Withania coagulans fruit extract antiulcerogenic effect: comparative study with lansoprazole and ranitidine in rats

Abstract

Background: Peptic ulcer disease (PUD) arises from an imbalance between harmful factors like gastric acid and pepsin, and the protective mechanisms of the gastrointestinal lining, particularly the mucus-bicarbonate barrier. Standard treatments include proton pump inhibitors (e.g., lansoprazole) and histamine H₂-receptor antagonists (e.g., ranitidine), but these can have adverse effects. Withania coagulans, a plant used in Ayurvedic medicine, has traditionally been considered to have anti-ulcer properties. This study investigated the potential of W. coagulans fruit extract to protect against gastric ulcers, possibly via H₂ receptor antagonism.

Aim: To evaluate the gastroprotective effects and underlying mechanisms of W. coagulans fruit extract in a rat model of gastric ulcer.

Methods: A dose-response study was conducted using rats divided into six groups: naïve, ulcer control, and four groups treated with W. coagulans extract (1, 5, 10, or 20 mg/kg). Acidified ethanol was used to induce ulcers. In another experiment, pylorus-ligated rats were used to assess the extract's effect on gastric acid secretion in response to dimaprit, a histamine analog. For efficacy comparison, rats were pretreated with W. coagulans, lansoprazole, or ranitidine before ulcer induction. Gastric tissues were analyzed for biochemical markers, including cytokines, mucus, prostaglandin E2 (PGE2), and myeloperoxidase activity.

Results: The 10 mg/kg dose was most effective in reducing gastric ulceration. The extract reduced gastric acid secretion, like H₂ blockers. It also showed stronger antioxidant activity in gastric tissues compared to lansoprazole and ranitidine. Additionally, it reduced pro-inflammatory cytokines (IL-1β, TNF-α, IL-6), increased anti-inflammatory cytokines (IL-10, TGF-β), enhanced mucus and PGE2 production, and lowered myeloperoxidase activity.

Conclusion: Withania coagulans fruit extract at 10 mg/kg significantly protects against acid-induced gastric ulcers. Its effects are comparable to H₂ receptor blockers and include notable antioxidant and anti-inflammatory benefits.

Keywords: Wister rats; Withania coagulans; anti-inflammatory; anti-oxidative stress; gastric ulcer protection; histamine blocker; lansoprazole; ranitidine.

Figure 1

(a) Ulcer index (mm) in the gastric mucosa of rats pretreated with 0 (control), 1, 5, 10 and 20 mg/kg Withania coagulans fruit extract then challenged with acidified ethanol. *denotes significance from control. Increasing number of signs denote increasing levels of sig. (p < 0.05; p < 0.001). (b) Ulcer index (mm) in the gastric mucosa of rats pretreated with 10 mg/kg W. coagulans fruit extract compared to Control, Lansoprazole and Ranitidine. Signs denote: *Sig from Control; †Sig. from Lansoprazole; p < 0.001.

Figure 2

(a) Gastric acid output (nmol/L/4hr) in gastric juice of rats after pylorus ligation and then administration of either of: 10 mg/kg W. coagulans fruit extract; distilled water (DH: O) + Dimaprit; W. coagulans fruit extract+ Dimaprit or DHO only (control). Signs denote: *Sig. from DH: O; #Sig.from Dimaprit; †Sig from W. coagulans. Increasing number of signs denote increasing levels of sig. (p < 0.05; p < 0.001). (b) Somatostatin contents (ng/ml) in gastric juice of rats after pylorus ligation and then administration either of: 10 mg/kg W. coagulans fruit extract; distilled water (DH: O) + Dimaprit; W. coagulans fruit extract+ Dimaprit or DHO only (control). Signs denote: *Sig. from D H2O (p < 0.01); #Sig. from D. H2O + Dimaprit (p < 0.01); €Sig from W. coagulans. Increasing number of signs denote increasing levels of sig. (p < 0.01; p < 0.001).

Figure 3

(a) Mucus content (μg/mg tissue) in the gastric mucosa of rats pretreated either with W. coagulans fruit extract (10 mg/kg); Lansoprazole (10 mg/kg); Ranitidine (20 mg/kg) or left as positive Control which were then challenged with acidified ethanol per os. The Naïve group was left untreated. Signs denote: *Sig. from Naïve; #Sig. from Control. Increasing number of signs denote level of sig. (p < 0.05; p < 0.01; p < 0.001). (b) PGE2 (pg/mg tissue) in the gastric mucosa of rats pretreated either with W. coagulans fruit extract (10 mg/kg); Lansoprazole (10 mg/kg); Ranitidine (20 mg/kg) or left as positive Control which were then challenged with acidified ethanol per os. The Naïve group was left untreated. Signs denote: *Sig. from Naïve; # Sig. from Control; †Sig. from Lansoprazole; ◇Sig. from Ranitidine. Increasing number of signs denote level of sig. (p < 0.05; p < 0.01). (C) ΝΟ (μM) in the gastric mucosa of rats pretreated either with W. coagulans fruit extract (10 mg/kg); Lansoprazole (10 mg/kg); Ranitidine (20 mg/kg) or left as positive Control which were then challenged with acidified ethanol per os. The Naïve group was left untreated. Signs denote: *Sig. from Naïve. Increasing number of signs denote level of sig. (p < 0.01; p < 0.001).

Figure 4

(a) MDA (μM) in the gastric mucosa of rats pretreated either with W. coagulans fruit extract (10 mg/kg); Lansoprazole (10 mg/kg); Ranitidine (20 mg/kg) or left as positive Control which were then challenged with acidified ethanol per os. Naïve was left untreated. Signs denote: *Sig. from Naïve; #Sig. from Control; †Sig from Lansoprazole; ◊Sig from Ranitidine (p < 0.05). (b) GSH (μM) in the gastric mucosa of rats pretreated either with W. coagulans fruit extract (10 mg/kg); Lansoprazole (10 mg/kg); Ranitidine (20 mg/kg) or left as positive Control which were then challenged with acidified ethanol per os. Naïve was left untreated. Signs denote: *Sig. from Naïve; #Sig. from Control; †Sig from Lansoprazole; ◊Sig from Ranitidine. Increasing number of signs denote increasing levels of sig. (p < 0.05; p < 0.01; p < 0.001). (c) CAT (nmol/ml/min) in the gastric mucosa of rats pretreated either with W. coagulans fruit extract (10 mg/kg); Lansoprazole (10 mg/kg); Ranitidine (20 mg/kg) or left as positive Control; which were then challenged with acidified ethanol per os. Naïve was left untreated. Signs denote: *Sig. from Naïve; #Sig. from Control; †Sig from Lansoprazole; ◊Sig from Ranitidine. Increasing number of signs denote increasing levels of sig. (p < 0.05; p < 0.01; p < 0.001). (d) SOD (U/ml) in the gastric mucosa of rats pretreated either with W. coagulans fruit extract (10 mg/kg); Lansoprazole (10 mg/kg); Ranitidine (20 mg/kg) or left as positive Control which were then challenged with acidified ethanol per os. Naïve was left untreated. Sign denotes: *Sig. from Naïve (p < 0.05).

Figure 5

(a) IL-1ẞ (pg/mg tissue) in the gastric mucosa of rats pretreated either with W. coagulans fruit extract (10 mg/kg); Lansoprazole (10 mg/kg); Ranitidine (20 mg/kg) or left as positive Control which were then challenged with acidified ethanol per os. Naïve was left untreated. Signs denote: *Sig. from Naïve; #Sig. from Control; †Sig from Lansoprazole; ◊Sig from Ranitidine. Increasing number of signs denote increasing levels of sig. (p < 0.05; p < 0.01; p < 0.001). (b) IL-6 (pg/mg tissue) in the gastric mucosa of rats pretreated either with W. coagulans fruit extract (10 mg/kg); Lansoprazole (10 mg/kg); Ranitidine (20 mg/kg) or left as positive Control which were then challenged with acidified ethanol per os. Naïve was left untreated. Signs denote: *Sig. from Naïve; #Sig. from Control; †Sig. from Lansoprazole; ◊Sig. from Ranitidine. Increasing number of signs denote increasing levels of sig. (p < 0.05; p < 0.001). (c) TNF-a (pg/mg tissue) in the gastric mucosa of rats pretreated either with W. coagulans fruit extract (10 mg/kg); Lansoprazole (10 mg/kg); Ranitidine (20 mg/kg) or left as positive Control which were then challenged with acidified ethanol per os. Naïve was left untreated. Signs denote: *Sig. from Naïve; #Sig. from Control; †Sig from Lansoprazole; ◊Sig from Ranitidine. Increasing number of signs denote increasing levels of sig. (p < 0.05; p < 0.01). (d) IL-10 (pg/mg tissue) in the gastric mucosa of rats pretreated either with W. coagulans fruit extract (10 mg/kg); Lansoprazole (10 mg/kg); Ranitidine (20 mg/kg) or left as positive Control which were then challenged with acidified ethanol per os. Naïve was left untreated. Sign # denotes: Sig. from Control (p < 0.05). (e) TGF-β (pg/mg tissue) in the gastric mucosa of rats pretreated either with W. Coagulans fruit extract (10 mg/kg); Lansoprazole (10 mg/kg); Ranitidine (20 mg/kg) or left as positive Control which were then challenged with acidified ethanol per os. Naïve was left untreated. Signs denote; *Sig. from Naïve; #Sig. from Control; †Sig from Lansoprazole; ◊Sig from Ranitidine. Increasing number of signs denote increasing levels of sig. (p < 0.05; p < 0.01; p < 0.001).

Figure 6

MPO (ng/mg tissue) in the gastric mucosa of rats pretreated either with W. coagulans fruit extract (10 mg/kg); Lansoprazole (10 mg/kg); Ranitidine (20 mg/kg) or left as positive Control which were then challenged with acidified ethanol per os. Naïve was left untreated. Signs denote: *Sig. from Naïve; #Sig. from Control; ◊Sig from Ranitidine. Increasing number of signs denote increasing levels of sig. (p < 0.05; p < 0.01; p < 0.001).

Figure 7

Light micrographs of hematoxylin–eosin-(H & E) stained sections of stomach of untreated and those treated with either Withania, Lansoprazole or Ranitidine. (A) Naive rats with normal gastric mucosa with pits, gastric glands, muscularis mucosa and submucosa; (B) Positive control with ulcer crater and hemorrhage. (C) Positive control group, as in B, showing severe hemorrhage and degeneration in the mucosal layer of the stomach. (D) Withania coagulans-treated group showing apical sloughing of gastric epithelium. No ulcer was observed; (E) Lansoprazole-treated group displaying apical sloughing and vacuolar degeneration of the mucosa; (F) Ranitidine-treated group showing focal hemorrhage, epithelial necrosis but no ulcer. m, mucosa; mm, muscularis mucosae; *ulcer. Scale bar = 50 μm.