Ample of evidence proved the gastroprotective effect of thymoquinone (TQ), the main constituent of Nigella sativa oil; however, the full mechanistic cassette on the gastric ulcer etiopathogenesis is not fully elucidated. The aim of the present work is to unveil some of the possible mechanisms. Animals were injected with vehicle, TQ (10 & 20mg/kg), omeprazole (10 & 20mg/kg) or their combination (10mg/kg). Thirty minutes later, pyloric ligation was carried out and followed consequently with ischemia for another 30min, abided by reperfusion for 120min. The ischemia/reperfusion insult increased the gastric acid secretion, acid output, and pepsin, as well as the gastric mucosal content/activity of lipid peroxide, proton pump and myeloperoxidase, along with ulcerindex. However, content/activity of gastric mucin, reduced glutathione, total nitric oxide, and superoxide dismutase were decreased. TQ, especially the high dose level, corrected the altered parameters in a comparable manner to that of the reference drug used, omeprazole. In addition, when the low doses were combined they add to each other to reach the effect of the high dose of either drug. These results showed that apart from its known antioxidant properties, TQ has novel gastroprotective mechanisms via inhibiting proton pump, acid secretion and neutrophil infiltration, while enhancing mucin secretion, and nitric oxide production.

BACKGROUND:

Nanostructured lipid carriers (NLCs), composed of solid and liquid lipids, and surfactants are potentially good colloidal drug carriers. Thymoquinone is the main bioactive compound of Nigella sativa. In this study, the preparation, gastroprotective effects, and pharmacokinetic (PK) properties of thymoquinone (TQ)-loaded NLCs (TQNLCs) were evaluated.

METHOD:

TQNLCs were prepared using hydrogenated palm oil (Softisan® 154), olive oil, and phosphatidylcholine for the lipid phase and sorbitol, polysorbate 80, thimerosal, and double distilled water for the liquid lipid material. A morphological assessment of TQNLCs was performed using various methods. Analysis of the ulcer index, hydrogen concentration, mucus content, and biochemical and histochemical studies confirmed that the loading of TQ into the NLCs significantly improved the gastroprotective activity of this natural compound against the formation of ethanol-induced ulcers. The safety of TQNLC was tested on WRL68 liver normal cells with cisplatin as a positive control.

RESULTS:

The average diameter of the TQNLCs was 75 ± 2.4 nm. The particles had negative zeta potential values of -31 ± 0.1 mV and a single melting peak of 55.85°C. Immunohistochemical methods revealed that TQNLCs inhibited the formation of ethanol-induced ulcers through the modulation of heat shock protein-70 (Hsp70). Acute hepatotoxic effects of the TQNLCs were not observed in rats or normal human liver cells (WRL-68). After validation, PK studies in rabbits showed that the PK properties of TQ were improved and indicated that the drug behaves linearly. The Tmax, Cmax, and elimination half-life of TQ were found to be 3.96 ± 0.19 hours, 4811.33 ± 55.52 ng/mL, and 4.4933 ± 0.015 hours, respectively, indicating that TQ is suitable for extravascular administration.

CONCLUSION:

NLCs could be a promising vehicle for the oral delivery of TQ and improve its gastroprotective properties.

OBJECTIVE:

Natural honey (NH) and Nigella sativa (NS) seeds have been in use as a natural remedy for over thousands of years in various parts of the world. The aim of this study was to assess the protective effects of NS (Nigella sativa) and NH (natural honey) on acetylsalicylic acid induced gastric ulcer in an experimental model with comparison to Cimetidine (CD).

STUDY DESIGN:

Experimental, case control study.

PLACE AND DURATION OF STUDY:

Pharmacology and Pathology Department of King Edward Medical University, Lahore, from June to August 2007.

METHODOLOGY:

The study was conducted on 100 male albino rats, divided into 5 groups, with 20 animals in each group. Group A was used as a control and treated with Gum Tragacanth (GT). Eighty animals of the other groups were given acetylsalicylic acid (0.2 gm/kg body weight for 3 days) to produce ulcers by gavage. Two animals from each group were sacrificed for the detection of gastric ulcers. The remaining 72 animals were equally divided in four groups (B, C, D and E). The rats in group B, C and D were given NS, NH, and CD respectively while those in E were kept as such.

RESULTS:

No gastric lesions were seen in control group A while all the animals in group E revealed gastriculcers. The animals of group B, C and D showed healing effects in 15/18 (83%), 14/18 (78%) and 17/18 (94%) animals grossly; 13/18 (72%), 14/18 (78%) and 16/18 (89%) rats showed recovery on microscopic examination respectively. The healing effects were almost the same in all three groups therefore, the statistical difference was not significant among them (p =0.40 and 0.65) while significant from group E (p=0.0000075, 0.0000016 and 0.0000012 respectively).

CONCLUSION:

NS and NH are equally effective in healing of gastric ulcer similar to cimetidine. Further broad spectrum studies as well as clinical trials should be conducted before the use of these products as routine medicines.

BACKGROUND/AIM:

A large number of diseases are ascribed to Helicobacter pylori (H. pylori), particularly chronic active gastritis, peptic ulcer disease and gastric cancer. Successful treatment of H. pylori infection with antimicrobial agents can lead to regression of H. pylori-associated disorders. Antibiotic resistance against H. pylori is increasing, and it is necessary to find new effective agents. Nigella sativa seed (NS), a commonly used herb, possesses in vitro anti-helicobacter activity. The present study was undertaken to evaluate the efficacy of NS in eradication of H. pylori infection in non-ulcer dyspeptic patients.

MATERIALS AND METHODS:

The study was conducted on 88 adult patients attending King Fahd Hospital of the University, Al-Khobar, Saudi Arabia, from 2007 to 2008, with dyspeptic symptoms and found positive for H. pylori infection by histopathology and urease test. Patients were randomly assigned to four groups, receiving i) triple therapy (TT) comprising of clarithromycin, amoxicillin, omeprazole [n= 23], ii) 1 g NS + 40 mg omeprazole (OM) [n= 21], iii) 2 g NS + OM [n= 21] or iv) 3 g NS + OM [n= 23]. Negative H. pylori stool antigen test four weeks after end of treatment was considered as eradication.

RESULTS:

H. pylori eradication was 82.6, 47.6, 66.7 and 47.8% with TT, 1 g NS, 2 g NS and 3 g NS, respectively. Eradication rates with 2 g NS and TT were statistically not different from each other, whereas H. pylori eradication with other doses was significantly less than that with TT (P < 0.05). Dyspepsia symptoms improved in all groups to a similar extent.

CONCLUSIONS:

N. sativa seeds possess clinically useful anti-H. pylori activity, comparable to triple therapy. Further clinical studies combining N. sativa with antibiotics are suggested.

BACKGROUND/AIM:

Previous studies on “Black seed” or “Black Cumin” Nigella sativa (NS) have reported a large number of pharmacological activities including its anti-ulcer potential. These studies employed either fixed oil, volatile oil components or different solvent extracts. In folkloric practices, NS seeds are taken as such, in the form of coarse dry powder or the powdered seeds are mixed with water. This study examines the effect of NS aqueous suspension on experimentally induced gastric ulcers and basal gastric secretion in rats to rationalize its use by herbal and Unani medicine practitioners.

MATERIALS AND METHODS:

The study was conducted at the Medicinal, Aromatic and Poisonous Plants Research Center, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Acute gastric ulceration was produced by various noxious chemicals (80% ethanol, 0.2 M NaOH, 25% NaCl and indomethacin) in Wistar albino rats. Anti-secretory studies were undertaken in a separate group of rats. Gastric wall mucus contents and non-protein sulfhydryl concentration were estimated, and gastric tissue was examined histopathologically.

RESULTS:

An aqueous suspension of Black seed significantly prevented gastric ulcer formation induced by necrotizing agents. It also significantly ameliorated the ulcer severity and basal gastric acid secretion in pylorus-ligated Shay rats. Moreover, the suspension significantly replenished the ethanol-induced depleted gastric wall mucus content levels and gastric mucosal non-protein sulfhydryl concentration. The anti-ulcereffect was further confirmed histopathologically.

CONCLUSION:

These findings validate the use of Black seed in gastropathies induced by necrotizing agents. The anti-ulcer effect of NS is possibly prostaglandin-mediated and/or through its antioxidant and anti-secretory activities.

The aim of this study was to assess the effects of hypothyroidism on the development of acute cold restraint stress gastritis in rats and protective effect of Nigella sativa at the beginning of the acute cold restraint stress. 60 rats were randomly divided into six groups; the control (groups I), surgically thyroidectomized group (group II), acute cold restraint stressed group (group III), surgically thyroidectomized plus stressed group (group IV),Nigella sativa oil group (group V) and surgically thyroidectomized plus stressed plus Nigella sativa oil group (group VI). Volume of gastric juice, number and size of ulcer, gastric malonaldehyde, gastric glutathione, gastric protein and serum thyroxine (T4) were measured. Significant increases both of number of gastric ulcerand malonaldehyde while decreases both of glutathione and protein levels in rats in groups III and IV in comparison with control group. While, insignificant increase were observed between control and both of groups II and VI. In rats, low thyroid hormone level increase stress gastritis, and this effect can be decreased by treatment with Nigella sativa.

To evaluate the role of reactive oxygen species in the pathogenesis of acute ethanol-induced gastric mucosal lesions and the effect of Nigella sativa L oil (NS) and its constituent thymoquinone (TQ) in an experimental model.

METHODS:

Male Wistar albino rats were assigned into 4 groups. Control group was given physiologic saline orally (10 mL/kg body weight) as the vehicle (gavage); ethanol group was administrated 1 mL (per rat) absolute alcohol by gavage; the third and fourth groups were given NS (10 mL/kg body weight) and TQ (10 mg/kg body weight p.o) respectively 1 h prior to alcohol intake. One hour after ethanol administration, stomach tissues were excised for macroscopic examination and biochemical analysis.

RESULTS:

NS and TQ could protect gastric mucosa against the injurious effect of absolute alcohol and promote ulcer healing as evidenced from the ulcer index (UI) values. NS prevented alcohol-induced increase in thiobarbituric acid-reactive substances (TBARS), an index of lipid peroxidation. NS also increased gastric glutathione content (GSH), enzymatic activities of gastric superoxide dismutase (SOD) and glutathione-S-transferase (GST). Likewise, TQ protected against the ulcerating effect of alcohol and mitigated most of the biochemical adverse effects induced by alcohol in gastric mucosa, but to a lesser extent than NS. Neither NS nor TQ affected catalase activity in gastric tissue.

CONCLUSION:

Both NS and TQ, particularly NS can partly protect gastric mucosa from acute alcohol-induced mucosal injury, and these gastroprotective effects might be induced, at least partly by their radical scavenging activity.

The aim of this study was to assess the possible protective effects of Nigella sativa (NS) and its constituent, thymoquinone (TQ) on ethanol-induced gastric mucosal damage in an experimental model. Forty male rats aged four months were divided into four groups (each group containing ten animals); the control group received physiologic saline (10 ml kg(-1)) and the ethanol group had taken 1 ml (per rat) absolute alcohol by gavage. The third and fourth groups also received NS (500 mg kg(-1)) and TQ (10 mg kg(-1)) by gavage 1 h before alcohol administration, respectively. Both drugs (NS and TQ) could protect the gastric mucosa against the injurious effect of absolute alcohol and promote ulcer healing as evidenced from the ulcer index values. Gastric damage was confirmed histomorphometrically by significant increases in the number of mast cells (MC) and gastric erosions in ethanol treated rats. The NS treatment significantly decreased the number of MC and reduced the area of gastric erosions. Likewise, TQ treatment was also able to reduce the number of MC and the gravity of gastric mucosal lesions, but to lesser extent compared to NS. Gastric tissue histamine levels and myeloperoxidase activities were found to be increased in ethanol treated rats, and NS or TQ treatment reversed these increases. Results obtained from this study suggest that both drugs, particularly NS could partly protect gastric mucosa from acute alcohol-induced mucosal injury, and these gastroprotective effects could be due to their antiperoxidative, antioxidant and antihistaminic effects.

Ischaemia/reperfusion (I/R) induced gastric lesion, is known to be linked with free radical (FR) formation. Therefore, this model was used to assess the antioxidant effects of Nigella sativa oil (N.O) and thymoquinone (TQ) on gastric mucosal redox state and gastric lesions, 1 and 24 h after reperfusion. Male Wistar rats were subjected to I/R and were injected with either N.O (2.5 and 5 ml/kg, p.o) or TQ (5, 20, 50 and 100 mg/kg, p.o). The results showed that I/R elevated the levels of lipid peroxide (LPX) and lactate dehydrogenase (LDH), while decreased those of reduced glutathione (GSH) and superoxide dismutase (SOD). These biochemical changes were accompanied by an increase in the formation of gastric lesions, which was reduced by either treatment. N.O tended to normalize the level of LDH, GSH and SOD. However, its effect to restore LPX was only seen 24 h after reperfusion. Moreover, the aforementioned parameters were nearly reinstated by TQ. On the other hand, high doses of TQ (50 and 100 mg/kg) severely reduced the GSH content, 1 h after reperfusion. These results indicate that both N.O and TQ possess gastroprotective effect against gastric lesions which may be related to the conservation of the gastric mucosal redox state.

The present work was done to investigate the possible effects of Nigella sativa oil (NSO) on gastric secretion and ethanol-induced ulcer in rats. Thirty two adult male rats were used in this study (four groups) and several parameters were determined to assess any degree of protection. It was found that the administration of NSO in rats produced a significant increase in mucin content and glutathione level and a significant decrease in mucosal histamine content. Ethanol administration produced a 100% ulcer induction with an ulcer score of 12.62+/-1.35 (mean+/-S.E., n=8). It caused a significant reduction in free acidity and glutathione level while it produced a significant increase in mucosal histamine content. When animals were pretreated with NSO before induction of ulcer, there was a significant increase in glutathione level, mucin content and free acidity and a significant decrease in gastric mucosal histamine content with a protection ratio of 53.56% as compared to the ethanol group. It can be concluded that NSO imparted a protective action against ethanol induced ulcer in rats.