxicity in mice via an antioxidant mechanism. Int Biochem Mol Biol. 1999;47:153–9. doi: 10.1080/15216549900201153. [DOI] [PubMed] [Google Scholar]
  45. Nagi MN, Almakki HA, Sayed-Ahmed MM, Al-Bekairi AM. Thymoquinone supplementation reverses acetaminophen-induced oxidative stress, nitric oxide production and energy decline in mice liver. Food Chem Toxicol. 2010;48:2361–5. doi: 10.1016/j.fct.2010.05.072. [DOI] [PubMed] [Google Scholar]
  46. Nili-Ahmadabadi A, Tavakoli F, Hasanzadeh G, Rahimi H, Sabzevari O. Protective effect of pretreatment withthymoquinone against Aflatoxin B1 induced liver toxicity in mice. Daru J Pharm Sci. 2011;19:282–7. [PMC free article] [PubMed] [Google Scholar]
  47. Payment P. Epidemiology of endemic gastrointestinal and respiratory diseases: Incidence, fraction attributable to tap water and costs to society. Water Sci Technol. 1997;35:7–10. [Google Scholar]
  48. Raza M, Alghasham AA, Alorainy MS, El-Hadiyah TM. Potentiation of valproate-induced anticonvulsant response by Nigella sativa seed constituents: the role of GABA receptors. Int J health Sci. 2008;2:15. [PMC free article] [PubMed] [Google Scholar]
  49. Rifat-uz-Zaman MSA, Khan MS. Gastroprotective and anti-secretory effect of Nigella sativa seed and its extracts in indomethacin-treated rats. Pak J Biol Sci. 2004;7:995–1000. [Google Scholar]
  50. Rooney S, Ryan M. Modes of action of alpha-hederin and thymoquinone, active constituents of Nigella sativa, against HEp-2 cancer cells. Anticancer Res. 2005;25:4255–4259. [PubMed] [Google Scholar]
  51. Salem EM, Yar T, Bamosa A, Al-Quorain A, Yasawy MI, Alsulaiman RM, Randhawa MA. Comparative study of Nigella Sativa and triple therapy in eradication of Helicobacter Pylori in patients with non-ulcer dyspepsia. Saudi J Gastroenterol. 2010;16:207–214. doi: 10.4103/1319-3767.65201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Salim EI, Fukushima S. Chemopreventive potential of volatile oil from black cumin (Nigella sativa L.) seeds against rat colon carcinogenesis. Nutr cancer. 2003;45:195–202. doi: 10.1207/S15327914NC4502_09. [DOI] [PubMed] [Google Scholar]
  53. Sayed-Ahmed MM, Aleisa AM, Al-Rejaie SS, Al-Yahya AA, Al-Shabanah OA, Hafez MM, Nagi MN. Thymoquinone attenuates diethylnitrosamine induction of hepatic carcinogenesis through antioxidant signaling. Oxid Med Cell Longev. 2010;3:254–261. doi: 10.4161/oxim.3.4.12714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Sharma PC, Yelne MB, Dennis TG. Database on medicinal plants used in Ayurveda. New Delhi: 2001. pp. 420–440. [Google Scholar]
  55. Shenawy E, Nahla S, Soliman MF, Reyad SI. The effect of antioxidant properties of aqueous garlic extract and Nigella sativa as anti-schistosomiasis agents in mice. Rev Inst Med Trop São Paulo. 2008;50:29–36. doi: 10.1590/s0036-46652008000100007. [DOI] [PubMed] [Google Scholar]
  56. Singh AP, Moniaux N, Chauhan SC, Meza JL, Batra SK. Inhibition of MUC4 expression suppresses pancreatictumor cell growth and metastasis. Cancer Res. 2004;64:622–30. doi: 10.1158/0008-5472.can-03-2636. [DOI] [PubMed] [Google Scholar]
  57. Suddek GM. Protective role of thymoquinone against liver damage induced by tamoxifen in female rats. Can J Physiol Pharmacol. 2014;92:640–4. doi: 10.1139/cjpp-2014-0148. [DOI] [PubMed] [Google Scholar]
  58. Suguna P, Geetha A, Aruna R, Siva GV. Effect of thymoquinone on ethanol and high fat diet induced chronic pancreatitis a dose response study in rats. Indian J Exp Biol. 2013;51:292–302. [PubMed] [Google Scholar]
  59. Torres MP, Ponnusamy MP, Chakraborty S, Smith LM, Das S, Arafat HA, Batra SK. Effects of thymoquinonein the expression of mucin 4 in pancreatic cancer cells: implications for the development of novel cancer therapies. Mol Cancer Ther. 2010;9:1419–1431. doi: 10.1158/1535-7163.MCT-10-0075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Yildiz F, Coban S, Terzi A, Ates M, Aksoy N, Cakir H, Ocak AR, Bitiren M. Nigella sativa relieves the deleterious effects of ischemia reperfusion injury on liver. World J Gastroenterol. 2008;14:5204–9. doi: 10.3748/wjg.14.5204. [DOI] [PMC free article] [PubMed] [Google Scholar]

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