الفهرس 
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Abstract
The current investigation was conducted to study the probable protective potential of some herbal drugs, namely Althaea officinalis (marshmallow) and Solanum nigrum (black nightshade) against gastric-ulcer induced experimentally in rats compared to omeprazole, misoprostol and sucralfate as reference anti-ulcer agents.
In the present investigation, preliminary phytochemical analysis of the prepared extracts (aqueous extract of Althaea officinalis and ethanolic extract of Solanum nigrum) used in this study was done followed by evaluation of their in-vitro anti-oxidant activity (DPPH assay). Then, one model of animal experiments has been involved which is rat pyloric ligation/indomethacin-induced gastric ulceration model. It was constructed to evaluate the possible anti-ulcer effects of the chosen herbal drugs as compared to standard drugs when used for 2 successive weeks.
The chosen doses for 14-day daily pretreatments in the model used were; Omeprazole (20 mg/kg, p.o.), Misoprostol (300 µg/kg, p.o.), Sucralfate (200 mg/kg, p.o.), Althaea officinalis (100 mg/kg, p.o.), Solanum nigrum (200 mg/kg, p.o.), Omeprazole (20 mg/kg, p.o.) + Sucralfate (200 mg/kg, p.o.), Omeprazole (20 mg/kg, p.o.) + Althaea officinalis (100 mg/kg, p.o.) and Omeprazole (20 mg/kg, p.o.) + Solanum nigrum (200 mg/kg, p.o.). All the standard and test drugs were administrated by oral feeding tube. Indomethacin dose was (25 mg/kg/once) was administrated by intra-peritoneal injection.
After the dosing period and collection of gastric juice, blood and tissue samples, The anti-ulcerogenic, gastro-protective and anti-oxidant potentials of the standard and test drugs were evaluated based on macroscopic examination (ulcer number, ulcer index and preventive index) and acid productivity parameters (gastric volume, titratable acidity and acid output), assessment of aggressive factors like peptic activity, gastric mucosal histamine and plasma gastrin contents, measurement of oxidative stress biomarkers as gastric mucosal superoxide-dismutase (SOD) activity and reduced glutathione (GSH), nitric oxide (NO) and malondialdehyde (MDA) contents, protective factors including gastric mucosal prostaglandin-E2 (PG-E2) and prostacyclin (PG-I2) contents, assessment of immunological factors like tumor-necrosis-factor-alpha (TNF-α), interleukin-1-beta (IL-1β), cystathionine-β-synthase (CBS) (as indicator of H2S) and heme-oxygenase-1 (HO-1) expressions, together with some enzyme activities in gastric mucosal tissue, like cyclo-oxygenase-1 (COX-1), cyclo-oxygenase-2 (COX-2), nitric-oxide-synthase-2 (NOS-2) (inducible) and nitric-oxide-synthase-3 (NOS-3) (endothelial). All these parameters were assessed via enzyme-linked immunosorbent assay (ELISA), western blot analysis and immune-florescence technique. Microscopic examinations were also performed by histopathological examination using routine hematoxylin and eosin (H&E) and special alcian blue staining for determination of gastric wall mucus (mucin content).
The findings of the current investigation can be summarized as follows:
1. Preliminary phytochemical analysis for Althaea officinalis extract was positive for carbohydrates, traces of tannins, flavonoids, traces of saponins and volatile oils. while preliminary phytochemical analysis for Solanum nigrum extract was positive for carbohydrates, tannins, flavonoids, saponins, sterols and triterpenoids, and alkaloids.
2. Aqueous extract of Althaea officinalis and ethanolic extract of Solanum nigrum showed free radical scavenging activities against DPPH.
3. Pyloric ligation/indomethacin administration to rats results in significant ulcerogenic effect as evidenced by a significant elevation in ulcer number, ulcer index, acid and pepsin productivity (gastric volume, acid output and peptic activity), accompanied with significant elevation in gastric mucosal MDA, histamine and blood gastrin contents. Additionally, significant elevation in COX-2 and NOS-2 enzyme activities and TNF-α and IL-1β contents were also reported. These were associated with significant reduction in gastric mucosal SOD activity, NO, GSH, PG-E2, PG-I2 and mucin contents accompanied gastric-ulceration with significant reduction in CBS and HO-1 enzyme expressions, and COX-1 enzyme activity and NOS-3/NOS-2 ratio.
4. Pretreatment with omeprazole for 14 days in a dose of 20 mg/kg/day, p.o., resulted in significant protection against pyloric ligation/indomethacin-induced gastric ulceration as shown by a significant reduction in ulcer number, ulcer index, providing a protection index of 65%. Also, it significantly reduced gastric mucosal MDA, histamine, and blood gastrin contents. Additionally, a significant reduction in TNF-α and IL-1β contents were also reported. These were associated with significant elevation in gastric mucosal SOD activity, NO, GSH, PG-E2 and mucin contents, and significant elevation in HO-1 enzyme expression and NOS-3/NOS-2 ratio.
5. Pretreatment with misoprostol for 14 days in a dose of 300 µg/kg/day, p.o., resulted in significant protection against pyloric ligation/indomethacin-induced gastric ulceration as shown by a significant reduction in ulcer number, ulcer index, providing a protection index of 57.5%. Also, it significantly reduced gastric mucosal MDA, histamine, and blood gastrin contents. Additionally, a significant reduction in NOS-2 enzyme activity and TNF-α and IL-1β contents were also reported. These were associated with significant elevation in gastric mucosal SOD activity, NO, GSH, PG-E2 and mucin contents, and significant elevation in HO-1 enzyme expression.
6. Pretreatment with sucralfate for 14 days in a dose of 200 mg/kg/day, p.o., resulted in significant protection against pyloric ligation/indomethacin-induced gastric ulceration as shown by a significant reduction in ulcer number, ulcer index, providing a protection index of 58.5%. Also, it significantly reduced gastric mucosal MDA, histamine, and blood gastrin contents. Additionally, a significant reduction in TNF-α and IL-1β contents was also reported. These were associated with significant elevation in gastric mucosal SOD activity, NO, GSH, PG-E2 and mucin contents, and significant elevation in HO-1 enzyme expression.
7. Pretreatment with Althaea officinalis for 14 days in a dose of 100 mg/kg/day, p.o., resulted in significant protection against pyloric ligation/indomethacin-induced gastric ulceration as shown by a significant reduction in ulcer number, ulcer index, providing a protection index of 56%. Also, it significantly reduced peptic activity, gastric mucosal MDA, histamine, and blood gastrin contents. Additionally, a significant reduction in NOS-2 enzyme activity and TNF-α and IL-1β contents was also reported. These were associated with significant elevation in gastric mucosal SOD activity, NO, GSH, PG-E2 and mucin contents, and significant elevation in HO-1 and CBS enzyme expressions.
8. Pretreatment with Solanum nigrum for 14 days in a dose of 200 mg/kg/day, p.o., resulted in significant protection against pyloric ligation/indomethacin-induced gastric ulceration as shown by a significant reduction in ulcer number, ulcer index, providing a protection index of 55.5%. Also, it significantly reduced gastric mucosal MDA, histamine, and blood gastrin contents. Additionally, a significant reduction in COX-2 and NOS-2 enzyme activities and TNF-α and IL-1β contents was also reported. These were associated with significant elevation in gastric mucosal SOD activity, NO, GSH, PG-E2 and mucin contents, and significant elevation in HO-1 and CBS enzyme expressions.
9. Pretreatment with a combination of omeprazole and sucralfate for 14 days in a dose of 20 mg/kg/day and 200 mg/kg/day, respectively, p.o., resulted in significant protection against pyloric ligation/indomethacin-induced gastric ulceration as shown by a significant reduction in ulcer number, ulcer index, providing a protection index of 67.5%. Also, it significantly reduced gastric mucosal MDA, histamine, and blood gastrin contents. Additionally, a significant reduction in COX-2 and NOS-2 enzyme activities and TNF-α and IL-1β contents was also reported. These were associated with significant elevation in gastric mucosal SOD activity, NO, GSH, PG-E2 and mucin contents, and significant elevation in HO-1 and CBS enzyme expressions.
10. Pretreatment with a combination of omeprazole and Althaea officinalis for 14 days in a dose of 20 mg/kg/day and 100 mg/kg/day, respectively, p.o., resulted in significant protection against pyloric ligation/indomethacin-induced gastric ulceration as shown by a significant reduction in ulcer number, ulcer index, providing a protection index of 63%. Also, it significantly reduced gastric mucosal MDA, histamine, and blood gastrin contents. Additionally, a significant reduction in COX-2 and NOS-2 enzyme activities and TNF-α and IL-1β contents was also reported. These were associated with significant elevation in gastric mucosal SOD activity, NO, GSH, PG-E2, PG-I2 and mucin contents, and significant elevation in HO-1 and CBS enzyme expressions.
11. Pretreatment with a combination of omeprazole and Solanum nigrum for 14 days in a dose of 20 mg/kg/day and 200 mg/kg/day, respectively, p.o., resulted in significant protection against pyloric ligation/indomethacin-induced gastric ulceration as shown by a significant reduction in ulcer number, ulcer index, providing a protection index of 67.5%. Also, it significantly reduced gastric mucosal MDA, histamine, and blood gastrin contents. Additionally, a significant reduction in COX-2 and NOS-2 enzyme activities and TNF-α and IL-1β contents was also reported. These were associated with significant elevation in gastric mucosal SOD activity, NO, GSH, PG-E2 and mucin contents, and significant elevation in HO-1 and CBS enzyme expressions.